Bronchopleural Fistula and Lymphocytic Empyema due to Histoplasma capsulatum

disseminated candidiasis, and bacteremia, 9 only one other case of isolated pulmonary Fusarium infection has been reported in the English-language medical literature. This occurred in a 5-year-old child after chemotherapy for a dysmyelopoietic syndrome. An infiltrate of the lower lobe of the right lung developed; serial sputum cultures were positive for F monilifomw. Though the child's fever resolved while he was receiving amphotericin therapy, the radiographic infiltrate persisted. The child subsequently underwent right lower lobectomy, with pathologic findings of extensive necrosis, infarction, and residual hypha! elements. Of interest is the fact that he resided in Nebraska; his father farmed in this region, and the child participated in the autumn harvest several weeks earlier. The authors attributed the development of infection to inhalation of a large inoculum of Fusarium during the harvest. 9 High-dose amphotericin B at 1 to 2 mglkg/d is the standard of therapy in cases of disseminated disease. 3 Some studies show synergism of amphotericin B and rifampin. 3 However, many isolates are resistant to amphotericin, and many failures are reported. 2 ·3 ·8 Recently, lipid complex preparations of amphotericin have been used with success in patients with disseminated disease who could not tolerate the standard preparation.l 2 .1 3 In the present case, lipid complex amphotericin B was used to attenuate the nephrotoxic effect and was effective in preventing further decline in the patient's renal status. Invasive Fusarium pneumonia should be added to the differential diagnosis for solid-organ transplant recipients in whom cavitary lung disease develops. This case confirms that lipid complex amphotericin B can be effective in the resolution of invasive Fusarium infection in patients who are not tolerant of the standard preparation of amphotericin B. REFERENCES 1 Young NA, Kwon-Chung KJ, Kubota TT, eta!. Disseminated infection by Fusarium moniliforme during treatment for malignant lymphoma. J Clin Microbial 1978; 7:589-94 2 Nelson PE, Dignani MC, Anaissie EJ. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbial Rev 1994; 7:479-504 3 Guarro J, Gene J. Opportunistic fusarial infections in humans. Eur J Clin Microbial Infect Dis 1995; 14:741-54 4 Cho CT, Vats TS, Lowman JT, et al. Fusarium solani infection during treatment for acute leukemia. J Pecliatr 1973; 83:1028-31 5 Merz WG, Karp JE, Hoagland M. Diagnosis and successful treatment of fusariosis in the compromised host. J Infect Dis 1988; 158:1046-55 6 Wheeler MS, McGinnis MR, Schell WA, e t a!. Fusarium infection in burned patients. Am J Clin Pathol 1981; 75: 304-11 7 Caplin I, Unger DL. Molds on the southern California deserts. Ann Allergy 1983; 50:260-63 8 Anaissie E, Kantarjian H, Ro J, et a!. The emerging role of fusaria! infections in patients with cancer. Medicine 1988; 67:77-83 9 Zach TL, Penn RG, Gnarra DJ, et al. Fusarium moniliforrne pneumonia. Nebr Med J 1987; 72:6-9 lO Valenstein P, Schell WA. Primary intranasal Fusarium infection. Arch Pathol Lab Med 1986; 110:751-54 11 Kurien M, Anancli V, Raman R, et al. Maxillary sinus 1130

fusariosis in immunocompetent hosts. J Laryngol Otol 1992; 106:733-36 12 Engelhard D, Eldor A, Polacheck I, et al. Disseminated visceral fusariosis treated with amphotericin B-phospholipid complex. Leuk Lymphoma 1993; 9:385-92 13 Wolff MA, Ramphal R. Use of amphotericin B lipid complex for treatment of disseminated cutaneous Fusarium infection in a neutropenic patient. Clin Infect Dis 1995; 20:1568-69

Bronchopleural Fistula and Lymphocytic Empyema due to Histoplasma capsulatum* James V. Richardson, MD; and Ronald B. George, MD, FCCP

A patient presented with chest pain, fever, and chills and developed a large pleural effusion while receiving antibiotic therapy. On a CT scan of the chest, multiple loculi of fluid were noted, and at surgery, a complex empyema with an associated bronchopleural fistula related to a granulomatous process in the lower lobe of the right lung was demonstrated. Cultures revealed Histoplasma capsulatum in the pleural fluid as well as in the pulmonary parenchymal process. (CHEST 1997; 112:1130-32) Key words: empyema; fungal infection; granuloma; Histoplasma capsulatum; histoplasmosis; mycosis; pleural effusion

Approximately 500,000 persons are infected with histoplasmosis in the United States annually.! A small percentage of patients develop pleural effusions secondary to this fungal infection,2 - 11 and empyema is extremely rare. 2 •3 .4·9 In a large series of pulmonary fungal infections reported in 1982, only one case of empyema due to Histoplasma capsulatum, which was associated with a bronchopleural fistula, was reported. 5 VIe present a case of pulmonary granulomatous infection due to H capsulatum which ruptured into the pleural cavity, resulting in a bronchopleural fistula and fungal empyema. The fistulous opening in the pleura was seen at thoracotomy. CASE REPORT A 53-year-old man, a former smoker, was initially referred to the hospital with a history of possible aspiration related to a hiatal hernia and an infiltrate of the lower lobe of the right lung. Bronchoscopy revealed no evidence of aspiration, and bronchial washings were noncliagnostic. Therapy with oral ciprofloxacin, 500 mg 3 times a day for 10 days, was initiated and, after 2 weeks, there was no significant change in the infiltrate. He was seen by a pulmonologist who recommended another therapeutic course *From Montgomery Carcliothoracic and Vascular Surgery (Dr. Richardson), Montgomery, Ala, and the Department of Medicine, (Dr. George), Louisiana State University School of Medicine, Shreveport. Manuscript received Octobe r 16, 1996; revision accepted February 27, 1997. Reprint requests: Ronald B. George, MD, FCCP, Dept of Medicine, LSUMC, 1501 Kings Highway, Shreveport, LA 71130-3932 Selected Reports

of ciprofloxacin, 500 mg 3 tim es a day, and continued observation. Over the ensuing several weeks, th e inHltrate largely disappeared, as shown on a radiograph, and was replaced b y a scar that was confirmed by a CT scan. The patient returned several weeks th ereafter with ahistory of fever, chills, and right-sided pleuritic pain. A chest x-ray film reveal ed a large right pleural effusion that was found on a CT scan to be multiloculated (Fig 1). ACT-guided thoracentesis was perform ed that produced opaque serous fluid with many WBCs (80% lymphocytes) but no orgarusms. The pleural fluid glucose level was 51 mgldL (normal, 70 to 100 mgldL) and the lactate dehydrogen ase value was 1,256 lUlL (normal, 91 to 180 IU/L). Total protein level was 4.5 gldL. The patient was advised to undergo an exploratmy thoracotomy of the right side. At surgery, a complex multiloculated ~ mpyema was encountered, which was purulent in nature. A decortication was performed, and all purulent material was removed. Perforation of the visceral pleura was encountered in the lower lobe of the 1ight lung; this was associated with a nodular inHltrate which was excised. The postoperative course was uncomphcated, and the patient was discharged on his 5th postoperative day. Histopathologic studies revealed a fibrinopurulent process in th e pleural specimens, with xetensive necrotizing granuloma formation, composed of granulation tissue with multinucleated giant cells. The wedge biopsy of the lung containing the nodule included purulent material, giant cells, caseous material, and histiocytes . Cultures of the material produced H capsulatum. No acid-fast bacilli or evidence of a mahgnant tumor was seen. The patient has had a satisfactory postoperative course with no evidence of recurrence or wound infection. He was treated with itraconazole, 200 mgld for 6 weeks, and has subsequently returned to work full-tim e as a warehouse worker.

DISCUSSION

H capsulatum, while causing thousands of pulmonary infections per year in the United States, rarely causes significant pleural pathology. t-u Kilburn and McKinseyt reported the incidence of pleural effusion as 1 to 5.7% in acute histoplasmosis. In a large series of pulmonary mycoses repmted from the University of Mississippi, only one case of empyema associated with H capsulatum infection was noted.s

FIGURE l. CT scan showing complex multiloculated empyema on th e right side of the c hest.

When the pleural space is involved, serous pleural effusions are present. The effusions are thought to result from visceral pleural inflammation, and rupture of a peripheral granuloma is uncommon. Dissemination of histoplasmosis to the pleural space may occur hematogenously as well. 6 Associated symptoms of pleuritis associated with histoplasmosis include chest pain, fever, anorexia, and malaise; chills are unusual. Pleural fluid examination commonly reveals an exudate with relatively high protein content and a predominance oflymphocytes. 6 Pericardia! involvement may rarely occur and probably is related to an inflammatory response in adjacent mediastinal lymph nodes.l 2 Lymphocytic empyemas associated with peripheral nodules usually are associated with mycobacterial infections of the lungs or mediastinal lymph nodes. In areas where endemic fungal respiratory infections are seen, the clinician should be aware that these mycoses may mimic the clinical findings of tuberculous pleurisy and empyema. Histologic material and pleural fluid should be examined and cultured for fungi, since the course of infection may be rapid if appropriate therapy is not given. This case demonstrates the direct extension of an H capsulatum granuloma from the lung into the pleural space, resulting in a fistulous tract and secondary fungal empyema. It clearly illustrates the pathogenesis of Histoplasma empyema, since a fistulous connection between the nodular granulomatous infiltrate and the pleural cavity was demonstrated at thoracotomy. The response to drainage and antifungal therapy is excellent once the proper diagnosis is made, and long-term sequelae are uncommon. This patient's postoperative recove1y and subsequent return to work are typical for patients undergoing empyemectomy and decortication. REFERENCES 1 Goodwin RA Jr, Prez RM. Histoplasmosis. Am Rev Respir Dis 1978; 117:929-56 2 Light RW. Pleural diseases . Philadelphia: Lea & Febiger, 1983 3 Lambert RS , George RB. Fungal diseases of tl1e pleura: clinical manifestations, diagnosis and treatment. Semin Respir Infect 1988; 3 3: 43-51 4 Kilburn CD, McKinsey DS. Recurrent massive pleural effusion due to pleural, pericardial, and epicardial fibrosis in histoplasmosis. Chest 1991; 100:1715-17 5 Newsom BD, Hardy JD. Pulmonary fungal infections: sUivey of 159 cases with surgical imphcations. J Thorac Cardiovasc Surg 1982; 83:218-26 6 George RB , Penn RL, Kinasewitz CT. Mycobacterial, fungal, actinomycotic and nocardial infections of the pleura. Chn Chest Med 1985; 6:63-75 7 Brewer PL, Himmelwlight JP. Pleural effusion due to infection with Histoplasma capsulatum. Chest 1970; 58:76-79 8 Schub HM , Spivey CG Jr, Baird CD. Pleural involvement in histoplasmosis. Am Rev Respir Dis 1966; 94:225-32 9 Johns LE Jr, Garrison RG, White TG. Bronchopleurocutaneous fistula due to infection with Histoplasma capsulatum. Chest 1973; 63:638-41 10 Goodwin RA Jr, Owens FT, Snell JD, eta!. Chronic pulmonary histoplasmosis. Medicine 1976; 55:413-52 11 Wheat LJ, Wass J, Norton J, e t !a. Cavitary histoplasmosis CHEST I 112 I 4 I OCTOBER, 1997

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occurring during th e two large urban outbreaks. Medicine 1984; 63:201-09 12 Wheat LJ, Stein L, Cmya BC, et al. Pe1icarditis as a manifestation of histoplasmosis during two large urban outbreaks. Medici ne 1983; 62:110-19

Giant Lymph Node Hyperplasia {Castleman's Disease) Presenting With Chylous Pleural Effusion* Ma·rk E. Blankenship, MD;' John Rowlett, MD; Lt Comdr Jeffrey W. Timhy, MC, USNR; RichardS. Roth, MD; and Robert E. Jones, MD

A case of giant lymph node hyperplasia (Castleman's disease) with an original presentation of a chylous pleural effusion occurred in a female adolescent. CT scans showed mediastinal lymphadenopathy. Lymph node biopsy was consistent with the plasmacytic variant of Castleman's disease. (CHEST 1997; 112:1132-33) Key words: Castleman's disease; chylous pleural effusion ; gia nt lymph node hyperpl asia

lymph node hyperplasia, first described by G iant Castleman et al in 1956, occurs in two valiants: 1

hyaline vascular and plasmacytic. Each subtype has distinctive histologic features. Castleman's disease ranges from an asymptomatic, incidental localized finding on a chest radiograph to an aggressive illness with systemic symptoms and involvement. As best as can be determined, only one previous case of Castleman's disease has been associated witl1 a chylous effusion at presentation. 2 Herein is a second case of Castleman's disease presenting with a chylous pleural effusion.

chest radiograph revealed bilateral pleural effusions with nearly complete opacification of th e left lung fi eld (Fig 1). A WBC count was 31,000/mm 3 , with 90% neutrophils. Diagnostic thoracentesis and th erapeu tic tube tiloracostomy (bilateral) were performed. A follow-up radiograph demonstrated incomplete resolution of the volume loss. Pleural fluid analysis revealed thick white fluid witl1 exudative indices (lactate dehydrogenase value, 1,173 U!L [serum U!L, 697; ratio, 1.68]; protein level, 5.6 giL [serum, 8.4 giL; ratio, 1.5]; WBC count, 290/mm 3 ; glucose, 27 mmol!L; pH, 7.05). Pleural fluid cultures were sterile. Sputum cultures grew Staphylococcus aureus. She was treated with ceftriaxone disodium. Twenty-four hours after admission, th e patient became afebrile and was less distressed. Serial chest radiographs showed persistent densities and a CT scan of the chest was performed. The CT scan de monstrated bilateral loculated effusions with more extensive disease in th e le ft hemithorax. An ante1ior mediastinal inflammatory mass effect was apparent. A decortication procedure performed via a le ft posterior lateral thoracotomy revealed a d nese, white rind encasing til e entire left lung. Pleural fluid obtained at the tim e of this procedure revealed a triglyceride level of 403 mgldL and a cholesterol level of 50 mgldL. The patient continued to have large output through the ches t tube and was subsequently kept from any oral intake. A Gastrografin (diatrizoate meglumine) swallow perform ed to rule out an esophageal injllly was negative. A subsequent pleural fluid analysis revealed an increased cholesterol level and c hy lomicrons. Chest tube drainage decreased wh ile th e patient was receiving nothing orally and parenteral hyperalimentation , but increased when enteral feedings were resumed. Another CT scan of th e chest showed iJ1creased anterior mediastinal adenopailiy. A left anterior mediastinotomy was performed for tissue diagnosis. The tissue specimen was consisten t witil th e plasmacytic variant of giant lymph node hyperplasia (Castleman's disease [Fig 2]) . This diagnosis was confirmed b y asecond pathologic review. The patient's postoperative course was complicated by ARDS requiring prolonged mechanical ventilatory support. She eventu ally was weaned from tl1e ventilator and was discharged home in satisfactory condition. She remains stable 2 years later, though she does have a moderately severe restri ctive lung disease as a result of intrathoracic fibrosis. The patient's latest pulmonary fun ction tests showed the following: FEV 1, 1.17 L (44% of predi cted value); FVC, 1.39 L (44% of predicted value); total lung capacity, 1.88 L (40% of

CASE REPORT A 13-year-old girl was admitted to th e hospital witl1 a 3-day history of fever, progressive dyspnea, and nonproductive cough. The patient had no significant prior illnesses. Noteworthy findings at til e time of physical examination included a distressed, tired appea1ing adolescent; the temperature was 39.2°C, and respiratmy rate was 30 breaths per minute. There was dullness to percussion in both lung bases; tl1is was greater in tl1e left lung than in the right. Chest auscultation revealed bilateral rhonchi and end-expiratory wheezes. No murmur or mb was detected. There was no palpable hepatosplenomegaly. Physical examination otherwise disclosed no abnormalities. A *From the Departmen ts of Surgery (D r. Blankenship ) and Pediatric and Adolescent Medicin e (Dr. Rowlett), Memorial Medical Center, Savannal1, Ga; the Division of Pulmonary Diseases Critical Care, Pensacola Naval Hospital, Pensacola, Fla (Dr. Timby); Savannah Infectious Diseases, Savannah, Ga (Dr. Roth ); and Cardio-Thoracic Surgery of Savannal1, Savannah, Ga (Dr. Jones). 1 Currently at the Colon and Rectal Clinic, PA, Houston. Manusc1ipt received August 29, 1996; revision accepted March 10, 1997. 1132

FIGURE l. Chest radiograph on admission showing large pleural effusion of the left hemithorax containing a chylous pleural effusion . Selected Reports