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.

The microbiome of the “sterile” pustules in palmoplantar pustulosis

“…PPP was defined as multiple creamy‐white pustules on erythematous desquamative plaques (see A) . Pompholyx was defined as acute recurrent vesicular eczema with many deep‐seated pruritic, painful, clear vesicles (see D) . PPP‐PVs with round yellowish areas surrounded by vessels in a linear arrangement were selected by dermoscopy (see B and C) .…”

Diagnostic histopathological features distinguishing palmoplantar pustulosis from pompholyx

“…Many reports have described the clinical, histological, immunological and genetic features of PPP patients, but the pathophysiology and etiology remain unclear . Histopathologically, the earliest PPP lesion is a spongiotic vesicle in the lower malpighian layer containing mononuclear cells and some neutrophils.…”

“…Many reports have described the clinical, histological, immunological and genetic features of PPP patients, but the pathophysiology and etiology remain unclear. 5,[8][9][10][11] Histopathologically, the earliest PPP lesion is a spongiotic vesicle in the lower malpighian layer containing mononuclear cells and some neutrophils. This progresses to a unilocular, well-delimited pustule within the epidermis that extends upwards to the undersurface of the stratum corneum.…”

“…Some dermatologists suppose that pompholyx vesicle is relevant to sweat glands; 14,15 however, a relationship between pompholyx and acrosyringium is histopathologically unlikely. 16 Soler et al 10 reported that aquaporins 3 and 10 expressed by keratinocytes play key roles in the pathogenesis of pompholyx. Thus, in general, pompholyx is regarded as an eczematous reaction around sweat glands.…”

Topical steroids and emollients in atopic eczema – which should be applied first?

“…These form channels which help regulate the flow of water within cells and are found throughout various tissues in the body (Day et al, 2014). In the epidermis aquaporin 3 and 10 play an important role in water balance, and are also involved in the movement of glycerol and urea, both important substances in helping the skin retain moisture (Soler et al, 2015). The early work by Olsson et al (2006) demonstrated altered aquaporin levels in the skin of patients with atopic eczema, particularly of aquaporin 3, and this imbalance is thought to contribute to the rapid and severe formation of dry skin seen in this condition.…”