Fungal infections are often classified as either
Opportunistic infections are those that develop mainly in immunocompromised hosts.
Primary infections can develop in immunocompetent hosts.
Fungal infections can be
Local fungal infections typically involve the skin (see Fungal Skin Infections Overview of Dermatophytoses Dermatophytoses are fungal infections of keratin in the skin and nails (nail infection is called tinea unguium or onychomycosis). Symptoms and signs vary by site of infection. Diagnosis is by... read more ), mouth (causing stomatitis Stomatitis Oral inflammation and ulcers, known as stomatitis, may be mild and localized or severe and widespread. They are invariably painful. (See also Evaluation of the Dental Patient and Gingivitis... read more ), and/or vagina (causing candidal vaginitis Candidal Vaginitis Candidal vaginitis is vaginal infection with Candida species, usually C. albicans. (See also Overview of Vaginitis.) Most fungal vaginitis is caused by C. albicans (candidiasis), which colonizes... read more ) and may occur in normal or immunocompromised hosts.
Systemic fungal infections can affect the skin and organs such as the lungs, eyes, liver, and brain and typically occur in immunocompromised hosts (see Opportunistic fungal infections Opportunistic fungal infections Fungal infections are often classified as either Opportunistic Primary Opportunistic infections are those that develop mainly in immunocompromised hosts. Primary infections can develop in immunocompetent... read more ).
(See also Antifungal Drugs Antifungal Drugs Drugs for systemic antifungal treatment include the following (see Table: Some Drugs for Systemic Fungal Infections): Amphotericin B (and its lipid formulations) Various azole derivatives (fluconazole... read more .)
Many fungi are opportunists and are usually not pathogenic except in an immunocompromised host. Causes of immunocompromise include AIDS, azotemia, diabetes mellitus, lymphoma, leukemia, other hematologic cancers, burns, and therapy with corticosteroids, immunosuppressants, or antimetabolites. Patients who spend more than several days in an intensive care unit can become compromised because of medical procedures, underlying disorders, and/or undernutrition.
Typical opportunistic systemic fungal infections (mycoses) include
Systemic mycoses affecting severely immunocompromised patients often manifest acutely with rapidly progressive pneumonia, fungemia, or manifestations of extrapulmonary dissemination.
Primary fungal infections usually result from inhalation of fungal spores, which can cause a localized pneumonia as the primary manifestation of infection.
In immunocompetent patients, systemic mycoses typically have a chronic course; disseminated mycoses with pneumonia and septicemia are rare and, if lung lesions develop, usually progress slowly. Months may elapse before medical attention is sought or a diagnosis is made. Symptoms are rarely intense in such chronic mycoses, but fever, chills, night sweats, anorexia, weight loss, malaise, and depression may occur. Various organs may be infected, causing symptoms and dysfunction.
Primary fungal infections may have a characteristic geographic distribution, which is especially true for the endemic mycoses caused by certain dimorphic fungi. For example,
Coccidioidomycosis Coccidioidomycosis Coccidioidomycosis is a pulmonary or hematogenously spread disseminated disease caused by the fungi Coccidioides immitis and C. posadasii; it usually occurs as an acute benign asymptomatic or... read more : Confined primarily to the southwestern US, Washington, northern Mexico, and Central and South America
Histoplasmosis Histoplasmosis Histoplasmosis is a pulmonary and hematogenous disease caused by Histoplasma capsulatum; it is often chronic and usually follows an asymptomatic primary infection. Symptoms are those of pneumonia... read more : Occurring primarily in the eastern and Midwestern US and parts of Central and South America, Africa, Asia, and Australia
Paracoccidioidomycosis Paracoccidioidomycosis Paracoccidioidomycosis is progressive mycosis of the lungs, skin, mucous membranes, lymph nodes, and internal organs caused by Paracoccidioides brasiliensis. Symptoms are skin ulcers, adenitis... read more (formerly, South American blastomycosis): Confined to that continent
However, travelers can manifest disease any time after returning from endemic areas.
When fungi disseminate from a primary focus in the lung, the manifestations may be characteristic, as for the following:
Progressive disseminated histoplasmosis: Generalized involvement of the reticuloendothelial system (liver, spleen, bone marrow)
Blastomycosis: Single or multiple skin lesions or involvement of the central nervous system, bone, or prostate
Coccidioidomycosis: Bone and joint infections, skin lesions, and meningitis
If clinicians suspect an acute or a chronic primary fungal infection, they should obtain a detailed travel and residential history to determine whether patients may have been exposed to certain endemic mycoses, perhaps years previously.
Pulmonary fungal infections must be distinguished from tumors and chronic pneumonias caused by nonfungal organisms such as mycobacteria Nontuberculous Mycobacterial Infections Mycobacteria other than the tubercle bacillus sometimes infect humans. These organisms (called nontuberculous mycobacteria) are commonly present in soil and water and are much less virulent... read more (including Mycobacterium tuberculosis). Specimens are obtained for fungal and mycobacterial culture and histopathology. Sputum samples may be adequate, but occasionally bronchoalveolar lavage, transthoracic needle biopsy, or even surgery may be required to obtain an acceptable specimen.
Fungi that cause primary systemic infections are readily recognized by their histopathologic appearance. However, identifying the specific fungus may be difficult and usually requires fungal culture or molecular diagnostics. The clinical significance of positive sputum cultures may be unclear if they show commensal organisms (eg, Candida albicans) or fungi ubiquitous in the environment (eg, Aspergillus species). Therefore, other evidence (eg, host factors such as immunosuppression, serologic evidence, tissue invasion seen on biopsy, radiologic findings) may be required to help establish a diagnosis.
Serologic tests may be used to check for many systemic mycoses if culture and histopathology are unavailable or unrevealing, although few provide definitive diagnoses. Particularly useful tests include the following:
Measurement of organism-specific antigens, most notably from Cryptococcus neoformans, Histoplasma capsulatum, and Aspergillus species (occasional cross-reactivity with other fungi has been noted with each of these serologic tests)
Serum beta-glucan, which is often positive in invasive candidiasis and aspergillus as well as Pneumocystis jirovecii infections
Complement fixation assays and newer enzyme immunoassays for anticoccidioidal antibodies, which are satisfactorily specific and do not require proof of rising levels (high titers confirm the diagnosis and indicate high risk of extrapulmonary dissemination)
Most other tests for antifungal antibodies have low sensitivity, specificity, or both and, because measurement of acute and convalescent titers is required, cannot be used to guide initial therapy.
Molecular diagnostics are emerging useful tools for identifying molecular components of certain fungal infections. Tests approved by the U.S. Food and Drug Administration include DNA probes that use culture specimens to identify Histoplasma, Blastomyces, and Coccidioides and polymerase chain reaction or DNA hybridization tests that use blood culture specimens to identify Candida. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF Mass spectroscopy Once an organism has been isolated by culture, it must be identified. Identification is important in determining management (eg, drug treatment, isolation measures). Non-nucleic acid–based identification... read more ) mass spectrometry done on culture specimens also can be done to identify multiple yeasts, including Candida species.