Pleural Effusion, Hepatitis and Hemolytic Anemia in a Twelve-Year-Old Male Child

A 12-year-old African-American male child, previously in good health, was hospitalized because of a 10-day history of worsening cough, abdominal pain and jaundice. The patient initially had nonproductive cough, followed by fever and abdominal pain, emesis and nonbloody diarrhea. There was no history of rashes, headaches, travel or sick contacts. Because of worsening cough and persistent abdominal pain, the patient sought medical evaluation. Physical examination revealed a well-developed and well-nourished male child with a temperature of 38.0°C, heart rate of 138 beats/min, respiratory rate of 20 beats/min and blood pressure of 150/62 mm Hg. The patient's skin and sclerae were mildly jaundiced. No cervical, axillary or inguinal lymphadenopathy was present. The oropharynx was erythematous without tonsilar hypertrophy or exudate. Cardiac examination revealed a regular rate and rhythm without gallops or murmurs. Wheezes and rales were present bilaterally with decreased breath sounds over the base of the right lung. The abdomen was soft with moderate tenderness in the right upper quadrant on deep palpation. The liver edge was palpable ∼1 to 2 cm below the right costal margin at the midclavicular line. The rest of the physical examination was normal. Laboratory evaluation showed a white blood cell count of 13 400/mm3 with 64% segmented neutrophils, 22% band forms and 9% lymphocytes. Hemoglobin was 8 g/dl, hematocrit 22.7%, platelets 249 000/mm3 and reticulocyte count 11%. The sedimentation rate was 131 mm/h. The chemistry profile on admission showed aspartate aminotransferase of 111 units/l, alanine aminotransferase of 427 units/l, lactate dehydrogenase of 1538 units/l, total bilirubin of 2 mg/dl and direct bilirubin of 0.5 mg/dl. The chest radiograph showed right middle lobe consolidation with a right pleural effusion. The patient was admitted and treatment was begun with intravenous cefuroxime. He continued to be febrile to 39.5°C. A repeat chest radiograph showed increasing consolidation of the right lung base with worsening right pleural effusion. On Hospital Day 5 the hemoglobin dropped to 6.4 g/dl. A series of laboratory studies confirmed the diagnosis. Nune Simonian, M.D. Donald Janner, M.D. Department of Pediatrics; Loma Linda University Medical Center; Loma Linda, CA For denouement see p. 176. DENOUEMENT-Continued from p. 174 This patient had multisystem infection caused by Mycoplasma pneumoniae. Both IgM and IgG antibodies for M. pneumoniae were strongly positive by enzyme immunoassay. M. pneumoniae is an important cause of community-acquired pneumonia. The frequency of disease caused by M. pneumoniae is age-related and depends on the epidemic or endemic prevalence of the organism in the community.M. pneumoniae is an uncommon cause of pneumonia in children younger than 5 years of age but is the leading cause of pneumonia in school age children and young adults.1 Pneumonia is the most prominent and frequent manifestation of M. pneumoniae infection.2 Infected humans are the only reservoir of infection. The incubation period is 2 to 3 weeks. In patients who develop pneumonia early signs include fever, malaise, headache and nonproductive cough. Coryza is infrequent; its presence suggests an alternative diagnosis.3 Clinical evidence of pneumonia often includes tachypnea, rales and wheezing. The radiographic manifestations of pneumonia caused by Mycoplasma can be variable, with bilateral diffuse infiltrates or lobar consolidation all being reported.3 Pleural effusion is a relatively frequent finding and may be observed in 14 to 24% of patients.2, 4 The presence of pleuropneumonia appears to be associated with more severe and prolonged course of illness.4 Although pneumonia is the most important clinical manifestation of M. pneumoniae infection, many nonpulmonary manifestations have been also described. Cutaneous manifestations of M. pneumoniae infection include exanthem and/or enanthem and are observed in 5 to 24% of cases.5 Several types of skin lesions may occur, including maculopapular, vesicular, bullous, petechial and urticarial rashes.3, 6 Occasionally this exanthem is severe and is associated with mucous membrane changes (Stevens-Johnson syndrome). A broad spectrum of neurologic complications including aseptic meningitis, encephalitis, cerebellar ataxia and transverse myelitis have been described.3, 5 Hemolytic anemia is also associated with M. pneumoniae infection. This is presumably related to the presence of cold agglutinins in serum which, at high concentration, may agglutinate erythrocytes at 37°C. Hemolytic anemia is usually mild although occasionally it may become severe and result in as much as a 50% reduction in hemoglobin concentration. The association of exanthem and pneumonia or of hemolytic anemia and pneumonia are considered to be strongly suggestive for the diagnosis of M. pneumoniae infection.6 Gastrointestinal findings in M. pneumoniae infection usually are limited to nausea, vomiting, abdominal pain and/or diarrhea. Hepatitis was once thought to be unusual, but recent studies suggest that liver dysfunction may be present in up to 30% of M. pneumoniae infection. Liver dysfunction was observed more frequently in patients with pleuropneumonia than in simple pneumonia cases.4 The mechanisms and clinical importance of liver dysfunction in M. pneumoniae infection remain to be clarified. Diagnosis ofM. pneumoniae infections is usually made serologically, given that culture of the organism is difficult. A cold agglutinin titer of 1:64 is present in the sera of 50% of infected patients; however, other common childhood viral illnesses, including Epstein-Barr virus infection, can also cause a rise in cold agglutinins.5 Complement-fixation antibody testing is the most widely available, although the glycolipid mixture used in this test is not specific for M. pneumoniae, which may lead to false positive results in other inflammatory conditions.7 Indirect immunofluorescence and enzyme immunosorbent assays have proved to be very useful in detection of specific antibodies, particularly IgM. IgM antibodies develop in the first or second week of illness, peaking during the third week and disappearing in about 6 weeks.7 A rapid 10-min card-based enzyme-linked immunosorbent assay designed to detect IgM anti-Mycoplasma antibodies demonstrated high sensitivity in a multicenter trial.8 Recently PCR which applies the gene coding for the p1 adhesion protein has been tested. Testing of nasopharyngeal aspirates resulted in a sensitivity of 85% and a specificity of 92%.9 Antimicrobial therapy is effective in decreasing the duration of symptoms of M. pneumoniae infection.2-5 Erythromycin is the preferred antimicrobial agent in children younger than 9 years. Tetracycline is equally effective and may be used in older patients. New macrolides, such as clarithromycin and azithromycin are also effective and may be better tolerated. Steroids in conjunction with proper antimicrobial therapy may be used in the management of severe pulmonary disease, encephalitis, hemolytic anemia and Stevens-Johnson syndrome.3 The reported patient had a chest tube inserted which was in place for 3 days and drained∼400 ml of transudate fluid. The patient was treated with erythromycin, 500 mg given orally four times a day. He became afebrile within 2 days after initiation of therapy. No transfusion was given and he remained well after discharge.