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Chromoblastomycosis

Chromoblastomycosis
Literature review current through: Jan 2024.
This topic last updated: Jan 25, 2022.

INTRODUCTION — Chromoblastomycosis (also known as chromomycosis) is a chronic, indolent, granulomatous fungal disease caused by the transcutaneous inoculation of propagules (conidia and/or mycelia) from several species of melanized fungi. Chromoblastomycosis occurs in tropical and subtropical climates and is one of the most common endemic implantation (subcutaneous) mycoses. The disease can have an important impact on public health and is officially recognized by the World Health Organization (WHO) as a neglected tropical disease (NTD) [1].

The infection begins at the site of inoculation, affects the cutaneous and subcutaneous tissues, and exhibits diverse clinical findings. Early disease often presents as erythematous macules or papules that develop verrucous or hyperkeratotic features (picture 1I). Without treatment, the infection slowly progresses to larger areas of skin involvement with nodular, verrucous, tumoral, plaque, or scar-like morphologies (picture 1A-E). Severe disease can be associated with tissue fibrosis and lymphedema, leading to physical disability (picture 2).

The diverse clinical findings of chromoblastomycosis mimic other infectious or noninfectious diseases. The diagnosis is confirmed through the identification of characteristic fungal elements called muriform cells (also known as sclerotic bodies or Medlar bodies) with a potassium hydroxide preparation or skin biopsy (picture 3).

Although early, small lesions of chromoblastomycosis can be treated with surgical removal, long-term oral antifungal therapy is the treatment of choice for more extensive disease. Severe disease is often refractory to treatment.

The clinical features, diagnosis, and management of chromoblastomycosis will be reviewed here. Several other implantation or subcutaneous mycoses are reviewed separately.

(See "Clinical features and diagnosis of sporotrichosis".)

(See "Eumycetoma".)

(See "Lobomycosis".)

(See "Mucormycosis (zygomycosis)".)

MICROBIOLOGY — Chromoblastomycosis is caused by melanized fungi (also known as pigmented, dematiaceous, phaeoid, or black fungi), primarily those in the Herpotrichiellaceae family [2]. Infections are primarily caused by two genera: Fonsecaea spp (F. pedrosoi, F. monophora, F. nubica, F. pugnacious, and F. brasiliensis) and Cladophialophora spp (C. carrionii and C. samoensis). F. pedrosoi and C. carrionii are the most frequent causes. Sporadically, Exophiala spp (E. dermatitidis, E. jeanselmei, and E. spinifera), Phialophora spp (P. verrucosa and P. richardsiae), and Rhinocladiella spp (R. aquaspersa, R. tropicalis, and R. similis) are isolated from patients with chromoblastomycosis [3-16].

EPIDEMIOLOGY AND RISK FACTORS — Melanized fungi are ubiquitous worldwide, especially in tropical and subtropical environments and organic microhabitats. Chromoblastomycosis is most prevalent in tropical and subtropical regions (figure 1). F. pedrosoi and C. carrionii, the most frequent etiologic agents, typically occur in humid or semiarid climates, respectively [17-20]. Scattered infections have been reported in temperate zones, and there are rare reports of chromoblastomycosis occurring after natural disasters in nonendemic areas [21,22].

The sources of infection for individuals at risk are soil and plant products. It is believed that during their saprobic life, the causative fungi of this disease live in soil and/or on diverse plant fragments (eg, leaves, spiny seeds, thorns, decaying wood, etc). Sporadically, wood fragments containing muriform cell-like structures have been found in histologic specimens of chromoblastomycosis [20,23].

In accordance with these findings, risk for infection is strongly associated with cutaneous trauma obtained during outdoor work or recreational activities, such as agropastoralism, hunting, and ecotourism [2,17]. Isolation of F. pedrosoi from plant parts responsible for the penetrating trauma that led to chromoblastomycosis has been reported [24,25]. In some endemic locations, chromoblastomycosis is considered an occupational disease, primarily affecting workers exposed to contaminated plant materials or soil, such as farm workers and gardeners [17-19].

The global burden of disease is not precisely known because, like many other endemic mycoses, chromoblastomycosis is not a reportable infectious disease. It is estimated that the incidence ranges from 1:6800 in Madagascar to 1:8,625,000 in the United States. The estimated annual global burden of this disease is around 10,000 cases [26]. Data from case series indicate that most patients are adult males [27-29]. In contrast to phaeohyphomycosis (also caused by melanized fungi), most patients are immunocompetent. Chromoblastomycosis is not an opportunistic infection [30].

PATHOGENESIS — Only select species of melanized fungi can survive in the human body after cutaneous penetration and cause clinical manifestations [2,17,31,32]. As with other pathogenic fungi, multiple virulence factors likely play a role in the development of the disease. A unique type of fungal dimorphism that results in a muriform cell architecture, the presence of melanin in the fungal cell wall, hydrophobicity, and cell adhesion are considered particularly important characteristics [2,33-35]. In addition, mechanisms that interfere with the host response may contribute to the persistence of infection:

Muriform cell architecture – The muriform cell architecture (brown, round or polyhedral structures) develops after transcutaneous inoculation and resists host defenses, facilitating disease progression [2]. They are highly resistant to immune system attack. Ultrastructural examination of muriform cells indicates that some muriform cells consist primarily of storage materials (eg, lipid, glycogen) and few organelles; these features may support the ability of etiologic fungi to remain dormant in tissue for extended periods and resist treatment [36]. The muriform cells multiply in the host tissues by planate dividing (scissiparity). Other terms used to refer to muriform cells include sclerotic bodies, Medlar bodies, fumagoid bodies, copper pennies, chestnut cells, and meristematic cells.

Cell adhesive properties and hydrophobicity – Fungal cell adhesive properties and hydrophobicity of fungal elements may support the adherence of fungal elements to host tissue, allowing for the transition to the muriform cell morphology [2].

Melanin – Melanin in fungal cell walls may support evasion of the host immune system. Proposed mechanisms include protection against proteolytic enzymes and oxygen or nitrogen derivatives as well as inhibition of phagocytosis [2].

Host immune response Cutaneous macrophages in association with a cell-mediated immune response play important roles in controlling fungal growth [37]. In immunocompetent hosts, the tissue reaction to fungal infection includes dense granulomatous infiltrates, microabscesses, and tissue proliferation [2,38].

Genetic factors may influence the ability of the host to resist infection. An increase in the relative risk for chromoblastomycosis has been detected in carriers of HLA-A29 [39,40]. In addition, caspase recruitment domain-containing protein 9 (CARD9) mutations favor the development of various fungal infections [41-45]. Although chromoblastomycosis prevails in males, it has not been determined whether hormonal factors are protective for females, as in paracoccidioidomycosis [46]. (See "Mycology and epidemiology of paracoccidioidomycosis", section on 'Sex distribution'.)

CLINICAL MANIFESTATIONS — Clinical manifestations of chromoblastomycosis first appear at the site of inoculation weeks to months after trauma. Patients may not recall the inciting trauma. Most often, the infection occurs in trauma-prone sites, such as exposed areas of the lower and upper limbs. Involvement of shoulders, trunk, buttocks, eyelids, nose, or ears also has been reported (picture 4) [2,27,38,47].

Chromoblastomycosis initially manifests as a solitary, erythematous macule that may evolve to a smooth, pink papule. Verrucous and hyperkeratotic features may subsequently appear (picture 1I). In the absence of early diagnosis and treatment, lesions can increase in size and/or spread locally, producing satellite lesions.

The manifestations of progressing disease are polymorphic [2,48]. Five morphologies usually occur [2]:

Nodular – Moderately elevated, soft, pink or violaceous growth with a smooth, verrucous, or scaly surface (picture 1A, 1F).

Verrucous – Markedly hyperkeratotic, warty, dry growth; often occurs along the border of the foot (picture 1B, 1G).

Tumorous – Prominent tumor-like masses with papillomatous or lobulated, cauliflower-like morphology, overlying epidermal debris and crusts; often occurs on the lower extremities (picture 1C).

Cicatricial – Flat plaques that expand peripherally with central atrophic scarring; often exhibit annular, arciform, or serpiginous configuration. The affected areas is often extensive (picture 1E).

Plaque – Erythematous to violaceous, slightly elevated, infiltrated, scaly plaque; marked lines of cleavage may be present. Often occurs on proximal limbs, shoulders, and buttocks (picture 1D, 1H).

The clinical manifestations depend upon factors such as fungal virulence, anatomic location of the infection, and the host response. Nodular, verrucous, and tumorous presentations are most commonly reported. Patients with advanced disease may have more than one morphology simultaneously (picture 5) [2,27,38,47].

Close examination of the surface of lesions often reveals numerous black dots or a "cayenne pepper" appearance. These small elements represent small hematic crusts, pigmented fungal structures, and transepidermal elimination of cellular debris [49,50].

In early disease, symptoms are minimal. As the disease progresses, pruritus becomes a dominant complaint and may be accompanied by local pain.

Spread of the infection is generally limited to the cutaneous and subcutaneous tissues. New lesions usually result from contiguous spread and/or the infrequent occurrence of lymphatic spread. Because lesions are intensely pruritic, it is thought that scratching may also contribute to cutaneous dissemination [2,27,38,47].

COMPLICATIONS — Potential complications of chromoblastomycosis include disabling tissue fibrosis, secondary infection, squamous cell carcinoma, and, rarely, internal organ involvement:

Tissue fibrosis – The slow, progressive course of chromoblastomycosis results in tissue fibrosis. Fibrotic reactions may also occur in response to the initiation of antifungal therapy. In most cases, the local fibrosis is an irreversible fibrotic process, and it is associated with mature collagen cross-linking due to transglutaminase and lysyl oxidase enzyme activity. These enzymes are detected at the circulating and tissue levels [51,52]. Potential sequelae include lymphatic blockage, stasis, lymphedema, and elephantiasis (picture 2). Depending on the site of infection, fibrosis may also lead to complications such as joint immobility and ectropion.

Bacterial infection – Secondary bacterial infection is a common complication of severe disease and may lead to osteomyelitis [2].

Squamous cell carcinoma – There are several reports of squamous cell carcinoma occurring in association with severe chromoblastomycosis. The chronicity of infection and association with bacterial infection and lymphedema may contribute to the development of malignancy [53]. The time to onset of malignancy has ranged from 5 to 36 years [2,54,55].

Internal organ involvement – Unlike sporotrichosis and mycetoma, chromoblastomycosis does not compromise deeper structures, such as tendons, muscles, fascia, and osteoarticular sites. Involvement of internal organs is rare [11]. Many early reports of chromoblastomycosis involving the brain or lung are now recognized as phaeohyphomycosis rather than chromoblastomycosis infections [56,57].

DIAGNOSIS — The possibility of chromoblastomycosis should be suspected in patients with persistent, slow-growing, cutaneous, verrucous or hyperkeratotic papules, nodules, or plaques who live in or traveled to tropical or subtropical regions. Black dots or a "cayenne pepper" appearance on the surface of affected skin is a helpful suggestive clinical feature (picture 3). The diagnosis can be confirmed through the detection of muriform cells with a potassium hydroxide (KOH) preparation or skin biopsy. Fungal cultures are used to identify the genus of the causative organism. Molecular methods are required for species identification [2,7].

History and physical examination — Because the physical findings are polymorphic, the differential diagnosis often includes a variety of diseases. Features that support a diagnosis of chromoblastomycosis include:

Patient resides in or has visited tropical or subtropical locations

History of outdoor occupation or recreation

History of injury at site of the initial lesion

Verrucous or hyperkeratotic papules, nodules, or plaques or cauliflower-like or scar-like lesions

Location on the extremity

Black dots or "cayenne pepper" appearance on surface of lesions

Pruritus (advanced lesions)

Slow rate of disease progression

The absence of any of these features does not exclude the diagnosis. In particular, because inoculation may occur weeks to months before the appearance of physical findings, patients may not recall the inciting injury.

Dermoscopy — The small, black dots on the surface of chromoblastomycosis lesions can be observed with naked eyes. However, dermoscopic evaluation can help to visualize these areas, supporting selection of the best specimen collection site for confirmation of fungal infection [58]. (See 'Confirmation of fungal infection' below and "Overview of dermoscopy".)

Confirmation of fungal infection — A diagnosis of chromoblastomycosis is typically confirmed through the identification of muriform cells with a KOH preparation or skin biopsy. A fungal culture is recommended to identify the causative organism.

Potassium hydroxide preparation — Examination of superficial skin scrapings from lesions of chromoblastomycosis with a potassium hydroxide (KOH) preparation can confirm the diagnosis through the detection of muriform cells and other brown-pigmented fungal structures. Sampling areas with visible black dots or the "cayenne pepper" appearance is preferred, as this may increase the likelihood of detecting fungal elements (picture 3). (See "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

A calcofluor white stain can be added to the KOH preparation if fungal elements are scarce. Calcofluor white is a fluorescent brightener that binds to cellulose and chitin in fungal cell walls and fluoresces when exposed to ultraviolet radiation, facilitating the detection of fungal elements.

Skin biopsy — As with KOH preparations, the preferred site for a skin biopsy is an area of affected skin with visible black dots or a "cayenne pepper" appearance [2]. The preferred type of biopsy is an elliptical incisional biopsy that includes epidermis, dermis, and subcutaneous tissue. The specimen can be divided, with one section sent for histopathologic examination and the second sent for culture. Alternatively, two punch biopsies can be performed. (See "Skin biopsy techniques".)

The hallmark histopathologic finding is the muriform cell, which may be observed alone or in clusters with routine hematoxylin and eosin staining. Muriform cells can be found inside multinucleated giant cells. Additional pathologic features include hyperkeratosis, pseudoepitheliomatous hyperplasia, irregular acanthosis, and pyogranulomatous inflammation [59,60].

Fungal cultures — A KOH preparation or skin biopsy typically confirms a diagnosis of chromoblastomycosis prior to the availability of culture results. Fungal cultures are recommended to identify the responsible organism.

Skin biopsy specimens are preferred over skin scrapings or exudative specimens for culture. Biopsy specimens are more likely to identify the etiologic agent because of decreased bacterial contamination. To further minimize bacterial contamination, antibiotic and cycloheximide-containing media can be used for cultivation [38].

All fungal causes of chromoblastomycosis manifest as slow-growing, darkly pigmented (black, brown, gray, or green) colonies on mycology agar media. With the exception of Exophiala species, which in the early stages present with a black yeast appearance, all causative fungi develop pigmented and dense aerial mycelia, usually velvety or floccose in appearance [2,38,61].

The identification of the causative genus occurs through recognition of the conidiophore micromorphology (picture 6). For accurate species identification, molecular identification with specific gene sequencing is needed [7,10].

Serology — In research studies, enzyme-linked immunosorbent assay (ELISA) and immunodiffusion techniques have identified immunoglobulin G (IgG) antibodies in individuals with chromoblastomycosis or in asymptomatic individuals living in endemic areas [62,63]. However, there are no commercial serologic tests to confirm a diagnosis of chromoblastomycosis.

DIFFERENTIAL DIAGNOSIS — The chronic, indolent, polymorphic lesions of chromoblastomycosis can resemble infections caused by viruses, bacteria, protozoa, and other fungi. In addition, various noninfectious diseases can mimic chromoblastomycosis (table 1). A potassium hydroxide preparation or skin biopsy demonstrating muriform cells distinguishes chromoblastomycosis from these disorders.

MANAGEMENT — No randomized trials have evaluated treatments for chromoblastomycosis. The approach to treatment is primarily based upon uncontrolled studies, case series, and expert opinion.

General approach — Treatment is recommended but can be challenging. The likelihood of complete cure appears to decrease with increasing severity of disease.

A classification system for disease severity helps to guide the approach to treatment [2]:

Mild disease – Solitary plaque or nodule less than 5 cm in diameter

Moderate disease – Single or multiple lesions with nodular, verrucous or plaque morphology, less than 15 cm in diameter, and involving a single or two adjacent skin areas

Severe disease – Extensive involvement of adjacent or nonadjacent skin areas

Surgical excision can be curative and is the recommended therapeutic approach for surgically amenable mild disease. However, most patients do not seek medical care at this stage, and surgery is less likely to be curative for moderate to severe disease. (See 'Surgical excision' below.)

The primary therapy for patients with moderate to severe disease is administration of an oral antifungal agent. Itraconazole is the most commonly used agent followed by terbinafine. Responses to treatment vary. Limited data suggest that other oral antifungal agents, such as posaconazole, also may be useful. (See 'Systemic antifungal agents' below.)

Refractory disease — The best approach to patients who fail a course of systemic antifungal therapy is unclear. Although high-quality data to support this approach are lacking, combinations of oral antifungal agents have been used for the treatment of disease refractory to a single agent. Among four patients with chromoblastomycosis refractory to oral antifungal monotherapy, a regimen in which terbinafine and itraconazole were given on alternate weeks was associated with clinical improvement or resolution [64]. Responses of refractory chromoblastomycosis to combination therapy with itraconazole and flucytosine is also documented in a small case series and case report [65,66]. The addition of physical therapies (eg, cryotherapy, heat therapy, laser therapy, or photodynamic therapy) to oral antifungal therapy also may be useful. (See 'Physical interventions' below.)

Treatment options

Surgical excision — Surgical excision can cure chromoblastomycosis and is the treatment of choice for patients with mild disease. The excision should extend into the subcutis, and there should be at least a 0.5 cm margin of healthy-appearing skin at all margins. Dermoscopic examination can aid in delineating an appropriate lateral margin. Surgical excision is not recommended for moderate to severe disease; the less well-defined clinical margins may increase risk for implantation of fungal elements into adjacent, healthy cutaneous or subcutaneous tissue during the procedure.

Systemic antifungal agents — The primary systemic antifungal therapies for chromoblastomycosis are itraconazole and terbinafine. In responders, clinical improvement (shrinkage and disappearance of cutaneous lesions) occurs slowly, typically occurring over multiple months.

Over time, the dense fibrosis occurring during therapy may reduce the availability of antifungal drugs at the tissular level. This may contribute to antifungal-resistant infections in patients with longstanding disease [67]. (See 'Complications' above.)

Itraconazole — Itraconazole is the most common oral antifungal agent prescribed for chromoblastomycosis. Adults are typically treated with 200 to 400 mg per day for 8 to 36 months. Reported cure rates range from 15 to 80 percent [2].

The efficacy of itraconazole is supported by small uncontrolled studies and case series. In an uncontrolled study of 19 patients with mild to severe chromoblastomycosis secondary to F. pedrosoi (18 patients) or F. compacta (1 patient) who were treated with either 100 or 200 mg of itraconazole twice daily, eight (all with mild to moderate disease) achieved clinical, mycologic, and histologic cure, seven (all with moderate to severe disease) had clinical cure but mycologic or histologic persistence, and the remaining four patients (all with severe disease) had clinical improvement but mycologic or histologic persistence [68]. The mean durations of treatment required for these responses were approximately 7, 25, and 18 months, respectively.

Pulsed dosing of itraconazole (400 mg per day given one week per month for 6 to 12 months) may be an effective alternative regimen. In a series of six patients with F. pedrosoi chromoblastomycosis, four achieved cure within 12 months of treatment [69]. Successful treatment of a patient with pulsed dosing for seven months is also documented [70].

Data are insufficient for definitive conclusions on the impact of the specific causative species on the response to itraconazole. However, in an uncontrolled study that included 14 patients with chromoblastomycosis treated with itraconazole for four to eight months, eight of nine patients with C. carrionii infections achieved apparent cure [71]. In contrast, only two of five patients with F. pedrosoi infections achieved this endpoint, both requiring adjunctive therapy (flucytosine or local heat).

Itraconazole therapy is generally well tolerated. Examples of potential side effects include gastrointestinal distress, skin eruptions, headache, sleepiness, dizziness, and hepatotoxicity. Liver function tests should be obtained prior to treatment in patients with preexisting liver disease. Liver function tests should also be obtained in patients who have been treated for more than one month. Side effects of itraconazole are reviewed in greater detail separately. (See "Pharmacology of azoles", section on 'Adverse effects'.)

Itraconazole has multiple drug interactions. Patients' medication lists should be reviewed carefully prior to treatment. (See "Pharmacology of azoles", section on 'Drug interactions'.)

Terbinafine — Terbinafine is the second most common oral antifungal agent given for chromoblastomycosis. Adult doses typically range from 250 to 500 mg per day, with the duration ranging from months to years, based upon severity of disease and the response to treatment.

An uncontrolled study and case reports support benefit of terbinafine for chromoblastomycosis [72-76]. In the uncontrolled study, after 12 months of terbinafine therapy (500 mg per day), 19 of 29 patients (66 percent) with F. pedrosoi infections attained complete healing (full clinical resolution or only residual scars, mycologic cure, and complete tissue scarring on histopathology) [72]. Full results for a smaller number of patients with C. carrionii infections were not reported, but the authors observed favorable preliminary responses.

An advantage of terbinafine is fewer drug-drug interactions than itraconazole. It is also hypothesized that antifibrotic properties of terbinafine may be beneficial in chromoblastomycosis.

Like itraconazole, terbinafine is usually well tolerated. Potential side effects include headache, gastrointestinal distress, taste disturbances, skin eruptions, and hepatotoxicity. Rare side effects include severe drug reactions (eg, drug reaction with eosinophilia and systemic symptoms [DRESS]), drug-induced lupus, pancytopenia, and pancreatitis.

Other systemic antifungal agents — A small uncontrolled study suggests that posaconazole, a newer antifungal agent, may treat chromoblastomycosis. Among six patients with chromoblastomycosis refractory to terbinafine, itraconazole, or flucytosine, four achieved complete clinical responses and one achieved a partial clinical response after treatment with 800 mg of posaconazole per day, given in two or four divided doses for up to 12 months [77].

Partial responses to voriconazole (200 mg twice daily) occurred in three patients with severe chromoblastomycosis refractory to itraconazole and terbinafine during 12 months of voriconazole therapy [78]. Isavuconazole has not been evaluated in this disease.

Although systemic amphotericin B, flucytosine (as monotherapy), ketoconazole, and thiabendazole have been used for chromoblastomycosis in the past, these drugs have been abandoned as routine therapies due to relatively poor efficacy and/or risk for serious side effects [2].

Physical interventions — In addition to surgical excision, other procedures have been employed for treatment, including cryotherapy, heat therapy, and light-based therapies. These therapies are most often used as adjuncts to systemic antifungal treatment with the goals of improving treatment responses, reducing the duration of oral antifungal therapy, and reducing the number of physical treatment sessions needed. In particular, administration of oral antifungal therapy can reduce the extent of disease, making lesions more amenable to physical treatments [79]:

Cryotherapy – During cryotherapy, liquid nitrogen is applied to affected skin with a cotton swab or spray device. Different durations of freezing have been used, ranging from 30 seconds to four minutes [2]. Two freeze-thaw cycles are typically performed during each treatment session. Although small lesions can be treated in entirety during a single cryotherapy session, larger lesions are often subdivided and lesion areas treated sequentially during subsequent sessions.

Benefit of cryotherapy is reported in uncontrolled and comparative studies [80-83]. One of the largest studies is an uncontrolled study in which 22 patients with chromoblastomycosis were treated with cryotherapy alone or in combination with itraconazole [80]. At the end of the study, nine patients were cured (clinically disease-free period of at least three years), eight were clinically disease free but had fewer than three years of follow-up at the end of the study, two remained on treatment for active lesions, and three had unsuccessful treatment. The average number of cryotherapy sessions administered was 6.7 (range 1 to 22 sessions).

Potential complications of cryotherapy include pain, edema, dyspigmentation, blistering, and scarring. Treatment of flexural areas is generally avoided to minimize risk for formation of restrictive scars.

Heat therapy – Heat therapy is performed based upon the knowledge that causative fungi have maximum growth temperatures from 42 to 46°C (107.6 to 114.8°F) [2]. Treatment involves the direct application of heat to lesional skin. In case reports, use of devices such as chemical pocket warmers and heating pads alone or in combination with oral antifungal therapy have been associated with improvement or disease resolution [84-88].

Light-based therapies – Resolution of chromoblastomycosis following carbon dioxide laser vaporization is documented in case reports [89,90]. Clinical improvement has been associated with photodynamic therapy alone or in combination with oral antifungal therapy and is documented in a small uncontrolled study and case reports [91-93].

Other therapies — Other therapies reported to be beneficial in small numbers of patients include topical imiquimod [94] and intramuscular glucan [95].

Criteria for cure — Long-term follow-up is necessary to confirm eradication of infection. Treatment can be discontinued when the following criteria are met:

Clinical resolution (disappearance of cutaneous manifestations with the exception of atrophic scarring) maintained for at least three to four months

Resolution of local pruritus and pain

Monthly skin biopsies demonstrating absence of fungal elements, epidermal atrophy, and replacement of granulomatous inflammation by chronic inflammation and dense fibrosis for three consecutive months

Negative monthly potassium hydroxide preparation for three consecutive months

Negative monthly tissue culture for three consecutive months

After treatment cessation, periodic clinical, mycologic, and histologic assessments are recommended to confirm cure [2,17,53,96]. Patients should be followed for at least two years with reassessments performed every three to four months, including a physical examination, potassium hydroxide preparation, skin biopsy, and tissue culture.

PREVENTION — The best way to prevent chromoblastomycosis is to avoid cutaneous trauma in endemic areas. Individuals with outdoor occupations in endemic areas should use protective equipment such as adequate clothing, shoes, and gloves.

SUMMARY AND RECOMMENDATIONS

Overview – Chromoblastomycosis is a chronic, indolent fungal infection caused by several species of melanized fungi. The most common causative organisms are Fonsecaea pedrosoi and Cladophialophora carrionii. Infection is typically limited to the cutaneous and subcutaneous tissue. (See 'Microbiology' above.)

Epidemiology – Chromoblastomycosis most often occurs in tropical or subtropical regions. The causative fungi can be found in soil and plant fragments, and infection usually results from cutaneous trauma. Individuals who engage in outdoor work or recreational activities in endemic areas are at greatest risk for infection. (See 'Epidemiology and risk factors' above.)

Pathogenesis – A variety of fungal virulence factors likely contribute to infection, including the ability of causative fungi to acquire a muriform cell architecture in tissue. Muriform cells (also known as sclerotic bodies, Medlar bodies, fumagoid bodies, copper pennies, chestnut cells, and meristematic cells) are resistant to host defenses and facilitate persistence of infection. (See 'Pathogenesis' above.)

Clinical manifestations – The clinical manifestations of chromoblastomycosis are polymorphic. The infection usually begins as an erythematous macule that progresses to verrucous or hyperkeratotic papules, nodules, or plaques (picture 1A-E, 1I). Pruritus is common and may be accompanied by local pain. Tissue fibrosis, lymphedema, secondary infection, and malignancy are potential complications. Internal organ involvement is rare. (See 'Clinical manifestations' above and 'Complications' above.)

Diagnosis – The diagnosis of chromoblastomycosis is confirmed through the detection of muriform cells in a potassium hydroxide preparation or skin biopsy (picture 3). Fungal cultures are used to identify the causative organism. (See 'Diagnosis' above.)

Management – The treatment of chromoblastomycosis can be challenging. Severe disease is often refractory to treatment. For small, solitary, well-defined lesions, we suggest surgical excision as initial treatment (Grade 2C). For more extensive disease, we suggest oral antifungal therapy rather than surgical excision as initial treatment (Grade 2C). Itraconazole and terbinafine are the most common oral antifungal therapies. Other interventions, such as cryotherapy, heat therapy, and light-based therapies, may be useful as adjunctive treatments. (See 'Management' above.)

Long-term follow-up is necessary to determine whether patients have achieved cure. Periodic clinical, mycologic, and histologic assessments are needed. (See 'Criteria for cure' above.)

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Topic 110103 Version 4.0

References

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