Chapter 189. Yeast Infections: Candidiasis, Tinea (Pityriasis) Versicolor, and Malassezia (Pityrosporum) Folliculitis

The genus Candida is comprised of a heterogeneous group of over 200 yeast species.1 Candida species are ubiquitous yeast-like fungi that form true hyphae, pseudohyphae, and budding yeasts. Candidiasis (or candidosis) refers to a diverse profile of yeast infections caused by members of the genus Candida, and predominantly by Candida albicans. Candida species are among the most common fungal pathogens to affect humans. While the skin, nails, mucous membranes, and gastrointestinal tract are typical sites of infection, Candida may involve any part of the body. Although considered opportunistic human pathogens, Candida species may also exist as commensal organisms of skin and mucosal membranes of the gastrointestinal, genitourinary, and respiratory tracts.

Epidemiology

Frequency

Candida are usually limited to human and animal hosts, however they have also been recovered from the hospital environment: countertops, air-conditioning vents, floors, respirators, and on medical personnel. Oropharyngeal colonization with Candida is observed in up to 50% of healthy individuals 2 and may also be detected in 40%–65% of normal stool samples. In addition, C. albicans exists as a commensal organism in the vaginal mucosa of 20%–25% of asymptomatic, healthy women3 and up to 30% of healthy pregnant women.4 Vulvovaginal candidiasis (VC) is the second most common cause of vaginitis in women.

Candida species are the most common cause of fungal infection in immunocompromised persons. More than 90% of persons infected with HIV not receiving highly active antiretroviral therapy (HAART) develop oropharyngeal candidiasis and 10% of these patients develop esophageal candidiasis.5–6 Candida species are now the fourth most commonly isolated pathogens from blood cultures in patients with systemic infections.7

Mortality/Morbidity

Most candidal infections are mucocutaneous. While in few cases there may be pronounced effect on morbidity, these infections do not lead to death. However, immunocompromised patients including hospitalized patients, may develop candidemia and disseminated candidiasis which have a 30%–40% mortality rate. In fact, systemic candidiasis causes more case fatalities than any other systemic mycosis.

Sex

Neither sex is predisposed to candidal colonization.

Age

Neonates and adults >65 years of age are most susceptible to candidal colonization and mucocutaneous candidiasis.

Etiology and Pathogenesis

Responsible for 50%–60% of all candidal infections, C. albicans is the most common candidal pathogen identified.8 C. albicans has its own virulence factors including adhesion molecules that permit attachment of the organism to other structures, proteinase secretions [aspartyl proteinases (SAP1-9)] that facilitate damage to cell envelopes, as well as the ability to convert to the hyphal form which is thought to be important for the virulence of C. albicans.9

The relative prevalence of C. albicans in clinical isolates is declining, and other species such as Candida glabrata, Candida parapsilosis,1,10 Candida tropicalis, Candida krusei,1,11 and Candida dubliniensis12 are increasingly being encountered as pathogens.13 C. glabrata and C. albicans account for approximately 70%–80% of Candida species recovered from patients with candidemia or invasive candidiasis. Other species of Candida have gained importance because of their frequent intrinsic resistance to systemic antifungal therapy. Certain patient populations are more susceptible to specific Candida species: the presence of C. parapsilosis should be considered in hospitalized patients and those with vascular catheters or prosthetic devices, while Candida tropicalis has been observed to cause candidemia in patients with leukemia and in those who have undergone bone marrow transplantation.

Clinical Manifestations

The mucocutaneous manifestations of candidiasis are represented by several distinct clinical syndromes.

Oral Candidiasis

Acute pseudomembranous candidiasis or thrush is the most common form of oral candidiasis. Predisposing factors include diabetes mellitus, systemic steroid and antibiotic use, pernicious anemia, malignancy, radiation to head and neck, and cell-mediated immunodeficiency2,15–16 (Table 189-1). Thrush appears as discrete white patches that may become confluent on the buccal mucosa, tongue, palate, and gingivae (Fig. 189-1A). This friable pseudomembrane resembles cottage cheese or milk curds and consists of desquamated epithelial cells, fungal elements, inflammatory cells, fibrin, and food debris (Figs. 189-1A–189-1C). Scraping the patches exposes a brightly erythematous surface underneath. Microscopic examination of this material reveals masses of tangled pseudohyphae and blastospores (Fig. 189-2). In severe cases, the mucosal surface may ulcerate.

Acute atrophic candidiasis (erythematous candidiasis), which occurs after sloughing of the thrush pseudomembrane,15 is observed most often in the setting of broad-spectrum antibiotic or systemic glucocorticoid therapy and human immunodeficiency virus infection.2 The most common location is on the dorsal surface of the tongue, where depapillated atrophic patches with minimal pseudomembrane formation are noted. There are both asymptomatic and symptomatic variants, the latter characterized by burning or pain.17

Chronic atrophic candidiasis (denture stomatitis) (Fig. 189-1B) is a common form of oral candidiasis seen in 24%–60% of denture wearers,18 and more commonly occurs in women. Chronic erythema and edema of the palatal mucosal surface in contact with the dentures is present. Presumably, the chronic low-grade trauma and occlusion caused by dentures predispose to candidal colonization and subsequent infection.19

Candidal cheilosis (angular cheilitis or perlèche) is characterized by erythema, fissuring, maceration, and soreness at the angles of the mouth (Fig. 189-1C). This condition is commonly encountered in habitual lip lickers and in elderly patients with sagging skin at the oral commissures. Loss of dentition, poorly fitting dentures, malocclusion, and riboflavin deficiency also predispose one to cheilosis. Cheilosis is often associated with chronic atrophic candidiasis in denture wearers.15

The differential diagnosis for oral candidiasis is summarized in Box 189-1.

Vaginal and Vulvovaginal Candidiasis

VC is the second most common cause of vaginitis, and approximately three-fourths of all women will experience an episode of VC in their lifetime. C. albicans causes 80%–90% of VC and is followed by C. glabrata in frequency.20 Risk factors for VC include systemic antibiotic or steroid use, diabetes mellitus, presence of an intrauterine device, wearing of tight-fitting and synthetic clothing, and immunosuppression.21,22 These factors disrupt vaginal flora of lactobacilli that serve to inhibit overgrowth of Candida.20

Recurrent VC, defined as four or more episodes per year, occurs in up to 10% of women.20 Changes in hormone levels during pregnancy and the luteal phase of the menstrual cycle may induce relapses. Use of genital cleansing solutions or douche may elicit a hypersensitivity response and increase susceptibility to Candida. Frequent sexual intercourse, resulting in vaginal abrasions and involving semen allergy, may also predispose women to recurrent VC.23 When none of the above mentioned factors is involved in VC, one should consider use of antibiotics, immunosuppression, or diabetes mellitus as potential contributors.24

Patients with VC present with a vaginal discharge associated with vulvar pruritus, burning, and occasional dysuria or dyspareunia. Examination shows thick curd-like whitish plaques on the vaginal wall with underlying erythema and surrounding edema that may extend to the labia and perineum. The cervix is normal upon speculum examination.25

Balanitis and Balanoposthitis

Candida spp. cause 30%–35% of infectious balanitis. Factors predisposing to candidal balanitis include diabetes mellitus, an uncircumcised state, and candidal vaginal infection in sexual partners. Occasionally, patients with balanitis complain of transient erythema and burning occurring shortly after intercourse. The eruption involving the penis is pruritic. Physical findings include white patches on the glans or prepuce. Small papules or fragile vesiculopustules on the glans or along the coronal sulcus (Fig. 189-3) break to leave erythematous erosions with a collarette of whitish scale. Infection may spread to the scrotum, gluteal folds, buttocks, and thighs. In diabetic or immunosuppressed patients, a severe edematous, ulcerative balanitis may occur.

Intertrigo

C. albicans has a predilection for colonizing skin folds, intertriginous zones in which the local environment is moist and warm. Usual locations for candidal intertrigo include the genitocrural, gluteal, interdigital, inframammary (Fig. 189-4) areas, and beneath the pannus and axillary areas. Predisposing conditions include obesity, diabetes mellitus, wearing of occlusive clothing and occupational factors.26 The pruritic eruption appears as macerated red erythematous patches and thin plaques with satellite vesiculopustules. These pustules enlarge and rupture, leaving an erythematous base with a collarette of easily detachable scale that contributes to further maceration and fissuring. Cutaneous candidal infection is diagnosed by the typical appearance of the eruption and confirmed by KOH examination and, when necessary, culture. See Box 189-2 for the differential diagnosis of intertriginous candidiasis.

Several clinical variants of Candida intertrigo deserve special mention. Candidal diaper dermatitis results from yeast colonization of the gastrointestinal tract and chronic occlusion with wet diapers. The eruption with pronounced red erythema first appears in the perianal region and spreads to the perineum and inguinal creases (Fig. 189-4C).27 Erosio interdigitalis blastomycetica refers to interdigital candidal or polymicrobial infection of the hands or feet, usually affects the third or fourth interdigital space, where moisture trapping is thought to underlie the condition (Fig. 189-4D). Candida miliaria affects the back in bedridden patients. The eruption begins as isolated vesiculopustules containing yeast, which spread over occluded regions on the back. Candida also colonizes and infects skin around wounds covered with occlusive dressings (Fig. 189-5). Broad-spectrum topical antibiotics contribute to these Candida wound infections.28

Generalized Cutaneous Candidiasis

This is an unusual form of cutaneous candidiasis that manifests as a diffuse eruption beginning as individual vesicles and spreading into confluent areas involving the trunk, thorax, and extremities. The associated generalized pruritus is increased in severity in the genitocrural folds, anal region, axillae, and hands and feet (Fig 189-6).

Candida Folliculitis

Superficial infection involving the infundibulum of hair follicles occurs also in the predisposed patient, most commonly in the setting of diabetes mellitus or immunocompromised states. KOH examination of the contents of follicular pustules distinguishes this condition from bacterial folliculitis.

Candidal Paronychia and Onychomycosis

Candidal infection of the nails and paronychial folds occurs most often in those with diabetes mellitus or who habitually immerse their hands in water (i.e., housekeepers, bakers, fishermen, and bartenders). In paronychia, there is initial redness, swelling and tenderness of the proximal and lateral nailfolds with retraction of the cuticle toward the proximal nail fold (Fig. 189-7). Pain and erythema may extend along the entire nail plate and nail bed.29,30 Candidal paronychia should be differentiated from acute bacterial paronychia or paronychia associated with hypoparathyroidism, celiac disease, acrodermatitis enteropathica (Chapter 130), reactive arthritis syndrome (Chapter 20), acrokeratosis paraneoplastica, and retinoid therapy. Candidal onychomycosis is associated with secondary nail thickening, ridging, whitish discoloration, and occasional nail loss.

Chronic mucocutaneous candidiasis (CMC) is characterized by chronic, treatment-resistant, superficial candidal infections of the skin, hair, nails, and mucous membranes. There is virtually no propensity for disseminated visceral candidiasis.

CMC is frequently associated with endocrinopathies including hypoparathyroidism, hypoadrenalism, and hypothyroidism, as well as conditions associated with specific abnormalities in cell-mediated immunity, such combined immune deficiency syndrome, DiGeorge syndrome, or patients with severely impaired T-cell function (i.e., AIDS). CMC first appearing in adulthood is often associated with thymoma.31 There are several more or less distinct clinical syndromes of CMC (Table 189-2)32–34 in which candidal infections cause oral thrush, diaper dermatitis, angular cheilitis (perlèche), lip fissures, nail and paronychial involvement, vulvovaginitis, and cutaneous involvement. The cutaneous eruption may appear with an erythematous, serpiginous border, or areas of brownish desquamation on a background of mild erythema (Fig. 189-8). Nail involvement is characterized by markedly thickened and dystrophic nail plates in which the entire thickness is invaded by Candida. The paronychial folds are red and edematous, there may be pus, and the fingertips are often bulbous (Fig. 189-7B).

The incidence of disseminated candidiasis is steadily rising as the prevalence of immunosuppressed patients with longer life spans has also increased. The responsible organisms, C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis,35 gain hematogenous access from the oropharynx or gastrointestinal tract when mucosal barrier function is compromised (e.g., by mucositis secondary to chemotherapy), or when intravenous catheters become contaminated. Multiple organ systems including gastrointestinal and respiratory may become involved.36 Recognition of a candidal eruption in the context of disseminated infection may be important to early diagnosis, as ante-mortem blood cultures are negative in a high percentage of patients with autopsy-proven systemic candidiasis.36 Approximately 10% of patients with disseminated candidiasis develop metastatic 0.5–1.0-cm nontender erythematous papules with a hemorrhagic or pustular center (Fig. 189-9) over the trunk and extremities associated with fever and myalgias.37 Some papules may be necrotic in appearance. The differential diagnosis for disseminated candidiasis is provided in Box 189-3.

Laboratory Findings

Direct microscopic examination of specimens for the presence of yeast or isolation of yeast in culture confirms infection. In superficial candidal infections, the diagnosis can be confirmed by microscopic examination skin scrapings or smears obtained from skin, nails, or mucosal surfaces that reveal hyphae, pseudohyphae, or budding yeast cells (Fig. 189-2). Potassium hydroxide smear, or Gram or methylene blue stain is useful for direct demonstration of fungal cells. Cultures from affected nails may help identify the etiologic agent responsible for onychomycosis (dermatophyte vs. yeast). C. albicans readily produce whitish mucoid colonies within 2–5 days on Sabouraud's agar with added antibiotics.

In systemic candidiasis associated with an eruption, the diagnosis may be confirmed from histopathologic examination and tissue culture of lesional skin. Blood cultures are positive in only 50%–60% of cases of disseminated infection.35 Serologic studies using immunodiffusion, counterimmunoelectrophoresis, and latex agglutination methods are fraught with false-negative and false-positive reactions which limit their utility in confirming diagnosis. Newer techniques to detect circulating candidal antigens (e.g., mannan or enolase) or metabolic products (e.g., arabinitol) show improved sensitivities and specificities in serial testing.38 Specifically, the serum (1,3)β-D-glucan detection assay (Glucatell, Fungitell) is a nonculture assay that measures level of β-glucan, a component of the fungal cell wall. In a large multicenter study, the assay yielded high sensitivity (75%–100%), specificity (88%–100%) and positive predictive value with highly reproducible results.39

Microscopic Studies

Since Candida sp. may infect virtually any organ system, specimens for laboratory examination will vary from body fluids to tissue samples. Direct microscopic examination of scrapings from mucosa, skin or nails for the presence of yeast provides bedside evidence to support the clinical diagnosis. Body fluids such as urine and cerebrospinal fluid should be centrifuged and the sediment examined directly to increase the probability of detecting yeast. Specimens must be treated with a clearing agent such as 10% KOH and ink before the material is examined. Candida appears as oval budding cells, elongated filamentous cells connected end-to-end (pseudohyphae), or septate hyphae (Fig. 189-2).

Pathology

Superficial candidiasis is characterized by subcorneal pustules on histopathological examination. Organisms are seldom seen within the pustules but rather are highlighted in the stratum corneum with periodic acid-Schiff (PAS) staining. Examination of a candidal granuloma shows marked papillomatosis and hyperkeratosis and a dense dermal infiltrate consisting of lymphocytes, granulocytes, plasma cells, and multinucleated giant cells. In systemic candidiasis with skin involvement, foci of yeast are observed in the dermis and within dermal vessels. Organisms are identified using PAS, methenamine silver, or methylene blue stains.

Treatment

Treatments used to manage Candida infections may vary based on species of Candida responsible for infection, sensitivity to specific antifungal drugs, anatomic location of infection, underlying disease, and immune status of the patient.

Guidelines in the management of candidiasis were updated in 2009 by the Infectious Disease Society of America.40 These guidelines include recommendations on the appropriate use of echinocandins, caspofungin, micafungin, and anidulafungin, along with voriconazole and posaconazole, as well as lipid formulations of amphotericin B. Fluconazole is still considered a first-line agent in nonneutropenic patients with candidemia or suspected to have invasive candidiasis. Therapeutic options in the management of invasive candidiasis and candidemia include triazoles as well as newer agents such as echinocandins.41,42 A brief discussion on the treatment of candidal infections is included herein. For a detailed review on current therapeutic strategies, please refer to Chapter 232.

Oral Candidiasis

Uncomplicated oral candidiasis may be treated with nystatin suspension 400,000–600,000 units four times per day, or clotrimazole troches 10 mg dissolved in the mouth five times per day. For recurrent cases, oral azoles (see Chapter 232) are proven to be more effective.

Candidal Vulvovaginitis and Balanitis

Two therapeutic approaches exist when considering treatment for candidal vaginitis. Topical imidazole preparations available over the counter, such as butoconazole, miconazole, and clotrimazole, as well as those available by prescription, including tioconazole, econazole, and terconazole are easy to use and effective over 3–7 days of treatment.24 These agents are also safe to use during pregnancy.43 Oral fluconazole, itraconazole, and ketoconazole offer efficacy similar to that of topical therapy (see Chapter 219). Prophylactic regimens to prevent recurrences include weekly clotrimazole 500-mg tablet used intravaginally or fluconazole 150 mg/week orally.24 The recommended treatment for candidal balanitis is topical clotrimazole cream or a single oral 150-mg dose of fluconazole.

Cutaneous

Candidal intertrigo has been treated successfully with topical antifungals (e.g., clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, and nystatin). Powder preparations also keep dry otherwise moist environments that facilitate candidal infections. Systemic antifungal therapy is recommended for extensive cutaneous infections, follicular involvement, or infections in immunocompromised patients.

Candidal Paronychia

Chronic paronychia due to Candida is often resistant to therapy. The most important aspects of therapy include minimizing contributing factors such as water exposures, as well as drainage of any abscess. Topical imidazole in solution form should be considered initially.26 Four percent thymol in ethyl alcohol (compounded by the pharmacy, as it is not commercially available) is drying to candida, and thus may be a suitable alternative. Oral azoles may also be used in otherwise refractory cases.29

Candidal Onychomycosis

Oral itraconazole or fluconazole (triazoles) appear to be most efficacious for candidal onychomycosis. Two treatment regimens are available: the daily dose or pulsed-dose regimen. Itraconazole, which is approved for use for onychomycosis in the United States, may be administered at 200 mg daily for 6 weeks for fingernails and for 12 weeks for toenails. It may also be administered in pulse therapy, 200 mg twice daily for 1 week per month, for a total of two pulses for fingernails and three pulses for toenails.44

Disseminated Candidiasis

Amphotericin B, available in newer lipid-based formulations, as well as caspofungin are effective in treating disseminated candidiasis (see Chapter 232).45

Chronic Mucocutaneous Candidiasis

Oral azoles are first line agents in the treatment of CMC. Regimens include fluconazole 100–400 mg/d or itraconazole 200–600 mg/d used until there is clinical improvement. Initial therapy for acute infection should always be followed by maintenance therapy with the same azole for life.

The genus Malassezia, formerly known as Pityrosporum, currently includes twelve species of lipophilic basidiomycetous yeast: Malassezia furfur, Malassezia pachydermatis, Malassezia sympodialis, Malassezia globosa, Malassezia restricta, Malassezia slooffiae, Malassezia obtusa, Malassezia dermatitis, Malassezia nana,46 Malassezia yamatoensis,47 Malassezia japonica,48 and Malassezia equi.49,50 In 1996, a new taxonomic classification 51 based specifically on morphologic, physiologic and ultrastructural features detected by molecular techniques allowed for the addition of several new species to the Malassezia genus.

The species of Malassezia may be differentiated by their nutritional requirements, morphology, and molecular biology.49,51 All Malassezia species require lipids for growth, because with the exception of M. pachydermatis which has the ability to produce phospholipase, they do not synthesize C14–C16 saturated fatty acids.52 Although previously recognized as a zoophilic organism, M. pachydermatis has been identified only recently as a human pathogen. In one study, the organism caused a series of infections in a neonatal care nursery, where M. pachydermatis was presumably spread to patients from health care workers whose pet dogs were colonized with the fungus.53 It was later shown that the vast majority of dog owners tested positive for M. pachydermatis on their hands.54 Other members of the genus, including M. sympodialis and M. slooffiae, are part of the normal skin flora.55 A few studies also linked M. sympodialis with neonatal cephalic pustulosis, also known as neonatal acne.56,57

Cutaneous infections with Malassezia take two main primary forms: (1) pityriasis versicolor and (2) pityrosporum folliculitis. However, Malassezia may also play some role in the course of other common skin diseases such as seborrheic dermatitis, atopic dermatitis, and psoriasis.49,58

Tinea (Pityriasis) Versicolor

Epidemiology

The prevalence of tinea versicolor in the United States is estimated to be 2%–8% of the population. The infection occurs more frequently in regions with higher temperatures and relative humidity. Tinea versicolor has a worldwide prevalence of up to 50% in the hot and humid environments and as low as 1.1% in colder climates.

Incidence of tinea versicolor is the same in all races, but the eruption is often more apparent in darker-skinned individuals due to resulting alteration in skin pigmentation. No sex predominance is apparent. Tinea versicolor is most common among adolescents and young adults, in whom lipid-producing sebaceous glands are more active.

Etiology and Pathogenesis

M. furfur can be cultured from both affected and normal skin and is considered part of the normal flora, particularly in sebum-rich areas of the body.59 Experimental inoculation of Malassezia under occlusion has resulted in infection.59 The resulting increase in humidity, temperature and CO2 tension appear to be important factors contributing to infection.60 While removal of occlusion promotes healing of the eruption, the organism may still be cultured from clinically uninvolved areas.60 Furthermore, this colonization of follicular structures facilitates a high recurrence rate.

M. furfur is a dimorphic, lipophilic organism that grows in vitro only with the addition of C12–C14 fatty acids such as olive oil and lanolin. Under appropriate conditions, it converts from the saprophytic yeast to the predominantly parasitic mycelial form, which causes clinical disease. Factors predisposing to mycelial transition include a warm, humid environment, hyperhidrosis, oral contraceptive, and systemic corticosteroid use, Cushing's disease, immunosuppression, and a malnourished state.59,61

The yeast may filter natural sunlight and interfere with normal tanning.62 Mayser et al discussed a specific compound synthesized by Malassezia called pityriacitrin that absorbs ultraviolet light.63 Other metabolites of M. furfur are listed on Box 189-4. Specifically, via lipases Malassezia metabolizes various fatty acids such as arachidonic or vaccenic acids and subsequently releases azelaic acid as one of the metabolites. Azelaic acid inhibits the action of the tyrosinase in the melanin production pathway, which results in persistent hypopigmentation of affected skin for months, and sometimes years.64 This hypopigmentation may be accentuated further in summer months if surrounding unaffected skin becomes tan.

While M. furfur had long been identified as the fungus causing tinea versicolor, M. globosa is now thought to be the predominant species involved in its pathogenesis.65

Clinical Findings

The typical presentation of tinea versicolor is scaly oval to round macules scattered over characteristic areas of the body, including the upper trunk, neck, and upper arms (Fig. 189-10). The macules often coalesce forming irregular shaped patches of pigmentary alteration. The color of patches varies from almost white to pink to reddish brown or fawn colored (Fig. 189-10C). The scale is characteristically described as dust-like or furfuraceous (Fig. 189-10D). Extensive scaling can be produced by lightly scraping a #15 scalpel blade over the involved skin.66 Patches may have a wrinkled surface appearance (Fig. 189-11) and this feature serves as a useful clinical pearl for the diagnosis. The presenting concern often relates to the cosmetic appearance of the eruption rather than any symptoms, since pruritus is usually mild or absent. The diagnosis made on clinical grounds is supported by Wood's light (365 nm) examination which may show yellow–orange fluorescence thought to be due to the presence of pteridine and is confirmed by microscopic KOH examination of the scale. Tinea versicolor tends to recur in warmer months of the year.

An inverse form of tinea versicolor is encountered predominantly in flexural areas.67 These sharply demarcated confluent pink erythematous patches may be confused with inverse psoriasis, seborrheic dermatitis, erythrasma, candidiasis, and dermatophytic infections. The differential diagnosis of tinea versicolor is presented in Box 189-5.

Laboratory Tests

Potassium hydroxide (KOH) preparation of skin scrapings demonstrates the characteristic fungal spores and short cigar-butt hyphae (“spaghetti and meatballs”). Visualization of fungal elements may be enhanced by the addition of methylene blue stain to the KOH preparation. Culture is rarely necessary and requires a lipid-containing medium (i.e., olive oil) to demonstrate growth.

Pathology

While the yeast may be identified with hematoxylin and eosin staining alone, visualization is enhanced through PAS stain. Microscopic examination reveals clusters of oval budding yeast cells 3.5 × 4.5 μm long with short, septate, and occasionally branching hyphae (Fig. 189-12) inhabiting the stratum corneum.

Diagnosis

The clinical appearance of tinea versicolor is usually characteristic, and KOH examination is confirmatory. A Wood's lamp examination may show orange–yellowish fluorescence of involved skin, suspected to be a due to pteridine. In some cases, however, the eruption may appear darker, rather than more fluorescent, than unaffected skin under the Wood's light.

Treatment

Tinea Versicolor

Several topical agents are useful in treating tinea versicolor, and these include selenium sulfide, zinc pyrithione, sodium sulfacetamide,68 ciclopiroxolamine,69 as well as azole70 and allylamine antifungal preparations.

A widely used and inexpensive protocol involves using selenium sulfide lotion 2.5%, which is applied liberally to affected areas for 7–10 minutes prior to rinsing. While daily use may be considered for extensive cases, application 3–4 times per week is adequate, and this frequency may be tapered further to once or twice monthly and used as a maintenance regimen to prevent recurrences. Alternatively, ketoconazole shampoo 2% is lathered on to affected areas and left for 5 minutes prior to rinsing; this treatment is repeated for three consecutive days.71 Terbinafine solution 1% applied twice daily to affected areas for 7 days has yielded cure rates of more than 80%.72

Although topical therapy is ideal for localized or mild infections, systemic treatment may be necessary for patients with extensive disease, frequent recurrences, or for whom topical agents have failed.73 Ketoconazole, fluconazole, and itraconazole are the preferred oral agents, and various dosing regimens are effective.74 Oral ketoconazole 200 mg daily for 7 or 10 days, or oral itraconazole 200–400 mg daily for 3–7 days is almost universally effective.75–76 Oral ketoconazole administered as a single 400 mg dose is an easy to use regimen with comparable results.75 Similarly, a single dose of oral itraconazole 400 mg has been shown to be more than 75% effective, and in one study, just as effective as itraconazole given for 1 week.77 Fluconazole is also effective when administered as a single oral dose of 400 mg.78 Oral terbinafine, an allylamine, is not recommended in the treatment of Malassezia related disorders, since the drug is not delivered efficiently to the skin's surface. The potential for drug toxicity and interactions via the influence of azoles on cytochrome p450 isoenzyme activity should be addressed when considering the use of oral azole agents to treat tinea versicolor.79

Prevention

Recurrence is common and regular maintenance application of any of the topical agents helps to reduce high rates of recurrence. While the condition does not leave any permanent scar or pigmentary changes, skin tone may take several months to return to normal. Prevention of recurrences is helpful in limiting long-lasting dyschromia. A regimen of one tablet a month of ketoconazole, fluconazole, and itraconazole has been used successfully to prevent recurrences.80

Pityrosporum (Malassezia) Folliculitis

Epidemiology

Malassezia organisms are observed as skin flora in 75%–98% of healthy people. Colonization by M. furfur begins soon after birth and peaks during adolescence and young adulthood, concomitant with an increase in sebaceous gland activity. No known racial or gender differences exist. Those living in warm and humid climates have higher incidences of Malassezia folliculitis.81

Etiology and Pathogenesis

Malassezia yeasts are classified as superficial mycoses that by definition do not invade past the cornified epithelium. However, in Pityrosporum folliculitis, follicular ostia, and central and deep segments of the hair follicle are involved by Malassezia, most commonly M furfur.82

Clinical Features

The chronic pruritic eruption of Malassezia (Pityrosporum) folliculitis appears as numerous monomorphic 2–4 mm follicular papules and papulopustules with perifollicular erythema on the upper trunk, neck, and upper arms of young and middle-aged adults (Fig. 189-13A). Some may have concomitant seborrheic dermatitis or tinea versicolor, and there have also been cases of associated recalcitrant acne vulgaris.83 KOH examination or culture may be required to distinguish this infection from the more common bacterial folliculitis. On occasion, histologic evaluation via skin biopsy may be necessary for diagnosis. Routine staining with hematoxylin and eosin may identify organisms, although Malassezia may be more easily visualized through PAS stain (Fig. 189-13B). Systemic diseases and pharmacologic agents that hasten growth of yeast, possibly through alterations in host immunity, facilitate infections of hair follicles. Some of these risk factors include pregnancy, diabetes mellitus, Hodgkin disease,84 cancer treated with epidermal growth factor receptor inhibitors,85 HIV infection, and therapy with oral antibiotics, corticosteroids and/or immunosuppressants. Other contributing factors include high heat and humidity and occlusion of the skin and hair follicles with cosmetics, lotions, sunscreens, emollients, olive oil, or clothing.86 As in the case of pityriasis versicolor, recurrence of Malassezia folliculitis is common. See Box 189-6 for the differential diagnosis of Malassezia folliculitis.

Laboratory Findings

To identify the Malassezia yeast forms, scale from involved skin should be scraped with a #15 scalpel blade onto a glass slide and treated with 10% KOH. Alternatively, cellophane tape used to pick up scales from the skin may be mounted on a glass slide with methylene blue that selectively stains the organisms.87 The microscopic appearance of the yeast is classically described as “spaghetti and meatballs” (Fig. 189-12), with fungal spores and short cigar-butt pseudohyphae.

Pathology

Malassezia organisms are noted in dilated follicular units, which may show keratin plugging and cellular debris (Fig. 189-10B). Staining with PAS or methenamine silver will reveal the oval single-budding yeast. When follicular walls rupture, there is a resulting mixed inflammatory infiltrate of lymphocytes, histiocytes, and neutrophils surrounding follicles. Microscopic examination of pustules usually shows budding yeast forms and spores, not hyphae.

Diagnosis

Diagnosis of Malassezia folliculitis is made on clinical grounds, and confirmed by KOH examination of scrapings. Skin biopsy is rarely necessary to make the diagnosis.

Treatment and Prognosis

Malassezia Folliculitis

Both topical and oral antifungal agents are effective agents in the treatment of Malassezia folliculitis and are commonly combined to hasten resolution and maintain clearance. Topical regimens include daily use of ketoconazole shampoo 2%, selenium sulfide lotion 2.5%, and ciclopirox olamine cream 0.77%. There are limited data on the use of systemic agents in treating Malassezia folliculitis. Commonly used regimens include oral ketoconazole 200 mg daily for 4 weeks, fluconazole 150 mg weekly for 2–4 weeks, and itraconazole 200 mg daily for 2 weeks.49,87 Oral terbinafine is not recommended in the treatment of Malassezia related disorders, since the drug is not delivered efficiently to the skin's surface.

Prevention

Recurrence is common. Because relapses almost always occur after treatment is complete, topical agents are continued indefinitely at reduced frequency as a preventative measure. Topical protocols used in the prevention of Malassezia folliculitis include selenium sulfide 2.5% lotion once weekly, ketoconazole 2% cream once weekly, and ketoconazole 2% shampoo 2–3 times weekly. Maintenance therapies with systemic agents include oral itraconazole 400 mg once monthly and oral fluconazole 200 mg once monthly.