Malassezia (Pityrosporum) Folliculitis

Background

Pityrosporum folliculitis (PF) is an inflammatory skin disorder that typically manifests as a pruritic, follicular papulopustular eruption distributed on the upper trunk of young to middle-aged adults. Weary et al first described Pityrosporum folliculitis in 1969, and, later in 1973, Potter et al^[1] identified Pityrosporum folliculitis as a separate clinical and histologic diagnosis. See the image below.

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Left: A 25-year-old man with complaints of slightly pruritic, monomorphic follicular papules, pustules, and secondary keloid on the upper trunk and ne....

Yeasts, specifically Malassezia furfur, are the pathogenic agents in Pityrosporum folliculitis. M furfur has been linked to several skin diseases, including seborrheic dermatitis, folliculitis, confluent and reticulated papillomatosis, and pityriasis versicolor.^{[2, 3]} In 1874, Malassez first described round and oval budding yeasts from scales of patients with seborrheic dermatitis. He coined the phrases "bottle bacillus of Unna" to describe the small oval cells in the scale and "spore of Malassez" to name the bud that is observed in association with the yeast. Saborouraud proposed the Pityrosporum genus in 1904 to describe the budding yeast cells without hyphal elements from normal skin. Later, in the 1900s, Pityrosporum ovale and Pityrosporum orbiculare were isolated by Castellani and Chalmers and Gordon, respectively.

These 2 yeast species, collectively with fungal forms, are classified as M furfur because of controversy and confusion of the grouping of various lipophilic yeasts and fungi of the skin. This grouping has simplified the classification to one name, which applies regardless of the morphology of the organism. With the advancement of technology, 7 species of Malassezia were recognized: M furfur,Malassezia pachydermatous,Malassezia sympodialis,Malassezia globosa,Malassezia obtusa,Malassezia restricta, and Malassezia slooffiae.^[4]

Pityrosporum folliculitis is caused by Malassezia species that are part of the cutaneous microflora and not by exogenous species.^[5] However, the focus of this article is M furfur, which is considered the pathologic agent of Pityrosporum folliculitis. Lesions are chronic, erythematous, pruritic papules and pustules, which occur in a follicular pattern. These lesions are usually present on the back and chest and, occasionally, on the neck, shoulders, upper arms, and face.

The diagnosis of Pityrosporum folliculitis is based on clinical suspicion of the classic presentation of pruritic papulopustules found in a follicular pattern on the back, chest, upper arms, and, occasionally the neck. They are rarely present on the face. An improvement in the lesions with empiric antimycotic therapy supports a clinical diagnosis of Pityrosporum folliculitis.

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Pathophysiology

M furfur (ie, P ovale and P orbiculare) is a lipophilic, saprophytic, budding, unipolar, dimorphic, gram-positive, double-walled, oval-to-round yeast. M furfur is part of the normal skin flora. It is suggested that the similar yeasts P orbiculare and P ovale are actually identical and that they are morphologic variants of M furfur.

Malassezia yeasts are classified as superficial mycoses that by definition do not invade past the cornified epithelium. In Pityrosporum folliculitis, however, the organism is present in the ostium and central and deep segments of the hair follicle.

Plugging of the follicle followed by an overgrowth of yeast that thrives in the sebaceous environment is believed to be the etiology. Malassezia yeasts require free fatty acids for survival. Usually, they are found in the stratum corneum and in pilar folliculi in areas with increased sebaceous gland activity such as the chest and back. The yeasts hydrolyze triglycerides into free fatty acids and create long-chain and medium-chain fatty acids from free fatty acids. The result is a cell-mediated response and activation of the alternative complement pathway, which leads to inflammation.

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Etiology

Pityrosporum folliculitis is caused by Malassezia yeasts, which are lipophilic. Several factors can lead to changes in immunity, sebum production, and the growth of skin flora. These factors help to produce favorable conditions for growth of these yeasts.

Systemic diseases and pharmacologic agents that encourage the growth of yeast, possibly because of alterations in immunity, include the following:

• Diabetes mellitus
• Cushing disease
• Hodgkin disease^[6]
• Cancer treated with cetuximab (IMC-C225; marketed under the name Erbitux), a chimeric (mouse/human) monoclonal antibody epidermal growth factor receptor (EGFR) inhibitor for the treatment of metastatic colorectal cancer and head and neck cancer^[7]
• HIV infection
• Corticosteroids and/or immunosuppressant therapy following organ transplantation^{[8, 9, 10]}
• Crohn disease treated with infliximab a monoclonal antibody against tumor necrosis factor alpha.^[11]

An increase in sebum production, such as that in pregnancy,^{[12, 13]} and high levels of androgens may potentiate the development of Pityrosporum folliculitis.

Antibiotics can alter normal skin flora, allowing the yeast to proliferate.

Pityrosporum folliculitis more frequently occurs in environments of high heat and humidity.

Occlusion of the skin and hair follicles with cosmetics, lotions, sunscreens, emollients, olive oil, or clothing creates favorable conditions for Pityrosporum folliculitis.

Anticonvulsant therapy and Down syndrome^[14] are other conditions that are associated with Pityrosporum folliculitis.

Other related and coexisting conditions may include the following:

• Seborrheic dermatitis
• Confluent and reticulated papillomatosis
• Systemic candidiasis^[15]

Some individuals seem to have an innate propensity for Pityrosporum folliculitis. In one experiment, Malassezia yeasts were applied to occluded forearm skin in patients with Pityrosporum folliculitis. Flares of Pityrosporum folliculitis occurred at the application site. In the same experiment, Pityrosporum folliculitis did not develop in patients with no prior diagnosis of the condition.

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Epidemiology

Frequency

United States

Malassezia organisms can be found on the skin in 75-98% of healthy people. These organisms are part of the normal skin florae of many individuals who do not have signs or symptoms of folliculitis or other disease. Colonization by M furfur begins soon after birth, and the peak presence of the yeasts occurs in late adolescence and early adult life, coinciding with increasing activity of sebaceous glands and concentration of lipids in the skin.

International

P ovale is present on 90-100% of the surface of healthy skin; higher numbers of the yeast are present on the chest and back. Certain climates influence the percentage of people with P ovale and the number of people with Pityrosporum folliculitis. People living in warm and humid climates have a higher incidence of Pityrosporum folliculitis. One clinic in the Philippines documented that 16% of all patient visits were a result of Pityrosporum folliculitis.^[16] A 2008 report from China cites that 1.5% off all dermatology patients were diagnosed with Pityrosporum folliculitis, most of them healthy, middle-aged males.^[17]

Race

No known racial differences in the frequency of Pityrosporum folliculitis exist.

Sex

Reports of Pityrosporum folliculitis vary from a male-to-female ratio of 1:1 to a predominance of one or the other sex. In the literature, the consensus is that the female-to-male ratio is 1.5:1.

Age

Pityrosporum folliculitis is recognized as one that affects youths and young and middle-aged adults^[18] ; Pityrosporum folliculitis is most common in those aged 13-45 years. However, 3 cases of Pityrosporum folliculitis occurred in an ICU setting in older individuals who were in consecutive beds, who received care from the same nursing staff, and who all received high-dose antibiotics.^[19] . The very young can also be affected.^[3]

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Prognosis

The prognosis in Pityrosporum folliculitis is good. With treatment, Pityrosporum folliculitis can completely resolve. Without treatment, Pityrosporum folliculitis can be pruritic.

Pityrosporum folliculitis may be a bothersome condition (ie, severe pruritus), but the lesions are benign. Some underlying conditions that predispose the patient to Pityrosporum folliculitis include diabetes mellitus, immunodeficiency, and systemic candidiasis^[20] ; these conditions may cause morbidity. Consider the presence of predisposing conditions when Pityrosporum folliculitis is diagnosed.

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History

The Pityrosporum folliculitis patient's history is that of a chronic, often extremely pruritic, papular and pustular eruption with perifollicular erythema most commonly on the back, upper arms, and chest.

The main differential diagnoses of Pityrosporum folliculitis are acne vulgaris and staphylococcal folliculitis. Often, patients have been treated with medication appropriate for acne vulgaris, resulting in no improvement or worsening of their condition.^[21] Recalcitrant acne should be reevaluated for potential Pityrosporum infection.^[22]

A history of hospitalization may also play a role in initial colonization.^[23]

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Physical Examination

Multiple, discrete, 2- to 4-mm erythematous monomorphic, papules and, later, pustules are observed. Lesions have a definite follicular pattern. Material expressed from pustules is white to yellow.

Pityrosporum folliculitis is present on body locations in which Malassezia organisms are most abundant: back and chest, neck, shoulders, scalp,^[24] upper arms (occasional), and face (rare).

Under a Wood light, bright blue or white fluorescence is observed in clinically uninvolved follicles in the location of the lesions.

Pityrosporum folliculitis often is mistaken for acne vulgaris; however, no comedones or cysts are associated with Pityrosporum folliculitis.^[25]

Many patients have coexisting seborrheic dermatitis.^[20]

See the image below.

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Left: A 25-year-old man with complaints of slightly pruritic, monomorphic follicular papules, pustules, and secondary keloid on the upper trunk and ne....

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Laboratory Studies

A potassium hydroxide (KOH) preparation may be helpful for microscopic identification of the yeasts associated with Pityrosporum folliculitis (PF).

Culturing and identification of the organism are rarely performed, and the tests usually are not available. For Malassezia yeasts to grow, olive oil must be added to the culture media. This is not a routine study for the mycology laboratory.

Shibata et al report the presence of galactomannan on cells of Malassezia species, which they suggest has not previously been reported in the literature. Results of their comparative antibody reaction studies lead them to suggest the potential for antigen detection as a diagnostic tool in Malassezia infection.^[27]

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Histologic Findings

The basic lesion observed at histologic evaluation is that of folliculitis. The ostium of the hair follicles is dilated, with keratin plugging, cellular debris, and an inflammatory infiltrate including lymphocytes, histiocytes, and neutrophils. Monocytic, perifollicular infiltrate, and mucin deposits are observed around the infundibulum. Some follicles may be cystic and ruptured.

Malassezia yeasts are observed in the central and deep follicle, but they are most densely present in the ostium and pilary canal. Periodic acid–Schiff (PAS) and Grocott-Gomori methenamine-silver staining reveal the oval single-budding yeast; however, these organisms can be observed without stain as well. No mycelial forms are observed with staining. Also detected are 2-4 µm PAS-positive spores in the entire follicle. Most often, spores are observed as aggregates. Both methylene blue and Parker ink staining have been suggested as useful to detect Malassezia; however, Parker ink is a more specific stain for the organism.

High titers of circulating immunoglobulin G antibodies against P ovale can also be detected in persons with this disease.^[28]

Skin biopsy is usually reserved for the diagnosis of lesions that resemble Pityrosporum folliculitis but are located on surfaces where Pityrosporum folliculitis less commonly occurs. A diagnosis of Pityrosporum folliculitis in these unusual locations may indicate more severe disease. Early biopsy should be considered in patients with significant immunosuppression, such as those with AIDS, because the differential is much broader in these patients.^{[29, 30]}

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This photo is high-power hematoxylin and eosin staining of a biopsy confirming Pityrosporum folliculitis. There is a hair shaft within a hair follicle....

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Medical Care

Both topical and oral antifungals are effective agents in the treatment of Pityrosporum folliculitis (PF). Oral antifungals have the advantage of dramatic, immediate clearing of the lesions and are the most effective treatment.^[31]

Patients have been successfully treated with oral pulse itraconazole and weekly fluconazole. M sympodialis is highly sensitive to terbinafine, while other species are more resistant to treatment with this medication.^[32]

A course of oral ketoconazole^[33] and topical ketoconazole shampoo is currently the recommended treatment.^[34] Oral medication should be discontinued when the lesions resolve. Because relapse almost always occurs when treatment is withdrawn, topical ketoconazole is indefinitely continued after successful initial treatment with oral medication.  

Other topicals that are used to treat Pityrosporum folliculitis are ciclopirox olamine cream, econazole cream, alcohol and salicylic acid solution (with or without benzoic acid 5%), propylene glycol 50% in water, and selenium sulfide shampoo.^[35] Other topical treatments with some reported success include tea tree oil, honey, tacrolimus, and cinnamic acid.^[36]

In cases associated with antibiotic use, discontinuing the antibiotic may be helpful.

Retinoids, which are used for comedones in acne, have no effect because no comedones are present in Pityrosporum folliculitis.^{[37, 38]}

Tetracycline does not help in Pityrosporum folliculitis, and it may exacerbate the condition by further destroying the normal bacterial skin flora and allowing further spread of Malassezia yeasts.

Other studies suggest topical photodynamic therapy with methyl aminolevulinate may be a potential therapy for recalcitrant Malassezia folliculitis.^[39]

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Consultations

No consultations are necessary in Pityrosporum folliculitis.

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Prevention

Advise patients with Pityrosporum folliculitis to avoid predisposing factors such as emollients, occlusive topicals, occlusive nylon clothing, immunosuppressants, steroids, and antibiotics.

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Long-Term Monitoring

Regular clinical follow-up may be necessary in Pityrosporum folliculitis (PF) to monitor the patient's condition and refill prescriptions.

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Medication Summary

The goal of pharmacotherapy for Pityrosporum folliculitis is to reduce morbidity and prevent complications.

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Ciclopirox (Loprox)

• Dosing, Interactions, etc.

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

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Ketoconazole (Extina, Nizoral shampoo, Xolegel)

• Dosing, Interactions, etc.

Clinical Context:  Ketoconazole is available as a tablet, a 2% cream, and a 1% or 2% shampoo. It is a midazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death.

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Econazole topical (Ecoza)

• Dosing, Interactions, etc.

Clinical Context:  Econazole is effective in cutaneous infections. It interferes with RNA and protein synthesis and metabolism. Econazole disrupts fungal cell wall permeability, causing fungal cell death.

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Class Summary

Antifungals are used in the first-line therapy of Pityrosporum folliculitis. The use of topical agents has few adverse effects besides an allergic reaction to the active medicine or inactive component. The mechanism of action usually involves the inhibition of pathways (eg, enzyme, substrate, transport) that are necessary for sterol and/or cell membrane synthesis, or the permeability of the cell membrane (polyenes) of the fungal cell is altered.

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Selenium sulfide topical (Tersi, Dandrex, Selsun Blue, Head & Shoulders)

• Dosing, Interactions, etc.

Clinical Context:  Selenium sulfide blocks the enzymes involved in epithelial tissue growth; use 1% or 2.5% shampoo and/or lotion.

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Class Summary

These agents are helpful in the treatment of itching and flaking associated with dermatitis.

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