Pediatric Tinea Versicolor

Tinea versicolor or pityriasis versicolor is a common superficial cutaneous fungal infection characterized by pityriasiform desquamation and hypopigmented or hyperpigmented macules formation, primarily located on the chest and back with tendency to spread. The condition is frequently asymptomatic; however, some patients occasionally report pruritus. Tinea versicolor results from an overgrowth of Malassezia furfur, which is part of normal skin flora and produces pigmentation changes when it flourishes beyond normal levels.

Historical data

The first clinical observation of pityriasis versicolor was by Willan in 1801.[1] The causative agent was isolated by Eichsted in 1846; 7 years later, the German surgeon Robin named it Microsporon furfur. Billon proposed a new family name Malassezia and subsequently proposed a new species name: Malassezia furfur. Clatelani and Chambers and, later, Gordon proposed the name Pityrosporon ovale or orbiculare and confirmed it role as a causative agent.[1]

M furfur is a dimorphic lipophilic organism that is able to exist in both yeast and mycelial forms and does not attack the hair shaft, nails, or mucous membranes. The infection is localized to the stratum corneum and chronically recurs in predisposed patients. It is more common during warmer months and in warmer climates. Sun exposure frequently makes the lesions more apparent because affected areas become hypopigmented. In temperate climates, patients develop the disease in the spring and summer. In the tropics, patients are more likely to have tinea versicolor throughout the year.[2]

Although M furfur is a component of normal flora, it is also an opportunistic pathogen.[3] The organism is considered a possible factor in other cutaneous diseases, including Pityrosporum folliculitis, confluent and reticulate papillomatosis, seborrheic dermatitis, the provocation of psoriatic lesions, and some forms of atopic dermatitis.[4]

Studies also show that tinea versicolor occurs with malnutrition and various diseases, including Cushing syndrome. Pregnancy and oral contraceptives may influence susceptibility, but firm data are lacking. Patients with AIDS may present with severe seborrhea but do not have a higher incidence of tinea versicolor. Systemic infections are attributed to Pityrosporum in extremely rare cases.

Different rare clinical forms have been described as follows:

• Papulous variant

• Erythematous and papulous variant in children

• Tinea versicolor with atypical localization on face

• Tinea versicolor with atypical localization on wrists

• Pityriasis versicolor alba

The nutritional requirement of M furfur is one of the most important factors that affect the growth of the organism on the skin. Studies show that lesion sites have a decrease in sebaceous gland secretions and water content, along with an increase in pH value compared with normal skin. M furfur is lipophilic, and the mycelial stage of M furfur can be induced in vitro by the addition of cholesterol and cholesterol esters to the appropriate medium. However, significantly more amino acids are extracted from the skin of infected patients, suggesting that amino acids, rather than lipids, are critical for the development of the disease. In vitro, the amino acid asparagine stimulates the growth of the organism, while glycine induces hyphal formation.

Patient immune response also affects infection. Studies suggest a reduced body response to the specific fungal elements that produce tinea versicolor. In various studies, defects in lymphokine production and natural killer T cells were found; phytohemagglutinin (PHA) and concanavalin A (Con A) stimulation was decreased; and interleukin (IL)–2, IL-10, and interferon (IFN)–g production by lymphocytes was decreased in affected patients. The exact pathophysiology of this disorder remains undefined, and additional studies are needed.

In patients with hypopigmentation, tyrosinase inhibitors competitively inhibit an enzyme necessary for melanocyte pigment formation. In hyperpigmented macules, the organism induces enlargement of melanosomes made by melanocytes in the basal layer of the epidermis.

M furfur is now the most commonly accepted name for the etiologic agent of tinea versicolor. Thus, P orbiculare, P ovale, and Malassezia ovalis are synonyms .

M furfur is a dimorphic lipophilic organism that is cultured only in media enriched with C12-sized or C14-sized fatty acids. Malassezia is able to exist in both yeast and mycelial forms, with yeast most commonly associated with saprofital form (P ovale). Historically, the name M furfur was used to designate the fungal pathogen of tinea versicolor before it is grown in culture. M furfur is not a dermatophyte, does not grow on dermatophyte test media (DTM), and does not respond to griseofulvin therapy.

With the advent of DNA sequencing, numerous pathogenic and nonpathogenic species were found. Some of them appear to be more common in certain areas of the world, and some are more likely to be pathogenic in one area and not in another. Much of the confusion was resolved with the taxonomic revision in 1996, based on sequencing of the large-subunit rRNA and nuclear DNA of more than 100 isolates of Malassezia species.[3] The genus Malassezia was revised to include 7 species: Malassezia globosa, Malassezia sympodialis, M furfur, Malassezia slooffiae, Malassezia pachydermatis, Malassezia restricta, and Malassezia obtusa. The clinical significance of each of these species is under investigation. A study of the epidemiology of Malassezia yeasts associated with pityriasis (tinea) versicolor in Canada revealed the most frequently isolated species included M sympodialis, M globosa, and M furfur.

One study found M globosa in 97% of patients with tinea versicolor; it was found alone in 60% of cases, was associated with M sympodialis in 29% of cases, and was associated with M slooffiae in 7% of cases.[3]  M sympodialis and M slooffiae were found in similar percentages on clinically uninvolved skin of the trunk, whereas M globosa was not isolated at other sites. Thus, some authors suggest that M globosa in its mycelial phase is the causative agent of tinea versicolor.[3, 4]

Frequency

United States

Depending on the method and sensitivity of sampling methods, Malassezia species may be found in as many as 18% of infants and 90-100% of adults. Clinical tinea versicolor is more common in areas with higher temperatures and higher relative humidities. The incidence of this condition is approximately 2-8% of the population. The exact incidence is difficult to assess because many affected individuals may not seek medical attention.

International

Tinea versicolor occurs worldwide, with an incidence rate of 50% in the humid, hot environment of Western Samoa and 1.1% in the colder environment of Sweden. In temperate zones, the onset occurs during the warmer months of the year, and the lesions generally fade in the cooler and drier months. In tropical countries, where heat and high humidity are more continuous, people develop more extensive and persistent disease.

Race

Although tinea versicolor is usually more apparent in darker-skinned individuals, the incidence of tinea versicolor appears to be the same in all races.

Sex

Females and males are equally affected.

Age

In temperate zones (including most of the United States), tinea versicolor is rare in children. Affected infants or children often have an atypical presentation. In temperate areas, the disorder is common in young adults aged 17-24 years. In tropical climates, tinea versicolor is more common in individuals aged about 20-30 years. Beyond age 40 years, lipid levels in the skin gradually decrease, and tinea versicolor becomes uncommon.

Prognosis is excellent. Although tinea versicolor is recurrent in some patients, the condition remains treatable.

Morbidity primarily results from the discoloration. The adverse cosmetic effect of lesions may lead to significant emotional distress, particularly in adolescents. Tinea versicolor frequently recurs despite adequate initial therapy. Even with adequate therapy, residual pigmentary changes may take several weeks to resolve.

The yeasts of the genus Malassezia have been associated with numerous other diseases that affect the human skin, such as Malassezia (Pityrosporum) folliculitis, seborrheic dermatitis, atopic dermatitis, psoriasis, confluent and reticulated papillomatosis, onychomycosis, and transient acantholytic dermatosis.

Tinea versicolor is caused by a fungus that is normally present on the skin surface and, therefore, is not considered a contagious disease. The disease causes no permanent sequelae, and any pigmentary alterations resolve entirely within a few months of adequate treatment. Effective therapy is available. Recurrences are common, and prophylactic therapy may be required.

Questioning the patient with tinea versicolor about skin or systemic diseases, current therapy, and drug allergies provides guidance in selecting an appropriate therapy. The following are factors that may be used to guide therapy:

• Other diseases, including renal disease, hepatic disease, and endocrine disease (eg, diabetes mellitus)

• History of HIV or other immunocompromising disorder, which can increase the severity of tinea versicolor

• Other skin disorders, including personal or family history of atopy or other eczematous conditions

• Current or recent topical or systemic therapy

• Drug allergies

• Seasonal variations in skin color

• Use of some body oils, which may supply additional nutrients to the M furfur

• Sweat associated with exercise, which may contribute to disease development and recurrence

Lesion characteristics

Skin lesions are either hypopigmented or hyperpigmented maculae in various shapes. Hyperpigmented maculae become hypopigmented after solar irradiation and subsequent tanning, as the name implies.

Lesions are either macules or very superficial plaques with fine scale that may not be evident except upon close examination. Even when scale is not apparent, when the skin is wiped with a wet cloth and scraped for examination, it yields a surprising amount of dirty-brown keratin. In some cases, lesions may appear atrophic (atrophying pityriasis versicolor).[5]

If not, the areas of dyschromia may represent residual effects of previously treated tinea versicolor. Occasionally, determining whether the lighter or darker skin is affected is difficult.

Lesions have relatively sharp margins and may be lighter or darker than the normal skin color. The lesions are frequently a light tan color in light-skinned individuals. The color of lesions varies from individual to individual, but each individual's lesions are approximately the same color. Lesions are evenly pigmented. The inflammatory border, relative central clearing, and erythema seen in most fungal infections are lacking.

Small lesions are usually circular or oval. Confluent patches with scattered circular or oval macules around the edges are common. Other lesions may be large enough to cover most of the trunk.

Lesions are usually asymptomatic but may be mildly pruritic. The pruritus is more intense when the patient is excessively warm.

Residual hypopigmentation, without overlying scale, may remain for many months following effective treatment. These areas may become more apparent following sun exposure, causing the patient to incorrectly suspect that the infection has recurred.

Examples of findings in tinea versicolor are shown in the images below.

Lesion distribution

The upper trunk is most commonly affected, but the lesions often spread to the upper arms, antecubital fossae, neck, abdomen, and popliteal fossae. Lesions in the axillae, groin, thighs, and genitalia are less common.[6] Facial, scalp, and palmar lesions occur in the tropics but are rare in temperate zones

In some patients, tinea versicolor primarily affects the flexural regions, the face or isolated areas of the extremities. This unusual pattern of tinea versicolor is seen more often in immunocompromised hosts and can be confused with candidiasis, seborrheic dermatitis, psoriasis, erythrasma, and dermatophyte infections.

Lesions that are imperceptible or doubtful are more visible using a Wood lamp in a darkened room.

The disease has benign course; however, it tends to have recurrences that must be properly treated. Some patients report for itching, burning and irritation of lesions. Severe depigmentation may cause significant psychological discomfort.

The diagnosis of tinea versicolor is usually made based on clinical examination findings; however, the diagnosis is easily confirmed with microscopic examination of scales soaked in 10-15% potassium hydroxide (KOH). See the images below.

Microscopic examination

Microscopic examination demonstrates the characteristic thick-walled spherical or oval yeast forms and coarse septate mycelium, often broken up into short filaments. This combination of mycelium strands and numerous spores is commonly referred to as "spaghetti and meatballs."

Liquid blue ink, methylene blue, or Swartz-Medrik stain can be added to the KOH preparation for better visualization of the causative organism.

Scales may also be removed using clear adhesive tape; they are then directly examined. The tape must be clear and is pressed several times over involved areas of skin. The tape is then lightly pressed, sticky side down, onto a microscope slide. A small drop of methylene blue or other appropriate stain is placed at the edge of the tape and allowed to run between the tape and the glass slide. Spores, often in grapelike clumps, and mycelium are easily seen. See the image below.

A few reports in literature have recently stated that 1% Chicago Sky Blue 6B (CSB) staining with 10% KOH is a new promising contrast diagnostic method for pityriasis versicolor, with 100% of sensitivity compared with 60.9% in culture.[7]

Cultures

M furfur is a dimorphic lipophilic organism, which is cultured only in media enriched with C12-sized to C14-sized fatty acids. It is not a dermatophyte, does not grow on DTM, and does not respond to griseofulvin therapy.

If inoculated into lipid-rich media, the scales of tinea versicolor show spherical yeasts that produce the mycelial phase of the normal flora yeast P orbiculare. Scales that show mycelium and clusters of oval yeasts on direct microscopy grow P ovale on culture.

Colonization by M furfur is especially dense in the scalp, the upper trunk, and the flexures. In patients with clinical disease, the organism occurs in both the filamentous (hyphal) and the yeast (spore) stage forms.

The disease does not require any imaging studies.

Wood lamp evaluation

Pityriasis versicolor showe blue-green fluorescence of macular dyschromic lesions if irradiated by ultraviolet light with wavelength of approximately 365 nm (black light). However, the test findings may be negative in individuals on antimycotic therapy of those who have recently showered because the fluorescent is water soluble.[8]

The characteristic histological changes include hyperkeratosis, parakeratosis, and slight acanthosis with a mild perivascular inflammatory infiltrate in the upper dermis. The organism is usually present in the upper layers of the stratum corneum, and electron microscopy reveals invasion between and within the keratinized cells.

M furfur is detected by hematoxylin and eosin (H and E) stain alone, although periodic acid-Schiff (PAS) or methenamine-silver staining facilitates detection.

Tinea versicolor can be treated with various agents, and skin color alterations usually resolve within a few months of treatment.[9] It does not leave any permanent scars or pigment changes.

Topical therapy alone is indicated for most patients. Systemic treatment is indicated for extensive involvement, for recurrent infections, or when topical therapy has failed. Because treatment is relatively easy and recurrence is common, therapy must be as safe, inexpensive, and convenient as possible. A plan for prophylactic therapy should be discussed with all patients to reduce the high recurrence rate.

Various regimens involve both topical and oral therapies.[10, 11] The most common is varying regimens of selenium sulfide lotion, topical zinc pyrithione, topical benzoyl peroxide, and topical therapy with imidazoles. Oral imidazole therapy is used in adults but less commonly in children.[12, 13, 14]

The disease does not require any surgical care.

Because studies indicate that tinea versicolor may associate with malnutrition the diet of patients have to be rational and not restrictive.

Activity limitations are not necessary. However, active patients who excessively perspire are more likely to develop recurrences.

Tinea versicolor has a high recurrence rate and may require frequent prophylactic treatment with intermittent topical or oral therapy.

Good personal hygiene may help limit recurrences. Specifically, patients should shower as soon as possible after participating in activities or exercise that produce significant perspiration.

Some authors recommend prophylaxsis with varying regimens of selenium sulfide shampoo or lotion.

Tinea versicolor tends to be associated with recurrences that must be properly treated.

Tinea versicolor responds well to both topical and oral antimycotic therapies. Some patients prefer oral therapy because of convenience, while others prefer the safety of topical therapies. Many effective topical therapies are available without prescription and can be used for suppressive therapy or for treating recurrences without the need for a follow-up visit. Traditional topical herbal therapies are still used in many parts of the world.[15]

Topical therapy alone is indicated for most patients. Systemic treatment may be indicated for patients with extensive involvement, those with recurrent infections, or those in whom topical therapy has failed.

Systemic azoles are highly effective against M furfur and are usually combined with topical antimycotics in severe cases, and new agents are being investigated.[16]  While oral fluconazole has been used in tinea versicolor, the results may be no better than with topical agents.[17, 18]

Class Summary

Selenium sulfide is effective against M furfur; it also has cytostatic effects on the epidermis and follicular epithelium, thus reducing corneocyte production. Azole, allylamine and other antifungal creams are also highly effective mycocides against M furfur.

Selenium sulfide topical (Selsun Blue, Exsel, Head & Shoulders)

Selenium sulfide is available as a shampoo or lotion in 1% or 2.5% concentrations. It is a safe and effective therapy that has been used for years. The principle advantages of selenium sulfide are its low cost, over-the-counter availability, and convenient application. However, it is an irritant, and some patients report itching or eczema after overnight applications. It may also stain clothes and bedding. Lotion is preferred in children and patients with sensitive skin.

Clotrimazole topical (Lotrimin-AF, Canesten)

Clotrimazole is an imidazole broad-spectrum antifungal agent. It inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Econazole topical (Ecoza)

Econazole is an antifungal agent that is a water-miscible base consisting of pegoxol 7 stearate, peglicol 5 oleate, mineral oil, benzoic acid, butylated hydroxyanisole, and purified water. The color of the soft cream is white to off-white and is for topical use only. It interferes with RNA and protein synthesis and metabolism. It disrupts fungal cell wall permeability, causing fungal cell death. Econazole exhibits broad-spectrum antifungal activity against many gram-negative organisms. It is effective in cutaneous infections.

Ketoconazole topical (Nizoral)

Ketoconazole is an imidazole broad-spectrum antifungal agent. It inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Oxiconazole (Oxistat)

Oxiconazole damages the fungal cell wall membrane by inhibiting the biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out and resulting in fungal cell death.

Sertaconazole (Ertaczo)

Sertaconazole is an imidazole broad-spectrum antifungal agent. It inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Ciclopirox (Batrafen, Loprox)

Ciclopirox interferes with the synthesis of DNA, RNA, and protein by inhibiting the transport of essential elements in fungal cells.

Naftifine (Exoderil, Naftin)

Naftifine is a broad-spectrum antifungal agent and synthetic allylamine derivative; it may decrease the synthesis of ergosterol, which, in turn, inhibits fungal cell growth.

Terbinafine topical (Lamisil)

Terbinafine inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal cell death. Use the medication until symptoms significantly improve. The duration of treatment should be greater than 1 week, but not greater than 4 weeks.

Butenafine (Mentax)

Butenafine inhibits squalene epoxidation, which, in turn, causes blockage of ergosterol biosynthesis (an essential component of fungal cell membranes). It is used topically for tinea (pityriasis) versicolor due to M furfur, tinea pedis (ie, athlete's foot), tinea corporis (ie, ringworm), and tinea cruris (ie, jock itch) due to Epidermophyton floccosum, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton tonsurans.

Class Summary

Systemic azoles are highly effective against M furfur and are usually combined with topical antimycotics in severe cases, and new agents are being investigated.

Ketoconazole oral (Nizoral)

Ketoconazole is an imidazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.  While available as both a topical and systemic agent, systemic use of the drug carries a black box warning and is inappropriate for conditions that are not severe or life-threatening. M furfur is eradicated by the presence of ketoconazole in outer skin layers.

Fluconazole (Diflucan)

Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. It has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Fluconazole is available as tablets for oral administration, as a powder for oral suspension, and as a sterile solution for intravenous use. It has fewer adverse effects and better tissue distribution than older systemic imidazoles. It is most commonly used in the treatment of candidiasis. While it has been used in tinea versicolor, the results may be no better than with topical agents.

Itraconazole (Sporanox, Orungal)

Itraconazole is a synthetic triazole antifungal agent that inhibits fungal cell growth by inhibiting the cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.