Ratio of immature cornified envelopes does not correlate with parakeratosis in inflammatory skin disorders

We have previously established a non-invasive method to evaluate the maturity of cornified envelopes (CEs), and have reported the appearance of immature CEs in the stratum corneum (SC) with poor barrier function, such as the SC of the face. The purpose of the present study was to evaluate CEs in inflammatory skin disorders, and to clarify the relationship between the appearance of the immature CEs and parakeratosis, which is often used as a marker for defective keratinization in inflammatory skin disorders. Cornified envelopes in the outermost SC of involved areas of psoriasis vulgaris (PV) and atopic dermatitis (AD) were strikingly heterogeneous, and consisted of immature CEs stained with anti-involucrin and mature CEs stained with Nile red, whereas CEs of the uninvolved areas were relatively homogeneous, exhibiting mature phenotype. The ratio of immature CEs was significantly higher in the involved areas of PV and AD than that in the corresponding uninvolved areas, suggesting that defective CE maturation may, at least in part, account for the inflammatory disorders. Simultaneous evaluation of CE maturity and parakeratosis was carried out by a combination of involucrin immunostaining and nuclear staining of detergent-dissociated corneocytes. In the involved area of PV, four types of corneocytes in regard to the combination of involucrin staining and nuclear remnant were observed, while both immature CEs and parakeratosis were more often detected in the involved areas of PV than in the uninvolved areas or the upper arm of healthy subjects as a normal control. Thus, corneocytes with involucrin-positive immature CEs were not always associated with parakeratosis at the cellular level. In the involved areas of PV, the ratio of immature CEs and that of parakeratosis were heterogeneous, depending on the cases, and no correlation between the ratios was observed. Inter-individual and intraindividual variations in CE maturity were also suggested by the heterogeneous localization of involucrin in the psoriatic epidermis as examined by immunohistochemistry. In addition, in the face of healthy subjects, four types of corneocytes were similarly detected, and the ratio of immature CEs was significantly higher than that of parakeratosis. These results obviously suggest that the maturation of CEs and disappearance of nuclei are differentially regulated in the epidermis.