Central nervous system histoplasmosis, a neurologic challenge: Report of two cases
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Keywords

Histoplasmosis
Central nervous system
Brain abscess
Pachymeningitis
Fungal meningitis
Myelitis

Abstract

Introduction: Histoplasmosis in the central nervous system is a fungal infection that affects 5% to 25% of patients with disseminated disease, being more common in immunocompromised patients.

Clinical cases: We examined two different cases: Case 1. A 62-year-old male presented with abdominal pain and weight loss. Histoplasma capsulatum was confirmed by colonic biopsy. He later presented convulsions and medullary syndrome with multiple supratentorial and infratentorial abscesses. CD4+ low was found; desnutrition and alcohol intake were the only explanations, as HIV tests were negative. The selected therapeutic scheme was amphotericin induction plus itraconazole for one year. Follow-up showed clinical improvement.

Case 2: A 51-year-old male presented with a 7-month clinical picture of weight loss, fever, dyspnea, and focal epilepsy. He had a recent HIV-positive diagnosis. Cerebrospinal fluid revealed hypoglycorrhachia and elevated protein levels, while brain resonance showed pachymeningeal enhancement. Histoplasmosis was confirmed by bone marrow biopsy, and other causes of pachymeningitis were ruled out. Treatment with amphotericin was initiated, leading to clinical improvement.

Discussion: Histoplasmosis typically presents as chronic basal meningitis, while abscesses, pachymeningitis, or spinal involvement are infrequent. Altered consciousness and headache are the main symptoms. The diagnosis is delayed in 60% of cases. Cerebrospinal fluid (CSF) findings include hyperproteinorrachia (77%), hypoglycorrhachia (53%), and lymphocytic pleocytosis (50%). Although culture and antigen studies are useful, they have limited performance; therefore, imaging and histopathological studies are fundamental. Treatment with amphotericin and itraconazole is necessary and reduces mortality.

Conclusion: Central nervous system infection by Histoplasma is an important challenge due to its variable clinical presentation and the complexity of diagnosis. Evidence remains limited; our cases are atypical and constitute the fourth and fifth cases reported in Colombia.

https://doi.org/10.22379/anc.v41i3.1919

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References

Muñoz-Rosa M, Rhyman N, Tobón-Orozco AM. Histoplasmosis: An endemic mycosis. overview of epidemiology, clinical features, diagnosis, and treatment. Infectio. 2025;29(2):106-116. https://doi.org/10.22354/24223794.1226

Araúz AB, Papineni P. Histoplasmosis. Infect Dis Clin North Am. 2021 Jun;35(2):471-491. https://doi.org/10.1016/j.idc.2021.03.011

Munera MI, Echavarria E. Histoplasmosis: correlacion clinico-radiologica. Medicina UPB. 1990;9(2):143-148.

Mathur M, Johnson CE, Sze G. Fungal infections of the central nervous system. Neuroimag Clin N Am. 2012;22(4):609-632. https://doi.org/10.1016/j.nic.2012.04.004

Thakur KT, Wilson MR. Chronic meningitis. Continuum (Minneap Minn). 2018;24(5):1298-1326. https://doi.org/10.1212/CON.0000000000000664

Góralska K, Blaszkowska J, Dzlkowlec M. Neuroinfections caused by fungi. Infection. 2018;46(4):443–459. https://doi.org/10.1007/s15010-018-1152-2

De Almeida SM, Imano ECM, Vicente VA, Gomes RR, Trentin AP, Zamarchi K, et al. Primary central nervous system infection by histoplasma in an immunocompetent adult. Mycopathology. 2020;185(2):331-338. https://doi.org/10.1007/s11046-019-00394-z

Tobón AM, Agudelo CA, Rosero DS, Ochoa JE, De Bedout C, Zuluaga A, et al. Disseminated histoplasmosis: A comparative study between patients with acquired immunodeficiency syndrome and non-human immunodeficiency virus-infected individuals. Am J Trop Med Hyg. 2005 Sep;73(3):576-582. https://doi.org/10.4269/ajtmh.2005.73.576

Riddell J, Wheat LJ. Central nervous system infection with Histoplasma capsulatum. J Fungi (Basel). 2019;5(3):70. https://doi.org/10.3390/jof5030070

De epe GS Jr. Histoplasma capsulatum. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 7th ed. Philadelphia (PA): Elsevier Churchill Livingstone; 2010:2949-2962.

Kauffman CA. Histoplasmosis. Clin Chest Med. 2009;30(2):217-225. https://doi.org/10.1016/j.ccm.2009.02.002

Singhi P, Saini AG. Fungal and parasitic CNS infections. Indian J Pediatr. 2019;86(1):83-90. https://doi.org/10.1007/s12098-017-2487-x

López LF, Valencia Y, Tobón ÁM, Velásquez O, Santa CD, Cáceres DH, et al. Childhood histoplasmosis in Colombia: Clinical and laboratory observations of 45 patients. Med Mycol. 2016 Oct 1;54(7):677-683. https://doi.org/10.1093/mmy/myw020

Wheat J, Myint T, Guo Y, Kemmer P, Hage C, Terry C, et al. Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine (Baltimore). 2018;97(13):e0245. https://doi.org/10.1097/md.0000000000010245

Cáceres DH, Gómez BL, Restrepo A, Tobón AM. Histoplasmosis y SIDA: factores de riesgo clínicos y de laboratorio asociados al pronóstico de la enfermedad. Infectio. 2012;16(s3):44-50. https://doi.org/10.1016/S0123-9392(12)70026-7

Falci DR, Monteiro AA, Braz Caurio CF, Magalhães TCO, Xavier MO, Basso RP, et al. Histoplasmosis, an underdiagnosed disease affecting people living with HIV/AIDS in Brazil: Results of a multicenter prospective cohort study using both classical mycology tests and histoplasma urine antigen detection. Open Forum Infect Dis. 2019;6(4):ofz073. https://doi.org/10.1093/ofid/ofz073

Pan American Health Organization; World Health Organization. Diagnosing and managing disseminated histoplasmosis among people living with HIV. Washington. D.C.: PAHO; 2020.

Brahmandam S, Brahmandam S, Pradhan S. Disseminated histoplasmosis in a solid organ transplant patient with rapid cns involvement. CHEST. 2019;156(4):A250. https://doi.org/10.1016/j.chest.2019.08.300

Contreras K, García P, Pinto J, Rodriguez P, González C, Vargas Brochero MJ. Histoplasmosis diseminada y síndrome hemofagocítico en trasplante renal. Rev Colomb Nefrol. 2017;4(1):93-98. https://doi.org/10.22265/acnef.4.1.250

Epelboin L, Dione A, Serris A, Blanchet D, Bidaud B, Walter G, et al. Histoplasmosis of the central nervous system: A case series between 1990 and 2019 in French Guiana. Am J Trop Med Hyg. 2021 May 10;105(1):125-129. https://doi.org/10.4269/ajtmh.20-1486

Gavito-Higuera J, Mullins CB, Ramos-Duran L, Olivas-Chacon CI, Hakim N, Palacios E. Fungal infections of the central nervous system: A pictorial review. J Clin Imaging Sci. 2016;6:24. https://doi.org/10.4103/2156-7514.184244

Tee TY, Tan YY, Husin M, Ibrahim KA, Rahman AKA, Mohd-Nasir MN, et al. Case report of chronic meningitis secondary to histoplasmosis in an immunocompromised patient. J Neurol Sci. 2023;455:121353. https://doi.org/10.1016/j.jns.2023.121353

Carod-Artal FJ, Venturini M, Gomes E, de Mello MT. Histoplasmosis crónica del sistema nervioso central en un paciente inmunocompetente. Neurología. 2008;23(4):263-268.

Simms A, Kobayashi T, Endelman L, Sekar P. Disseminated histoplasmosis presenting as bilateral lower extremity paresis. Int J Infect Dis. 2020;95:265-267. https://doi.org/10.1016/j.ijid.2020.03.072

Nathan CL, Emmert BE, Nelson E, Berger JR. CNS fungal infections: A review. J Neurol Sci. 2021;422:117325. https://doi.org/10.1016/j.jns.2021.117325

Campos LG, Bedinot da Conceição TM, Krüger MS, Perez JA, Duarte JA. Infecção do sistema nervoso central: os achados de imagem sugestivos de fungo como causa. Radiol Bras. 2021;54(3). https://doi.org/10.1590/0100-3984.2020.0093

Ramírez JA, Reyes-Montes MDR, Rodríguez-Arellanes G, Pérez-Torres A, Taylor ML. Central nervous system histoplasmosis: An updated insight. Pathogens. 2023 May 5;12(5):681. https://doi.org/10.3390/pathogens12050681

Tai YF, Kullmann DM, Howard RS, Scott GM, Hirsch NP, Revesz T, et al. Central nervous system histoplasmosis in an immunocompetent patient. J Neurol. 2010;257:1931-1933. https://doi.org/10.1007/s00415-010-5629-x

Klumpp L, Liu-Young G, Modi F, Jordan J, Shah R. Reactivation of histoplasmosis disseminated into the central nervous system presenting as a stroke. Cureus. 2019;11(12):e6525. https://doi.org/10.7759/cureus.6525

Nguyen FN, Kar JK, Zakaria A, Schiess MC. Isolated central nervous system histoplasmosis presenting with ischemic pontine stroke and meningitis in an immune-competent patient. JAMA Neurol. 2013;70(5):638-641. https://doi.org/10.1001/jamaneurol.2013.1043

Hollands LJ, Vergouwen MDI, Greving JP, Wermer MJH, Rinkel GJE, Algra AM. Management decisions on unruptured intracranial aneurysms before and after implementation of the PHASES score. J Neurol Sci. 2021 Mar 15;422:117319. https://doi.org/10.1016/j.jns.2021.117319

Hariri OR, Minasian T, Quadri SA, Dyurgerova A, Farr S, Miulli DE, et al. Histoplasmosis with deep CNS involvement: Case presentation with discussion and literature review. J Neurol Surg Rep. 2015;76(1):167-172. https://doi.org/10.1055/s-0035-1554932

Estrada-Bellmann I, Camara-Lemarroy CR, Flores-Cantu H, Calderon-Hernandez HJ, Villareal-Velazquez HJ. Hemichorea in a patient with HIV-associated central nervous system histoplasmosis. Int J STD AIDS. 2016;27(1):75-77. https://doi.org/10.1177/0956462414564608

Recker MJ, Housley SB, Lipinski LJ. Indolent nonendemic central nervous system histoplasmosis presenting as an isolated intramedullary enhancing spinal cord lesion. Surg Neurol Int. 2021 Aug 9;12:392. https://doi.org/10.25259/SNI_345_2021

Khalaf SA, Patel P, Caruso C, Parrett T, Bran A. CNS histoplasmosis as a gliosarcoma mimicker: The diagnostic dilemma of solitary brain lesions. IDCases. 2022;27:e01364. https://doi.org/10.1016/j.idcr.2021.e01364

Klein CJ, Dinapoli RP, Temesgen Z, Meyer FB. Central nervous system histoplasmosis mimicking a brain tumor: Difficulties in diagnosis and treatment. Mayo Clin Proc. 1999;74(8):803-807. https://doi.org/10.4065/74.8.803

Kumar B, Agarwal D, Meena DS, Vaswani S, Sowmya-Sri D, Kumar D, et al. CNS histoplasmosis coexisting with pulmonary tuberculosis in a HIV negative patient: Case report. BMC Infect Dis. 2024;24:1297. https://doi.org/10.1186/s12879-024-10068-x

Batra V, Khararjian A, Wheat J, Zhang SX, Crain B, Baras A. From suspected Creutzfeldt-Jakob disease to confirmed histoplasma meningitis. BMJ Case Rep. 2016;2016:bcr2016214937. https://doi.org/10.1136/bcr-2016-214937

Ranganath S, McGhie TA, Larosa S, Lehman W, Fader R. Clinical and laboratory diagnosis of central nervous system histoplasmosis. Am J Med. 2012;125(10):e1-2. https://doi.org/10.1016/j.amjmed.2011.12.011

Block KC, Myint T, Raymond-Guillen L, Hage CA, Davis TE, Wright PW, et al. Improvement in diagnosis of histoplasma meningitis by combined testing for histoplasma antigen and immunoglobulin g and immunoglobulin m anti-histoplasma antibody in cerebrospinal fluid. Clin Infect Dis. 2018;66(1):89-94. https://doi.org/10.1093/cid/cix706

Myint T, Bloch KC, Raymond-Guillen L, Wheat LJ. Detection of (1,3) -?-d-Glucan in cerebrospinal fluid in Histoplasma meningitis. Open Forum Infect Dis. 2017;4(s1):S76. https://doi.org/10.1093/ofid/ofx163.013

Babady NE, Buckwalter SP, Hall L, Le Febre KM, Binnicker MJ, Wengenack NL. Detection of blastomyces dermatitidis and histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol. 2011;49(9):3204-3208. https://doi.org/10.1128/JCM.00673-11

Makis W, Rakheja R, Probst S. Appearance of CNS histoplasmosis on 18F-FDG PET / CT with MRI correlation. BJR Case Rep. 2016;2(3):20150443. https://doi.org/10.1259/bjrcr.20150443

Aboabdo M, Mishkin A. Antifungal therapy for the treatment of CNS infections. Curr Fungal Infect Rep. 2024;18:146-153. https://doi.org/10.1007/s12281-024-00492-6

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):807-825. https://doi.org/10.1086/521259

Negroni R. Clinical spectrum and treatment of classic histoplasmosis. Rev Iberoam Micol. 2000;17:159-167.

Potosí JA, Gutiérrez YM, González FE. La importancia de la correlación clínico- epidemiológica en el diagnóstico temprano de la histoplasmosis: reporte de dos casos clínicos en Popayán, Colombia. Biomédica. 2023;43(s1):2023. https://doi.org/10.7705/biomedica.6782

Lizarazo J, Gutierrez P, Chaves O, Peña Y, Castañeda E. Histoplasmosis localizada del sistema nervioso central en un niño inmunocompetente. Acta Neurol Colomb. 2010;26(2).

Osorio N, López Y, Jaramillo JC. Histoplasmosis del sistema nervioso central en un paciente inmunocompetente. Biomédica. 2014;34(4):506-513. https://doi.org/10.7705/biomedica.v34i4.2135

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