Connecting the dots; disseminated histoplasmosis mimicking an infliximab-induced sarcoid-like reaction in anti-PL7 antisynthetase syndrome —a case report

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum . Immunosuppressed patients are at risk of developing severe disseminated disease. We report a case of disseminated histoplasmosis resulting most likely from reactivation of a latent infection more than four decades after initial exposure in a patient receiving long-term immunosuppressive therapy for connective tissue disease-associated interstitial lung disease (ILD), illustrating diagnostic challenges that can occur. A 72-year-old man of Hindustani descent with ILD secondary to anti-PL7-positive antisynthetase syndrome had been receiving long-term therapy with mycophenolate mofetil. Following a provisional diagnosis of Crohn’s disease, his treatment was switched to infliximab. Follow-up high-resolution computed tomography demonstrated the development of multiple new pulmonary micronodules. Extensive microbiological evaluation of bronchoalveolar lavage fluid yielded negative results. Treatment with corticosteroids for a presumed infliximab-induced sarcoid-like reaction was initiated; however, the radiological abnormalities progressed. Subsequent lung biopsy revealed necrotising granulomatous inflammation. Prolonged fungal culture of lung tissue yielded Histoplasma capsulatum after four weeks, establishing the diagnosis of disseminated histoplasmosis with pulmonary and abdominal involvement. In immunocompromised patients presenting with a new inflammatory granulomatous lung disease emerging during treatment, reactivation of histoplasmosis should be considered in the differential diagnosis, even when exposure occurred many years earlier.