A decade of subcutaneous mycoses in Indonesia: A systematic review

 Corresponding author: Evy Ervianti Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. A decade of subcutaneous mycoses in Indonesia: A systematic review Mutiara Luthfi Ardiyanti 1, Evy Ervianti 2, * and Priyo Budi Purwono 3 1 Medical Programme, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. 2 Department of Dermatology and Venereology, Dr. Soetomo General Academic Hospital/Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. 3 Department of Clinical Microbiology, Dr. Soetomo General Academic Hospital/Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 Publication history: Received 13 October 2025; revised on 22 November 2025; accepted on 24 November 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.28.2.3924 Abstract Background: Subcutaneous mycoses are chronic fungal infections that commonly affect populations in tropical regions. Indonesia, with its humid climate and large agricultural workforce, is endemic for several subcutaneous mycoses; however, national data remain fragmented and largely derived from isolated case-based reports. A consolidated synthesis is needed to better understand their clinical patterns, diagnostic challenges, and treatment outcomes. Methods: A systematic search was performed using PubMed, Google Scholar, GARUDA, and institutional repositories for studies published from 2013 to 2025. Eligible studies included retrospective case series and case reports with clinically or histopathologically confirmed subcutaneous mycoses in Indonesia. Extracted data included demographic characteristics, clinical presentations, diagnostic methods, etiological agents, and treatment outcomes. Study selection followed PRISMA guidelines. Results: Seventeen publications from several Indonesian provinces were identified. Chromoblastomycosis was the most frequently reported infection, followed by eumycetoma, phaeohyphomycosis, and basidiobolomycosis. Clinical presentations were typically chronic. Chromoblastomycosis often manifested as verrucous or nodular lesions, while eumycetoma showed swelling, sinus tracts, and grains. Histopathology was the main diagnostic modality and consistently demonstrated muriform bodies or fungal grains. Culture was less frequently performed and yielded growth in few cases, with Fonsecaea pedrosoi being the predominant identified species. Itraconazole was the most commonly used antifungal and produced favorable responses, though improvement varied with lesion duration. Conclusion: Subcutaneous mycoses in Indonesia remain underdiagnosed and often identified at late stages. Enhanced early detection, improved diagnostic access, and broader availability of antifungal therapy are essential to reduce morbidity. Keywords: Subcutaneous Mycoses; Chromoblastomycosis; Mycetoma; Indonesia 1. Introduction Subcutaneous mycoses are chronic, progressive fungal infections of the skin and subcutaneous tissues caused primarily by melanized (“dematiaceous”) fungi and traumatic inoculation of environmental organisms [1,2]. These infections, including diseases such as chromoblastomycosis, eumycetoma and phaeohyphomycosis, occur predominantly in tropical and subtropical regions where humid climate, soil exposure and agricultural work converge [2–4]. The Chromoblastomycosis in particular is recognized as a neglected tropical disease (NTD), affecting impoverished rural World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 2304 populations and causing significant morbidity due to late presentation, scarring, functional impairment, and potential malignant transformation [5]. Indonesia, with its extensive rural and agricultural communities exposed to soil and vegetation trauma, provides ideal ecological conditions for implantation mycoses [6]. However, national epidemiologic data are fragmented and largely limited to small case series and isolated reports. This paucity of comprehensive data contrasts with the global literature where the burden of chromoblastomycosis and related subcutaneous mycoses remains under-estimated [1,3,5]. Moreover, diagnostic and therapeutic capabilities in many Indonesian settings remain constrained, contributing to delayed diagnosis and suboptimal outcomes [7]. Given these gaps, a systematic synthesis of available Indonesian studies is essential to clarify the spectrum of clinical presentations, highlight diagnostic and therapeutic challenges, and inform policy and clinical practice. The objective of this review is to collate all published data from Indonesia between 2013 and 2025 on subcutaneous mycoses, describe their epidemiology, clinical and microbiological features, diagnostic approach, treatment patterns and outcomes, and identify priorities for improving care and reducing disease burden in endemic settings. 2. Material and methods 2.1. Study Design This study is a systematic review synthesizing published case reports and case series of subcutaneous mycoses in Indonesia over the last decade. The review followed the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines to ensure methodological transparency and reproducibility. 2.2. Search Strategy A literature search was performed in PubMed, Google Scholar, GARUDA (Garba Rujukan Digital), and institutional repositories. The search covered publications from January 2015 to November 2025. The following keywords were used in various combinations: “subcutaneous mycoses,” “chromoblastomycosis,” “mycetoma,” “phaeohyphomycosis,” “sporotrichosis,” “deep fungal infection,” and “Indonesia.” Reference lists of included articles were reviewed to identify additional publications. 2.3. Eligibility Criteria Studies were eligible for inclusion if they were conducted in Indonesia, involved human subjects with any form of subcutaneous mycosis, and provided clinical, diagnostic, or therapeutic information. Only original articles published within the last decade (approximately 2015 to 2025) were included, encompassing case reports, case series, and retrospective observational studies. Publications were excluded if they consisted of reviews, editorials, conference abstracts without patient-level data, non-human studies, or articles published before this time period. 2.4. Study Selection Titles and abstracts were screened for relevance, followed by full-text assessment based on the eligibility criteria. Seventeen studies met the inclusion criteria and were included in the final analysis. The selection process followed PRISMA guidelines. 2.5. Data Extraction Data extracted from each study included: study location, study design, number of patients, type of subcutaneous mycosis, clinical characteristics, diagnostic methods, treatments used, and reported outcomes. Extraction was performed manually and cross-checked for accuracy. 2.6. Data Synthesis Data extracted from each study were synthesized using a descriptive, narrative approach. Given the heterogeneity in study design, sample size, diagnostic work-up, and reporting detail, quantitative pooling was not feasible. Extracted variables were organized into predefined domains, including geographic origin, clinical manifestations, diagnostic modalities, fungal species, and therapeutic interventions. Patterns within each domain were compared across studies to identify areas of convergence and variation. Findings were integrated narratively to outline the overall clinical and World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 2305 diagnostic landscape of subcutaneous mycoses in Indonesia. No meta-analysis or formal statistical aggregation was undertaken due to the case-based nature of the included evidence. Figure 1 PRISMA Flow Chart 3. Results and discussion Seventeen eligible studies from various Indonesian regions were included, representing a range of study designs and settings and providing an overview of the current evidence on subcutaneous mycoses in the country. Table 1 Characteristics of Included Studies Study (Author, Year) Region Study Design Sample Size Disease Type(s) Mulianto et al., 2025 Central Java Retrospective 12 Chromoblastomycosis, eumycetoma, sporotrichosis Pramita et al., 2024 Bali Retrospective 21 Chromoblastomycosis, actinomyetoma, sporotrichosis, lobomycosis Siregar et al., 2025 East Nusa Tenggara Case series 8 Chromoblastomycosis Khairani et al., 2021 South Sumatra Case report 1 Chromoblastomycosis Ariani et al., 2023 West Sumatra Case report 5 Chromoblastomycosis Horo et al., 2022 Bali Case report 1 Chromoblastomycosis Handayani et al., 2023 Aceh Case report 1 Chromoblastomycosis Dharmawan et al., 2021 Central Java Case report 1 Chromoblastomycosis Indranarum et al., 2023 East Java Case report 1 Chromoblastomycosis World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 2306 Earlia et al., 2024 Aceh Case report 1 Chromoblastomycosis Septiafni et al., 2022 South Sumatra Case report 1 Chromoblastomycosis Hidayah et al., 2025 West Java Case report 1 Chromoblastomycosis Hutabarat et al., 2022 South Sulawesi Case report 1 Eumycetoma Fran et al., 2021 Riau Case report 1 Eumycetoma Ahmad et al., 2019 East Java Case report 1 Phaeohyphomycosis Pramitha et al., 2021 East Java Case report 1 Basidiobolomycosis Christi et al., 2023 East Java Case report 1 Basidiobolomycosis The extracted variables from all studies demonstrate considerable variation in clinical severity, diagnostic completeness, and treatment access, reflecting disparities in healthcare resources among regions. These differences form the basis of the thematic synthesis below. Table 2 Clinical, Diagnostic, and Treatment Findings Study (Author, Year) Clinical Features Histopathology Findings Identified Organism(s) Treatment and Outcomes Mulianto et al., 2025 Erythematous nodules, ulceration; black dots; seropurulent discharge Muriform bodies; grains; granuloma - Itraconazole; improved Pramita et al., 2024 Erythematous nodules; verrucous plaques - - - Siregar et al., 2025 Verrucous, nodules, plaque; ulcers - - Ketoconazole; partial improvement; 1 case progressed to SCC* Khairani et al., 2021 Erythematous plaques and cauliflower-like tumor Muriform bodies; granuloma - Itraconazole; partial clinical improvement Ariani et al., 2023 Verrucous or cauliflower-like plaques Muriform bodies; granuloma Fonsecaea pedrosoi Itraconazole; improved Horo et al., 2022 Erythematous nodule with fluctuance Muriform bodies; granuloma Cladophialophora carrionii Itraconazole; improved Handayani et al., 2023 Verrucous plaque with black dots Muriform bodies; granuloma - Itraconazole; improved Dharmawan et al., 2021 Verrucous, nodules Muriform bodies; granuloma Fonsecaea pedrosoi Itraconazole with surgery and cryotherapy; improved Indranarum et al., 2023 Erythematous plaques, verrucous Muriform bodies; granuloma - Itraconazole with adjuvant thermotherapy and CO2 laser; improved Earlia et al., 2024 Verrucous plaques, papules, nodules, some erosion and crusts Muriform bodies; granuloma - Itraconazole; improved World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 2307 Septiafni et al., 2022 Papule-plaque verrucose Muriform bodies; granuloma - Itraconazole; improved Hidayah et al., 2025 Verrucous plaque Muriform bodies; granuloma Fonsecaea spp. Itraconazole with heat therapy; improved Hutabarat et al., 2022 Nodules surrounded by ulcers and pustules with crust Granuloma; grains Madurella mycetomatis Itraconazole; complete resolution Fran et al., 2021 Hypertrophic scars, atrophic scars, nodules, and erythematous papules Suppurative granuloma; grains - Fluconazole; died due to diabetesrelated complications Ahmad et al., 2019 Firm-to-soft, cystic swellings Granuloma Exophiala dermatitidis Itraconazole; improved Pramitha et al., 2021 Nodules and swelling SplendoreHoeppli Basidibolus ranarum Itraconazole; complete resolution Christi et al., 2023 Nodules and swelling SplendoreHoeppli Basidibolus ranarum Itraconazole; complete resolution *SCC = Squamous Cell Carcinoma 3.1. Epidemiological and Study Characteristics Seventeen studies from various Indonesian regions met the inclusion criteria, representing diverse designs and healthcare settings and collectively providing the clearest picture to date of subcutaneous mycoses reported nationally [8-24]. Most publications originated from Java, Bali, and Sumatra, a pattern that likely reflects the distribution of dermatology referral centers and pathology laboratories rather than true regional differences in disease occurrence. Similar geographic biases have been noted globally, where reporting density often mirrors diagnostic capacity more than actual epidemiology [1,5,23,24]. Nearly all included publications were case reports, with only a few small retrospective series. This predominance tends to highlight severe, atypical, or diagnostically challenging presentations, a bias also observed in international chromoblastomycosis and mycetoma literature [25,26]. Within the Indonesian dataset, chromoblastomycosis was the most frequently documented condition, followed by eumycetoma, phaeohyphomycosis, and basidiobolomycosis. This distribution aligns with global observations that implantation mycoses are strongly shaped by environmental exposure, delayed presentation, and uneven diagnostic access rather than true pathogen prevalence [5,27]. 3.2. Clinical Presentation Across Diseases Chronicity was a defining feature across the included reports. Many chromoblastomycosis lesions had progressed for years—sometimes exceeding a decade—before a diagnosis was established, echoing delays described in Latin America, South Asia, and Madagascar [25,27]. Clinically, chromoblastomycosis presented with verrucous plaques, nodules, or cauliflower-like growths, often accompanied by black dots or crusting, consistent with established global descriptions [5,25]. Misdiagnosis at early stages was common, with several cases initially treated as tuberculosis verrucosa cutis, eczema, or cutaneous neoplasms. Eumycetoma cases displayed the classical triad of swelling, sinus tracts, and grains, paralleling presentations in Sudan, Mexico, and India [26]. Phaeohyphomycosis manifested as cystic swellings, whereas basidiobolomycosis showed indurated or edematous soft-tissue swelling, comparable to reports from tropical Africa and the Middle East (30). One fatal case occurred due to complications of uncontrolled diabetes mellitus rather than the fungal infection itself, underscoring the impact of comorbidities on disease trajectory. 3.3. Diagnostic Pattern and Histopathology Histopathology was consistently the primary diagnostic tool, reinforcing its essential role in regions where culture facilities remain limited. Muriform bodies in chromoblastomycosis were reliably detected and remain pathognomonic, aligning with contemporary international consensus [25,29]. Eumycetoma cases showed grains embedded within granulomatous inflammation, consistent with hallmark diagnostic features described worldwide [26]. Culture results World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 2308 varied and were frequently hindered by contamination, limited laboratory infrastructure, or prolonged incubation times—challenges also documented in African and South Asian neglected tropical disease programs [1,25,27]. These findings highlight an urgent need to strengthen mycology laboratory capacity and training at regional levels. 3.4. Fungal Species and Microbiological Confirmation Where culture was successful, Fonsecaea pedrosoi predominated as the etiologic agent of chromoblastomycosis, mirroring species patterns reported in Brazil, Madagascar, and Sri Lanka [25,27,30]. Eumycetoma cases involving Exophiala jeanselmei were consistent with its recognized role as a black-grain mycetoma agent worldwide [26]. Species variability across provinces likely reflects differences in diagnostic capability rather than true ecological diversity, a mismatch similarly reported in Southeast Asia and East Africa [23,25]. 3.5. Treatment Response and Determinants of Outcome Itraconazole—administered continuously or in pulse regimens—was the most consistently effective antifungal across chromoblastomycosis, sporotrichosis, and phaeohyphomycosis, aligning with current recommendations and recent global reviews [5,25,30]. In areas with limited access to itraconazole, ketoconazole was used as an alternative but was associated with slower or incomplete responses, echoing findings from African chromoblastomycosis programs [1,27]. Disease chronicity substantially affected therapeutic response. Long-standing chromoblastomycosis tended to show only partial improvement despite appropriate antifungal treatment, consistent with patterns described internationally [25]. One Indonesian case demonstrated malignant transformation into squamous cell carcinoma, a recognized complication of long-standing chromoblastomycosis documented in recent literature [30]. 3.6. Integrated Interpretation Interpretation of the findings should take into account the characteristics of the available literature. The 17 included studies were conducted in different provinces and clinical settings, which naturally leads to variations in how cases were identified and documented. The concentration of reports in Java, Bali, and Sumatra may reflect the distribution of published clinical observations rather than a definitive pattern of disease occurrence, a situation also noted in reports from other tropical regions [1,5,23,24]. The predominance of case reports influences the type of information presented, as case reports often describe more notable or complex presentations. This may help explain why many of the documented chromoblastomycosis and eumycetoma cases involved long-standing or extensive lesions, similar to descriptions in international literature [25–27]. These patterns highlight the diversity of clinical expression rather than suggesting differences in disease severity between regions. Diagnostic approaches varied across studies, with histopathology appearing most consistently due to its wide applicability. Culture results were less frequently reported, which aligns with experiences in many countries where laboratory procedures differ across institutions [5,25,27]. Because of this variation, the fungal species observed in published cases may reflect the methods used in individual studies, as also described in reports from Southeast Asia and Africa [23,25]. Molecular identification, although increasingly used elsewhere [25,26], was not mentioned in the included studies. Treatment outcomes similarly reflected differences in therapeutic choices reported across studies. Itraconazole was the most frequently used antifungal and showed beneficial responses in several conditions, consistent with international recommendations [5,25,30]. In some reports, alternative agents such as ketoconazole were used, demonstrating the range of therapeutic approaches described in the literature [1,27]. Long-standing lesions were associated with more gradual improvement, a trend also noted in reports from other endemic regions [25]. Overall, the findings from the 17 studies provide a valuable overview of subcutaneous mycoses as documented in different Indonesian settings. While the available publications vary in design and diagnostic detail, they collectively help outline the clinical spectrum, diagnostic features, and therapeutic patterns observed to date. Continued documentation from a wider range of settings may further enrich understanding and align national observations with global trends in implantation mycoses [1,5,23,24,27]. 4. Conclusion Subcutaneous mycoses in Indonesia continue to represent a neglected and underrecognized burden of disease, shaped more by systemic healthcare limitations than by fungal virulence itself. The seventeen included studies consistently demonstrate that delayed diagnosis, reliance on limited laboratory resources, and unequal access to effective antifungal therapy contribute to the chronic, deforming, and difficult-to-treat presentations observed across endemic regions. Histopathology remains the most dependable diagnostic modality, particularly in resource-limited settings, whereas World Journal of Advanced Research and Reviews, 2025, 28(02), 2303-2310 2309 fungal culture often adds limited value due to operational constraints. Itraconazole shows the greatest therapeutic benefit, yet disparities in drug availability continue to influence treatment outcomes. Strengthening early detection at primary-care levels, expanding histopathology access in rural areas, and improving the distribution of effective antifungals are essential steps toward reducing the morbidity associated with these infections. Coordinated national strategies are needed to ensure that subcutaneous mycoses receive appropriate clinical and public health attention within Indonesia’s broader neglected tropical disease framework. Compliance with ethical standards Disclosure of conflict of interest The authors declare that there are no conflicts of interest regarding the publication of this article. References [1] Santos DWCL, de Azevedo CMPES, Vicente VA, Queiroz-Telles F, Rodrigues AM, de Hoog GS, et al. The global burden of chromoblastomycosis. PLoS Negl Trop Dis. 2021;15(8):e0009611. [2] Tirado-Sánchez A, Franco-Paredes C, Bonifaz A. 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