Просмотр полной версии : Index of Suspicion

Постараюсь публиковать здесь интересные клинические случаи по детским болезням.
К участию и обсуждению приглашаются все желающие.
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Case 1
Presentation

A 21-month-old boy known to have chronic gastroesophageal reflux is brought to your office for a second opinion regarding poor growth. Born at term, he was diagnosed as having reflux at 3 weeks of age due to arching and crying with feedings. He was noticed to be failing to thrive initially at 12 months of age when, despite adequate caloric intake, his weight percentile had fallen from the 75th to the 5th percentile over 6 months. His height and head circumference have remained between the 10th and 25th percentiles. He has experienced intermittent episodes of constipation and frequent colds and ear infections. He walked at 15 months of age and says about 150 words.

His evaluation has included multiple laboratory tests, including cystic fibrosis and celiac disease screening, thyroid function tests, CBC, measurement of electrolytes, and urinalysis. He has been evaluated by pediatric gastroenterology, and despite a formula change and multiple antireflux medications, his weight has remained in the 5th percentile. A pH probe study and endoscopy performed at 20 months of age demonstrated only mild reflux. He has had negative skin testing for food allergies.

The diagnosis is revealed after additional history and a laboratory test are obtained.
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Case 1 Discussion

On further questioning, the child’s mother mentioned that he drinks about 70 to 80 oz of fluid a day! Generally, he drinks 40 oz of water, 16 oz of rice milk, and two to three cans of liquid dietary supplement. This excessive thirst started at about 6 months of age. He awakens three to five times a night asking for water, and his wet diapers are noted to be incredibly heavy.

Measurement of urine electrolytes demonstrated concentrations of sodium below 5 mEq/L (5 mmol/L) and chloride below 20 mEq/L (20 mmol/L), with urine osmolality below 50 mOsm/L while the serum osmolality was high-normal at 303 mOsm/L. In retrospect, previous urinalysis results had been abnormal because of a specific gravity of 1.005, although the other indices had been normal. His serum chloride value had been mildly elevated at 109 mEq/L (109 mmol/L), but his sodium value was normal at 144 mEq/L (144 mmol/L).

The boy was admitted to the hospital for a water deprivation test, which showed an increase of serum sodium (from 144 to 152 mEq/L [144 to 152 mmol/L]), increase in serum osmolality (from 297 to 310 mOsm/L), no change in urine osmolality (range, 64 to 77 mOsm/L), and continued passage of dilute urine (specific gravity below 1.003). His weight decreased 5% (9.4 kg to 8.95 kg), and his urine volume averaged 16 mL/kg per hour.

After an injection of arginine vasopressin (AVP), his urine osmolality and specific gravity remained low at 70 mOsm/L and 1.002, respectively. His urine output was more than 30 mL/kg per hour during the subsequent hour after injection. The diagnosis of congenital nephrogenic diabetes insipidus (CNDI) was confirmed.

The Signs
Causes of polyuria and polydipsia can be differentiated based on laboratory values. Solute diuresis can be identified by finding a urine-to-plasma osmolality ratio greater than 0.7. Examples of solute diuresis are diabetes mellitus and intrinsic renal disease, which can be determined by routine chemistries. Water diuresis, in addition to a urine-to-plasma osmolality of less than 0.7, demonstrates a urine specific gravity below 1.010. Three common causes of water diuresis are compulsive water drinking, central diabetes insipidus (CDI), and nephrogenic diabetes insipidus (NDI).

Compulsive water drinking can be differentiated from diabetes insipidus (DI) by laboratory testing, if the history is not forthcoming. Interestingly, compulsive water drinkers often have a preference for ice water and are less likely to have nocturia. Low serum osmolality combined with low urine osmolality suggests compulsive water drinking.

CDI often can be suspected on the basis of history, as when the patient manifests brain tumor, head trauma, or CNS infection. In approximately 25% of cases, no cause can be determined.

It is important to differentiate congenital from acquired causes of NDI, such as drug effects, electrolyte disorders, urinary tract obstruction, and systemic disorders such as sickle cell anemia. It is helpful to recall that acquired NDI can be caused by primary renal disease, systemic disease with renal involvement, medication effects, and miscellaneous conditions.

Making the Diagnosis
If the patient can drink freely, the baseline serum sodium concentration generally normalizes, and there is no evidence of dehydration. A first step to distinguish NDI from other causes of polydipsia is to collect a 24-hour urine sample. For a small child, a shorter collection period may be necessary. The finding of polyuria in a patient who is dehydrated and has an elevated serum sodium concentration as well as hypo-osmolar urine implies a renal concentration defect. The diagnosis of NDI is confirmed by a water deprivation test, with results showing the inability to concentrate the urine despite the release of vasopressin.

The water deprivation test involves dehydrating the patient and testing for changes in specific laboratory values. Generally, the criteria for dehydration are 3% to 5% weight loss, orthostasis, a plateau in urine osmolality, or hypernatremia. Urine volume, osmolality of plasma and urine, and electrolyte values are followed closely. A plasma vasopressin level is measured at the start and completion of dehydration.

Both types of DI are characterized by the inability to concentrate urine after water deprivation. The urine osmolality usually remains below 200 mOsm/kg H2O, and the urine specific gravity remains below 1.010. On the other hand, compulsive water drinkers pass concentrated urine (urine osmolality >500 mOsm/kg H2O) after being deprived of water. Patients who have CDI demonstrate inadequate concentrations of vasopressin after a water deprivation test, but concentrations are elevated in those having NDI. To distinguish CDI further from NDI, vasopressin is administered. Individuals who have CDI have a significant increase (usually >50%) in urine osmolality after vasopressin is administered either intranasally, subcutaneously, or intravenously. Patients having NDI maintain a low urinary osmolality (usually <200 mOsm/kg).

The Condition
CNDI is a genetically inherited error, with 90% of cases being X-linked and 10% involving an autosomal recessive or autosomal dominant mechanism. The distal nephron is insensitive to the antidiuretic effects of AVP, which leads to the production of large amounts of hypotonic urine. Normally, in the collecting duct, AVP from the posterior pituitary gland binds with the vasopressin type-2 receptor (V2R), which activates adenylate cyclase to increase cyclic AMP. This reaction stimulates protein kinase A, which redistributes aquaporin-2 water channels (AQP2), permitting the apical plasma membrane to become permeable to water. As a result, water flows from the tubular lumen to the medullary interstitium, which produces concentrated urine. In the X-linked form, the mutation exists in the V2R gene; in the autosomally inherited forms, the mutation is in the AQP2 gene.

Clinical Features
Classic features of DI are polyuria and polydipsia, which can lead to hypernatremic dehydration. The excessive fluid intake also may blunt the appetite. Nonspecific signs and symptoms include failure to thrive, recurrent fevers due to dehydration, vomiting or poor feeding, and constipation. More severe manifestations are seizures and mental retardation, which occurs rarely because awareness of the disorder has increased. Physical findings may be normal or the patient may show signs of dehydration and irritability.

Treatment
CNDI is treated by dietary restrictions and medication. Sodium intake is reduced to 0.7 mEq/kg per day, and protein intake is decreased to 8% of total caloric intake to decrease renal solute load and decrease the volume of urine required for solute excretion. Thiazide diuretics, often coupled with potassium supplements, or potassium-sparing diuretics with dietary changes paradoxically can reduce urine volume by 20% to 50%. Amiloride and prostaglandin synthetase inhibitors have been used in combination with thiazide diuretics. Nonsteroidal anti-inflammatory drugs are useful in the acute setting to reverse hyperosmolality. It is important to remember that an increase in urine osmolality to more than 200 mOsm/kg H2O has a dramatic effect on urinary losses.

Lessons for the Clinician
A comprehensive history is essential in determining a cause for failure to thrive. Growth failure can be a presenting sign of CNDI. It is important to ask not only about inadequate urination and oral intake, but also about polyuria and polydipsia.


Laurie Liang, MD
Kaiser Santa Clara Hospital, Santa Clara, Calif

Case2
Presentation

A 3-year-old boy is seen in the ED because of a "bloodshot eye." Several weeks ago he was hit in the eye with a ball. Two days ago his eye became red but has not bothered him. He has had no ocular discharge, fever, or respiratory symptoms. He comes from a disrupted family complicated by parental drug use and has siblings in foster care. He has not received routine care, although he was seen regularly in infancy and is fully immunized.

Physical examination reveals an active, well-nourished toddler who has conjunctival injection and a blood layer in the anterior chamber of his right eye (hyphema). There appears to be no vision in his affected eye, and a red reflex cannot be obtained. There are no signs of facial trauma, strabismus, or pigmented yellow lesions around the eye. Examination of the skin shows no petechiae or bruising except on the anterior shins. The child is admitted for management of hyphema.

Laboratory findings include a WBC count of 8.5x103/mcL (8.5x109/L), Hgb concentration of 12 g/dL (120 g/L), platelet count of 275x103/mcL (275x109/L), international normalized ratio of 1, and partial thromboplastin time of 41 seconds. A skeletal survey shows no fractures. Imaging confirms the cause of the hyphema.
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Case 2 Discussion

Further history revealed that the child’s right eye has glowed like a "cat’s eye" when viewed from across the room since he was 24 months old. CT scan revealed a calcified mass within the right globe and no abnormalities of the left globe. The findings of a calcified mass within the globe on CT scan were consistent with retinoblastoma.

The Condition
Hyphema in children most commonly occurs after blunt or lacerating trauma, but the differential diagnosis is broad. Spontaneous hyphema can arise from juvenile xanthogranuloma, leukemia, hemophilia, thrombocytopenia, aspirin or warfarin ingestion, and intraocular tumors such as retinoblastoma.

Although hyphema in children usually resolves without sequelae, complications can ensue and include increased intraocular pressure, optic atrophy, synechiae between the iris and the lens, and corneal blood staining. Because complications are more common with rebleeding, initial management is aimed at preventing further bleeding. Placement of a hard metal shield to protect the eye (Fox shield) is an important preventive step. Bed rest or quiet ambulation should be instituted, along with elevation of the head of the bed. Admission should be strongly considered for all children, especially if there is any question of compliance. Because patients who have sickle cell hemoglobinopathy are at higher risk for complications, Hgb electrophoresis should be obtained if the diagnosis is in question.

Ophthalmologic consultation is required for any child presenting with hyphema to prevent late sequelae. The ophthalmologist administers medicines that lower intraocular pressure, decrease inflammation, and prevent synechiae. Surgical intervention is considered if intraocular pressure cannot be managed with maximal medical therapy or if corneal blood staining occurs.

The Underlying Condition
Retinoblastoma, although rare, is the most common malignant intraocular tumor in children (incidence of 1 in 17,000) and must be considered in any case of spontaneous hyphema. The tumor typically is diagnosed in the first years after birth. The initial sign usually is leukocoria, and family members often describe a glow or cat’s eye appearance. Retinoblastoma also can present with strabismus, hyphema, and periocular inflammation resembling orbital cellulitis. The disease can be familial or sporadic and can present unilaterally or bilaterally. Bilateral disease almost always is familial. A mutation of the retinoblastoma gene (a tumor suppressor gene) on chromosome 13 is responsible for tumor development. Metastasis is uncommon. Spread can occur by direct extension along the optic nerve into the brain or the subarachnoid space or through the bloodstream to bone, bone marrow, lung, and lymph nodes. When retinoblastoma is diagnosed, both parents and all siblings should be examined for retinoblastoma.

The management of retinoblastoma involves a multidisciplinary team using multiple modalities that prioritize tumor eradication. Careful and judicious attempts should be made to preserve vision. Treatments include chemotherapy, external beam radiation, laser photocoagulation, enucleation, or combinations of these approaches. Although enucleation remains the most common treatment for unilateral disease, the trend in more recent years has been toward less frequent use of this approach, probably because of the more effective use of other approaches such as radiation, chemotherapy, and laser therapy. The prognosis for patients who have unilateral retinoblastoma without optic nerve invasion or metastasis is excellent, with more than 90% survival among those using current therapy. However, if tumor is disseminated, the mortality increases substantially. Surgical washout, which sometimes is performed for bleeding in the eye, carries the potential for dissemination, which could have proved a lethal choice for this child.

Lessons for the Clinician
The possibility of retinoblastoma should be entertained for any child who develops a spontaneous hyphema. In this case, the child’s complicated social situation might have led the clinician to suspect nonaccidental trauma as the cause of the child’s hyphema, delaying the diagnosis. When the retina cannot be visualized, it is imperative to obtain an imaging study to rule out disease in the posterior pole.


Carrie Phillipi, MD, PhD
Laurie Christensen, MD
John Samples, MD
Oregon Health and Science University, Portland, Or

The knotty problem in an infant girl's groin
Jul 1, 2005
By: Doran L. Fink, MD, PhD, Janet R. Serwint, MD

Mid-afternoon, and you're working at the pediatric clinic of your university hospital. With the beautiful spring weather outside, you've seen few acute care visits today; itchy eyes and runny noses in otherwise healthy children have established an unusually relaxing pace! Only one patient remains to be seen: a nearly 3-month-old girl whose mother is concerned about a "knot in the baby's groin."

Mom greets you with an uneasy smile as you enter the examination room. "It hasn't gone away," she says. "I think it's gotten bigger."

Instantly, you remember that the last time you saw the infant was four weeks ago—at her 2-month-old health maintenance visit. She had a diaper rash.

Reviewing your notes from that encounter, you recall that the rash had appeared one week before that visit. Apart from that, your patient was growing well, without complaints of fever, cough, congestion, diarrhea, or emesis. She was afebrile; vital signs were normal for age. You noted a pink, macular, anterior inguinal rash with satellite lesions that suggested diaper candidiasis. You also noted a firm, nontender, 1 x 1-cm mass in the right inguinal area that was freely mobile. Otherwise, the exam was unremarkable with no other rash or palpable mass.

Having decided that the inguinal rash was most consistent with a candidal infection and the mass most consistent with a reactive lymph node, you prescribed nystatin cream to be applied until three days after the rash resolved. You instructed the mother to return to the clinic if either the rash or the lymph node persisted for longer than several weeks. Now, four weeks later, she informs you that the rash did indeed improve within a week after the nystatin was started. The mass in the right groin has not disappeared as expected, however; instead, she reports that its size has nearly doubled!

The patient takes her lumps On further questioning, you learn that the mass has been present continuously over the past four weeks. It has remained nontender and does not appear to bother the baby when it is touched or when it is manipulated during a diaper change. The patient has regular, soft, yellow-to-brown bowel movements several times a day; no blood is obvious in the stool. She has had no emesis and has been taking formula well—four ounces every four or five hours. She has still not had a fever.

Today, rectal temperature is 36.4° C; heart rate, 150/min; and respirations, 42/min. Weight is 3.91 kg (between 5th and 10th percentiles for postconceptual age, tracking along her expected growth velocity). Overall, she is alert and active and appears well. The anterior fontanelle is soft; sclerae are clear; and a pupillary red reflex is present bilaterally. Tympanic membranes are unremarkable. Oropharynx is moist with no enanthem. Neck is supple without lymphadenopathy. Examination of the heart and lungs is unremarkable. The abdomen is soft and nontender, with normal bowel sounds and no organomegaly.

When you remove the girl's diaper, you discern the firm, freely mobile subcutaneous mass in the right inguinal region, midline along the path of the inguinal canal. The mass is 2 x 1.5 cm, nontender on palpation and manipulation, nonpulsatile, and lacking overlying skin changes. Turning to the left inguinal region, you palpate two firm, mobile, nontender masses, each 0.5 x 0.5 cm. You find no other palpable masses. Surveying the baby's skin carefully, you find no rashes anywhere. There are several small areas of hypopigmentation along the inguinal creases and inner thighs.

You're intrigued by the persistence of these inguinal masses. As a first step, the mother—20 years old, with negative serologic tests for syphilis, hepatitis B, and HIV infection—recounts her daughter's medical history for you.

The patient was born prematurely, at 35 weeks' gestation, product of an identical twin pregnancy. Vaginal delivery was complicated by breech presentation; the baby required positive pressure ventilation for several minutes for respiratory distress. Apgar score was 3 at one minute, 7 at five minutes, and 8 at 10 minutes. She was admitted to the neonatal intensive care unit, where she remained stable on room air. A workup for sepsis was negative. After two days in the NICU, she was transferred to the well-baby nursery. Three days later, she was discharged with her twin sister.

The patient had unremarkable health maintenance visits at 1 and 3 weeks of age. At 7 weeks, she was evaluated by your partner for an erythematous, maculopapular, scaling rash on the face and shoulders. Hydrocortisone 1% cream was prescribed for presumed seborrheic dermatitis, and the rash resolved after one week. She had no further medical concerns until that 2-month-old visit. At each visit, weight was at the 10th percentile for postconceptual age.

Differential diagnosis of inguinal mass in an infant

The patient takes no medications at the moment, has no known drug allergies or exposures to animals or insects, and has not traveled outside her home city. Her mother confirms a negative family history of inguinal hernia, malignancy, immunodeficiency, and lymphoproliferative disorders. The girl's twin sister has had no medical problems.

You suspect that the inguinal mass may be something other than a simple reactive lymph node that arose from candidal dermatitis. Although it has the feel of an enlarged lymph node, its persistence and gradual growth over the past four weeks—despite resolution of the rash—is somewhat unusual.

You consider possible causes of isolated inguinal lymphadenopathy:
reaction to infection of the inguinal area or lower extremities by various pathogens
bacterial infection of the lymph node itself
malignancy, including lymphoproliferative disorders
an immunodeficient state
an infiltrative process

You are reassured that many of these potentially serious conditions are quite rare in young infants and most often present with generalized, rather than localized, lymphadenopathy. You also wonder whether the mass is truly a lymph node. Its proximity to the inguinal canal suggests herniated bowel, omentum, or, even, an ovary. Femoral artery aneurysm is also a consideration, although an unlikely one because the mass is nonpulsatile. Last, you keep in mind other soft-tissue masses, such as fibroma and neuroma.

Pictures don't lie
Faced with a large differential diagnosis, you decide that imaging may narrow your focus or even identify the problem definitively. You discuss the case with the medical center's pediatric radiologist and together decide that ultrasonography (US) would most likely provide useful information, and would also have the benefits of quick performance and low risk.2 Good fortune! There's time in today's radiology schedule to perform the study.

The baby heads off to the radiology suite with her mother. Twenty minutes later, the radiologist calls you back. The sonogram revealed an indeterminate, well-defined hypervascular mass in the region of the inguinal canal. The right ovary could not be visualized, but the mass doesn't resemble normal or enlarged ovary, bowel, or adenopathic tissue. The radiologist recommends that you strongly consider herniated omentum—even though a lymph node or herniated ovary cannot be excluded.

As you wait for your patient to return, you contemplate what to do next. The sonogram suggests a hernia but she has no history of intestinal symptoms, no findings of acute abdomen on exam, and no tenderness in the mass. This may not be a surgical emergency, but you're uneasy about the persistence and gradual growth of the mass over almost a month's time.

You reason that, because US could not definitively identify the mass, evaluation by a surgeon may be warranted sooner rather than later. By the time she returns, you've arranged an appointment in the pediatric surgery clinic later that week.

Time to go inside Two days pass. You take a call from the surgeon, who is as perplexed as you are. He has decided to admit the girl that evening for exploratory surgery. His thinking is similar to yours: The preoperative differential diagnosis favors hernia with entrapped ovary versus lymphadenopathy. Preoperative lab tests, including a complete blood count, comprehensive metabolic profile, and coagulation panel, have already been performed, and all results are within normal limits.

Later that day, the surgeon pages you at home. Exploration of the right inguinal area revealed no hernia, and he removed a single large lymph node. Your patient tolerated the procedure well and was discharged home from the recovery unit. The excised node has been sent for histopathologic analysis.

Bumpy ride ahead?
Ten days later, you receive the pathology report. Analysis of the lymph node revealed a paracortical histiocytic infiltrate with antigen markers indicative of an immature dendritic cell tumor, or early-stage Langerhan cell histiocytosis. The mass did hide something sinister after all! Although the report confirms your suspicions, you still have questions about the disease and the prognosis.

You discuss the patient's history with the pediatric oncologist who participated in the analysis of the node. He proposes, in retrospect, that the earlier facial and inguinal rashes may have been transient cutaneous manifestations of histiocytic disease. He further explains that excision of the lymph node may have been curative and that chemotherapy isn't indicated. Full-body imaging is necessary, however, to detect any occult tumors or skeletal lesions. He also recommends periodic close follow-up at your office and with the staff of the oncology clinic.

Langerhan cell histiocytosis (LCH) is a disorder of abnormal dendritic cell proliferation characterized by the presence of pathologic Langerhan cells (a type of dendritic cell, or histiocyte) within the centers of proliferation. Once known as histiocytosis X, LCH is a disease of diverse clinical presentations that encompass several conditions once thought to be distinct pathologic entities, including:
eosinophilic granuloma (localized bone lesions)
Hand-Schuller-Christian disease (multiple organ involvement characterized by a classic triad of skull defects, diabetes insipidus, and exophthalmos)
Letterer-Siwe disease (visceral lesions involving multiple organs)
Hashimoto Pritzker variant (congenital skin lesions that may resolve by 2 or 3 months of age but can recur).

Other histiocytic disorders feature proliferation of cell types other than the Langerhan cell, such as hemophagocytic lymphohistiocytosis (HLH), histiocytoma with macrophage phenotype, and Rosai-Dorfman disease (benign painless cervical lymphadenopathy with occasional extra-nodal involvement).3 Although LCH is the most common form of childhood histiocytosis, it is rare, affecting only one in 25,000 children annually.

The initial clinical presentation of LCH is varied and depends on the organ systems involved. In single-system LCH, only one organ or tissue is affected. For example, skin rash is the only manifestation in approximately 10% of cases. The rash often appears on the scalp and in flexural areas as reddish papules that progress to vesicles, pustules, or ulcers, followed by depigmentation and, eventually, healing. Often, the rash is mistaken for seborrheic dermatitis in newborns and infants.

LCH can also present as disseminated disease that affects multiple organs and tissues. Osteolytic bone lesions, manifesting as painful swelling, are present in more than 80% of cases. Other affected organs can include bone marrow, liver, spleen, lung, the central nervous system, and, more rarely, the gastrointestinal and genitourinary systems. Lymph node enlargement occurs in only 10% of cases, usually at initial presentation.

When LCH—in any form—is suspected, guidelines recommend a comprehensive workup of chest radiography and a skeletal survey, CBC, coagulation studies, and a liver function panel. A bone scan or body computed tomography scan may be helpful in certain cases. Definitive diagnosis requires biopsy and histopathologic analysis of a suspected lesion. Hallmarks of LCH include positive staining for the histiocytic markers CD-1a and S-100, as well as the presence of the Langerhan cell organelle, or Birbeck granule, within pathologic histiocytes.

Management of LCH depends on the extent of organ system involvement. Mild cutaneous disease may require only close observation or treatment with local corticosteroids. Severe cutaneous disease or multisystem disease may require extensive chemotherapy. Outcome correlates well with extent of disease involvement: Patients whose disease is more disseminated at presentation are at greater risk of relapse and death.

When do you watch the big picture? Your patient's case illustrates the challenge faced by a primary care provider when addressing common complaints with a wide differential diagnosis. Although careful history-taking and physical examination are often helpful in narrowing possibilities, potentially lethal rare diseases such as LCH may, in an early stage, offer few, if any, clues to help distinguish them from more common, less serious conditions. Our recommendation is not to be overzealous in pursuing zebras but to give thoughtful attention to the big picture when a constellation of symptoms evolves over time, and to take every opportunity to re-evaluate the differential diagnosis.

How quickly should workup of a suspected unusual condition proceed? In the case of your patient, the decision to send her for prompt surgical evaluation arose from two critical factors: persistence and gradual enlargement of the mass over more than one month despite resolution of the perineal rash and the inability of US to definitively identify its nature or visualize the right ovary.

Plan of observation You call the baby's mother to deliver the news. She is alarmed to hear "tumor" but relieved that the disease may have been cured by the surgery. You prepare the family for her upcoming visit to the oncology clinic. Information offered by the oncologist proves helpful as you carefully explain the details of the diagnosis and address her mother's concerns.

The family returns two weeks later for the twins' 4-month-old health maintenance visit. Your patient has done well since her operation and has no complaints. Her sister remains healthy too. The physical exam is unremarkable—you find neither a rash nor lymphadenopathy. She has had her first oncology clinic appointment and has undergone several imaging studies since you saw her last. A skeletal survey showed no bony lesions, and a full-body CT scan revealed only five small pulmonary nodules on the right side, suggesting asymptomatic pulmonary histiocytic disease. There is no remaining evidence on imaging of the left-sided inguinal nodes that you observed. Repeat lab tests were normal. The baby will alternate seeing you and then the oncologist at least once a month, and she will undergo serial imaging study and lab testing every three months. If she remains symptom-free from her knotty problem—if things go smoothly now!—the frequency of visits and testing may, gradually, decrease over time. Although the oncologist does not believe that the twin sister is at elevated risk of LCH, you will monitor her for clinical signs of disease at her well-child visits.

DR. FINK is a third-year resident in pediatrics, and DR. SERWINT is director of pediatric resident education and associate professor of pediatrics, both at Johns Hopkins University School of Medicine, Baltimore.

"That ever this should be!" The cellulitis that would not go away
The next patient waiting to be seen at your office today is a previously healthy 2-year-old girl who, according to her father when he called for an appointment, developed a "pimple-like" swelling on the lateral aspect of her right middle finger three days ago. Now, he tells you that he expressed "green fluid" from the lesion, and that erythema developed around it over the following two days. You examine the lesion, offer a diagnosis of cellulitis, and promptly begin treatment with amoxicillin-clavulanic acid.
"Full many shapes ... in crimson colours came"
Within one week of that office visit, however, the family notes progression of the process: Red streaks extend to the base of the middle finger, where a firm nodule develops. Despite multiple antibiotic changes that you institute—cephalexin, ceftriaxone, cefadroxil—the girl's condition does not improve over the ensuing four weeks.
You decide that the best course now is to consult an infectious disease specialist. A radiograph of the hand is taken and read as normal, excluding the possibility of chronic osteomyelitis. The consultant is concerned about the presence of an unusual, or resistant, organism. She institutes a trial of clindamycin but does not obtain material for culture, while you arrange referral to a plastic surgeon to have a biopsy performed.
"I fear thy skinny hand!"
At admission for biopsy, the parents confirm the absence of fever throughout the girl's illness. She has been acting well, they report, and has not had other skin lesions on the affected finger, including vesicles or puncture wounds by a thorn, or any musculoskeletal problems. The medical history includes infrequent episodes of otitis media and well-controlled atopic dermatitis. She does not take medications other than the antibiotics you recently prescribed. Immunizations are current. She is not allergic to medications.
The family reports that they have a pet cat but deny that the girl has been bitten or scratched by the animal. The family, including your patient, has not traveled outside the northeastern region of the United States or visited a farm in recent months. The girl has no known exposure to plants or moss, or to a person with tuberculosis. The family history is negative for chronic infection, immunodeficiency, and recurrent skin infection. One parent and one sibling have atopic dermatitis and food allergy. The patient is developmentally normal.
When you examine the girl, who is sitting on her mother's lap, she is somewhat apprehensive but does not appear to be in acute distress. She easily engages in conversation and play, and uses her right hand with little evidence of discomfort. You record vital signs: temperature, 36.2°C; heart rate, 112/min; respirations, 22/min; and blood pressure, 85/55 mm Hg. She is at the 25th percentile for height and weight for her age.
The physical exam is unremarkable except for the known findings on the right hand. The middle finger of that hand is swollen and erythematous but nontender. There is also as a pea-sized nodule in mid-dorsum on the right hand.
"Now wherefore stopp'st thou me?"
You consider the diagnostic possibilities—infectious and noninfectious. An osteoid osteoma of the finger, you recall, may not be painful and is not associated with fever. Ewing sarcoma and osteosarcoma typically do not occur in toddlers, and it is the long bones that are most often involved. Because of the girl's multiple lesions and the nonworrisome radiographic findings, you conclude that neither a benign nor a malignant tumor of bone is likely.
More and more, you are convinced that this patient has an unusual infection. (More and more, you feel like that Ancient Mariner of epic poetry—your search for a diagnosis like his voyage across a sea of unusual and inexplicable creatures and unexpected occurrences in "The Rime of the Ancient Mariner." Would the hero of Samuel Taylor Coleridge's puzzling 18th-century work know just how you feel as you confront this challenging investigation?)
You begin with a more mundane undertaking, however, by considering the most common organisms associated with cellulitis in an immunocompetent host. Staphylococcus aureus and Streptococcus pyogenes are the most common bacterial causes of cellulitis and osteomyelitis in children; methicillin-resistant S aureus should be considered, given its recent increase in incidence in children. Streptococcus pneumoniae and Haemophilus influenzae can cause facial and buccal cellulitis but probably not a hand cellulitis. Pasteurella multocida and Bartonella henselae are associated with cat bites and scratches. You even find cases in the literature of tularemia related to a cat bite. All these pathogens will need to be considered.
Now, what about infection with a more unusual organism? Cutaneous anthrax is commonly characterized by an eschar, absent here. As you think about the pattern of a line of nodules with erythema, you consider that the infection may fit the category of nodular or sporotrichoid lymphangitis—except that the nodules do not extend very far up her hand. Nocardia species are present in soil, and traumatic inoculation can cause this type of nodular cellulitis in a normal host. Sporotrichosis (caused by Sporothrix schenckii) is transmitted from plants (especially those with thorns), moss, and hay through small breaks in the skin; ulcerations of painless bumps are typically noted within three weeks of the onset of symptoms. Mycobacterium marinum can produce this picture after exposure to an aquatic environment.
As you are about to begin your investigation of possible uncommon sources of infection, the ID specialist heads out of the patient's room and stops you. She is smiling.

"As I was leaving the room," she says, "I said to her parents, 'I have one more question. Do you have a fish tank?' Mom replied, 'No. But we have a fish bowl. She helps us clean it every weekend.'"
"Yea, slimy things did crawl with legs"
The consultant orders a battery of laboratory tests, including a complete blood count. The white blood cell count is 11.4 X 103/mL, with a differential count of 39% polymorphonuclear neutrophils, 50% lymphocytes, 9% monocytes, and 2% eosinophils; hemoglobin, 12.3 g/dL; platelets, 343 X 103/mL. The C-reactive protein level is 0.1 mg/dL.
Biopsy of the skin in the affected area reveals a focal area of necrosis that is consistent with acute and chronic inflammation. A Gram stain is negative for bacteria, with 3+ polymorphonuclear neutrophils. Acid-fast staining is weakly positive for bacilli. Specimens are taken for bacterial and fungal cultures.
Those cultures eventually return negative. However, the acid-fast culture grows Mycobacterium marinum—and that jibes with the parents' comment about their fish bowl! The organism is sensitive to clarithromycin, rifampin, trimethoprim-sulfamethoxazole, and minocycline. The ID specialist is still smiling!
A course of clarithromycin and rifampin is started and, initially, the finger appears to improve. Approximately one month later, however, the nodule at the base of the finger enlarges and continues to do so. A three-month course of antibiotics ensues, but does not succeed in eliminating the nodule. The girl undergoes incision and drainage. Staining of material from the nodule reveals rare acid-fast organisms. A culture no longer grows M marinum, however.
She continues antibiotic therapy for a total of six months. One year later, your patient continues to do well and has no problem with recurrence.
"I fear thee, ancient Mariner!"
Like all Mycobacterium species, M marinum resides in macrophages. Hosts sequester the pathogen in granulomas, leading to long-term infection. M marinum infects fish and frogs, and was first isolated in saltwater fish in a Philadelphia aquarium in 1926. In 1951, the organism was identified in humans. The great majority of diagnoses are associated with fish tank, lake, pond, and swimming pool exposures. The annual incidence is 0.27/100,000 persons.
M marinum infection is most often limited to skin, where manifestations develop eight to 30 days after exposure at a site of minor skin disruption. Erythematous papules, nodules, or plaques erupt with or without purulent drainage. Infection may extend proximally in a nodular pattern. Although complications are unlikely, tenosynovitis, arthritis, bursitis, and osteomyelitis have been reported; disseminated infection is rare in an immunocompetent host. Treatment is based on the extent of disease. Generally, a prolonged course of an antimicrobial agent is administered. Surgical debridement may also be required for treatment to be effective.
In fish, M marinum infects numerous organs, resulting in a wasting syndrome, nodular lesions, ulceration and loss of scales, necrotic fins, discoloration, and rapid breathing. Because 25% of cases of M marinum infection occur in people who work with aquariums, a recent survey examined fish sales representatives' knowledge of M marinum infection (so-called fish tank granuloma) and their strategies for preventing infection. Of 40 salesmen, only six reported that they "knew the disease well"; 30 said they "knew about it, but ignored it." Thirty-three percent were introduced to the condition during their training to become an aquarium worker. Only eight were "concerned about human disease"; three of those had acquired an infection and five knew someone who had. Importantly, the majority of sales representatives immersed their ungloved hands in fish tanks daily, admitting that they discount the importance of fish tank granuloma.
"Water, water, everywhere"
When you see a patient with an erythematous skin lesion and fever, think of a staphylococcal or streptococcal infection first, of course, and treat the patient appropriately. In this time of increasingly common MRSA infection, remember to obtain material for culture whenever possible (see "Fighting a rising tide of MRSA infection in the young"). But if your patient fails to improve as expected, or if fever is absent, move to clarify the history and consider unusual organisms. That might help you swim toward the correct diagnosis—"alone on a wide wide sea!"

DR. YOUTH is director of the pediatric residency program at The Barbara Bush Children's Hospital at Maine Medical Center, Portland, Maine, where DR. JEWELL is a pediatric hospitalist and DR. MCCARTHY is director of the division of pediatric infectious diseases.

Delayed growth and sexual development in a 15-year-old: A rose by any other name

By Jane C. Lee, et al

The 15 1/2-year-old seated in your office is obviously uncomfortable. He has been referred for evaluation by his physician because of decreased growth and failure to develop secondary sexual characteristics, or, as he puts it, "not developing like the other boys." A copy of his growth chart has been sent along with the consultation request. Growth had been along the 75th percentile until age 10 years, with a rather dramatic decrease to the 5th percentile occurring in the last five- and-one-half years. The weight curve has been less affected.

According to Mother, the birth history is unremarkable and her son achieved normal developmental milestones. His past medical history is noteworthy only for a right-sided inguinal hernia repair at age 8 years. He is taking no medications and, except for growth and development, his health has been good. There is no history of unexplained fevers, abdominal pain, diarrhea or constipation, rashes, or exercise intolerance.

The family history is reviewed carefully. The young man has three siblings: two older sisters, both of whom had normal pubertal progression and growth with regular menses, and one prepubertal, healthy, 10-year-old sister. Mother is 5 feet 2 inches tall and reports menarche at 13 years. Father is 5 feet 9 inches, but his developmental history is unknown.

On physical examination, the youngster's vital signs are normal. His height, 158 cm, and arm span are the same, although the upper-to-lower body segment ratio (height minus the distance from the symphysis pubis to the floor) is 0.82; a normal ratio is >0.9. He appears healthy but younger than his age. Moderate gynecomastia is present. There are no signs of secondary sexual characteristics, including axillary hair, acne, or body odor. He is Tanner stage 2 for pubic hair and has a bilateral testicular volume estimated to be 2 cm3. His stretched penile length is 4.5 cm by 3 cm, clearly prepubertal. The neurologic examination is unremarkable, including normal visual fields.

The history and physical examination substantiate the delayed growth and sexual development but do not provide an obvious answer to the cause. The onset of puberty in males in the United States is 9 to 14 years, so this young man is clearly beyond the norm. In the general population the incidence of delayed puberty is less than 1%, with less than 2% of 14-year-old males and just 0.4% of 15-year-old males remaining prepubertal.

The first sign of pubertal development in males is scrotal reddening and thinning, followed by testicular enlargement to more than 2.5 cm in the longest axis, clearly not present here. This youngster's early pubic hair development is perhaps related to androgens produced by the adrenals, since the testes appear to be underdeveloped. It is clear that a further assessment needs to be performed.

Sniffing out the likely causes

As you complete the physical examination you consider the diagnostic possibilities and plan for evaluation. The young man's medical history has disclosed no evidence of chronic illness, head trauma, or nutritional disorders or other quirks. The mother's and sisters' pubertal progressions seem normal, and, although the father is unavailable, mother recollects no known unusual history in that sphere. Constitutional delay, the most common cause of pubertal delay, seems unlikely given growth at the 75th percentile until age 10 years. Children with constitutional delay usually demonstrate a slowing of linear growth during the first three years of life, with subsequent growth below but parallel to the 5th percentile. And, there is often a family history of pubertal delay, which does not appear to be the case here. Nevertheless, although the growth pattern is not typical, constitutional delay cannot be excluded entirely.

Could the cause be primary testicular failure? The testes are certainly small enough. Disorders in this group, also known as hypergonadotropic hypogonadism, are characterized by elevated levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the serum. Failure to produce testosterone results in the overproduction of these gonadotropins because of a lack of feedback to the hypothalamic-pituitary axis. Primary testicular failure may be congenital, as with Klinefelter syndrome (46 XXY), or acquired, as with viral orchitis (mumps or Coxsackie B viruses) or iatrogenic causes (radiotherapy or chemotherapy).The latter seem unlikely, but Klinefelter syndrome may be on the list of possibilities. The young man does have somewhat eunuchoid proportions.

Could the problem be central? Perhaps there is a hypothalamic or pituitary cause, disorders that fall into the category known as hypogonadotropic hypogonadism. The deficiencies in gonadotropins may be absolute or partial, congenital or acquired (sarcoidosis and head trauma, for instance), functional (related to exercise, anorexia, or anabolic steroids) or structural (craniopharyngioma or germinoma). Then there is the ever present idiopathic (we don't know the cause) isolated gonadotropin deficiency and Kallmann syndrome. Hmmm.... Kallmann syndrome. Hypogonadism associated with lack of the sense of smell!

Take time to smell the roses

The history is not complete. You turn to the youngster and ask, "How do you like the smell of roses?" He looks startled and replies, "What do you mean?" Mother suddenly interjects that her son douses himself with cologne. He protests, but then admits that he really cannot smell well.

The simple question and response provides direction for an evaluation. Gonadotropins are ordered and a magnetic resonance imaging study of the brain is scheduled.

The serum gonadotropins are appropriate for Tanner stage 2 of sexual development, but the levels are not appropriate for the young man's chronologic age, which should be in the Tanner 4 or 5 range. The levels reflect hypogonadotropism. The MRI scan report supports your diagnostic suspicion: absent left olfactory sulcus, hypoplastic right olfactory sulcus, and a small pituitary gland, findings consistent with Kallmann syndrome!

Mastre de San Juan, in the mid-19th century, first described the anatomic association between absent olfactory lobes and underdeveloped genitalia in a male with sexual infantilism.Kallmann and Schoenfeld later attributed a genetic basis to this disorder when they observed three families with the condition. DeMorsier is credited with noting the association of hypogonadism and anosmia with agenesis of the olfactory bulb, which he named olfactogenital dysplasia.

Kallmann syndrome is an uncommon disorder with a prevalence of 1 in 10,000 live births and with a male to female ratio of 3.9 to 1.3 Isolated GnRH deficiency may occasionally be detected in the neonatal period when an infant presents with cryptorchidism and microphallus. More typically, GnRH deficiency presents in adolescence when secondary sexual characteristics fail to develop. Unlike patients with constitutional delay, children with Kallmann syndrome may have normal height until adolescence, when they fail to manifest a growth spurt. Eunuchoid proportions are common, with arm spans typically 5 cm greater than height, and upper-to-lower segment ratios less than 0.9.

Impairment of smell may be partial (hyposmia) or complete (anosmia) in this syndrome. Neither patients or families may notice the impairment, especially when the defect is not complete. Testing with graded dilutions of pure scents is necessary to determine a defect in the sense of smell.Affected individuals are still able to smell irritants such as smoke and skunks, however.

Individuals with Kallmann syndrome may have associated physical and neurologic abnormalities, including cleft lip and palate, imperfect facial fusion, sensorineural deafness, cerebellar ataxia, oculomotor abnormalities, and seizure disorders, among other findings.

The most common form of Kallmann syndrome appears to be inherited in an X-linked pattern, although autosomal recessive and dominant forms have been described. Genetic linkage studies have localized the X-linked form to the so-called KAL gene on Xp22.3, which codes for an adhesion molecule that allows olfactory neurons expressing gonadotropin-releasing factor to migrate to the brain from the olfactory placode.Interestingly, there is considerable heterogeneity in families with this disorder. In the same family, some members may have gonadal deficiencies without loss of smell and others may have loss of smell without abnormalities in gonadal function.

How often do we ask about the sense of smell during routine office visits? Not often. But, given an adolescent with pubertal delay and small testes, you have the chance of smelling like a rose if you ask and discover that the youngster lacks function of cranial nerve I!

У 35 летней женщины с первичной аменореей при первом опросе наш врач выяснил,что она вообще не различает запахи :" Не могу отличить. пахнет ли бензином или жаренной картошкой, все удивляются " . Удивляются минимум 20 лет - все знакомые, все врачи...

У 35 летней женщины с первичной аменореей при первом опросе наш врач выяснил,что она вообще не различает запахи :" Не могу отличить. пахнет ли бензином или жаренной картошкой, все удивляются " . Удивляются минимум 20 лет - все знакомые, все врачи...
Вообще-то алгоритм простой. Удивился - открыл книгу.
А это что-то многовато будет.
Но наверняка красавчики продолжают работать и продолжают удивляться.
А потом мы удивляемся.

Sore throat, fever, intensifying malaise and abdominal pain: Will le diagnostic escape you?

Sunil K. Sood et al

One of your patients, a 16-year-old boy who's been healthy until now, was brought to the ED earlier today, you are informed, complaining of three days of throat and abdominal pain, fever, and swelling of the neck.

The ED physician goes on to describe that she found abdominal tenderness and erythema of the oropharynx but that her exam was otherwise unremarkable. Lab test results show anemia (hemoglobin, 11.9 g/dL); thrombocytopenia (platelet count, 90 X 103/?L) and hyperbilirubinemia (total bilirubin, 4.3 mg/dL; direct bilirubin, 1.4 mg/dL). Liver function tests are normal. A throat culture for group A Streptococcus, a hepatitis panel, and a heterophil antibody assay for Epstein-Barr virus (EBV) have been ordered, but the patient is being released before results are returned because he appears otherwise well. His parents have been told to follow up with a visit to your office tomorrow.

The next day, before your patient arrives, you check on those pending test results. The heterophil antibody assay is negative, as is the hepatitis panel. But you're not feeling very enlightened: The heterophil assay can be negative in early EBV disease and, with liver function normal, hepatitis is unlikely, anyway.

In walks your patient, looking tired but not in distress. You confirm the history; on the physical exam, you note scleral icterus and a swollen submandibular lymph node—but nothing else. You order an EBV serologic study and a Coombs' test but, because he looks well, you send him home once again, with a presumptive diagnosis of early EBV infection as the cause of the throat pain, lymphadenopathy, scleral icterus, and splenomegaly.

Mais il retourne!

But the following day, the boy's parents call your office. They are increasingly concerned. His abdominal pain has become worse, they tell you, he can no longer tolerate even fluids, and the fever continues. And he is feeling more and more lethargic. Uncertain how to proceed, you direct them to bring the boy back to the ED, where you will meet them, for further evaluation.

When you meet the family at the hospital, the boy—now on day 5 of symptoms—appears tired. Vital signs are stable. The physical exam is significant for an erythematous oropharynx, scleral icterus and, now, enlarged, right-sided, submandibular, matted lymph nodes. You note abdominal tenderness upon palpation of the right upper quadrant, without guarding or hepatosplenomegaly. Reflecting on the earlier test results, you send off for new blood tests and are surprised by the continuing presence of anemia (hemoglobin, 10.6 g/dL); thrombocytopenia (platelets, 67 X 103/?L) and hyperbilirubinemia (total bilirubin, 7.4 mg/dL; direct bilirubin, 4.2 mg/dL). Blood is drawn for culture.

You decide to admit the boy to the pediatric floor for rehydration and further workup of this intriguing constellation of symptoms. Throughout the day, the fever continues and he begins to have intermittent episodes of shaking chills. The chills abate soon enough, but the patient continues to look ill and the diagnosis remains a mystery.

You step back to consider where things stand. Infectious mononucleosis can certainly prompt this presentation, but EBV titers and the heterophil assay were completely negative. Hepatitis can present this way, but the history and test results are inconsistent. Could this be an autoimmune hemolytic anemia? That's doubtful: The Coombs' test was negative. And how to explain the progressive abdominal pain?

ID will think of something (peut-?te) At this point, after so much physical inspection of no conclusiveness, you seek a subspecialist's opinion. The intern doing an infectious disease elective examines the patient. Afterward, in presenting the case to the ID attending physician, she reports that what has been described as enlarged submandibular lymph nodes is, in her estimation, a tender neck mass under the mid-sternocleidomastoid muscle.

The ID attending has a hunch! He rushes in to palpate the patient's neck, and confirms his speculation. He tells the mystified floor resident, "Order a neck CT and you'll have your diagnosis."

Merveilleux pour voir—c'est le diagnostic!

Computed tomographic scanning of the neck reveals thrombosis of the right internal jugular vein consistent with a diagnosis of Lemierre syndrome, also known as necrobacillosis and postanginal septicemia.Intravenous clindamycin and ceftriaxone are started and the patient is transferred to the pediatric intensive care unit because of developing dyspnea and pleuritic chest pain, and to allow closer observation. Contrast-enhanced CT of the chest performed later showed multiple small nodules consistent with pulmonary septic emboli.

Lemierre syndrome (LS) is characterized by an oropharyngeal infection that is followed by jugular vein thrombophlebitis and subsequent metastatic emboli. LS was first described by Courmont and Cade in 19002 but, in 1936, was named after the French physician Andre Lemierre, who reviewed 20 cases of the syndrome3—of which eight had a fatal outcome seven to 15 days after onset of symptoms.

The oropharynx is the primary site of infection in most cases of LS, although parotitis, otitis media, mastoiditis, sinusitis, and odontogenic infection have all been implicated as underlying sources of the infection.LS is most often caused by Fusobacterium necrophorum, a member of the normal flora of the oral cavity and, to a lesser extent, of the gastrointestinal tract and the female genital tract. (A pathogen was not isolated in this case, most likely because initial blood cultures were not inoculated in an anaerobic bottle.) F necrophorum is an obligate anaerobic, gram-negative bacillus that can become invasive in previously healthy adolescents and young adults. Virulence is attributed to production of lipopolysaccharide endotoxin and exotoxins, such as leukocidin, hemolysin, lipase, and cytoplasmic toxin. Other pathogens are also implicated in LS: species of Streptococcus, Bacteroides, and Peptostreptococcus, and Eikenella corrodens.

Why does F necrophorum become invasive in some healthy persons and lead to LS, as it did in your patient? The reason is unclear, but alteration of the oropharyngeal mucosa during prior viral infection may be a major factor. Signs and symptoms of LS are a consequence of infection of the parapharyngeal space, which is divided by the styloid process into anterior muscular and posterior neurovascular compartments. Involvement of the anterior compartment results in neck pain and swelling below the angle of the mandible (as seen in your patient), trismus, and dysphagia. Infection of the posterior compartment at the location of the internal jugular vein causes complications, such as thrombophlebitis and severe sepsis with metastatic emboli, most often to the lungs.

Other possible sites of embolic disease include the liver; joints, leading to septic arthritis and osteomyelitis; bone marrow, causing infarcts and pancytopenia; kidneys, leading to transient hematuria and an elevated serum creatinine level; and, seldom, the brain, resulting in meningitis. Pyomyositis, hepatosplenomegaly with abscess and a slightly elevated level of liver enzymes, and mild hyperbilirubinemia as a result of a direct toxic effect on the hepatobiliary system have all been described in conjunction with LS.

How would you suspect this diagnosis the next time around? Think of LS in a febrile adolescent who has non-improving pharyngeal pain or a biphasic course. You'd make a tentative diagnosis of LS on clinical grounds—recall this patient's presenting complaints of fever, neck and abdominal pain, jaundice, and chills—and order a contrast-enhanced CT scan of the neck, chest radiograph, and blood cultures in aerobic and anaerobic bottles. F necrophorum can sometimes be cultured from the metastatic site of infection.

Doppler ultrasound is the most commonly used—and the preferred—modality for evaluating internal jugular vein thrombosis because it is less expensive and less invasive than imaging studies. Some experts assert that contrast-enhanced CT is the imaging method of choice because of its superior sensitivity. Still others recommend magnetic resonance imaging for evaluating internal jugular vein thrombosis, calling it superior to other diagnostic modalities because it is even more sensitive and provides soft-tissue contrast without contrast or radiation. Metastatic infection can be diagnosed with a chest radiograph to document pulmonary septic emboli and with abdominal ultrasonography or high-resolution CT (or both) to look for hepatic or splenic involvement.

The primary treatment of LS is antibiotics. Although all isolates in a recent report from Wisconsin were ? lactamase-negative, resistance is often reported, and most experts recommend ? lactamase-resistant antibiotics with anaerobic activity. Appropriate choices are: clindamycin, ?-lactam and ?-lactamase combinations (ticarcillin-clavulanate, ampicillin-sulbactam), metronidazole, and a carbapenem.

Some authorities recommend anticoagulation when septic emboli do not resolve with antibiotic therapy, or when evidence exists of internal jugular vein thrombi propagating to the cavernous sinus, or both. The duration of anticoagulation is generally no longer than three months. Other potentially appropriate treatments include surgical drainage of soft-tissue abscesses and suppurative fluid collections and surgical ligation of the internal jugular vein when septic emboli persist despite appropriate antibiotic treatment.

As for this patient, he was discharged on oral clindamycin to complete a six-week course of antibiotics. He was also started on IV heparin and discharged on oral warfarin for a total of three months because of persistent small lung opacities that were presumed to be sterile resolving emboli. The boy recovered completely and was weaned from warfarin without sequelae.

Lemierre syndrome had become uncommon in the antibiotic era. Yet an increase in its incidence has been noted in recent years—perhaps as the use of antibiotics to treat nonstreptococcal pharyngitis has declined. We generally think of throat and neck pain in an adolescent as harmless—mais attention! LS remains a possible complication—and a rapidly progressive and potentially lethal one at that!

All in her head? Intermittent headache and vomiting in a 12-year-old

By Alyssa Harrison, MD

This 12-year-old girl is a rare visitor to your office. But today she's here, accompanied by her mother, with a complaint of headache and vomiting. The symptoms developed two weeks earlier, she reports, and have occurred intermittently since. Pain is localized to the occipital region but is occasionally bilateral frontal, occurs more often in the afternoon, and persists severely for five to 15 minutes and then dully thereafter. She doesn't complain of photophobia but does describe halos around objects, and tells you that colors "look weird" during headaches.

The patient had three episodes of vomiting on one day when the headache was present, two episodes on another. The vomiting was not self-induced, she insists, and was not associated with abdominal pain. She has not been awakened during the night or early morning by headache or vomiting; in fact, she reports, sleep relieves the headaches.

The girl cannot identify any triggers for the headaches, although her mother confesses to significant—but unspecified—family stress. Acetaminophen, the only medication that the girl takes, does not provide relief. She reports having had her first menstrual period two months earlier but not having one since.

The girl's medical history is vague. The mother recounts evaluation for rapid head growth in infancy, including a computed tomographic (CT) scan of the brain. There was a question of hydrocephalus at the time, but she was never treated surgically; the family was eventually reassured that follow-up was unnecessary. You perform a quick check of her head circumference: it's at the 98th percentile.

The family history reveals some interesting, perhaps relevant, information. Her mother has a history of migraine headache since 17 years of age, although symptoms subsided as she grew older. The mother's second pregnancy was complicated by birth defects, including hydrocephalus, and resulted in spontaneous abortion. The girl's father had congenital hydrocephalus that required placement of a shunt.

The physical examination shows you a well-appearing teenaged girl. Vital signs are normal, as is her general exam. No focal neurologic abnormalities are detected, and fundi show sharp disk margins.
Proceeding lacking clear direction

You consider the need for further work-up. Certainly, headache is a common complaint in children and adolescents, but rarely one that signals serious disease; clinical laboratory testing, electroencephalography, and brain imaging are usually uninformative. Are there features in this patient that prompt specific concerns? The visual aura, vomiting, and family history in the mother support classic migraine headache, although the occipital location and short duration are less typical. Recent stress could be the trigger for migraine or tension headache. You are most concerned about headache caused by intracranial pathology, however. It is reassuring to note that her headaches are marked by afternoon (as opposed to early morning) onset, that she has symptom-free intervals, and that the neurologic and funduscopic exams are normal.

Still, her uncertain history and strong family history of hydrocephalus create lingering doubt. Could macrocephaly in infancy be related to her current symptoms? You decide that brain imaging is indicated and order a CT scan of the head.

The patient and her mother—and you—are relieved to learn that the cranial CT is unremarkable. Confident that the headaches must be related to recent stress, they decline a trial of antimigraine medication. They agree to keep a headache diary and to return for follow-up in one month.
Two heads may not be better than one

At the next visit, you detect significant discrepancy between the history provided by the patient and her mother's account of her illness. Having failed to maintain a headache diary, the girl can only report that the headaches continue at a rate of least three times a week. Her mother disagrees: They're much less frequent. The patient insists that the pain is still severe (she rates most headaches at 8, on a scale of 1 to 10). General features of the headache are unchanged, although vomiting has completely resolved. But her mother disputes her, again, on the intensity of the headaches; she says she is sympathetic to her daughter's situation but is concerned that the girl is seeking secondary gain with her ongoing complaint. The mother's perception is that the headaches aren't incapacitating, occur at school only very rarely, and may allow her daughter to "escape" some of the conflict at home. You discuss this possibility further with mother and daughter, and all agree that counseling, with attention to stress management, should be initiated as soon as possible.
Milking the history

A long time passes before you see this patient again. She fails to keep several appointments. In a telephone conversation with you, her mother attributes the missed appointments to continued family stressors but reports that her daughter has generally been well.

Fifteen months later, the girl returns for a routine physical examination. Review of the time since her last visit reveals that the headaches have continued but are more easily tolerated. She does, however, have a new concern: Her first menses—reported longer than one year ago now—was the only one she experienced. She recalls that the vaginal blood flow on that occasion was scant and lasted only two days. She admits that she just assumed that her body "wasn't ready" to start menstruation, but now wonders aloud to you whether such a pattern—really, no pattern at all—is normal.

Breast development began more than three years ago; breasts and pubic hair are now Tanner stage IV. Growth has decelerated slightly (her height is at the 50th percentile for age) and weight has been steady at the 95th percentile. She has no complaint of hirsutism, acne, or galactorrhea. She denies cyclic abdominal pain, cold intolerance, constipation, change in skin or hair texture, decreased energy level, sexual activity, and taking medications or using illicit drugs or alcohol. She has pursued interscholastic sports, but not seriously.

She has no appreciable hirsutism, acne, striae, or acanthosis nigricans. Inspection of the external genitalia shows a normal vulva without clitoromegaly. A digital pelvic exam confirms a patent vaginal canal and palpable cervix. The only other change she notes is difficulty with vision during the past year. Indeed, although a prior vision screening examination yielded 20/20 acuity, her best effort at this visit demonstrates 20/100 acuity. Visual fields by confrontation seem normal.

The history of amenorrhea in this well-developed girl intrigues you, and you conclude that it deserves attention. A single episode of menses suggests normal anatomy, and you ponder the differential diagnosis of secondary amenorrhea. Is this symptom independent of her earlier complaint of headache, or is it related—somehow?
Down into the cellar for a diagnosis

You order tests of thyroid-stimulating hormone (TSH), luteinizing hormone, follicle-stimulating hormone (FSH), prolactin, dehydroepiandrosterone, and testosterone. TSH, gonadotropin, and testosterone levels are normal, but the prolactin level returns markedly elevated at 183 ng/mL (normal, 2.8 to 29.2 ng/mL). Dehydroepiandrosterone is also elevated at 14.8 ng/mL (normal, 1.5 to 7 ng/mL).

Magnetic resonance imaging (MRI) of the brain confirms your suspicion. A mass 0.8 x 1.2 cm is visualized within the left pituitary fossa. It does not appear to impinge on the optic chiasm, but does displace the left internal carotid artery and cavernous sinus. Reproductive endocrinologic and neurosurgical consultations are obtained and treatment for prolactinoma is initiated.

A prolactinoma is a benign tumor of the pituitary gland that leads to hypersecretion of the hormone prolactin. The tumor is rare in children compared to its prevalence among adults, although pituitary tumors do constitute approximately 2.7% of supratentorial tumors of childhood. In younger age groups, adrenocorticotropic hormone-secreting tumors are the most common pituitary adenomas, whereas prolactinoma predominates by adolescence.Girls are affected more often—by a ratio as high as 4.5:1—although prolactinomas are usually larger in boys by the time they are identified.

In addition to its lactogenic effect, prolactin may affect the hypothalamic-pituitary-gonadal axis. Presenting symptoms of prolactinoma reflect hyperprolactinemia or mass effect, and often include headache, arrested growth, and delayed puberty. In girls, amenorrhea or galactorrhea may be the initial complaint; boys may rarely demonstrate gynecomastia. Enlargement of the pituitary may cause compression of the optic chiasm, resulting in visual disturbances such as bitemporal hemianopia (tunnel vision).

Under normal circumstances, prolactin is secreted episodically from the pituitary gland and regulated by chronic dopamine inhibition, yielding a serum concentration of 1 to 20 ng/mL. Many physiologic and pathologic factors affect secretion of prolactin; stress, exercise, routine breast examination, a number of medications (phenothiazines, benzodiazepines, cimetidine, and metoclopramide, for example), and illicit drugs may cause a modest elevation. Hormonal changes of pregnancy, hypothyroidism, and polycystic ovary syndrome can also cause hyperprolactinemia. These clinical scenarios typically elevate the prolactin level to 30 to 100 ng/mL. Concomitant rise in dehydroepiandrosterone may occur as a result of prolactin receptors in the adrenal gland. A prolactin level >100 ng/mL suggests a prolactin-secreting tumor and should be further explored by brain imaging.

Because routine head CT may provide suboptimal images of the sellar region or lack the sensitivity to detect very small lesions, pituitary pathology is best defined by MRI. Once a prolactinoma is delineated radiologically, it is classified on the basis of its size as a microadenoma (<1 cm in diameter) or a macroadenoma (>1 cm). Size often correlates with the degree of hyperprolactinemia and may influence the approach to management.

Both microadenomas and macroadenomas must be treated if symptoms are to be relieved, normal menstrual cycles and fertility restored, and the patient protected from further complications. Because a microadenoma does not necessarily progress to a macroadenoma, the decision to treat is based on the clinical scenario. Direct extension of a macroadenoma poses an ongoing risk of loss of vision, destruction of the pituitary, and hypopituitarism—mandating more urgent need for treatment. In addition, most adolescents with a prolactinoma are estrogen-deficient and therefore suffer significant bone loss if not treated.

Dopamine agonist therapy has replaced surgery as the mainstay of treatment for adolescents with prolactinoma. Bromocriptine, once daily, or cabergoline, twice weekly, decreases the level of circulating prolactin, ultimately shrinking the tumor in most patients. Common side effects—including headache, nausea, and dizziness secondary to postural hypotension—are less likely when using newer, long-acting formulations of these drugs. Duration of therapy depends on the patient's response, although few prolactinomas are self-limited. Despite the striking reduction in the size of the tumor prompted by medication, it is never eliminated and lifelong pharmacotherapy is often required to sustain remission.

When a prolactinoma is refractory to medical management or a patient cannot tolerate dopamine agonist medications, then trans-sphenoidal surgery or, more rarely, radiation therapy may be required. These alternatives are avoided as first-line interventions because they carry a high risk of severe complications, especially in cases of macroadenoma.

It is essential to provide long-term follow-up for patients with prolactinoma. Routine monitoring of clinical status, measurement of the prolactin level, examination for visual field changes, and observation of the appearance of the tumor with MRI should be performed every three to six months during the initial phase of therapy. Especially close surveillance is needed during pregnancy and in the peripartum period. Dopamine agonist therapy is discontinued upon recognition of pregnancy, thereby increasing the risk that a macroadenoma will expand and related complications will develop.

Pituitary adenomas, including prolactinomas, are rarely fatal, but associated endocrinopathy may exert a profound effect on the patient's quality of life. Early evaluation and intervention are necessary to prevent permanent consequences of unrestrained tumor growth, especially during vulnerable periods of rapid sexual and skeletal development.

Pediatricians, and parents, often attribute headache to psychosocial stressors, particularly in adolescents, based on a consistent history and physical exam. This may often be true, but these patients should nevertheless be followed carefully for evolving symptoms or clinical changes that suggest an alternative cause. Before you conclude that the problem is all in the patient's head, consider this: It just might be.

Здесь любопытна еще информация по ДЭАС и пролактину- пролактин рассматривается как один из потенциальных стимуляторов продукции стероидов - и как блокатор 5- альфа редуктазы. Поэтому как увеличение ДЭАС, так и отсутствие при этом существенных изменений оволосения- клинически банальная ситуация. В целом пролактиномы как причина первичной аменореи при наличии телархе и пубархе должны четко осознаваться практическими врачами.Очень хороший пример, спасибо.

Asymptomatic Inflammatory Bowel Disease Presenting With Mucocutaneous Findings
Sheila S. Galbraith et al.

Abbreviations: IBD, inflammatory bowel disease • 6-MP, 6-mercaptopurine • ESR, erythrocyte sedimentation rate

Inflammatory bowel disease (IBD) is a group of gastrointestinal disorders characterized by relapsing and remitting signs and symptoms. Intestinal manifestations such as abdominal pain, diarrhea, fever, weight loss, and extraintestinal manifestations including mucocutaneous lesions, iritis, and arthritis may be associated with IBD. Mucocutaneous lesions are relatively common during the course of IBD. Less commonly, however, they can be a presenting finding, thereby alerting the clinician to the diagnosis of IBD before the onset of gastrointestinal symptoms. We describe 9 children from 2 medical institutions in whom mucocutaneous lesions preceded abdominal manifestations and led to an early diagnosis of IBD.

Patient 1
A 6-year-old white boy presented with a 5-month history of intermittent upper-lip swelling associated with eczematous skin changes and gingival edema (Fig 1). Over the subsequent 3 years, he developed worsening of the upper-lip swelling as well as angular cheilitis and lower-lip involvement (Fig 2). He denied any systemic symptoms including facial paralysis, abdominal pain, and diarrhea. A biopsy specimen from the oral mucosa showed a hyperplastic mucosa with spongiosis and a dense lymphocytic infiltrate with small granulomas in the submucosa. Patch tests, complete blood count, tuberculosis skin tests, chest radiograph, and pulmonary function tests were within normal limits.
A repeat biopsy was planned because of lack of improvement with several therapies including topical steroids, antihistamines, amoxicillin-clavulanate, and minocycline for presumed Melkersson-Rosenthal syndrome. On returning to the clinic for biopsy, his mother mentioned a perianal pustule that had been present for some time. Given this new information, the oral biopsy was not performed; he instead was referred to a gastroenterologist. The patient was found to have microcytic anemia (hemoglobin: 11.1 g/dL; mean corpuscular volume: 75 fL) and hypoalbuminemia (3.3 g/dL) at that time. Esophagogastroduodenoscopy was unremarkable; however, patchy erythema, erosions, and pseudopolyps were seen during colonoscopy. Biopsies from the colon showed gastritis, terminal ileum granulomas, and granulomatous colitis, confirming the diagnosis of Crohn's disease.

The perianal lesion proved to be a fistula, and 6-mercaptopurine (6-MP) was started. Metronidazole was added intermittently to treat the fistula further. There was mild improvement of the granulomatous cheilitis; however, the fistula remained patent. Infliximab was started, with complete resolution of the oral lesions, closure of the fistula, and normalization of laboratory abnormalities after 3 infusions. He is in clinical and biochemical remission without intestinal or extraintestinal manifestations while maintained on scheduled 8- to 10-week-interval infliximab therapy.

Patient 2
An 8-year-old white boy had a 2-year history of recurrent oral ulcerations with hyperplastic ridges in the inferior gingival sulcus bilaterally (Fig 3). He denied any gastrointestinal symptoms. A previous oral biopsy was reviewed and showed a small granuloma in the submucosa. He also had a history of perianal skin tags and fissures. Gastrointestinal evaluation revealed esophagitis, gastritis, and multiple aphthous ulcers in the sigmoid colon. Biopsy specimens showed esophagitis with granulomas and granulomatous colitis consistent with Crohn's disease. Work-up subsequently revealed hypoalbuminemia (3.2 g/dL) and an elevated erythrocyte sedimentation rate (ESR) (32 mm/hour). Monotherapy with 6-MP resulted in resolution of his oral ulcers.
Patient 3
A 12-year-old obese white boy (body mass index: 97th percentile) presented with a 6-month history of an erythematous plaque on his right lower extremity that more recently had become warm to the touch, tender, and ulcerated with indurated violaceous borders (Fig 4). The patient denied any trauma to the area. Two biopsies performed elsewhere were consistent with folliculitis, and the patient had been treated with Augmentin and topical antibiotics with no improvement. Repeat biopsy showed suppurative folliculitis which, along with the typical clinical presentation, was consistent with pyoderma gangrenosum. Fungal culture and acid-fast bacillus stains were negative. His ESR was slightly elevated (14 mm/hour). The patient denied any gastrointestinal complaints, but upper and lower endoscopy showed multiple ulcerations in the gastric antrum and ileum. Biopsy specimens showed gastritis, ileitis, and crypt destruction with giant-cell reaction in the colon consistent with Crohn's disease. He initially received intralesional corticosteroids for the pyoderma gangrenosum; however, after the diagnosis of Crohn's disease was made, infliximab and methotrexate were initiated, which led to almost complete resolution of the pyoderma gangrenosum.

In our series of children with silent IBD, mucocutaneous lesions appeared before gastrointestinal signs as the manifestation of Crohn's disease (8 of 9) or ulcerative colitis (1 of 9). (Table 1 provides a summary of these cases.) Of the 9 patients, 8 were male, and the mean age was 8 years. Although patients with IBD tend not to be overweight, 2 of our patients were obese (patients 3 and 8). Six children presented with oral manifestations, 1 had genital lesions, and 2 had pyoderma gangrenosum. All patients were asked about gastrointestinal symptoms, fever, weight loss, and joint pain at presentation and denied any such symptoms. The majority of our patients (7 of 9) had perianal lesions at presentation; however, several of the perianal lesions were not discovered on initial evaluation but only became apparent during subsequent examinations. The time to diagnosis of IBD after development of the mucocutaneous findings ranged from 1 month to 42 months. In general, patients with oral and perianal lesions experienced a longer time until diagnosis compared with patients with lesions that presented elsewhere. One patient (patient 8) was diagnosed with Crohn's disease on repeat endoscopy after the initial endoscopy that was performed 1.5 years prior was normal. In all patients followed after instituting therapy, the mucocutaneous lesions responded to therapy for their IBD.

Although IBD typically presents with gastrointestinal complaints, mucocutaneous lesions have been reported to occur in 15% to 44% of cases and, when present, can precede gastrointestinal symptoms.1,2,3,4 Gregory and Ho5 reviewed the mucocutaneous lesions of IBD and divided them into specific, reactive, and miscellaneous categories (Table 2).

Although uncommon in children, pyoderma gangrenosum is a common mucocutaneous feature of IBD. Typically, the early papulopustules or hemorrhagic bullae rapidly enlarge, become necrotic, and ulcerate. The ulcerations have a characteristic violaceous, undermined border (Fig 4). Lesions can occur on any part of the body but are most frequently located on the lower extremities. Pyoderma gangrenosum is characterized by pathergy (predilection for lesions in areas of trauma); thus, aggressive debridement must be avoided. Twenty percent of adult patients with pyoderma gangrenosum will have associated IBD.6 It is associated more commonly with ulcerative colitis than Crohn's disease, occurring in 5% to 12% and 1% to 2% of patients, respectively.3,5,7 Pyoderma gangrenosum is uncommon in children, with 4% of cases reported in children <15 years old.8 Although IBD is the most common underlying cause of pyoderma gangrenosum in children, pyoderma gangrenosum in children can be associated with several other systemic disorders including immunodeficiencies (primary and HIV related), leukemia, hepatitis, and arthritis.9,10 The occurrence of pyoderma gangrenosum preceding gastrointestinal symptoms in IBD has only been described in a few patients.6,8,11

Perianal lesions including skin tags, fistulas, fissures, and abscesses are characteristic of Crohn's disease and occur during the course of IBD in 60% to 82% of patients; however, 25% to 30% of patients show perianal lesions before gastrointestinal complaints.12,13 The majority of our patients with Crohn's disease (6 of 8), as well as our 1 patient with ulcerative colitis, were noted to have perianal lesions before gastrointestinal symptoms. It is interesting to note that the 2 patients with Crohn's disease who did not have perianal lesions had pyoderma gangrenosum as their initial finding. Of the patients with perianal lesions, in only 2 (patients 8 and 9) was the perianal lesion the presenting complaint. This suggests that perianal lesions may often be present before gastrointestinal complaints but are less often brought to the attention of the physician, especially in adolescent boys.

Although not as well documented, oral lesions associated with IBD are relatively common, occurring in 6% to 20% of patients.14 When present, they are the presenting sign/symptom in approximately one half of cases.1,4,15–1617 In addition, more recent reviews have found an increased prevalence of various oral lesions in IBD, particularly in children. Barnard and Walker-Smith found that 80% of pediatric patients with Crohn's disease and 41% of children with ulcerative colitis had oral lesions in their series of patients.18 In reviews by Pittock et al19 and Plauth et al,4 48% and 66% of patients with Crohn's disease, respectively, were found to have oral manifestations, with an increased prevalence in children.

A variety of specific and nonspecific oral lesions can occur (Table 3). Differences in the percentage of patients with IBD described with oral lesions may relate to specific versus nonspecific oral findings reported. Aphthous ulcers are considered by many to be nonspecific, as they can be seen in up to 20% of the general population; however, aphthae are usually more extensive and persistent when associated with IBD.15 The descriptive term "orofacial granulomatosis" has been used for any granulomatous process of unknown etiology involving the oral cavity,16 which includes disorders previously described as granulomatous cheilitis and partial Melkersson-Rosenthal syndrome. Orofacial granulomatosis is a common manifestation in children with IBD and is typified by recurrent or persistent swelling of the lips, cheeks, gingiva, or oral mucosa with characteristic noncaseating granulomas on histologic examination. Many patients with orofacial granulomatosis do eventually develop gastrointestinal disease consistent with Crohn's disease.20,21 "Cobblestoning" refers to nodular granulomatous swellings that result in a cobblestone appearance of the oral mucosa, particularly on the labial and buccal mucosa. Along with mucosal tags, cobblestoning is highly suggestive of Crohn's disease. Pyostomatitis vegetans, on the other hand, is more characteristic of ulcerative colitis. It is characterized by multiple pustules, erosions, and ulcers on a diffuse erythematous background with vegetations or folding of the gingival and buccal mucosa. Deep, linear ulcers surmounted by hyperplastic folds occur in the gingival sulci and are also specific for IBD.

Genital findings associated with IBD are also more common in Crohn's disease and in children.1 Genital involvement includes vulvar swelling, skin tags, pustules, abscesses, fistulas, fissures, ulcerations, and vaginal discharge.22 Penile and scrotal lesions are less common and include subcoronal ulcers as well as penile and scrotal edema.23 Twenty-five percent of genital Crohn's disease presents before gastrointestinal complaints.1

Although there are few cases reported in the pediatric literature, mucocutaneous lesions presenting as the initial sign of IBD is relatively common and can be an important clue in making the diagnosis of IBD before the development of gastrointestinal symptoms. We have identified 9 pediatric patients with asymptomatic IBD presenting with mucocutaneous lesions. The majority of these patients had oral and/or perianal lesions. Because oral disease, in general, is uncommon in children, we believe that IBD is a common etiology for persistent oral lesions in the pediatric population. Children and adolescents with unexplained oral mucous membrane lesions such as lip/mucosal swelling, gingival hyperplasia, cobblestoning of the oral mucosa, or deep linear ulcerations should have a good history taken regarding gastrointestinal symptoms, fever, and weight loss as well as an examination of the rectal and genital mucosa to seek other mucocutaneous clues of IBD that may not be mentioned to the physician. We would also recommend additional work-up including complete blood count, iron levels, ESR, albumin, occult blood in the stool, and serial endoscopies with biopsies to aid in the diagnosis if suspicions are high.
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К сожалению, для таблиц и фотографии нет места.

"The time is out of joint": Pain, paresthesias, and weakness in a preadolescent

Your patient is a 10-year-old Latino girl brought to the clinic by her very concerned mother. The complaint is leg and joint pain—severe enough to make walking difficult. The visit comes after your colleague at the clinic saw the girl about a month ago for an unusual rash described in the record as a brownish, linear, papular eruption, possibly urticaria pigmentosa. He prescribed hydroxyzine.

Three weeks later, you read, your colleague saw the girl again, this time for a complaint of pain in the left wrist, symptoms of a common cold, and a barky cough of approximately two weeks' duration. She complained that she was feeling generally tired. He prescribed azithromycin for suspected Mycoplasma infection. Examination of the hands and arms was unremarkable. He instructed the mother to watch for joint swelling.

QD: Pain and a long nap

Now, five days after that last visit, the patient has returned with pain in the back, legs, and small joints of the fingers. Walking is difficult, she tells you. There is still a slight cough. She does not have a fever and does not complain of a sore throat or ocular or urinary symptoms. There is no nausea, vomiting, diarrhea, or constipation.

The girl denies weight loss or diminished appetite. She does complain of generalized fatigue and increased sleepiness: She takes a three-hour nap every day after school! You begin by taking the history.

Your patient is in the fourth grade and, her mother reports, is a good student. She lives with her mother and a younger, school-age brother. Her parents have been separated for about nine months; the father is involved in his children's life on an almost daily basis, the mother reports. She denies a history of domestic violence in the family.

The medical history is noncontributory. The girl was delivered at term. She has no history of hospitalization, surgery, or serious illness; has been fully immunized; and does not have known drug allergies. Hydroxyzine and azithromycin are her only medications over the past several months. She has had no recent exposure to ticks, has not been camping, and has not traveled recently. She has had no recent illnesses other than "colds" and "coughs" and no gastrointestinal problems.

The family history is positive for osteoarthritis on the maternal side, and a maternal grandmother who has rheumatoid arthritis.

On physical examination, your general impression is of a well-nourished, well-developed, slightly obese girl who is not in acute distress. The earlier rash over the left forearm is barely noticeable.

Height is at the 50th percentile for age; weight, between the 75th and 90th percentiles. Vital signs are unremarkable: Blood pressure, 107/59 mm Hg; pulse, 69/min; temperature, 97.3°F; and respiratory rate, 22/min. The ear, nose, and throat exam is benign. Oral mucosa is moist and without lesions. There is no conjunctival injection. Bilateral red reflexes are clear. Heart sounds are normal; no heart murmur is heard. Breath sounds are clear. The abdomen is soft and nontender; bowel sounds are present; and you do not palpate any masses or hepatosplenomegaly.

The genitalia are normal and Tanner Stage I. You note no cervical, axillary, or inguinal lymphadenopathy. The neck is supple without thyromegaly.

The patient expresses pain in the metacarpophalangeal and interphalangeal joints of both hands and describes pain in almost all other joints—neck, spine, and large and small joints of the extremities, including shoulders, hips, elbows, and knees. On thorough examination of those joints, you cannot detect swelling, erythema, effusion, or increased warmth over the skin—the tenderness she expresses over the metacarpophalangeal and interphalangeal joints by palpation notwithstanding. The pain is elicited in all small finger joints by passive motion, by wrist movements, and by examination of the large joints of the lower extremities, including knees and hips. She appears to have hyperflexible finger joints. Gait is guarded but there is full range of motion in all joints.

Much pain, no findings

You know that joint complaints are common in children and, in most cases, transient. Arthritis, defined as swelling of a joint or limitation of motion accompanied by heat, pain and tenderness, is much less common than arthralgia (simple joint pain). Disorders of periarticular inflammation may mimic arthritis.


Causes of arthritis and periarticular disorders

A number of thoughts come to mind about the differential diagnosis (see the table - не включена, Алон) in this patient—thoughts that are confounded by the constellation of symptoms. Could this be juvenile rheumatoid arthritis? Should you consider connective tissue disease, such as systemic lupus erythematosus (SLE)? Lack of a true arthritis or systemic or constitutional symptoms (other than the fatigue), plus the absence of fever, however, cast doubt on these possibilities.

What about inflammatory bowel disease, which can present with arthritis? Even if swelling of a joint were documented, it would likely affect only a few large joints—not all joints of the body.

Chronic active hepatitis can present with arthralgia, confined to single joints, but often several joints are involved, usually the large ones.

A migratory polyarthritis may be seen in mycoplasmal infection; this is an interesting possibility, considering that the girl has had a cough and a urticarial rash, although an atypical one.

What about Sch?nlein-Henoch purpura? The rash associated with this vasculitis of unknown cause—purpuric, petechial, or, occasionally, urticarial—is characteristic and most prominent on the lower extremities, although it sometimes occurs on the arms and face, and rarely, on the trunk. Arthralgias, with periarticular swelling involving a few joints, occur in approximately 40% of cases. Abdominal pain, nephritis, hypertension, and unusual areas of edema are common. Your patient's mother insists that she has noted intermittent swelling of her daughter's hands and feet, but you cannot appreciate this or other symptoms of Sch?nlein-Henoch purpura.

Hypermobility syndrome? Alone, this is not likely to affect all joints of the body at the same time.

Hypersensitivity arthritis—so-called serum sickness—caused by a drug or virus and accompanied by joint swelling, is a possibility. The condition can also be associated with edema of the hands and feet and urticarial rash.

Reactive arthritis after pharyngitis or gastrointestinal infection crosses your mind. This can involve single or multiple joints, and can be migratory. Other than the cold that the mother reported early this month, the girl has not had a sore throat or any GI problems.

Your diagnosis, for now, is generalized arthralgia, possibly postviral or of other infectious cause. You turn to basic laboratory work: complete blood count, erythrocyte sedimentation rate, C-reactive protein, comprehensive metabolic profile, urinalysis, antinuclear antibody titers, rheumatoid factor, anti-streptolysin O titer, and parvovirus titers. You also order radiographs of the hands and both hips.

You advise ibuprofen for pain and recommend follow-up in one week.

Most of the lab results arrive on a Friday afternoon. Other than an elevated anti-streptolysin O (ASO) titer of 718 and a positive antinuclear antibody (ANA) titer of 1:160 in a speckled pattern, the tests are normal, including an ESR of 12 mm/hr and C-reactive protein <0.4 mg/L. Some nitrates are noted on urinalysis. The metabolic profile shows that liver function is normal; only the CO2 is slightly low at 18.6 mEq/L. All films are read as normal by the radiologist.

In light of the elevated ASO titer, you elect to treat the girl with a 10-day course of amoxicillin—lack of evidence of poststreptococcal arthritis notwithstanding. When you call the mother with results, she reports that the girl's pain is intensifying, and you also prescribe acetaminophen with codeine for relief over the weekend.

"Born to set it right"?

Your patient returns to the clinic on Monday. She is now unable to walk well without assistance and is brought into your office in a wheelchair! She complains of dizziness, and tells you that she has had "a hard time breathing" and that "it hurts to cough."

Such an abrupt change in mobility is of major concern. You consider other explanations. Is the pain of muscular origin—myalgias or myositis? Perhaps this is dermatomyositis or scleroderma—given the history of an unusual linear-looking rash and pain on palpation over the extremities.

As for the cough and, now, shortness of breath, and the increasing weakness of the extremities and truncal musculature, you wonder: Is this true weakness or pain-induced? The mother reports that the patient is unable to sleep supine and has to be propped up in bed. You do not elicit any new findings on the physical exam—no joint swelling or erythema of the skin—but she is complaining of pain in all joints upon even minimal movement, to the point that it is difficult to examine passive range of motion without causing excruciating pain. She can move her legs but minimally; arm movements are limited. She expresses numbness and tingling of the hands. She now complains of intermittent swelling of the hands and feet.

The patient does not complain of dry mouth or difficulty swallowing; likewise, no dry eye or any other ocular symptoms. She does have episodes of shortness of breath and chest pain, particularly at night but also at school today. The school nurse notified the mother about this development, which was the occasion for today's visit. There is no abdominal pain or burning upon urination. No genital ulcers. Mother reports no depression, anxiety, or sleep disturbance.

As for the skin, the patient denies tightness, hair loss, or nodules. She does complain that her skin is pale, cold, and sweaty, and that her hands and feet at times become reddish or livid. Raynaud disorder comes to mind, but she has good peripheral pulses, distal extremities are pink, and skin is warm to the touch. You note two long, narrow, parallel track-like lesions along the lateral aspect of the left forearm, about one centimeter apart and reaching above the left elbow. They are barely palpable and have turned whitish.

Overall, you observe few objective findings. The lungs are clear to auscultation, and she is not in respiratory distress. Breath sounds are equal bilaterally. Heart sounds are not distant; no murmur or friction rub is noted. You have no reason to suspect pleuritis or pericarditis, which might explain the shortness of breath and chest pain. Oxygen saturation is 96% at room air; respiratory rate, 20/min.

You are puzzled—very much so. Because of her pain, you have a difficult time performing the neurologic exam, and find it impossible to assess deep-tendon reflexes. The Babinski sign is absent. Cranial nerves are grossly intact.

Confusion compounded

You order tests of anti-double stranded (DS) DNA, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH); repeat urinalysis and urine culture; and a chest radiograph and electrocardiogram. The chest radiograph shows mild peribronchial thickening. The ECG is normal for age. The CPK level is normal at 55 U/L; LDH is normal at 152 U/L; and the anti-DS DNA is 227 U/mL (positive, >120 U/mL). Urine culture of a clean-catch specimen grows >100,000 gram-negative bacilli. Parvovirus B19 titers come back with no significant level of detectable IgG or IgM antibodies. You suspect SLE now, but can't confine yourself to that diagnosis because of the normal ESR and acute-phase reactant levels.

You decide to refer your patient to a rheumatologist within the larger network of a children's hospital. There, your patient spends four days as an inpatient in a general pediatric ward. Lab tests are repeated; the ANA and anti-DS DNA tests are normal. That's somewhat of a surprise: The specificity of the ANA test is low enough to be elevated even in a healthy person or by transient causes. Considering the initial titer of the anti DS-DNA and the context of the case overall, you conclude that the ANA result is most likely laboratory error.

Other lab results arrive: The ASO titer is 800 IU/mL (normal, <200 IU/mL), and the LDH is 504 U/L—both elevated for age. Urine culture grows Escherichia coli, and the patient is treated accordingly.

A purified protein derivative test is placed and recorded as 9 mm in diameter—considered positive given that, by the history, there are several possible exposures to tuberculosis, including her great-grandfather, who had been given a diagnosis of drug-resistant tuberculosis earlier in the year. But this is later judged to be a nonsignificant contact because your patient had not been in direct contact with him. A repeat chest radiograph is normal. The girl is referred to the health department of her county of residence for treatment of latent tuberculosis infection with INH prophylaxis.

The rheumatologist's general impression is that the arthralgia is likely viral or postinfectious. She cannot rule out a later-manifesting malignancy, such as leukemia.

During the hospitalization, the patient experiences significant paresthesias and pain—at times so extreme that she cannot tolerate the weight of a bedsheet. An opiate analgesic is prescribed, from which she is weaned before discharge. The judgment of the team is that, throughout her stay and in contrast to her pain, she appears comfortable and happy—raising the question of a somatization disorder. She is able to walk a few steps, with support, during hospitalization but requires a wheelchair at discharge.

Symptoms waxing and waning and still unable to walk more than a few steps, your patient shows up at your office for post-discharge follow-up. No more complaints of difficulty breathing. No pain any longer in the arms. No swelling of joints or rash noted, and no fever. She seems stable and tells you that she doesn't need the anti-inflammatory medications at the moment.

You take a deep breath yourself—a pain-free one.

"O cursed spite!"

To your surprise, the girl returns to see you only five days later, complaining that she "feels worse." Pain has intensified in her arms, hips, and back. She complains of numbness of the legs although there is no loss of bladder or bowel control. She denies headache or blurred or double vision. She cannot walk.

You perform a neurologic exam, but you cannot elicit any clear corresponding objective findings and are at a loss to explain the waxing and waning of symptoms. You begin to think of possible psychosomatic or psychiatric disorders: Neurasthenia? Fibromyalgia? Psychogenic pain as a part of a conversion reaction? You cannot identify stressors in the history other than her parents' separation nine months ago; when questioned, mother and patient deny, for a second time, any domestic violence or significant psychogenic trauma. Could this be a case of atypical Guillain-Barr? syndrome, with paresthesias and hyperesthesias predominant, or a course of the syndrome with a pseudomyopathic picture, with waxing and waning symptoms in this chronic inflammatory neuropathic disorder?

That's not your gut feeling so far into the case, however; something among the pieces just does not fit. You call a colleague who is a neurologist and request consultation. He reviews the case and is most inclined to entertain Guillain-Barr? syndrome rather than vasculitis—especially in light of progressive ascending paresthesias and neuropathic pain. Upon examination, lower-extremity strength is 3/4 of 5. Deep-tendon reflexes are absent and toes are down-going. His plan is to obtain a magnetic resonance imaging scan of the brain and complete spine. He'll also perform electromyography (EMG) and nerve conduction-velocity studies. He decides to start the patient on gabapentin (Neurontin).

Needle EMG cannot be performed because the patient cannot tolerate the test. Nerve conduction-velocity studies are normal, as are all neuroimaging findings. Lumbar puncture is deferred.

The neurologist prescribes water physiotherapy twice a week, which, over the next two weeks, seems to improve the patient's mobility and relieve her pain. She still requires the use of a wheelchair but can move her legs somewhat, and can readily use her arms to push herself around.

Meanwhile, repeat tests of inflammatory markers all return normal. As for cytomegalovirus and Epstein-Barr virus titers, IgG antibodies are detected in low titers for both viruses and IgM antibodies are absent—a combination that makes recent infection unlikely. CMV and EBV titers are not retested.

Can it get worse?

Approximately eight weeks after the onset of her illness, your patient returns to see you. She complains of feeling poorly again. The pain in her arms, legs, and back is worse. She cannot move her right arm and must eat and write with her left hand. She again has experienced difficulty breathing at night. She had been to the neurologist two days earlier for follow-up; he prescribed a course of high-dose steroids for possible vasculitis. However, you recommend to the mother to hold off steroids because there is insufficient diagnostic evidence for vasculitis. Your rheumatology colleague at the children's hospital network agrees with your action. You express suspicion that the team could be dealing with a conversion reaction because no consistent evidence of physical illness has manifested during eight weeks of follow-up. You agree to admit the patient to the hospital again but under the rheumatology service, with neurology and psychiatry services in consultation.

Faced with a two-week wait for inpatient placement for the girl, you conclude that skin biopsy from the chronic rash might be helpful to rule in or out possible vasculitic changes. The biopsy is interpreted as chronic folliculitis with negative immunofluorescence.

You approach the mother about the possibility that her daughter's symptoms are psychological. She finds that difficult to accept, however, and prefers a somatic explanation for her daughter's illness.

Mind, not matter

At the girl's second hospitalization, opinion coalesces that her illness is not rheumatologic, and she is admitted under the neurology service. Investigation reveals total anesthesia below L5, although the balance of the sensory and motor exam is inconsistent with that finding and does not fit any neurologic distribution. Although some features suggest a psychosomatic disorder, chronic inflammatory neuropathy cannot be excluded.1,2

The patient does not appear in distress or concerned during the investigation, and again seems content and calm. She is easily suggestible. Once provided with stepwise recommendations for regaining her health, and sensation and mobility in her extremities, she improves in a short time and is discharged after six days, having made a full recovery.3

The neurology and psychiatry services' conclusion is that her parents' separation has been a significant stressor for the girl—especially because she has a close relationship with her father.4 Notably, approximately one year before the patient exhibited symptoms, her maternal uncle was paralyzed from the neck down in a car crash and is in a wheelchair. How much, you are left to wonder, might this event have unconsciously influenced her symptom "selection"?

Things are set right again

Your patient does well, without relapse, after psychological counseling and pediatric follow-up. At the beginning of a new school year, she is eager to return to the classroom.

This case illustrates the need to suspect a conversion disorder in children when the neurologic or somatic outline is difficult to clarify and all instrumental and clinical laboratory tests do not support a precise pathologic pattern or disease entity. Further exploration of behavioral or emotional problems and other stressors can be the missing key to the diagnosis.
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DR. ESTEP is an assistant professor of pediatrics at Texas Tech University Health Science Center

A 10-month-old boy presents to the ED with a 1-day history of poor feeding and a fluctuating level of consciousness. There has been no fever, vomiting, diarrhea, or cough.

On physical examination, the child looks ill and mottled. His temperature is 101.5°F (38.6°C), heart rate is 180 beats/min, respiratory rate is 60 breaths/min, blood pressure is 70/40 mm Hg, and oxygen saturation is 86% in room air. He requires 10 L of oxygen to maintain his oxygen saturation above 95%. His heart sounds are normal, capillary refill is 3 seconds, and femoral pulses are weak. Both lungs are clear, and the liver is palpable 5 cm below the right costal margin. The remainder of the physical findings are normal.

The patient is given a 20-mL/kg bolus of normal saline intravenously as well as ceftriaxone. The hypotension does not improve. Initial laboratory findings are: WBC count, 66.4x103/mcL (66.4x109/L) (polymorphs 64%, bands 15%, lymphocytes 10%); Hgb, 1.06 g/dL (106 g/L); and platelets, 848x103/mcL (848x109/L). The bedside glucose value is normal. Venous gas measurements include: pH, 7.23; PCO2, 42 mm Hg; bicarbonate, 17 mEq/L (17 mmol/L); and base excess, –9 mmol/L. Serum lactate is 72.1 mg/dL (8.0 mmol/L). A chest radiograph reveals a small left-sided infiltrate, a small pleural effusion, and a normal heart size. ECG shows small voltages, ST segment elevation in leads V2 through V5, and electrical alternans. A diagnostic test is performed.
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Cardiac involvement was suspected on initial assessment when the liver was noted to be enlarged. Furthermore, the child did not respond clinically to the fluid bolus, as would be expected in hypovolemic shock or septic shock without cardiac involvement. The electrocardiographic findings were highly suspicious for cardiac tamponade, and a bedside echocardiogram revealed a large pericardial effusion measuring 3 cm in diameter. Pericardiocentesis yielded 60 mL of purulent pericardial fluid, after which the patient’s blood pressure and perfusion improved almost instantaneously. Subsequent blood and pleural fluid cultures grew Streptococcus pneumoniae.

Differential Diagnosis
This child presented with a fluctuating level of consciousness and was found to be in shock on initial assessment. The differential diagnosis of his clinical picture is broad and includes septic shock, hypovolemic shock, hemorrhagic shock, cardiogenic shock, neurogenic shock, toxic ingestion, and nonaccidental injury. Echocardiography demonstrated the cause of this child’s shock to be cardiac tamponade from a large pericardial effusion.

Acute pericarditis with pericardial effusion in children can be caused by bacterial infection, viral infection, collagen vascular disease (systemic lupus erythematosus), malignancy, metabolic disease, or postpericardiotomy syndrome. In some cases, no cause can be found. Bacterial (purulent) pericarditis in childhood is caused most commonly by Staphylococcus aureus. The next most common pathogens are Neisseria meningitidis, Haemophilus influenzae, and S pneumoniae.

Pathogenesis
Patients who develop bacterial pericarditis are found frequently to have preceding or concurrent infections, including pneumonia, osteomyelitis, meningitis, septic arthritis, pyomyositis, and pyelonephritis. This child had radiographic evidence of pneumonia with a small pleural effusion. Bacteria are believed to invade the pericardium by direct extension from the neighboring pleura or lung or from transmission through the blood from another infected site. In some cases of meningococcal meningitis, an immunologically induced antibody response to the bacterial infection causes inflammation and fluid accumulation within the pericardial space. The discovery of pericarditis several days after the onset of infection and the absence of bacteria in the pleural fluid supports this mechanism.

Clinical Presentation and Diagnosis
Pericardial effusion with tamponade is diagnosed clinically by signs such as tachycardia, hypotension, elevated jugular venous pressure, muffled heart sounds, hepatomegaly, narrow pulse pressure, and pulsus paradoxus (systolic blood pressure during inspiration is lowered markedly). A pericardial friction rub may be present as well, but is less common in larger effusions where the large amount of fluid prevents friction. The presence of an enlarged cardiac shadow on chest radiography is supportive, as are the ECG findings of low voltages, raised ST segments, and when cardiac tamponade is present, electrical alternans. Electrical alternans, defined by the QRS amplitude increasing and decreasing on alternate beats, is caused by the beat-to-beat swinging motion of the heart with large pericardial effusions (Figure). Definitive diagnosis is made by echocardiography, which is safe, rapid, and noninvasive and has a high degree of sensitivity for the detection of pericardial effusion. The hallmark of the echocardiographic diagnosis of pericardial tamponade is diastolic collapse of the atrial and ventricular walls.

Treatment
Bacterial pericarditis is treated with specific antibiotics, which should be selected to target the suspected organism. Associated infection or illness can provide guidance in the selection. Pericardiocentesis is indicated to relieve the symptoms of cardiac tamponade. Rapidly accumulating effusions are more likely to present with symptoms. Pericardiocentesis also is useful for diagnostic purposes; pleural fluid can be sent for cytologic and biochemical analysis as well as culture for bacteria, fungi, and viruses. Except in emergencies, this procedure should be performed by a cardiologist, cardiovascular surgeon, or thoracic surgeon under echocardiographic guidance. Diuretics are contraindicated in the setting of symptomatic cardiac tamponade because the cardiac output is highly dependent on ventricular filling. By the same token, endotracheal intubation and mechanical ventilation can cause an acute decrease in ventricular filling that may lead to sudden cardiac arrest.

Conscious sedation and analgesia are recommended when performing pericardiocentesis. Under aseptic conditions, an 18-gauge needle is attached to a three-way stopcock and a 50-mL syringe. The needle is inserted just under the xiphoid process, directed toward the left shoulder tip, and advanced with constant suction. The heart should be monitored during the procedure, enabling the detection of arrhythmias that may occur when the myocardium is touched. Other techniques have been described in the literature, including subxiphoidal tube drainage and irrigation with thrombolytics, as well as pericardiectomy. Pericardiectomy usually is reserved for patients who have loculated effusions or recurrent pericarditis and are at higher risk for constrictive pericarditis.

Lessons for the Clinician
When a patient presents with clinical signs of shock, the clinician should examine the patient carefully for signs of cardiac tamponade. If clinical signs are present, immediate chest radiography should be performed to determine heart size and an ECG obtained to assess for small voltages, ST segment changes, and electrical alternans. Echocardiography is essential for definitive diagnosis and for facilitating guided pericardiocentesis to relieve cardiac tamponade.


Adam Cheng, MD
Jennifer Russell, MD
The Hospital for Sick Children, Toronto, Ontario, Canada

A 19-month-old girl is brought to the ED because of abdominal pain for the last week, fever for 5 days, and crying on urination together with constipation for 2 days. She had passed several watery stools without mucus or blood prior to the last bowel movement.

On physical examination, the girl appears uncomfortable and mildly dehydrated. Her temperature is 103.1°F (39.5°C), pulse is 148 beats/min, blood pressure is 121/78 mm Hg, and respiratory rate is 28 breaths/min. She has diffuse abdominal tenderness and mild distention without guarding or rebound. Her bowel sounds are normal, and no hepatomegaly or splenomegaly is noted.

The WBC count is 26.8x103/mcL (26.8x109/L), with 77% neutrophils, 5% bands, 13% lymphocytes, and 5% mononuclear cells. Her Hgb is 10.6 g/dL (106 g/L), Hct is 31.3% (0.31), and platelet count is 666x103/mcL (666x109/L). The child has normal serum concentrations of sodium, potassium, chloride, urea nitrogen, creatinine, and glucose. Findings on urinalysis are normal. A radiograph of her abdomen shows dilated loops and fecal material throughout the colon. An imaging test leads to the correct diagnosis.
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Abdominal CT revealed a complex cystic mass involving much of the pelvis. The mass was predominant on the left side but also contiguous with the cecum. This mass represented an abscess that had formed from a ruptured appendix. Evidence of mild hydronephrosis and hydroureter on the left, probably due to the pelvic mass, also was seen. Triple antimicrobial therapy with gentamicin, metronidazole, and ampicillin was initiated and continued for 5 days. Repeat abdominal CT showed a persistent pelvic abscess compressing the rectum. The child underwent transanal drainage of the abscess and was scheduled for elective appendectomy.

Differential Diagnosis
Acute abdominal pain is a common complaint in children. Children, especially young children, are poor at localizing pain to an abdominal quadrant. Therefore, a wide range of possible disorders needs to be considered. The causes of abdominal pain are age-related.

Intussusception occurs typically in infants between approximately 6 months and 2 years of age. The clinical presentation is characterized by attacks of colicky abdominal pain, during which the child draws up the legs, followed by periods of relaxation and sometimes profound somnolence. During the colicky episodes, the child appears pale and returns to having normal color when the pain passes. Currant jelly stools are passed by about 33% of patients and represent mucosal injury. Failure to pass a bowel movement at the usual interval also can occur. On abdominal radiographs, a mass lesion can be seen indenting the colon, with or without signs of bowel obstruction. Plain radiographs also may appear normal in this disorder.

Acute gastroenteritis is the most common diagnosis recorded when appendicitis is missed. The child presents with vomiting, diarrhea, and abdominal pain. The diarrhea may be preceded by severe abdominal pain and abdominal wall rigidity, mimicking acute abdominal inflammation. Bloody stools may cause further confusion because this picture mimics intussusception. Although enteritis due to Yersinia enterocolitica or Y pseudotuberculosis has been named "the great imitator" of appendicitis, affected patients usually have substantial diarrhea.

The symptoms of bowel obstruction include bile-stained vomiting, pain, and abdominal distention, with a paucity or absence of bowel gas distal to the level of the obstruction. In children, the site of the obstruction almost always is in the small bowel. Causes of obstruction include incarceration of a hernia, postoperative adhesive obstruction, malrotation, volvulus, and a Meckel diverticulum causing volvulus or intussusception. Radiologically, the typical pattern of a bowel obstruction is distended loops of bowel proximal to the obstruction, absence of gas distally, and multiple short air-fluid levels, often referred to as a "ladder" pattern.

Appendicitis also can mimic urinary tract infection. Caution must be exercised in interpreting findings on urinalysis because mild pyuria, hematuria, and bacteriuria can be present if an inflamed appendix is located adjacent to a ureter or to the bladder.

Pain may be associated with abdominal masses, with constipation, or less often, with anuria if the mass obstructs the bladder outlet. Imaging is required to identify the originating organ of the mass, to determine its nature (solid or cystic), and in the case of malignant lesions, to aid tumor staging. Ultrasonography usually can identify the organ of origin.

Children who have mesenteric adenitis present with abdominal pain that may be severe, which raises concern about a disorder requiring surgery, especially appendicitis. Often, there is a preceding history of upper respiratory tract infection. There may be recurrent attacks. Abdominal radiographs show normal results. Ultrasonography reveals enlarged (>1 cm) nodes around the root of the mesentery, occasionally with edema of the mesentery.

Signs and symptoms of inflammatory bowel disease include abdominal pain, weight loss, diarrhea, and the passage of bloody stools. Although adolescents and young adults between 15 and 35 years of age are affected most often, the disease has been diagnosed in infants as young as 18 months of age.

Henoch-Sch?nlein purpura (HSP), a common vasculitic disease affecting children between 2 and 8 years old, results in a constellation of findings, including a purpuric rash occurring on the lower extremities, abdominal pain, renal involvement, and arthritis. However, any of the components may be absent, which often leads to confusion in diagnosing the condition. The second most frequent element of HSP is colicky abdominal pain, which occurs in up to 65% of cases and may be severe and associated with vomiting. The pain may mimic that of acute intraperitoneal inflammatory disease.

Incarcerated hernias usually present with irritability from abdominal pain. Otitis, pharyngitis, and upper respiratory tract infections may present with abdominal pain. Right basal pulmonic consolidation can refer pain to the abdomen. Food poisoning and sickle cell pain crisis commonly present with abdominal pain; in these cases, however, a previous history can narrow the search.
The Condition
Appendicitis is the most common abdominal surgical emergency in infants and young children, but rarely is it considered in children younger than 3 years of age.
In young children, the typical history seldom is obtained. Because the disease can progress rapidly and escape detection, the child often presents with pyrexia and poorly localized abdominal pain, frequently with signs of septicemia, peritonitis, and bowel obstruction. If a pelvic abscess already has developed, diarrhea may be the presenting complaint. Children younger than 2 years of age usually have diarrhea as a primary symptom. Children who have a retrocecal appendix may present with right upper quadrant or flank pain. Due to the difficulty in evaluating these young patients who have abdominal pain, the perforation rate is higher (30% to 65%) than in adults. Because the omentum is less developed in children, perforations are less likely to be "walled-off" or localized, leading to generalized peritonitis.
Laboratory Findings
Leukocytosis and an increased concentration of C-reactive protein usually are present. WBCs may be present in the urine and cause confusion by suggesting urinary tract infection. If the clinical and hematologic findings are sufficiently typical, no radiologic investigation need be undertaken
Radiologic Assessment
Positive radiographic findings include the presence of a fecalith in the RIF (in approximately 30% of cases) and a localized ileus with mildly dilated loops of bowel. As sepsis advances, the properitoneal fat line blurs. Free air in the abdomen (pneumoperitoneum) is not a typical feature of a perforated appendix because the inflammatory mass prevents release of the luminal gas. A subphrenic abscess may occur if the sepsis is untreated and is seen as an air-fluid level in the subdiaphragmatic region.
CT of the pelvis and RIF, especially an intravenous contrast-enhanced procedure, with or without colonic contrast, is a useful and sensitive technique for identifying an inflamed appendix. A calcified appendicolith is well demonstrated by CT, as are postoperative fluid or pus collections.
On ultrasonography, the normal appendix appears as a tubular structure with a maximum transverse diameter of 6 mm located in the RIF, with good visualization of all layers of the bowel. The appearance of an abscess depends on the stage of evolution, but an abscess usually appears as an area of mixed solid and fluid echoes in the RIF. When there is rupture and peritonitis, abscess collections may be found in the pelvis or the subhepatic or subphrenic region.
Management
When perforated appendicitis is suspected, preoperative broad-spectrum antibiotic therapy is indicated because of the high morbidity that results from intra-abdominal abscess, peritonitis, and wound infection. Appendectomy is performed with or without drainage of the peritoneal cavity, and antibiotics are continued for 7 to 10 days. Occasionally, a localized abscess is treated with antibiotics with or without open or percutaneous drainage, with appendectomy scheduled as an elective procedure in 4 to 6 weeks. Children who have nonperforated appendicitis require minimal preoperative preparation with intravenous fluids and antibiotics. Although the use of antibiotics in uncomplicated appendicitis is controversial, it has decreased the incidence of postoperative wound infections.

MD
John H. Stroger, Jr
Hospital of Cook County, Chicago, Ill

A 17-year-old Caucasian girl is admitted to the hospital because of pain, swelling, and redness of her left leg for 6 months, with occasional low-grade fevers.

Previously, cellulitis had been diagnosed and antistaphylococcal antibiotics prescribed on more than one occasion, with temporary improvement. Cultures of the cellulitis had yielded Staphylococcus aureus sensitive to all antistaphylococcal antibiotics. CBC, ESR, liver and renal function tests, calcium, phosphorous, antinuclear antibody (ANA), rheumatoid factor (RF), and blood cultures resulted in normal or negative findings. Radiographs of the pelvis, hip, femur, knee, tibia, fibula, ankle, and lumbosacral spine, as well as a venogram and bone scan, were interpreted as normal. Arthrocentesis yielded normal results. Additionally, she had been admitted repeatedly for strict bed rest, elevation of the extremity, and intravenous antibiotics, with no sustained resolution of swelling, redness, or pain.

She had been traveling to various islands of the western Pacific as a member of a soccer team prior to the onset of her symptoms.

Physical findings today are normal, with the exception of redness, pain, and warmth over the left calf and anterior portion of the lower left leg, with pitting edema involving the calf, pretibial region, ankle, foot, and knee area, although results of the knee examination are normal. Pulses and strength are normal.
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This patient had experienced numerous episodes of disease in her left lower leg that involved variable degrees of swelling, erythema, warmth, and pain. Her clinical picture suggested both inflammation of unknown cause and secondary infection. To complicate the picture, she demonstrated features of chondromalacia of the left patella, which the clinicians thought might be related to the lower extremity disease, perhaps through infection. The differential diagnosis included cellulitis, septic arthritis, osteomyelitis, thrombophlebitis, collagen vascular disease, necrotizing fasciitis, pyomyositis, compartment syndrome, immunodeficiency, venomous insect or snake bite, and lymphedema.

By the time of admission to this hospital, an extensive evaluation had been completed, eliminating many of the diagnoses on the list, including septic arthritis (negative arthrocentesis), chronic osteomyelitis (negative radiograph, bone scan, and blood culture), thrombophlebitis (negative venogram), and collagen vascular disease (negative RF and ANA and normal ESR).

With necrotizing fasciitis, progression should be more acute. Signs and symptoms of pyomyositis should progress and by 6 months would require surgical management for resolution. With compartment syndrome, there should be a history of pain on exercising. Immunodeficiency is unlikely given the onset of symptoms at age 17 years and absence of risk factors for human immunodeficiency virus. There was no history of snake or insect bite.

One other important diagnostic consideration is lymphedema. This finding can occur in lymphedema praecox (Meige disease), which is a primary lymphedema with onset in adolescence and usually is a diagnosis of exclusion. In addition, several secondary causes of lymphedema include tumors; postradiation fibrosis; retroperitoneal fibrosis; infection (including filariasis); and postinflammatory scarring from trauma, surgery, or burns. Lymphoscintigraphy can be used to differentiate primary from secondary lymphedema.

In this patient, filariasis was an intriguing possibility given her travel history. Filariasis is a roundworm infestation that can lead to massive lymphedema of the legs and genitalia. Diagnosis is made by reviewing blood smears for microfilariae or by antigen immunoassay. In this case, blood smears were negative.

The Condition
This patient’s diagnostic dilemma was solved dramatically one day on rounds when she was discovered to be applying a constrictive tourniquet around her leg just above the knee. When she was confronted, she became withdrawn and denied she was doing anything. With one-to-one nursing supervision to ensure no further placement of the tourniquet, the redness and swelling resolved rapidly. A psychiatrist was consulted, and factitious illness was diagnosed.

This unusual presentation is a striking example of how physicians can be deceived by patients who have factitious disorders and can be compelled into performing extensive and invasive diagnostic procedures. In retrospect, one diagnostic clue could have been a zone of demarcation between the normal and edematous areas caused by the tourniquet. Careful re-examination after the true cause had been revealed did show that finding, which had not been evident on previous examinations.

Psychosomatic illnesses have a wide spectrum of presentations and are common in adolescents. Frequently, they are manifestations of underlying psychological disease, but they also can be seen in healthy adolescents during stressful situations. Examples include adjustment disorders, somatization disorders, conversion disorders, hypochondriasis, malingering, and factitious disorder.

According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Edition 4 (DSM IV), adjustment disorders relate to a difficult adjustment to a situation that is out of proportion to the circumstances. In these disorders, stress can lead to physical symptoms. Examples include tension headaches, palpitations, neurodermatitis, and tremor.

In somatization disorders such as conversion disorder and hypochondriasis, a variety of symptoms can present vaguely and imprecisely over a period of several years. There must be a significant impairment in functioning or a history of no explanation of symptoms after an appropriate assessment. The patient often goes to many different physicians and frequently has underlying anxiety and depression.

Conversion disorder is characterized by neurologic or other somatic symptoms that do not fit biologic explanations. The patient benefits from these symptoms by avoiding stressful conflict (primary gain) and evokes attention and sympathy for being stricken with often dramatic symptoms (secondary gain). For patients who have hypochondriasis, there is an exaggerated preoccupation or belief that they have a serious disease.

There are three mental health disorders in which an individual intentionally produces symptoms: malingering, factitious illness, and factitious illness by proxy. In malingering, the patient voluntarily, deliberately, and purposefully produces his or her symptoms to achieve some goal, such as gaining insurance money, avoiding military service, obtaining drugs, or avoiding work.

In factitious illness, or M?nchhausen syndrome, the patient produces signs or symptoms to assume the sick role. Examples of clinical presentations include factitious fever, induced infections, and hypoglycemia caused by exogenous insulin injections. There was one reported case of a tourniquet placed around the wrist, which mimicked reflex sympathetic dystrophy. "M?nchhausen syndrome by proxy" is a term used when a caregiver induces signs or symptoms in a child.

Patients who have factitious illness often have a vague and inconsistent history. When questioned in detail, they frequently have an extensive knowledge of diseases and may have a medical background. Patients commonly become hostile about not being diagnosed correctly and demand and request medications and procedures that are medically unnecessary. The cause of factitious illness is unknown. The diagnosis requires a high degree of suspicion and often is difficult to prove. The patient frequently uses the symptoms to gain attention and recognition. Prolonged psychotherapy is recommended.

Lessons for the Clinician
This case reminds clinicians always to consider the possibility of factitious illness in patients who present with atypical clinical manifestations. Careful observation of the patient in the hospital, including video surveillance, may be necessary to confirm the diagnosis, although clinicians contemplating video surveillance should consult the hospital attorney and risk management office to be sure they are acting legally. Once the diagnosis is considered, clinicians should avoid harmful invasive procedures or treatment with potentially toxic medications.


James J. Burns, MD
Baystate Medical Center, Springfield, Mass

A12-month-old girl is brought to the ED after a seizurelike episode. On awakening from a nap, she screamed and then became stiff. Her eyes rolled back, and she began to shake. Both arms and legs were involved symmetrically. The episode lasted 2 minutes, after which she appeared tired. She has been well recently, with no fever or respiratory symptoms.

Her mother reports a history of similar episodes over the last 3 months, with increasing frequency in the last week (up to 10/d), but no medical attention has been sought until now. The child has had no serious illnesses, is receiving no medications, has no allergies, and has not been immunized (by parental choice). She walked at 10 months of age, but in the last week has become unsteady, stumbling when walking. The family history is noncontributory.

The physical examination reveals an alert child who has normal tone, strength, reflexes, and vital signs. All other physical findings also are normal; specifically, no focus of infection is evident.

Blood chemistry levels include: sodium, 137 mEq/L (137 mmol/L); potassium, 5.4 mEq/L (5.4 mmol/L); calcium, 10.4 mg/dL (2.60 mmol/L); and magnesium, 2.43 mg/dL (1.00 mmol/L). The blood glucose level is 37.8 mg/dL (2.1 mmol/L), and liver function test results are normal. The WBC count is 11.5x103/mcL (11.5x109/L), Hgb level is 12.2 g/dL (122 g/L), and platelet count is 347x103/mcL (347 x109/L). A full evaluation for sepsis is negative. CT of the head shows normal findings. Additional testing confirms the diagnosis.
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The girl was admitted to the hospital and started on an intravenous dextrose solution to stabilize her blood glucose. The infusion was interrupted, and repeated blood glucose testing and symptom monitoring were instituted. When hypoglycemia (glucose <50 mg/dL [2.7 mmol/L]) was reached, metabolic studies consisting of measuring serum carnitine, urine organic acids, and plasma amino acids and free fatty acids were carried out to rule out an inborn error of metabolism. All results were normal.

In addition, a critical sample (a measure of various metabolic precursors and hormones involved in glucose regulation taken during an episode of hypoglycemia) was drawn and revealed a glucose value of 1.4 mg/dL (0.8 mmol/L) (asymptomatic). The cortisol concentration was 24.4 mcg/dL (673 nmol/L). The reference range for a morning level is 4.3 to 22.4 mcg/dL (119 to 618 nmol/L); a high value represents a normal response to hypoglycemia. The growth hormone concentration was 12.35 ng/mL (543.4 pmol/L). The reference range for a normal growth hormone value during an episode of hypoglycemia is greater than 8.0 ng/mL (352 pmol/L). The insulin level was 11.4 mcU/mL (82 pmol/L), which was in the normal range (6.0 to 27.0 mcU/mL [43.1 to 193.7 pmol/L]), but during hypoglycemia, insulin should be suppressed (<5.0 mcU/mL [35.9 pmol/L]). Therefore, her value was inappropriately high, given her physiologic state.

MRI of the head and EEG to rule out CNS abnormalities gave normal results. Repeated episodes of asymptomatic hypoglycemia occurred during the first few days in the hospital, then stabilized with initial intravenous dextrose therapy followed by treatment with diazoxide, an inhibitor of insulin release. No additional seizures occurred. The patient was discharged from the hospital on diazoxide (10 mg/kg in three daily doses) and with a glucagon kit and instructions on treating hypoglycemia.

An MRI of the abdomen obtained as an outpatient revealed a discrete mass in the tail of the pancreas, amenable to resection, suggesting the presence of an insulinoma that explained the patient’s hypoglycemia. She underwent a partial pancreatectomy to remove the tumor. Since the surgery, she has been weaned from diazoxide and has had stable blood glucose concentrations.

The Disorder
Insulinomas are extremely rare in children. Although most present as isolated tumors, they may be associated in younger children with the condition known as multiple endocrine neoplasia type I, which is characterized by hyperparathyroidism, pituitary adenomas, and pancreatic adenomas. Symptoms and signs are due primarily to the effects of hypoglycemia on the CNS (tremulousness, poor feeding, irritability, anxiety, dizziness, seizure, coma), may be present for days to years, and may be misdiagnosed as neurologic or psychiatric disease. In 30% to 40% of patients, the hyperinsulinism is caused by a discrete region of adenomatous hyperplasia, but all pancreatic beta cells can be involved (both hyperplasia and hypersecretion), and this determination can affect the treatment plan.

Diagnosis
In general, persistent or recurrent hypoglycemia can result from three mechanisms. Lack of substrate can be due to prolonged fasting, inborn errors of energy metabolism (affecting gluconeogenesis, glycogenolysis, or fatty acid oxidation), and ketotic hypoglycemia. Increased utilization of glucose can result from hyperinsulinemia, either endogenous (infant of a diabetic mother, diffuse or focal hyperinsulinism) or exogenous. The third mechanism involves an inadequate response or deficiency of counterregulatory mechanisms designed to raise blood glucose, causes of which can be endocrinologic (cortisol deficiency, growth hormone deficiency, panhypopituitarism) or toxin-mediated (ethanol, salicylates, propranolol). In a 12-month-old child, the most likely causes are hyperinsulinism, hypopituitarism, adrenal insufficiency, or ketotic hypoglycemia. The critical sample helps to differentiate these diagnoses.

The diagnosis of hyperinsulinemia should be considered in any case of hypoglycemia, particularly if episodes are persistent or recurrent and when other mechanisms have been ruled out. Endogenous hyperinsulinemia is diagnosed by demonstrating inappropriately high insulin and C-peptide levels in the face of hypoglycemia (exogenous administration of insulin causes high insulin, but low C-peptide levels). Indirect measures of hyperinsulinism include lack of ketones in the face of hypoglycemia, an increased glycemic response to glucagon, and an increased glucose requirement (>15 mg/kg per min).

In this case, interpretation of the critical sample showed a normal response of the counterregulatory hormones. The insulin level, although reported as within the normal range, was inappropriately high for the circumstance; insulin should be suppressed completely by hypoglycemia. Additional evidence of hyperinsulinemia was provided by the absence of plasma ketones. Again, although reported as normal, this finding is inappropriate for the circumstance; hypoglycemia should trigger fat oxidation and ketogenesis, but in this case, the presence of insulin inhibited ketogenesis.

Treatment
Once hyperinsulinemia is diagnosed, differentiating between focal (discrete insulinoma) and diffuse disease (infant of a diabetic mother, persistent hyperinsulinemic hypoglycemia of infancy, diffuse hyperinsulinism) has important implications for treatment. Focal disease can be treated pharmacologically, but also may be amenable to partial surgical resection; diffuse disease is less amenable to partial resection. There are two primary pharmacologic options, the first being diazoxide (10 mg/kg per day orally divided into three doses), an inhibitor of insulin release. Major adverse effects include hirsutism, fluid retention, and neutropenia. Octreotide (5 to 20 mcg/kg per day by subcutaneous injection every 6 to 8 h), a somatostatin analogue that inhibits insulin secretion (as well as glucagon and growth hormone), also can be used. Adverse effects include abdominal discomfort, cholelithiasis, and transient growth impairment.

Many approaches have been attempted to localize focal disease. Radiologic studies have not been as successful as hoped, with MRI being the best, correctly localizing up to 45% of insulinomas. A newer, more invasive approach, consisting of selective sampling of pancreatic veins for insulin levels following stimulation with calcium gluconate, has an overall accuracy of up to 94%, but is not yet widely available. Isolated insulinomas localized to the tail of the pancreas are potentially curable with partial resection; diffuse disease, particularly if resistant to pharmacologic treatment, may require subtotal pancreatic resection. Although this procedure cures the hyperinsulinemia, the child ultimately may develop diabetes mellitus from the resulting relative insulin deficiency, once growth exceeds pancreatic function. Unfortunately, the timing of this complication is unpredictable, requiring ongoing monitoring.

Lessons for the Clinician
Investigation of any child presenting with a seizure must include a blood glucose measurement. Hypoglycemia is treated easily, and hypoglycemic seizures may be refractory to anticonvulsant therapy. Hyperinsulinemia, specifically as caused by insulinoma, is a rare condition but one important to diagnose. Obtaining a true hypoglycemic blood sample is vital in making the diagnosis. It is important to remember that results of critical samples must be considered in context. Although the laboratory may report a result as being normal, that level may not be appropriate for the physiologic state. Accurate localization of insulinomas can affect the treatment, allowing the possibility of a cure without sequelae in focal disease.


Marielena DiBartolo, MD
Robert I. Stein, MD
Children’s Hospital of Western Ontario, University of Western Ontario, London, Ontario, Canada
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Хочется подчеркнуть, что у таких больных важно определять КЩС во время эпизода гирогликемии . При отсутствии ацидоза круг диф.диагностики существенно сужается
(практически - до гиперинсулинизма и проблем с обменом жиров).
Кстати, а если бы сахар был нормален, то о каком заболевании при подобной клинике важно было бы подумать?

Первое, о чем я бы подумала при НЕ фебрильных судорогах, это, конечно, эпилепсия. Второе - эпилептические приступы, вторичные к процессу в голове. Но, поскольку, первичное обследование включает глюкозу крови, а результаты EEG, CT И MRI -отрицательные, то надо искать другую причину гипогликемии (факт - нашли.) У маленьких детей презентация диабета часто именно в форме гипогликемии, которая может сопровождаться судорогами. Но, слава Б-гу, поставить диагноз сахарного диабета сегодня - это не самое сложное. :)

Hepatosplenomegaly, pancytopenia, coagulopathy: Big words about a feverish infant
Oct 1, 2005
By: Fasika Woreta et al.
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You meet your new patient late one afternoon on the general pediatric service of your tertiary care hospital. He is a 2-month-old boy of Native American and Puerto Rican descent who has been undergoing evaluation of fever, hepatomegaly, and pancytopenia of uncertain cause.

You familiarize yourself with what has become a rocky infancy for this baby. He was in generally good health until two weeks ago when, you learn, he developed a rotavirus infection. The diarrhea was improving, but had not resolved, when, one week before admission, he developed a fever as high as 104° F and had a generalized tonic-clonic seizure. He was transported to a nearby community hospital and found to be anemic (hematocrit, 20%). There, he was given a transfusion of packed red blood cells. Multiple cultures (blood, urine, and CSF) were obtained and were ultimately negative. Empiric antibiotics were started for possible sepsis.

Over the next five days, the boy developed pancytopenia, ascites, hepatomegaly, direct hyperbilirubinemia, and coagulopathy, requiring transfusions of platelets, fresh frozen plasma, vitamin K, and additional packed RBCs. Bone marrow aspiration and biopsy showed normal cellularity, trilineage hematopoiesis, and no abnormal cells.

He was transferred to the pediatric intensive care unit (PICU) of your hospital for further evaluation and management of the coagulopathy and pancytopenia. There, these problems persisted and were managed with frequent blood product support (fresh frozen plasma, platelets, cryoprecipitate). Transjugular liver biopsy showed cholestasis with normal architecture and no evidence of intrahepatic disease. Biopsy specimens were sent for fungal, viral, and bacterial cultures and were ultimately negative.

Infectious disease, gastroenterology, and immunology specialists were consulted. Today, after three days in the PICU, the patient's transfusion-dependence had apparently resolved, he was no longer febrile and, after narrowing antibiotic coverage to cefotaxime, he was transferred to your care.

Arriving jaundiced and swollen

The brief history is significant for two infections. The infant was hospitalized at 11 days of age for respiratory syncytial virus bronchiolitis, which resolved without apparent complication. He then developed rotavirus infection. Neither is unusual, you consider, for a newborn in a late winter month.

The boy is the product of a full-term pregnancy; the mother is 29 years old, gravida 3, para 3. She confides that she is a recovering heroin addict who used heroin through the first trimester of this pregnancy. She received prenatal care, and routine prenatal testing was negative, including an HIV antibody test. The baby received hepatitis B vaccination at birth but has not yet received the 2-month-old vaccination. Medications include ranitidine (Zantac), which he has taken since he was 1 month old for gastroesophageal reflux disease.

The family history is significant for epilepsy in his mother and paternal grandfather. He has a 2-year-old brother and an 8-year-old half-sister, both in good health. He lives with his mother in a group home for previously incarcerated mothers who are recovering from heroin addiction.

On physical examination, you observe a baby who is alert and does not appear toxic but is diffusely jaundiced. He is now afebrile, with a pulse of 130/min and a respiratory rate of 48/min. Blood pressure is 102/57 mm Hg; O2 saturation, 98% on room air. Weight is 4.8 kg (at the 25th percentile, weight-for-age).

Physical examination is notable in several regards. Sclerae are icteric. The neck is supple without lymphadenopathy. Abdominal examination is remarkable for prominent distension, with a positive fluid wave and a liver palpable 4 cm below the right costal margin. There is splenomegaly, which had not been noted earlier; the spleen is palpable 3 cm below the costal margin. Extremities are well perfused, with a capillary refill of less than two seconds. There is a right femoral line in place, without erythema of surrounding skin. There is nonpitting trace edema of the lower extremities and marked scrotal edema. The rest of the examination is unremarkable.

Laboratory tests obtained in the PICU on the day of transfer show a white blood cell count of 2.2 X 103/μL, with 16% neutrophils, 71% lymphocytes, 12% monocytes, and 1% eosinophils. He is neutropenic, with an absolute neutrophil count of 0.34 X 103/μL. Hemoglobin (8.3 g/dL) and hematocrit (24.2%) are decreased; the platelet count is extremely low at 29 X 103/μL. Total bilirubin (8.9 mg/dL) and direct bilirubin (6.1 mg/dL) are significantly elevated. Aspartate aminotransferase (81 U/L [normal, 0-37 U/L]) and gamma glutamyl transferase (550 IU/L [normal, 12-55 IU/L]) are elevated, but alanine aminotransferase and alkaline phosphatase levels are within normal limits. Fibrinogen is low at 55 mg/dL (normal, 150-450 mg/dL); a d-dimer test is elevated at 6.62 mg/L (normal, 0.43-2.24 mg/L); prothrombin time is slightly elevated at 15.8 seconds; and the activated partial thromboplastin time is normal for age at 40 seconds. Albumin is 2.9 g/dL. Serum electrolytes and creatinine are normal.

The differential is broad

You consider how extensive the differential diagnosis is in an acutely ill 2-month-old with pancytopenia. Ingestion of a toxic substance (including prescription and over-the-counter medications), an infectious process, immune disorders, metabolic disorders, and hematologic processes such as leukemia, lymphoma, or a hemophagocytic syndrome—all could result in pancytopenia and prompt your patient's clinical picture. The boy is being given ranitidine, which can cause hepatotoxicity. Could the recent rotavirus infection explain the clinical picture? You've read case reports of viremia from rotavirus, with systemic manifestations. Notably, the extensive infectious disease workup has been unrevealing: serologic tests for enteroviruses, Histoplasma, Cryptococcus, HIV, hepatitis A and C antibody, cytomegalovirus and Epstein-Barr virus (EBV) antibody, Toxoplasma antibody, parainfluenza, influenza, adenovirus, respiratory syncytial virus, parvovirus, and Haemophilus influenzae type b antigen all return negative. Stool cultures for Salmonella, Shigella, Yersinia, and Campylobacter and a test for rotavirus antigen are also negative. So is a purified protein derivative skin test for Mycobacterium tuberculosis (none was placed on the mother or siblings).

More tests are needed

You decide to order abdominal computed tomography with intravenous contrast. The scan reveals hepatomegaly and an enlarged spleen with an irregular appearance, possibly indicating small implants, abscesses, or infarcts. A doppler ultrasound scan to further evaluate the splenic lesions shows splenomegaly but no areas of abnormal signal.

On the fourth day after transfer, the infant again begins spiking a fever, to a maximum axillary temperature of 104° F. The femoral line is removed and antibiotic coverage is broadened, although cultures of cerebrospinal fluid, blood, urine, and stool continue to show no growth. Persistent pancytopenia is managed with multiple blood and platelet transfusions. On the fifth day, blood cultures return positive for presumptive Enterococcus and the antibiotic coverage is appropriately broadened.

Given the boy's deterioration, you ask the hospital's pediatric hematologists to review the initial bone marrow biopsy and aspirate from the other hospital and to comment on the slightly increased number of histiocytes in the background. They also note one phagocytic histiocyte, which may be normal. Despite an unimpressive bone marrow, the team is concerned that your patient's clinical picture is highly suspicious for hemophagocytic lymphohistiocytosis; repeat bone marrow aspiration and biopsy, along with a lumbar puncture, are performed. Additional laboratory tests are ordered, and you take note of an elevated ferritin level (1,098 ng/mL [normal, 10-300 ng/mL]) and elevated serum triglycerides (237 mg/dL [normal, <150 mg/dL]).

.

An unfortunate answer

A few hours after the procedures, you receive an urgent call from the hematologist to come view the slides. The aspirate reveals numerous histiocytes in the process of hemophagocytosis. Vacuolized histiocytes are also visible in the CSF. The diagnosis of hemophagocytic lymphohistiocytosis (HLH) is made and the patient is evaluated emergently by the oncology consultants for chemotherapy.

That night, your patient has an acute decompensation, with increased work of breathing, decreased O2 saturation, and hypotension. He is intubated and transferred to the PICU. The following day, chemotherapy with the HLH-2004 protocol—cyclosporine, etoposide, and dexamethasone is initiated.

Over the next week, the boy develops renal failure, fulminant hepatic failure, worsening coagulopathy, an inability to maintain serum glucose hemostasis, and persistent seizures. Eight days after the diagnosis was established, and one day short of being 3 months old, support is withdrawn and he is pronounced dead.

The challenge: A nonspecific presentation

Hemophagocytic lymphohistiocytosis, also known as hemophagocytic syndrome, encompasses a heterogeneous group of disorders that share a nonspecific clinical picture comprising fever, hepatosplenomegaly, and cytopenia resulting from uncontrolled macrophage activation and subsequent phagocytosis of blood cells.

Two distinct forms of the disease have been described: a primary, or familial, form, inherited as an autosomal-recessive disorder, and a secondary, or sporadic, form that has been associated with a variety of infections, autoimmune diseases, and malignancies, and with several genetic immunodeficiency syndromes.

A retrospective Swedish study estimated the annual incidence of familial HLH to be 1.2 cases for every 100,000 children.3 Peak age of diagnosis is between 1 and 6 months, with 70% to 80% of cases presenting before 1 year. Gender distribution is thought to be even.

Pathophysiology Although the pathophysiology of HLH is poorly understood, it is hypothesized to be a disorder of immune regulation, with a failure of cytolytic lymphocyte function resulting in hypersecretion of cytokines and subsequent uncontrolled activation of lymphocytes and macrophages. The sera of patients who have HLH have been found to have a strikingly high level of numerous cytokines, including interferon gamma, TNF alpha. Several studies have demonstrated markedly reduced or complete absence of cytotoxic T cell and natural killer activity in patients with HLH. The cytotoxic T lymphocytes and natural killer cells are effector lymphocytes that share a common cytotoxic pathway required for defense against viral infections. This cytotoxic pathway is disrupted in HLH; when the disruption occurs with intercurrent infection, it induces lethal immune deregulation (in some forms of HLH).

Two genetic mutations have been identified in patients with familial HLH. One gene is on chromosome 10 and encodes a protein called perforin, an important mediator of cytotoxic T cells and natural killer cell cytotoxicity. Cytotoxic cells kill their targets primarily through a localized secretion of toxic granules, and perforin is thought to be essential for this process. This mutation is estimated to account for 20% to 40% of cases of familial HLH. More recently, mutations in the hMunc13-4 gene, on chromosome 17, have been identified in a subset of patients with familial HLH. Like perforin, hMunc13-4 also participates in cytotoxic granule release. Without proper cytotoxic granule release, the activity of activated macrophages goes unchecked and leads to cytokine release and phagocytosis.

A variety of infectious agents can provoke secondary HLH and can trigger the familial form of the disorder. Viruses are most often implicated, with EBV reported to be the most common cause. Other viruses reported to trigger HLH include CMV, human herpesvirus, varicella-zoster virus, herpes simplex virus, adenoviruses, and parvovirus B19. EBV-associated HLH is important to diagnose because it is associated with a more fulminant course and higher mortality rate.

Diagnosis Signs and symptoms of HLH vary widely. The principal clinical features are fever and hepatosplenomegaly. Other common clinical findings include rash, lymphadenopathy, and neurologic symptoms. The latter are seen in as many as 75% of cases, may be the presenting sign, are highly variable, and include seizures, lethargy, cranial nerve findings, abnormal tone, and ataxia.

Common laboratory findings include pancytopenia, direct hyperbilirubinemia, hypertriglyceridemia, hyperferritinemia, and hypofibrinogenemia. Hyponatremia, hypoalbuminemia, elevated LDH, coagulopathy, transaminitis, and CSF pleocytosis with mononuclear cells and an elevated protein level have also been reported.

The pathognomonic histopathologic finding is numerous histiocytes actively phagocytosing blood cells—erythrocytes, mostly, but also leukocytes and platelets. The most frequently involved organs are bone marrow, lymph nodes, the CNS, liver, and spleen. An initial bone marrow specimen may not demonstrate phagocytosis; repeat aspiration may be necessary to establish the diagnosis. A key learning point, therefore, is that an initially negative bone marrow specimen should not rule out HLH or delay immediate treatment if other diagnostic criteria are met.

The familial and the infectious forms of HLH are often indistinguishable clinically. Diagnosis of the familial form can be made by an established positive family history or demonstration of mutations in the perforin or hMunc13-4 genes. Also suspect familial HLH in the presence of parental consanguinity or age of onset earlier than 1 or 2 years. Measurement of perforin expression in natural killer cells and CD8+ lymphocytes and mutational analysis of the perforin and hMunc13-4 genes can be performed in patients with HLH.

Prognosis and therapy Without bone marrow transplantation, familial HLH is uniformly fatal soon after birth; median survival is two to three months. The prognosis is better in the majority of secondary forms, with recovery reported in 60% to 70% of cases. The exception is EBV-associated HLH, in which recovery is thought to be much less likely. In a 1996 study of 122 patients with HLH, overall estimated five-year survival was 22%. Among patients who underwent bone marrow transplantation, five-year survival was 66%; for those receiving chemotherapy with etoposide or another single chemotherapeutic agent, five-year survival was 10.1%.

In 1994, the Histiocyte Society initiated a prospective collaborative therapeutic study of the disorder (HLH-94) with the aim of improving survival. The protocol comprised an initial eight weeks of treatment with etoposide and dexamethasone. Following that, children with familial or recurring HLH, or both, continued with etoposide and dexamethasone in combination with cyclosporine for as long as one year. Subsequently, bone marrow transplantation (the only curative treatment for primary HLH) was performed if a donor became available. Intrathecal methotrexate was also used in cases of CNS involvement. This protocol resulted in an overall survival of 55% at median follow-up of 3.1 years and a three-year probability of survival of 62% after marrow transplantation. Although survival of children with HLH is still poor, therefore, it has greatly improved over the past decade. In the most recent revision of this protocol (HLH-2004), cyclosporine is administered at the start of therapy.

Although it can be difficult to distinguish the primary form of HLH from secondary forms, the distinction is important: Familial HLH is uniformly lethal without bone marrow transplantation. A child who has presumed secondary HLH and who has experienced complete resolution following immunochemotherapy should be monitored carefully for relapse.

Early treatment is thought to be beneficial when feasible because a response to treatment is less likely subsequent to CNS involvement and bone marrow failure.

The diagnosis of HLH is challenging—and often delayed for several reasons, including this rare disorder's variable, nonspecific manifestations and clinicians' lack of awareness of it. Because of the aggressive nature of HLH and the likely need for early treatment, early diagnosis is crucial. Consider HLH, therefore, in any child in whom fever, hepatosplenomegaly, and cytopenia go unexplained, because early treatment may be life-saving

18-летний юноша осмотрен в приемном отделении по поводу 2-х недельной истории диарреи и слабости. Лечащий врач поставил д-з "Вирусный гастроэнтерит". За 4 дня до осмотра в п/о его диаррея стала более частой, появилась рвота без примеси крови и желчи, усилилась слабость. Он отрицает позывы наличие дефекаций по ночам, но отмечает, что был один эпизод недержания кала. Отрицает боли в животе, ночные поты, потерю веса, желтуху сыпь, частые немотивированные синяки или кровотечения.Нет истории о путешествиях или каких либо других нерутинных особенностей жизни. В медицинском анамнезе - псориаз. В семейном анамнезе нет указаний на Inflamattory Bowel Disease или Celiac dis., но у дедушки со стороны матери был " разрыв кишки". Нет истории кровотечений или нарушения свертываемости.
При осмотре :бледный, хорошо развитый юноша без признаков какой-либо недостаточности (in no distress). Без температуры, ч.с.с. 119/мин. , АД 148/72 , ч.д.д. в норме. Вес 90 персентиль, рост 75 персентиль. При осмотре головы, ушей, носа и глотки - нет иктеричности, но отмечается язва на левой миндалине. При аускультации сердца - систолический шум 1/6 по левой стернальной линии. Живот мягкий, б/б, печень не пальпируется, палпируется край селезенки. При ректальном осмотре - кровь. Фиссуры нет. На коже нет петехий , расчесов, сыпи...
Пациент госпитализирован для обследования. Диаррея остается, в кале большое кол-во крови и слизи.
Лаборатория:
- WBC 22,300 cells/mm (мм куб)
Neut -44%
Lymph-9%
Mono-7%
Bands-36%
eos-1%
metamyelocytes-1%
myelocytes-2%
-Hb -8,3 g/dl
-MCV -63
-RSW -19,4%
-PLT -38000/mm (мм куб)
-ESR (CОЭ)- 24 mm/h
Ретикулоцитов 4,5%, в периферическом мазке - фрагменты эритроцитов, овалоциты, слезовидные клетки (teardrops) и гипохромия.
-BUN -13mg/dL, creatinin - 1,5 mg/dL
-ALT -1030 IU/L
-AST -746 IU/L
-GGT -73 IU/L
-Alk Phos -133 IU/ L
-Bil total -0,4 mg/dL
-Albumin - 2,9g/ dL
-PT -19,8 sec.
-PTT -29,4 sec.
-INR -1,8
-LDD - 1118 IU/L
-Uric acid - 8,8 mg/dL
В моче 2 эритроцита, следы кетона, небольшое кол-во белка и 26 гиалиновых цилиндров.
Посев кала, а также анализ на глистов и паразитов, а также на токсин клостридии - отрицательно.
Посев крови - отрицательно.
Тест на гепатиты и ЦМВ -отрицательный, тест на ЕБВ - нет речи об острой инфекции (prior infection). Повторные анализы крови и печеночных проб показали возвращение к норме. Почечные пробы вернулись к норме. Осмотрен окулистом на предмет выявления колец Kayser-Fleischer - не найдено, церулоплазмин сыворотки и уровень меди - в норме и в крови , и в моче.

Что делать дальше, по Вашему мнению? (Я-то ответ знаю, выложу через пару дней в ординаторской... :p )
P.S. Прошу прощения за некую корявость перевода. :)

Не забывая о других возможностях (например, IBD и пр.), я бы на первое место в списке диф.диагнозов поставил Hemolytic-uremic syndrome.

Что делать дальше, по Вашему мнению? (Я-то ответ знаю, выложу через пару дней в ординаторской... :p )

Пришлите также ответ мне на личку.
Не описаны лимфоузлы пациента, не описано наличие или отсутствие температуры
Кроме всего прочего я бы обследовал на HIV и сделал стернальную пункцию

"Не описаны лимфоузлы пациента, не описано наличие или отсутствие температуры"

Олег, читайте внимательно! Что же я зря старалась, переводила :)

Ирина, я, конечно, протяну руки к щитовидной железе( хоть и отсутствие узла меня не удивит), и для спокойствия душевного закажу метанефрины и кальцитонин крови ( Т.е у Вас заказала бы, а у нас закажу метанефрины мочи и кальцитонин крови )..Вряд ли я права при 90-ой персентили массы тела, но все же. Ну и ТТГ - просто так, для порядка ( хоть для тиротоксикоза и типичны не диарея. а гипердефекация).

Может у него энтерогеморрагическая кишечная палочка завелась? :) Хотя ХЗ, это + к перечисленному, конечно

"Не описаны лимфоузлы пациента, не описано наличие или отсутствие температуры"

Олег, читайте внимательно! Что же я зря старалась, переводила :)

Я прочитал внимательно. лимфоузлы не описаны. температура - только отсутствие повышения при осмотре. а в анамнезе?!

Вообще, думаю, что авторы этого текста сознательно выпустили некоторые детали))

Олег прав! Скрывается какая-то пакость.Что обычно при презентациях клинических случаев на конференциях ( реальных или виртуальных)
Я думаю, что имеет место какой-то хитрый паразит с энтеропеченочным циклом путешествий в организме(может быть даже амеба). Поэтому предлагаю ( хотя готов к двойке)
1- Поднаркозная колоноскопия с биопсиями если показаны. ( Да, это можно сделать с тромбоцитами 38,000)
2-Stool for ova and parasites
3- консультация инфекциониста.( он сдесь нужен больше,чем эндокринолог)
П.С. Др. Ира, укажите пожалуйста ссылочку на "разбор полетов"

Олег прав! Скрывается какая-то пакость.Что обычно при презентациях клинических случаев на конференциях ( реальных или виртуальных)
Я думаю, что имеет место какой-то хитрый паразит с энтеропеченочным циклом путешествий в организме(может быть даже амеба). Поэтому предлагаю ( хотя готов к двойке)
1- Поднаркозная колоноскопия с биопсиями если показаны. ( Да, это можно сделать с тромбоцитами 38,000)
2-Stool for ova and parasites
3- консультация инфекциониста.( он сдесь нужен больше,чем эндокринолог)
П.С. Др. Ира, укажите пожалуйста ссылочку на "разбор полетов"

А анализы-то к норме вернулись. Была бы амеба - имхо, не вернулись бы. + Посев кала, а также анализ на глистов и паразитов, а также на токсин клостридии - отрицательно.

думаю, что имеет место какой-то хитрый паразит
да, скорее всего или инфекция, или патология крови (или их сочетание).
ГУС маловероятен, так как нет почечной недостаточности и не тот возраст.
Привлекает внимание также фраза "повторные анализы крови показали возвращение к норме"
Интересно, тромбоциты тоже вернулись к норме? и лейкоциты, и СОЭ, и гемоглобин???!

Papadoctor - молодец!(Насчет колоноскопии).
Но все по порядку.
Следующее обследование УЗИ живота с Доплером.
Результаты:
-Нет кровотока в левой портальной вене. Но нормальный кровоток в правой портальной, главной портальной и селезеночных. Небольшое увеличение селезенки, неспецифическое утоньшение стенки желчного пузыря и небольшое кол-во свободной жидкости в животе. Почки и ечень в норме. Поскольку выявилась вероятность тромбоза портальной вены, был прекращен вит К и не назначено лечение fresh frosen pasma.

Следующее обследование - КТ живота + ангиография подтвердило выраженный субокклюзивный тромбоз портальной и мезентериальной венозных систем ,пятнистость печени (patchy enhancement) и изменения в colon, предполагающие колит. Никаких данных за аппендицит, перфорацию или другой септический процесс в животе.

Следующее обследование - КТ живота + ангиография подтвердило выраженный субокклюзивный тромбоз портальной и мезентериальной венозных систем ,пятнистость печени (patchy enhancement) и изменения в colon, предполагающие колит. Никаких данных за аппендицит, перфорацию или другой септический процесс в животе.
Вау! Теперь я сдаюсь. Потому что теперь полностью не понимаю венозного тромбоза с тромбоцитами 38000 и РТ-20.Разве, что-то механическое селективно блокирует эти две венозные системы :confused: Назначаю миксинг-стадис и жду вердикта умных гематологов
Да, а что с этой язвой на миндалине???
П.С. Наливайте, не томите плииз.

Обследование по поводу первичной причины гиперкоагуляции:
-Фактор V Leiden и протромбин G20210A мутация -отрицательно
-activated protein C resistance - норма
-низкий антитромбин 111 и низкую активность протеина С и протеина S объяснили заболеванием печени или остаточными явлениями тромбоза.
- нет данных за синдром антифосфолипидных антител
-нормальный tissue thromboplastin inhibition indexes
-отрицательный hexagonal lipid neutralization test
-нормальные антикардиолипины
-нормальные антитиреодные антитела
-пациент гетерозиготен по метиленететагидрофолат редуктазе, но уровень гомоцистеина в норме.
-нет данных за ночную пароксизмальную гемоглобинурию, как причину тромбоза (сделали flow cytometry).

Сделали колоноскопию.
-Слизистая колон диффузно воспалена и отечна , рыхлая, с язвами в мукозе, характерна для панколита. Терминальный отдел илеум без особенностей.
-Биопсия - острый колит с воспаленными псевдомембранами, субмукозные тромбы и образованными абсцессами крипт. Не найдено вирусных включений, организмов или гранулем. Нет хронических изменений. Заключение : тромботический/ишемический колит.
Пациент был переведен в отд.интенсивной терапии для лечения антикоагуляции на фоне гастроинтестинального кровотечения. Лечили гепарином.

Как по вашему, что еще осталось сделать для уточнения и подтверждения диагноза?

Пациент был переведен в отд.интенсивной терапии для лечения антикоагуляции на фоне гастроинтестинального кровотечения. Лечили гепарином.
Для лечения гиперкоагуляции наверно имелось в виду?
И если это ишемический колит и кишечное кровотечение, то наверное это они возникли на фоне локальной коагулопатии а не наоборот?
Как по вашему, что еще осталось сделать для уточнения и подтверждения диагноза?
Какая причина может быть для замедления кровотока? Скорее всего механическая. Ни УЗИ ни КТ как будто не выявили ничего особенного в печени - может быть сделать еще сцинти?..
И как-то не находят пока своего объяснения язва на миндалине, лейкоцитоз со сдвигом формулы, СОЭ. Или они нормализовались?..

Thalassemia?( (mediterranian (jewish) kid,anemia,teardrop cells...)

Ни УЗИ ни КТ как будто не выявили ничего особенного в печени - может быть сделать еще сцинти?..
Ни в коем случае :))
С каким radiopharmaceutical и с какой целью?

Как по вашему, что еще осталось сделать для уточнения и подтверждения диагноза?
Serum ferritin,Fe

Была сделана сигмоидоскопия с биопсией несколькими днями позже для последующего уточнения диагноза. Биопсия: искажение архитектоники восходящего отдела(left colon),лимфоплазматическое воспаление ламина проприа, острый криптит и абсцессы крипт.Т.о. признаки хр. воспаления мукозы с активным воспалением более всего предполагают IBD (inflammatory bowel disease).
Колит пролечен преднизолоном и сульфосалазином.
Выписан домой на преднизолоне, мезаламине (Asacol) и 6-ти месячный курс Warfarin.
Повт. УЗИ через 3 мес. - нет признаков тромбоза.
Последующее наблюдение - состояние хорошее,нет болей в животе и кровавых поносов.
Окончательный диагноз: УЛЬЦЕРАТИВНЫЙ КОЛИТ С ВТОРИЧНОЙ ГИПЕРКОАГУЛЯЦИЕЙ И ТРОМБОЗОМ ПОРТАЛЬНЫХ И МЕЗЕНТЕРИАЛЬНЫХ ВЕН.

М-да... Спасибо.

Наличие внутрисосудистого тромбоза особых сомнений не вызывало с самого начала (фрагментированные эритроциты, тромбоцитопения...) Я выбрал почку в качестве места тромбоза, т. к. течение заболевания показаось мне достаточно характерным - понос, ухудшение, потенурия, улучшение. В то же время, конечно, IBD оставалась возможной, особенно после упоминания язвы во рту. Итересно было бы исключить и холангит.
В целом хороший случай, хотя чуть запутанное описание. Спасибо.

"Не забывая о других возможностях (например, IBD и пр)"


Алон первый сказал IBD...

А описание - слово в слово из Pediatrics за август 2005 года. Там еще есть "Дискуссия".
Сейчас выложу.
:)

А описание - слово в слово из Pediatrics за август 2005 года.
Что-то не припомню.Дай ссылку, плз. :)

Дикуссия. (Ох как много!) :)
У пациента необычная комбинация диарреи, которая стала кровавой, тромбоцитопении,значительное повышение печеночных энзимов и удлиненное протромбиновое время.В ДД входит:
-ГУС
-Острый инфекционный гепатит
-Злокачественность (malignancy)
-Хр. заболевание печени.
Но ни один из этих диагнозов не объясняет полностью клиническую картину. IBD, конечно, может вызывать диаррею с кровью, но нужно было также найти объяснение для тромбоцитопении, выраженного повышения печеночных ферментов и абнормального протромбинового времени. Активная IBD привела к вторичной гиперкоагулопатии, которая, в свою очередь, привела к тромбозу, который и объясняет все находки в этом случае.

Что-то не припомню.Дай ссылку, плз. :)
//gateway.ut.ovid.com - Ovid : KIM: J Pediatr, Volume 147(2).August 2005.267-...
Я не знаю, будет ли работать ссылка, я заходила на работе через "тохну Макаби" :)

Подробности ДД острого тромбоза печеночных вен и гиперкоагуляции (из той же статьи )готова выложить в "ординаторской".

J Pediatr, Volume 147(2).August 2005.267-...
А описание - слово в слово из Pediatrics за август 2005 года.
Ну, вот - это ж разные журналы :)

Наличие внутрисосудистого тромбоза особых сомнений не вызывало с самого начала (фрагментированные эритроциты, тромбоцитопения...) Я выбрал почку в качестве места тромбоза, т. к. течение заболевания показаось мне достаточно характерным - понос, ухудшение, потенурия, улучшение. В то же время, конечно, IBD оставалась возможной, особенно после упоминания язвы во рту. Итересно было бы исключить и холангит.
В целом хороший случай, хотя чуть запутанное описание. Спасибо.
Да, описание действительно несколько хаотичное и, скорее всего, некоторые моменты или опущены или подчишенны.Но у меня сложилось впечатление, что в клинике преобладала кровавая диаррея с нарушением синтетической функции печени ( высокое РТ и низкий албумин) - поэтому и с ДД полез в ж...Anyway, respect!

Я бы тоже начала с ж...живота. Мы сегодня с коллегами обсуждали этот случай на работе, и все решили, что начинать надо было с УЗИ живота. Хотя, м.б , они все делали одновременно, просто изложение такое...
Алон, то, что это разные журналы, я знаю, но сообразила позже, когда попыталась посмотреть одну статью в Pediatrics и - упс!- не могу. Просят денег :)

CLINICAL CHALLENGES: 18 YEAR OLD MALE WITH BLOODY DIARRHEA
[GRAND ROUNDS]
KIM, HELEN J. MD; NEWMAN, BEVERLEY MD; KELJO, DAVID J. MD, PHD

Department of Pediatrics, Division of Gastroenterology, Department of Radiology, University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh.
Reprint requests: David J. Keljo, MD, PhD, Gastroenterology Department, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh PA 15213. E-mail: [Ссылки могут видеть только зарегистрированные и активированные пользователи].
Submitted for publication Aug 19, 2004; last revision received Mar 11, 2005; accepted Apr 5, 2005.
CT: Computed tomography; IBD: Inflammatory bowel disease

CASE PRESENTATION
An 18-year-old boy presented to the emergency department with a 2-week history of diarrhea and fatigue. His diarrhea was watery and nonbloody, occurring several times a day. A diagnosis of viral gastroenteritis had been made by his primary care physician. Four days before admission, his diarrhea became more frequent, accompanied by nonbloody, nonbilious emesis, and worsening fatigue. His parents noted that he looked pale and had low-grade temperatures. He denied night-time stooling but admitted to having 1 episode of fecal incontinence. He denied abdominal pain, night sweats, weight loss, jaundice, rash, easy bruising, or bleeding. There was no recent travel or unusual exposures. Medical history was notable for psoriasis. Family history was negative for inflammatory bowel disease or celiac disease but was positive for a maternal grandfather with a “ruptured colon.” There was no family history of bleeding or clotting disorders.

Physical examination revealed a pale, well-grown boy in no distress. He was fever free, with tachycardia to 119 beats/min and hypertension with a blood pressure of 148/72 mm Hg, and he had a normal respiratory rate. His weight plotted to the 90th percentile and height plotted to the 75th percentile for age. Head, ears, eyes, nose, and throat examination showed no scleral icterus but revealed an ulcer on the left tonsil. Cardiac examination revealed a I/VI systolic murmur along the left sternal border. His abdomen was not distended and not tender with no hepatomegaly; however, a spleen tip was palpable. A rectal examination revealed gross blood with no fissures or tags. On skin examination, there were no bruises, petechiae, or rashes.

The patient was admitted to the hospital for further evaluation. While hospitalized his diarrhea became grossly bloody with mucus.

Initial laboratory results included a white blood cell count of 22,300 cells/mm3 with a differential of 44% neutrophils, 36% bands, 9% lymphocytes, 7% monocytes, 1% eosinophils, 1% metamyelocytes, and 2 % myelocytes. Hemoglobin was 8.3 g/dL, hematocrit 25.8 %, with a low mean corpuscular volume of 63 and elevated red cell volume distribution width of 19.4%. Platelet count was 38,000/mm3. The reticulocyte count was 4.5 %. The peripheral smear revealed red blood cell fragments, ovalocytes, teardrop cells, and hypochromia. Blood urea nitrogen level was 13 mg/dL, and creatinine was 1.5 mg/dL. Liver function tests revealed elevated alanine aminotransferase of 1030 IU/L, aspartate aminotransferase of 746 IU/L, alkaline phosphatase of 133 IU/L, gamma-glutamyltransferase of 73 IU/L, total bilirubin of 0.4 mg/dL, and albumin of 2.9 g/dL. The prothrombin time was elevated at 19.8 seconds, with an activated partial thromboplastin time of 29.4 seconds, and an elevated international normalized ratio of 1.8. The lactate dehydrogenase was 1118 IU/L, and uric acid was 8.8 mg/dL. Erythrocyte sedimentation rate was 24 mm/h. Urinalysis revealed 2 red blood cells, trace ketones, small amount of protein, and 26 hyaline casts.

Evaluation for infectious enteritis with stool cultures, ova, and parasites, and Clostridium difficile toxin proved negative. Blood cultures were negative. Tests for infectious hepatitis including a hepatitis panel and cytomegalovirus antigen were negative. Epstein-Barr virus titers were consistent with a remote prior infection. Serial complete blood count and liver function tests revealed that the low platelet count and elevated transaminases returned toward normal levels. Renal function remained normal throughout the admission. An opthalmologic examination was negative for Kayser-Fleischer rings, and serum ceruloplasmin and copper levels, as well as 24-hour urinary copper levels, were within normal limits.

Abdominal ultrasonography with Doppler scanning revealed no flow in the left portal vein, but patent and normal flow direction in the right portal, main portal, and splenic veins. There was a mildly enlarged spleen, nonspecific gallbladder wall thickening, and a moderate amount of free fluid within the abdomen. The kidneys and liver were otherwise normal. Because there was evidence of possible thrombosis in the portal vein by ultrasound examination, initial therapy with vitamin K was discontinued, and fresh frozen plasma was not administered.

A computed tomography (CT) angiogram was obtained to further evaluate for possible thrombosis in the portal system and to inspect the liver and colon. This imaging revealed extensive subocclusive thrombosis of the portal and mesenteric venous systems, patchy enhancement of the liver, and colonic changes suggestive of colitis (Figure). There was no suggestion of appendicitis, ruptured appendix or other source of abdominal sepsis.



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Figure. Images from the portal venous phase of a contrast enhanced CT scan. A, Almost complete thrombosis of the intrahepatic portal venous branches (arrows). Liver has patchy heterogeneous appearance with peripheral geographic areas of low attenuation. B, Subocclusive thrombus of portal confluence and medial splenic vein (black arrows). Splenic flexure of colon has thickened, edematous walls (white arrows) with prominent mucosal enhancement. C, Enlarged superior mesenteric vein with subocclusive thrombus (black arrow). Walls of descending and transverse colon (white arrows) are thickened and edematous with prominent mucosal enhancement.

--------------------------------------------------------------------------------

The patient was evaluated for known primary causes of hypercoagulable states. The evaluation was negative for factor V Leiden and prothrombin G20210A mutations. There was normal activated protein C resistance. Low antithrombin III, protein C activity, and protein S activity were believed to be caused by liver disease or the recent thrombosis itself. There was no evidence of an antiphospholipid antibody syndrome, with normal tissue thromboplastin inhibition indexes, negative hexagonal lipid neutralization test, normal anticardiolipin and antithyroid antibody levels, and normal dilute Russell viper venom time. The patient was heterozygous for the methylenetetrahydrofolate reductase thermolabile variant (C677T) but had normal homocysteine levels. Flow cytometry was negative for paroxysmal nocturnal hemoglobinuria as a cause of thrombosis.

A colonoscopy was performed. At colonoscopy the colon was found to be diffusely inflamed and edematous with mucosal ulceration and friability, indicating a pancolitis. The terminal ileum was not inspected. Biopsy specimens revealed acute colitis with inflammatory pseudomembranes, organizing submucosal thrombi, and crypt abscess formation. No viral inclusions, organisms, or granulomas were appreciated. There were no chronic changes at this point. Concern was raised about a thrombotic/ischemic colitis.

The patient was transferred to the intensive care unit for optimal management of anticoagulation in the face of active gastrointestinal bleeding. Heparin was used for anticoagulation.

A sigmoidoscopy with biopsy was performed on a later date to further delineate the underlying diagnosis. These biopsy specimens of the left colon showed architectural distortion and lamina propria lymphoplasmacytic inflammation with gland lift-off, acute cryptitis, and crypt abscesses. These features of chronic mucosal injury with active inflammation were more suggestive of chronic inflammatory bowel disease. The colitis was treated with prednisone and sulfasalazine. The patient was eventually discharged on prednisone, mesalamine (Asacol), and a 6-month course of warfarin. Repeat abdominal ultrasound examination approximately 3 months after the initial ultrasound examination revealed patent portal vessels with no evidence of thrombus. On follow-up visits, the patient's ulcerative colitis was noted to be under good control, with resolution of abdominal pain and bloody diarrhea. The final diagnosis was ulcerative colitis with secondary hypercoagulable state and portal and mesenteric vein thrombosis.

DISCUSSION
The patient presented with the unusual combination of diarrhea that became bloody, thrombocytopenia, markedly elevated liver enzymes, and prolonged prothrombin time. A number of diagnoses were considered and excluded by the treating team after testing. These included hemolytic uremic syndrome, acute infectious hepatitis, malignancy, and chronic liver disease. None of these diagnoses fully explained the constellation of findings. Inflammatory bowel disease certainly could have caused diarrhea that became bloody, but an additional explanation was needed for the thrombocytopenia, marked elevation of liver enzymes, and abnormal prothrombin time. Active inflammatory bowel disease resulting in a secondary hypercoagulable state leading to portal and mesenteric vein thrombosis explains all of the key findings of the case.

It is difficult to make a clinical diagnosis of acute portal vein thrombosis. The common presenting symptoms are extremely vague—abdominal pain, anorexia, and vomiting.1 Extension of the thrombus into the mesenteric venous system may progress to intestinal ischemia and infarct,2,3 with marked abdominal pain and development of peritoneal signs. The marked elevation of liver enzymes seen in this patient is not a reported feature of acute portal vein thrombosis,4 except in the immediately post-liver-transplantation setting.5,6 In the case at hand with extensive clot formation, the degree of elevation may represent ischemic insult from diffuse clotting in small intrahepatic vessels as well. (The heterogeneous enhancement of the liver seen at CT scanning would be compatible with this.) Portal hypertension may develop if the thrombus persists, leading to related signs of splenomegaly, esophageal varices, and gastrointestinal bleeding.3 If the tests are done, the diagnosis is easily made by ultrasonography with Doppler scanning and computed tomography.3 Both anticoagulant therapy with heparin and thrombolytic therapy with urokinase have been successfully used to prevent progression to portal hypertension and intestinal infarct.2,3,7 Peritonitis and signs of intestinal infarction require excision of necrotic bowel.2

Deep vein thromboses are uncommon in childhood and always raise the question of a hypercoagulable state. Hypercoagulable states may occur as a result of inherited coagulation disorders or acquired coagulation risk factors.8,9 The most common inherited procoagulant disorder would be factor V resistance to the anticoagulant activity of activated protein C, caused by the Leiden mutation in factor V. Somewhat less common is the procoagulant G20210A mutation in the prothrombin gene. Deficiency of or resistance to the anticoagulant proteins antithrombin III, protein C, and protein S are recognized causes of hypercoagulability. Hyperhomocystinemia can predispose to thrombosis. An inherited cause of hyperhomocystinemia is deficiency of methylenetetrahydrofolate reductase. Paroxysmal nocturnal hemoglobinuria is an acquired genetic mutation in the multipotential hematopoietic stem cell, which predisposes to thrombosis.9,10 Antiphospholipid antibodies are well-recognized risk factors for thromboses.

Secondary causes of hypercoagulation must also be kept in mind when evaluating any patient with thrombosis. These acquired risk factors include infection, dehydration, immobility, prior surgery, placement of a central venous catheter, and medications such as corticosteroids and oral contraceptives.8 Disease states that involve protein loss such as nephrotic syndrome 8,9,11 (or colitis—see below) are associated with an increased risk of thrombosis. Inflammatory diseases such as malignancies, systemic lupus erythematosis, and inflammatory bowel disease are also associated with a prothrombotic state.9

Deep vein thrombosis is a recognized complication of inflammatory bowel disease (IBD). The reported incidence of thrombotic complications in IBD to ranges from 1% to 6.7%.12 The prevalence in one postmortem study was 39%.12 Thrombosis with IBD tends to occur in younger patients 13,14 and is associated with a high mortality rate (8%).14 Nine percent of thromboembolic events in IBD are found in the portal venous system, and this is associated with a mortality rate as high as 50%.15 Cerebral vascular events, including cerebral venous thrombosis, carotid artery thromboembolism, and retinal branch artery occlusion, account for 10% of thrombotic events in IBD and are associated with high mortality and neurologic morbidity rates.15 Thrombi affecting the pulmonary, gonadal, cardiac, and peripheral vessels have also been described.15 Because of the increased risk of thrombosis, thromboprophylaxis with low-molecular-weight heparin of all hospitalized patients with IBD has been suggested, although it has not yet been studied.16 The pathogenesis of the thrombotic complications of IBD appears to be multifactorial. Some studies cite a high incidence of inherited procoagulant disorders in patients with IBD 17; however, no inherited disorder has been found more frequently in patients with IBD than in the general population.12,16 Inflammation results in elevated platelet counts and elevated levels of the procoagulant factors V, VIII, fibrinogen, and von Willebrand factor.16 It decreases levels of the clot-stabilizing factor XIII, which may counter the procoagulant effects of inflammation.16 Fecal losses and consumption in the microvasculature of anticoagulant factors protein C, protein S, and antithrombin III could increase clotting tendency.16 Folic acid and vitamin B12 deficiency can be seen in patients with IBD and can contribute to elevated homocysteine levels, which promote thrombosis through an unknown mechanism.16 Antiphospholipid antibodies are somewhat more common in patients with IBD.16 Other prothrombotic factors common in patients with IBD include dehydration, immobility, central venous catheters, steroid use, and prior surgery.

Recent evidence suggests that although greater than 50% of children with portal vein thrombosis are deficient in 1 or more anticoagulant proteins, they do not appear to have a higher prevalence of hereditary prothrombotic disorders.18 Inflammation, dehydration, and decreased levels of protein S, protein C, and antithrombin III likely contributed to the thrombosis in this case.

Although it seems hazardous to treat a patient bleeding from colitis with heparin, heparin has actually been used in therapeutic trials to treat ulcerative colitis. These trials were based on the theory that thromboses in the microvasculature and resultant ischemia contributed to the disease process.19 One prospective study with unfractionated heparin resulted in improvement of ulcerative colitis clinical activity, inflammatory laboratory values, and histologic changes.20 In one small randomized trial the efficacy of heparin in treating active colitis was similar to that of steroids, and the heparin did not exacerbate the bleeding.21 The apparently beneficial effect of heparin in ulcerative colitis has been hypothesized to be related to anticoagulant effect, enhanced mucosal repair by promotion of growth factor activity, and antiinflammatory effects.22

A 7-week-old girl of Middle Eastern descent is admitted to the hospital for a cough of 10 days’ duration that is worsening and has produced posttussive emesis for the last 7 days. An episode of perioral cyanosis lasting less than 1 minute was noted 5 minutes after a feeding. There has been no fever, rhinorrhea, emesis, or diarrhea. The baby was born at term without perinatal complications.

Three days into her illness, the child’s pediatrician had placed her on nebulized bronchodilator therapy for presumed viral bronchiolitis. Re-evaluation on the day of admission shows no improvement. A chest radiograph reveals marked cardiomegaly with clear lung fields.

The physical examination reveals a well-nourished baby who looks alert but manifests slightly decreased activity. Her heart rate is 130 beats/min, respiratory rate is 35 breaths/min, blood pressure is 85/45 mm Hg, and pulse oximetry saturation is 100% in room air. The child’s length is at the 95th percentile, and her weight and head circumference are at the 75th percentile. Auscultation reveals scattered end-expiratory wheezes, more prominent at the bases, but no grunting, retractions, or nasal flaring. A soft grade I/VI systolic flow murmur that does not radiate is audible at the left sternal border. Both heart sounds are normal. The baby appears well perfused and has normal femoral pulses. The rest of her physical findings are normal.

CBC, electrolyte levels, and liver function tests all yield normal results.

Что будем делать дальше?

Что будем делать дальше?
Будем делать ИЗИ сердца, искать порок.

Какие еще мнения?

ИМХО,у ребенка есть признаки сердечной недостаточности по малому кругу.Возможно надо назначать дигоксин.И делать УЗИ,искать ВПС.

м.б. ЭКГ? потом ЭХО?

Если я правильно поняла, шум в сердце есть? Вялость, слабость, кашель.
Хотелось бы увидеть клинический анализ крови.

CBC, electrolyte levels, and liver function tests all yield normal results.Наташа, CBC - это по-американски клинический анализ крови.

Наташа, CBC - это по-американски клинический анализ крови.Чьёрт. Все равно, хочу его увидеть. :rolleyes:

м.б. ЭКГ? потом ЭХО?
An ECG revealed tall QRS complexes with inverted T waves consistent with a strain pattern indicative of left ventricular hypertrophy. The PR interval was slightly shortened at 80 msec. An echocardiogram revealed moderate-to-severe hypertrophic cardiomyopathy affecting both ventricles. Diastolic dysfunction was moderate to severe.
Что дальше будем делать?

84/45 - это низкое давление для новорожденого?

Нет.
Впрочем, массу можно ребенка?

Она не новорожденная. Ей 7 недель. Практически, 2-хмесячная.
Наталья, это все, что я могу сказать про вес.well-nourished baby . The child’s length is at the 95th percentile, and her weight and head circumference are at the 75th percentile. Это не я задачку придумала. Это американцы противные ее придумали, а нас, бедных израильских врачей, заставляют решать, когда мы сдаем шлав бет (второй экзамен на звание специалиста). :)

А для двухмесячной давление у нее нормальное?

Ну, давайте думать! Что имеем?
1) cough of 10 days’ duration that is worsening and has produced posttussive emesis for the last 7 days.
2) An episode of perioral cyanosis lasting less than 1 minute was noted 5 minutes after a feeding.
3)There has been no fever, rhinorrhea, emesis, or diarrhea.
4)The baby was born at term without perinatal complications.
5)viral bronchiolitis не подтверждается.
6)A chest radiograph reveals marked cardiomegaly with clear lung fields.
7)well-nourished baby who looks alert but manifests slightly decreased activity
8)На ECG -high-voltage QRS complexes with a shortened PR interval, left ventricular hypertrophy.
9) На ЭХО - moderate-to-severe hypertrophic cardiomyopathy affecting both ventricles.
ДД?

Ну, наверное, нужно подумать о причинах гипертрофическиx кардиомиопатий у новорожденных. Пойду думать. :)

От своих соотечественников жду только поганок!!! Давайте шукать нарушения обмена различных важных веществ. Начнем от болезни Гоше и далее по длинному списку! Я в scrubs ( опер-костюм) так что можете швырять помидорами!

Метаболическая идея - good. Но при Гоше вроде бы другая клиника. Пойду дальше думать.

P.S. Нет ли у мамы диабета?

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В общем, если мама не диабетик, то, наверное, здесь нужно искать. Пойду спать.

Хотелось бы сделать суточный мониторинг для исключения аритмий.

Странно: ЭХО есть, а Допплера нет. Как так?

Надо все-таки сначала исключить всякую ерунду типа AtrioVentricular septal defect. Ведь все явления, обнаруженные на ультразвяке и рентгене появились не в одночасье..

Я думаю, ерунда не получится. Гипертрофия обоих желудочков. Пападоктор прав. Дело серьезное. Что-то не синтезируется.

P.S. Нет ли у мамы диабета?
Если бы был, это бы было в условии задачи. :)

Значит что-то не синтезируется или не метаболизируется.

Слово сказано :)

The clinical picture clearly indicated a hypertrophic cardiomyopathy. Viral titers for coxsackievirus, enterovirus, and Epstein-Barr virus were negative. Carnitine levels were normal. Based on the ECG and echocardiographic results, suspicion was high for Pompe disease. A skin biopsy for fibroblast culture and a blood assay for acid alpha-glucosidase activity revealed diminished activity, thus confirming the diagnosis.

The Disorder
Pompe disease belongs to a group of inborn errors of metabolism referred to as glycogen storage diseases. These diseases are caused by a deficiency or absence of one of the enzymes involved in glycogen metabolism that results in the accumulation of glycogen in tissues. Glycogen storage diseases are classified numerically based on the chronologic order in which the enzyme was discovered. Pompe disease is a type II glycogen storage disease.

The enzyme defect in Pompe disease involves lysosomal acid alpha-glucosidase or acid maltase. This enzyme is responsible for the degradation of glycogen in lysosomes, technically making Pompe disease a lysosomal storage disease. The incidence of Pompe disease is 1 in 40,000 live births; it is transmitted in an autosomal recessive pattern. The gene locus for the enzyme has been localized to chromosome 17q25.2. No ethnic predilection exists.

The range of phenotypic expression is wide, varying in age of onset and organ involvement, but all variations involve a myopathy. The infantile form is the most severe. It is associated with cardiomegaly and hypotonia, with death occurring usually before the age of 2 years. Affected children typically appear normal at birth but soon develop generalized muscle weakness, feeding difficulties, macroglossia, hepatomegaly, and progressively worsening heart failure due to hypertrophic cardiomyopathy. The classic ECG finding consists of high-voltage QRS complexes with a shortened PR interval (Fig. 1). Death usually results from cardiorespiratory failure or from aspiration pneumonia.

The juvenile-onset form usually presents in adolescence but can manifest as early as age 1 year with delayed motor development or difficulty walking. Affected children develop oromotor dysfunction and swallowing difficulties. Death may occur before the second decade from cardiorespiratory failure. The degree of cardiomegaly is variable, but overt cardiac failure unusual. An adult form also presents as a slowly progressive myopathy.

A Misleading Sign
This case shows that not all wheezing should be assumed to be a result of acute bronchiolitis. Wheezing occasionally is heard in patients who have congestive heart failure. In hypertrophic cardiomyopathic states, the reduction in ventricular compliance and relaxation leads to elevated diastolic and end-diastolic pressures, which cause elevated left atrial pressure and volume and increased pulmonary venous and pulmonary capillary pressure. If the latter exceeds the plasma oncotic pressure, interstitial lung fluid develops initially, followed by alveolar edema. The clinical counterparts are moist rales and, occasionally, wheezing. Marked cardiomegaly, as in this case, can cause wheezing by extrinsic pressure on airways.

Differential Diagnosis
Given the unique and acute constellation of findings, the differential diagnosis of infantile Pompe disease is limited. However, valuable time can be lost between the onset of symptoms and consideration of the diagnosis. Most infants survive only a few months beyond the time of diagnosis, necessitating the need for a rapid diagnosis so supportive therapy can be started. Diagnosing this condition requires considerable suspicion and awareness of the disease on the part of pediatricians and specialists. In older children, signs and symptoms can be insidious and attenuated, thus delaying the diagnosis.

Diseases that have been mistaken for infantile Pompe disease because they cause either hypotonia or cardiomyopathy include Werdnig-Hoffman disease, hypothyroidism, myocarditis, endocardial fibroelastosis, Krabbe disease, congenital muscular dystrophy, and respiratory chain disorders. Few, if any, diseases are associated with both hypotonia and cardiomyopathy in infancy. Werdnig-Hoffman disease, a type of spinal muscular atrophy (SMA), presents with hypotonia but also can be associated with structural congenital heart defects, but not cardiomyopathy. Type III SMA is associated with hypotonia and dilated cardiomyopathy but presents in adolescence. Congenital hypothyroidism is associated with hypotonia but not (usually) cardiomyopathy. The presence of hypotonia along with cardiomegaly virtually confirms the diagnosis of Pompe disease. Diseases that can mimic some of the symptoms of the juvenile form include poliomyelitis, limb-girdle muscular dystrophy, Becker muscular dystrophy, and myasthenia gravis.

Laboratory Findings
Laboratory findings consist of elevated creatine kinase, AST, and lactate dehydrogenase levels. Chest radiography reveals massive cardiomegaly and often provides the first clue that the child has Pompe disease. Echocardiography and electrocardiography are used to assess the degree and severity of cardiac involvement. Echocardiography demonstrates hypertrophic cardiomyopathy with thickening of both ventricles and the interventricular septum. ECG findings are as mentioned previously. Muscle biopsy shows the presence of vacuoles that stain positively for glycogen. The definitive diagnosis is established by testing for the absence or reduced levels of acid alpha-glucosidase in muscle, cultured skin fibroblasts, or blood. Skin biopsy is preferred.

Therapy
No definitive treatment exists for Pompe disease. A high-protein diet may be beneficial in the juvenile and adult forms. Nocturnal ventilatory support for patients who have late-onset disease improves the quality of life and can be beneficial during the phase of respiratory decompensation. Recent clinical trials involving enzyme replacement therapy with recombinant acid alpha-glucosidase have shown a decrease in cardiomegaly and improved cardiac and skeletal muscle function, with increased survival. These trials offer some hope in the treatment of an otherwise devastating disease.

Lessons for the Clinician
Pompe disease is a rare but devastating disease that has a unique constellation of signs and symptoms. Diagnosis requires a high degree of suspicion; a timely diagnosis can help ensure that the child receives proper supportive therapy. This case also illustrates how an uncommon disease such as Pompe disease can present with common symptoms such as coughing or wheezing.

Мы вчера в чате долго это обсуждали, и я ушла спать, будучи уверенная, что Яна напишет свою логичную версию сразу. Ан нет, пришлось подтолкнуть. Яне медаль.

Очень интересно и полезно.Спасибо.

Is there any treatment?


Individuals with Pompe disease are best treated by a team of specialists (such as cardiologist, neurologist, and respiratory therapist) knowledgeable about the disease, who can offer supportive and symptomatic care. The discovery of the GAA gene has led to rapid progress in understanding the biological mechanisms and properties of the GAA enzyme. As a result, an enzyme replacement therapy has been developed that has shown, in clinical trials with infantile-onset patients, to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation. A drug called alglucosidase alfa (Myozyme©), has received FDA approval for the treatment of Pompe disease.
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

P.S. Не, мне не надо медаль. Я эту знала задачку. Sorry :)))))

A 7-year-old-girl who has type 1 diabetes mellitus is admitted to the hospital with a 1-month history of intermittent weakness of her lower extremities associated with pain in her feet and lower legs. The weakness is worse in the morning, when she is unable to walk. She has no associated numbness, and her weakness is not related to activity, food, or cold.

The physical examination reveals an alert, oriented girl who has normal cardiovascular, pulmonary, and abdominal findings. The neurologic examination shows intact cranial nerves. She has good tone and strength levels of 5/5 in her arms and 4/5 in her legs, with preserved sensation and deep tendon reflexes throughout. She is able to bear weight with help but cannot take any independent steps. Laboratory tests to determine the cause of her muscle weakness show a normal CBC and chemistry panel, thyroid-stimulating hormone level of 0.97 U/L (normal, 0.35 to 5.5 U/L), free thyroxine of 15.6 pmol/L (normal, 11.5 to 22.7 pmol/L), creatine kinase of 66 U/L, ESR of 40 mm/hr, and ECG that shows a corrected QT interval of 0.44.
Предположения по диагнозу? Чем и как его можно подтвердить?

А электролиты входят в chemistry panel ?

Да.
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A 7-year-old-girl who has type 1 diabetes mellitus is admitted to the hospital with a 1-month history of intermittent weakness of her lower extremities associated with pain in her feet and lower legs. The weakness is worse in the morning, when she is unable to walk. She has no associated numbness, and her weakness is not related to activity, food, or cold.

The physical examination reveals an alert, oriented girl who has normal cardiovascular, pulmonary, and abdominal findings. The neurologic examination shows intact cranial nerves. She has good tone and strength levels of 5/5 in her arms and 4/5 in her legs, with preserved sensation and deep tendon reflexes throughout. She is able to bear weight with help but cannot take any independent steps. Laboratory tests to determine the cause of her muscle weakness show a normal CBC and chemistry panel, thyroid-stimulating hormone level of 0.97 U/L (normal, 0.35 to 5.5 U/L), free thyroxine of 15.6 pmol/L (normal, 11.5 to 22.7 pmol/L), creatine kinase of 66 U/L, ESR of 40 mm/hr, and ECG that shows a corrected QT interval of 0.44.
Предположения по диагнозу? Чем и как его можно подтвердить?
Конверсия тревоги? Мамашку "нежно" попытать "чё было" месяцок назад...
З.Ы. Заметки психиатра, на полях:)

А какая норма кретинкиназы?

Because of the unusual manifestations of the child's muscle weakness involving only the lower extremity, with no cranial nerve involvement, no relationship to activity, worsening of weakness on school days, and improvement during holidays and weekends, in addition to a recent history of school difficulty, a diagnosis of conversion disorder was entertained.

A simple test strongly supported that diagnosis; 1 mL of intravenous normal saline was administered to the child after it was explained to her that this could cure her illness. Shortly after the injection, the child stood up alone and walked unassisted back and forth in the hallway. Psychiatric consultation identified school as a major stressor in the patient's life. The presence of type 1 diabetes, with its daily testing and insulin injections, was identified as a vulnerability that might have triggered the conversion reaction.

Physical therapy was initiated and the parents advised about the nature of the problem. Strategies were offered to alleviate the stressors in the child's life. The family also was advised to shift attention from the child's symptoms and to focus on recovery. The girl responded well to treatment, and follow-up showed better coping abilities and amelioration of her muscle weakness.

The Condition
Conversion disorder should be suspected when a patient's symptoms do not fit into the framework of known medical illnesses or when appropriate evaluation reveals no organic disease or plausible pathophysiologic explanation. Conversion disorders in children do not indicate a major psychiatric disorder but represent the child's subconscious plea for help in situations in which he or she cannot cope. These situations can arise from a variety of stressors, such as struggles in school, family disharmony, and sexual and physical abuse. Symptoms are referable to the CNS in 65% of children who have conversion disorders. The most usual presentations are episodic loss of awareness, such as pseudoseizures and syncope; motor dysfunction, including gait disturbances and paresis; sensory abnormalities, primarily pain and numbness; and disorders of the special senses.

Diagnosis
Once the diagnosis of conversion disorder is suspected in a child who has persistent and debilitating symptoms, a sensible evaluation plan should be created. In severe cases, hospitalization may be warranted. During the evaluation, focused investigation and testing should be pursued to be reasonably certain that there is no medically treatable cause. Psychiatric evaluation instituted simultaneously should concentrate on five main areas: 1) the levels of stress or anxiety in the child and family, 2) any special predisposing vulnerabilities in the child that might lower the threshold for coping with stress and anxiety (eg, learning disabilities, peer pressures, problems of body image, chronic illness, and family disharmony or conflict), 3) a possible temporal relationship between a specific stress and the onset of symptoms, 4) role models from whom the symptoms might have been learned, and 5) evidence of primary or secondary gain from the symptom.

Differential Diagnosis
The differential diagnosis of a child presenting with intermittent muscle weakness includes familial periodic paralysis (hypokalemic or normokalemic); metabolic myopathies, including myophosphorylase deficiency and mitochondrial deficiency; limb-girdle muscular dystrophy; myasthenia gravis; and endocrinopathies such as thyroid disorders and adrenal disorders. Delineation of the clinical pattern and laboratory testing should allow the clinician to determine if any of these disorders is present. If no other disorder fits and if significant stress is evident, a psychosomatic cause should be considered.

Treatment
Once the evaluation has been completed, a treatment plan is presented to the parents and the child. The first step is to explain that the symptom is real but that no organic disease has been demonstrated. Anxiety or stress has led to the symptom, and this element must be understood and relieved for the child to get better. The treatment must be tailored to the problem, with set goals and the provision of positive feedback as goals are achieved. In addition to measures aimed at understanding and relieving stress, treatment for a patient complaining of weakness might involve "graded" physical therapy.

Removing the secondary gain achieved by the symptom is essential for recovery and to eliminate perpetuation of the symptom. Examples of secondary gain include missed school days and increased parental attention because of the symptom. It is essential that the treatment provide "escape with honor" and that the regimen give some control to the child. After discharge, continued psychotherapy should be aimed at allowing the child to give up the sick role and cope with future stress and anxiety more productively.

Prognosis
Except for children who have pseudoseizures, most children who have a conversion disorder have no underlying major mood disorder or psychiatric illness. Major mood disorders have been identified in 32% of children who have pseudoseizures. A history of sexual abuse is common in patients who have conversion disorders.

Because children are still in the formative stages of personality development, the adult diagnosis "hysterical personality," now called "histrionic personality disorder," is questionable when applied to children who have conversion disorder. Histrionic personality disorder comprises a constellation of traits, including dependency, immaturity, egocentricity, attention-seeking behavior, and manipulation. With timely intervention, the child who has a conversion disorder will develop better coping abilities and give up the sick role, thus aborting perpetuation of the symptom and progression to an adult histrionic personality disorder.

Further Observations
This patient had a chronic illness and had become aware of its power to influence the adults in her world. Another example of this effect is that pseudoseizures are common in children who have true epilepsy.

Clinical testing should be judicious because the tests themselves promote anxiety and confirm and reinforce the power and seriousness of the symptom. The child herself is deceived about the source of her symptoms, and families of children who have conversion disorders tend to have conversion symptoms, reinforcing the impressionable child's symptomatology. The clinician must be firm in the diagnosis of conversion and resist his or her own anxiety, which tends to produce the need to do more testing. The simple test employing intravenous saline was an effective diagnostic tool in this case, but it is important that clinicians undertake such procedures with sensitivity to avoid their being perceived by the patient as a trick, potentially undermining trust.

The use of physical therapy was a face-saving treatment for the patient and more likely to be acceptable to patient and parents than a purely psychiatric approach, which can be counterproductive if instituted at the wrong time. Similarly, early hospitalization can raise the stakes ominously. Sometimes, psychotherapy will be acceptable if the reason given for recommending such treatment is "to help you cope with the stress of being ill for so long."

Lessons for the Clinician
Conversion disorder represents a child's expression of a difficult or stressful situation through a physical symptom. The pediatrician, being familiar with the child and parents, should be able to gain the trust of the child and identify stressors and difficulties in the child's life. Psychiatric referral and sometimes hospitalization are crucial for the recovery of children whose symptoms are prolonged and unresponsive to counseling by the pediatrician.

А какая норма кретинкиназы?
После 100 первых часов жизни от 5 до 130 (Нельсон).

Думаю, что быстрей всех эту задачу решат анестезиологи-реаниматологи.

A 10-month-old boy is brought to a community ED because he started vomiting last night and “has not and “has not been the same since.” This morning, his mother noted that he was breathing fast. He had a low-grade fever this morning, but none prior. He has had no weight loss or diarrhea and
has not been exposed to illness. Intravenous access is obtained, and the child is intubated because of respiratory distress and is flown to a children’s
hospital.On examination, the boy’s temperaturei s 37.6°F (99.7°C), heart rate is 158 beats/min, and blood pressure is 90/44 mm Hg. His respiratory rate had been 60 breaths/min prior to being intubated.He is a plump, robust infant who is sedated on the ventilator. Faint crackles are audible in his lungs. His skin is warm and well perfused.The rest of his findings are normal.
Laboratory findings include glucose,
176 mg/dL (9.8 mmol/L);
sodium 140 mEq/L (140 mmol/L);
potassium, 3.1 mEq/L (3.1 mmol/);
chloride, 115 mEq/L (115 mmol/L);
bicarbonate, 10 mEq/L (10 mmol/L);
calculated anion gap, 15 mEq/L(15 mmol/L);
BUN, 5 mg/dL (1.8 mmol/L);
creatinine,0.3 mg/dL (26.5 mcmol/L).
A blood gas reveals a pHof 7.29 with
a bicarbonate level of 14 mEq/L(14 mmol/L),a carbon dioxide concentration
of 14 torr, and a base deficit
of
18.6 mEq/L.
His WBC count is
14.9103/mcL (14.9109/L) with
71% neutrophils and 2% bands.
He is started on vasoactive medication for hypotension and treated for sepsis, but the clinicians are concerned that he has had minimal fever and no rash, and the laboratory findings are puzzling.

An additional blood test reveals the diagnosis.

37.6°F (99.7°C),
Хоррошая опечатка! :)
Не совсем понимаю, за что ребенок переведен на ИВЛ (только из-за одышки 60 в минуту и крепитации в легких?) Гемодинамика стабильная, нарушений периферического кровообращения нет, тем не менее, проводится инотропная поддержка (кстати, чем и в какой дозе?). Что на рентгеновском снимке?

Наталья, вся, имеющаяся в условии информация, выложена. :)

В качестве подсказки :) :
Какой ведущий клинический синдром имеется в наличии у этого младенца?

Метаболический ацидоз с компенсаторной гипервентиляцией. Анионовая щель присутствует. Нужно делать toxscreen и скорее всего получим отравление салицилатами.

Discussion

1)The child had an anion gap acidosis,
but no evidence of a disorder that
would cause lactic acidosis.
2)Although
he had been vomiting for 12 hours,
he had no other insensible losses to
explain the rapid deterioration.
3) Diabetic
ketoacidosis seemed unlikely
because his glucose level never exceeded
200 mg/dL (11.1 mmol/L).

The wide anion gap acidosis
prompted measurement of salicylate
concentrations, although there was
no history of ingestion. Salicylates
were present at a toxic level of
60 mg/dL (4.3 mmol/L). The patient
was alkalinized immediately and
dialyzed. In 24 hours, he was extubated
and was doing well.

Laboratory Clues

Severe dehydration from vomiting or
diarrhea can cause a significant lactic
acidosis due to tissue hypoxemia and
hypoperfusion. However, this child
had only a brief history of vomiting.
The rapid breathing and respiratory
distress that required intubation led
the clinicians to consider an underlying
metabolic derangement. Other
disorders to consider in this case are
methanol toxicity, uremia, diabetic
ketoacidosis, paraldehyde ingestion,
iron and isoniazid toxicities, lactic acidosis,
and ethylene glycol ingestion.
The addition of salicylism to the list
creates the “MUDPILES” mnemonic.
In this case, the child’s mother
later discovered that one of the siblings
had given the infant several
adult aspirin tablets. Although the
ingestion history was not known at
the time of admission, a thorough
investigation of the child’s wide anion
gap acidosis led to the diagnosis.
Other supporting laboratory findings
included the potassium concentration
of 3.1 mEq/L (3.1 mmol/L) and
serum bicarbonate level of 10 mEq/L
(10 mmol/L).

The Disorder

Aspirin toxicity remains one of the
most serious ingestions in the pediatric
population. Despite the recent
declining incidence, there still are approximately
16,000 cases yearly of
aspirin overdose in this country, resulting
in 30 to 35 deaths. An acute
toxic dose for a child is greater than
150 mg (approximately one half of a
325-mg adult tablet) per kg. Although
overall use of aspirin has decreased,
most households in the
United States still contain salicylates
in one form or another (tablets, bismuth
compounds, keratolytic agents).

Pathophysiology

Salicylates have a broad scope of action,
especially in toxic doses, because
of their ability to uncouple oxidative
phosphorylation, inhibit
amino acid synthesis, and inhibit
Krebs cycle enzymes. The emesis and
nausea that patients experience after
aspirin ingestion are related to direct
gastric irritation. Other effects include
altered hearing (usually tinnitus),
fever, and altered mental status
that can range from agitation to seizures
to stupor and coma.
In the initial phase of aspirin overdose,
patients experience respiratory
alkalosis due to direct stimulation of
the CNS respiratory drive. To correct
this alkalosis, bicarbonate is excreted
in the urine, causing alkaluria. Initially,
potassium also is excreted in
the urine, leading to global hypokalemia.
In the next phase of salicylate
toxicity, the kidneys attempt to preserve
the potassium level by an exchange
for hydrogen ions in the
urine. This paradoxic aciduria in the
face of a respiratory alkalosis is a hallmark
of aspirin toxicity.
In the final stages of aspirin overdose,
hyperpnea continues as a response
to the primary metabolic acidosis.
This exaggerated breathing
contributes further to insensible water
losses. Although adults tend to
have a mixed respiratory alkalosis and
metabolic acidosis, acidosis often
predominates in young children. Finally,
as in this infant, salicylates increase
pulmonary vasculature permeability,
leading to noncardiogenic
pulmonary edema.

Laboratory Evaluation

Several studies should be ordered in
cases of suspected salicylate toxicity.
Electrolytes, BUN, creatinine, arterial
blood gases, complete blood
count, and liver function tests should
be checked immediately. Hypokalemia
is common and can be severe.
Salicylate levels should be checked
immediately if ingestion is suspected
and subsequently checked every 2 to
4 hours until decreasing or reaching
less than 30 mg/dL (2.2 mmol/L).
Although levels typically peak 4 to
6 hours after aspirin ingestion and
correlate poorly with clinical symptoms,
prolonged peaking of salicyindex
of suspicion
426 Pediatrics in Review Vol.27 No.11 November 2006
lates occurs with ingestion of entericcoated
tablets or in the presence of
any obstruction in the GI tract, such
as a pill bezoar or pylorospasm.
As in this patient, if the diagnosis
is uncertain, additional laboratory
testing should be undertaken to rule
out other causes of anion gap acidosis.
Serum lactate, osmolarity, and a
urinalysis looking for ketones can be
helpful. It also may be useful to measure
iron and alcohol levels (looking
for methanol and ethylene glycol).
As always, a thorough history is indicated,
particularly focusing on all
medications, including over-thecounter
items, in the household.

Treatment

If the patient is alert, activated charcoal
should be administered. Gastric
lavage usually is not recommended
unless the ingestion is believed to
have been a large, life-threatening
dose and has been brought to medical
attention within 1 hour. Most
important in the treatment of salicylism
is the correction of multiple metabolic
derangements and dehydration.
Initially, fluid boluses should be
considered in the face of severe dehydration.
Caution must be exercised
in the presence of pulmonary edema
or renal failure.
Alkalinization enhances salicylate
elimination and should be instituted
promptly. A goal for serum pH
should be approximately 7.5, with a
goal for urinary pH of greater than
7.5. Standard recommendations suggest
using a 1 to 2-mEq/kg bolus of
bicarbonate followed by a sodium bicarbonate
drip. Because persistent
hypokalemia may interfere with alkalinization
of the urine and salicylate
excretion, it is critical to add potassium
to fluids in patients who do not
have renal failure.
Dialysis should be instituted if the
serum salicylate level is greater than
100 mg/dL (7.2 mmol/L) in acute
toxicity or if there are signs of pulmonary
edema, renal failure, persistent
altered mental status, worsening vital
signs such as fever, or congestive
heart failure.
Intubation might be considered
in the most seriously ill patients. Clinicians
should realize, however, that
intubation of the patient poisoned by
salicylates can be dangerous. The patient’s
own ability to hyperventilate
and regulate acidosis is suppressed,
and he or she may develop worsening
acidosis.
Rarely do long-term sequelae result
from salicylate toxicity. When
recognized and treated early, most
pediatric patients do very well.

Lessons for the Clinician

It is important to consider salicylism
in the differential diagnosis of a child
who has an anion gap acidosis. In this
case, a careful review of the initial
history, physical findings, and laboratory
studies narrowed the differential
diagnosis significantly. Early recognition
and treatment can be life-saving.

A 4-year-old Arabic boy has experienced leg pain for the past 2 months. He localizes the pain to the middle of his right thigh, sometimes extending to his knee. He is able to run and play, but pain recurs at the end of vigorous play, is worse at the end of the day, and often wakes him at night. It is relieved by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). There is no history of trauma, redness, swelling, fever, weight loss, or rashes. The patient has had no similar complaints in the past. There is no family history of bone or joint diseases. He was born in the United States but has lived in Lebanon for the past year.

On physical examination, the boy's temperature is 99.1 F (37.3 C), pulse is 108 beats/min, respiratory rate is 28 breaths/min, and blood pressure is 103/68 mm Hg. He localizes pain to the middle of his right thigh, but there is no tenderness, swelling, or erythema in that area. There is full range of motion at both the right hip and knee joints, and strength is 5/5.

Laboratory values include a WBC count of 8.5x103/dL (8.5x109/L), Hgb level of 13.3 g/dL (133 g/L), platelet count of 455x103/dL (455x109/L), ESR of 22 mm/hr, and C-reactive protein level of 2.85 mg/dL.

Что предложим в плане обследования?

Рентген нужно сделать.
Если мне не изменяет память, боли подобного характера, купирующиеся аспирином, характерны для...остеоид-остеомы...Или я ошибаюсь?

A plain radiograph of the right hip and femur showed an approximately 1-cm, focal, lytic lesion with sclerotic margins at the interior cortex of the proximal right femoral diaphysis. There was no evidence of periosteal reaction, associated soft-tissue mass, or pathologic fracture. The soft tissue was unremarkable. The visualized hip and pelvis were within normal limits. Findings were believed to be consistent with osteoid osteoma, and the CT scan made that diagnosis more certain . Histologic examination of a specimen obtained by CT-guided biopsy of the lesion confirmed the diagnosis of osteoid osteoma.

Новорожденный младенец переведен в отделение патологии новорожденных из-за выраженных усиленных движений грудной клетки при дыхании через 15 минут после рождения. Роды вагинальные, без осложнений, Апгар 9/9.
При осмотре педиатром в отделении патологии новорожденных через 20 минут после рождения отмечается следующее:
Т 37 P.R., ЧСС 158, ЧДД 42, АД 55/16, Sat O2 100%
Аускультация легких в норме, небольшая ретракция м/реберных промежутков, нет выраженного респираторного дистресса.
При аускультации сердца - громкий голосистолический шум, лучше всего слышен по правой стернальной линии сверху, акроцианоз новорожденных, капиллярный возврат 3 сек.
Неврология - активный, нормальный новорожденный.
-----
Ваши предположения? Что бы это могло быть?

ruptv,

Надо полагать, пациент не кардиологический?) Диафрагмальная грыжа?

ruptv,
Диафрагмальная грыжа?
Нет.
-----

Первое о чем подумал: стеноз аорты

стеноз аорты
На основании чего?

1. У ребенка имеются симптомы которые можно расценить как синдром малого сердечного выброса (среднее давление 29, циркуляторные нарушения акроцианоз, наполняемость капиллров 3 сек, форсирует дыхание)
2. Шум на основании сердца справа в проекции аорты громкий систолический
3. Ухудшение состояния после рождения возможно связано с закрытием ОАП

Первое впечатление в дифференциальной диагностике о ВПС с обструкцией выносящего тракта левых отделов с дуктус-зависисмым системным кровотоком. Возможны ли другие варианты - надо подумать.

Жаль, что не угадала:)
Уважаемый Денис, мне тоже аортальный стеноз первым пришел в голову. Поэтому я о нем и...не написала. Показалось(?), что задачка с подвохом.

Нет, это не стеноз.

3. Ухудшение состояния после рождения


Возможно, я не совсем четко выразилась. Состояние ребенка было стабильным.

-----
На ЭКГ - подъем ST.
Может быть есть еще мнения? Интересно, что скажут педиатры...

Мать ребенка здорова? Каков уровень ТТГ у матери и ребенка?

Я бы исключила ОАП.

Основные причины низкого диастолического давления у детей:
1) аортальная регургитация вследствие повреждения или мальформации клапана
2) большой РДА
3) системно-легочный шунт при таком пороке, как Blalock-Taussig шунт или центральный шунт
4) антигипертензивные препараты
Неадекватный коронарный кровоток может вызвать миокардиальную ишемию вплоть до инфаркта миокарда у младенца, механизм развития которого отличается от механизма развития ИМ у взрослых.
В целом, диастолическое давление менее 25 считается слишком низким у младенцев.
------
Ребенку было сделано ЭХО, и на ЭХО был выявлен достаточно редкий врожденный порок: левожелудочко-аортальный тоннель. Суть в отсутствии клапана между левым желудочком и аортой. В резуьтате, кровь свободно ходит туда-сюда при систоле и при диастоле. У ребенка имеется выраженная аортальная регургитация (3+). Степень регургитации такова, что коронарные артерии не успевают наполниться кровью во время диастолы, что не обеспечивает нормальную перфузию коронарных артерий.
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Лечение, в данном случае, хирургическое.

12-летняя девочкв с жалобами на боли в груди в теч. недели, усиливающиеся при дыхании и в положении на спине. В теч. последних 10-ти дней держится Т и в теч. 5-ти дней продуктивный кашель.
При осмотре нормальная, хорошо развитая девочка ( 95% по весу и росту ) без признаков дистресса. Т - 37.7, пульс - 123/мин., ЧДД - 20/мин, АД 130/60, Sat. 95% кожа чистая, сухая на животе и конечностях.
Насморк, в ушах при осмотре - тимпаностомические трубочки, при аускультации сердца и легких - ничего особенного, кашель усиливается на вдохе или лежа. По всем остальным системам органов - без особенностей. кожа чистая, сухая на животе и конечностях.
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Ваши предложения по дальнейшему обследованию.
Нужна ли еще какая-нибудь информация?

Нужны дополнительные данные, чтобы дифференцировать заболевания
с поражением перикарда и плевры

Общий анализ крови с лейкоцитарной формулой, СОЭ
Рентген грудной клетки
ЭХО-КГ

Можно еще поискать энтеровирусы Коксаки В.

Общий анализ крови с лейкоцитарной формулой, СОЭ
Рентген грудной клетки

WBC - 15.9
Neutr - 83%
Lymph -6%
Bands - 2%
Hgb- 8.9 g/dL ( 89 g/L)
Plt - 318 000

На обзорном снимке гр.клетки - два отдельных затемнения ( к сожалению, других подробностей нет ). СОЭ нет.

ЭХО-КГС какой целью?

Ира, и никаких подробностей где эти затемнения ? В какой доле ? Делалась ли реакция Манту , есть ли реакция плевры ?

С какой целью?

По описанию, боли в грудной клетке у девочки похожи по характеру на плевральные боли и есть детализация, что усиливаются в положении лежа. Такой характер болей может быть при перикардите, при котором боли усиливаются в положении лежа, при глубоком вдохе и кашле и уменьшаются в сидячем положении при наклоне кпереди. Вовлеченность перикарда подтверждалась бы типичными изменениями сегмента ST и зубца T на ЭКГ, увеличением тени сердца на рентгенограмме и наличием перикардиального выпота по ЭХО-КГ.

На обзорном снимке гр.клетки - два отдельных затемнения ( к сожалению, других подробностей нет ).

первичный туберкулезный комплекс?

Подсказка.:)

в ушах при осмотре - тимпаностомические трубочки
И еще. До сих пор "не сделан" ( вернее, никто не предложил один очень простой анализ, входящий в любой протокол обследования ребенка с Т ).

Обший анализ мочи?

Разрешите дополнить условия задачи по оригиналу, потому что пропушены некоторые важные моменты:

12-летняя девочка с жалобами на боли в груди в течение недели, усиливающиеся при дыхании и в положении на спине. В течение последних 10-ти дней держится Т и в течение 5-ти дней продуктивный кашель.
…
Два месяца назад она испытывала боли и отек в области правого коленного сустава, которые в настоящее время прошли. С того же времени у нее отмечались повторные эпизоды среднего отита, достаточно серьезные, что потребовалась двухсторонняя тимпаностомия. Кроме того, у нее отмечается вторичная аменорея в течение 2-х месяцев. В последние два дня отмечает, что моча чайного цвета.
Она отрицает потерю веса, ночную потливость, поверхностные травмы и воспаление в синовиальных суставах.
Ее семья недавно переехала из Флориды в земледельческую общину Южной Калифорнии
…
При осмотре нормальная, хорошо развитая девочка ( 95% по весу и росту ) без признаков дистресса. Т - 37.7, пульс - 123/мин., ЧДД - 20/мин, АД 130/60, Sat. 95% кожа чистая, сухая на животе и конечностях.
Насморк, в ушах при осмотре - тимпаностомические трубочки, при аускультации сердца и легких - ничего особенного, кашель усиливается на вдохе или лежа. По всем остальным системам органов - без особенностей. кожа чистая, сухая на животе и конечностях.

WBC - 15.9 Neutr - 83% Lymph -6% Bands - 2%
Hgb- 8.9 g/dL ( 89 g/L) ( Уменьшение на 30 г/л в течение месяца)
Plt - 318 000

На обзорном снимке гр.клетки - два отдельных узелка.
В анализах мочи протеинурия и гематурия.

________
дальше текст не доступен.
Я пасс, нужна какая-то толстая книжка по диффузным заболеваниям соединительной ткани.

Да ето же наверное гранулематоз Вегенера (если уж из хитрых суспишенов на отит, узелки в легких, лихорадку и пр.) :bo: Насчет отсутствия анализа мочи-то и правда плохо.

Разрешите дополнить условия задачи по оригиналу, потому что пропушены некоторые важные моменты:



Ну...так неинтересно.:)

Я же ожидала, что кто-нибудь поинтересуется анамнезом, кто-нибудь предложит какие-нибудь обследования...
А так - что? Задачка для студентов...:)

Да ето же наверное гранулематоз ВегенераНу конечно!:)

Прежде здоровая 8-мимесяная девочка поступает в ER с 2-хдневной историей Т 39.5
В теч. последних 12 часов девочка ведет себя беспокойно: плачет, просится на руки, но и на руках не успокаивается. Аппетит снижен в теч. последних суток, мочится, как обычно. При осмотре беспокойна, но успокаивается на руках, нет признаков ОРЗ, кожа чистая, обычной окраски, сыпи нет, лимфоузлы в норме, движения во всех суставах в полном объеме, Т -38.3, ЧДД - 38, ЧСС - 111, АД - 90/60.
По органам - без особенностей. Отводит руку врача при попытке осмотреть ей живот.
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Ваши предложения по пути следования к диагнозу?

Sepsis workup с люмбальной пункцией

WBC - 11,8 ( 38% Lymph 55%и Neutr ); ОАМ - норма, CSF - 1 эритроцит, 1 лейкоцит, глюкоза и белок в норме.
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Каковы предложения по дальнейшей тактике?

Выяснить когда был стул в последний раз, его консистенцию, количество. Понаблюдать ребенка в покое как себя ведет, положение в постели. Обязательно пропальпировать живот, лучше во время сна или может быть на фоне неглубокого наркоза на предмет образований, локальной боли. Может быть УЗИ брюшной полости, малого таза - объемные образования, выпот. На острый живот похоже. Высокая температура, которая предваряет начало смущает.

Клиника очень неспецифична. Нейроинфекции, остеомиелит, острые воспалительные заболевания брюшной полости ... начало - изменения поведения и повышение температуры.
Если определяются признаки острого воспалительного процесса в брюшной полости, то дальнейшая нозоологическая диагностика - задача хирурга. Исключать надо, в первую очередь, заболевания, требующие экстренной хирургической помощи:
аппендицит, инвагинацию, некроз опухоли, абсцесс, кишечную непроходимость.

Повторный осмотр во сне. При пальпации живота девочка немедленно проснулась и разразилась пронзительным длительным плачем ( 30 мин.)
На первом месте диагноз Intussusception. Однако, УЗИ живота этот диагноз не подтвердило.
СТ с контрастом подтвердило д-з О.аппендицит.
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Чему это учит молодых врачей? (с):)
О.аппендицит у детей моложе 3-х лет - очень редкая патология. Признаки заболевания весьма неспецифичны, поэтому в реале такой д-з ставится чаще всего с задержкой.
Наиболее частая причина Т и болей в животе у детей в возрасте до 1 года - AGE.
На втором месте - Intussusception.
Если поступает маленький ребенок с клиникой, описаной выше, и нет улучшения несмотря на адекватную регидрацию, надо думать об аппендиците. К сожалению, б-во младенцев к этому времени уже развивают перфорацию.

Молодые врачи намотали на ус. Спасибо.

11-тинедельный младенец поступает в п/о с 3-хдневной историей кашля, насморка и общей простуды. Т дома была 38.4, но, в целом, ребенок себя чувствует хорошо, аппетит не снижен, физиологические отправления ( количество и "качество":) памперсов ) обычны для ребенка.
При поступлении в п/о Т 39.0, нос "забит", ребенку сделали глубокий сакшен и дали кислород через "очки" 1 л/мин, т.к. ЧДД была 60/мин.
Rapid-test RSV, influenza А, В - отрицательные. Снимок легких - перибронхиальное усиление (?) -thickening - легочного рисунка. Через час ребенок продолжает оставаться с тахипное, но нет признаков респираторного дистресса.
При осмотре в отделении - хорошо развитый малыш удовлетворительного питания, вес 4.735 кг ( 10-й центиль ). Нос немного "забит", ЧДД 55/мин, небольшая ретракция м/р промежутков, при аускультации дыхание проводится во все отделы, никаких посторонних звуков нет. Сатурация кислорода крови при комнатном воздухе 100%. ЧСС 168/мин. Остальной осмотр без особенностей.
Через н-ко часов ЧДД увеличивается до 80/мин, ЧСС - до 180/мин. Ребенок становится менее активным, отказывается от бутылочки. Появляется мраморность кожи и выраженная сонливость. Капиллярный возврат 4 сек. Ребенок получает болюсно физ.р-р из расчета 20мл/кг.
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Внимание, вопрос!:)
Какой/ие лабораторный тест/ы подтвердят диагноз?

Тяжесть состояния обусловлена шоком. Причина не ясна.
"Какой/ие лабораторный тест/ы подтвердят диагноз?"
- выжать из лаборатории все, что возможно.
Развернутый анализ крови, общий анализ мочи
КЩС, газы крови
Биохимический профиль (натрий, калий, кальций, осмолярность сыворотки, глюкоза, белок, АСТ, АЛТ, билирубин, мочевина, лактат)
Кровь на стерильность.

Попытаю счастья....:ah:
Муковисцидоз, легочная форма?-потовая проба.

Dr.Ira!Любую критику восприму конструктивно!
:bo:

Рина! я тоже про муковисцедоз вчера подумала, но побоялась написать:ah:

побоялась написать:ah:

А вот это зря:). Чего бояться то? :)

Лаборатория:
Na - 162 mEq/L (162 mmol/L)
K - 7.0 mEq/L ( 7.0 mmol/L)
Cl - 128.0 mEq/L (128 mmol/L )
Bicarbonate < 5 mEq/L ( 5 mmol/L )
BUN - 25 mg/dL ( 8,9 mmol/L )
Creatinine - 1,0 md/dL (88,4 mcmol/L )
Glucosae > 600,0 mg/dL ( 33,3 mmol/L )
An arterial blood gas :
pH - 6,86
pCO2 - 31,5
pO2 - 51
Base excess - 27,4 mEq/L

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Диагноз?
Дополнительные обследования ( нужно или нет?)
Какая дополнительная информация нужна?

Анамнез жизни?Запах ацетона есть от ребенка?

Какая дополнительная информация нужна?
- сахар и кетоновые тела в моче
- гликированный гемоглобин

Дебют сахарного диабета? диабетический кетоацидоз
Нужно дифференцировать от транзиторных гипергликемий на фоне других заболеваний.

Какая дополнительная информация нужна?
- сахар и кетоновые тела в моче
- гликированный гемоглобинЗачем? Что это даст сейчас?
Нужно дифференцировать от транзиторных гипергликемий на фоне других заболеваний.Например?

диабетический кетоацидоз


Верно. Диабетический кетоацидоз.
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Дополнительная информация.
Выяснилось, что у матери ребенка ДМ 1 был диагностирован в 8-мимесячном возрасте, у бабушки ребенка - в 4-хмесячном возрасте, у сводного брата в 2.5-летнем возрасте. У ребенка была старшая сестра, которая умерла в возрасте 3-х месяцев. Родителям тогда сказали, что это SIDS. За день до своей смерти, у девочки появились признаки простуды, включая учащенное дыхание. Она была осмотрена в ER и выписана домой, где и умерла ночью, во сне.
Настоящий ребенок родился на 39 нед. вес 3.49 кг путем CS у матери, страдающей диабетом 1 типа, принимавшей инсулин во-время беременности и выкуривавшей 4 - 5 сигарет в день.
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Ребенок переведен в ОРИТ и получает соответствующее лечение. Что еще из обследований необходимо сделать младенцу?

Ребенок переведен в ОРИТ и получает соответствующее лечение. Что еще из обследований необходимо сделать младенцу?

Обследование с целью определения дальнейшей тактики?
определение лабораторных показателей каждые 1-3 часа;
мониторинг ЭКГ;
неврологический статус+ невролог;
глюкометрия каждые 30-60минут.

определение лабораторных показателей каждые 1-3 часа;
мониторинг ЭКГ;
неврологический статус+ невролог;
глюкометрия каждые 30-60минут.О.К.
А можете объяснить, для чего каждое, из предложенных Вами, исследование?

О.К.
А можете объяснить, для чего каждое, из предложенных Вами, исследование?

1.контроль состояния, корректировка инфузионной терапии.
2.проверка уровня калия(повышение-заострение зубцов Т;понижение-уплощениеТ+волны U).
3.не пропустить отек мозга.
4.коррекция инфузионной терапии( введение 5% глюкозы).

После стабилизации состояния, ребенку была сделана СТ головы в связи с тем, что у ребенка отмечалась выраженная сонливость.
На СТ - церебральная эдема, желудочковые кровоизлияния и тромбоз кортикальной вены. Нейрохирург, после осмотра, остановился на решении консервативного ведения ребенка.
Sepsis work up - все посевы вернулись отрицательными. Т.е. Т была вызвана вирусной инфекцией.
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Чему это учит молодых врачей:) или Lessons for Clinician

Младенец с тахипное, особенно в зимний период, требует широкого и всеобемлющего ДД. Например, этот малыш имел все признаки банальной вирусной инфекции, однако, тахипное было непропорционально выражено по сравнению с предполагаемой вирусной инфекцией. При тахипное 80/мин ожидаемы аускультативные находки ( которых не было у этого младенца) если бы речь шла о поражении дыхательных путей ( ОРВИ, пневмония и т.п. ) Далее, если бы речь шла об инфекции дыхательных путей, то витальные показатели ( в том числе, и ЧДД ) должны были бы улучшиться после сакшен. Этого не произошло.
Отличить респираторный дистресс, вызванный вирусной инфекцией от дыхания Куссмауля бывает, подчас, достаточно сложно, особенно у 2х-месяного младенца. В данном случае, тщательно собраный анамнез, семейная история, внимательное отношение к деталям помогло врачам достаточно быстро поставить диагноз и начать лечение.