Fungal, Bacterial, and Viral Infections of The Skin Part 1

Despite its large surface area and constant exposure to the environment, the skin resists infection well. The most important protective factor is an intact stratum corneum, the tough barrier of protein and lipid formed on the cutaneous surface by the underlying epidermis.1 This barricade impedes invasion by environmental pathogens, and its dryness discourages colonization and growth of the many organisms that require moisture to survive, such as gram-negative bacilli. Furthermore, the constant shedding of cells of the epidermis impedes most microbes from establishing permanent residence.

Some organisms, however, can attach to skin cells and reproduce there; the normal cutaneous flora comprises primarily aerobic, gram-positive cocci and bacilli in densities ranging from about 102 organisms/cm2 on dry skin to 107 organisms/cm2 in moist areas, such as the axilla.2 This resident population inhibits harmful organisms from colonizing the skin by occupying binding sites on the epidermal cells, competing for nutrients, producing antimicrobial substances, and maintaining the skin surface at a low pH (about 5.5). Anaerobes are sparse except in areas with abundant sebaceous glands, such as the face and chest; in the deeper portions of these sites, as well as in hair follicles, anaerobes reach concentrations of 104 to 106 organisms/cm2.

Cutaneous infections occur when the skin’s protective mechanisms fail, especially when trauma, inflammation, maceration from excessive moisture, or other factors disrupt the stratum corneum. The organisms causing infection may originate from the victim’s own resident flora, either on the skin or on adjacent mucous membranes, but many come from other people, animals, or the environment.


Dermatophyte Infections

Dermatophytes are fungi (molds) that can infect the skin, hair, and nails. These organisms, which include Trichophyton, Microsporum, and Epidermophyton species, are classified as an-thropophilic, zoophilic, or geophilic, depending on whether their primary source is humans, animals, or the soil, respective-ly.3 Geophilic dermatophyte infections occur sporadically, primarily among gardeners and farm workers. Zoophilic der-matophytes (Trichophyton and Microsporum species) may have a restricted range of hosts (e.g., M. persicolor infects only voles) or may afflict many different animals (e.g., T. mentagrophytes can infect mice and other rodents, dogs, cats, and horses). Human infections with zoophilic species have occurred after exposure to dogs, cats, horses, cattle, pigs, rodents, poultry, hedgehogs, and voles.

Anthropophilic dermatophytes are the most common cause of fungal skin infections in humans. Transmission of these infections occurs from direct contact between people or from exposure to desquamated skin cells present in the environment— arthrospores can survive for months. Direct inoculation of the spores through breaks in the skin can lead to germination and subsequent invasion of the superficial cutaneous layers.

Dermatophyte infections occur more frequently in certain ethnic groups and in people with impaired cell-mediated immunity. Many of the anthropophilic dermatophyte infections occur more often in one gender or age group.4

Infection of the scalp, for example, is primarily a disease of children. Involvement of the feet and groin is most common in adolescents and young adults, especially males, but is unusual in children. Nail infection is more frequent in both men and women of advancing age. The reasons for these differences are unknown.

The anthropophilic dermatophytes also have unique geographic distribution patterns. The most common cause of scalp infection in the United States, for example, is T. tonsurans, but in Southeast Asia and the Middle East, it is T. violaceum. These differences may relate to climatic or racial factors.

The various forms of dermatophytosis, also called ringworm, are named according to the site involved. These infections include tinea capitis (scalp), tinea corporis (body), tinea barbae (beard area of men), tinea faciei (face), tinea cruris (groin), tinea pedis (feet), tinea unguium (nails), and tinea manuum (hands). The characteristic skin lesion is an annular scaly patch [see Figure 1], though the clinical appearance varies not only with the site involved but also with the host’s immune status and the type of infecting organism. In general, anthro-pophilic species elicit little inflammation and cause chronic infections. Zoophilic and geophilic species, however, often provoke intense inflammation, which sometimes leads to eradication of the organisms and healing without treatment.

Clinical presentations

Tinea Capitis

Tinea capitis occurs primarily in children but may develop in adults—especially the elderly, those who are unkempt, and the impoverished. Transmission can occur between humans by the sharing of combs, brushes, or headgear. Only Microsporum and Trichophyton species cause tinea capitis. Infection begins with invasion of the stratum corneum of the scalp skin. The hairs then become infected, in one of three microscopic patterns: ectothrix, endothrix, or favus. In ectothrix, the spores are outside the hair shaft and destroy the cuticle; in endothrix, they lie within the hair and do not affect the cuticle; and in favus, broad hyphae and air spaces form within the hair, but spores are absent. In all three types, scaling, hair loss, and inflammation of varying degrees are present.5

Classic annular lesion of tinea corporis shows a raised or vesicular margin with central clearing.

Figure 1 Classic annular lesion of tinea corporis shows a raised or vesicular margin with central clearing.

A typical kerion presenting as a zoophilic Microsporum canis infection of the scalp (tinea capitis).

Figure 2 A typical kerion presenting as a zoophilic Microsporum canis infection of the scalp (tinea capitis).

T. tonsurans, the major cause of tinea capitis in adults, characteristically produces a noninflammatory infection with either well-demarcated or irregular and diffuse areas of scaling and alopecia. Because the swollen hairs may fracture a few millimeters from the epidermis in this endothrix infection, the scalp sometimes appears to be marked by small black dots. Like all infections with Trichophyton species, these scalp lesions do not fluoresce under a Wood light.

T. schoenleinii causes favus, characterized by an inflammatory crust (scutulum) in which hair appears to be matted in the dried, yellow exudate. Hair shedding late in the infection is common because the hair shaft is not damaged until the infection is well advanced.

M. audouinii, which causes an ectothrix infection, produces well-delineated, noninflammatory patches of alopecia in which the hair breaks at the epidermal surface and is often dull gray because of the presence of numerous spores on the surface of the hair shaft. As in all Microsporum infections, these lesions flu-oresce under a Wood light. The most severe inflammation, usually from a zoophilic species, results in a kerion, a painful, boggy mass in which follicles may discharge pus and in which sinus tracts form [see Figure 2]. Crusting and matting of adjacent hairs are common, and cervical lymph nodes may enlarge.

Tinea Corporis

Tinea corporis typically appears as a single lesion or multiple circular lesions with scaling, well-delineated margins, and a raised, erythematous edge. Often, they have an area of central clearing. The amount of inflammation varies; when the inflammation is intense, pustules, vesicles, and even bullae may occur. Sometimes, involvement of the hair follicles in the middle of a patch of scaling erythema leads to perifollicular nodules, a condition called Majocchi granuloma. This condition usually occurs on the legs of patients infected with T. rubrum.

 (a) The scaling of tinea pedis appears between and under the toes and on the plantar surface. (b) Tinea pedis may also present as vesicles.

Figure 3 (a) The scaling of tinea pedis appears between and under the toes and on the plantar surface. (b) Tinea pedis may also present as vesicles.

In immunocompromised hosts, subcutaneous abscesses may develop.

Tinea Barbae

Tinea barbae occurs in adult men and involves the skin and coarse hairs of the beard and mustache area. The usual cause is a zoophilic species, primarily T. verrucosum and T. mentagrophytes, which are organisms that commonly infect cattle and horses. The victims are generally farm workers, and the infection usually causes erythema, scaling, and follicular pustules. Many hairs become loose and are easily removed with a forceps.

Tinea Faciei

Tinea faciei occurs as an infection of the face in women and children and infection of the area outside the mustache and beard in men. The usual causes are T. rubrum and T. mentagro-phytes; these organisms reach the face through direct inoculation or by spreading from another site of infection on the body. Patients often complain of itching and burning, and symptoms may worsen after exposure to sunlight. The lesions may be scaly, annular erythematous patches, but often they are indistinct red areas with little or no scaling.

Tinea Cruris

Tinea cruris, infection of the groin, is much more common in men than women and is often associated with infection of the feet. T. rubrum and E. floccosum are the most common causes. The lesions are usually red, scaling, sharply demarcated areas with raised, erythematous borders. The infection, which affects the medial portion of the upper thighs but consistently spares the scrotum, may extend to the buttocks, abdomen, and lower back. Vesicles, nodules, pustules, and maceration may be present.

Tinea Pedis

Tinea pedis is most frequently caused by T. rubrum, E. flocco-sum, and T. mentagrophytes. The most common form consists of fissuring, scaling, and maceration in the interdigital spaces, especially between the fourth and fifth toes. A second type involves scaling, hyperkeratosis, and erythema of the soles, heels, and sides of the feet. In this kind of tinea pedis, the lesions occur in a so-called moccasin distribution pattern [see Figure 3a]. The plantar skin may become very thick and scaly. A third form demonstrates an inflammatory pattern characterized by vesicles, pustules, or even bullae, usually on the soles [see Figure 3b].

An important complication of tinea pedis is streptococcal cel-lulitis of the lower leg. Streptococci do not ordinarily survive on normal skin, but the presence of fungal disease apparently permits streptococci of various groups, including A, B, C, and G, to colonize the toe webs.6 From this location, these bacteria may invade the skin damaged by the tinea pedis or migrate to locations higher up the leg and enter the skin through any defects.

Tinea Unguium

Nail involvement usually occurs from adjacent fungal infection of the hands or feet. The organisms typically invade the nail from the distal or lateral borders, and infection spreads proximally. The nails are thickened, opaque, and yellowish to brownish. They may crack or crumble, and often, subungual hyperkeratosis lifts the nail plate from the underlying bed (a condition known as onycholysis) [see Figure 4]. Splinter hemorrhages are common.

Nails are usually thickened, cracked, and crumbly in tinea unguium; subungual debris may be present, as shown.

Figure 4 Nails are usually thickened, cracked, and crumbly in tinea unguium; subungual debris may be present, as shown. 

Tinea Manuum

Tinea manuum is an infection of the hands. Most cases have accompanying involvement of the feet; inexplicably, usually only one hand is affected (so-called two-feet, one-hand disease). The most common finding is scaling or hyper-keratosis of the palms and fingers. Occasionally, vesicles, papules, or follicular nodules form on the dorsal surface of the hands.

Diagnosis

Clinicians should suspect dermatophyte infection in patients with any scaling, erythematous eruption and in patients whose nails exhibit the characteristics of tinea unguium (see above). The diagnosis can be confirmed by microscopy or culture of properly obtained specimens. The optimal method of obtaining specimens from the skin is by scraping the scaly lesions; specimens from the nails are best obtained by taking fragments of subungual debris.

The specimen is prepared for microscopic examination by first placing it on a glass slide and treating it with potassium hydroxide (KOH), which digests the keratin of the skin, nails, and hair, and then heating it to hasten the process. The basic culture medium for isolating dermatophytes is an agar containing Sabouraud medium, often combined with antibiotics to eliminate bacteria and with cycloheximide to inhibit sapro-phytic fungi. Growth is usually apparent in 3 to 14 days. Der-matophyte test medium culture can be used in the office and is both accurate and inexpensive.7 When both KOH preparations and cultures are negative, a biopsy may be useful in identifying the infecting organism, usually by special tissue stains such as periodic acid-Schiff or Gomori methenamine-silver stains.

Treatment

Tinea corporis, tinea cruris, tinea pedis, and tinea faciei respond to topical agents applied once or twice daily to the affected area, usually for 2 to 4 weeks. Good choices include azoles (e.g., miconazole, econazole, or clotrimazole) or terbinafine. The cost of the preparation can dictate which agent to prescribe. Tinea pedis often recurs after effective therapy, especially in cases of the moccasin form of the disease. When infection reappears, the previous therapy can be resumed without loss of effectiveness.

Oral therapy is necessary for extensive lesions, for infection involving the hair or hair follicles (e.g., tinea capitis and tinea barbae), for tinea unguium, and, often, for tinea manuum and various forms of dermatophytoses in immunocompromised hosts. Five oral agents are currently available: griseofulvin, ke-toconazole, itraconazole, fluconazole, and terbinafine. Griseo-fulvin, a fungistatic agent, is the oldest oral treatment available and is still useful, primarily in infections not involving the nails. Griseofulvin reduces the serum levels of barbiturates and warfarin. Some patients receiving griseofulvin note a diminished tolerance to alcohol.

The azoles include ketoconazole, itraconazole, and flucona-zole; like griseofulvin, they are fungistatic. Ketoconazole is usually well tolerated, but hepatotoxicity occurs in about 1 in 10,000 patients, typically after several weeks of use. Flucona-zole and itraconazole are very expensive, but they provide protracted levels of antibiotic in the nails, allowing short or intermittent courses of therapy for tinea unguium. Both fluconazole and itraconazole can cause gastrointestinal disorders, rashes, and, occasionally, hepatotoxicity and can have serious interactions with several medications, including cyclosporine, digox-in, and quinidine. Ketoconazole, itraconazole, and fluconazole can interact with other medications; pharmacologic sources should be consulted for potential interactions.

Terbinafine, also an expensive medication, is an allylamine. Unlike both griseofulvin and the azoles, which are fungistatic, terbinafine is fungicidal. It achieves high levels of drug in the nails, and the drug persists for many weeks after discontinuance. Its few side effects include gastrointestinal reactions and, occasionally, skin rashes. Hepatotoxicity and hematologic abnormalities are rare, and drug interactions are uncommon.

These oral antifungals are quite effective for tinea capitis. The adult dosage for griseofulvin is 500 mg twice daily for 8 weeks. The other agents are effective when given for 1 to 3 weeks. Daily doses are as follows: itraconazole, 200 mg; flu-conazole, 200 mg; and terbinafine, 250 mg. Of these, griseoful-vin is the least expensive, but some T. tonsurans isolates are resistant to it. All these medications are effective in cases of tinea barbae, Majocchi granuloma, extensive tinea corporis, and tinea manuum that are unresponsive to topical agents. Griseo-fulvin and terbinafine appear to be superior to fluconazole and itraconazole for the treatment of tinea capitis.8

Tinea unguium is difficult to eradicate, particularly in the toenails. The most effective agent is terbinafine, administered at a dosage of 250 mg daily for 6 weeks for fingernail infections and for 12 weeks for toenail involvement.9 Because terbinafine persists in the nails for many weeks, it continues to exert anti-fungal effects long after it is discontinued. The terbinafine regimens produce short-term eradication of infection in about 70% to 90% of patients with fingernail infection and in about 50% to 80% of patients with toenail infection. Relapse is common, and patients often require a second course of treatment. About 75% of patients who receive one or more courses of terbinafine will have a clinical cure 5 years later. This therapy is very expensive, and clinicians must decide in each case whether treatment is warranted.

Yeast Infections

Yeasts are unicellular fungi that reproduce by budding. They may form filamentous projections, which, unlike the hy-phae of molds, do not contain separate cells. Accordingly, they are called pseudohyphae. Candida species are not part of the normal skin flora, but they commonly reside in the orophar-ynx, vagina, and colon. From these locations, they may cause infections in adjacent traumatized skin. Alternatively, with reduction in the other flora or with impaired host defense mechanisms, these yeasts may proliferate in large numbers to produce lesions on the mucosal surfaces of the mouth and vagina.

Malassezia furfur (also called Pityrosporum orbiculare or P. ovale) is a yeast that requires lipids for growth. It normally colonizes the skin of adults, especially of the scalp and upper trunk, where the presence of sebum is highest. For unknown reasons, these organisms, which are ordinarily commensals, can become pathogenic and cause tinea versicolor (also known as pityriasis versicolor) or folliculitis. Cogent evidence suggests that these organisms cause seborrheic dermatitis and dandruff.

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