The key role of aquaporin 3 and aquaporin 10 in the pathogenesis of pompholyx

Abstract Pompholyx remains a chronic skin affliction without a compelling pathophysiological explanation. The disease is characterized by the sudden onset of vesicles exclusively in the palms and soles which generally resolves. However, the disease may progress and the vesicles may expand and fuse; with chronicity there is deep fissuring. Multiple therapeutic approaches are available, but the disease is often resistant to conventional treatments. Currently, oral alitretinoin is used for patients with resistant chronic disease; however, this therapy is only approved for use in the UK, Europe and Canada. In this paper we wish to put forward a hypothesis: exposure to water and the subsequent steep osmotic gradient imbalance are key factors driving skin dehydration seen in pompholyx patients once the disease becomes chronic. The mechanistic explanation for the epidermal fissuring might lie in the over-expression across the mid and upper epidermis, including the stratum corneum, of two water/glycerol channel proteins aquaporin 3 and aquaporin 10, expressed in the keratinocytes of afflicted pompholyx patients. The over-expression of these two aquaporins may bridge the abundantly hydrated dermis and basal epidermis to the outer environment allowing cutaneous water and glycerol to flow outward. The beneficial effects reported in alitretinoin-treated patients with chronic hand eczemas may be due potential regulation of aquaporin 3 and aquaporin 10 by alitretinoin.