ORIGINAL ARTICLE New Approaches to the Treatment of Pemphigus

Grando, Sergei A.
January 2004
Journal of Investigative Dermatology Symposium Proceedings;Jan2004, Vol. 9 Issue 1, p84
Academic Journal
In pemphigus vulgaris, treatment with systemic glucocorticosteroids is life saving; it may, however, cause severe side effects, including death. A patient with pemphigus vulgaris and myasthenia gravis was treated for approximately five years with the cholinomimetic Mestinon (pyridostigmine bromide), Imuran (azathioprine), and a topical corticosteroid gel before the need to introduce systemic glucocorticosteroids. Because activation of keratinocyte acetylcholine receptors also has been shown to abolish pemphigus IgG–induced acantholysis in cultured keratinocyte monolayers, a clinical trial of Mestinon was initiated in patients with active pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic autoimmune multiorgan syndrome (also known as paraneoplastic pemphigus). First results indicate that nonsteroidal treatment of pemphigus is possible. Mestinon may be used to slow down progression of the disease and to treat mild cases with chronic lesions on limited areas. Stimulation of the keratinocyte– acetylcholine axis may lead to a therapeutic effect through any of the following mechanisms: (1) stimulating keratinocyte cell-to-cell attachment; (2) accelerating re-epithelialization; and (3) competing with the disease-causing pemphigus antibodies, preventing them from attachment to keratinocytes. Glucocorticosteroids and various types of steroid-sparing drugs used to treat pemphigus exhibit cholinergic side effects, including effects on expression and function of keratinocyte adhesion molecules, that are very similar to those produced by the cholinomimetic drugs. Further elucidation of the mechanisms underlying therapeutic efficacy of antiacantholytics may shed light on the immunopharmacological mechanisms of pemphigus antibody–induced acantholysis.


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