In these common soil organisms (also called dematiaceous fungi), melanin causes the hyphae and/or conidia to be darkly pigmented (brown/black). The term phaeohyphomycosis is used to describe any infection with a pigmented mold. This definition encompasses two specific syndromes—eumycetoma and chromoblastomycosis—as well as all other types of infections caused by these organisms. It is important to note that eumycetomas can be caused by hyaline molds as well as brown-black molds and that only about half of all mycetomas are due to fungi. Actinomycetes cause the remainder (Chap. 162). Most of these fungi cause localized subcutaneous infections after direct inoculation, but disseminated infection and serious visceral focal infections also occur, especially in immunocompromised patients.
A large number of pigmented molds can cause human infection. All are found in the soil or on plants, and some cause economically important plant diseases. The most common cause of eumycetoma is Madurella species, but hyaline molds such as Scedosporium species also cause this syndrome. Fonsecaea and Cladophialophora species are responsible for most cases of chromoblastomycosis. Disseminated infection and focal visceral infections are caused by a variety of dematiaceous fungi; Alternaria, Exophiala, Curvularia, and Wangiella species are among the more common molds reported to cause human infection.
Epidemiology and Pathogenesis
Most infections, including all cases of eumycetoma and chromoblastomycosis, are acquired by inoculation through the skin. These two syndromes are seen almost entirely in tropical and subtropical areas and occur mostly in rural laborers who are frequently exposed to the organisms. Inhalation into the upper or lower respiratory tract leads to localized infection of sinuses and, in immunocompromised patients, to pneumonia and sometimes hematogenous dissemination. Several organisms, specifically Cladophialophora bantiana and Rhinocladiella mackensiei, are neurotropic and likely to cause CNS infection.
Eumycetoma is a chronic subcutaneous and cutaneous infection that usually occurs on the lower extremities and that is characterized by swelling, development of sinus tracts, and the appearance of grains that are actually colonies of fungi discharged from the sinus tract. As the infection progresses, adjacent fascia and bony structures become involved. The disease is indolent and disfiguring, progressing slowly over years. Complications include fractures of infected bone and bacterial superinfections.
Chromoblastomycosis is an indolent subcutaneous infection characterized by nodular, verrucous, or plaque-like painless lesions that occur predominantly on the lower extremities and grow slowly over months or years. There is hardly ever extension to adjacent structures, as is seen with eumycetoma. Long-term consequences include bacterial superinfection, chronic lymphedema, and (rarely) the development of squamous cell carcinoma.
Dematiaceous molds are the most common cause of allergic fungal sinusitis and a less common cause of invasive fungal sinusitis. Keratitis occurs with corneal inoculation. Many patients, including some who are immunocompromised, develop only localized infection manifested by cyst-like subcutaneous lesions at the site of inoculation. Other immunocompromised patients have pneumonia and disseminated infection, including CNS involvement, and are quite ill.
The specific diagnosis of infection with a pigmented mold is established by growth of the organism in culture. However, in eumycetoma, a tentative clinical diagnosis can be made when a patient presents with a lesion characterized by swelling, sinus tracts, and grains. Histopathologic examination and culture are necessary to ensure that the etiologic agent is a mold and not an actinomycete. In chromoblastomycosis, the diagnosis rests on the histologic demonstration of sclerotic bodies in the tissues; culture merely establishes which pigmented mold is causing the infection. Sclerotic bodies are dark brown, thick-walled, septate fungal forms that resemble large yeasts and define the syndrome. For disseminated infections and nonsubcutaneous focal infections, growth of the organism is essential to differentiate infection with a hyaline mold (e.g., Aspergillus or Fusarium) from that due to a pigmented mold. No serologic or non-culture-based methods are currently available to aid in the diagnosis of phaeohyphomycoses.
Treatment of eumycetoma and chromoblastomycosis involves both surgical extirpation of the lesion and use of antifungal agents. Surgical removal of the lesions of both eumycetoma and chromoblastomycosis is most effective if performed before extensive spread has occurred. In chromoblastomycosis, cryosurgery and laser therapy have been used with variable success. The antifungal agents of choice are itraconazole, voriconazole, and posaconazole. The most experience has accrued with itraconazole; there is less experience with the newer azoles, which are active in vitro and have been reported to be effective in a few patients. Flucytosine and terbinafine also have been used to treat chromoblastomycosis.
Disseminated and focal visceral infections are treated with the appropriate antifungal agent; the choice of agent is based on the location and extent of the infection, in vitro testing, and clinical experience with the specific infecting organism. AmB is not effective against many of these organisms but has been used successfully against others. Again, the most experience has been obtained with itraconazole, which is effective for localized infections. Voriconazole and posaconazole are likely to play an increasing role in therapy for both localized and disseminated infections. Chromoblastomycosis and eumycetoma are chronic indolent infections that are difficult to cure without surgical excision, but these are not life-threatening diseases. Disseminated or focal visceral infections with pigmented molds in immunocompromised patients are associated with high mortality rates unless immunosuppression can be diminished and effective antifungal agents prescribed promptly.