Malassezia (Pityrosporum) Folliculitis

Practice Essentials

Malassezia (Pityrosporum) folliculitis (MF) 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. Pityrosporum folliculitis was first described by Weary et al in 1969, and it was identified as a separate clinical and histologic diagnosis by Potter et al in 1973.

Yeasts, Malassezia furfur in particular, are the pathogens in MF. M furfur has been linked to several skin diseases, including seborrheic dermatitis, folliculitis, confluent and reticulated papillomatosis, and pityriasis versicolor.^{[1, 2, 3]}  In 1874, Malassez described round and oval budding yeasts from scales of patients with seborrheic dermatitis, using the phrases "bottle bacillus of Unna" for the small oval cells in the scale and "spore of Malassez" for the bud associated with the yeast. In 1904, Saborouraud proposed the genus Pityrosporum for the budding yeast cells without hyphal elements from normal skin. Later in the 1900s, the species Pityrosporum ovale and Pityrosporum orbiculare were isolated.

As a consequence of controversy and confusion regarding the grouping of various lipophilic yeasts and fungi of the skin, these two yeast species, collectively with fungal forms, were reclassified under a single name, M furfur, which applies regardless of the morphology of the organism. Subsequent advances in technology led to the recognition of seven species of Malassezia: M furfur, Malassezia pachydermatis, Malassezia sympodialis, Malassezia globosa, Malassezia obtusa, Malassezia restricta, and Malassezia slooffiae.^[4]  Additional species have since been identified.^[1]

MF 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 primary pathologic agent of MF. 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 MF is based on clinical suspicion of the classic presentation of pruritic papulopustules found in a follicular pattern on the back, the chest, the 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 MF. (See Presentation and Workup.)

Both topical and oral antifungals are effective therapeutic agents for this condition. Although many patients improve with topical azole medications, some cases require oral therapy. Patients have been successfully treated with oral pulse itraconazole and weekly fluconazole. M sympodialis is highly sensitive to terbinafine, whereas other species are more resistant to it. Oral ketoconazole is no longer recommended. Oral medication should be discontinued when the lesions resolve. (See Treatment.)

In 2023, the European Academy of Dermatology and Venereology (EADV) published a position statement containing recommendations for the diagnosis and treatment of MF.^[6]  (See Guidelines.)

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

MF is believed to result from plugging of the follicle followed by an overgrowth of yeast that thrives in the sebaceous environment. 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

MF 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^[7]
• Cancer treated with cetuximab, a chimeric (mouse/human) monoclonal antibody epidermal growth factor receptor (EGFR) inhibitor for the treatment of metastatic colorectal cancer and head and neck cancer^[8]
• HIV infection
• Corticosteroids and/or immunosuppressant therapy following organ transplantation^{[9, 10, 11]}
• Crohn disease treated with infliximab, a monoclonal antibody against tumor necrosis factor (TNF)-α^[12]

An increase in sebum production, such as that in pregnancy,^{[13, 14]} and high levels of androgens may potentiate the development of MF.

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

MF occurs more frequently 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 MF.

Anticonvulsant therapy and Down syndrome^[15] are other conditions that are associated with MF.

Other related and coexisting conditions may include the following:

• Seborrheic dermatitis
• Confluent and reticulated papillomatosis
• Systemic candidiasis^[16]

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

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Epidemiology

United States and international statistics

Malassezia organisms can be found on the skin in 75-98% of healthy people in the United States. These organisms are part of the normal skin flora 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.

Worldwide, P ovale has been found to be present on 90-100% of the surface of healthy skin, with higher numbers noted on the chest and back. Certain climates influence the percentage of people with this organism and the number of people with MF. People living in warm and humid climates have a higher incidence of MF. One clinic in the Philippines documented that 16% of all patient visits were a result of this condition.^[17] A 2008 report from China found that 1.5% of all dermatology patients were diagnosed with MF, most of them healthy middle-aged males.^[18]

Age-, sex-, and race-related demographics

MF is recognized as a condition that affects youths and young and middle-aged adults,^[19]  most commonly between the ages of 13 and 45 years. However, Archer-Dubon et al reported three cases that occurred in an intensive care unit (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.^[20]  Very young individuals can also be affected.^[3]

Reports of the relative frequency of MF in males and females have varied, ranging from a male-to-female ratio of 1:1 to a predominance of one sex or the other. Literature from the past decade has suggested that the female-to-male ratio might be a little higher.^[21]

No racial differences in the frequency of MF are known to exist.

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Prognosis

The prognosis is good. With treatment, MF can completely resolve; without treatment, MF lesions are classically pruritic. Although MF may be quite bothersome (as a result of severe pruritus), the lesions are benign.

Among the underlying conditions that predispose the patient to MF are diabetes mellitus, immunodeficiency, and systemic candidiasis^[22] ; these conditions may cause morbidity. The presence of such predisposing conditions should be taken into account when MF is diagnosed.

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History

In Malassezia (Pityrosporum) folliculitis (MF), the patient's history is typically that of a chronic, often pruritic, papular and pustular eruption with perifollicular erythema most commonly on the back, upper arms, and chest.

The main differential diagnoses to consider are acne vulgaris (AV) and staphylococcal folliculitis. Often, patients with MF have been treated with antibiotics or another medication that is appropriate for AV, with the result that their condition does not improve or even worsens.^[23] Recalcitrant acne should be reevaluated for potential Malassezia infection.23 MF can coexist with AV in the same patient.

A history of hospitalization may also play a role in initial colonization.^[24]

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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. Lesions are present on body locations where Malassezia organisms are most abundant: back and chest, neck, shoulders, scalp,^[25] upper arms (occasional), and face. (See the image below.)

View Image

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

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

Dermoscopy may demonstrate perifollicular erythematous papules and pustules with "dirty-white" perilesional scale.^[26]

As noted, MF is often mistaken for AV; however, no comedones or cysts are associated with MF.^[27]

Patients may also have coexisting seborrheic dermatitis.^[22]

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Laboratory Studies

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

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.^[29] This is not a routine study for the mycology laboratory.

Shibata et al reported the presence of galactomannan on cells of Malassezia species, and the results of their comparative antibody reaction studies led them to suggest the potential for antigen detection as a diagnostic tool in Malassezia infection.^[30]

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Procedures

Dermoscopy may be a helpful adjunct in the diagnosis of MF.^[31]

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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 that includes 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. (See the image below.) Periodic acid–Schiff (PAS) and Grocott-Gomori methenamine-silver stains 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- to 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 for detecting Malassezia; however, Parker ink is a more specific stain for the organism.

View Image

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

High titers of circulating immunoglobulin G (IgG) antibodies against P ovale can also be detected in persons with this disease.^[32]

Skin biopsy is usually reserved for the diagnosis of lesions that resemble those of MF but are located on surfaces where MF is less common. A diagnosis of MF 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.^{[33, 34]}

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Medical Care

Both topical and oral antifungals are effective agents in the treatment of Malassezia (Pityrosporum) folliculitis (MF). Oral antifungals have the advantage of dramatic, immediate clearing of the lesions and are the most effective treatment.^[35]

Patients have been successfully treated with oral pulse itraconazole and weekly fluconazole. M sympodialis is highly sensitive to terbinafine, whereas other species are more resistant to treatment with this medication.^[36]

Many patients improve with topical azole medications, but some cases warrant oral therapy. A course of oral ketoconazole was previously the treatment of choice, but given the potential for severe adverse events with this medication, it is no longer recommended.^[21] 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 MF 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.^[37] Additional topical treatments with some reported success include tea tree oil, honey, tacrolimus, and cinnamic acid.^[38]

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

Retinoids, which are used for comedones in acne, have no effect in MF because no comedones are present.^{[39, 40]}

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

Some authors have suggested that topical photodynamic therapy with methyl aminolevulinate may be a potential therapy for recalcitrant MF.^[41]

In 2023, the European Academy of Dermatology and Venereology (EADV) published a position statement containing recommendations for the treatment of MF.^[6] (See Guidelines.)

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Prevention

Patients with MF should be advised 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 to monitor the patient's condition and refill prescriptions.

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EADV Recommendations for Treatment of Malassezia (Pityrosporum) Folliculitis

In 2023, the European Academy of Dermatology and Venereology (EADV) published a position statement containing recommendations for the diagnosis and treatment of Malassezia (Pityrosporum) folliculitis (MF).^[6]

Grade A (ie, strongly supported) treatment recommendations included the following.

• Immunocompetent patients - Topical azoles once or twice daily for 2-4 weeks; selenium sulfide once daily for 3 days, then once weekly intermittently; ciclopirox (gel 0.77%, cream 1.5%, or shampoo 1.5%) twice daily for 2-4 weeks; propylene glycol 50% in water twice daily for 3 weeks; zinc pyrithione 1% once or twice daily for 2-4 weeks
• Immunocompromised patients - Itraconazole 100-200 mg/day for 1-4 weeks; fluconazole 100-200 mg/day for 2-3 weeks or 300 mg/wk for 3 weeks
• Patients with concurrent liver disease - Same as for immunocompetent

Grade B (ie, moderately supported) treatment recommendations included the following.

• Immunocompetent patients - Fluconazole 200 mg/day for 1-2 weeks or 200-300 mg/wk for 3 weeks; itraconazole 200 mg/day for 1-2 weeks
• Immunocompromised patients - Topical azoles once or twice daily for 2-4 weeks; selenium sulfide once daily for 3 days, then once weekly intermittently; ciclopirox (gel 0.77%, cream 1.5%, or shampoo 1.5%) twice daily for 2-4 weeks; propylene glycol 50% in water twice daily for 3 weeks; zinc pyrithione 1% once or twice daily for 2-4 weeks
• Patients with concurrent liver disease - Itraconazole 100-200 mg/day for 1-2 weeks; fluconazole 150-300 mg/wk for 2 weeks

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Medication Summary

The goal of pharmacotherapy for Malassezia (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 Malassezia (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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Terbinafine (Lamisil)

• Dosing, Interactions, etc.

Clinical Context:  Terbinafine inhibits squalene epoxidase, reducing cell membrane ergosterol synthesis, causing inhibition of fungal cell-wall synthesis and subsequently fungal cell death.

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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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