Malassezia Disease
Also known as: Malassezia Infection, Malassezia Folliculitis, Seborrhoeic Dermatitis and Malassezia
Malassezia are lipophilic basidiomycete yeasts that form part of the normal skin mycobiome, where they account for more than 90 percent of fungal sequences from sebum rich areas of the scalp, face, and upper trunk. Disease results from a change in host conditions (sebum, sweat, barrier function, immunity, occlusion, and drugs) and not from a new acquisition. The associated diseases range from common and benign (dandruff and seborrhoeic dermatitis) to rare invasive fungaemia in infants receiving parenteral lipids.
| Feature | Detail |
|---|---|
| Lipid dependence | All species except Malassezia pachydermatis lack fatty acid synthase and need exogenous lipid (olive oil, long chain fatty acids) for growth in vitro |
| Species | At least 18 are described. The commonest in human disease are Malassezia globosa, Malassezia restricta, Malassezia sympodialis, Malassezia furfur, Malassezia slooffiae, Malassezia obtusa, and Malassezia dermatis; Malassezia pachydermatis is zoophilic (dogs) |
| Morphology | Small (2 to 8 micrometres) round to oval yeasts with unipolar budding from a broad base, a collarette, and, in some conditions, short hyphae. The "spaghetti and meatballs" appearance in pityriasis versicolor is the hyphal and yeast phase together |
| Enzymes | Lipases and phospholipases hydrolyse sebum triglycerides to free fatty acids; oleic and arachidonic acid are irritants and inflammatory in susceptible skin, and saturated acids are consumed |
| Metabolites | Indoles (malassezin, pityriacitrin, and others) affect melanocytes and the aryl hydrocarbon receptor, with ultraviolet protective and immune modulating effects |
| Culture | Modified Dixon agar, Leeming and Notman agar, or Sabouraud agar with olive oil overlay, at 30 to 35 degrees Celsius for 5 to 14 days; colonies are cream and dull |
| Disease | Association with Malassezia | Main points |
|---|---|---|
| Dandruff | Strong | Non inflammatory scaling of the scalp; response to antifungals |
| Seborrhoeic dermatitis | Strong | Inflamed, scaly, greasy areas on the scalp, face, and chest; antifungals are effective |
| Malassezia (pityrosporum) folliculitis | Strong | Itchy monomorphic follicular papules and pustules |
| Pityriasis versicolor | Strong | Scaly pigment change on trunk, in warm climates |
| Atopic dermatitis (head and neck) | Moderate | IgE sensitisation to Malassezia antigens; responds to antifungals |
| Psoriasis, scalp | Possible | May worsen with Malassezia |
| Confluent and reticulated papillomatosis | Weak, uncertain | Some respond to antifungals |
| Blepharitis | Moderate | Eyelid margin inflammation |
| Otitis externa | Moderate | Flaking and itching of the ear canal |
| Catheter related fungaemia | Causal | Lipid dependent species in infants and adults on parenteral lipid |
| Peritonitis (peritoneal dialysis), pneumonia, meningitis | Rare causal | Immunosuppressed and neonatal hosts |
| Zoonotic Malassezia pachydermatis infection | Causal | Health care workers and neonates, linked to pet dogs |
Pathogenesis
Susceptible individuals have an abnormal response to Malassezia metabolites. Lipase activity releases unsaturated fatty acids that penetrate the stratum corneum, disturb barrier function, and cause inflammation, with innate immune activation (Toll like receptors, interleukin 1, and interleukin 8), complement, and alterations in lipid composition.
Dandruff and seborrhoeic dermatitis lie on a spectrum. Factors that worsen disease include sebum production (puberty and adulthood), cold dry weather, stress, sleep deprivation, immunosuppression, and neurological disease.
Conditions with high prevalence are HIV infection (30 to 80 percent, often severe and extensive), Parkinson disease, stroke, facial palsy, depression, Down syndrome, and drugs (lithium, interferon, and some neuroleptics, and haloperidol). Infantile seborrhoeic dermatitis (cradle cap) is common in the first months of life and settles by 6 to 12 months.
Clinical features
- Scalp: adherent greasy yellow scales over erythema (seborrhoeic dermatitis), or fine white flaking without erythema (dandruff); itch.
- Face: erythema and fine scale over the glabella, eyebrows, nasolabial folds, perinasal skin, and ears; blepharitis of the lid margins.
- Trunk: presternal, interscapular, and flexural scaling, with annular and petaloid forms.
- Body folds: axillae and groin, where it can resemble flexural psoriasis or candidiasis.
- Infantile: thick greasy scalp scale, with possible spread to face and nappy area, and often no itch.
- HIV related: extensive, severe, and relapsing disease.
Differential diagnosis
| Condition | Points that separate it |
|---|---|
| Psoriasis, scalp and flexural | Sharply demarcated, silvery scaling, nail changes, extensor disease |
| Atopic dermatitis | Itch, flexural pattern, personal and family atopy |
| Tinea capitis and tinea faciei | Hair loss, broken hairs, positive microscopy and culture |
| Rosacea | Flushing, telangiectasia, papules and pustules, without prominent scale |
| Contact dermatitis | Exposure history and distribution |
| Systemic lupus erythematosus and dermatomyositis (face) | Photodistribution, autoantibodies, systemic features |
| Pemphigus foliaceus | Erosions, scaling crusts, acantholysis on biopsy |
| Langerhans cell histiocytosis (infants) | Petechial and crusted lesions, resistant to treatment, biopsy |
| Candidal intertrigo | Satellite pustules and positive culture |
Treatment
| Agent | Regimen | Notes |
|---|---|---|
| Ketoconazole 2 percent shampoo | Applied to wet scalp, left for 5 minutes, twice weekly for 2 to 4 weeks, then once weekly or fortnightly for maintenance | First line for scalp and body; also used as a body wash |
| Ketoconazole 2 percent cream or foam | Twice daily for 4 weeks (cream) or once daily for 2 to 4 weeks (foam) | Face and trunk |
| Ciclopirox 1 percent shampoo or 0.77 percent cream | Shampoo twice weekly for 4 weeks; cream twice daily for 4 weeks | Antifungal and anti inflammatory |
| Selenium sulphide 1 to 2.5 percent | Applied to scalp for 10 minutes, 2 to 3 times weekly | Irritant and may discolour hair; avoid around eyes |
| Zinc pyrithione 1 to 2 percent shampoo | Used 2 to 3 times weekly | Antifungal and antibacterial |
| Coal tar, salicylic acid | Shampoo or scalp preparations 2 to 3 times weekly | For thick adherent scale |
| Low potency corticosteroids | Hydrocortisone 1 percent or desonide 0.05 percent once or twice daily for 1 to 2 weeks on the face; betamethasone valerate 0.1 percent scalp lotion once or twice daily for 1 to 2 weeks | Short courses for inflammation; avoid prolonged use on the face (atrophy, telangiectasia) |
| Calcineurin inhibitors | Tacrolimus 0.1 percent ointment or pimecrolimus 1 percent cream twice daily for 2 to 4 weeks | Steroid sparing for the face and eyelids |
| Roflumilast 0.3 percent foam | Once daily for 8 weeks | Phosphodiesterase 4 inhibitor approved for seborrhoeic dermatitis in adults and children from 9 years |
| Oral itraconazole | 200 mg once daily for 7 days, then 200 mg once monthly in some regimens | Severe or extensive disease, HIV; interactions and heart failure caution |
| Oral fluconazole | 200 to 300 mg once weekly for 2 to 4 weeks | Limited evidence |
| Oral terbinafine | 250 mg daily for 4 weeks | Some benefit, weaker than itraconazole |
| Infantile seborrhoeic dermatitis | Emollient or plain oil to soften scale, gentle brushing, ketoconazole 2 percent cream or shampoo for persistent cases, hydrocortisone 1 percent for short courses | Self limited; avoid selenium and tar products in infants |
| HIV related | Antiretroviral therapy with topical azoles; recurrence is common | Immune restoration improves disease |
Relapse is the rule. Maintenance with a medicated shampoo or antifungal once or twice weekly keeps disease in remission, and triggers are addressed.
Malassezia folliculitis follows occlusion of follicles and overgrowth of yeast in the follicular lumen. Predisposing factors are humid or hot climates, sweating and occlusive clothing, oily skin, corticosteroids, broad spectrum antibacterials (including long term acne treatment), diabetes, immunosuppression (haematological malignancy, transplant, and HIV), and pregnancy.
- Clinical features: itchy, uniform (monomorphic) follicular papules and pustules, 2 to 4 mm in diameter, on the upper back, chest, shoulders, upper arms, and sometimes the face and neck. There are no comedones, in contrast to acne.
- Diagnosis: a smear from expressed follicular contents with potassium hydroxide or stained with Gram, Giemsa, or methylene blue shows numerous budding yeasts with unipolar budding; biopsy shows yeast in dilated follicles with a neutrophilic or lymphocytic infiltrate and follicular rupture. Culture with lipid supplement is not needed for diagnosis, and the response to antifungals confirms it. Wood lamp may show pale yellow green follicular fluorescence.
- Differential diagnosis: acne vulgaris (comedones, mixed lesions, no itch), bacterial folliculitis (pustules with neutrophils, positive bacterial culture), eosinophilic pustular folliculitis, steroid acne, drug eruptions, and candidal folliculitis.
| Treatment | Regimen |
|---|---|
| Topical, first line for mild disease | Ketoconazole 2 percent shampoo as a body wash, left on for 5 to 10 minutes, daily for 3 to 7 days or weekly for 2 to 4 weeks; selenium sulphide 2.5 percent lotion for 10 minutes daily for 7 days; ciclopirox 1 percent; propylene glycol 50 percent in water twice daily for 2 weeks |
| Oral itraconazole | 200 mg once daily for 1 to 4 weeks (most responses in 2 weeks), for extensive or refractory disease |
| Oral fluconazole | 100 to 200 mg once daily for 1 to 4 weeks, or 150 to 300 mg once weekly |
| Maintenance | Ketoconazole shampoo once weekly to monthly, or oral itraconazole 200 mg once a month, for patients who relapse |
| Triggers | Stop unnecessary antibacterials and corticosteroids, reduce occlusion, and manage diabetes |
About half or more of adults with atopic dermatitis of the head and neck have IgE antibodies to Malassezia and positive skin tests. Antifungal therapy (itraconazole 100 to 200 mg once daily for 7 days then 200 mg once monthly, or ketoconazole shampoo and cream) improves head and neck disease in sensitised patients. Dupilumab associated head and neck dermatitis in a few patients has responded to topical azoles.
- Blepharitis: lid margin hygiene, warm compresses, and ketoconazole 2 percent cream or shampoo diluted for lid use.
- Otitis externa: ear canal scaling and itching, treated with topical azoles (clotrimazole 1 percent solution twice daily for 1 to 2 weeks).
- Psoriasis of scalp: antifungal shampoo is used alongside psoriasis treatment.
- Pityriasis versicolor: hypopigmented or hyperpigmented, finely scaly macules on the trunk and proximal arms in warm, humid climates; treated with topical azoles, selenium sulphide, or short courses of oral itraconazole or fluconazole.
Malassezia fungaemia affects preterm infants on parenteral nutrition with intravenous lipid emulsion through central venous catheters, and adults with parenteral nutrition, haematological malignancy, or prolonged intensive care stay. Lipid in the infusate supports growth, and catheter biofilm is the source.
Presentation includes fever, apnoea, thrombocytopenia, and respiratory deterioration with interstitial infiltrates, sometimes pneumonia, endocarditis, or meningitis. Colonisation of neonatal skin is common, hands of staff and parents (including those with pet dogs) transmit Malassezia pachydermatis, and outbreaks in neonatal units have occurred.
- Diagnosis: standard blood cultures are often negative. Bottles are supplemented with lipid (olive oil overlay on Sabouraud agar or Dixon agar), incubated at 32 to 35 degrees Celsius for 5 to 14 days, and the laboratory is told that Malassezia is suspected. Catheter tip culture and a lysis centrifugation method have been used, and direct examination of the buffy coat or catheter blood with Gram or calcofluor stain shows small budding yeasts with collarettes. Beta D glucan is negative or variable. MALDI-TOF identification works with a library that includes Malassezia.
- Treatment: remove the central venous catheter, stop or reduce intravenous lipid (and use lipid free parenteral nutrition where possible), and give antifungal therapy. Amphotericin B deoxycholate 0.5 to 1 mg per kg daily (neonates 1 mg per kg daily) is the drug of choice, with lipid formulations also used. Fluconazole 6 mg per kg daily (neonates 6 to 12 mg per kg daily, adults 400 mg daily) and voriconazole are alternatives for susceptible isolates, and echinocandins are intrinsically inactive. Treatment continues for 14 days after the first negative culture and clearance of the catheter, or longer with deep infection.
- Prevention: strict hand hygiene, minimal use of lipid in neonates, and reducing catheter days, with pet ownership noted as a risk in neonatal units.
Azoles (ketoconazole, itraconazole, fluconazole, and voriconazole), ciclopirox, selenium sulphide, and zinc pyrithione are active. Amphotericin B is active. Allylamines (terbinafine) have weaker activity, and echinocandins have no activity. Standardised testing needs lipid supplemented media, and there are no clinical breakpoints.
