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We welcome the article by Lin et al,1 “Localized Pemphigus Foliaceus Induced by Topical Imiquimod Treatment,” the first case report of imiquimod-induced localized pemphigus foliaceus. Only 2 months after this first case report, a second one was published.2 We would like to address several aspects of the possible mechanisms involved in the induction of pemphigus foliaceus by topical imiquimod treatment.
Pemphigus is generally considered to stem from a genetic predisposition to the disease triggered and/or exacerbated by one or more exogenous factors,3 including topical contact, in which case it is called contact pitalicigus.4 This subgroup of induced pemphigus can be elicited by a systemic effect via absorption or by direct alteration of skin structure that causes the formation of neoantigens and later pemphigus antibodies. Other possible mechanisms are activation of enzymes that cause keratinocyte disaggregation, inhibition of enzymes that cause keratinocyte aggregation, or generalized allergic reaction such as contact dermatitis or contact urticaria that leads to pemphigus.3
In their article, Lin et al1 refer to the production of interferon induced by the use of imiquimod. Topical imiquimod is known to induce the production of interferon alfa, tumor necrosis factor (TNF) α, interleukin (IL) 1, IL-1 receptor antagonist, IL-6, IL-8, IL-10, IL-12, and additional cytokines.5 Most of these cytokines can either induce pemphigus or are found in high levels in the serum of patients with pemphigus.
Pemphigus vulgaris and pemphigus foliaceus have been reported to be induced by interferon alfa,6 - 7 and high interferon alfa levels have been reported in these diseases.8 Increased serum levels of TNF-α have been reported in pemphigus vulgaris and have been correlated with disease activity.9 Involvement of TNF-α has also been reported in pemphigus vulgaris acantholysis via urokinase plasminogen activator.10 Anti–TNF-α was recently reported to be effective in the treatment of pemphigus vulgaris.11 Pemphigus foliaceus has been shown to be associated with TNF-α gene polymorphism in position-308.12
High levels of IL-1 have been measured in patients with endemic pemphigus foliaceus.13 Interleukin 1 also plays a part in pemphigus vulgaris acantholysis via urokinase plasminogen activator.10 Increased serum levels of IL-6 have been reported in pemphigus vulgaris and have been correlated with disease activity.9 In contrast, IL-8 immunoreactivity was not altered in autoimmune bullous diseases, including pemphigus.14 Some studies have reported low or undetectable levels of IL-10 in serum samples of patients with pemphigus,15 -Â 16 whereas others report high IL-10 levels.17 Serum IL-12 levels in patients with endemic pemphigus foliaceus (fogo selvagem) were found to be increased.18
We conclude that topical imiquimod can induce contact pemphigus via the induction of production of several cytokines, among them interferon.
Correspondence: Dr Brenner, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv 64239, Israel (derma@tasmc.health.gov.il).
Financial Disclosure: None.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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