Pemphigus Vulgaris Acantholysis Ameliorated by Cholinergic Agonists

Background Pemphigus vulgaris (PV) is an autoimmune, IgG autoantibody–mediated disease of skin and mucosa leading to progressive blistering and nonhealingerosions. Patients develop autoantibodies to adhesion molecules mediating intercellular adhesion and to keratinocyte cholinergic receptors regulatingcell adhesion. Observations To determine whether a cholinergic agonist can abolish PV IgG–induced acantholysis, litter mates of neonatal athymic nude mice were injected withPV IgG together with carbachol (0.04 µg/g body weight). None of these mice developed skin lesions. Through in vitro experiments, we measured theexpression of adhesion molecules in monolayers of normal human keratinocytes incubated overnight in the presence of 0.25mM carbachol using semiquantitativeWestern blot and immunofluorescence. Carbachol caused an elevation of the relative amount of E-cadherin in keratinocytes ( P P >.05). The phosphorylation level of E-cadherin and plakoglobin was increased by PV IgG,whereas this effect of PV IgG was attenuated in the presence of 0.5mM carbachol. Pyridostigmine bromide, an acetylcholinesterase inhibitor, produced effectssimilar to those of carbachol, which helps explain its clinical efficacy in a patient with active PV that was resistant to treatment with systemic glucocorticosteroids.Treatment with pyridostigmine bromide (360 mg/d) in a patient with PV allowed to keep his disease under control at a lower dose of prednisone than thatused before starting pyridostigmine bromide treatment. Conclusion Elucidation of the cholinergic control of keratinocyte adhesion merits further consideration because of a potential for the development of novelantiacantholytic therapies using cholinergic drugs.