Spreading of Psoriatic Plaques: Alteration of Epidermal Differentiation Precedes Capillary Leakiness and Anomalies in Vascular Morphology
Journal of Investigative Dermatology
To ap proach the temporal relationship between alterations in keratinization and capillary leakiness in psoriasis, we studied the topography of these anomalies in spreading psoriatic lesions . Histological and immunohistochemical studies were performed on skin biopsies obtained from normal individuals and from psoriatic patients. In th e latter case, biopsies were taken in uninvolved skin, in the center of lesions, and at the edge of evolving plaques (spanning uninvolved and involved skin) .
... involved skin) . Alterations in epidermal differentiation were assessed by the distribution of filaggrin, involucrin, and epidermal membrane-bound transglutaminase. Capillary leakiness was A !though the phenotypical alterations characteristic of epidermal lesions occurring in psoriasis have been extensively studied, both with histologic [1-7J and with immunohistologic methods     , the etiology of the disease remains mysterious and the relationship berween the various symptoms is Uicknown. For example, although vascu lar changes and alterations in terminal epidermal differentiation are the two major features of stable psoriatic lesions, it is still unknown whether these alterations represent two independent fearures of the pathologic process, or whether they are linked by a causa l relationship. Ul trastructural studies of the coiled, dilated, and twisted capillaries found at the level of psoriatic lesions showed that the change fro m an arterial to a venous character occurred in the intrapapillary capillary, often well before the apex of th e loop. The existence of a fenes trated endothelium in the papillary portion of the psoriatic vessels [ 19) may explain the transcapill ary leakage of plasma proteins (albumin and immunoglobulin G) previously detected in ex-Manuscript received February 22, 1989; accepted for publication J an uary 17, 1990. Reprin t requests to: Dominique Parent, Experimental Dermatology Unit, Erasme Hospital, 808, Route de Lennik, B-1070 Bruxelles, Belgium. Abbreviations: BSA: bovi ne serum albumin EpTg: epidermal membrane bound transglutaminase FITC: flu orescein isothiocyanatc HPS: Hemalun/phloxin/safran staining Ig: immunoglobulin MoAb: monoclonal antibody PAS: Periodic acid-Schiff staining PBS: phosph ate-buffered saline PoAb: polyclonal antibody :TIUTC: tetramethylrhodamine isothiocyanate evaluated by the abundance of plasma proteins such as albumin, fibrinogen, and immunoglobulin G within the epidermis. Typical alterations of epidermal differentiation were already obvious at the edge of the lesions, in areas devoid of vessel abnormalities and leakiness, or significant cellular infiltration. These results strongly suggest that, during the formation of a psoriatic plaque, defects in keratinocyte differentiation precede the development of vascular anomalies. J Invest Dermato/95:333-340, 1990 tensive psoriasis  . Indeed, after i1"Uecting labeled albumin intravenously and measuring its passage in the extravascular fluid of newly formed suction blisters, it was possible to show that vascular permeability was increased at the level of involved psoriatic skin [21 J. Moreover, the presence of various plasma proteins in lesional psoriatic epidermis has been shown by immunohistology by J ablonska et al [22J,Johannesson et al [23), Fyrand [24J, and Bernard et al . On the other hand, defects in epidermal differentiation are dram atic in psoriatic lesions. The most classical features are a granulosis and parakeratosis, showing that the last steps of epidermal differentiation are impaired [4) . Psoriatic keratinocytes follow an abnormal differentiation pathway [8J , as demonstrated by a premature appearance of involucrin and epidermal membrane-bound transglutaminase f9, 10), an abnormal synthesis of keratins , an altered p attern of lectin binding [14 -17), and the expression of Psi-3 antigen [9 ,18}. In order to determine whether alterations in keratinocyte differentiation, on the one hand, and capillary morphology and function, on the other, could be linked by a causal relationship, we studied the distribution of these anomalies as a function of the distance to the center of the lesion in spreading psoriatic plaques. To approach the chronology of these anomalies, biopsies spanning uninvolved and involved skin were performed. Because alterations in the periphery of a spreading lesion are more recent than those found closer to the center of the lesion, the topography of the lesions reflects the temporal sequence of events. We observed that the leakage of plasma proteins appears secondary to alterations in keratinocyte different!ation. MATERIALS AND METHODS Skin Samples Punch biopsies were cut into two pieces. One was fixed in fonnol, the other was quick frozen in Tissue Tek OCT 0022-202X/90/S03.50