Chromoblastomycosis (CBM), otherwise known as chromomycosis is an indolent, chronic cutaneous granulomatous fungal infection caused by melanized fungi, primarily from the Herpotrichiellaceae family (1, 2–4). The disease is a long-standing infection that typically occurs after fungal elements are introduced into the skin through trauma, particularly among individuals engaged in agricultural and soil-related activities (4). It represents one of the most prevalent subcutaneous mycoses in endemic areas and carries a substantial public health burden (5, 6) because of causing progressive morbidity, disfiguring lesions, and functional impairment, often leading to social stigma and poor quality of life (7–9).

The global incidence of CBM is difficult to determine due to its non-notifiable status and the limited availability of data, which mainly consist of small case series or reports (7). Although believed to have a similar overall burden to mycetoma, its geographic distribution and incidence in endemic regions remain poorly defined (7, 10).

CBM presents with a heterogeneous clinical picture, ranging from mild skin lesions at the site of fungal implantation to severe, disfiguring lesions (11). All age groups can be affected; however, individuals engaged in soil-related occupations are at higher risk of morbidity. This disease affects primarily males (80%), typically presenting between 43 and 56 years of age. It most commonly affects the lower limbs (60%), with an average duration of 10.8 years before diagnosis (12). Studies on CBM are generally limited. For instance, in Ethiopia, a retrospective study identified 12 CBM cases among 20 subcutaneous mycoses, with 75% male predominance and a median age of 44 years (13). The prevalence is higher in tropical and subtropical regions, including Latin America, Africa, and Asia (14). In resource-limited settings, underreporting, a lack of surveillance system, and barriers to care underestimate the true incidence, delay diagnosis, and hinder effective public health planning. Untreated CBM can result in debilitating tissue fibrosis, lymphedema, secondary bacterial infection, and squamous cell carcinoma (15, 16). This review focuses on the epidemiology, pathogenesis, diagnosis, treatment, and prognosis of CBM in marginalized populations to address knowledge gaps and provide a theoretical foundation for improving early case detection and treatment.

The clinical picture of CBM was first described with documented cases in the early 20th century, with the initial report dating back to Brazil in 1914 (17). Since then, understanding of the disease has greatly evolved, including identification of its etiologic fungi, pathological features, and treatment. The disease, formerly called chromomycosis in some regions. However, chromoblastomycosis is now the preferred term, as it reflects the distinctive presence of the so-called ‘chromoblasts,’ or muriform or sclerotic cells, in the infected tissues. These muriform or sclerotic cells are clusters of fungal cells and are pathognomonic for the diagnosis (18).

In recognition of its epidemiological and public health significance, CBM was designated as a Neglected Tropical Disease (NTD) by the World Health Organization (WHO) in 2017 (19). This inclusion underscores the disease’s disproportionate impact on vulnerable populations and the need for enhanced surveillance, better diagnostic capabilities, and more effective treatment options. The designation also aligns CBM with similar chronic fungal NTDs, like mycetoma and paracoccidioidomycosis, reflecting shared challenges related to poverty, healthcare access, and persistent morbidity (20).

CBM is primarily caused by melanized fungi, especially within the Herpotrichiellaceae family. According to available databases, common causative agents are Fonsecaea species (F. pedrosoi, F. erecta, F. nubica, and F. brasiliensis) and Cladophialophora species (C. carrionii and C. yegresii). Fonsecaea (especially F. pedrosoi) and Cladophialophora (C. carrionii) species are the most frequent causative agents worldwide (21). Molecular tools have identified several rare or emerging agents, improving pathogen detection. These include Fonsecaea monophora, genetically distinct from F. pedrosoi and exhibiting clinical differences, and recently described Fonsecaea pugnacius, associated with disseminated disease (22). Other rare agents include Exophiala species, causing systemic infections in immunocompetent children, and a non-sporulating Rhytidhysteron species, notable for its rare pathogenicity in humans (13, 23–26).

Regarding risk factors, a few studies indicate that the primary sources of infection are soil and plant materials, with the causative fungi living saprobically on leaves, thorns, seeds, and decaying wood. The risk of infection is strongly associated with cutaneous trauma during outdoor work or recreational activities, including agriculture, hunting, and ecotourism. In some endemic regions, CMB is considered an occupational disease, primarily affecting farm workers, gardeners, and others exposed to contaminated plant matter or soil (32, 39, 40).

The pathogenesis begins with the traumatic introduction of fungal elements into the skin from environmental sources. Once the fungus penetrates the skin, it triggers a chronic granulomatous lesion with fibrosis, progressive tissue proliferation, and formation of multiple micro–abscesses, mediated by a dominant T–helper type 2 (Th2) immune response. Within the affected tissue, sclerotic bodies become embedded, giving rise to the characteristic polymorphic cutaneous lesion. Chronic tissue involvement can cause functional impairment and, rarely, malignant transformation. The pathogenesis involves both fungal adaptation and the host’s chronic inflammatory response, driving disease progression and morbidity (12, 37).

CBM is caused by a limited group of melanized fungi. These fungi possess several virulence factors that are likely to play a role in the disease development, including a unique dimorphism resulting in sclerotic body formation characterized by the presence of melanin in the cell wall, hydrophobicity, and strong cell adhesion (41). Sclerotic bodies, also referred to as muriform cells, or Medlar bodies, are thick–walled, brown, polyhedral structures that resist host immune defenses, retain the capacity for replication and dormancy, and thereby contribute to the chronicity and therapeutic recalcitrance of the infection (42).

Fungal cell adhesion and hydrophobicity promote tissue attachment and muriform cell transition, while melanin protects against host immunity (43). Host responses, mainly macrophages and cell–mediated immunity, induce granulomatous inflammation and micro–abscesses, controlling fungal growth in immunocompetent individuals. Additionally, genetic factors may increase susceptibility, while hormonal influences in females are uncertain (1). Understanding the pathogenesis of CBM requires integrating fungal biology, host immunity, and tissue pathology to address its chronic nature and therapeutic challenges.

Clinical manifestations usually appear at the site of skin trauma, and the duration of illness ranges from a few weeks to months after inoculation (11, 44). Initially, the lesions usually present as solitary erythematous macules or papules, most commonly on exposed areas of the limbs, and are often asymptomatic or only mildly pruritic (44). As disease progresses (late–stage), the lesions may evolve into nodular, verrucous, tumorous, plaque, or cicatricial forms, sometimes exhibiting multiple morphologies simultaneously, and are often accompanied by pruritus, local pain, and characteristic black dots or a cayenne pepper appearance (Figure 2) (45). The infection spreads contiguously and occasionally via lymphatics, with clinical progression influenced by fungal virulence, lesion location, and host immunity (12, 46). In resource–limited settings, patients often present with late–stage disease due to a lack of awareness and limited access to advanced healthcare. This creates a delay in diagnosis, usually postpone effective therapy and increase the risk of complications.

Diagnosis of CBM remains challenging. It demands strong clinical suspicion because of its varied presentation, the nature of disease progression, and limited awareness among physicians (29). It should be suspected in patients with persistent, slow–growing, verrucous lesions or those residing in or visiting tropical and subtropical regions. The appearance of cayenne pepper or small black dots on lesions suggests the diagnosis, but definitive confirmation requires identification of muriform or sclerotic bodies (Medlar bodies or copper pennies) in clinical samples via direct microscopy, histopathology, biopsies, or fine needle aspiration (21, 22). These pigmented, thick–walled, round to polyhedral fungal cells with internal septations (muriform cells) are pathognomonic for diagnosis (Figure 3). Histopathology typically reveals pseudoepitheliomatous hyperplasia, granulomatous inflammation, micro abscesses, and muriform cells (47, 48).

In addition to that, dermoscopy enhances visualization of black dots, facilitating targeted sampling for fungal confirmation. Serology (ELISA or immunodiffusion) can detect antibodies for research purposes (48). Diagnostic methods include:

Furthermore, molecular diagnosis plays a key role in CBM by enabling accurate species–level identification of the causative fungi, improving diagnostic certainty, guiding antifungal selection based on known susceptibility patterns, and supporting prognostic assessment and treatment monitoring (48–50).

Careful history and physical examination are crucial for early detection. Key supportive features include outdoor activity, prior trauma at the lesion site, extremity involvement, pruritus in advanced disease, and slow progression, though their absence does not rule out the diagnosis. In resource–limited settings, history and direct microscopy of fine needle aspirates or biopsies can be used for diagnosis where advanced facilities are unavailable (50) (Figure 4).

Chronic, polymorphic lesions can mimic viral, bacterial, protozoal, or fungal infections, as well as noninfectious dermatologic conditions. Demonstration of muriform cells on KOH or biopsy is diagnostic (Table 2).

Treatment of CBM poses significant challenges due to its non–mandatory reporting status, prolonged use of antifungal drugs, and frequently suboptimal therapeutic responses. No randomized controlled trials or consensus guidelines currently exist for the treatment of CBM, which highlights a significant evidence gap. Consequently, current treatment strategies are primarily informed by case reports, case series, expert consensus, and uncontrolled studies, with treatment decisions guided by the severity and extent of the disease. Disease severity is categorized as mild (solitary lesion <5 cm), moderate (single or multiple lesions <15 cm confined to one or two adjacent areas), or severe (extensive involvement of adjacent or nonadjacent areas). Overall, pharmacotherapy remains the cornerstone of treatment, whereas surgical intervention may be appropriate for selected cases with mild disease (4, 24).

Patients who fail standard oral therapy may benefit from combination antifungal regimens or adjunctive physical therapy. Alternating itraconazole and terbinafine or itraconazole plus flucytosine is used. Adjunctive physical interventions can increase cure rates (58).

Physical therapy modalities play an important adjuvant role in treatment, such as cryotherapy, heat therapy, and light–based therapies (62, 63).

Chronic CBM can cause disabling complications such as tissue fibrosis, lymphedema, secondary infections, and, rarely, malignant transformation. Interestingly, malignant transformation to squamous cell carcinoma is a rare but recognized complication of CBM, reported in approximately 1% of cases in large series from Madagascar. Prolonged disease duration spanning several decades, chronic inflammation, repeated tissue damage, and fibrosis are considered potential risk factors contributing to malignant degeneration (64, 65) (Table 3).

The post–treatment phase of CBM assessment is the most critical period for ensuring long–term success of therapy and preventing relapse. Following active treatment, patients need systematic evaluation to confirm clinical and mycological cure (66). To achieve lasting remission and prevent recurrence, sustained surveillance, laboratory confirmation, and preventive care are crucial (38, 67). Cure is established through clinical and mycological criteria (68), the clinical criteria are as follows:

The delivery of CBM services in Ethiopia remains limited and fragmented, reflecting broader health system challenges. As a neglected fungal disease, CBM suffers from low awareness among both healthcare workers and communities, resulting in frequent misdiagnosis and prolonged morbidity. Cases of CBM and other NTDs are commonly encountered in outpatient settings, particularly among patients from rural and agricultural areas where access to dermatology services and diagnostic facilities is scarce. Consequently, many patients receive delayed or inadequate treatment (69).

Several health system barriers hinder effective CBM service delivery. These include poor integration of CBM into primary healthcare, a shortage of trained personnel, and limited availability of diagnostic tools such as microscopy and histopathology at peripheral health facilities. Access to effective antifungal therapy is inconsistent, with high costs and unreliable supply chains further restricting care. In addition, weak surveillance and reporting systems lead to underestimation of the disease burden, impeding informed planning and resource allocation for NTDs. Limited domestic funding, minimal research capacity, and low community awareness further contribute to delays in diagnosis, treatment, and long–term management of CBM (70).

The governance and policy environment in Ethiopia poses additional challenges to the prevention, diagnosis, and management of CBM and other neglected fungal diseases. Despite the presence of formal health governance structures, gaps persist in leadership, coordination, and implementation capacity across administrative levels. Fragmentation among national, regional, and district health authorities, limited multisectoral engagement, and weak accountability mechanisms impede effective program implementation, particularly for under–recognized conditions. Inconsistent coordination, uneven communication, and policy execution bottlenecks further weaken health governance and oversight frameworks (71).

Furthermore, underdeveloped surveillance and routine health information systems for conditions not systematically tracked such as subcutaneous mycoses, significantly limit progress. Weak reporting mechanisms and persistent data gaps reduce the visibility of CBM in official health records, constraining policymakers’ ability to accurately estimate disease burden and prioritize appropriate public health responses (72).

Although CBM and other subcutaneous mycoses are endemic in Ethiopia, they remain largely absent from national disease control priorities due to limited disease mapping and inadequate surveillance data (33). National health policies predominantly focus on high–burden communicable diseases, maternal and child health, and selected priority neglected tropical diseases, resulting in the exclusion of deep fungal infections.

While existing health sector strategies provide a framework for integrating disease control into primary healthcare, weak governance structures, insufficient financing, logistical constraints, and underdeveloped health information systems limit the effective mainstreaming of non–priority diseases. These gaps perpetuate delayed recognition, inadequate service delivery, and limited policy attention for CBM in Ethiopia.

Improving service delivery for skin–related neglected tropical diseases in Ethiopia requires addressing critical gaps in awareness, diagnosis, treatment access, and research. Integrating CBM and other neglected fungal skin diseases into primary healthcare and dermatology services is essential for early detection, particularly in rural and agricultural settings.

Capacity building through continuous training of healthcare workers or one health principle regular lecture on clinical recognition, diagnosis, and long–term management is equally important. Expanding access to basic diagnostic services such as microscopy and histopathology peripheral laboratories would reduce diagnostic delays and mismanagement. Ensuring affordable access to essential antifungal medicines through inclusion in the national essential medicines list, the appointment of dedicated program managers, implementation of national control programs or mass drug administration (MDA) strategies, and the establishment of clear referral pathways for complex cases is also critical.

Sustained progress will require increased domestic financing, stronger government ownership of neglected fungal disease programs, and enhanced community awareness to promote early care–seeking and reduce stigma. Strengthening local research and surveillance systems is necessary to generate context–specific evidence, inform policy, and support long–term control of CBM in Ethiopia.

CBM is a long–standing, skin–related neglected tropical disease associated with substantial morbidity, social stigma, and reduced quality of life. Its global prevalence varies across regions, with higher rates reported in specific endemic areas, however, limited clinical recognition and weak public health surveillance likely result in significant underestimation of the true disease burden. Early diagnosis, accurate fungal identification, and prolonged antifungal therapy are essential to prevent complications and improve outcomes.

Early case detection is particularly critical in resource–limited settings. Strengthened surveillance systems and molecular epidemiological studies are needed to better define disease distribution and burden. Investment in healthcare infrastructure, prevention strategies, and community engagement, alongside multidisciplinary research in endemic countries, is vital to address existing knowledge gaps and reduce CBM–related morbidity.

Future efforts in CMB should prioritize rapid, affordable diagnostics, particularly molecular tools that enable early, species–level identification. Well–designed clinical studies are needed to rigorously evaluate multimodal therapy, including optimized antifungal combinations and adjuncts like cryotherapy, phototherapy, and immunomodulators. Advances in virulence profiling and antifungal susceptibility testing will help refine therapeutic strategies, while improved surveillance and implementation models are essential to address the disproportionate burden in resource–limited settings. Together, these directions offer a pathway toward more effective, accessible, and durable control of this neglected mycosis. The One Health approach may represent an important way forward for future policy and programmatic action in addressing rare conditions.