CHYLOTHORAX ASSOCIATED WITH HISTOPLASMOSIS IN A CHILD

Abstract

Histoplasmosis is the most common systemic fungal infection in the United States. Pulmonary disease caused by Histoplasma capsulatum is generally asymptomatic and self-limiting. When it is symptomatic, clinical features include fever, nonproductive cough, headaches, pleuritic chest pain, weight loss, malaise and night sweats. Roentgenographic changes may include bilateral lower lobe infiltrates and hilar adenopathy.1 Pleural effusions are present in <5% of cases.1 Chylothorax has not been described previously in association with histoplasmosis. We report a child with histoplasmosis who presented with a large pleural effusion discovered to be a chylothorax. We review chylothorax and pulmonary histoplasmosis in children. Case report. EW, a 3-year-old Caucasian girl, was referred to the pediatric pulmonology clinic for evaluation of an abnormal chest roentgenogram (CXR). Six months earlier she had been treated with oral amoxicillin/clavulanic acid for right lower lobe pneumonia. A follow-up CXR was normal. One month before referral to our center she was evaluated in the emergency department for the acute onset of fever, tachypnea, chills, malaise and abdominal pain associated with choking and coughing while eating. Elevation of the right hemidiaphragm with volume loss in the right middle lobe and right lower lobe was demonstrated on a CXR. The emergency department physician prescribed oral cephalexin, but this was changed to oral clarithromycin by her family physician the next day. Her symptoms resolved with a 2-week course of clarithromycin, but a repeat CXR at the end of that therapy was unchanged. She was referred to our clinic to be evaluated for possible obstruction of the bronchus intermedius caused by an aspirated foreign body or a mucus plug. She had also had a 4-pound weight loss during the previous 6-month period before her referral. There was no history of recurrent vomiting, trauma to the chest, foreign travel, ill contacts, loose stools, wheezing, recurrent otitis media, sinusitis, night sweats or hemoptysis. EW frequently fed the birds around her family's bird feeders. She appeared thin but was otherwise active and in no respiratory distress. Vital signs were temperature 36.2°C, pulse 117/min, respirations 26/min, blood pressure 105/61 cm Hg, height 90.7 cm (10% for age) and weight 12 kg (10% for age). Breath sounds were decreased over the right middle and lower lung segments on auscultation with no crackles, wheezes or rubs. There were no chest wall retractions, heart murmurs or clubbing of the fingers. The sweat chloride concentration was normal. Flexible fiberoptic bronchoscopy performed with bronchoalveolar lavage (BAL) demonstrated extrinsic compression of the right lower lobe bronchus but no foreign body or mucus plug in the bronchus intermedius. The BAL material was composed predominantly of alveolar macrophages with occasional lymphocytes, polymorphonuclear leukocytes and bronchial epithelial cells. Oil red O stain was negative. Stains for acid-fast bacilli, potassium hydroxide and calcofluor white were negative. A Gram-stained smear of the BAL fluid demonstrated a moderate number of white blood cells but no organisms. Cultures for respiratory viruses, fungus and mycobacteria were negative. The bacterial culture grew a few colonies of Staphylococcus aureus resistant only to penicillin and erythromycin. Computerized tomography of the chest demonstrated a large right pleural effusion, a right hilar lymph node and a subcarinal mass. There was a subpleural granuloma in the right middle lobe and areas of atelectasis in the right lung. Right thoracentesis was performed and 250 ml of milky pleural fluid were removed. The pleural fluid had a pH of 8.4, lactate dehydrogenase 548 units/l, protein 5100 mg/dl, glucose 70 mg/dl, triglyceride 2545 mg/dl, 5184 white blood cells (94% lymphocytes, 6% monocytes) and 864 red blood cells. Specific stains (acid-fast bacilli, KOH and calcofluor white) were negative as was an examination for neoplastic cells. A Gram-stained smear had no organisms. Cultures for viruses, fungi, mycobacteria and aerobic and anaerobic bacteria were negative. Subsequently urine Histoplasma antigen immunoassay was negative. The serum complement fixation (CF) titer for yeast phase antibody was 1/128, and serum immunodiffusion for the M band was positive. EW was given a diet containing fat only in the form of medium chain triglycerides (MCT).2 She was discharged 4 days after admission. In the pediatric pulmonology clinic 3 weeks later, there was no reaccumulation of the pleural effusion on CXR. Her activity level had increased but she had not gained weight. Physical examination was normal and she was given a regular diet. Two months later she had gained 1.2 kg of weight and was asymptomatic. Discussion. Chylothorax results from the escape of chyle from the lymphatic system into the thoracic cavity caused by an obstruction of lymph flow or a laceration of the thoracic duct. Surgical injury to the thoracic duct is the cause of ˜50% of all chylothoraces in children.3 Other less frequent causes of iatrogenic chylothorax are thrombosis of the left subclavian vein resulting from an indwelling catheter, complications during radical neck dissection and trauma. The site of traumatic rupture is commonly in the region of the 9th or 10th thoracic vertebra.4 Spontaneous chylothorax results from extrinsic compression or infiltration of the thoracic duct. In both cases an increase in intraductal pressure occurs with formation of dilated collateral channels which ultimately drain into the pleural space.5 Tumors, especially lymphoma,6 or enlarged lymph nodes as in tuberculosis7 or sarcoidosis8 can lead to the development of spontaneous chylothorax. The clinical manifestations of chylothorax are those related to the presence of fluid in the thoracic cavity,3 such as fatigue, dyspnea, heaviness and discomfort in the affected side.9 With nontraumatic chylothorax the onset of symptoms is usually gradual. The diagnosis of chylothorax is established by measuring the triglyceride concentration in the pleural fluid. If the concentration is >110 mg/dl the patient probably has a chylothorax. If the triglyceride concentration is <50 mg/dl the patient does not have a chylothorax. Demonstration of chylomicrons in the pleural fluid by lipoprotein analysis confirms the diagnosis of chylothorax.10 Management of chylothorax includes a thoracentesis with complete drainage of the chyle, use of MCT as the major source of dietary fat and replacement of nutrient losses. Because MCT is absorbed directly into the portal venous blood and contributes little to chylomicron formation, lymph flow is greatly reduced. Cessation of chylous effusion occurs largely toward the end of the second week of treatment. If chyle reaccumulates rapidly, a 4- to 5-week trial of fasting and parenteral hyperalimentation is recommended.2 For patients unresponsive to nonoperative treatment, surgical correction of the fistula or ligation of the thoracic duct should be considered. Our patient was evaluated for pulmonary histoplasmosis because of the compatible clinical findings and frequent exposure to bird excreta in a histoplasmosis-endemic area. Microscopic examination of pleural fluid and culture were negative for the organism. This is not unusual in histoplasmosis.1 Serologic tests were helpful in making the diagnosis in our patient. The CF test in our patient was positive at a titer of 1/128. Precipitating antibodies, detected by immunodiffusion tests, may also be helpful in the diagnosis of histoplasmosis but they are less sensitive than CF. The presence of an M band is less specific for active infection and may persist after recovery or may be demonstrated after histoplasmin skin testing. The H band has higher diagnostic value because it disappears after the acute infection. The presence of both H and M bands is highly specific for active histoplasmosis.11 The M band was positive in our patient but the H band was negative. Histoplasma antigen can be measured in the urine, serum and cerebrospinal fluid by means of radioimmunoassay. Antigenuria is present in 90% of patients with disseminated histoplasmosis, 20% of patients with acute self-limited pulmonary disease and <10% of patients with chronic pulmonary cavitary disease.12 Antigenuria was not present in our patient. Acute symptomatic pulmonary histoplasmosis in a normal host rarely requires treatment in that complete recovery occurs in most cases. Indications for treatment with amphotericin B or a suitable azole include patients with severe immunodeficiency who develop acute pulmonary histoplasmosis; chronic pulmonary histoplasmosis; lymphadenitis of the hilar, paratracheal and mediastinal nodes if there is encroachment on a major vital structure; or disseminated histoplasmosis.13 Our patient was not treated with antifungal agents.