Cryptococcus and Coccidioides in Sarcoidosis

To the Editor—We read with great interest Kuberski and Yourison’s hypothesis that Coccidioides spp. and other dimorphic fungi may be the precipitants of sarcoidosis in a proportion of cases [1]. We would like to suggest additional ways to test this hypothesis, as well as suggesting that Cryptococcus spp. be included in the list of fungi considered possible precipitants. A single-center study of severe infections in 585 patients with sarcoidosis from France found that fungi were the most common cause of severe infections after mycobacteria [2]. Ten of the 16 severe infections were fungal, and Cryptococcus neoformans and Pneumocytis jirovecii were the most common causes. While the P. jirovecii infections are likely the result of the immunosuppressants used to treat sarcoidosis, this is not as clearly the case for Cryptococcus. A study of all cases of cryptococcosis in the French national mycosis registry, for example, found 18 cases where the individual had preexisiting or contemporaneous sarcoidosis [3]. In 6 cases, the diagnosis of cryptococcosis was made before immunosupressants were commenced. This association may be due to the low CD4 T-cell count associated with sarcoidosis [4], but it may also reflect individuals whose dysregulated immune response to Cryptococcus resulted in sarcoid. As Kuberski et al. note, negative fungal polymerase chain reactions of formalin-fixed sarcoid tissue biopsies would not rule out these fungi as precipitants in the sarcoid. If a dysregulated immune response to various fungi (and other antigens) were responsible for sarcoid, then assessing the antibody and cell-mediated immune responses to a panel of fungi in patients with a new diagnosis of sarcoid would be instructive. Finding enhanced responses to specific fungi in sarcoid cases vs controls would constitute evidence supportive of the fungi-sarcoid hypothesis.