Epidermal kinetic alterations required to generate the psoriatic phenotype: a reappraisal

Abstract

Objectives: Although there have been major advances in understanding immunopathogenesis of psoriasis, the basic processes causing psoriatic morphology remain to be identified.

Materials and methods: Our group has designed a systematic review of studies (1962-2009) on keratinocyte kinetics in psoriasis. We obtained data from MEDLINE, PubMed, Current Contents, reference lists and specialist textbooks. A general equation for evolution of the differentiated epidermis has been analysed. Necessary conditions for observed qualitative change in homeostasis between normal skin and established psoriatic lesions were determined.

Results and discussion: Increase in the number of cell divisions (or imbalance in symmetric division rates of committed progenitor cells) and/or decrease in physiological apoptosis in the germinative compartment, together with feedback loops that limit thickening of the skin, are required to generate psoriatic morphology, that is, to increase the absolute size but decrease relative size of the differentiated cell compartment with respect to the germinative compartment.

Figure 1

The epidermis consists of a proliferative compartment (P) and a differentiated compartment (D). Proliferative cells undergo division at rate f. A fraction of the daughter cells is proliferative and the rest is differentiated. Their contribution to variation of the proliferative and differentiated compartments is b and 1 − b respectively. Differentiated cells are lost at the surface by desquamation at a rate g. In psoriatic epidermis, there is increase in size of the proliferative compartment with elongation of rete ridges and increase in absolute size and decrease in relative size of the differentiated compartment. Normal skin and established psoriatic lesions are considered to be steady states of cell dynamics, with cell production and cell loss balancing each other.