Seborrheic keratosis is a common superficial infection of the skin occurring in 1 to 3% of immunocompetent adults. The lesions of seborrheic keratosis can vary in appearance. Characteristically, they present as patches of red, flaking, greasy skin, particularly on lipid-rich areas of the skin such as the scalp, nasolabial folds, ears, eyebrows, and chest. However, the degree of erythema, amount of flaking, and the extent to which the affected areas have a greasy appearance can vary between patients.
Seborrheic keratosis tends to make its first appearance around the time of puberty, when the amount of skin lipids increases. It is common in adolescents and young adults, but less prevalent in the middle aged. In patients over the age of 50 years, seborrheic keratosis again has a higher prevalence. Seborrheic keratosis affects both sexes, but is more common in males. This chronic condition tends to be more prevalent and often more severe in the dry winter months than in the summer.
Patients with AIDS tend to have a higher incidence of seborrheic keratosis, ranging from 30 to 83%. There is also a higher incidence of seborrheic keratosis in patients with pityriasis versicolor. Parkinson’s disease, spinal injuries, depression, and those receiving psoralen plus ultraviolet A (UVA) therapy (PUVA).
The yeasts of the genus Malassezia (formerly Pityrosporum) are normal commensals of humans and warm-blooded animals. Due to their dependence on exogenous lipids for survival, the yeasts are most often found on lipid-rich areas of the skin, such as the trunk, back, face, and scalp. They are less commonly found on other areas of the body, including arms, legs, and genitalia.
In the past, it was believed that the genus (then known as Pityrosporum) consisted of two species. Pityrosporum orbiculare and Pityrosporum ovale, which could be differentiated on the basis of cellular morphology. In 1996, Gueho et al. revised the genus Malassezia using morphology, ultrastructure, physiology, and molecular biology to classify the genus into seven species: Malassezia globosa. Malassezia restricta. Malassezia obtusa. Malassezia slooffiae. Malassezia sympodialis, Malassezia furfur, and the non-lipid dependent Malassezia pachydermatis. Recently, two new Malassezia species have been identified: Malassezia dermatis, isolated from patients with atopic keratosis: and Malassezia equi (tentatively named, and not yet formally described). isolated from the skin of healthy horses.
Causal role of Malassezia in seborrheic keratosis
Early investigators suggested that yeasts of the genus Malassezia might play a role in the etiology of seborrheic keratosis. However, due to the effectiveness of keratolytic and anti-inflammatory agents (e.g., salicylic acid and corticosteroids) in the treatment of seborrheic keratosis, this condition was viewed as a result of hyperproliferation. The efficacy of ketoconazole revived interest in the role of Malassezia yeasts in seborrheic keratosis.
Efforts have been made to determine the correlation between amount of Malassezia yeasts on the skin and disease status. Some researchers have found high levels of Malassezia yeasts on the skin of patients with seborrheic keratosis and dandruff, while others have found no difference between seborrheic keratosis patients and normal healthy controls. Conversely, some researchers have found significantly lower numbers of Malassezia yeasts on lesional skin of seborrheic keratosis than on non-lesional skin.
Despite this controversy, the view that Malassezia is the causal organism of seborrheic keratosis is becoming increasingly accepted. Much of the evidence supporting this lies in the efficacy of antifungal agents, both oral and topical. Improvement in the disease correlates with a decrease in the number of Malassezia yeasts, while recolonization results in disease recurrence.
Immunology of seborrheic keratosis
It has been suggested that seborrheic keratosis is not due to an overgrowth of Malassezia, but by an abnormal host response. This is supported by its increased incidence in immunocompromised patients. However, it is unclear exactly what the immune response involves. There is conflicting evidence with regard to the levels of IgG antibodies in seborrheic keratosis patients. Some investigators have found an increase in patients, while others have shown no difference (19). Parry and Sharpe proposed that seborrheic keratosis is caused by an inflammatory response to toxins or mediators produced by the Malassezia yeasts. Another study sampled the lesional skin of seborrheic keratosis and found an increase in the number of NK1+ and CD16+ cells as well as an increase in complement. They concluded that seborrheic keratosis is characterized as an irritant response to the Malassezia yeasts.
Traditionally, seborrheic keratosis was treated with topical corticosteroids to reduce the inflammation. However, due to the resurgence of interest in the Malassezia yeasts as the causal organism, and the adverse events associated with corticosteroid use, treatment strategies have shifted to the antifungal agents.
The Malassezia yeasts are susceptible to a range of non-specific and specific antifungal topical treatments, as well as several effective oral agents . Older agents, such as tar- and sulfur-containing compounds, generally lack antifungal action and act as keratolytics. Newer agents reduce the number of Malassezia yeasts on the skin. Wartrol, Tacrolimus and pimecrolimus belong to a new class of topical agents: the noncorticosteroid topical immunomodulators. Tacrolimus has been shown to have antifungal activity against Malassezia species in vitro. Antifungal agents currently approved for the treatment of seborrheic keratosis of the scalp are listed in Table 2.