ENDEMIC MYCOSES (DIMORPHIC FUNGI)
Dimorphic fungi exist in discrete environmental niches as molds that produce conidia, which are their infectious form. In tissues and at temperatures of >35°C, the mold converts to the yeast form. Other endemic mycoses—histoplasmosis, coccidioidomycosis, and blastomycosis—are discussed in Chaps. 236, 237, and 238, respectively.
Sporothrix schenckii is a thermally dimorphic fungus that is found worldwide in sphagnum moss, decaying vegetation, and soil.
Epidemiology and Pathogenesis
Sporotrichosis most commonly infects persons who participate in outdoor activities such as landscaping, gardening, and tree farming. Infected animals can transmit S. schenckii to humans. An outbreak of sporotrichosis in Rio de Janeiro that began in 1998 and that has involved >2000 people has been traced to cats, which are highly susceptible to this infection. Sporotrichosis is primarily a localized infection of skin and subcutaneous tissues that follows traumatic inoculation of conidia. Osteoarticular sporotrichosis is uncommon, occurring most often in middle-aged men who abuse alcohol, and pulmonary sporotrichosis occurs almost exclusively in persons with chronic obstructive pulmonary disease who have inhaled the organism from the environment. Dissemination occurs rarely, almost always in markedly immunocompromised patients, especially those with AIDS.
Days or weeks after inoculation, a papule develops at the site and then usually ulcerates but is not very painful. Similar lesions develop sequentially along the lymphatic channels proximal to the original lesion (Fig. 243-1). Some patients develop a fixed cutaneous lesion that can be verrucous or ulcerative and that remains localized without lymphatic extension. The differential diagnosis of lymphocutaneous sporotrichosis includes nocardiosis, tularemia, nontuberculous mycobacterial infection (especially that due to Mycobacterium marinum), and leishmaniasis. Osteoarticular sporotrichosis can present as chronic synovitis or septic arthritis. Pulmonary sporotrichosis must be differentiated from tuberculosis and from other fungal pneumonias. Numerous ulcerated skin lesions, with or without spread to visceral organs (including the central nervous system [CNS]), are characteristic of disseminated sporotrichosis.
Several nodular lesions that developed after a young boy pricked his index finger with a thorn. A culture yielded S. schenckii. (Courtesy of Dr. Angela Restrepo.)
S. schenckii usually grows readily as a mold when material from a cutaneous lesion is incubated at room temperature. Histopathologic examination of biopsy material shows a mixed granulomatous and pyogenic reaction, and tiny oval or cigar-shaped yeasts are sometimes visualized with special stains. Serologic testing is not useful.
Guidelines for the management of the various forms of sporotrichosis have been published by the Infectious Diseases Society of America (Table 243-1). Itraconazole is the drug of choice for lymphocutaneous sporotrichosis. Fluconazole is less effective; voriconazole and posaconazole have not been used for sporotrichosis. Saturated solution of potassium iodide (SSKI) also is effective for lymphocutaneous infection and costs much less than itraconazole. However, SSKI is poorly tolerated because of adverse reactions, including metallic taste, salivary gland swelling, rash, and fever. Terbinafine appears to be effective but has been used in few patients. Treatment for lymphocutaneous sporotrichosis is continued for 2–4 weeks after all lesions have resolved, usually for a total of 3–6 months. Pulmonary and osteoarticular forms of sporotrichosis are treated with itraconazole for at least 1 year. Severe pulmonary infection and disseminated sporotrichosis, including that involving the CNS, are treated initially with amphotericin B (AmB), which is followed by itraconazole after improvement has been noted. Lifelong suppressive therapy with itraconazole is required for AIDS patients. The success rate for treatment of lymphocutaneous sporotrichosis is 90–100%, but other forms of the disease respond poorly to antifungal therapy.
TABLE 243-1Suggested Treatment for Endemic Mycoses ||Download (.pdf) TABLE 243-1Suggested Treatment for Endemic Mycoses
|Disease ||First-Line Therapy ||Alternatives/Comments |
|Cutaneous, lymphocutaneous ||Itraconazole, 200 mg/d until 2–4 weeks after lesions resolve || |
SSKI, increasing dosesa
Terbinafine, 500 mg bid
|Pulmonary, osteoarticular ||Itraconazole, 200 mg bid for 12 months ||Lipid AmBb for severe pulmonary disease until stable; then itraconazole |
|Disseminated, central nervous system ||Lipid AmBb for 4–6 weeks || |
Itraconazole, 200 mg bid after AmB for 12 months
Itraconazole maintenance for AIDS patients: 200 mg/d until CD4+ T cell count has been >200/μL for 12 months
|Chronic (adult form) ||Itraconazole, 100–200 mg/d for 6–12 months ||TMP-SMX, 160/800 mg bid for 12–36 months |
|Acute (juvenile form) ||AmBc until improvement ||Itraconazole, 200 mg bid after AmB for 12 months |
|Mild or moderate ||Itraconazole, 200 mg bid for 12 weeks ||Itraconazole maintenance for AIDS patients: 200 mg/d until CD4+ T cell count has been >100/μL for 6 months |
|Severe ||AmBc until improvement || |
Itraconazole, 200 mg bid after AmB for 12 weeks
Itraconazole maintenance: as for mild or moderate disease
Etiologic Agent, Epidemiology, and Pathogenesis
Paracoccidioides brasiliensis is a thermally dimorphic fungus that is endemic in humid areas of Central and South America, especially in Brazil. A striking male-to-female ratio varies from 14:1 to as high as 70:1 (in rural Brazil). Most patients are middle-aged or elderly men from rural areas. Paracoccidioidomycosis develops after the inhalation of aerosolized conidia encountered in the environment. For most patients, disease rarely develops at the time of the initial infection but appears years later, presumably after reactivation of a latent infection.
Two major syndromes are associated with paracoccidioidomycosis: the acute or juvenile form and the chronic or adult form. The acute form is uncommon, occurs mostly in persons <30 years old, and manifests as disseminated infection of the reticuloendothelial system. Immunocompromised individuals also manifest this type of rapidly progressive disease. The chronic form of paracoccidioidomycosis accounts for ∼90% of cases and predominantly affects older men. The primary manifestation is progressive pulmonary disease, primarily in the lower lobes, with fibrosis. Ulcerative and nodular mucocutaneous lesions in the nares and mouth—another common manifestation of chronic paracoccidioidomycosis—must be differentiated from leishmaniasis (Chap. 251) and squamous cell carcinoma (Chap. 105).
The diagnosis is established by growth of the organism in culture. A presumptive diagnosis can be made by detection of the distinctive thick-walled yeast, with multiple narrow-necked buds attached circumferentially, in purulent material or tissue biopsies.
Itraconazole is the treatment of choice for paracoccidioidomycosis (Table 243-1). Ketoconazole is also effective but more toxic; voriconazole and posaconazole have been used with success in a few cases. Sulfonamides also are effective and are the least costly agents, but the response is slower and the relapse rate higher. Seriously ill patients should be treated with AmB initially. Patients with paracoccidioidomycosis have an excellent response to therapy, but pulmonary fibrosis is often progressive in those with chronic disease.
Etiologic Agent, Epidemiology, and Pathogenesis
Penicillium marneffei is a thermally dimorphic fungus that is endemic in the soil in certain areas of Vietnam, Thailand, and several other southeastern Asian countries. The epidemiology of penicilliosis is linked to bamboo rats, which are infected with the fungus but rarely manifest disease. The disease occurs most often among persons living in rural areas in which the rats are found, but there is no evidence for transmission of the infection directly from rats to humans. Infection is rare in immunocompetent hosts, and most cases are reported in persons who have advanced AIDS. Infection results from the inhalation of conidia from the environment. The organism converts to the yeast phase in the lungs and then spreads hematogenously to the reticuloendothelial system.
The clinical manifestations of penicilliosis mimic those of disseminated histoplasmosis and include fever, fatigue, weight loss, dyspnea, diarrhea (in some cases), lymphadenopathy, hepatosplenomegaly, and skin lesions, which appear as papules that often umbilicate and resemble molluscum contagiosum (Chap. 220e).
Penicilliosis is diagnosed by culture of P. marneffei from blood or from biopsy samples of skin, bone marrow, or lymph node. The organism usually grows within 1 week as a mold that produces a distinctive red pigment. Histopathologic examination of tissues and smears of blood or material from skin lesions shows oval or elliptical yeast-like organisms with central septation and can quickly establish a presumptive diagnosis.
Patients who have severe disease should be treated initially with AmB until their condition improves; therapy can then be changed to itraconazole (Table 243-1). Patients who have mild symptoms can be treated from the start with itraconazole. For patients with AIDS, suppressive therapy with itraconazole is recommended until immune reconstitution (related to successful therapy for HIV infection with antiretroviral drugs) is evident. Disseminated penicilliosis is usually fatal if not treated. With treatment, the mortality rate is ∼10%.
In these common soil organisms (also called dematiaceous fungi), melanin causes the hyphae and/or conidia to be darkly pigmented. 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. 199). Most of the involved fungi cause localized subcutaneous infections after direct inoculation, but disseminated infection and serious focal visceral 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. 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. Recently, Exserohilum species have caused a large outbreak of severe, sometimes fatal CNS and osteoarticular infections following the injection of methylprednisolone contaminated with this fungus.
Epidemiology and Pathogenesis
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. Other infections with dematiaceous molds are acquired by inhalation, by traumatic inoculation into the eye or through the skin, or by injection of contaminated medication. Melanin is a virulence factor for all the pigmented molds. Several organisms, specifically Cladophialophora bantiana and Rhinocladiella mackenziei, are neurotropic and likely to cause CNS infection. In an immunocompromised patient or when a pigmented mold is injected directly into a deep structure, these organisms become opportunists, invading blood vessels and mimicking better-known opportunistic infections, such as aspergillosis.
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 superinfection.
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 to 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 traumatic corneal inoculation. Even in many immunocompromised patients, inoculation through the skin generally produces localized cyst-like, nodular lesions at the entry site. However, other immunocompromised patients develop pneumonia, brain abscess, or disseminated infection. Epidural injection of Exserohilum-contaminated steroids has led to meningitis, basilar stroke, epidural abscess or phlegmon, vertebral osteomyelitis, and arachnoiditis.
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 confirm that the etiologic agent is a mold and not an actinomycete. In chromoblastomycosis, the diagnosis rests on the histologic demonstration of sclerotic bodies (dark brown, thick-walled, septate fungal forms that resemble large yeasts) in the tissues; culture establishes which pigmented mold is causing the infection. For other 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 assays for pigmented molds are available. Polymerase chain reaction (PCR) assays are increasingly used in the diagnosis of infection due to pigmented molds but are available only through fungal reference laboratories.
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; less experience has been gained 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. Chromoblastomycosis and eumycetoma are chronic indolent infections that are difficult to cure but are not life-threatening.
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. The most experience has accrued with itraconazole in the treatment of localized infections. Voriconazole is increasingly used when infections are disseminated or involve the CNS because this drug reaches adequate concentrations within the CNS and because both IV and well-absorbed oral formulations are available. The role of posaconazole has not been established but will likely expand. Disseminated and focal visceral infections, especially those involving the CNS, are associated with high mortality rates.
OPPORTUNISTIC FUNGAL INFECTIONS
Two genera of hyaline (nonpigmented) molds, Fusarium and Scedosporium, and one yeast-like genus, Trichosporon, have become prominent pathogens among immunocompromised patients. Infections caused by Fusarium and Scedosporium species overlap with invasive aspergillosis in their clinical manifestations, and, when seen in tissues, these organisms appear similar to Aspergillus. In the immunocompetent host, these fungi cause localized infections of skin, skin structures, and subcutaneous tissues, but their role as causes of infection in immunocompromised patients will be emphasized in this section.
Etiologic Agent, Epidemiology, and Pathogenesis
Fusarium species, which are found worldwide in soil and on plants, have emerged as major opportunists in markedly immunocompromised patients. Most human infections follow inhalation of conidia, but ingestion and direct inoculation also can lead to disease. An outbreak of severe Fusarium keratitis among soft contact lens wearers was traced back to a particular brand of contact lens solution and individual contact lens cases that had been contaminated. Disseminated infection is reported most often in patients who have a hematologic malignancy, are neutropenic, have received a stem cell or solid organ transplant, or have a severe burn.
In immunocompetent persons, Fusarium species cause localized infections of various organs. These organisms commonly cause fungal keratitis, which can extend into the anterior chamber of the eye; cause loss of vision; and require corneal transplantation. Onychomycosis due to Fusarium species, while basically an annoyance in immunocompetent patients, is a source of subsequent hematogenous dissemination and should be aggressively sought and treated in neutropenic patients. In profoundly immunocompromised patients, fusariosis is angioinvasive, and clinical manifestations mimic those of aspergillosis. Pulmonary infection is characterized by multiple nodular lesions. Sinus infection is likely to lead to invasion of adjacent structures. Disseminated fusariosis occurs primarily in neutropenic patients with hematologic malignancies and in allogeneic stem cell transplant recipients, especially those with graft-versus-host disease. Disseminated fusariosis differs from disseminated aspergillosis in that skin lesions are extremely common with fusariosis; the lesions are nodular or necrotic, are usually painful, and appear over time in different locations (Fig. 243-2).
Painful necrotic foot lesion that developed over a week in a woman who had acute leukemia and who had been neutropenic for 2 months. Fusarium species were grown from a punch biopsy. (Courtesy of Dr. Nessrine Ktaich.)
The diagnostic approach usually includes both documentation of the growth of Fusarium species from involved tissue and demonstration of invasion by histopathologic techniques that show septate hyphae in tissues. The organism is difficult to differentiate from Aspergillus species in tissues; thus, identification with culture is imperative. An extremely helpful diagnostic clue is growth in blood cultures, which are positive in as many as 50% of patients with disseminated fusariosis. There are no serologic assays for Fusarium. PCR techniques have proved useful but are available only through fungal reference laboratories.
Fusarium species are resistant to many antifungal agents. A lipid formulation of AmB (at least 5 mg/kg daily), voriconazole (200–400 mg twice daily), or posaconazole (300 mg daily) is recommended. Many physicians use both a lipid formulation of AmB and either voriconazole or posaconazole because susceptibility information is not available when therapy must be initiated. Serum drug levels should be monitored with either azole to ensure that absorption is adequate and with voriconazole to avoid toxicity. Mortality rates for disseminated fusariosis have been as high as 85%. With the improved antifungal therapy now available, mortality rates have fallen to ∼50%. However, if neutropenia persists, the mortality rate approaches 100%.
The genus Scedosporium includes several pathogens. The major causes of human infections are Scedosporium apiospermum, which in its sexual state is termed Pseudallescheria boydii, and S. prolificans. The S. apiospermum complex encompasses several species but will be referred to here simply as S. apiospermum.
Epidemiology and Pathogenesis
S. apiospermum is found worldwide in temperate climates in tidal flats, swamps, ponds, manure, and soil. This organism is known as a cause of pneumonia, disseminated infection, and brain abscess in near-drowning victims. S. prolificans is also found in soil but is more geographically restricted. Infection occurs predominantly through inhalation of conidia, but direct inoculation through the skin or into the eye also can occur.
Among immunocompetent persons, Scedosporium species are a prominent cause of eumycetoma. Keratitis as a result of accidental corneal inoculation is a sight-threatening infection. In patients who have hematologic malignancies (especially acute leukemia with neutropenia), recipients of solid organ or stem cell transplants, and patients receiving glucocorticoids, Scedosporium species are angioinvasive, causing pneumonia and widespread dissemination with abscesses. Pulmonary infection mimics aspergillosis; nodules, cavities, and lobar infiltrates are common. Disseminated infection involves the skin, heart, brain, and many other organs. Skin lesions are not as common or as painful as those of fusariosis.
Diagnosis depends on the growth of Scedosporium species from involved tissue and the demonstration of invasion by histopathologic techniques that show septate hyphae in tissues. Culture evidence is essential because Scedosporium species are difficult to differentiate from Aspergillus in tissues. Demonstration of tissue invasion is essential because these ubiquitous environmental molds can be mere contaminants or colonizers. S. prolificans can grow in blood cultures, but S. apiospermum usually does not. There are no serologic assays for Scedosporium. PCR techniques have proved useful but are available only through fungal reference laboratories.
Scedosporium species are resistant to AmB, echinocandins, and some azoles. Voriconazole is the agent of choice for S. apiospermum, and posaconazole also has been used for this infection. S. prolificans is resistant in vitro to almost every available antifungal agent; the addition of agents such as terbinafine to a voriconazole regimen has been attempted because in vitro data suggest possible synergy against some strains of S. prolificans. Mortality rates for invasive S. apiospermum infection are ∼50%, but those for invasive S. prolificans infection remain as high as 85–100%.
The genus Trichosporon contains many species, some of which cause localized infection of hair and nails. The major pathogen responsible for invasive infection is Trichosporon asahii. Trichosporon species grow as yeast-like colonies in vitro; in vivo, however, hyphae, pseudohyphae, and arthroconidia can also be seen.
Epidemiology and Pathogenesis
These yeasts are commonly found in soil, sewage, and water and in rare instances can colonize human skin and the human gastrointestinal tract. Most infections follow fungal inhalation or entry via central venous catheters. Systemic infection occurs almost exclusively in immunocompromised hosts, including those who have hematologic malignancies, are neutropenic, have received a solid organ transplant, or are receiving glucocorticoids.
Disseminated trichosporonosis resembles invasive candidiasis, and fungemia is often the initial manifestation of infection. Pneumonia, skin lesions, and sepsis syndrome are common. The skin lesions begin as papules or nodules surrounded by erythema and progress to central necrosis. A chronic form of infection mimics hepatosplenic candidiasis (chronic disseminated candidiasis).
The diagnosis of systemic Trichosporon infection is established by growth of the organism from involved tissues or from blood. Histopathologic examination of a skin lesion showing a mixture of yeast forms, arthroconidia, and hyphae can lead to an early presumptive diagnosis of trichosporonosis. The serum cryptococcal antigen latex agglutination test may be positive in patients with disseminated trichosporonosis because T. asahii and Cryptococcus neoformans share polysaccharide antigens.
Rates of response to AmB have been disappointing, and many Trichosporon isolates are resistant in vitro. Voriconazole appears to be the antifungal agent of choice and is used at a dosage of 200–400 mg twice daily. The mortality rates for disseminated Trichosporon infection have been as high as 70% but are decreasing with the use of newer azoles, such as voriconazole; however, patients who remain neutropenic are likely to succumb to this infection.
SUPERFICIAL CUTANEOUS INFECTIONS
Fungal infections of the skin and skin structures are caused by molds and yeasts that do not invade deeper tissues but rather cause disease merely by inhabiting the superficial layers of skin, hair follicles, and nails. These agents are the most common cause of fungal infections of humans but only rarely cause serious infections.
The lipophilic yeast Malassezia is dimorphic in that it lives on the skin in the yeast phase but transforms to the mold phase as it causes disease. Most species require exogenous lipids for growth.
Epidemiology and Pathogenesis
Malassezia species are part of the indigenous human flora found in the stratum corneum of the back, chest, scalp, and face—areas rich in sebaceous glands. Disease is more common in humid areas. The organisms do not invade below the stratum corneum and generally elicit little if any inflammatory response.
Malassezia species cause tinea versicolor (also called pityriasis versicolor), folliculitis, and seborrheic dermatitis. Tinea versicolor presents as flat round scaly patches of hypo- or hyperpigmented skin on the neck, chest, or upper arms. The lesions are usually asymptomatic but can be pruritic. They can be mistaken for vitiligo, but the latter is not scaly. Folliculitis occurs over the back and chest and mimics bacterial folliculitis. Seborrheic dermatitis manifests as erythematous pruritic scaly lesions in the eyebrows, moustache, nasolabial folds, and scalp. The scalp lesions are termed cradle cap in babies and dandruff in adults. Seborrheic dermatitis can be severe in patients with advanced AIDS. Fungemia and disseminated infection occur rarely with Malassezia species—almost always in premature neonates receiving parenteral lipid preparations through a central venous catheter.
Malassezia infections are diagnosed clinically in most cases. If scrapings are collected on a microscope slide on which a drop of potassium hydroxide has been placed, a mixture of budding yeasts and short septate hyphae is seen. In order to culture M. furfur from those patients in whom disseminated infection is suspected, sterile olive oil must be added to the medium.
Topical creams and lotions, including selenium sulfide shampoo, ketoconazole shampoo or cream, terbinafine cream, and ciclopirox cream, are effective in treating Malassezia infections and are usually given for 2 weeks. Mild topical steroid creams are sometimes used to treat seborrheic dermatitis. For extensive disease, itraconazole (200 mg/d) or fluconazole (200 mg/d) can be used for 5–7 days. The rare cases of fungemia caused by Malassezia species are treated with AmB or fluconazole, prompt removal of the catheter, and discontinuance of parenteral lipid infusions. Malassezia skin infections are benign and self-limited, although recurrences are the rule. The outcome of systemic infection depends on the host’s underlying conditions, but most infected infants do well.
DERMATOPHYTE (MOLD) INFECTIONS
The molds that cause skin infections in humans include the genera Trichophyton, Microsporum, and Epidermophyton. These organisms, which are not components of the normal skin flora, can live within the keratinized structures of the skin—hence the term dermatophytes.
Epidemiology and Pathogenesis
Dermatophytes occur worldwide, and infections with these organisms are extremely common. Some organisms cause disease only in humans and can be transmitted by person-to-person contact and by fomites, such as hairbrushes or wet floors, that have been contaminated by infected individuals. Several species cause infections in cats and dogs and can readily be transmitted from these animals to humans. Finally, some dermatophytes are spread from contact with soil. The characteristic ring shape of cutaneous lesions is the result of the organisms’ outward growth in a centrifugal pattern in the stratum corneum. Fungal invasion of the nail usually occurs through the lateral or superficial nail plates and then spreads throughout the nail; when hair shafts are invaded, the organisms can be found either within the shaft or surrounding it. Symptoms are caused by the inflammatory reaction elicited by fungal antigens and not by tissue invasion. Dermatophyte infections occur more commonly in male than in female patients, and progesterone has been shown to inhibit dermatophyte growth.
Dermatophyte infection of the skin is often called ringworm. This term is confusing because worms are not involved. Tinea, the Latin word for worm, describes the serpentine nature of the skin lesions and is a less confusing designation that is used in conjunction with the name of the body part affected—e.g., tinea capitis (head), tinea pedis (feet), tinea corporis (body), tinea cruris (crotch), and tinea unguium (nails, although infection at this site is more often termed onychomycosis).
Tinea capitis occurs most commonly in children 3–7 years old. Children with tinea capitis usually present with well-demarcated scaly patches in which hair shafts are broken off right above the skin; alopecia can result. Tinea corporis is manifested by well-demarcated, annular, pruritic, scaly lesions that undergo central clearing. Usually one or several small lesions are present. In some cases, tinea corporis can involve much of the trunk or manifest as folliculitis with pustule formation. The rash should be differentiated from contact dermatitis, eczema, and psoriasis. Tinea cruris is seen almost exclusively in men. The perineal rash is erythematous and pustular, has a discrete scaly border, is without satellite lesions, and is usually pruritic. The rash must be differentiated from intertriginous candidiasis, erythrasma, and psoriasis.
Tinea pedis also is more common among men than among women. It usually starts in the web spaces of the toes; peeling, maceration, and pruritus are followed by development of a scaly pruritic rash along the lateral and plantar surfaces of the feet. Hyperkeratosis of the soles of the feet often ensues. Tinea pedis has been implicated in lower-extremity cellulitis, as streptococci and staphylococci can gain entrance to the tissues through fissures between the toes. Onychomycosis affects toenails more often than fingernails and is most common among persons who have tinea pedis. The nail becomes thickened and discolored and may crumble; onycholysis almost always occurs. Onychomycosis is more common in older adults and in persons with vascular disease, diabetes mellitus, and trauma to the nails. Fungal infection must be differentiated from psoriasis, which can mimic onychomycosis but usually has associated skin lesions.
Many dermatophyte infections are diagnosed by their clinical appearance. If the diagnosis is in doubt, as is often the case in children with tinea capitis, scrapings should be taken from the edge of a lesion with a scalpel blade, transferred to a slide to which a drop of potassium hydroxide is added, and examined under a microscope for the presence of hyphae. Cultures are indicated if an outbreak is suspected or the patient does not respond to therapy. Culture of the nail is especially useful as an aid to decisions about both diagnosis and treatment.
Dermatophyte infections usually respond to topical therapy. Lotions or sprays are easier than creams to apply to large or hairy areas. Particularly for tinea cruris, the affected area should be kept as dry as possible. When patients have extensive skin lesions, oral itraconazole or terbinafine can hasten resolution (Table 243-2). Terbinafine interacts with fewer drugs than itraconazole and is generally the first-line agent. Onychomycosis does not respond to topical therapy, although ciclopirox nail lacquer applied daily for a year is occasionally beneficial. Itraconazole and terbinafine both accumulate in the nail plate and can be used to treat onychomycosis (Table 243-2). These agents are more effective and better tolerated than griseofulvin and ketoconazole. The major decision to be made with regard to therapy is whether the extent of nail involvement justifies the use of systemic antifungal agents that have adverse effects, may interact with other drugs, and are costly. Treating for cosmetic reasons alone is discouraged. Relapses of tinea cruris and tinea pedis are common and should be treated early with topical creams to avoid development of more extensive disease. Relapses of onychomycosis follow treatment in 25–30% of cases.
TABLE 243-2Suggested Oral Treatment for Extensive Tinea Infections and Onychomycosis ||Download (.pdf) TABLE 243-2Suggested Oral Treatment for Extensive Tinea Infections and Onychomycosis
|Antifungal Agent ||Suggested Dosage ||Comments |
|Extensive Tinea Skin Infection |
|Terbinafine ||250 mg/d for 1–2 weeks ||Adverse reactions minimal with short treatment period |
|Itraconazolea ||200 mg/d for 1–2 weeks ||Adverse reactions minimal with short treatment period except for drug interactions |
|Terbinafine ||250 mg/d for 3 months ||Slightly superior to itraconazole; monitor for hepatotoxicity |
|Itraconazolea || |
200 mg/d for 3 months
200 mg bid for 1 week each month for 3 months
|Drug interactions frequent; monitor for hepatotoxicity; rarely causes hypokalemia, hypertension, edema; use with caution in patients with congestive heart failure |