Robert M. Rogers, M.D. and Jack L. Lesher, Jr., M.D.

Pityriasis (tinea) versicolor

Pityriasis, or tinea, versicolor is a very common superficial fungal disease of the skin caused by the genus of lipophilic yeast known as Malassezia. Though commonly referred to as tinea versicolor, pityriasis is a fitting descriptive term used to denote any dermatosis characterized by branny desquamation. Versicolor refers appropriately to the varied hues of the lesions clinically. Seven species of the genus Malassezia are human pathogens, with M. furfur and M. globosa most commonly indicted as causative agents in pityriasis versicolor. Frequently the older names Pityrosporum ovale and P. orbiculare are encountered in the literature for the now correct Malassezia furfur. In addition to tinea versicolor, Malassezia species may cause folliculitis, inverse tinea versicolor, and rarely systemic disease in pediatric patients on parenteral lipid supplementation.

Pityriasis versicolor occurs in either sex, most commonly in post-pubertal age groups. Found in all geographic regions, cases are more common in tropical climates and subtropical areas with high temperatures and increased humidity. Cases found in these regions tend to be more severe. Other factors that contribute to the development of pityriasis versicolor include malnutrition, Cushing's disease, immunosuppression, oral contraceptives and heredity.

The lesions of pityriasis versicolor are found on the "seborrheic areas" of the body, most notably the trunk. This is consistent with Malassezia's opportunistic nature and lipid requirement for growth. Lesions exhibit a slightly branny or furfuraceous scale and may be flat, nummular or evenconfluent (Figure 1).

Figure 1. Lesions from pityriasis versicolor exhibit a slight branny scale and may be flat, papular, nummular, or even confluent. Slides are from the National Library of Dermatologic Teaching Slides.

Lesion shades vary from white to red brown. Lesions may be pruritic and erythematous. In addition to the trunk, other body areas affected may include the proximal extremities and face (more common in children). In extreme cases, even the distal extremities may have some involvement. Malassezia folliculitis usually presents as pruritic pustules of the trunk.

Malassezia may be found on normal unaffected skin, but biopsy of lesions demonstrates the hyphal forms of the yeast invading the stratum corneum. The yeast may also be visualized within the follicle admixed with debris in Malassezia folliculitis. Clinical suspicion can be readily confirmed by microscopically observing these hyphae and budding cells ("spaghetti and meatballs") in KOH (10% potassium hydroxide) preparations of scales scraped from lesions. In a similar fashion, scale may be lifted from lesions with cellophane tape, prepped with methylene blue and examined microscopically for Malassezia. Culture is rarely needed, but if performed requires the addition of a lipid source, such as olive oil, to the growth medium.

There are a number of treatments available for pityriasis versicolor, both topically and orally. These treatments have various mechanisms, including fungistatic, fungicidal and nonspecific destruction of the stratum corneum. Fortunately, most of these are very effective; however, there can be atendency for the disease to recur. Zinc pyrithione shampoo, applied for five to ten minutes and then rinsed off every evening for one to two weeks has therapeutic and prophylactic effects. Topical selenium sulfide 2 ½ % shampoo is effective when applied for 15 minutes, and washed off well, every day for three days; or for one or two overnight applications. Topical azole, triazole, allylamine, imidazole, benzylamine and hydroxpyridone antifungals have shown efficacy when applied twice daily for 2-3 weeks.

Multiple vehicles may be used with preparations like NizoralÃ’ shampoo providing significant ease of application. Specific topicals such as ketoconazole and bifonazole may be effective as a single dose. For extensive or recurrent lesions and with patients whom compliance is an issue, oral therapy is sometimes used. Ketoconazole has been used at a 200 mg dose daily for 5-7 days, or 400 mg once weekly for two weeks. Itraconazole has been very effective at a dose of 200 mg daily for five to seven days. Also single doses of fluconazole 400 mg have been effective. Neither terbinafine nor griseofulvin has been effective when used orally for pityriasis versicolor, although topical terbinafine twice daily for 1 to 2 weeks is effective. To prevent relapse of pityriasis versicolor, particularly in the warmer months, a zinc pyrithione soap lather may be applied to the body at least two or three times weekly.

Candidiasis

Candidiasis is an infection of the skin, mucous membranes, and occasionally internal organs caused by yeast of the genus Candida. Most frequently these infections are due to Candida albicans but other species with increasing frequency cause human disease. Candida species are normal inhabitants of the gastrointestinal tract, but rarely colonize the skin unless there is some break in the integument, for example from dermatitis, cracks, or fissures. Candida species are dimorphic fungi that occur as a budding yeast or blastoconidia phase, and a mycelial or pseudomycelial phase. Usually the mycelial phase is the form causing superficial disease, while the yeast or blastoconidia is the colonizing or hematogenously disseminating form.

Candida infections of the skin and mucous membranes results from an interplay between a variety of Candida virulence factors (for example, hyphae formation, contact sensing, and lytic enzymes), and a variety of host defense mechanisms (including epidermal proliferation, T-cell immunity, phagocytosis, and immunoglobulins). Any factor that adversely affects normal immune function may predispose a person to candidiasis. Examples include: genetic susceptibilities, such as Down's syndrome and chronic mucocutaneous candidiasis; endocrine disorders such as diabetes; malignancies; immunodeficiency states; debility due to chronic or advanced disease; and prolonged use of antibiotics, corticosteroids, or immunosuppressive agents. Heat, humidity, and friction between skin surfaces are environmental factors that may also contribute to infection.

Candidiasis may display a wide clinical spectrum of diseasewith varied patterns of infection of the skin, mucosa and internal organs. Infections solely limited to the skin and mucous membranes (Figure 2) are referred to as superficial candidiasis. The usual sites of the infection include the skin folds; the perioral, vulvovaginal, and anal mucocutaneous junctions; and the nail unit.

Figure 2. Superficial candidiasis infections are limited to the skin and mucous membranes. Slides are from the National Library of Dermatologic Teaching Slides

In immunocompromised or debilitated patients, candidiasis may become systemic and disseminated. This life threatening infection commonly occurs in neutropenic patients via extension from a colonized gastrointestinal tract, aspiration, or by invasion through an impaired mucosa or integument.

The most common cutaneous pattern of Candida infection is candidal intertrigo. The genitocrural and gluteal folds, the submammary region, and the interdigital spaces of the hands and feet are usually affected. These often pruritic lesions may begin as vesicles, pustules or erythematous plaques, and eventually lead to maceration and fissuring, leaving behind a denuded, red base. Often the central lesion is bordered by a number of discrete pustules in a "satellite pattern".

Cutaneous candidal infection in the diaper area of infants is one cause of so-called diaper dermatitis (Figure 3). The occlusive nature of the diaper appears to create an environment ripe for candidal colonization. Erythematous or pustular lesions radiate out from the perianal area into the gluteal folds, and subsequently spread to the rest of the perineum, genitalia, buttocks, and thighs.

Figure 3. Candidial infection in infants, in the diaper area, has been called diaper dermatitis.

Slide is from the National Library of Dermatologic Teaching Slides.

This is not to be confused with congenital cutaneous candidiasis, where a papular or vesiculopustular eruption occurs over the face, neck, trunk, limbs, as well as the palms and soles. Congenital cutaneous candidiasis is most often noted at birth or within twelve hours after delivery, and is presumably caused by ascending infection of the skin by Candida albicans through the birth canal. Most of these infants do not demonstrate signs of systemic infection, but the disorder has been fatal in infants with low birth weight or preterm delivery.

Candidal infection of the nail unit may occur, usually caused by Candida albicans or C. parapsilosis. Candida paronychia is usually the result of chronic water exposure and trauma. The proximal or lateral nail folds may be affected, with erythema, edema, scaling, and occasionally a purulent discharge. A resultant onychodystrophy may occur with a greenish-yellow discoloration under the nail. This is usually attributed to secondary invasion by Pseudomonas aeruginosa. Actual invasion of the nail plate is rare, but in the inherited disorder chronic mucocutaneous candidiasis nail plate invasion does occur. In this disorder, patients have chronic and recurrent Candida albicans infections of the skin, nails, and mucous membranes associated with abnormalities of cell-mediated immunity. Chronic mucocutaneous candidiasis may be associated with other disorders such as autoimmune diseases and endocrinopathies.

The most common oral form of candidiasis is thrush or pseudomembranous candidiasis. In this infection, removable white plaques occur on the mucosal surfaces of the mouth (Figure 4). Characteristically, these lesions may be removed by scraping, yielding an erythematous red base.

Figure 4. Slide is from the National Library of Dermatologic Teaching Slides.

Several other forms of oral candidiasis have been described and may be associated with thrush. Perleche, or angular cheilitis, may present with burning, tenderness and erythema, cracking, fissuring or maceration of the oral commissures. An erythematous, edematous candidal infection of the palate associated with denture colonization has been described, especially with ill-fitting dentures worn for long periods of time. Erythematous candidiasis may present as atrophic, painful, red patches of the tongue or lips, commonly associated with antibiotic administration.

Another common form of mucosal candidiasis is Candida vulvovaginitis and balanitis. In the former, vaginal mucous membranes are inflamed, with associated pruritus, erythema, and a creamy white discharge. Candida balanitis usually occurs in uncircumcised males and presents as erythema and pustules, with exudate, on the glans penis or prepuce. Both of these infections may later spread to the perineal areas as intertrigo.

In all of the aforementioned candidal infections, KOH microscopy of scrapings from lesions will usually reveal yeast and hyphae consistent with candidiasis. Material may be sent on Sabouraud's dextrose agar for confirmatory fungal culture.

Treatment involves use of the appropriate topical and/or oral antifungal agent but importantly must address host and environmental factors as well. Heat, humidity and tight fitting clothing should be avoided, and moist or occluded areas must be "dried out". This is especially important in intertrigo, paronychia associated with wet work, and diaper dermatitis where frequent diaper changes and proper skin hygiene are essential. All underlying diseases, such as diabetes, should be identified and controlled.

Numerous effective topical agents are currently available. One of the most commonly used agents is nystatin, which is available in a number of vehicles for treating oral and cutaneous candidiasis. The azole family of topical antifungals (e.g. ketoconazole, clotrimazole, econazole, or oxiconazole) is also effective. Ciclopirox, terbinafine, naftifine, Castellani's paint and thymol may also be used. The topical antifungals are usually rubbed in once or twice daily for approximately two weeks, and for a week after the signs of the infection have apparently cleared. In significant cutaneous or mucous membrane candidal infections, the oral azole agents such as ketoconazole, fluconazole, or intraconazole are very effective.

A variety of oral treatment regimens are available, usually involving daily therapy for a week or two. There are certain infections, for example vaginal candidiasis, for which single dose oral therapy with fluconazole has been advocated. Disseminated life threatening candidiasis requires treatment with systemic antifungals. Amphotericin B, with or without flucytosine, historically has been first line therapy, but fluconazole, and the newer agents voriconazole and caspofungin can be used.

References:

1. Faergemann J. Pityrosporum infections. In: Elewski BE (ed) Cutaneous Fungal Infections. Blackwell Science, Malden, MA; 1998: 73-89.
2. Lesher, Jr., JL. Therapeutic agents for dermatologic fungal diseases. In: Elewski BE (ed). Cutaneous Fungal Infections. Blackwell Science, Malden, MA; 1998: 321-346.
3. Faergemann, J. Tinea versicolor (tinea pityriasis versicolor). In: Demis DJ (ed). Clinical Dermatology. Lippincott-Raven, Philadelphia; 1995: 3(17-2), 1-11.
4. Pappas AA, Ray TL. Cutaneous and disseminated skin manifestations of candidiasis. In: Elewski BE (ed). Cutaneous Fungal Infections. Blackwell Science, Malden, MA; 1998: 91-118.
5. Hay RJ. Yeast infections. Dermatol Clin 1996; 14: 113-124.
6. Pereyo NE, Lesher, Jr., JL. Candidiasis. In: Demis DJ (ed). Clinical Dermatology. Lippincott-Raven, Philadelphia; 1997; 17-16: 1-22.
7. Gupta AK, et al. Pityriasis Versicolor. Dermatol Clin 2003; 21(3): 413-29.
8. Groll AH, et al. Clinical pharmacology of antifungal compounds. Infect Dis Clin North Am. 2003 Mar; 17(1): 159-91.
9. Darmstadt GL, et al. Congenital cutaneous candidiasis: Clinical presentation, pathogenesis and management guidelines. Pediatrics 2000; 105(2): 438-44.

Questions: Pityriasis and Candidiasis

1. An 18-year-old man comes to you with a complaint of a rash that has been present over the summer months. On your exam you find hypopigmented macular lesions with slight branny scaling involving primarily the trunk. A KOH examination will show:

A) Yeast forms only
B) Hypheal forms only
C) Hyphae and yeast ("spaghetti and meatballs")
D) Pseudomonas
E) Sulfur granules

2. A 35-year-old, overweight woman has recurrent candida infections in the crural folds. Which of the following should be ruled out:

A) Thyroid disease
B) Diabetes
C) Addison's disease
D) Crohn's disease
E) Concurrent strep infection

3. Systemic treatment for severe extensive tinea versicolor would include:

A) Griseofulvin
B) Terbinafine
C) Ketoconazole
D) Penicillin
E) Amphotericin B