Review
The role of Malassezia in atopic dermatitis affecting the head and neck of adults

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Atopic dermatitis is a common chronic skin condition. A subset of patients with head and neck dermatitis may have a reaction to Malassezia flora fueling their disease. Although there are no documented differences in Malassezia species colonization, patients with head and neck atopic dermatitis are more likely to have positive skin prick test results and Malassezia-specific IgE compared with healthy control subjects and patients with atopy without head and neck dermatitis. There is no clear relationship with atopy patch testing. The reaction to Malassezia is likely related to both humoral- and cell-mediated immunity. Clinically, Malassezia allergy may be suspected in patients with atopic dermatitis and: (1) head and neck lesions; (2) exacerbations during adolescence or young adulthood; (3) severe lesions recalcitrant to conventional therapy; and (4) other atopic diseases. There is literature to suggest that these patients will benefit from a 1- to 2-month course of daily itraconazole or ketoconazole followed by long-term weekly treatment.

Section snippets

The presence of Malassezia on atopic skin

Many studies have sought to find a differential pattern of Malassezia colonization on skin affected by AD compared with healthy skin.2, 4, 5, 6, 7, 8, 9, 10 However, the published results are mixed (Table I). There is no convincing proof that the skin of patients with AD is more heavily colonized with Malassezia or is colonized with different species of Malassezia, when compared with healthy control subjects or patients with seborrheic dermatitis.

The challenges of proper sampling, in vitro

The immune response to Malassezia in patients with AD: Skin prick test, specific IgE, and atopy patch test

Numerous clinical studies have measured the immune response of patients with AD to Malassezia antigens using the skin prick test (SPT), specific IgE, and atopy patch test (APT). It is important to note that these studies have not consistently compared the immunologic response to Malassezia with the immunologic response to other common cutaneous flora such as Candida, staphylococci, streptococci, and Trichophyton. Compared with healthy control subjects, patients with atopy are more likely to

Immunologic basis for the response to Malassezia in patients with AD

Thus far, we have outlined the laboratory evidence describing the immune reaction against the skin flora Malassezia that may be a factor contributing to some cases of refractory HND. It is also important to describe the molecular and cellular mechanisms of the interaction of yeasts with the host. Fig 1 illustrates a potential pathway for the altered skin barrier associated with AD and the increased Malassezia antigen load to stimulate both the innate immune system (keratinocytes, dendritic

Source of immunologic reactivity: Classic major histocompatibility complex–restricted antigen presentation versus superantigen stimulation

The above studies provide evidence of increased immunologic reactivity to Malassezia in certain patients with AD, but they do not trace the cellular source (T lymphocytes, B lymphocytes, monocytes, or natural killer cells) of measured cell proliferation or cytokine production. This carries significant implications to support an underlying mechanism of classic major histocompatibility complex (MHC)-restricted antigen presentation or superantigen stimulation.

Several studies have examined the

Possible pathway for the development of HND

In conclusion, the following hypothetic scenario is attractive: at or after puberty, the Malassezia colonization on the head and neck area increases in density as a result of increased sebaceous gland activity and/or transformation of the predominant Malassezia genotypes. The endogenous impaired barrier function defect in AD and the changes in Malassezia colonization expose the immune system of patients with AD to Malassezia antigens. Some patients then develop T-helper 2 skewed B-cell– and/or

Clinical signs and symptoms of HND

The forehead, eyelids, and neck are almost constantly affected in patients with a Malassezia allergy (Fig 2).24, 54 The majority of patients (up to 86%) report manifestations of AD in typical regions of the body as a child followed by flaring in the head and neck region at puberty or young adulthood.25, 54 This correlates with the typical time of increased sebum production and potential fluctuation in Malassezia genotypes.3, 24

This clinical observation has been confirmed with laboratory testing

Treatment strategies

Ketoconazole and itraconazole are the most frequently studied therapeutic agents for patients with AD and Malassezia allergy (Table II). They are highly effective anti-Malassezia agents, with in vitro testing of 125 genotypes of 11 Malassezia species from patients with AD and healthy volunteers showing that all genotypes were susceptible to both itraconazole and ketoconazole.62 Further, tacrolimus was synergistic against Malassezia with either agent.62

In vivo studies have shown significant

Summary

In summary, Malassezia allergy should be suspected in patients whose AD: (1) includes head and neck lesions; (2) worsened during adolescence or young adulthood; (3) is severe and recalcitrant to therapy; and (4) is associated with other concurrent atopic diseases. There is significant literature to suggest that these patients will benefit markedly from a 1- to 2-month course of daily itraconazole or ketoconazole followed by chronic treatment with twice-weekly itraconazole or ketoconazole. In

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    Funding sources: None.

    Disclosure: Dr Bechtel has been a paid consultant and is on speakers bureau for Genetech, Abbott, Centocor, and Biogen-Idec. Dr Zirwas has received honoraria from Coria Labs and Astellas Pharma. Dr Darabi and Ms Hostetler have no conflicts of interest to declare.

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