Travel related histoplasmosis – a diagnostic challenge in a patient with tumor necrosis factor alpha (TNF-α) inhibitor therapy

Abstract

Introduction In a non-endemic setting, disseminated histoplasmosis is a rare travel-related health problem of immunosuppressed returnees from endemic regions. Methods We describe the case of a 68-year-old man with rheumatoid arthritis and tumor necrosis factor alpha (TNF-α) inhibitor treatment-related immunodeficiency, who suffered from disseminated histoplasmosis after traveling to Brazil. Based on this case, we discuss challenges and pitfalls associated with the diagnosis of disseminated histoplasmosis in a non-endemic setting. Results The disease mimicked a hemophagocytic lymphohistiocytosis (HLH) like syndrome. Histoplasma capsulatum was microscopically detected in bronchoalveolar fluid and bone marrow aspirate smears, but was initially misclassified as Leishmania spp., another class of pathogens, which may cause HLH like syndromes in immunocompromised individuals. Discussion Since the clinical symptoms of histoplasmosis are nonspecific and physicians in non-endemic regions might not be familiar with this disease pattern, there is a risk of delayed diagnosis of travel related cases. Taking a thorough travel history is key in unclear cases of illness in immunocompromised patients.

Pulmonary infections in the returning traveler

“…Most cases were clinically not severe, although disseminated forms were also identified in these immunocompetent travelers (8%) [45]. Atypical presentations may occur, mainly in immunosuppressed travelers or those with comorbidities [46]. Histoplasmosis in travelers may therefore remain an underdiagnosed entity and should be suspected in patients with pneumonia in the adequate epidemiological context, especially if suggestive radiologic findings are present (pulmonary nodules, typically multiple and with peripheral distribution occur in many cases) [45].…”

Closing the Gap in Proteomic Identification of Histoplasma capsulatum: A Case Report and Review of Literature

“…Since the yeast form of H. capsulatum replicates in macrophages, efficient host adaptive immunity and, specifically, the Th1 immune response are required to activate phagocytic cells and clear the infection [6]. In this regard, treatments with TNF-alpha inhibitors, which are commonly used among patients with inflammatory-autoimmune diseases, can impair the Th1 immune response, increasing the risk of disseminated histoplasmosis [10]. Additionally, biologics, i.e., IL-17 inhibitors and IL-12/23 inhibitors, which are commonly used among patients with inflammatory-autoimmune diseases such as psoriasis and inflammatory bowel diseases (IBD), may predispose to mycotic infections [11,12].…”

“…Culture and histopathological analyses, showing the characteristic intracellular forms of the fungus in infected tissues, are considered, to date, the gold standard for the diagnosis of histoplasmosis [10]. Unfortunately, H. capsulatum may be misidentified in histologic sections as Candida glabrata and Sporothrix schenckii due to the variety of morphologically similar small yeast forms.…”