Table 3.

Clinical manifestations of endemic mycoses and risk factors for disseminated disease.

	Asymptomatic infections	Sites of initial infection	Distant spread/disseminated disease	Conditions predisposing to disseminated disease
Coccidioidomycosis	Asymptomatic infections in majority of immunocompetent individuals	Pneumonia, often as mild respiratory illness Rarely primary cutaneous lesions at the site of inoculation due to injury	Fungemia, lymphadenopathy, skin lesions (in the vicinity of infected lymph nodes manifesting as abscesses, ulcers, gummata, retracting scars), osteoarticular involvement, meningitis	HIV infection PID Patients on anti-TNF-alpha monoclonal antibodies Chemotherapy, organ transplant and HSCT, immunosuppressants Diabetes mellitus, cardiopulmonary disease, pregnancy Higher risk of dissemination in African-American and Filipino
Histoplasmosis	Mostly acquired during childhood as asymptomatic infection	Most are self-limiting Acute pulmonary histoplasmosis: fever, cough, dyspnea, enlarged mediastinal, or hilar lymph nodes Chronic pulmonary histoplasmosis: cavitating lung lesions Rarely primary cutaneous lesions by injury—chancre, lymphangitis, nodular gummata	Fungemia, hepatomegaly, splenomegaly, bone marrow involvement, pancytopenia, reactive hemophagocytosis, oropharyngeal ulcers, gastrointestinal bleeding, endocarditis, skin lesions (molluscum-like papules, nodular/gummatous lesions), meningeal involvement, adrenal (Addison’s disease)	HIV infection PID Patients on anti-TNF-alpha monoclonal antibodies Chemotherapy, organ transplant, and HSCT, immunosuppressants
Paracoccidioidomycosis	Asymptomatic infections in majority of immunocompetent individuals	Juvenile form: generalized lymphadenopathy, hepatosplenomegaly, lesions in the skin, oral and intestinal mucosa, bone involvement Chronic (“adult”) form: pneumonia, mucosal lesions in the oropharyngeal or nasal region, palatal ulceration extending to the gums and tongue	Involvement of the digestive tract, pancreas and adrenal glands; hepatomegaly, splenomegaly	HIV infection PID
Blastomycosis	Asymptomatic infections in majority of immunocompetent individuals	Pneumonia Rarely primary skin involvement at the site of inoculation due to injury, manifesting as lymphangitis, ulcers, nodules, verruca	Skin involvement (nodules, gummata, abscesses, ulcers)	Uncommon association with acquired immunodeficiencies; no case of PID identified in individuals with blastomycosis
Talaromyces marneffei infection	Asymptomatic infections in majority of immunocompetent individuals	Localized skin disease due to direct inoculation Lymphadenitis Pneumonia	Fungemia, pneumonia, hepatomegaly, splenomegaly, lymphadenopathy, bone marrow involvement, osteoarticular involvement, cutaneous lesions, neurological manifestations	HIV infection PID Individuals with autoantibodies against IFN-gamma Splenectomy, diabetes mellitus, autoimmune disease Chemotherapy, organ transplant and HSCT, immunosuppressants Novel anti-cancer target therapies, e.g., anti-CD20 monoclonal antibodies, kinase inhibitors
Sporotrichosis	Most cases are acquired through traumatic implantations, often with spontaneous resolution	Skin infections may progress into chronic cutaneous, subcutaneous, or deeper infections involving the lymphatics, fascia, muscles, cartilage and bones	Occasional cases of pulmonary or disseminated disease: multiple skin lesions at non-contiguous sites, mucosal (nasal, oral, conjunctival), osteoarticular, pulmonary and meningeal involvement	HIV infection PID Chemotherapy, organ transplant and HSCT, immunosuppressants Diabetes mellitus, alcoholism, cirrhosis, malnutrition

HIV, human immunodeficiency virus; HSCT, hematopoietic stem cell transplant; IFN, interferon; TNF, tumor necrosis factor; PID, primary immunodeficiencies.