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Stratum Corneum Structure and Function Correlates with Phenotype in Psoriasis

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Stratum Corneum Structure and Function Correlates with Phenotype in Psoriasis Stratum Corneum Structure and Function Correlates with Phenotype in Psoriasis Ruby Ghadiall y, Jeffrey T. Reed, and Peter M. Elias Dermatology Service, Veterans Administration Medica l Center, San Francisco, and Department of Dermatology, University of Ca lifomia School of Medicine, San Francisco, Cali forn ia, U.S.A. Psoriatic epidermis demonstrates a defective pro­ cellular domains largely devoid of lalnellae. In con­ gram of growth and differentiation, including an trast, patients with chronic plaque psoriasis and abnormal permeability barrier. Despite the fact that sebopsoriasis displayed a lesser increase in transepi­ damage to the epidermis often initiates the disease, dermal water loss, normal numbers of lamelIar bodies psoriasis is commonly viewed as triggered by aber­ with only a few retained organelles, and abundant rant immune phenomena in deeper skin layers. Per­ extracellular lamellar material (although a normal meability barrier homeostasis requires the formation unit bilayer pattern did not form). Thus, both func­ and secretion of lamellar body contents, as well as the tionally and structurally, permeability barrier ho­ extracellular processing of lamellar body contents meostasis was more disrupted in erythrodermic and into lamellar bilayers. To address the hypothesis that active plaque psoriasis than in chronic plaque psori­ psoriasis is triggered by exogenous rather than inter­ asis and sebopsoriasis; i.e., the extent of defective nal factors, we assessed permeability barrier func­ barrier function correlated with abnorlnalities in the tion, lamellar body structure, and extracellular la­ known mechanisms of barrier repair, including la­ mellar bilayer formation in untreated patients with mellar body production and extracellular bilayer for­ different psoriatic phenotypes. Subjects with erythro­ mation. These findings are consistent with the hy­ derma and active plaque phenotypes displayed ele­ pothesis that both the initial appearance of psoriasis vated trans epidermal water loss levels, increased (Koebner phenomenon) and changes in disease phe­ numbers of epidermal lamellar bodies (many of notype are driven by alterations in barrier function. which failed to be secreted); i.e., corneocytes dis­ Key lVol,ds: bal'riel' f"llctioll/"ltmstl'llct"l'e/lamellal' bodies. played retained cytosolic lamellar bodies, and extra- ] Invest Derlllatol 107:558-564, 1996 n.volved psoriatic skin reportedlY.disP.lays de fective perme­ the stratum granulosum (S G)-SC interface (Elias and Menon, ability barrier function with transepidermal water loss 1991). Altho ugh little is known about permeability barrier ho­ (TEWL) levels up to 20 times normal (Felsher and Roth­ m eostasis in humans, in rodents barrier abrogation is followed by man, 1945; Grice and Bettley, 1967; Frost and Weinstein, (1) rapid secretion of performed epidermal LB, (2) replenishment of 1968; Grice el aI, 1973; Tagami and Yoshikuni, 1985) . the cytosol with n ewly fo rmed LB with further secretion of LB IC urr ent dogm a suggests that the epidermal changes in psonasls contents, and (3) formation of lam ell ar bilayers in the SC inter­ result from primary trigger factors released by abnormal circulating stices, leading to barri er recovery (Menon el aI, 1992a). Epidermal T cell s (Bos, 1988; Griffiths and Voorhees, 1992) and possibly other lipid syn thesis is required to sustain this process (Menon el aI, 1985; cell types in deeper skin layers (Sa iag et aI, 1985; Schubert and Grubauer el aI, 1989), and epidermal DNA synthesis also m ay C hristophers, 1985). Although this view could explain the rela­ contribute to barrier homeostasis (Proksch ci aI, 1991). tively uncomm o n guttate Aares that fo ll ow upper respiratory Because a primary barrier insult could be the m echanism that illnesses, and perhaps psoriatic erythroderm a, it igno res the impor­ underlies the Koehner phenom eno n , we have re- evaluated the tant role o f primary insults to the epidermis (Koebner phenome­ relatio nship betw een epidermal barrier function and epidermal non) as the trigger of m ost typical psoriatic lesio ns (Eyre and structure leading to lamell ar bi layer fo rmatio n in psoriasis. Prior Krueger, 1982). attempts to characterize the structural basis of psoriasis provide few Epidermal permeabili ty barrier integrity requires the organization insights about this relationship: both increased (Mottaz and Zelick­ of stratum corneum (SC) Li pids into extracellular lam ellar bilayers son, 1975; Lupulescu el aI, 1979) and normal (Bonneville el ai, fo ll owing the secretion of epidermal lam ell ar body (LB) contents at 1968) numbers of LB have been reported, all reportedly with normal internal structure (Mottaz and Zeli ckson , 1975; Bonneville e/ aI, 1968). Unfortunately, prio r studies did not correlate differ­ M'1I1uscript received February 12, 1996; revised April '12, 1996; accepted ences in LB m orphology with lesion phenotype. M oreover, they for publication May 21, 1996. did not correlate barrier function of the psoriatic lesions with the Rcprint requests to: Ruby Ghadially, M.D., Dcrmatology Serv ice (190), V.A. Medi cal Center, 4150 Clement Street, San Fran cisco, CA 94121. morphology of the LB secretory system . Finally, because of the lack Abbreviations: TEWL, transcpidermal water loss; EFAD, essential fatty of suitable post-fIxation m ethods, prior studies have not addressed acid deficiency; [,(3. lame ll ar body; SC, stratum corneum; SG, stratum the in tegrity of the SC extracellular lamellar bilayers in psoriasis. gral1ui oslIIn. Using ruthenium tetroxide (RuO.) post-fixation, it is now possible 0022-202X/96/S10.S0 • Copyright © 1996 by T he Society for In vestigative Dermatology, Inc. 558 VOL. 107, NO. 4 OCTOBER 1996 EPIDERMAL OAR.R.1ER IN PSORIAS IS 559 to obtain reproducible, accurate, ultrastructural images of the SC Table I. The Abnormality in Barrier Function in interstices (Hou et ai, 1991). In this study, we correlated perme­ Psoriasis Correlated with the Sev erity of the Psoriatic ability barrier status with ultrastructure of the LB secretory system Phenotype" and SC extracellular bilayers, in relation to disease p henotype. Our results suggest that disease p henotype correlates w ith abnorm ali ties Involved Skin Uninvolved Skin TEWL (g/ m2/ h) Significance TEWL (g/ m2/h) in LB structure, exocytosis, and the extracellular processing of secreted LB contents. These structural abnormalities, in turn, Erythroderma (n = 3) 36.4 ± 2.26 p ';; 0.001 3.5 ± 1. 0 correlate with the exten t of the barrier abnormali ty in psoriasis. Our P ,;; 0.005 results support the hypoth esis that primary barrier insults trigger the Active Plaque (n = 8) 16.1 ± 0.97 p :=; 0.001 3.9 ± 0.4 acute psoriatic phenotype. p ,;; 0.005 Chronic Plaque (n = 12) 9.0 ± 1.9 p < 0.05 4.1 ± 0.5 MATERIALS AND METH ODS Normal (n = 8) 4.8 ± 0.4 Sources of Tissue After obtaining informed consent, skin biopsies were (/ TE\VL was measured in patients w ith diffe rent psoriatic phenotypes . Measure­ obtained from the involved and uninvolved, adjacent sacral skin of 17 mentS were taken fro lll the ;lflcc tcd area and ;m adjacent area of uninvolved skin. T he patients with psoriasis (untreated for at least 2 wk), as well as 8 normal sex­ most severe phenotype (erythroderm a) displays the highest TEWL, approximiltely '10 and age-matched controls (homologous skin sites). T he psoria tics included times the uninvolved skill. R esults are presented ti S mean :t: SEM. 1 patient with sebopsariasis (involved sample fro m scalp rather than sacrum); i.e., psoriasiform scalin g of the scalp with minimal ski n involve­ ment elsewhere; 8 patients with chronic plaque psoria sis (l esions stationary for over 6 months); 3 patients 'with active, inAalll111a tory plaque psori asis; Uninvolved Epidertnis in Psoriasis Displays Normal Archi­ and 5 wi th acute, generalized erythroderma. Of these patients, 7 had tecture Post-fixation with standard osmium tetroxide fixation functional studies performed, as weB (sec below). provides excel.l ent preservation of LB structure. As in previo us studies (Ghadially et ai, 1992), cross-sectional images ofLB in both F unctional Studies TEWL meas urcments were performed 0 11 Icsions fram a separate cohort of untreated psoriatic subjects using a Servomed normal and uninvo lved psoriatic epidermis dem onstrated a trilam­ evaparimeter (Pinnagada " I nl, 1990). Meas urements were made on psori­ inar limiting m embrane and internal lam ellar disc-like structures aric lesions of 3 patients with acute erythroderma, 8 patients with active consisting of prominent dense lamellae separated by an electron­ inAa mmatory plaque psoriasis, and 12 patients with chroni c plaq ue psorias is. lucent band and divided cen trally by a mino r, striated electron­ TEWL al so was measured on contralateral or adjacent uninvolved skin in dense band (not shown; see Ghadiall y e/ ai, 1992). In no ne of the each of the patients. Biopsies also were obtaincd from 7 of these patiell ts (2 control samples examined did we find retained LB structures in with acute erytlu'oderma, 1 with active plaq ue psoriasis, and 4 with chronic com eocytes. Lamel.l ar bilayers w ithin the intercellular spaces dis­ plaque psoriasis). T he data Ii-om these patients were pooled witl, ti, e data p layed the characteristic unfurled pattern in the lower one o r two from those for whom functional or morphologic studies donc were 'lVail­ able, because the results were sil11jiar. T hree 111 caSUrCITICn ts ,vcre taken fro nl SC layers w ith m ature lamell ar bilayer basic unit structures filJing each site and the mean value then determined. Data from cach group were the interstices of the mid- to o uter SC (Fig lA, inset). T hus, these analyzed and the mean ± SEM determined. Statistical differcnces were studies show that th e uninvolved epidermis in psoriasis displays calculated usin g the Studcnt's tvvo-tail ed t tes t.
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