Mycetoma and Dematiaceous Fungal Infections

Definition

Dematiaceous fungi represent a large group of fungal organisms characterized by the presence of abundant melanin in the cell wall. This melanin gives rise to a brown-black coloration on artificial culture media and in histopathologic specimens. A related term, phaeohyphomycosis, refers broadly to infection by these pigmented fungi. The two terms are often used interchangeably. Dematiaceous fungal infections generally fall into three broad categories: mycetoma (e.g., Madura foot), chromomycosis (also known as chromoblastomycosis), and phaeohyphomycosis. ^,

Epidemiology

Dematiaceous fungi are found in the environment worldwide. Allergic fungal sinusitis associated with dematiaceous fungi appears to be more common in the southern United States. Chronic infections of the lower extremities are more commonly seen in men and in tropical areas. Chromomycoses are more prevalent in rural populations in the tropics and are hyperendemic in certain geographic areas such as Madagascar, India, Brazil, and other poorer countries in Africa and South America. Cutaneous infections usually occur as a result of minor skin trauma and direct inoculation of the organism.

Phaeohyphomycosis is an important emerging fungal infection in medically advanced regions, particularly among immunocompromised patients such as recipients of solid organ and hematopoietic stem cell transplants, patients with prolonged neutropenia, and other immunocompromised individuals. Risk factors for extracutaneous infection include intravenous drug use, chronic sinusitis, freshwater immersion, and chronic immunosuppression. Phaeohyphomycosis is reported in human immunodeficiency virus (HIV)-infected patients but is far less common than other opportunistic fungi. Extracutaneous invasive disease can also occur in otherwise normal patients but is much less common. Subtle host immune abnormalities, including CARD -9 mutations and other disorders associated with T _H 17 deficiency, have been identified in a subset of these previously “normal” individuals.

Dematiaceous fungal infections can be seen following invasive procedures in health care settings. In the United States, a striking example was an epidemic of fungal meningitis, epidural abscess, sacroiliitis, vertebral osteomyelitis, discitis, and peripheral arthritis that involved over 750 persons and was caused by Exserohilum rostratum following injection of contaminated methylprednisolone acetate from a single compounding pharmacy. Previous reports of infection caused by Exophiala species following contaminated steroid injections, infected breast implants, other prosthetic materials, and, rarely, contaminated intravascular catheters and intravenous fluids underscore the importance of these organisms as potential health care–associated pathogens.

Mycetoma has a global distribution ( E-Fig. 314-1 ), but it occurs primarily in the tropical zones. The disorder is quite prevalent in India, Latin America, the Middle East, and sub-Saharan Africa (the “mycetoma belt”). Sudan has a particularly high burden of mycetoma. Indigenously acquired mycetoma is sporadic in North America and Europe. The relative frequency of actinomycetoma and eumycetoma differs among geographic areas. Eumycetoma is more common in India and Africa, whereas actinomycetoma is more common in Central and South America. The causative agents of mycetoma differ in their geographic distribution. For example, Scedosporium apiospermum is the most common agent of mycetoma in North America, and Actinomadura and Nocardia species are predominant in Central and South America. Leptosphaeria senegalensis and Madurella mycetomatis are predominant in sub-Saharan Africa and India.

The ratio of male to female patients with mycetoma is 5 : 1. The disease is typically seen in rural areas and in persons susceptible to local trauma and contamination from soil. Hence, farmers, gardeners, woodcutters, herders, and people who work outside while barefoot are more susceptible to this infection.

Pathobiology

Most cases of chromomycosis are caused by three species: Fonsecaea pedrosoi, Cladosporium carrionii , and Phialophora verrucosa . The distinctive histologic appearance is characterized by the presence of thick-walled, dark brown bodies known as sclerotic cells or copper pennies , which represent individual organisms and may be seen in clusters or as single cells. The etiologic fungi causing chromomycosis are indistinguishable on histologic examination of tissue.

Mycetoma is caused by two groups of organisms: (1) the filamentous aerobic actinomycetes (actinomycetoma) and (2) a wide range of saprophytic soil and woody plant fungi (eumycetoma). Eumycetoma accounts for about 50% of cases of mycetoma. A variety of Nocardia ( Chapter 306 ) species (e.g., Nocardia brasiliensis, Nocardia asteroides ), Actinomadura species (e.g., Actinomadura pelletieri, Actinomadura madurae ), and Streptomyces species (e.g., Streptomyces somaliensis ) cause actinomycetoma. Most cases of eumycetoma are due to Madurella species (e.g., Madurella mycetomatis causes 70% of all cases of eumycetoma worldwide). Other causes of eumycetoma include some nondematiaceous fungi such as Fusarium species, Acremonium species, Scedosporium apiospermum, and several phaeohyphomycetes, including Exophiala and Curvularia species. Eumycetoma is further characterized on the basis of the color of the granular drainage: white- to yellow-grain mycetomas (white piedra) are typically caused by hyalohyphomycetes (e.g., S. apiospermum, Fusarium species, Acremonium species), and black-grain eumycetomas are caused by Madurella species and other less common fungi.

Local trauma (e.g., wood splinters), introduces a mycetoma-causative organism into the skin and subcutaneous tissues, initiates a chain of events that leads to chronic, suppurative granulomatous inflammation, tumefaction, formation of multiple fistulous tracts and sinuses, deep abscesses, fibrosis, and scar formation. Infection can extend to adjacent connective tissue across the lines of least resistance (fascia) and ultimately to bones, muscles, nerves, and tendon sheaths, thereby leading to gross anatomic distortion of the affected site.

The genetics and immunopathogenesis of mycetoma are not well defined, but it appears that there are differences in host susceptibility as some infected persons have impaired or delayed hypersensitivity reactions or polymorphisms in genes encoding for chemokines (e.g., CCL50) and cytokines (e.g., interleukin-10). Mycetoma does not appear to be more common in immunocompromised hosts.

Clinical Manifestations