Pulmonary cryptococcosis is caused by inhalation of cryptococcus species found in various environmental sources. C. neoformans, an encapsulated yeast from, is the most common pathogen in human disease. We report a case of a non-acute pulmonary cryptococcosis secondary to C.albidus, a non-capsulated organism, in a patient with rheumatoid arthritis treated with infliximab.
73 year old female with long standing rheumatoid arthritis recently started on inflixmab, presented with anorexia and weight loss of few months duration; Her PPD status was unknown prior to starting anti TNF therapy. Her physical exam was only significant for cachexia. Her CBC and chemistries were within normal limits, ESR 125, C-RP of 10. The chest radiograph showed bilateral multiple cavitary opacities [Fig 1]. CT scan of the chest confirmed a subpleural distribution of these nodules. Transbronchial biopsy from the largest lesion showed necrotizing granulomatous inflammation [Fig 2]; tissue culture grew Cryptococcus albidus. She was treated with fluconazole with clinical and radiographic improvement.
Pulmonary cryptococcosis occurs rarely in immunocompetent individuals. Cell-mediated immunity, including TNF alpha secretion, plays a major role in the immunity against this infection. Among the genus Cryptococcus, C.neoformans is the major human pathogen. Thus far, the literature reports four cases of pulmonary cryptococcosis in patients receiving anti-TNF therapy (2). The clinical presentation is usually of a non-acute pneumonia, with constitutional symptoms, and non-specific respiratory complaints. Occasionally it can take a form of acute respiratory failure and extrapulmonary disease. The described radiologic findings of pulmonary cryptococcosis encompass three major patterns: solitary or multiple pulmonary nodules in a subpleural location, with or without cavitation, segmental or lobar consolidation and interstitial micronodular or reticulonodular pattern. (3,4) The diagnosis of pulmonary cryptococcosis is established by either culture obtained from bronchial washings or lung biopsy or by direct histologic identification of the fungus in the lung tissue. Cryptococcus albidus, a non-neoformans species of the genus Cryptococcus, is generally regarded as a rare cause of disease (3,5) There have been only 15 previously reported cases in which this organism has been isolated as a pathogen, 3 of which were localized to the lung; none was reported in patients receiving anti TNF therapy. C. albidus disease spectrum also includes summer-type hypersensitivity pneumonitis, described in the Japanese population. The treatment of cryptococcal disease is usually with amphotericin B, and its lipid derivatives, flucytosine, and azoles especially fluconazole. (1) To our knowledge this is the first case of Cryptococcus albidus pneumonia in a patient on anti TNF therapy.
Anti-TNF therapy is becoming the accepted standard of care for several rheumatologic disorders. Given the potency of its immune suppression one speculates that unrecognized organisms will become pulmonary pathogens in the immediate future. We advocate early tissue sampling and thorough microbiologic examinations in patients on TNF antagonists to guide therapy.
J.A. Faress, None.