Impairment of 5-alpha reductase may not be germane to the pathogenesis of vulvar lichen sclerosus.

Grover's disease (GD) is a transient or persistent, monomorphous, papulovesicular, asymptomatic or pruritic eruption classified as non-familial acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis remains controversial. The purpose of this study was to investigate antibody-mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used the most sensitive proteomic technique for an unbiased analysis of IgA-and IgG-autoantibody reactivities. Multiplex analysis of autoantibody responses revealed autoreactivity of all 11 GD patients with cellular proteins involved in the signal transduction events regulating cell development, activation, growth, death, adhesion and motility. Semiquantitative fluorescence analysis of cultured keratinocytes pretreated with sera from each patient demonstrated decreased intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera induced BAD expression, indicating that binding of autoantibodies to keratinocytes alters expression/function of their adhesion molecules and activates apoptosis. We also tested the ability of GD sera to induce visible alterations of keratinocyte shape and motility in vitro but found no specific changes. Thus, our results demonstrated that humoral autoimmunity in GD can be mediated by both IgA and IgG autoantibodies. At this point, however, it is impossible to conclude whether these autoantibodies cause or are caused by the disease. Antidesmoglein antibodies may be triggered by exposure to immune system of sequestered antigens due to disintegration of desmosomes during primary acantholysis. Clarifying aetiology of GD will help improve treatment, which currently is symptomatic and of marginal effectiveness.

The outermost layer of the skin, the stratum corneum, consists of non-viable keratin-filled cells, or corneocytes, embedded in a matrix of lipids. The boundary of the cells consists of cross-linked proteins with covalently bound lipids on the outer surface. The spaces between cells are filled with a mixture of ceramides, cholesterol and fatty acids. The stratum corneum provides a protective barrier against water loss through the skin and limits the penetration of potentially harmful substances from the environment. Among the covalently bound lipids on the corneocyte surface are omega-hydroxyacylsphingosine and omega-hydroxyacyl-6-hydroxysphingosine. The previously suspected presence of omega-hydroxyacylphytosphingosine is confirmed in this report through its specific isolation and characterization based on chromatographic behaviour and proton magnetic resonance spectral data.

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