Chapter 17. Autosensitization Dermatitis

Autosensitization dermatitis refers to a phenomenon in which an acute dermatitis develops at cutaneous sites distant from an inflammatory focus, and where the secondary acute dermatitis is not explained by the inciting cause of the primary inflammation. The classic presentation of autosensitization is that seen in patients with venous stasis disease,1 where as many as 37% of patients have been reported to develop at least one episode of autosensitization,2 and those with dermatophyte infections, where 4–5% reported having had dermatophytid reactions.3

The term autosensitization dermatitis was coined in 1921 by Whitfield to describe reaction patterns ranging from a generalized, erythematous, morbilliform, and urticarial eruption after blunt trauma to a generalized, petechial, papulovesicular dermatitis after the acute irritation of chronic stasis dermatitis.4 Subsequently, the vesicular id reactions associated with infections caused by tuberculosis,5 histoplasmosis,6 dermatophytes,7 and bacteria8 were included under this rubric.9–11 Noneczematous reaction patterns, including erythema multiforme12 and neutrophilic lobular panniculitis,13 have also been ascribed to autosensitization associated with various infections. Other precipitating factors for autosensitization have included the application of irritant or sensitizing chemicals,14 ionizing radiation,15,16 and retained suture material.17

Although the disease was originally thought to be due to autosensitization to epidermal antigens,11 this concept has not been experimentally verified. In murine studies designed to determine whether keratinocyte-derived proteins can serve as antigenic carriers for hapten, Fehr et al18 derived major histocompatibility complex-restricted, T-cell receptor α/β, CD4+ T-cell clones that proliferated in response to keratinocyte extracts unconjugated to hapten. In these studies, such autoreactive T-cell clones could not be derived after treatment with irritants. Nonetheless, the authors speculated that T cells autoreactive to keratinocyte antigens may be generated during the course of contact hypersensitivity and lead to the development of an id reaction.

In the most extensive study to date,1 only 4 of 81 patients with autosensitization dermatitis had serum antibodies cytotoxic to autologous or homologous skin. However, the role of such autoantibodies in mediating the disorder, even in these four patients, must be interpreted cautiously, given the high frequency of epidermal autoantibodies in the normal adult population.19

In an experiment in which guinea pigs were injected with autologous skin, Wilhelmj et al20 reported dermatitis in 2 of 11 guinea pigs, but it was not clear whether these reactions were immunologic and, if so, what the causal allergen(s) was. Other investigators using similar techniques have been unable to induce cutaneous disease in animals by means of epidermal extracts.21 In contrast, 19 of 24 patients with active autosensitization who were intradermally challenged with water-soluble extracts of autologous epidermal scale developed a reaction.22

The term autosensitization is probably a misnomer. The disease is more likely due to a hyperirritability of the skin induced by either immunologic or nonimmunologic stimuli. Factors such as irritation, sensitization, infection, and wounding, which are known to precipitate autosensitization, have been reported to release a variety of epidermal cytokines.23,24 Once hematogenously disseminated in sufficient amounts, these cytokines could heighten the sensitivity of skin to a variety of nonspecific, but otherwise innocuous, stimuli, producing a pattern of “spillover” reactions25 that have been classically termed autosensitization. Such a hypothesis would account for (a) the results in humans of delayed-type hypersensitivity testing with autologous epidermal scale,22 (b) the histopathologic findings noted in the disease (see section “Clinical Findings”), and (c) the activated T lymphocytes occasionally observed in the blood of patients with autosensitization.26 The characteristic distribution of the disease might perhaps be explained if the skin overlying the arms and legs was found to contain increased numbers of, or more avid receptors for, various cytokines than the skin of the face or hands. Such a geographic variation in the distribution of bullous pemphigoid antigen has been observed and hypothesized to account for the clinical patterns of this autoimmune disease.27 Application of modern biotechnological tools should provide insight into the mysteries of autosensitization.

Typically, 1 to 2 weeks after an acute inflammation, an extremely pruritic, symmetric, scattered, erythematous eruption with macules, papules, and vesicles develops (Fig. 17-1). The eruption involves the forearms, thighs, legs, trunk, face, hands, neck, and feet in descending order of frequency.2,11 During the evolution of the dermatitis, its morphology may change in a manner consistent with the chronicity (i.e., vesicles to scale). Histopathologically, the findings are not pathognomonic: spongiotic epidermal vesicles associated with a superficial, perivascular lymphohistiocytic infiltrate of the dermis, which may contain scattered eosinophils.28 Immunophenotypic studies of skin have revealed that most of the lymphocytes in the epidermis are CD3+ and CD8+ T cells, whereas those in the dermis are primarily CD4+.25 In the majority of individuals with autosensitization,1 deposition of antibody or complement in affected skin is not detected.

As previously mentioned, noneczematous autosensitization patterns have also been reported. Both erythema multiforme12 and neutrophilic lobular panniculitis13 have been reported to be induced by a variety of infectious processes. The histology in these cases is consistent with the reaction pattern for erythema multiforme and lobular panniculitis, respectively.

See Box 17-1.

The eruption often persists and spreads until the underlying causative primary site of inflammation is treated.

Treatment is best directed toward the inciting disease. The frequently weeping, vesicular eruption of autosensitization benefits from drying agents such as aluminum sulfate and calcium acetate. Given the likely involvement of cytokines and inflammatory mediators sensitive to glucocorticoids29 or macrolactams,30 systemic and/or topical treatment with these drugs may be helpful. To prevent the secondary effects of excoriation, pruritus must be controlled with topical antipruritic agents or oral antihistamines. However, one must remain alert to the possibility of inducing an allergy in existing dermatitic skin with topical medicaments.