This 15-year-old black girl was evaluated as an outpatient for a 45-pound weight loss during the previous 9 months. During this time, she had virtually no symptoms, save for mild fatigue. Although she was described as a picky eater, she ate three reasonable meals each day. She is unhappy about the weight loss and denies vomiting or trying to lose weight.
A review of systems was entirely unremarkable, including no history of vomiting, diarrhea, fever, rashes, or respiratory symptoms. Her menses had been normal. There was no significant travel history. She lives at home with her parents and one dog. Throughout this time, she had not missed a day of school. Family history was unremarkable.
On physical exam, she was thin but otherwise healthy appearing. Weight was 52 kg and height was in the 25th percentile. HEENT exam was unremarkable. Optic fundi were normal. There was no significant adenopathy. Lungs were clear. Cardiac exam was normal. Abdomen was soft and nontender without masses. She was Tanner 3 for pubic hair, Tanner 4 for breasts. Back was straight without tenderness. Neurologic examination was normal.
Robert Listernick, MD, moderator: First thoughts?
Robert Tanz, MD, general academic pediatrician: Obviously, an eating disorder strongly needs to be considered in any adolescent with mysterious weight loss. I'd like to make sure that the weight loss has been documented. Finally, fatigue is very nonspecific. I'd like to know how her day-to-day activities have been affected.
Dr. Listernick: All good questions. The weight loss was documented in the physician's office. She and her parents adamantly deny that she has an eating disorder. Despite her weight loss and fatigue, her affect is normal and she has been participating in all her school and extracurricular activities, although none of them require significant physical exertion. She was appropriately concerned about her unexplained weight loss.
Robert Garofalo, MD, adolescent medicine physician: This doesn't sound like an eating disorder, but I would certainly make sure to explore the possibility of psychological trauma that could have led to depression.
Dr. Listernick: How should we proceed?
Dr. Tanz: After exploring all the psychological issues, I'd want to determine if there's an occult medical cause for the weight loss. Even if you thought that she had an eating disorder, y ou 'd want to document her metabolic condition and look for evidence of such conditions as malabsorption, chronic renal failure, chronic acidosis, or electrolyte disturbances.
Dr. Listernick: Could she have a malabsorption disorder and lose 45 pounds without any gastrointestinal symptoms?
Karan Emerick, MD, pediatrie gastroenterologist: Unusual, but it happens. In particular, teenagers may be reticent to share symptoms with parents or physicians. However, upon probing, symptoms such as abdominal pain or a change in bowel habits may surface.
Dr. Listernick: In that case, if you had been referred this patient who adamantly denied any symptoms on repeated questioning, how would you have proceeded?
Dr. Emerick: I'd look for evidence of intestinal inflammation with a stool Hemoccult, complete blood count (CBC), erythrocyte sedimentation rate (ESR), and serum albumin. I would also perform a celiac antibody panel. I wouldn't perform any more invasive testing without definite evidence of an inflammatory process.
Dr. Garofalo: I just want to make it clear that the possibility of an eating disorder needs to be thoroughly explored before it's dismissed, regardless of the initial history. Getting a better assessment of her intake would be important.
Dr. Listernick: How useful are prospective 3-day diet records?
Rae Ellen Kavey, MD, pediatrie cardiologist: They are not reliable in overweight people who may misrepresent their intake. However, they are useful in thinner individuals. In regard to this patient, I would be extremely concerned and wouldn't let her leave my office without knowing the results of the laboratory evaluation. Even then, I would probably admit her to the hospital.
Dr. Garofalo: I have a somewhat different take on the situation. Adolescents with an eating disorder and this degree of weight loss are fairly common. Assuming that both her exam and laboratory evaluation are normal, I believe that this can be handled as an outpatient initially.
Dr. Listernick: She was seen by a subspecialist at another institution. Her evaluation included hemoglobin 10 g/dL, MCV 85, white blood cell (WBC) count 4,200/mm3 with a normal differential, and ESR 71 mm/hour. The following tests were normal: electrolytes, liver function testing, celiac antibody panel, thyroxine, thyroid stimulating hormone, urinalysis, and antibody screening for inflammatory bowel disease.
Dr. Emerick: The IBD First Step panel is a series of antibodies (neutrophil-specific nuclear autoantibody, IgG and IgA anti-Saccharomyces cervisiae antibodies, and anti-OmpC IgA) that are fairly sensitive for determining the presence of inflammatory bowel disease but not very specific. I prefer to use this panel to confirm the presence of disease in someone in whom I have a high index of suspicion. It is absolutely not a worthwhile screening tool.
Dr. Tanz: Could this child have tuberculosis (TB)?
Ben Katz, MD, pediatrie infectious disease physician: TB is said to be the great imitator. However, with that said, this degree of weight loss without fever, sweats, or other symptoms would be extremely unusual. Still, I probably would have performed a chest x-ray as part of my initial evaluation if I had seen her.
Dr. Listernick: During the next 4 weeks, she continued to lose weight but remained asymptomatic. A bariurn examination of the small intestine was normal. She came to the emergency department after four days of ill-defined chest pain and fatigue. There were no other complaints. In general, she said she felt well and had a cheery affect At this time, her pulse was 90, respiratory rate 1 2, and blood pressure 110/60. The remarkable findings on examination were limited to the cardiopulmonary exam. There were markedly decreased breath sounds halfway up each hemithorax. Sl was normal and S2 was physiologically split Although there were no murmurs, she had a very loud pericardial friction rub heard throughout the precordiura
Abnormalities on laboratory evaluation included hemoglobin 8.5 g/dL, ESR 112 mm/hour, albumin 2.7 g/dL. Hepatic and renal function was otherwise normal.
Mary Wyers, MD, pediatrie radiologist: The chest x-ray shows bilateral pleural effusions. There is also marked globular enlargement of the cardiac shadow, the socalled "water-bottle" shaped heart. This is highly suggestive of a large pericardial effusion. There are no pulmonary infiltrates. A computed tomography scan of the chest demonstrated a huge pericardial effusion as well as the pleural effusions. There was essentially no aeration of the left lung because the heart totally filled the left hemithorax. There were some moderately enlarged mediastinal lymph nodes.
Dr. Kavey: The echocardiogram demonstrated a huge pericardial effusion within which were multiple strands and clumps of fibrinous debris which suggest a chronic process. Just the fact that this child was asymptomatic from a cardiovascular standpoint and was sitting up and talking without distress points to the effusion's chronicity. The right atrium was significantly compressed by the effusion suggesting that in time there will be clinical cardiovascular compromise. From a cardiologist's standpoint, massive pericardial effusions are caused by either collagen vascular disease, malignancy, or, very rarely, infection such as from human immunodeficiency virus.
Dr. Listernick: Could this be the result of an infectious process?
Dr. Katz: From an infectious disease standpoint, I try to distinguish between acute and chronic pericarditis. Historically, acute, purulent pericarditis has been primarily caused by Staphylococcus aureus and Hemophilus influenzae type b, although just about any bacterial pathogen has been described. Obviously, Hemophilus cases are now extremely rare following the introduction of the vaccine. Enteroviruses are the most common cause of acute viral pericarditis. Granulomatous pericarditis, caused by such agents as TB or fungi, tends to present with a slower, more indolent course.
Dr. Listernick: Should TB be a serious consideration in this patient?
Dr. Katz: She absolutely should have a tuberculin skin test placed. However, while it's probably the most likely infectious disease in this patient, I believe that the absence of other systemic signs such as fever makes TB fairly unlikely.
Dr. Listernick: How likely is cancer?
Reggie Duerst, MD, pediatrie oncologist: She certainly could have a lymphoma, given the mediastinal lymphadenopathy, or perhaps some form of sarcoma. Still, this is an unusual presentation of whatever is the correct diagnosis, particularly with the absence of fever.
Dr. Listernick: I have to admit that when I first heard the story and examined her, I was sure that she had sarcoidosis.
Michael Miller, MD, pediatrie rheumatologist: It's unusual to see this degree of pleural effusions in an adolescent with sarcoidosis. However, since published series don't have large numbers of pediatrie patients, all bets are off. Lupus is a definite possibility in an adolescent with pleural and pericardial effusions, but I would have expected some abnormalities in the CBC, such as leukopenia, anemia, or thrombocytopenia.
Dr. Listernick: I'm still fixated on sarcoidosis. How does it usually present in pediatrics?
Dr. Miller: Symptoms in children are often constitutional, including weight loss, fever, fatigue, and night sweats. The lungs are the most frequently involved organ, but pulmonary symptoms may be minimal or absent Other common presenting manifestations include arthritis, lymphadenopathy, uveitis, and rash. I should add that a serum angiotensin-converting enzyme is neither sensitive nor specific for the diagnosis of sarcoidosis. If it has any utility, it's for following disease activity in a patient with an established diagnosis.
Dr. Listernick: She was admitted to the intensive care unit and a pericardial drain was placed. Approximately 150 cc of bloody fluid was removed initially. The red blood cell count was 612,000/mm3 and the WBC count was 356/mm3 with 60% lymphocytes and 35% neutrophils. The glucose was 72 mg/dL and the protein 5.9 g/dL. Gram stain and acid fast stains were negative. Bacterial, viral, mycobacterial, and fungal cultures were ultimately negative. No malignant cells were seen. The following tests were negative: antinuclear antibodies, anti-double stranded DNA antibodies, complement levels, and Coombs test.
Dr. Katz: The pericardial cell count is not indicative of an infection. In bacterial pericarditis, the WBC count is usually at least 10,000/mm3 if not greater with a predominance of neutrophils. TB is usually a more indolent process with a lower WBC count, not this low, and a lymphocytic predominance. In addition, a normal pericardial fluid glucose is inconsistent with TB.
Dr. Duerst: While unlikely, I still wouldn't totally eliminate the possibility of a malignancy even with normal pericardial fluid cytology. I think that both pericardial and mediastinal lymph node biopsies are important final steps in this patient.
Dr. Miller: I would agree that a pericardial biopsy is crucial. I would hesitate to arrive at a rheumatologic diagnosis without clear evidence of the absence of either a malignancy or an infection.
Maria Proytcheva, MD, pediatrie hematopathologist: There were no specific findings on the pericardial tissue which just showed some fibrosis and inflammatory cells. In particular, there were no granulomas. The lymph nodes demonstrated small sheaths of plasma cells, a nonspecific finding which is seen in many conditions, particularly collagen-vascular diseases.
Dr. Listerai ck: How should we interpret all this information?
Dr. Miller: I believed that she best fit into a heterogeneous group of patients who have been labeled with the diagnosis of undifferentiated connective tissue disease. These patients have characteristics of a number of different rheumatologic disorders without meeting the diagnostic criteria for a single disease. Most importantly, malignancy and infection have to be excluded before this diagnosis can be made.
Dr. Listemick: So that there's no confusion, this is a different diagnosis from mixed connective tissue disease (MCTD)?
Dr. Miller: Yes. MCTD is a distinct subset of lupus, patients who have nephritis, myositis, and arthritis who also have high titers of antibody against ribonuclear protein.
Dr. Listemick: What is their long-term prognosis?
Dr. Miller: The National Institutes of Health performed a large study involving around 400 adults with this diagnosis. They couldn't find any distinguishing characteristics which would help diagnose or prognosticate. However, there was a clear subset of patients who had increased mortality associated with progression to scleroderma. There's no evidence that treatment will prevent this disease progression.
Dr. Listemick: What treatment was recommended for this girl?
Dr. Miller: I treated her with "pulse" corticosteroids at a dose of 30 mg/kg/day of methylprednisolone up to a dose of 1 gram divided four times daily, similar to what we give to lupus patients with active disease.
Dr. Listerai ck: How has she responded?
Dr. Miller: Extremely well. Her symptoms of fatigue have disappeared and her pericarditis has not returned. I switched her to oral prednisone from which she has been almost totally weaned without a recrudescence of her symptoms. She's at risk for developing chronic restrictive pulmonary disease so we will be following her pulmonary function testing.
Dr. Listerai ck: Thank you, everybody.