Portal de Periódicos da CAPES

Index of Suspicion

1997; American Academy of Pediatrics; Volume: 18; Issue: 7 Linguagem: Inglês

10.1542/pir.18.7.248

1529-7233

Debbie West, Harry J. Shaia, William E. Wear,

This section of Pediatrics in Review reminds clinicians of those conditions that can present in a misleading fashion and require suspicion for early diagnosis. Emphasis has been placed on conditions in which early diagnosis is important and that the general pediatrician might be expected to encounter, at least once in a while. The reader is encouraged to write possible diagnoses for each case before turning to the discussion, which is on the following page. We invite readers to contribute case presentations and discussions.A 4-month-old girl is seen in clinic because of fever as high as 102°F (38.8°C) for 4 days and an anterior cervical mass. She appears only mildly ill. The mass measures 4 cm by 2 cm and is firm and very tender. No erythema or warmth is noted. Lymphadenitis is diagnosed and she is given an oral cephalosporin. Two days later, because she has not improved, she is admitted to the hospital, where a computed tomographic (CT) scan reveals a cluster of large lymph nodes without evidence of abscess. Intravenous nafcillin is administered and she is discharged 4 days later on oral medication when her temperature is close to normal.The baby is readmitted less than 1 week later because the mass has enlarged and fever has returned. Her liver edge is palpable 2 cm below the right costal margin. There is an erythematous, scaling rash on her scalp that is thought to be seborrhea. Testing for human immunodeficiency virus is negative, but serology for Epstein-Barr virus is positive. She is sent home on an oral cephalosporin; when seen 2 weeks later, her adenopathy has regressed markedly. She still has low-grade fever, and her mother reports that she has decreased appetite and activity, but she does not look ill.One week later the baby is brought to the emergency department because of 2 days of fever and 1 day of vomiting. Her temperature is 105.5°F (40.8°C) and her abdomen is strikingly distended. After intravenous rehydration, an abdominal CT scan is performed that leads to an additional procedure, revealing her diagnosis.A 16-year-old boy is brought to the emergency department after awakening in a state of extreme anxiety, crying and hyperventilating. He complains of cramping of his legs and numbness and tingling of his extremities. The boy denies any history of drug abuse, shortness of breath, or chest pain. Yesterday, while playing basketball, he vomited and passed out momentarily, but recovered and went home.Other than his obvious state of distress, his physical examination is considered normal. He is treated with bag rebreathing. After treatment,his arterial blood gases are pH, 7.36; Po2, 67 mm Hg;Pco2, 45 mm Hg; and O2saturation, 99%. His symptoms subside and he is sent home.The patient returns 6 hours later with recurrent symptoms. His respirations are 40 breaths/min, dropping to 12 breaths/min after bag breathing. He demonstrates positive Chvostek and Trousseau signs. Blood chemistries are as follows:sodium, 141 mEq/L; chloride, 97 mEq/L; CO2, 32 mEq/L; potassium, 5.2 mEq/L;blood urea nitrogen, 9 mg/dL; creatinine, 0.8 mg/dL; creatine phosphokinase,1,380 mU/mL; lactic acid dehydrogenase, 40 U/L; albumin, 4.7 g/dL; total calcium, 5.4 mg/dL; phosphate, 6.8 mg/dL; and magnesium, 1.6 mg/dL. An electrocardiogram discloses a bradycardia of 54 beats/min and a QT interval of 480 msec (normal, <430 msec). Findings on chest radiography are normal.A previously healthy 3-year-old boy is playing outdoors when he suddenly shrieks loudly. His parents run to his side and find him frightened, drooling out of the right corner of his mouth, and unable to respond verbally to questions, although he appears alert. As he walks into the house, his gait is clumsy and ataxic. Over the next 10 to 15 minutes he appears increasingly confused. He continues to drool and develops a vacant,glassy-eyed gaze. As he attempts to get up, his right arm and leg appear weak and he falls onto his right side.He is taken to the emergency department where he is noted still to be drooling and confused. He can speak,but his speech is garbled and nonsensical. His blood pressure is 90/60 mm Hg and his heart rate is 120 beats/min. Neurologic examination reveals right-sided weakness. A complete blood count, electrolyte levels, and renal and liver function test results all are normal. A urine toxicology screen is negative. Over the next 4 hours his signs and symptoms resolve completely and he is sent home.The boy does well until 9 days later, when he awakens in the morning and is noted to have drooling from the right corner of his mouth, ataxia, expressive aphasia, and confusion. His right side again is weak, and he stumbles and falls toward that side. He is taken to his pediatrician’s office and observed for 2 hours, at which point he has returned to normal except for mild right lower extremity weakness. A diagnostic procedure performed later that day reveals the reason for his alarming episodes.The abdominal CT scan showed a massively enlarged liver containing multiple hypodense lesions and a slightly enlarged spleen that had similar lesions. Liver biopsy demonstrated histiocytes, confirming a diagnosis of Langerhans cell histiocytosis. Characteristic tennis racquet-shaped Birbeck granules were seen in the cytoplasm of the histiocytes on electron microscopy. The baby’s condition at the time of her third admission was a result of an intercurrent viral gastroenteritis that had caused moderate dehydration. Her white blood cell count was 12,400/mm3with a normal differential count. Chest radiography findings were normal,and all cultures for bacterial infection yielded negative results. She stabilized quickly with intravenous fluids and supportive care.Histiocytosis is a rare disorder that results from the abnormal or uncontrolled proliferation of normal antigen-presenting cells. Langerhans histiocytosis, which is synonymous with class I histiocytosis, encompasses the group of disorders previously called histiocytosis X and includes Letterer-Siwe disease, Hand-Schüller-Christian disease,and eosinophilic granuloma. Class II consists of infection-associated hemophagocytic syndrome and familial erythrophagocytic lymphohistiocytosis. Class III is the “malignant” form of the disease and includes acute monocytic leukemia and histiocytic lymphoma. These patients have the cell markers for histiocytosis as well as for the specific malignancy. Their cell counts also meet the criteria for the given malignancy. The lymphoma is specifically histiocytic.Histiocytosis often mimics other diseases. The rash of histiocytosis,which is seen in 30% to 50% of patients, is an erythematous flaky or scaly rash that usually involves the scalp but also may involve the back,palms, and soles. As in this case, it may be mistaken for seborrheic dermatitis. Petechiae and hemorrhage also are found. Bone is the organ affected most frequently (80% to 100% of patients), and the presentation usually is osteolytic lesions of the skull or vertebral body collapse. “Free-floating teeth” are seen when the mandible or maxilla are involved. Lymph node involvement can cause strikingly enlarged nodes, but tenderness and warmth are not typical. As in this patient, lymphadenopathy is the presenting feature in many cases,particularly in children; lymph node involvement is found in 33% to 42% of patients. Bone pain, rash, and lymphadenopathy, in combination or alone,are the most common clinical characteristics of histiocytosis.Chronic otitis media is common;persistently draining ears can result from involvement of mastoid bones. Liver disease is present in 20% of older patients and up to 71% of infants and can manifest as hepatomegaly, jaundice, ascites, fibrosis,and liver failure.Lung involvement is seen in 15%to 25% of patients but is the most common cause of mortality in long-term survivors. Central nervous system involvement is much less frequent and includes pituitary dysfunction with diabetes insipidus, growth failure,and exophthalmos due to granulomatous lesions behind the orbit. Some patients may present with constitutional signs and symptoms such as fever, irritability, and malaise.Prognosis and treatment depend on the number of organ systems involved. Single bony lesions may resolve spontaneously or require only curettage. Multiorgan disease may require chemotherapy, as in this case. Current thinking about treating histiocytosis is to do what is necessary to restore the patient’s functioning to normal and to prevent disability, aiming at control while allowing the disease to resolve over time.Children older than 2 years who have only bone involvement have a 5-year survival rate of 95%. Children older than 2 years who have one or more systems involved have a survival rate as high as 90%. Children younger than 2 years as well as those who have hepatosplenomegaly, lymph nodes bigger than 5 cm, honeycomb lung disease, or bone marrow involvement have a 5-year survival rate of 60%. The child presented received chemotherapy and looked very well at 7 months of age. Her prognosis,however, must remain guarded because her liver was involved.This infant’s situation is instructive in that she presented with fever and lymphadenopathy and later developed more features of histiocytosis. It is not unusual for the rash of histiocytosis to mimic that of seborrhea. This child had a liver edge 2 cm below the right costal margin on her second hospitalization, which is consistent with normal liver size or mild hepatomegaly. A liver span is not recorded in her record and may have indicated more than mild enlargement. At the time, it was believed that any hepatomegaly was caused by Epstein-Barr infection. In retrospect, it is likely that she had significant liver enlargement at the time of the clinic visit 1 week prior to her third admission. Because she looked well and her adenopathy had regressed significantly, it is possible that the hepatomegaly was overlooked.A number of other disorders can cause lymph node involvement,including the more common forms of bacterial adenitis, mycobacterial adenitis, cat-scratch disease,lymphoma, infectious mononucleosis,and malignant processes. Histiocytosis,although rare, should be considered in a child who has lymphadenopathy that does not fit well into other categories. As always, careful following of any child in whom illness does not resolve completely is necessary if the clinician is to detect the true cause.Hyperventilation can induce a respiratory alkalosis, which in turn increases the association of calcium with albumin, causing a decrease in ionized calcium. This metabolic change can produce generalized weakness,paresthesias, muscle cramping, and tetany. Anxiety resulting from the symptoms of hyperventilation can stimulate an epinephrine response, which may cause further hyperventilation as well as tachycardia. More severe reductions in ionized calcium can cause life-threatening consequences, such as seizures, laryngospasm, and cardiac arrhythmias. Hyperventilation alone in an otherwise healthy individual would not be expected to cause these severe reactions.A person who is chronically hypocalcemic may have a lower-than-normal ionized serum calcium level but be asymptomatic because his or her body has “adjusted” to this chronic hypocalcemic state. In such an individual, further decline of an already low ionized calcium level might be sufficient to cause more severe symptoms. This patient’s hyperventilation, whatever its cause,adversely affected an already abnormal state of calcium metabolism.Because hyperventilation alone reduces ionized calcium in the blood but has no effect on total calcium,this boy’s total calcium level of 5.4 mg/dL cannot be explained by hyperventilation alone. He has an underlying disorder of calcium metabolism.Chronic renal disease can cause hypocalcemia, but the normal serum creatinine and blood urea nitrogen levels in this case ruled out that disorder. Besides renal disease, disorders of parathyroid hormone (PTH) are the other more common causes of hypocalcemia. In primary hypoparathyroidism, PTH levels are low. If PTH levels are normal or high,the patient may be afflicted with pseudohypoparathyroidism (PHP),which results from end-organ resistance to the effects of PTH. This patient had a serum intact parathyroid hormone level of 224 pg/mL (normal,10 to 55 pg/mL). (Measurement of the intact hormone, as opposed to circulating hormone fragments, is the most useful assessment in evaluating the secretion of PTH.) Thus, he had PHP, which caused his low serum calcium level and led to his signs and symptoms.PTH regulates serum calcium by its action on kidney, bone, and intestine. In the renal tubular cells,PTH increases calcium reabsorption and phosphate secretion. It also increases serum concentrations of 1,25-dihydroxyvitamin D3, which enhances calcium absorption in the intestine. Calcium resorption from bone and absorption from the intestine also are stimulated by PTH. This patient had inadequate PTH effect because of end-organ resistance to the hormone.PHP has several forms. Type Ia is the familial disorder know as Albright hereditary osteodystrophy, which manifests early in life with physical features of short stature, thick neck,obesity, and mental retardation. Type Ib does not have these physical features and typically manifests later in life. Patients who have type Ib PHP may have calcification of the basal ganglia and cataracts of the lens. In rare cases, patients who have type Ib can develop lytic lesions of the bone.A laboratory procedure, the Ellsworth-Howard test, in which exogenous PTH is given and the effects on urinary composition are measured, can help differentiate the variants of PHP. In normal individuals,cyclic adenosine monophosphate(cAMP) mediates the action of PTH on the kidney and can be measured in the urine. Patients who have type I PHP fail to excrete cAMP and phosphate; those who have the rarer type II, which clinically is similar to type Ib, excrete cAMP but not phosphate.Following administration of exogenous PTH to this patient, his urine levels of cAMP and phosphate were low. A bone scan revealed no lytic lesions, but computed tomographic scan disclosed calcification of the basal ganglia. Clinical and laboratory findings were consistent with the diagnosis of type Ib PHP. Two other interesting aspects of his condition were the elevated creatine phosphokinase level, which was caused by prolonged tetanic contractions that resulted in rhabdomyolysis and returned to normal after he was stabilized, and the bradycardia. Although one might expect tachycardia from an epinephrine response, his heart rate was low,presumably due to the prolonged refractory period of the myocardial tissue due to the hypocalcemia.Hyperventilation can have many causes. A severe anxiety reaction is the most common etiology in adolescents. When the history does not support anxiety or the hyperventilation does not subside, other causes should be suspected. Diabetic ketoacidosis and aspirin poisoning must be considered and can be evaluated by history,serum electrolyte determination, and urinalysis. Reactive airway disease is excluded readily by auscultation of the lungs. Other causes are uncommon.The symptoms of hyperventilation due to anxiety in an otherwise healthy patient usually respond promptly to rebreathing of exhaled air. Emergency treatment for a symptomatic patient who has low total serum calcium is intravenous infusion of calcium gluconate at a rate of 2 mg/kg of elemental calcium over 10 minutes. Serum calcium should be monitored frequently and the dose repeated as necessary. Calcium solutions are irritating if extravasated. Other phosphate or bicarbonate drugs are incompatible with calcium solutions.Long-term management of HPT and PHP includes lifelong treatment with a high-calcium and low-phosphate diet, supplemental oral calcium, and vitamin D derivatives. Vitamin D enhances the absorption of calcium from the intestine. Presently used vitamin D derivatives are ergocalciferol for short-term effect and calcitriol for maintenance. The serum calcium is monitored and therapy is aimed at maintaining a low normal level. Urine calcium levels are followed to avoid the complications of hypercalciuria (hematuria and renal calculi). Excessive serum phosphate levels are treated with aluminum hydroxide preparations, which bind phosphate,to prevent ectopic calcifications. PTH is not available commercially for long-term therapy. If it were available and practical to use, it would be useful only in patients who have primary hypoparathyroidism.The boy underwent a computed tomographic (CT) scan of the head, which revealed a high-density area in the region of the left caudate and putamen, consistent with a recent hemorrhage in the distribution of a branch of the left middle cerebral artery. He was transferred to a tertiary care center, where an exhaustive evaluation failed to find a specific cause for his stroke. It was thought that most likely he had experienced the rupture of a small arteriovenous malformation(AVM). He had no obvious neurologic sequelae from the stroke.Although stroke occurs infrequently in children, this young boy exhibited one sign that might have made the clinician suspect this diagnosis. The most common clinical feature in children older than 1 year who have strokes is the sudden onset of hemiparesis or weakness. In trying to reconstruct the chain of events in this boy’s clinical course, the clinicians caring for him postulated that he may have had a small bleeding episode—perhaps a small leak from which he quickly recovered—that caused the first episode. The bleeding is believed to have stopped spontaneously but recurred in a more catastrophic form to cause the second episode. His complete recovery speaks to the resilience and adaptability of the brain.Transient ischemic attacks, in which cerebral perfusion is compromised but a true stroke does not occur, can cause temporary neurologic deficits, followed by complete recovery within 24 hours. These episodes may precede both thrombotic and embolic strokes.Strokes in older children have myriad etiologies that can be separated into embolic, thrombotic, and hemorrhagic groups. Congenital heart disease is a common cause of embolic stroke in children. Cyanotic lesions pose the greatest risk. Patent foramen ovale and other defects involving right-to-left-side shunting also are common causes. Thus,echocardiography is an essential part of the evaluation of most children who suffer a stroke.Hemorrhagic strokes frequently are associated with coagulation disorders. The possible existence of X-linked hemophilia A or B should be investigated in any male child who has a hemorrhagic stroke by obtaining levels of factors VIII and IX. Severe thrombocytopenia is the cause of intracranial hemorrhage in a small number of patients and may be due to idiopathic thrombocytopenic purpura,malignancy, or severe infection.Arteriovenous malformation is the most common cause of hemorrhagic stroke in preadolescent children and occurs more often in boys. Intracranial aneurysms are found more commonly in adolescents than in preschool children and usually are due to vascular developmental abnormalities.Subarachnoid hemorrhage occurs most often in children who have incurred trauma and is manifested by severe headache, altered mental status,and focal neurologic deficits. Sickle cell disease is associated with cerebral infarction more often than with other forms of stroke, but also can cause subarachnoid or intraparenchymal hemorrhage.Thrombosis can occur following vascular dysplasia, which occurs in moyamoya disease, fibromuscular dysplasia, neurofibromatosis, and other disorders. Thrombosis can result from vasculopathies or vascular injuries; vasculitis, as occurs in autoimmune disorders such as systemic lupus erythematosus; and hematologic abnormalities. Therefore,determining the presence or absence of various anticoagulants or clotting factors usually is an appropriate part of the evaluation of a child who has had a stroke.Both CT scan and magnetic resonance imaging (MRI) will document the structural changes that occur in a stroke at any age. CT imaging can be performed more rapidly, but MRI will provide greater resolution and allow detection of smaller infarctions. In the newborn, an electroencephalogram(EEG) often is performed in the baby who has focal seizures. Localized abnormalities on the EEG may raise the suspicion of stroke and lead to imaging studies.Cerebral arteriography must be considered for the child who has a stroke in which the cause is not evident from other forms of imaging. If the patient has an AVM or an aneurysm, surgery may correct it. Even if a small AVM is present, it may be obscured transiently by acute hemorrhage, leading some clinicians to repeat the angiogram a few months after the acute hemorrhage has resolved in search of a malformation.