Chromoblastomycosis (Chromomycosis)- An Overview

Chromoblastomycosis (Chromomycosis) is a long-term fungal infection that affects the skin and the subcutaneous tissue, which is the layer of tissue under the skin. It is also known as a chronic subcutaneous mycosis, which means a persistent fungal infection of the deeper layers of the skin.

The infection is caused by different types of fungi that belong to a group called dematiaceous fungi. These are fungi that have dark pigments in their cell walls, which give them a brown or black color. Some of the common fungi that cause chromoblastomycosis are:

• Fonsecaea pedrosoi
• Phialophora verrucosa
• Cladophialophora carrionii
• Cladophialophora bantiana
• Exophiala spp.

These fungi are widely distributed in the environment, especially in soil, wood, and decaying plant material. They are more common in tropical and subtropical regions, where the climate is warm and humid.

The infection usually occurs when the fungi enter the skin through a minor injury, such as a cut or a puncture from a thorn or a splinter. The injury may not be noticed or remembered by the person, as the symptoms may take months or years to appear.

The infection grows slowly and spreads locally, forming raised and crusted lesions on the skin. These lesions may be red, gray, or brown in color, and may have black dots on the surface. The lesions may be single or multiple, and may affect any part of the body, but most often the limbs.

The infection may cause itching, pain, swelling, or ulceration of the affected area. It may also cause complications such as secondary bacterial infection, lymphatic obstruction, elephantiasis (enlargement of the limb), squamous cell carcinoma (a type of skin cancer), or spread to other organs through the blood or lymph vessels.

Chromoblastomycosis is not a life-threatening condition, but it can be very difficult to cure and may cause disability and disfigurement. The treatment options include antifungal medications (such as itraconazole, terbinafine, or voriconazole), surgery, heat therapy, cryotherapy (freezing), laser therapy, or photodynamic therapy (using light and a photosensitizing agent). The treatment may last for months or years, and may need to be combined or repeated.

The prevention of chromoblastomycosis involves avoiding contact with soil, wood, or plant material that may contain the fungi, especially in areas where the infection is common. Wearing protective clothing such as gloves, shoes, and long sleeves may help prevent injuries that may allow the fungi to enter the skin. Seeking medical attention for any suspicious skin lesions may help diagnose and treat the infection early.

Chromoblastomycosis (Chromomycosis) is caused by a group of fungi known as dematiaceous fungi. These are fungi that have a dark pigmentation in their cell walls due to the presence of melanin. They are also called black fungi, black yeasts, microcolonial fungi or meristematic fungi. They are widely distributed in the environment, especially in soil, wood, and decaying plant matter. They are more common in tropical and subtropical regions.

There are many species of dematiaceous fungi that can cause chromoblastomycosis, but the most common ones are:

• Fonsecaea pedrosoi: This is the most prevalent species worldwide, accounting for about 60% of cases. It is found mainly in Central and South America, Africa, and Asia.
• Cladophialophora carrionii: This is the second most common species, responsible for about 25% of cases. It is endemic to arid and semi-arid regions of Venezuela, Colombia, and other parts of South America.
• Phialophora verrucosa: This is the third most common species, causing about 10% of cases. It is widely distributed in tropical and subtropical areas, especially in Asia and Africa.

Other less common species include:

• Fonsecaea compacta
• Fonsecaea monophora
• Cladophialophora bantiana
• Rhinocladiella aquaspersa
• Exophiala jeanselmei
• Exophiala spinifera
• Wangiella dermatitidis
• Mudurella spp.
• Scedosporium prolificans

These fungi reproduce asexually by forming spores called conidia, which can be dispersed by air or water. They can also form hyphae (filaments) or yeast-like cells depending on the environmental conditions. They can infect humans through traumatic inoculation of the skin by contaminated objects such as thorns, splinters, or needles.

The dematiaceous fungi have some unique features that make them more resistant to environmental stresses and immune responses. One of them is the melanin in their cell walls, which protects them from oxidative damage, UV radiation, and phagocytic enzymes. Another one is their ability to form sclerotic bodies or muriform cells, which are thick-walled, pigmented cells with multiple septa that resemble a brick wall. These cells are very difficult to kill by antifungal drugs or host defenses .

Chromoblastomycosis is a chronic fungal infection that results from the traumatic inoculation of fungal spores into the skin and subcutaneous tissue via minor injuries, such as cuts, scratches, or thorn pricks . The spores may come from contact with soil, wood, or dead plant debris that are contaminated with dematiaceous fungi.

The fungi responsible for chromoblastomycosis possess adhesion and invasion mechanisms that allow them to colonize and penetrate the epidermis and dermis. They also produce melanin in their cell walls, which confers a protective advantage by scavenging free radicals and hypochlorite that are produced by phagocytic cells. The melanin also gives color to the fungal spores and the fungal hyphae produced during the germination and reproduction of these fungi. This gives the fungi a pigmentation that produces colored skin lesions and skin manifestations.

The host immune response to the fungal infection is characterized by a granulomatous inflammation with epithelioid cells, multinucleated giant cells, lymphocytes, and plasma cells. The fungal elements are visualized as brown septate cells called sclerotic bodies or Medlar bodies, which are pathognomonic of chromoblastomycosis . These bodies are extruded trans-epidermally and are seen as black dots on the surface of the lesions.

The infection may remain asymptomatic or oligosymptomatic for several years before it manifests clinically. The moderate appearance of the disease is characterized by localized pain and intensified itching which progresses to severe disease associated with edema and secondary bacterial infection which may limit body motions and activities. The chronic disease shows manifestations of chronic lymphoedema and development of ankylosis and non-invasive squamous cell carcinoma which may lead to patient disablement.

Chromoblastomycosis is a chronic fungal infection that affects the skin and subcutaneous tissue, usually on the limbs. The infection begins at the site of inoculation by a minor injury, such as a cut with a splinter or a thorn, that introduces the fungal spores into the skin. The infection progresses slowly and may remain asymptomatic for years before producing clinical signs and symptoms.

The general manifestations of chromoblastomycosis include :

• Small firm red or grey bump (papule) at the site of inoculation, which grows very slowly (about 2 mm per year).
• Warty dry nodule or plaque with a scaly or crusty surface, which may develop central scarring and healing (pseudoepitheliomatous hyperplasia).
• Black dots on the surface of the lesion, representing the extrusion of fungal elements (muriform cells or sclerotic bodies) through the epidermis.
• Enlargement of the affected limb due to lymphedema and tissue fibrosis (elephantiasis).
• Spread of the infection to new sites by autoinoculation or lymphatic dissemination, resulting in satellite lesions around the primary lesion or distant lesions on other body parts.
• Itching (pruritus) and pain in the affected area, which may be mild or severe depending on the extent and duration of the infection.
• Secondary bacterial infection, which may cause suppuration, ulceration, and malodor of the lesion.
• Squamous cell carcinoma, which may develop in longstanding lesions as a rare complication.

The clinical features of chromoblastomycosis may vary depending on the causative agent, the host immune response, and the environmental factors. The infection may mimic other skin conditions, such as other fungal infections (eg, sporotrichosis, mycetoma), bacterial infections (eg, tuberculosis, leprosy), protozoal infections (eg, leishmaniasis), or noninfectious diseases (eg, psoriasis, lupus erythematosus). Therefore, a definitive diagnosis requires laboratory confirmation by direct examination and culture of clinical specimens.

Chromoblastomycosis is a chronic fungal infection that mainly affects people who have frequent contact with soil, decomposing vegetation, or organic matter. The infection occurs when the skin is injured by thorns, splinters, or other sharp objects that carry the fungal spores. Therefore, some of the risk factors for chromoblastomycosis are:

• Occupation and environmental exposure: People who work or live in rural areas, especially in tropical and subtropical regions, are more likely to get chromoblastomycosis. This includes farmers, laborers, coconut harvesters, lumberjacks, and vendors of farm products .
• Lack of protective clothing: People who do not wear shoes, gloves, or garments that cover their skin are more exposed to the fungal spores and the risk of skin trauma.
• Poor nutrition and hygiene: People who have low nutritional status or poor hygienic habits may have a weaker immune system and a higher susceptibility to chromoblastomycosis.
• Immunocompromised status: Although chromoblastomycosis is not associated with specific immunocompromised diseases or treatments, people who have a reduced immune function may have a more severe or refractory infection .

Chromoblastomycosis is considered a neglected tropical disease by the World Health Organization (WHO) and affects mainly poor and marginalized populations. Prevention and control measures include wearing protective clothing, avoiding skin trauma, improving nutrition and hygiene, and seeking early diagnosis and treatment.

Dematiaceous fungi are a large and diverse group of molds that can cause various types of skin and systemic infections in humans and animals. They are characterized by the presence of melanin in their cell walls, which gives them a dark brown to black color. Melanin is a complex polymer that can protect the fungi from environmental stressors such as UV radiation, oxidative damage, temperature fluctuations, and host immune responses. Melanin is also involved in the formation of sclerotic bodies or muriform cells, which are thick-walled, multiseptate structures that are resistant to phagocytosis and antifungal drugs. Sclerotic bodies are the hallmark of chromoblastomycosis, a chronic subcutaneous infection caused by several dematiaceous fungi.

The pathogenic mechanisms by which dematiaceous fungi cause disease are not fully understood, especially in immunocompetent individuals. However, some factors that may contribute to their virulence include:

• Adhesion and invasion: Dematiaceous fungi can adhere to and invade various host tissues, such as skin, mucosa, blood vessels, and brain. They can produce extracellular enzymes, such as proteases, lipases, and phospholipases, that degrade host cell membranes and extracellular matrix. They can also modulate host cell signaling pathways and induce apoptosis or necrosis of host cells.
• Immune evasion and modulation: Dematiaceous fungi can evade or modulate the host immune response by various mechanisms, such as masking their antigens with melanin, inhibiting phagosome maturation and acidification, suppressing cytokine production and inflammatory responses, inducing immunosuppressive molecules such as IL-10 and TGF-beta, and manipulating T cell differentiation and polarization.
• Biofilm formation: Dematiaceous fungi can form biofilms on various surfaces, such as medical devices, catheters, implants, and contact lenses. Biofilms are complex communities of microorganisms embedded in a matrix of extracellular polymeric substances. Biofilms can enhance the survival and persistence of the fungi by providing protection from host defenses, antifungal drugs, and environmental stressors. Biofilms can also facilitate the dissemination of the fungi to other sites of infection.
• Genetic diversity and adaptation: Dematiaceous fungi have a high degree of genetic diversity and plasticity, which allows them to adapt to different environmental conditions and hosts. They can undergo genetic changes such as mutations, recombination, hybridization, horizontal gene transfer, and gene duplication or deletion. They can also express different phenotypes depending on the environmental cues, such as temperature, pH, oxygen levels, nutrient availability, and host factors.

Chromoblastomycosis (Chromomycosis) is a chronic fungal infection that manifests as various types of skin lesions on the exposed parts of the body, especially the limbs. The infection usually begins at the site of inoculation by a minor trauma from contaminated vegetative material, such as a thorn or a splinter. The clinical features of chromoblastomycosis depend on the duration, extent, and severity of the infection, as well as the immune status of the host.

The following are some of the common clinical features of chromoblastomycosis:

• Nodular lesions: These are moderately elevated, fairly soft, dull to pink or violaceous nodules with a smooth, verrucous, or scaly surface. They may grow slowly and become tumorous over time. They are often found on the lower extremities .
• Tumoral lesions: These are tumor-like masses that are prominent, papillomatous, sometimes lobulated, and covered partially or entirely with epidermal debris and crusts. They have a "cauliflower-like" appearance and may ulcerate and bleed. They are more exuberant and occur mainly on the lower extremities .
• Cicatricial lesions: These are non-elevated lesions that have an enlarged peripheral extension and atrophic scarring. They have a central healing with an annular, arciform, or serpiginous outline. They can occur extensively on various parts of the body .
• Plaque lesions: These are slightly elevated lesions that occur in various sizes and shapes with infiltration. They are reddish to violaceous in color with a scaly surface and may have marked lines of cleavage. They are generally found on the higher parts of the limbs .
• Verrucous lesions: These are outwardly hyperkeratotic lesions that are warty, dry, and rough. They are commonly found along the border of the foot or hand .
• Elephantiasis: This is a condition of chronic lymphedema that results from the obstruction of lymphatic vessels by inflammatory tissue and fibrosis. It causes swelling and thickening of the skin and subcutaneous tissue, leading to deformity and disability of the affected limb .
• Squamous cell carcinoma: This is a rare complication of long-standing chromoblastomycosis that involves malignant transformation of the epidermis. It presents as an ulcerated or fungating mass that may invade deeper tissues and metastasize .

The lesions of chromoblastomycosis may be asymptomatic or associated with local pain, itching, burning, or discharge. They may also be complicated by secondary bacterial infection, lymphangitis, or osteomyelitis . The infection may spread to new sites by autoinoculation or lymphatic dissemination. The disease may also affect other organs such as the lungs, bones, joints, central nervous system, or eyes in rare cases.

The clinical features of chromoblastomycosis may mimic other infectious or non-infectious skin conditions such as sporotrichosis, mycetoma, leishmaniasis, tuberculosis, leprosy, syphilis, psoriasis, discoid lupus erythematosus, or squamous cell carcinoma . Therefore, a definitive diagnosis requires laboratory confirmation by direct examination or histopathology of skin samples for the presence of characteristic fungal elements called muriform cells (also known as sclerotic bodies or Medlar bodies) .

The diagnosis of chromoblastomycosis (chromomycosis) is based on the following methods:

• Clinical diagnosis: The appearance of the lesions, especially the late-stage ones, can be suggestive of chromoblastomycosis. However, early lesions may be confused with other skin infections, such as dermatophytosis (ringworm) or leishmaniasis. Therefore, clinical diagnosis alone is not sufficient and should be confirmed by laboratory tests .

• Direct examination and microscopy: The most definitive diagnostic method is the identification of the characteristic sclerotic bodies (also called Medlar bodies, muriform cells, or copper pennies) in the clinical samples, such as lesion exudates, skin scrapings, crusts, aspirated debris, and tissue fragments . These are thick-walled, dark-pigmented, round to polyhedral cells with transverse and longitudinal septa, resembling a brick wall . They can be seen by using 20-40% KOH wet mount, hematoxylin-eosin staining, or Fontana-Masson staining for melanin . Calcofluor white dye stain can also be used to visualize the fungal elements.

• Culture: Culture is needed to identify the causative species of dematiaceous fungi, which include Fonsecaea pedrosoi, Phialophora verrucosa, Cladophialophora carrionii, and others . The fungi form brown to black colonies on mycological agar and produce conidia that can be examined by KOH wet mount . However, culture may be difficult, slow, or unreliable for some species .

• Histological examination: Histological examination of tissue samples or biopsies can reveal granulomatous inflammation in the dermis with epithelioid cells and giant cells. The sclerotic bodies can also be seen within the granulomas or extruded through the epidermis .

• Molecular identification: Molecular methods, such as polymerase chain reaction (PCR), can be used to detect and differentiate the causative species of chromoblastomycosis by targeting specific regions of the ribosomal DNA or other genes . This can be useful when culture is negative or inconclusive.

• Immunological examination: Immunological methods, such as enzyme-linked immunosorbent assay (ELISA), can be used to measure the antibody response to the fungal antigens in the serum of patients with chromoblastomycosis . This can be helpful for monitoring the disease activity and treatment response.

Chromoblastomycosis is a chronic fungal infection that is difficult and prolonged to treat. It may require a combination of physical and pharmacological therapies, depending on the extent and severity of the disease. The main goals of treatment are to eradicate the fungal infection, prevent complications such as secondary bacterial infections and squamous cell carcinoma, and improve the quality of life of the patients.

Physical Therapies

Physical therapies aim to remove or destroy the infected tissue by surgical or non-surgical methods. They may be used alone or in combination with antifungal drugs. Some of the physical therapies for chromoblastomycosis are:

• Surgery: Surgical excision of the lesions is an effective method for localized and small lesions. However, it may not be feasible for extensive or multiple lesions, and it may cause scarring and deformity. Surgery may also be combined with skin grafting or flap reconstruction to improve the cosmetic outcome.
• Cryotherapy: Cryotherapy involves freezing the lesions with liquid nitrogen or other cryogens. It is a simple and inexpensive method that can be used for small and superficial lesions. However, it may cause pain, blistering, necrosis, and scarring, and it may not be effective for deep or large lesions.
• Laser therapy: Laser therapy uses high-intensity light beams to vaporize the infected tissue. It is a relatively new and promising method that can be used for small and superficial lesions. It has the advantages of being less invasive, less painful, and more precise than surgery or cryotherapy. However, it may be costly, require specialized equipment and trained personnel, and cause thermal injury or pigmentation changes.
• Photodynamic therapy (PDT): PDT involves applying a photosensitizing agent to the lesions and then exposing them to a specific wavelength of light. The light activates the agent and generates reactive oxygen species that kill the fungal cells. PDT is a novel and experimental method that has shown some efficacy in chromoblastomycosis. It has the advantages of being selective, non-invasive, and less toxic than antifungal drugs. However, it may cause photosensitivity reactions, pain, inflammation, and edema.

Pharmacological Therapies

Pharmacological therapies involve using antifungal drugs to inhibit or kill the fungal cells. They may be used alone or in combination with physical therapies or other antifungal drugs. Some of the pharmacological therapies for chromoblastomycosis are:

• Itraconazole: Itraconazole is an azole antifungal drug that inhibits the synthesis of ergosterol, a component of the fungal cell membrane. It is the most effective and widely used drug for chromoblastomycosis . It is usually given orally at a dose of 200 to 400 mg/day for 6 to 12 months or until clinical and mycological cure. It has the advantages of being well-tolerated, having good oral bioavailability, and having a broad spectrum of activity against dematiaceous fungi. However, it may cause side effects such as nausea, headache, rash, liver toxicity, and drug interactions.
• Terbinafine: Terbinafine is an allylamine antifungal drug that inhibits the synthesis of squalene epoxidase, an enzyme involved in ergosterol biosynthesis. It is the second most frequently used drug for chromoblastomycosis . It is usually given orally at a dose of 250 to 500 mg/day for 6 to 12 months or until clinical and mycological cure. It has the advantages of being well-tolerated, having good oral bioavailability, and having a synergistic effect with itraconazole. However, it may cause side effects such as nausea, headache, rash, liver toxicity, and taste disturbance.
• Other azoles: Other azoles such as posaconazole, voriconazole, and isavuconazole are newer antifungal drugs that have similar mechanisms of action as itraconazole but have different pharmacokinetic and pharmacodynamic properties. They have shown some efficacy in chromoblastomycosis , especially in cases refractory to itraconazole or terbinafine. They are usually given orally at various doses depending on the drug and the patient`s weight. They have the advantages of having better penetration into tissues, having broader spectrum of activity against dematiaceous fungi, and having fewer drug interactions than itraconazole. However, they may cause side effects such as nausea

Chromoblastomycosis is a chronic fungal infection that has shown resistance to some antifungal therapies, such as fluconazole and amphotericin B. Therefore, the use of broad-spectrum therapies, such as itraconazole and terbinafine, are recommended . However, not all patients respond to these drugs, and some may require long-term treatment or combination therapy.

One of the factors that contributes to the antifungal resistance of chromoblastomycosis agents is the presence of melanin in their cell walls. Melanin is a pigment that protects the fungi from oxidative stress, hypochlorite, and hydrolytic enzymes produced by the host immune system. Melanin also interferes with the penetration and action of some antifungal drugs, such as amphotericin B.

Another factor that may influence the antifungal susceptibility of chromoblastomycosis agents is the genetic diversity and heterogeneity of the causative species. Different species and strains may have different mechanisms of resistance or adaptation to antifungal drugs, such as efflux pumps, biofilm formation, or enzymatic degradation.

Therefore, it is important to identify the specific etiologic agent of chromoblastomycosis and to perform in vitro susceptibility testing before initiating antifungal therapy. Based on minimum inhibitory concentrations (MICs), some of the most effective antifungal drugs against chromoblastomycosis agents in vitro are posaconazole, terbinafine, itraconazole, and voriconazole. However, these results may not always correlate with the clinical outcome, and other factors, such as drug pharmacokinetics, host immunity, and drug interactions, should also be considered.

Chromoblastomycosis is a chronic fungal infection that can have serious consequences for the affected individuals, such as physical disability, disfigurement, and increased risk of secondary infections and malignancies. Therefore, prevention and control of this disease are important public health goals, especially in tropical and subtropical regions where it is more prevalent.

However, prevention and control of chromoblastomycosis are challenging due to several factors, such as:

• The ubiquitous presence of the causative fungi in the environment, especially in soil, wood, and decaying plant matter.
• The lack of specific vaccines or prophylactic agents against the infection.
• The difficulty in diagnosing the disease in its early stages, when it may be asymptomatic or oligosymptomatic.
• The refractoriness of the infection to many antifungal drugs and the need for prolonged and expensive treatment.
• The limited access to health care and antifungal therapy in many endemic areas.

Despite these challenges, some measures can be taken to prevent and control chromoblastomycosis, such as:

• Educating the population at risk about the disease, its transmission, clinical manifestations, diagnosis, and treatment options.
• Promoting the use of protective clothing and footwear, especially among agricultural workers and other occupations that involve contact with soil or plant materials that may contain the fungi.
• Avoiding walking barefoot in endemic areas, as this may increase the chance of traumatic inoculation of the fungi through skin abrasions or wounds.
• Seeking medical attention promptly if any suspicious skin lesion appears, especially if it persists or enlarges over time.
• Following the prescribed antifungal therapy regimen strictly and monitoring the response to treatment by clinical, mycological, and histopathological criteria.
• Reporting any cases of chromoblastomycosis to the local health authorities for surveillance and epidemiological purposes.

By implementing these measures, it may be possible to reduce the incidence and prevalence of chromoblastomycosis and improve the quality of life of the affected individuals. However, more research is needed to develop new strategies for prevention and control of this neglected tropical disease.

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