Clinical and histopathological presentation of Histoplasmosis in the oral cavity - A Systematic review
Abstract
Objective: Oral lesions can be an early indicator of systemic histoplasmosis, especially in immunocompromised patients. The main aim of this review was to summarise demographic and clinical findings and correlate them with histopathological findings.
Material and Methods: The literature search included articles published on oral histoplasmosis from databases like PubMed, Scopus, Web of Science and EMBASE. The included articles provided information regarding sociodemographic and clinical data, human immunodeficiency virus (HIV) infection status, histopathological features, treatment, and outcome. This review included 30 case reports encompassing a total of 92 individual cases, of which 34 were HIV‑positive.
Results: The oral manifestation was observed as a disseminated form in all HIV patients. Oral histoplasmosis is clinically presented as a painful ulcerated lesion commonly seen in the tongue, gingiva, palate, and buccal mucosa. Histopathologically, sheets of histiocytes with yeast-like cells, inflammatory infiltrate, and multinucleated giant cells were seen. Histopathological findings are essential for an early diagnosis of oral histoplasmosis since it could mimic other diseases clinically. Itraconazole was found to be an effective treatment for oral histoplasmosis.
Conclusions: Oral lesions of histoplasmosis can occur in non-endemic countries and immunocompetent individuals. Histopathological findings are essential for an early diagnosis of oral histoplasmosis since it could mimic other diseases clinically.
References
Akin L, Herford AS, Cicciù M. Oral presentation of disseminated histoplasmosis: a case report and literature review. J Oral Maxillofac Surg. 2011;69(2):535-41. https://doi.org/10.1016/j.joms.2010.05.053. Epub 2010 Dec 9. PMID: 21145642.
Gopalakrishnan R, Nambi PS, Ramasubramanian V, Abdul Ghafur K, Parameswaran A. Histo-plasmosis in India: truly uncommon or uncom-monly recognised? J Assoc Physicians India. 2012; 60:25-8. PMID: 23777021.
Mittal N, Patil A, Singhal P, Bal MM, Rane SU, Thiagarajan S. Histoplasmosis of the Head and Neck Region Mimicking Malignancy: A Clinic-Pathological Predicament. Turk Patoloji Derg. 2023;39(2):133-139. https://doi.org/10.5146/tjpath.2022.01585. PMID: 35989588; PMCID: PMC1 05 18199.
Joseph Wheat L. Current diagnosis of histo-plasmosis. Trends Microbiol. 2003;11(10):488-94. https://doi.org/10.1016/j.tim.2003.08.007. PMID: 14 557032.
Falci DR, Hoffmann ER, Paskulin DD, Pasqu-alotto AC. Progressive disseminated histo-plasmosis: a systematic review on the performance of non-culture-based diagnostic tests. Braz J Infect Dis. 2017;21(1):7-11. https://doi.org/10.1016/j.bjid.2016.09.012. Epub 2016 Nov 19. PMID: 27875685; PMCID: PMC9425517.
Singh S, Verma N, Chawla R, Saikia TJ. Primary oral histoplasmosis in an immunocompetent host masquerading as malignancy. J Oral Maxillofac Pathol. 2023;27(3):540-542.
https://doi.org/10.4103/jomfp.jomfp_204_23. Epub 2023 Sep 12. PMID: 38033977; PMCID: PMC10683917.
Smith R, Lee A, Gottlieb T, Eckstein R, Meng L. Another case of histoplasmosis in a non-endemic area. Pathology. 2006;38(4):378-80. https://doi.org/10.1080/00313020600820781. PMID: 16916738.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. https://doi.org/10.1136/bmj.n71.PMID:33782057; PMCID: PMC: 8005924.
Sigera LSM, Gunawardane SR, Malkanthi MA, Jayasinghe RD, Sitheeque MAM, Tilakaratne WM, Jayasekera PI. Histoplasma capsulatum Caused a Localized Tongue Ulcer in a Non-HIV Patient-A Case From Nonendemic Country. Ear Nose Throat J. 2020;99(6):379-381. https://doi.org/10.1177/0145561319844246. Epub 2019 May 7. PMID: 31064244.
Chroboczek T, Dufour J, Renaux A, Aznar C, Demar M, Couppie P, Adenis A. Histoplasmosis: an oral malignancy-like clinical picture. Med Mycol Case Rep. 2018;19:45-8. https://doi.org/10.1016/j.mmcr.2017.11.001
Sharma D, McKendry A, Nageshwaran S, Cartledge J. A case of oral ulceration and disseminated histoplasmosis in HIV infection. Int J STD AIDS. 2012;23(7):522-3. https://doi.org/10.1258/ijsa.2011.011261. PMID: 22844011.
Mohammed S, Sinha M, Chavan P, Premalata CS, Shivaprakash MR, Chakrabarti A, Jayshree RS. Oral histoplasmosis masquerading as oral cancer in HIV-infected patient: a case report. Med Mycol Case Rep. 2012;1:85-7. https://doi.org/10.1016/j.mmcr.2012.09.002
Stefan AJ, Herc ES, Gudipati S, Brar I, Vitale A, Tariq Z. Atypical presentation of progressive disseminated histoplasmosis in a patient recently diagnosed with AIDS. Int J Infect Dis. 2023;127:45-47. https://doi.org/10.1016/j.ijid.2022.11.036. Epub 2022 Dec 1. PMID: 3646 2572.
Mehta A, Desai S, Desai N, Mookerjee A. Disseminated histoplasmosis: missed oppor-tunistic infection in a HIV-infected patient. BMJ Case Rep. 2013;2013:bcr2013201062. https://doi.org/10.1136/bcr-2013-201062. PMID: 24136913; PMCID: PMC3822158.
Noratikah AH, Ajura AJ, Lau SH. Oral histoplasmosis in Malaysia: A retrospective analysis of cases reported in Stomatology Unit, Institute for Medical Research during 1995-2016. Trop Biomed. 2018;35(4):1041-1048. PMID: 33601851.
Couppié P, Clyti E, Nacher M, Aznar C, Sainte-Marie D, Carme B, Pradinaud R. Acquired immunodeficiency syndrome-related oral and/or cutaneous histoplasmosis: a descriptive and comparative study of 21 cases in French Guiana. Int J Dermatol. 2002;41(9):571-6. https://doi.org/10.1046/j.1365-4362.2002.01590.x. PMID: 12358826.
Medina JB, Monguilhott-Falbo F, Teixeira-Leite C, Trierveiler M, Braz-Silva PH, Ortega KL. Mucocutaneous histoplasmosis as the first manifestation of AIDS. Spec Care Dentist. 2024;44(4):1059-1064. https://doi.org/10.1111/scd.12972. Epub 2024 Feb 6. PMID: 38321578.
de Paulo LF, Rosa RR, Durighetto Júnior AF. Primary localized histoplasmosis: oral manifestations in immunocompetent patients. Int J Infect Dis. 2013;17(2):e139-40. https://doi.org/10.1016/j.ijid.2012.11.004. Epub 2012 Dec 4. PMID: 23219033.
Brazão-Silva MT, Mancusi GW, Bazzoun FV, Ishisaki GY, Marcucci M. A gingival manifestation of histoplasmosis leading diagnosis. Contemp Clin Dent. 2013;4(1):97-101. https://doi.org/10.4103/0976-237X.111621. PMID: 23853464; PMCID: PMC37 03707.
Ge L, Zhou C, Song Z, Zhang Y, Wang L, Zhong B, Hao F. Primary localized histoplasmosis with lesions restricted to the mouth in a Chinese HIV-negative patient. Int J Infect Dis. 2010;14 Suppl 3:e325-8. https://doi.org/10.1016/j.ijid.2010.04.002. Epub 20 10 Jul 1. PMID: 20591715.
Fortuna, G., Mignogna, M.D. Oral histoplasmosis of a healthy man in a non-endemic area. Infection. 2011; 39:497–498 https://doi.org/10.1007/s15010-011-0147-z
Patil K, Mahima VG, Prathibha Rani RM. Oral histoplasmosis. J Indian Soc Periodontol. 2009; 13(3):157-9. https://doi.org/10.4103/0972-124X.60230. PMID: 20379415; PMCID: PMC2848788.
Souza BC, Munerato MC. Oral manifestation of histoplasmosis on the palate. An Bras Dermatol. 2017;92(5 Suppl 1):107-109. https://doi.org/10.1590/abd1806-4841.20175751. PMID: 29267463; PMCID: PMC5726694.
Linder KA, Kauffman CA. Histoplasmosis: epide-miology, diagnosis, and clinical manifestations. Current Fungal Infection Reports.2019;13:120-8. https://doi.org/10.1007/s12281-019-00341-x
Guttal KS, Naikmasur VG, Bathi RJ, Rao R. Lingual ulceration in disseminated histoplasmosis. J Calif Dent Assoc. 2010;38(3):193-5. PMID: 20369452.
Bose D, Brizuela M. Fungal Infections of the Oral Mucosa. 2024 Feb 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. PMID: 36251829.
Narayana N, Gifford R, Giannini P, Casey J. Oral histoplasmosis: an unusual presentation. Head Neck. 2009;31(2):274-7. https://doi.org/10.1002/hed.20882. PMID: 18798316.
Folk GA, Nelson BL. Oral Histoplasmosis. Head Neck Pathol. 2017;11(4):513-516. https://doi.org/10.1007/s12105-017-0797-y. Epub 2017 Feb 20. PMID: 28220360; PMCID: PMC5677060.
Iqbal F, Schifter M, Coleman HG. Oral presentation of histoplasmosis in an immunocompetent patient: a diagnostic challenge. Aust Dent J. 2014;59(3):386-8. https://doi.org/10.1111/adj.12187. Epub 2014 Jul 21. PMID: 24819556.
Klein IP, Martins MA, Martins MD, Carrard VC. Diagnosis of HIV infection on the basis of histoplasmosis-related oral ulceration. Spec Care Dentist. 2016;36(2):99-103. https://doi.org/10.1111/scd.12147. Epub 2015 Nov 24. PMID: 26597996.
Kumar P, Gupta S, Garg A, Urs A, Augustine J, Sharma P, Khurana N. Oral Localized Lesion on the Tongue in an Immunocompetent Individual: A Report of a Rare Case With a Comprehensive Review of the Literature. Cureus. 2023. 15(1): e33469. https://doi.org/10.7759/cureus.33469. PMID: 36 751234; PMCID: PMC9900046.
Wheat LJ, Slama TG, Norton JA, Kohler RB, Eitzen HE, French ML, Sathapatayavongs B. Risk factors for disseminated or fatal histoplasmosis. Analysis of a large urban outbreak. Ann Intern Med. 1982;96(2):159-63. https://doi.org/10.7326/0003-4819-96-2-159. PMID: 7059062.
Sanjeevi A, Clark BL, Aguirre A, Verghese BG. Chronic disseminated histoplasmosis in a patient on fingolimod therapy: A case report and review of the literature. Clinical Immunology Communications. 2024;6:1-4. https://doi.org/10.1016/j.clicom.2024.06.002
Khetarpal S, Mhapsekar T, Nagar R, Parihar A. Oral histoplasmosis masquerading as acute necrotizing ulcerative gingivitis: A rare case report. Int J Health Sci (Qassim). 2019;13(5):37-40. PMID: 31501651; PMCID: PMC6728130.
Oda D, MacDougall L, Fritsche T, Worthington P. Oral histoplasmosis as a presenting disease in acquired immunodeficiency syndrome. Oral Surg Oral Med Oral Pathol. 1990;70(5):631-6. https://doi.org/10.1016/0030-4220(90)90413-m. Erratum in: Oral Surg Oral Med Oral Pathol 1991;71(1):76. McDougal L [corrected to MacDougall L]. PMID: 2234884.
Dogenski LC, Pasqualotto EM, Dutra MJ, Rovani G, Trentin MS, De Carli JP. Uncommon case of histoplasmosis with oral manifestation: A case report of diagnosis in a South American patient. Int J Surg Case Rep. 2022; 93:106920. https://doi.org/10.1016/j.ijscr.2022.106920. Epub 2022 Mar 9. PMID: 35290848; PMCID: PMC8918853.
Vidyanath S, Shameena P, Sudha S, Nair RG. Disseminated histoplasmosis with oral and cutaneous manifestations. J Oral Maxillofac Pathol. 2013;17(1):139-42. https://doi.org/10.4103/0973-029X.110722. PMID: 23798850; PMCID: PMC3687172.
Kumar A, Rattan V, Rai S, Nambiyar K. Localized Oral Histoplasmosis in an Immunocompetent Patient: A Rare Occurrence with Review of the Literature. J Maxillofac Oral Surg. 2020;19(3):355-358. https://doi.org/10.1007/s12663-019-01273-2. Epub 2019 Aug 13. PMID: 32801527; PMCID: PMC7410996.
Ocansey BK, Kosmidis C, Agyei M, Dorkenoo AM, Ayanlowo OO, Oladele RO, Darre T, Denning DW. Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities. PLoS Negl Trop Dis. 2022;16(2):e0010111. https://doi.org/10.1371/journal.pntd.0010111. PMID: 35202403; PMCID: PMC8870498.
Azar MM, Hage CA. Laboratory Diagnostics for Histoplasmosis. J Clin Microbiol. 2017;55(6):1612-1620. https://doi.org/10.1128/JCM.02430-16. Epub 2017 Mar 8. PMID: 28275076; PMCID: PMC5442517.
Vasconcellos ICDS, Dalla Lana DF, Pasqualotto AC. The Role of Molecular Tests in the Diagnosis of Disseminated Histoplasmosis. J Fungi (Basel). 2019;6(1):1. https://doi.org/10.3390/jof6010001. PMID: 31861302; PMCID: PMC7151051.
Mignogna MD, Fedele S, Lo Russo L, Ruoppo E, Lo Muzio L. A case of oral localized histoplasmosis in an immunocompetent patient. Eur J Clin Microbiol Infect Dis. 2001;20(10):753-5. https://doi.org/10.1007/s100960100592. PMID: 11757982.
Sriram S, Hasan S, Saeed S, Ahmad SA, Panda S. Primary Tuberculosis of Buccal and Labial Mucosa: Literature Review and a Rare Case Report of a Public Health Menace. Case Rep Dent. 2023;2023:6543595. https://doi.org/10.1155/2023/6543595. PMID: 37842328; PMCID: PMC 10569891.
Qureini A, King C, Numan L, Jadhav K, Foxworth J, Bamberger D. Disseminated histoplasmosis presenting as dental lesion in the absence of a vital organ, the thymus. IDCases. 2019;18:e00635. https://doi.org/10.1016/j.idcr.2019.e00635. PMID: 31692524; PMCID: PMC6804924.
Kamboj M, Rathee R, Narwal A, Devi A, Gupta A, Sivakumar N. Primary Oral Histoplasmosis in Immunocompetent Host: Case Series with Review of Literature. Indian J Otolaryngol Head Neck Surg. 2022;74(Suppl 3):5639-5644. https://doi.org/10.1007/s12070-021-02974-2. Epub 2021 Nov 12. PMID: 36742512; PMCID: PMC9895471
Wheat J, Sarosi G, McKinsey D, Hamill R, Bradsher R, Johnson P, Loyd J, Kauffman C. Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30(4):688-95. https://doi.org/10.1086/313752. Epub 2000 Apr 20. PMID: 10770731.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. © 2024.





