Granular parakeratosis - a unique acquired disorder of keratinization

Axillary granular parakeratosis is a recently described condition presentin g with erythematous hyperkeratotic papules and plaques. We report on nine w omen and one man with eruptions not only localized to the axillae. Biopsy s pecimens were investigated by histology, immunohistochemistry, electron mic roscopy, immune-electron microscopy, and in situ hybridization. In general, the epidermis was hyperplastic and showed a well. preserved stratum granul osum. In the upper dermis a discrete perivascular CD4+ T-cell infiltrate wa s found, CD1+ dendritic cells were absent from the epidermis. The distribut ion pattern of the epidermal keratins (keratin 5/14, 1/10) and the expressi on of involucrin was regular. The horny layer was excessively thickened and parakeratotic. The nuclear remnants showed marginal chromatin condensation and were reactive for the nick-end labeling technique using TdT-mediated d UTP-biotin. The corneocytes were characteristically replete with basophilic granules which showed both ultrastructural features of keratohyalin granul es and immunoreactivity for filaggrin. Loricrin was expressed irregularly i n small L-granules. Granular parakeratotic cells revealed regular developme nt of a cornified envelope while cell membranes and desmosomes remained und egraded. In conclusion, our studies on granular parakeratosis suggest a bas ic defect in processing of profilaggrin to filaggrin that results in a fail ure to degrade keratohyalin granules and to aggregate keratin filaments dur ing cornification. Associated abnormalities of the cell surface structures and dysregulation of cornified envelope components may account for the rete ntion hyperkeratosis. Further studies are necessary to clarify the etiology of this unique, acquired disorder of keratinization that localizes to inte rtriginous areas and body folds.