The therapeutic use of topical contact sensitizers in benign dermatoses

Abstract

Topical therapy using contact sensitizers has been practised since the 1960s to treat conditions associated with an altered immunological state. Dinitrochlorobenzene, squaric acid dibutyl ester and diphencyprone are most commonly employed in the therapy of alopecia areata and viral warts. Few dermatology departments in the U.K. provide such treatment. This systematic review discusses the various contact sensitizers used for topical immunotherapy, the methodology of treatment, factors influencing efficacy and likely adverse effects.

Drug discovery for alopecia: gone today, hair tomorrow

“…There have been a number of topical ‘sensitizing’ agents such as diphenylcyclopropenone, employed that are known as ‘topical immunotherapy.’ These compounds have in common the ability to cause the induction and periodic elicitation of allergic contact dermatitis as they act as potent contact allergens [110]. There is a decrease in CD4 to CD8 T-cell ratio from 4:1 to 1:1 [111] together with a decrease in lymphocytes and Langerhans cells in the HF bulb. Happle proposed [112] the concept of ‘antigenic competition,’ where an allergic reaction generates suppressor T cells that nonspecifically inhibit the autoimmune reaction against an HF antigen.…”

Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

“…Buckley and Vivier [18] reviewed many of the clinical trials using contact sensitizers to induce viral wart regression. They pointed out that very few of these studies had the proper control groups or randomization, making many of the observations biased and hard to gather conclusions from.…”

“…Application was stopped when there were no visible warts. The mechanism of action for these contact allergens affecting viral warts is not well investigated, although it is theorized that the allergen application induces alterations in cytokine levels, nonspecific inflammation causing wart regression, and haptenation inducing hapten-specific immune responses [18]. It is likely that CHS/ACD-like reactions are occurring in the wart site, although there is little evidence for this.…”

“…Overall, the clearances of warts ranged from 7 to 100% in the trials with a median clearance rate of 62%. It was also seen that long-term, hapten-dependent treatment was needed to cause regression [18]. …”

“…Hapten-carrier conjugates have been used in the past as drug-abuse therapies [9, 10], inducing an immune response against the drug of interest. Haptens have also been used to create autoimmune models in mice, such as IBD [11–17], and to cause viral wart regression via epifocal hapten application [18, 19]. The ability of haptens to cause autoimmunity and wart regression is an important concept to consider when applying the use of haptens to cancer immunotherapy setting, as the immune response to cancer is similar to an autoimmune response [20].…”