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. 2022 Sep 15;8(1):21.
doi: 10.1186/s40794-022-00178-2.

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

Eveline Hofmann  1 , Konrad Mühlethaler  2 , Matthias Pollak  3 , Daniel Ott  4 , Nora Bienz  5 , Stefan Zimmerli  6 , Cédric Hirzel  6
Affiliations

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

Eveline Hofmann et al. Trop Dis Travel Med Vaccines. .

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.

Keywords: Hemophagocytic lymphohistiocytosis; Histoplasmosis; Immunocompromised; Returning traveler; TNF-α inhibitor.

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Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
CT scan at hospital admission. Chest CT scan shows extensive bilateral pulmonary infiltrates with large pulmonary effusions and mediastinal lymphadenopathy
Fig. 2
Fig. 2
Morphology of Histoplasma capsulatum yeasts. A Hemorrhagic (erythrocytes blue arrows) bronchoalveolar fluid with intracellular Histoplasma capsulatum (black arrow) yeasts measuring 3-4 µm. B Peripheral blood smear with Histoplasma capsulatum yeasts (black arrows) within a macrophage (red arrow), eryhthrocytes (blue arrows), and thrombocytes (yellow arrows). The Histoplasma capsulatum yeasts exhibit the typical ovoid shape
Fig. 3
Fig. 3
Leishmania amastigotes in a bone marrow aspirate. In the individual amastigotes (black arrows), the characteristic kinetoplast (red arrows) and the nucleus (yellow arrows) are clearly visible
See this image and copyright information in PMC

References

    1. Wood KL, Hage CA, Knox KS, Kleiman MB, Sannuti A, Day RB, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. m J Respir Crit Care Med. 2003;167(9):1279–82. doi: 10.1164/rccm.200206-563OC. - DOI - PubMed
    1. Jr Deepe GS. Modulation of infection with Histoplasma capsulatum by inhibition of tumor necrosis factor-alpha activity. Clin Infect Dis. 2005;41(Suppl 3):S204–7. doi: 10.1086/429999. - DOI - PubMed
    1. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807–25. doi: 10.1086/521259. - DOI - PubMed
    1. Ashbee HR, Evans EG, Viviani MA, Dupont B, Chryssanthou E, Surmont I, et al. Histoplasmosis in Europe: report on an epidemiological survey from the European Confederation of Medical Mycology Working Group. Med Mycol. 2008;46(1):57–65. doi: 10.1080/13693780701591481. - DOI - PubMed
    1. Jr Deepe GS. Outbreaks of histoplasmosis: The spores set sail. LoS Pathog. 2018;14(9):e1007213. doi: 10.1371/journal.ppat.1007213. - DOI - PMC - PubMed