Isolation of Alternaria alternata in an HIV-Positive Patient: Emerging Pathogen or Opportunistic Colonizer?

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Mirko Benvenuti, Lucia Taramasso, Silvia Francesca Riva, Antonio Biagio, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6972590/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Mar, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted 7 You are reading this latest preprint version Abstract We report a case of a person living with HIV presenting chronic dorsal-nuchal lesions resembling mycosis but distinct from common fungal infections. The lesions showed abundant exudate, dark brownish borders, and ulceration. Microscopic examination and cultures on SDA and DTM media identified Alternaria alternata , a rare opportunistic pathogen mostly affecting immunocompromised patients. Notably, the patient had well-controlled HIV (RNA 500 cells/mm³. This case highlights that rare fungal infections remain a risk for potentially vulnerable individuals, even under effective HIV treatment. Figures Figure 1 Figure 2 Figure 3 Introduction Alternaria is a genus of dematiaceous, melanin-producing fungi characterized by pigmented hyphae, belonging to the phylum Ascomycota, and widely distributed in the environment [ 1 ]. Species within this genus are recognized as plant pathogens [ 2 ], major contributors to bronchial diseases and allergic reactions in humans [ 3 ], and, more rarely, as causative agents of phaeohyphomycosis [ 4 ]. When acting as human pathogens, they are typically isolated in individuals with compromised or suppressed immune systems, such as organ transplant recipients or untreated HIV-positive patients [ 5 – 8 ]. Nevertheless, several infections have also been documented in immunocompetent individuals [ 5 , 9 , 10 ]. This case is of particular interest as the fungus was isolated from a patient with confirmed HIV infection who remained immunocompetent due to effective antiretroviral therapy. It highlights that fungal infections—including those caused by uncommon pathogens—continue to pose significant risks to vulnerable or highly exposed populations, even when effective treatment is in place. Patient and methods A 45-year-old man with a confirmed HIV infection, currently receiving antiretroviral therapy (ART) consisting of a fixed-dose combination tablet of emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir alafenamide 25 mg, presented with dermatitis-like lesions on the upper back and neck. Laboratory evaluation revealed the following: HIV RNA < 50 copies/mL, CD4 + lymphocyte count of 1104 cells/mm³, normal complete blood count and liver function tests, total cholesterol 209 mg/dL, HDL 39 mg/dL, LDL 160 mg/dL, with normal triglyceride and glucose levels, and a normal urinalysis. The patient reported no concurrent medications. At the recommendation of the attending infectious disease specialist, a dermatological consultation was conducted. The skin lesions first appeared in July 2024 and were described as serpiginous, erythematous, and diffusely desquamative. Previous treatments with antibiotics and topical corticosteroids had not led to clinical improvement. The lesions showed spontaneous partial remission, often followed by hyperpigmentation. Examination of the skin revealed marked photodamage on the upper trunk, particularly in the right lateral cervical region, right subclavicular area, and left axillary cavity. At the time of observation, the lesions appeared infiltrated, slightly elevated, exudative, and pruritic. Samples were collected by skin scraping for both microscopic examination and fungal culture. Concurrently, signs of active pityriasis versicolor were noted on the trunk. The samples were cultured on Sabouraud Dextrose Agar (SDA) prepared in the laboratory with the following composition: Bactoagar 10.0 g, soymeal peptone 10.0 g, D(+) glucose 5.0 g, chloramphenicol 0.1 g, and cycloheximide 0.5 g per 1 L of distilled water. Additionally, Dermatophyte Test Medium (DTM) was used, purchased from Merck Italy, Via Monte Rosa 93–20149 Milan (MI). The inoculated culture plates were incubated at 25°C under conditions of high relative humidity, with 12-hour light/dark cycles maintained until full fungal growth was observed. Results Microscopic analyses of the cultured fungal samples were performed using the Scotch tape method and staining with lactophenol cotton blue. In parallel, direct examination of the tissue specimens under light microscopy was conducted following potassium hydroxide (KOH) preparation. The tissue macerate revealed diffuse cellular debris, indicative of tissue necrosis. Alternaria alternata conidia were detected throughout the samples, with hyphal elements observed (Fig. 1 , Fig. 2 ) , suggesting that the infection may have penetrated deeper dermal layers over time. A significant bacterial presence was also noted, predominantly cocci. An unexpected finding was the high density of Demodex folliculorum mites ( Fig. 3 ) , with counts exceeding five mites per sample, levels typically associated with chronic inflammatory dermatoses such as rosacea [ 11 , 12 ]. The interaction between Demodex spp. and cutaneous pathogenic fungi remains poorly understood, though it has been hypothesized that these mites may act as vectors for other microorganisms, including fungi [ 13 ]. This potential synergy warrants further investigation. Fungal cultures, incubated in a microbiological heater, showed moderate-to-rapid colony growth by the third day. The colonies displayed a cottony, downy texture with a rough surface; their coloration was whitish on the surface and dark brown on the reverse side. Examination of hyphal structures and conidial development was performed on mature colonies via Scotch tape sampling and lactophenol cotton blue staining. Simultaneously, colonies of Candida spp. emerged on both culture media (SDA and DTM), suggesting a possible co-infection, although yeast cells were not visualized in the direct microscopic analysis, raising the possibility of contamination or transient colonization. Definitive identification of Alternaria alternata was achieved by amplification and sequencing of the Alt a 1 mRNA gene, showing 95% identity with Alternaria alternata Alt a 1 mRNA, complete coding sequence (GenBank: U62097.1), thereby confirming the pathogen. Fungal infections often pose diagnostic challenges due to their nonspecific clinical presentation, which may mimic other dermatological conditions [ 14 ]. Although opportunistic mycoses are generally associated with immunocompromised states [ 15 ], fungal lesions involving various cutaneous layers frequently lack distinguishing features, complicating clinical recognition. In cases of phaeohyphomycosis, melanin pigments produced by the fungus may serve dual roles as virulence factors and agents of antifungal resistance [ 16 ]. The detection of fungal conidia known to represent the resistant form of the organism [ 17 ] may help explain the persistence or recurrence of infection following completion of antifungal therapy. The observed lesions were also characterized by post-inflammatory hyperpigmentation, a typical aftermath of Alternaria -induced inflammation. Notably, in vivo studies have shown that Alternaria alternata can induce eosinophilic and neutrophilic recruitment and stimulate the production of pro-inflammatory interleukins [ 18 ], thereby exacerbating the inflammatory process and complicating diagnostic efforts. Additionally, mutations in the CARD9 gene have been associated with increased susceptibility to fungal infections and higher recurrence rates [ 19 ]; however, genetic testing for CARD9 mutations was not performed in the present case. Conclusion Dermatomycoses represent a heterogeneous group of superficial and, at times, deep fungal infections that are often challenging to diagnose and treat effectively. Despite the availability of antifungal therapies, treatment success frequently requires prolonged courses, and even then, the risk of recurrence remains substantial. These infections can be further complicated by atypical presentations, resistance mechanisms, and coexisting skin conditions that mask their clinical manifestations. This case report holds particular significance as it highlights the potential for infections caused by uncommon pathogens such as Alternaria alternata to occur even in patients who are technically immunocompetent but clinically vulnerable—such as individuals with controlled HIV infection. The presence of high CD4 + counts and undetectable viral load might traditionally suggest a low risk for opportunistic fungal infections. However, this case challenges assumption and raises important clinical questions regarding fungal pathogenicity in hosts who are immunologically reconstituted but potentially exposed to chronic skin microtrauma, photodamage, or cutaneous dysbiosis. Of particular concern is the tendency to exclude fungal etiologies in the differential diagnosis when clinical features are nonspecific or when lesions mimic inflammatory dermatoses, such as eczema, psoriasis, or contact dermatitis. This underscores the importance of maintaining a high index of suspicion for fungal pathogens, especially dematiaceous fungi, in persistent or recurrent cutaneous lesions that do not respond to standard antibacterial or anti-inflammatory treatments. From a diagnostic standpoint, this case emphasizes the critical role of direct microscopic examination in identifying fungal elements, including hyphae and conidia. The visualization of these structures under light microscopy requires not only appropriate staining techniques (e.g., KOH, lactophenol cotton blue) but also a meticulous and experienced approach, as fungal elements may be sparse or morphologically subtle, particularly in chronic or partially treated infections. This case thus not only enriches the clinical understanding of fungal skin infections in non-classically immunocompromised patients but also points to broader gaps in our diagnostic algorithms and pathogen recognition paradigms. It serves as a reminder of the complex interplay between host, pathogen, and environment in cutaneous infections and the need for multidisciplinary collaboration, between infectious disease specialists, dermatologists, and microbiologists, to ensure accurate diagnosis and effective treatment. Declarations Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflicts of interest/Competing interests The authors declare that they have no conflicts of interest or competing interests. Ethics approval This report adhered to the tenets of the Declaration of Helsinki Consent to participate Informed consent was obtained from the patient Written Consent for publication Participant provided written consent for the anonymized data to be used in publications. Availability of data and material The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Code Availability Not applicable. Author contributions MB conceptualization, writing, laboratory analysis, LT and SFR provided clinical data and treated the patient and re-viewed the manuscript, ADB and ECC contributed to manuscript preparation. All the authors have read and approved the final version of the manuscript References Hsiao CH, Yeh LK, Chen HC, et al. Clinical characteristics of Alternaria keratitis. J Ophthalmol. 2014;2014. doi:10.1155/2014/536985 DeMers M. Alternaria alternata as endophyte and pathogen. Microbiology (Reading). 2022 Mar;168(3):001153. doi: 10.1099/mic.0.001153. Abel-Fernández E, Martínez MJ, Galán T, Pineda F. Going over Fungal Allergy: Alternaria alternata and Its Allergens. J Fungi (Basel). 2023 May 18;9(5):582. doi: 10.3390/jof9050582. Kieselová K, Gomes T, Santiago F, Martinha H. Emerging Cutaneous Phaeohyphomycosis Caused by Alternaria infectoria. Acta Med Port. 2021 Nov 2;34(11):774-778. doi: 10.20344/amp.13496. Kim G, Yoo SJ, Yoo JR, Seo KB. The first case report of thorn-induced Alternaria alternata infection of the hand in an immunocompetent host. BMC Infect Dis. 2022 Mar 29;22(1):304. doi: 10.1186/s12879-022-07280-y. Aragón-Miguel R, Calleja-Algarra A, Morales-Raya C, López-Medrano F, Pérez-Ayala A, Rodríguez-Peralto JL, Ortiz-Romero PL, Maroñas-Jiménez L. Alternaria infectoria skin infection in a renal transplant recipient: an emerging phaeohyphomycosis of occidental countries? Int J Dermatol. 2017 Jul;56(7):e153-e155. doi: 10.1111/ijd.13563. Wiest PM, Wiese K, Jacobs MR, Morrissey AB, Abelson TI, Witt W, Lederman MM. Alternaria infection in a patient with acquired immunodeficiency syndrome: case report and review of invasive alternaria infections. Rev Infect Dis. 1987 Jul-Aug;9(4):799-803. doi: 10.1093/clinids/9.4.799. Kaur R, Dhakad MS, Goyal R, Bhalla P, Dewan R. Spectrum of Opportunistic Fungal Infections in HIV/AIDS Patients in Tertiary Care Hospital in India. Can J Infect Dis Med Microbiol. 2016;2016:2373424. doi: 10.1155/2016/2373424. Chen J, Yao H, Yuan X, Yan L, Tang G, Yan K, Shen X. Palatal perforation caused by Alternaria alternata infection in an immunocompetent adolescent. Int J Infect Dis. 2023 Sep;134:207-210. doi: 10.1016/j.ijid.2023.06.019. Gürcan S, Pişkin S, Kiliç H, Temelli BA, Yalçin O. Immün sistemi sağlam bir konakta Alternaria alternata ile oluşan deri enfeksiyonu [Cutaneous infection caused by Alternaria alternata in an immunocompetent host]. Mikrobiyol Bul. 2009 Jan;43(1):163-7. Turkish. PMID: 19334395. Trave I, Micalizzi C, Gasparini G, Cozzani E, Parodi A. Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum. Clin Exp Dermatol. 2021 Dec;46(8):1434-1440. doi: 10.1111/ced.14731. Trave I, Salvi I, Schiavetti I, Canepa P, Silva C, Parodi A, Cozzani E. Presence of Demodex spp. on the face and scalp in patients affected by papulopustular rosacea of face. Ital J Dermatol Venerol. 2024 Aug;159(4):425-429. doi: 10.23736/S2784-8671.24.07877-0. Vanam HP, Mohanram K, K SRR, Poojari SS, P R A, Kandi V. First Report of Concomitant Tinea Faciei and Pityriasis Folliculorum: A Dermatomicrobiological Rarity. Cureus. 2018 Jul 20;10(7):e3017. doi: 10.7759/cureus.3017. Howell SA. Dermatopathology and the Diagnosis of Fungal Infections. Br J Biomed Sci. 2023 Jun 7;80:11314. doi: 10.3389/bjbs.2023. Conant MA. Fungal infections in immunocompromised individuals. Dermatol Clin. 1996 Jan;14(1):155-62. doi: 10.1016/s0733-8635(05)70336-3. Arcobello JT, Revankar SG. Phaeohyphomycosis. Semin Respir Crit Care Med. 2020 Feb;41(1):131-140. doi: 10.1055/s-0039-3400957. Levitz SM, Diamond RD. Mechanisms of resistance of Aspergillus fumigatus Conidia to killing by neutrophils in vitro. J Infect Dis. 1985 Jul;152(1):33-42. doi: 10.1093/infdis/152.1.33. Shin SH, Ye MK, Lee DW, Chae MH, Choi SY. Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model. PLoS One. 2020 Jun 16;15(6):e0234731. doi: 10.1371/journal.pone.0234731. Quan C, Li X, Shi RF, Zhao XQ, Xu H, Wang B, Wang XP, Hu WG, Cao H, Zheng J. Recurrent fungal infections in a Chinese patient with CARD9 deficiency and a review of 48 cases. Br J Dermatol. 2019 May;180(5):1221-1225. doi: 10.1111/bjd.17092. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 Mar, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Editorial decision: Revision requested 22 Oct, 2025 Reviews received at journal 05 Aug, 2025 Reviewers agreed at journal 15 Jul, 2025 Reviewers invited by journal 13 Jul, 2025 Editor assigned by journal 04 Jul, 2025 Submission checks completed at journal 03 Jul, 2025 First submitted to journal 25 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6972590","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":484695986,"identity":"d1b5f4c6-a47b-4caf-bcb9-d47c14baa89b","order_by":0,"name":"Mirko Benvenuti","email":"data:image/png;base64,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","orcid":"","institution":"University of Genoa","correspondingAuthor":true,"prefix":"","firstName":"Mirko","middleName":"","lastName":"Benvenuti","suffix":""},{"id":484695987,"identity":"141614e8-8e4e-4218-8d3b-8c4cc757d9be","order_by":1,"name":"Lucia Taramasso","email":"","orcid":"","institution":"IRCCS Ospedale Policlinico San Martino","correspondingAuthor":false,"prefix":"","firstName":"Lucia","middleName":"","lastName":"Taramasso","suffix":""},{"id":484695988,"identity":"ff920c07-b4ca-4538-98e7-1893e272ef1f","order_by":2,"name":"Silvia Francesca Riva","email":"","orcid":"","institution":"IRCCS Ospedale Policlinico San Martino","correspondingAuthor":false,"prefix":"","firstName":"Silvia","middleName":"Francesca","lastName":"Riva","suffix":""},{"id":484695989,"identity":"a5b32c3e-48d9-43f1-98dd-ef6d63851c20","order_by":3,"name":"Antonio Biagio","email":"","orcid":"","institution":"IRCCS Ospedale Policlinico San Martino","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Biagio","suffix":""},{"id":484695990,"identity":"3637d645-c381-45b6-864c-98ea97f8775f","order_by":4,"name":"Emanuele Claudio Cozzani","email":"","orcid":"","institution":"Ospedale Policlinico San Martino IRCCS","correspondingAuthor":false,"prefix":"","firstName":"Emanuele","middleName":"Claudio","lastName":"Cozzani","suffix":""}],"badges":[],"createdAt":"2025-06-25 08:53:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6972590/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6972590/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42399-026-02288-w","type":"published","date":"2026-03-10T15:57:41+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86786649,"identity":"1e1a28c8-a676-463e-9680-1dec80915a75","added_by":"auto","created_at":"2025-07-15 14:12:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":502459,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eAlternaria alternata \u003c/em\u003econidia observed under light microscopy. The fungal elements were identified in a potassium hydroxide (KOH) preparation obtained from the patient’s necrotic skin lesion. Characteristic muriform conidia with transverse and longitudinal septa are visible. A reference scale is included to indicate relative size and support morphological identification.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6972590/v1/ec1e0d57b24be0373f79eba7.png"},{"id":86787300,"identity":"35585ee7-be2e-48f8-a815-60c45163b330","added_by":"auto","created_at":"2025-07-15 14:20:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":947078,"visible":true,"origin":"","legend":"\u003cp\u003eA dense aggregation of melanized fungal elements is observed, each characterized by thickened cell walls and pronounced dark pigmentation. These features are commonly associated with increased resistance to environmental stressors and may suggest a heightened potential for pathogenic behavior.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6972590/v1/19ffcde24e695969f99cd18d.png"},{"id":86787299,"identity":"b07ffca2-7551-47e7-8259-b4dada98f07b","added_by":"auto","created_at":"2025-07-15 14:20:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":797054,"visible":true,"origin":"","legend":"\u003cp\u003ePresence of \u003cem\u003eDemodex folliculorum\u003c/em\u003e observed in the lesion sample. The elevated mite density within the inflamed skin is of notable clinical relevance. Demodex mites can aggravate cutaneous lesions by inducing mechanical damage to the pilosebaceous units and superficial epithelium, thereby compromising the skin barrier. This mechanical disruption not only stimulates a local immune response with increased production of pro-inflammatory cytokines, such as interleukins and TNF-α, but may also facilitate the penetration and colonization of opportunistic pathogens, including bacteria and fungi. Their presence may thus contribute both to persistence and the polymicrobial nature of chronic skin lesions.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6972590/v1/f86c0773ba7800866046bc2f.png"},{"id":104739298,"identity":"205c47e6-eec0-427d-824d-1d230978f929","added_by":"auto","created_at":"2026-03-16 16:00:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2995679,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6972590/v1/108ae68c-1e63-42e4-8f78-81a927796565.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Isolation of Alternaria alternata in an HIV-Positive Patient: Emerging Pathogen or Opportunistic Colonizer?","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eAlternaria\u003c/em\u003e is a genus of dematiaceous, melanin-producing fungi characterized by pigmented hyphae, belonging to the phylum Ascomycota, and widely distributed in the environment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Species within this genus are recognized as plant pathogens [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], major contributors to bronchial diseases and allergic reactions in humans [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and, more rarely, as causative agents of phaeohyphomycosis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. When acting as human pathogens, they are typically isolated in individuals with compromised or suppressed immune systems, such as organ transplant recipients or untreated HIV-positive patients [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Nevertheless, several infections have also been documented in immunocompetent individuals [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This case is of particular interest as the fungus was isolated from a patient with confirmed HIV infection who remained immunocompetent due to effective antiretroviral therapy. It highlights that fungal infections—including those caused by uncommon pathogens—continue to pose significant risks to vulnerable or highly exposed populations, even when effective treatment is in place.\u003c/p\u003e"},{"header":"Patient and methods","content":"\u003cp\u003eA 45-year-old man with a confirmed HIV infection, currently receiving antiretroviral therapy (ART) consisting of a fixed-dose combination tablet of emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir alafenamide 25 mg, presented with dermatitis-like lesions on the upper back and neck. Laboratory evaluation revealed the following: HIV RNA \u0026lt; 50 copies/mL, CD4 + lymphocyte count of 1104 cells/mm³, normal complete blood count and liver function tests, total cholesterol 209 mg/dL, HDL 39 mg/dL, LDL 160 mg/dL, with normal triglyceride and glucose levels, and a normal urinalysis. The patient reported no concurrent medications. At the recommendation of the attending infectious disease specialist, a dermatological consultation was conducted. The skin lesions first appeared in July 2024 and were described as serpiginous, erythematous, and diffusely desquamative. Previous treatments with antibiotics and topical corticosteroids had not led to clinical improvement. The lesions showed spontaneous partial remission, often followed by hyperpigmentation. Examination of the skin revealed marked photodamage on the upper trunk, particularly in the right lateral cervical region, right subclavicular area, and left axillary cavity. At the time of observation, the lesions appeared infiltrated, slightly elevated, exudative, and pruritic. Samples were collected by skin scraping for both microscopic examination and fungal culture. Concurrently, signs of active pityriasis versicolor were noted on the trunk. The samples were cultured on Sabouraud Dextrose Agar (SDA) prepared in the laboratory with the following composition: Bactoagar 10.0 g, soymeal peptone 10.0 g, D(+) glucose 5.0 g, chloramphenicol 0.1 g, and cycloheximide 0.5 g per 1 L of distilled water. Additionally, Dermatophyte Test Medium (DTM) was used, purchased from Merck Italy, Via Monte Rosa 93–20149 Milan (MI). The inoculated culture plates were incubated at 25°C under conditions of high relative humidity, with 12-hour light/dark cycles maintained until full fungal growth was observed.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eMicroscopic analyses of the cultured fungal samples were performed using the Scotch tape method and staining with lactophenol cotton blue. In parallel, direct examination of the tissue specimens under light microscopy was conducted following potassium hydroxide (KOH) preparation. The tissue macerate revealed diffuse cellular debris, indicative of tissue necrosis. \u003cem\u003eAlternaria alternata\u003c/em\u003e conidia were detected throughout the samples, with hyphal elements observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e, suggesting that the infection may have penetrated deeper dermal layers over time. A significant bacterial presence was also noted, predominantly cocci. An unexpected finding was the high density of \u003cem\u003eDemodex folliculorum\u003c/em\u003e mites \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e, with counts exceeding five mites per sample, levels typically associated with chronic inflammatory dermatoses such as rosacea [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The interaction between \u003cem\u003eDemodex\u003c/em\u003e spp. and cutaneous pathogenic fungi remains poorly understood, though it has been hypothesized that these mites may act as vectors for other microorganisms, including fungi [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This potential synergy warrants further investigation.\u003c/p\u003e\u003cp\u003eFungal cultures, incubated in a microbiological heater, showed moderate-to-rapid colony growth by the third day. The colonies displayed a cottony, downy texture with a rough surface; their coloration was whitish on the surface and dark brown on the reverse side. Examination of hyphal structures and conidial development was performed on mature colonies via Scotch tape sampling and lactophenol cotton blue staining. Simultaneously, colonies of \u003cem\u003eCandida\u003c/em\u003e spp. emerged on both culture media (SDA and DTM), suggesting a possible co-infection, although yeast cells were not visualized in the direct microscopic analysis, raising the possibility of contamination or transient colonization. Definitive identification of \u003cem\u003eAlternaria alternata\u003c/em\u003e was achieved by amplification and sequencing of the \u003cem\u003eAlt a 1\u003c/em\u003e mRNA gene, showing 95% identity with \u003cem\u003eAlternaria alternata Alt a 1\u003c/em\u003e mRNA, complete coding sequence (GenBank: U62097.1), thereby confirming the pathogen. Fungal infections often pose diagnostic challenges due to their nonspecific clinical presentation, which may mimic other dermatological conditions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although opportunistic mycoses are generally associated with immunocompromised states [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], fungal lesions involving various cutaneous layers frequently lack distinguishing features, complicating clinical recognition.\u003c/p\u003e\u003cp\u003eIn cases of phaeohyphomycosis, melanin pigments produced by the fungus may serve dual roles as virulence factors and agents of antifungal resistance [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The detection of fungal conidia known to represent the resistant form of the organism [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] may help explain the persistence or recurrence of infection following completion of antifungal therapy. The observed lesions were also characterized by post-inflammatory hyperpigmentation, a typical aftermath of \u003cem\u003eAlternaria\u003c/em\u003e-induced inflammation. Notably, in vivo studies have shown that \u003cem\u003eAlternaria alternata\u003c/em\u003e can induce eosinophilic and neutrophilic recruitment and stimulate the production of pro-inflammatory interleukins [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], thereby exacerbating the inflammatory process and complicating diagnostic efforts. Additionally, mutations in the \u003cem\u003eCARD9\u003c/em\u003e gene have been associated with increased susceptibility to fungal infections and higher recurrence rates [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]; however, genetic testing for \u003cem\u003eCARD9\u003c/em\u003e mutations was not performed in the present case.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDermatomycoses represent a heterogeneous group of superficial and, at times, deep fungal infections that are often challenging to diagnose and treat effectively. Despite the availability of antifungal therapies, treatment success frequently requires prolonged courses, and even then, the risk of recurrence remains substantial. These infections can be further complicated by atypical presentations, resistance mechanisms, and coexisting skin conditions that mask their clinical manifestations.\u003c/p\u003e\u003cp\u003eThis case report holds particular significance as it highlights the potential for infections caused by uncommon pathogens such as \u003cem\u003eAlternaria alternata\u003c/em\u003e to occur even in patients who are technically immunocompetent but clinically vulnerable\u0026mdash;such as individuals with controlled HIV infection. The presence of high CD4\u0026thinsp;+\u0026thinsp;counts and undetectable viral load might traditionally suggest a low risk for opportunistic fungal infections. However, this case challenges assumption and raises important clinical questions regarding fungal pathogenicity in hosts who are immunologically reconstituted but potentially exposed to chronic skin microtrauma, photodamage, or cutaneous dysbiosis.\u003c/p\u003e\u003cp\u003eOf particular concern is the tendency to exclude fungal etiologies in the differential diagnosis when clinical features are nonspecific or when lesions mimic inflammatory dermatoses, such as eczema, psoriasis, or contact dermatitis. This underscores the importance of maintaining a high index of suspicion for fungal pathogens, especially dematiaceous fungi, in persistent or recurrent cutaneous lesions that do not respond to standard antibacterial or anti-inflammatory treatments. From a diagnostic standpoint, this case emphasizes the critical role of direct microscopic examination in identifying fungal elements, including hyphae and conidia. The visualization of these structures under light microscopy requires not only appropriate staining techniques (e.g., KOH, lactophenol cotton blue) but also a meticulous and experienced approach, as fungal elements may be sparse or morphologically subtle, particularly in chronic or partially treated infections. This case thus not only enriches the clinical understanding of fungal skin infections in non-classically immunocompromised patients but also points to broader gaps in our diagnostic algorithms and pathogen recognition paradigms. It serves as a reminder of the complex interplay between host, pathogen, and environment in cutaneous infections and the need for multidisciplinary collaboration, between infectious disease specialists, dermatologists, and microbiologists, to ensure accurate diagnosis and effective treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest/Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest or competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis report adhered to the tenets of the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the patient\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWritten Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipant provided written consent for the anonymized data to be used in publications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMB conceptualization, writing, laboratory analysis, LT and SFR provided clinical data and treated the patient and re-viewed the manuscript, ADB and ECC contributed to manuscript preparation. All the authors have read and approved the final version of the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHsiao CH, Yeh LK, Chen HC, et al. Clinical characteristics of Alternaria keratitis. J Ophthalmol. 2014;2014. doi:10.1155/2014/536985\u003c/li\u003e\n\u003cli\u003eDeMers M. \u003cem\u003eAlternaria alternata\u003c/em\u003e as endophyte and pathogen. Microbiology (Reading). 2022 Mar;168(3):001153. doi: 10.1099/mic.0.001153.\u003c/li\u003e\n\u003cli\u003eAbel-Fern\u0026aacute;ndez E, Mart\u0026iacute;nez MJ, Gal\u0026aacute;n T, Pineda F. Going over Fungal Allergy: \u003cem\u003eAlternaria alternata\u003c/em\u003e and Its Allergens. J Fungi (Basel). 2023 May 18;9(5):582. doi: 10.3390/jof9050582. \u003c/li\u003e\n\u003cli\u003eKieselov\u0026aacute; K, Gomes T, Santiago F, Martinha H. Emerging Cutaneous Phaeohyphomycosis Caused by Alternaria infectoria. Acta Med Port. 2021 Nov 2;34(11):774-778. doi: 10.20344/amp.13496.\u003c/li\u003e\n\u003cli\u003eKim G, Yoo SJ, Yoo JR, Seo KB. The first case report of thorn-induced Alternaria alternata infection of the hand in an immunocompetent host. BMC Infect Dis. 2022 Mar 29;22(1):304. doi: 10.1186/s12879-022-07280-y.\u003c/li\u003e\n\u003cli\u003eArag\u0026oacute;n-Miguel R, Calleja-Algarra A, Morales-Raya C, L\u0026oacute;pez-Medrano F, P\u0026eacute;rez-Ayala A, Rodr\u0026iacute;guez-Peralto JL, Ortiz-Romero PL, Maro\u0026ntilde;as-Jim\u0026eacute;nez L. Alternaria infectoria skin infection in a renal transplant recipient: an emerging phaeohyphomycosis of occidental countries? Int J Dermatol. 2017 Jul;56(7):e153-e155. doi: 10.1111/ijd.13563.\u003c/li\u003e\n\u003cli\u003eWiest PM, Wiese K, Jacobs MR, Morrissey AB, Abelson TI, Witt W, Lederman MM. Alternaria infection in a patient with acquired immunodeficiency syndrome: case report and review of invasive alternaria infections. Rev Infect Dis. 1987 Jul-Aug;9(4):799-803. doi: 10.1093/clinids/9.4.799.\u003c/li\u003e\n\u003cli\u003eKaur R, Dhakad MS, Goyal R, Bhalla P, Dewan R. Spectrum of Opportunistic Fungal Infections in HIV/AIDS Patients in Tertiary Care Hospital in India. Can J Infect Dis Med Microbiol. 2016;2016:2373424. doi: 10.1155/2016/2373424.\u003c/li\u003e\n\u003cli\u003eChen J, Yao H, Yuan X, Yan L, Tang G, Yan K, Shen X. Palatal perforation caused by Alternaria alternata infection in an immunocompetent adolescent. Int J Infect Dis. 2023 Sep;134:207-210. doi: 10.1016/j.ijid.2023.06.019.\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;rcan S, Pişkin S, Kili\u0026ccedil; H, Temelli BA, Yal\u0026ccedil;in O. Imm\u0026uuml;n sistemi sağlam bir konakta Alternaria alternata ile oluşan deri enfeksiyonu [Cutaneous infection caused by Alternaria alternata in an immunocompetent host]. Mikrobiyol Bul. 2009 Jan;43(1):163-7. Turkish. PMID: 19334395.\u003c/li\u003e\n\u003cli\u003eTrave I, Micalizzi C, Gasparini G, Cozzani E, Parodi A. Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum. Clin Exp Dermatol. 2021 Dec;46(8):1434-1440. doi: 10.1111/ced.14731.\u003c/li\u003e\n\u003cli\u003eTrave I, Salvi I, Schiavetti I, Canepa P, Silva C, Parodi A, Cozzani E. Presence of Demodex spp. on the face and scalp in patients affected by papulopustular rosacea of face. Ital J Dermatol Venerol. 2024 Aug;159(4):425-429. doi: 10.23736/S2784-8671.24.07877-0.\u003c/li\u003e\n\u003cli\u003eVanam HP, Mohanram K, K SRR, Poojari SS, P R A, Kandi V. First Report of Concomitant Tinea Faciei and Pityriasis Folliculorum: A Dermatomicrobiological Rarity. Cureus. 2018 Jul 20;10(7):e3017. doi: 10.7759/cureus.3017. \u003c/li\u003e\n\u003cli\u003eHowell SA. Dermatopathology and the Diagnosis of Fungal Infections. Br J Biomed Sci. 2023 Jun 7;80:11314. doi: 10.3389/bjbs.2023.\u003c/li\u003e\n\u003cli\u003eConant MA. Fungal infections in immunocompromised individuals. Dermatol Clin. 1996 Jan;14(1):155-62. doi: 10.1016/s0733-8635(05)70336-3. \u003c/li\u003e\n\u003cli\u003eArcobello JT, Revankar SG. Phaeohyphomycosis. Semin Respir Crit Care Med. 2020 Feb;41(1):131-140. doi: 10.1055/s-0039-3400957. \u003c/li\u003e\n\u003cli\u003eLevitz SM, Diamond RD. Mechanisms of resistance of Aspergillus fumigatus Conidia to killing by neutrophils in vitro. J Infect Dis. 1985 Jul;152(1):33-42. doi: 10.1093/infdis/152.1.33.\u003c/li\u003e\n\u003cli\u003eShin SH, Ye MK, Lee DW, Chae MH, Choi SY. Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model. PLoS One. 2020 Jun 16;15(6):e0234731. doi: 10.1371/journal.pone.0234731. \u003c/li\u003e\n\u003cli\u003eQuan C, Li X, Shi RF, Zhao XQ, Xu H, Wang B, Wang XP, Hu WG, Cao H, Zheng J. Recurrent fungal infections in a Chinese patient with CARD9 deficiency and a review of 48 cases. Br J Dermatol. 2019 May;180(5):1221-1225. doi: 10.1111/bjd.17092.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6972590/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6972590/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe report a case of a person living with HIV presenting chronic dorsal-nuchal lesions resembling mycosis but distinct from common fungal infections. The lesions showed abundant exudate, dark brownish borders, and ulceration. Microscopic examination and cultures on SDA and DTM media identified \u003cem\u003eAlternaria alternata\u003c/em\u003e, a rare opportunistic pathogen mostly affecting immunocompromised patients. Notably, the patient had well-controlled HIV (RNA\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/ml) and a CD4\u0026thinsp;+\u0026thinsp;count\u0026thinsp;\u0026gt;\u0026thinsp;500 cells/mm\u0026sup3;. This case highlights that rare fungal infections remain a risk for potentially vulnerable individuals, even under effective HIV treatment.\u003c/p\u003e","manuscriptTitle":"Isolation of Alternaria alternata in an HIV-Positive Patient: Emerging Pathogen or Opportunistic Colonizer?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-15 14:12:05","doi":"10.21203/rs.3.rs-6972590/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-22T12:48:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-05T07:57:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39764047872575719057352535966559858374","date":"2025-07-15T12:58:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-13T15:14:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-04T05:07:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-04T02:51:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2025-06-25T08:48:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"62a115b2-c0a9-4e27-868d-dcdf93471795","owner":[],"postedDate":"July 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T16:00:42+00:00","versionOfRecord":{"articleIdentity":"rs-6972590","link":"https://doi.org/10.1007/s42399-026-02288-w","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2026-03-10 15:57:41","publishedOnDateReadable":"March 10th, 2026"},"versionCreatedAt":"2025-07-15 14:12:05","video":"","vorDoi":"10.1007/s42399-026-02288-w","vorDoiUrl":"https://doi.org/10.1007/s42399-026-02288-w","workflowStages":[]},"version":"v1","identity":"rs-6972590","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6972590","identity":"rs-6972590","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}