Significance and Pathogenesis of Basal Keratinocyte Herniations in Psoriasis Madalene C. Y. Heng, M.B., F.R.A.C.P., Suni G. Kloss, B.A. , Craig S. Kuehn, B.S., and David G. Chase, Ph.D. Department of Medicin e, Division of Dermatology, U CLA San Fernando Vall ey Internal Medicine Program, Veterans Administration Medica l Center, Sepul veda, California, U .S.A. U sing transmISSIOn electron microscopy, we studied, ria sis are associated with electron-lucent areas suggestive quantitatively, b asal keratinocyte h erniations (BKH) in re­ of proteolytic enzyme release. Their apparent association lation to the other basem ent membrane zone changes in with Langerhans cells, neutrophils, macrophages, and psoriatic lesions of varying clinical activity, and in p so­ endothelial cells may point to these cells as the source of riasiform skin diseases. BKH appears to correlate with dis­ proteolytic enzymes in psoriasis. BKH may prove to be a ease activity. They do not occur p assively as a result of the useful marker for clinical psoriasis. J Invest D ermatol 87:362- formation of gaps in the basal lamina. BKH in active p so- 366, 1986 ytoplasmic processes fro m basal keratinocytes pro­ completely resolved lesions, marked only by hyperpigm entation truding into the dermis through gaps in the basal (6 biopsies), and from uninvolved skin (10 biopsies) at least 10 lamina, have been 'observed by several in vestigators cm from the nea res t psoriati c lesion. [1 ,2] in involved psoriatic skin. We have subse­ Controls: The control population provided biopsies of normal . quently referred to these as basa l keratinocyte her­ skin from 4 nonpsoriati c patients (age- and sex-matched) , and Cniations or BKH [3,4]. However, their role in psori asis remains from the involved skin of 10 patients with the following pso­ unclear. Loss of integrity of the keratinocyte basement membrane riasiform skin diseases: seborrheic dermatitis (2 patients), pityri­ has been described in psoriasis [1 ,5-7]. and BKH have been thought asis rubra pilaris (1 patient), and 1 patient each with the following: to occur passively as a consequence of the formati on of ga ps in contact eczema (rubber chemicals), generalized eczema from the­ the basal lamina [2]. In this study, we have attempted to show, ophylline, pustular eczema palms and soles, primary irritant der­ by a series of studies, that the frequency of BKH correlated with matitis from Campho-phenique, contact dermatitis (nickel). li­ clinical activity; that the presence ofBKH could serve as a marker chen simplex chronicus , and li chen planus. for active psorias is; that BKH in active disease were associated with electron-lucent areas, suggestive of proteolytic autodiges­ Light and Electron Microscopy Four-millimeter punch biop­ tion; and that their apparent association with Langerhans cell s, sies were taken and divided 10ngitudinal1y with a sharp scalpel. neutrophils, dermal macrophages, and endothelial cell s suggests One hiM of each biopsy was fixed in 10% neutral buffered for­ that these cells, w hi ch are know n producers of proteolytic en­ malin and processed for light microscopy. The paraffin sections zymes, may playa role in BKH formation. were stained with hematoxylin and eosin. The other half w as fixed in 2.5% glutaraldehyde, buffered to pH 7.3 with 0. 1 M PATIENTS AND METHODS sodium phosphate, postfixed in osmium tetroxide, treated en bloc with tanmc acid, dehydrated in alcohol and propylene oxide, and Patient Population All the patients and controls attended the embedded in a mixture of Epon 812 and Araldite 502. Silver Outpatient Dermatology Clinics at the Veterans Administration sections were cut on a Sorval MT 2B ultramicrotome with a Medical Center, at Sepulveda, California. They were divided into diamond knife (Dupont) and examined with a Philips EM 201 the following groups. transmission electron microscope. Patiel'lls: Biopsies were obtained fro m 36 psoriatic patients. Clin­ Analysis of Data The fr equency of BKH was determined as ical detai ls have been summarized in Table I. Biopsies were taken follows. A series of slightly overlapping electron micrographs from acute, untreated psoriatic plaques (4 patients), pustular le­ were taken of a 150-250 ,uin length of basement membrane for sions (3 patients), eruptive and/or generalized psoriasis (3 pa­ each patient and control, and printed at a constant magnification ti ents), treated patients with plaques without areas of resolution of 17,000 x. The basement membrane lengths were measured on (5 patients), treated patients with plaques containing areas of res­ a graphics tablet connected to an Apple II plus microcomputer. olution (3 patients), resolving generali zed psoriasis (2 patients), The number of herniati ons and other basement membrane zone (BMZ) changes were counted as the length of basal lamina was measured with the graphics tablet. Manuscript received July 31, 1985 ; accepted for publication February 18, 1986. Supported by a Veterans Adminis tration Merit Proposal Grant. RESULTS Reprint requests to: Madalene C. Y. Heng, M .B., Division of Der­ matology (1 11 F) , Veterans Administration M edica l Center, 16111 Plum­ Analysis of the data obtained from psoriatic lesions of varying mer Street, Sepul veda, California 91343. clinical activity shows that BKH (Fig la) were most numerous Abbreviations: in untreated eruptive, p!lstuJar, generalized psoriasis (9.1 ± 1.4 BKH: basal keratinocyte h ern i a~ i on(s) BKH per 200,um basal lamina length), less numerous (3.8 ± 0.7 BMZ: basement membrane zone BKH per 200 ,um basal lamina length) in treated psoriatic lesions 0022-202X/86/S03.S0 Copyright © 1986 by The Society for Investigative Dermatology, Inc. 362 VOL. 87, NO.3 SEPTEMBER 1986 BASAL KERATINOCYTE HERNIATIONS IN PSORIASIS 363 Table I. Frequency of Basal Keratinocyte H erniation (BKH) and Basement Membrane Zone Abnormalities in Psoriasis and Controls Lamina Lucida Basal Lamina C hanges Dilatations BKH (no.l200 f..Lm basa l lamina length) N o. of Patients (no.l200 f..Lm basal (no.l200 f..Lm basal C linical Status (biopsies) Gaps Thinning Reduplication lamina length) lamina length) Psoriasis: Treatedlresolving 10 13.5 :±: 1. 6 34.9 :±: 4.9 30.0 :±: 2.6 21.4 :±: 2.1 3.8 :±: 0.7 Untreated 10 40.6 :±: 1. 9 76.5 ± 5.3 11.1 :±: 1.3 41.0 :±: 1.7 9.1 :±: 1.4 Completely resolved 6 5.4 ± 0.6 19.8 ± 0.9 59.3 :±: 0.9 5.4 :±: 0.8 0 Uninvolved 10 2.2 :±: 0.2 9.7 ± 0.9 10.8 :±: 0.9 4.9 :±: 0.4 0 Controls (nonpsoriatics): Pityriasis rubra pilaris 1 52.2 102. 6 3.6 51.0 1 Eczema (all types) 6 13.6 26.2 33.8 16.0 0 Lichen planus 1 12.0 29.0 39.6 18.7 0 Normal skin 4 0.2 1.0 1.1 0.8 0 without areas of resolution, very infrequent in treated psoriatic the purpose of statistical analysis, the psoriatic group was divided plaques with areas of resolution (1.2 ± 0.4 BKH per 200 ,um into 4 subgroups: involved untreated, treatedlresolving, com­ epidermal length), and absent in areas that showed complete clin­ pletely resolved, and uninvolved. An analysis of variance shows ical resolution. They were absent from uninvolved psoriatic skin, that the treated group is significantly different (p < 0.01) from from normal non psoriatic skin, and from a number of common that of the treated, resolved, and uninvolved groups with regard dermatoses. These resuits have been summarized in Table I. For to BKH frequency. Figure 1. a, Electron micrograph showing a basal keratinocyte herniation (BKH) con­ sisting of a cytoplasmic process from the basal keratinocyte (BK), protruding through a gap (between arrowheads) in the basal lam­ ina, into the dermis (D) . Note the e1ectron­ lucent area (A) adjacent to the BKH, sugges­ tive of proteolytic autodigestion. LL = dil­ atation of the lamina lucida; LD = lamina densa. Bar = 1 f..L. b, Electron micrograph of a healing psoriatic plaque, showing re­ duplication of the lamina densa (LD) . Note also a gap (between arrowheads) in the basal lamina, and multiple dilatations of the lam­ ina lucida (LL). E = epidermis, D = der­ m is. Bar = 1 f..L. c, Electron micrograph of a treated psoriatic plaque (steroids), show­ ing a BKH of the central variety, protruding into the dermis (D) through a gap (between arrowheads) in the lamina densa (LD). Note localized dilatations (LL) of the lamina lu­ cida. BK = basal keratinocyte. Bar = 1 f..L. 364 HENG ET AL THE JOURNAL OF INVESTIGATIVE DERMATOLOGY An examination of the distribution of BKH in relation to the were also found in uninvolved and healed psori atic skin as well other BMZ changes, such as gaps (Fig 1b) , thinned areas (Fig 1a ) as in a number of control diseases, and are, therefore, not as useful in the lamina densa, and dilatations of the lamina lucida (Fig 1b) as BKH as markers for the presence of the clinical psoriatic lesion. revealed that altho ugh these BMZ abnormalities were, in general, The presence of BKH also in pityriasis rubra pilaris, a disease most numerous in the involved psoriatic lesions, there was no characteri zed by hyperproli fera tion as is psoriasis, and the pres­ correlation between the number of gaps in the lamina densa and ence of BKH-like structures in a num ber of tumors [8-11) would the frequency ofBKH found (Table I). These BMZ changes were suggest that BKH may playa role in hyperproliferation. By pro­ also found in all the control psoriasiform lesions studied. In pit­ viding a means whereby epidermal and stro mal elements ca n react yriasis rosea, BKH were noted, but in a fre quency far lower than more intimately, over a larger surface area, it is possible that that found in psoriasis.