A speculative view of atopic dermatitis: barrier dysfunction in pathogenesis.

The development of atopy or atopic dermatitis is undoubtedly influenced by immunological abnormality. However, the question of factors which induce tolerance breakthrough and hypersensitivity to non-selective multiple antigens in atopy has remained unanswered. The broad clinical spectrum of this disease cannot be explained simply by allergy or immunological abnormalities. This speculative article is the first attempt to answer these questions and to explain the concept of atopic dermatitis by the barrier dysfunction theory based on our experimental results which demonstrated and increased permeability of the stratum corneum in patients with atopic dermatitis. We consider immunological abnormality and mucocutaneous barrier dysfunction as two major defects of atopy or atopic dermatitis. The wide range of clinical manifestations presented by this disease can be more easily comprehended by partial overlapping of these two core abnormalities. A mucocutaneous barrier defect readily allows penetration of multiple antigens or haptens. Repeated encounters with allergens may induce not only tolerance breakthrough and non-selective hypersensitivities but also enhancement of the allergic inflammation. On the other hand, an allergic inflammation stemming from the immunological abnormalities breaks down barrier functions. This sequence results in a 'vicious circle', which plays the most important role in pathogenesis of atopic dermatitis and probably of other atopic diseases.