Systemic mycoses

These fungi are not confined to the skin but they cause systemic infections. Clinical spectrum ranges from being asymptomatic to causing life threatening infections. Some cause opportunistic infections in immunocompromised individuals.

Histoplasma capsulatum

It is a dimorphic fungus endemic in Ohio and Mississippi River valleys. Infection is transmitted by inhalation of spores. It is present in soil contaminated by bird droppings and in bat infested caves. Most infections are asymptomatic. It can present with fever, pneumonia like symptoms, skin ulcers and granulomas especially look out for palatal ulcers or disseminated form in AIDS patients with hepatosplenomegaly and lymphadenopathy. For laboratory diagnosis, sputum smears stained by Giemsa or bone marrow and tissue biopsy will show intracellular, budding yeasts in macrophages. Culture will show tuberculate macroconidia and elliptical microconidia with septate hyphae at 25 degree C. Growth at 37 degree C will show cream colonies with budding yeast forms. Past or present infection will give a positive delayed hypersensitivity test. ELISA, CFT and Immunodiffusion test for antibodies and DNA probes to detect fungal nucleic acids can be done.

Blastomyces dermatitidis

This is again a dimorphic fungus endemic in the Great Lakes area, Ohio and Mississippi. Infection occurs by inhalation of spores. It presents clinically as pneumonia like symptoms, fever, chest pain. Disseminated form shows abscess formation, osteomyelitis etc. It may cause skin nodules, ulcers and fistulas following local inoculation due to trauma. The only way you can confidently differentiate from Histoplasmosis is by microscopy which shows thick walled yeast form with “broad-based” budding. Colonies at 37 degree C will be creamy, yeast like while at room temperature will show septate hyphae and pyriform conidia. Yeast forms will be seen on tissue biopsy as well. Nucleic acid detection can be made by DNA probes. CFT, RIA , Immunodiffusion and ELISA can detect antibodies.

Coccidioides immitis

It is endemic in southwestern USA in California, Southern Nevada, Arizona, etc. Coccidioidomycosis is also called Desert Valley fever or Desert Rheumatism or San Joaquin Valley Fever. Infection is caused by the inhalation of arthrospores. Clinically it presents as fever, chronic cough mimicking tuberculosis, myalgia, arthralgias and erythema nodosum. It may disseminate in immunocompromised individuals causing meningitis, osteomyelitis, lymphadenopathy, etc. Diagnosis is done primarily by tissue biopsy which shows characteristic thick walled spherules with endospores. It is a dimorphic fungus. Culture at room temperature will show hyphae and rectangular or barrel shaped arthrospores. Antibody detection is by ELISA, CFT and precipitation tests. A delayed hypersensitivity skin test to fungal antigen coccidioidin becomes positive during the infection but remains positive for a few more years after clinical cure.

Paracoccidioides brasiliensis

It is a dimorphic fungus endemic in South American continent. Infection is acquired by the inhalation of spores. It presents as fever, cough, lymphadenopathy, splenomegaly, oral and buccal ulcers and hepatomegaly. Adrenal glands may be involved in disseminated disease. Laboratory diagnosis is by microscopy and biopsy showing typical “mariner’s wheel” appearance due to multiple cells budding from a single yeast cell. Culture can be done. Serology by CFT, ELISA, CIEP and precipitation tests can be used to confirm the diagnosis.

Cryptococcosis

Cryptococcus neoformans is most pathogenic to humans among the members of the genus Cryptococcus. Cryptococcus gattii is also seen in some cases. Exposure to pigeon droppings, old buildings etc. carries high risk of infection from inhalation. Infections are seen in immunocompetent as well as immunodeficient individuals. It is the AIDS-defining illness for 60-70% of HIV-infected patients. Disease presents as fever, cough, chest pain in the pulmonary form and fever, neck stiffness, headache, vomiting, impaired consciousness, seizures etc in cryptococcal meningitis. Inoculation into skin can cause papules and subcutaneous nodules. Diagnosis is done by India Ink preparation of csf which shows the yeast cell surrounded by a halo due to the capsule. On histopathology specimens, H and E and PAS , mucicarmine stains will show budding yeast cells. It grows as mucoid colonies in culture. It is urease positive. A rapid test on csf based on latex agglutination can be done to detect the capsular antigen.

A photomicrograph of C. neoformans stained with India ink.

Candidiasis

Candida are commensal organisms in the upper respiratory, gastrointestinal and female genital tracts. It causes skin and subcutaneous tissue infections and intravenous catheter associated infections. Diabetes Mellitus, antibiotic therapy, moist skin folds, obesity and immunodeficiencies predispose to Candidiasis. The source of infection is often endogenous. Candida albicans is the most commonly implicated species.

Clinical features: It has varied manifestations. Commonly presents as oral thrush with white patches in the oral cavity; vulvovaginitis with curd like, white discharge, itching and burning; intertrigo which is an inflamed lesion of skin folds ; diaper rash especially if diapers are not changed frequently; esophagitis; paronychia which is infection of the nail fold; onychomycosis and systemic infections like endocarditis, UTI, pneumonia, meningitis, arthritis and endophthalmitis. Chronic mucocutaneous candidiasis is an interesting condition in which lesions are seen only on the skin and mucosa. It results from deficient cell mediated immunity.

Laboratory diagnosis of Candidiasis: Diagnosis is made by demonstration of budding yeast cells and pseudohyphae in samples such as sputum, csf, swabs , biopsy etc. They are Gram positive. Presence of pseudohyphae indicates tissue invasion and active infection. Culture shows creamy colonies. Germ tube test is positive in C.albicans. ELISA, latex agglutination, Immunoblot, CIEP can be used for antibody detection. PCR and DNA probes can help in the diagnosis of systemic infections.

Stained using the Gram-stain technique, this photomicrograph revealed these Candida albicans fungal spores, that had been suspended in an animal serum specimen, and allowed to grow, giving rise to filamentous germ tubes.