Chromoblastomycosis

Chromoblastomycosis ICD-10-CM B43.9

Are You Confident of the Diagnosis?

• What you should be alert for in the history

A history of transcutaneous trauma with organic matter, such as rotting wood and soil, as well as plant thorns and debris is typical. Occupation often plays a role, with the majority of lesions observed on the extremities of outdoor rural workers, typically barefoot, such as agriculturalists, labourers, and individuals engaged in forest or bush clearance. Less frequently, animal-associated trauma, such as a horse buck cock’s spine and insect bite or sting, is identified as the portal of entry.

The initial lesion appears at the inoculation site after an uncertain incubation period and presents as a skin-colored macule. The lesion later evolves into a pink papule with a raised smooth surface that gradually increases in size over a few weeks before becoming scaly. The initial skin lesions can then grow and evolve into several different clinical forms including nodular, tumoral (cauliflower-like), verrucous, or those with a scar-like appearance. More than one type of clinical variant can be observed in the same patient. Lower limbs are the most commonly affected areas. The progression of the disease is especially slow and asymptomatic, which may delay the seeking of medical treatment for years or decades.

• Characteristic findings on physical examination

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The initial lesion is a single skin-colored papule or nodule with scaling at the site of the inoculation; occasionally, the early lesions resemble a dermatophyte infection with a dull red or violet color. The lesions may have different appearances: nodular, tumoral, verrucous, cicatricial, plaques, or all of these. The most common presentation is tumoral (cauliflower-like).

After the initial nodule, new nodules and verrucous plaques appear, usually after several months or years, with islands or normal skin between them. With time, the plaques become large with a cauliflower aspect (large vegetations) and the characteristic “black dots” of hemopurulent material that bleed easily due to the fragile granulation tissue (Figure 1, Figure 2, Figure 3).

Figure 1.

Figure 2.

Figure 3.

Lesions can reach 10-20 cm in diameter, and as lesions extend they leave areas of sclerotic or keloidal scarring. No systemic symptoms are described. While lower limbs are the most commonly affected areas, infection in the upper limbs, ear pinna, buttocks, and nose have been reported in the literature.

Although initially asymptomatic, over time, itching becomes the predominant symptom of the disease which can be accompanied by local pain in moderate to severe disease. Due to pruritus, satellite lesions or peripheral expansion of the primary site may develop by autoinoculation. Contiguous lymphatic spread may also occur, as well as lymphatic compromise, which can lead to elephantiasis. Bacterial superinfections are common and occur in over 60% of patients according to some studies. In severe cases, lymphedema and ankylosis occur which may alter the clinical appearance. The disease, however, typically remains confined to the subcutaneous fat and does not involve the underlying muscle or bone. In severe cases and in the immunocompromised, however, the disease may involve underlying tissues and non-invasive squamous cell carcinomas may arise.

• Expected results of diagnostic studies

The diagnosis of chromoblastomycosis relies on the clinical presentation and on the identification of the fungi in the tissue. To confirm a clinical diagnosis, a direct microscopy of a scraping taken from the black dots visible on the surface of the skin can be done. The black dots represent transepidermal elimination of fungi. The direct examination of the black dots in 10% potassium hydroxide will demonstrate thick-wall, multiseptae, brown sclerotic cells that are pathognomonic of chromoblastomycosis. These cells are also known as “copper pennies,” “Medlar bodies,” or “muriform cells,” and are present irrespective of the causative species.

Due to the slow-growth and the poor morphologic differentiation of these fungal species, culture is commonly inconclusive.

Histopathologic examination shows a granulomatous process and marked epithelial hyperplasia with transepithelial elimination and the presence of muriform cells (dark-wall polyhedral structures). Polymerase chain reaction (PCR) has been developed for the identification of Fosecaea spp. and Cladophialophora carrionii. Serologic tests such as ELISA can be useful in the evaluation of the therapeutic response, but like PCR it is not available in most endemic settings.

• Diagnosis confirmation

The differential diagnosis of the verrucous lesions should include the following entities:

• Verrucous leishmaniasis has a warty appearance and is usually seen in the extremities.

• Verrucous tuberculosis is an exogenous infection on the skin due to Mycobacterium tuberculosis. It presents as a single verrucous plaque with an inflammatory border showing slow peripheral extension.

• Sporotrichosis presents as a subcutaneous nodule that ulcerates. It is asymptomatic and is more commonly located at the upper limbs and face. Lymphadenopathy develops in a cordlike pattern and cultures are essential to confirm the diagnosis.

• Verrucous carcinoma may present as cauliflower-like papillomas with a pebbly surface that extend and coalesce over large areas; it usually involves the oral cavity, larynx, esophagus, and genitalia.

• Paracoccidiomycosis is a pulmonary infection with mucocutaneous involvement. Lesions are most often localized on the centrofacial area.

• Lobomycosis commonly affects the pinna of the ear. The lesions are well-defined and lobulated and typically look like a keloid over keloids. The diagnosis is confirmed by direct microscopy and the use of Grocott-Gomori methenamine-silver nitrate.

Who is at Risk for Developing this Disease?

Chromoblastomycosis is a worldwide disease but occurs mostly in tropical and subtropical areas of Africa, Asia, and South America. It is an endemic disease in the tropics, with particular foci in Madagascar, Brazil, India, southern China, Venezuela, Colombia, Mexico, and the Dominican Republic.

This infection is also considered an occupational disease in many tropical and temperate countries. It is observed in rural workers (especially in those that do not wear shoes), and in people engaged in forest or bush clearance, which leads to lower limb involvement after trauma. It is more common in males 30-50 years of age engaged in agriculture (70% of cases) and in lower socioeconomic classes.

What is the Cause of the Disease?

• Etiology

The fungal species identified as the etiologic cause of chromoblastomycosis can be considered as black molds with saprobiotic life in organic matter (like rotting wood), plants, flowers, and soil. Five fungi have been associated with chromoblastomycosis.

The most common pathogen is Fonsecaea pedrosoi in areas with high pluviometric index. F. pedrosoi is the only species isolated in tropical areas, such as the evergreen forest in the Brazilian Amazon or in the northern part of Madagascar, and is very prevalent in zones such as southern Brazil, Uruguay, and northern Argentina. Phialophora verrucosa is the second most prevalent fungus.

Cladosporium carrionii is identified only in spiny desert areas such as northern Venezuela, the Australian bush, southern Madagascar, and Cuba. Cladophialaphora boppii and Fonsecaea compacta have also been described as etiological pathogens but are not common.

• Pathophysiology

Once the etiologic agent gains entrance through the transcutaneous puncture wound, an enabling survival process starts. Depending on the site of infection, evolution time, and individual host response, the primary lesion can present as a nodular, tumorous, verrucous (most common), cicatricial, or plaqulous lesion. The lesions are considered a biologic adaptation which allows the agent to survive in the host tissue environment.

Chromoblastomycosis activates the humoral and the cell-mediated immune system. Specific antibodies such as IgG1, IgM, and IgA have been identified in patients with chromoblastomycosis; however, as with many other chronic fungal infections, the humoral immune response does not seem to be protective.

Polymorphonuclear neutrophils are one of the first lines of defense of cell-mediated immunity. The typical granulomatous reaction associated with the neutrophil-rich purulent abscesses is an unsuccessful phagocytosis of brown, thick-walled fungal cells. Macrophages, identified as giant or epithelioid cells, are highly activated with a subsequent secretion of tumor necrosis factor- alpha. T lymphocytes, especially CD4 cells, are identified at the periphery of the granulomas. A T-helper profile is associated with verrucous and severely extensive forms.

Fibroblast activity is observed, linked to deformation of the adnexae and to a prominent expression of transforming growth factor-ß. An irreversible fibrotic process characterizes the lesions.

Systemic Implications and Complications

The most common complications are: secondary bacterial infections, ulceration, secondary lymphedema, disability of the affected limb, and transformation into squamous cell carcinoma.

Treatment Options

Treatment options are summarized in Table I.