Granular parakeratosis - a unique acquired disorder of keratinization

Axillary granular parakeratosis is a recently described condition presenting with erythematous hyperkeratotic papules and plaques. We report on nine women and one man with eruptions not only localized to the axillae. Biopsy specimens were investigated by histology, immunohistochemistry, electron microscopy, immuno-electron microscopy, and in situ hybridization. In general, the epidermis was hyperplastic and showed a well preserved stratum granulosum. In the upper dermis a discrete perivascular CD4+ T-cell infiltrate was found, CD1+ dendritic cells were absent from the epidermis. The distribution pattern of the epidermal keratins (keratin 5/14, 1/10) and the expression 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 dUTP-biotin. The corneocytes were characteristically replete with basophilic granules which showed both ultrastructural features of keratohyalin granules and immunoreactivity for filaggrin. Loricrin was expressed irregularly in small L-granules. Granular parakeratotic cells revealed regular development of a cornified envelope while cell membranes and desmosomes remained undegraded. In conclusion, our studies on granular parakeratosis suggest a basic defect in processing of profilaggrin to filaggrin that results in a failure to degrade keratohyalin granules and to aggregate keratin filaments during cornification. Associated abnormalities of the cell surface structures and dysregulation of cornified envelope components may account for the retention hyperkeratosis. Further studies are necessary to clarify the etiology of this unique, acquired disorder of keratinization that localizes to intertriginous areas and body folds.