{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:20:02Z","timestamp":1791418802247,"version":"4.3.3"},"reference-count":66,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Histoplasmosis is the most common endemic mycosis in North and Central America, particularly in the Ohio and Mississippi River Valleys. Progressive disseminated histoplasmosis (PDH) occurs in \u223c1 in 2,000 acute infections and may present atypically with multiorgan involvement, especially in immunocompromised hosts. We describe a case of PDH complicated by macrophage activation syndrome (MAS)\/hemophagocytic lymphohistiocytosis (HLH) in a patient with dermatomyositis who was receiving long-term immunosuppressive therapy. She developed two uncommon manifestations of PDH: biopsy-proven cellulitis and intracellular yeasts within neutrophils on a peripheral blood smear. Diagnosis was delayed because of fungal antigen cross-reactivity and overlapping clinical and laboratory features of PDH and MAS\/HLH. This case highlights the importance of early recognition, timely treatment, and coordinated multidisciplinary management. Our patient died 17 days after admission, underscoring the high mortality rate of MAS\/HLH-associated histoplasmosis.<\/jats:p>","DOI":"10.4269\/ajtmh.24-0802","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T15:04:07Z","timestamp":1755011047000},"page":"773-780","source":"Crossref","is-referenced-by-count":1,"title":["Progressive Disseminated Histoplasmosis with Dermatomyositis and Macrophage Activation Syndrome\/Hemophagocytic Lymphohistiocytosis"],"prefix":"10.4269","volume":"113","author":[{"given":"Ashton D.","family":"Hall","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Salibindla","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Dubocq-Cabrera","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea M.","family":"Rotert","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Balog","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S.","family":"Deepe","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Haglund","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Curr Fungal Infect Rep","first-page":"120","article-title":"Histoplasmosis: Epidemiology, diagnosis, and clinical manifestations","volume":"13","author":"Linder","year":"2019"},{"key":"b2","series-title":"Am J Trop Med Hyg","first-page":"982","article-title":"Histoplasma capsulatum: More widespread than previously thought","volume":"90","author":"Antinori","year":"2014"},{"key":"b3","series-title":"Mycopathologia","first-page":"843","article-title":"Re-drawing the maps for endemic mycoses","volume":"185","author":"Ashraf","year":"2020"},{"key":"b4","series-title":"PLoS Pathog","first-page":"e1007213","article-title":"Outbreaks of histoplasmosis: The spores set sail","volume":"14","author":"Deepe","year":"2018"},{"key":"b5","series-title":"Clin Infect Dis","first-page":"1295","article-title":"The geographic distribution of dimorphic mycoses in the United States for the modern era","volume":"76","author":"Mazi","year":"2023"},{"key":"b6","series-title":"J Fungi","first-page":"236","article-title":"Pulmonary histoplasmosis: A clinical update","volume":"9","author":"Barros","year":"2023"},{"key":"b7","series-title":"Infect Dis Clin North Am","first-page":"207","article-title":"Histoplasmosis","volume":"30","author":"Wheat","year":"2016"},{"key":"b8","series-title":"Emerg Infect Dis","first-page":"2100","article-title":"Molecular detection of Histoplasma capsulatum in Antarctica","volume":"28","author":"Moreira","year":"2022"},{"key":"b9","series-title":"MMWR Morb Mortal Wkly Rep","first-page":"1","article-title":"Summary of notifiable infectious diseases and conditions\u2014United States, 2015","volume":"64","author":"Adams","year":"2017"},{"key":"b10","article-title":"Reportable Fungal Diseases by State.","year":"2024"},{"key":"b11","series-title":"MMWR Morb Mortal Wkly Rep","first-page":"239","article-title":"Surveillance for coccidioidomycosis, histoplasmosis, and blastomycosis during the COVID-19 pandemic\u2014United States, 2019\u20132021","volume":"73","author":"Williams","year":"2024"},{"key":"b12","series-title":"Emerg Infect Dis","first-page":"370","article-title":"Epidemiology of histoplasmosis outbreaks, United States, 1938\u20132013","volume":"22","author":"Benedict","year":"2016"},{"key":"b13","series-title":"Am J Epidemiol","first-page":"156","article-title":"Pulmonary histoplasmosis associated with exploration of a bat cave","volume":"110","author":"Lottenberg","year":"1979"},{"key":"b14","series-title":"MMWR Morb Mortal Wkly Rep","first-page":"289","article-title":"Cave-associated histoplasmosis outbreak among travelers returning from Costa Rica\u2014Georgia, Texas, and Washington, December 2024-January 2025","volume":"74","author":"Ghai","year":"2025"},{"key":"b15","series-title":"Clin Infect Dis","first-page":"S102","article-title":"Histoplasmosis and blastomycosis","volume":"22","author":"Bradsher","year":"1996"},{"key":"b16","series-title":"Rheumatol Int","first-page":"405","article-title":"A rare trigger for macrophage activation syndrome","volume":"31","author":"Agarwal","year":"2011"},{"key":"b17","series-title":"Adv Rheumatol","first-page":"28","article-title":"Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: Two rare sides of the same devastating coin","volume":"64","author":"Sztajnbok","year":"2024"},{"key":"b18","series-title":"Case Rep Crit Care","first-page":"6612710","article-title":"Hemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis in rheumatologic disease","volume":"2021","author":"Kusne","year":"2021"},{"key":"b19","series-title":"Blood","first-page":"2308","article-title":"Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited","volume":"144","author":"Henter","year":"2024"},{"key":"b20","series-title":"Lancet","first-page":"1503","article-title":"Adult haemophagocytic syndrome","volume":"383","author":"Ramos-Casals","year":"2014"},{"key":"b21","series-title":"Proc Am Thorac Soc","first-page":"169","article-title":"Histoplasmosis","volume":"7","author":"Knox","year":"2010"},{"key":"b22","series-title":"Medicine (Baltimore)","first-page":"263","article-title":"Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks","volume":"62","author":"Sathapatayavongs","year":"1983"},{"key":"b23","series-title":"Ann Intern Med","first-page":"331","article-title":"A large urban outbreak of histoplasmosis: Clinical features","volume":"94","author":"Wheat","year":"1981"},{"key":"b24","series-title":"Infect Dis Clin North Am","first-page":"471","article-title":"Histoplasmosis","volume":"35","author":"Ara\u00faz","year":"2021"},{"key":"b25","series-title":"Med Mycol Case Rep","first-page":"100662","article-title":"Fatal misdiagnosis of progressive disseminated histoplasmosis","volume":"45","author":"Vasilopoulou","year":"2024"},{"key":"b26","series-title":"EJHaem","first-page":"545","article-title":"Disseminated histoplasmosis mimicking hematologic malignancy in a patient with human immunodeficiency virus","volume":"3","author":"Kallen","year":"2022"},{"key":"b27","series-title":"Clin Microbiol Rev","first-page":"115","article-title":"Histoplasmosis: A clinical and laboratory update","volume":"20","author":"Kauffman","year":"2007"},{"key":"b28","series-title":"Med Mycol Case Rep","first-page":"18","article-title":"Hemophagocytic lymphohistiocytosis secondary to progressive disseminated histoplasmosis presenting as cellulitis","volume":"33","author":"Puing","year":"2021"},{"key":"b29","series-title":"Transplant Proc","first-page":"4313","article-title":"Progressive disseminated histoplasmosis presenting as cellulitis in a renal transplant recipient","volume":"37","author":"McGuinn","year":"2005"},{"key":"b30","series-title":"Am J Trop Med Hyg","first-page":"459","article-title":"Skin lesions of disseminated histoplasmosis resembling Kaposi\u2019s sarcoma","volume":"108","author":"Kawashima","year":"2023"},{"key":"b31","series-title":"Intern Med","first-page":"141","article-title":"Disseminated histoplasmosis presenting with panniculitis and macrophage activation syndrome in a patient undergoing immunosuppressive therapy for mixed connective tissue disease (MCTD)","volume":"64","author":"Kawashima","year":"2025"},{"key":"b32","series-title":"An Bras Dermatol","first-page":"96","article-title":"Histoplasma panniculitis in a patient with systemic lupus erythematosus","volume":"94","author":"Flores-Bozo","year":"2019"},{"key":"b33","series-title":"Medicine (Baltimore)","first-page":"162","article-title":"Systemic histoplasmosis: A 15-year retrospective institutional review of 111 patients","volume":"86","author":"Assi","year":"2007"},{"key":"b34","series-title":"JAMA","first-page":"1916","article-title":"Histoplasma in circulating blood","volume":"207","author":"Jacobs","year":"1969"},{"key":"b35","series-title":"Case Rep Infect Dis","first-page":"7403878","article-title":"An Italian case of disseminated histoplasmosis associated with HIV","volume":"2019","author":"Papalini","year":"2019"},{"key":"b36","series-title":"Am J Med","first-page":"28","article-title":"Systemic fungal infections complicating renal transplantation and immunosuppressive therapy: Clinical, microbiologic, neurologic and pathologic features","volume":"43","author":"Rifkind","year":"1967"},{"key":"b37","series-title":"Can Med Assoc J","first-page":"587","article-title":"Histoplasmosis and thrombocytopenic purpura: Transmission by renal homotransplantation","volume":"93","author":"Hood","year":"1965"},{"key":"b38","series-title":"Case Rep Med","first-page":"215207","article-title":"A case of disseminated histoplasmosis detected in peripheral blood smear staining revealing AIDS at terminal phase in a female patient from Cameroon","volume":"2012","author":"Ebenye","year":"2012"},{"key":"b39","series-title":"Acta Clin Belg","first-page":"356","article-title":"Disseminated histoplasmosis: Case report and review of the literature","volume":"73","author":"Evrard","year":"2018"},{"key":"b40","series-title":"Curr Trop Med Rep","first-page":"129","article-title":"Diagnostic methods for histoplasmosis: Focus on endemic countries with variable infrastructure levels","volume":"1","author":"Scheel","year":"2014"},{"key":"b41","series-title":"J Fungi","first-page":"196","article-title":"Evolving epidemiology, improving diagnostic tests and their importance for the correct diagnosis of histoplasmosis","volume":"11","author":"Schmidt","year":"2025"},{"key":"b42","series-title":"J Clin Microbiol","first-page":"1612","article-title":"Laboratory diagnostics for histoplasmosis","volume":"55","author":"Azar","year":"2017"},{"key":"b43","series-title":"Clin Infect Dis","first-page":"1169","article-title":"Cross-Reactivity in Histoplasma capsulatum variety capsulatum Antigen Assays of Urine Samples from Patients with Endemic Mycoses","volume":"24","author":"Wheat","year":"1997"},{"key":"b44","series-title":"Curr Top Microbiol Immunol","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/82_2018_114","article-title":"Histoplasma capsulatum: Mechanisms for pathogenesis","volume":"422","author":"Mittal","year":"2019"},{"key":"b45","series-title":"Transpl Infect Dis","first-page":"213","article-title":"False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis","volume":"14","author":"Vergidis","year":"2012"},{"key":"b46","series-title":"Clin Vaccine Immunol","first-page":"638","article-title":"Histoplasmosis-associated cross-reactivity in the BioRad platelia Aspergillus enzyme immunoassay","volume":"14","author":"Wheat","year":"2007"},{"key":"b47","series-title":"J Infect","first-page":"80","article-title":"False-positive Aspergillus galactomannan (GM) assay in histoplasmosis","volume":"56","author":"Narreddy","year":"2008"},{"key":"b48","series-title":"Mycoses","first-page":"25","article-title":"Disseminated Penicillium marneffei infection in an HIV-positive female from Thailand in Germany","volume":"42","author":"Rimek","year":"1999"},{"key":"b49","series-title":"J Clin Microbiol","first-page":"2929","article-title":"Cryptococcus neoformans galactoxylomannan contains an epitope(s) that is cross-reactive with Aspergillus galactomannan","volume":"43","author":"Dalle","year":"2005"},{"key":"b50","series-title":"Clin Infect Dis","first-page":"917","article-title":"Treatment with piperacillin-tazobactam and false-positive Aspergillus galactomannan antigen test results for patients with hematological malignancies","volume":"38","author":"Adam","year":"2004"},{"key":"b51","series-title":"Diagn Microbiol Infect Dis","first-page":"113","article-title":"Cross-reactivity of non-Aspergillus fungal species in the Aspergillus galactomannan enzyme immunoassay","volume":"59","author":"Cummings","year":"2007"},{"key":"b52","series-title":"Curr Fungal Infect Rep","first-page":"127","article-title":"Role of serological tests in the diagnosis of mold infections","volume":"12","author":"Richardson","year":"2018"},{"key":"b53","series-title":"J Biomed Sci","first-page":"42","article-title":"Diagnosis of invasive fungal infections: Challenges and recent developments","volume":"30","author":"Fang","year":"2023"},{"key":"b54","series-title":"Infect Dis Clin North Am","first-page":"145","article-title":"Histoplasmosis","volume":"39","author":"Eichenberger","year":"2025"},{"key":"b55","series-title":"Curr Opin Allergy Clin Immunol","first-page":"410","article-title":"Hemophagocytic lymphohistiocytosis and related disorders","volume":"6","author":"Filipovich","year":"2006"},{"key":"b56","series-title":"Blood","first-page":"44","article-title":"External validation of the HLH-2004 diagnostic criteria and H-score for diagnosis of hemophagocytic lymphohistiocytosis in adults","volume":"136","author":"Croden","year":"2020"},{"key":"b57","series-title":"Clin Infect Pract","first-page":"100488","article-title":"Disseminated histoplasmosis induced hemophagocytic lymphohistiocytosis in an immunocompromised patient","volume":"26","author":"El Bardai","year":"2025"},{"key":"b58","series-title":"Clin Infect Dis","first-page":"807","article-title":"Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America","volume":"45","author":"Wheat","year":"2007"},{"key":"b59","series-title":"J Allergy Clin Immunol Pract","first-page":"1508","article-title":"Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: Consensus statements by the HLH Steering Committee of the Histiocyte Society","volume":"6","author":"Ehl","year":"2018"},{"key":"b60","series-title":"BMJ Case Rep","first-page":"bcr2017221264","article-title":"Safe usage of anakinra and dexamethasone to treat refractory hemophagocytic lymphohistiocytosis secondary to acute disseminated histoplasmosis in a patient with HIV\/AIDS","volume":"2017","author":"Ocon","year":"2017"},{"key":"b61","series-title":"Can J Infect Dis Med Microbiol","first-page":"7107326","article-title":"Histoplasmosis-associated hemophagocytic lymphohistiocytosis: A review of the literature","volume":"2019","author":"Jabr","year":"2019"},{"key":"b62","series-title":"Open Forum Infect Dis","first-page":"ofv055","article-title":"Histoplasmosis-induced hemophagocytic syndrome: A case series and review of the literature","volume":"2","author":"Townsend","year":"2015"},{"key":"b63","series-title":"Front Cell Infect Microbiol","first-page":"847950","article-title":"Hemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis in HIV seronegative patients: A case report and review of the literature","volume":"12","author":"Chen","year":"2022"},{"key":"b64","series-title":"Arthritis Rheumatol","first-page":"1714","article-title":"The 2022 EULAR\/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis\/macrophage activation syndrome (HLH\/MAS)","volume":"75","author":"Shakoory","year":"2023"},{"key":"b65","series-title":"Front Med (Lausanne)","first-page":"735796","article-title":"High mortality of HLH in ICU regardless etiology or treatment","volume":"8","author":"Bichon","year":"2021"},{"key":"b66","series-title":"Haematologica","first-page":"269","article-title":"Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy","volume":"104","author":"Yoon","year":"2019"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/4\/article-p773.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/4\/article-p773.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/4\/article-p773.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T17:30:17Z","timestamp":1759339817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/4\/article-p773.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":66,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.24-0802","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}