BLSTER-SPREAD NDUCED BY FNGER-PRESSURE, A DAGNOSTC SGN N PEMPHGUS* A dignostic nd pthognomonic feture of pemphigus vulgris (cutus) is the reduction or loss of cohesion between the epiderml cells. This phenomenon, clled cntholysis, is ccompnied by intercellulr edem nd dmge to the intercellulr bridges. n contrst, the microscopic picture of bullous pemphigoid or pemphigus vulgris chronicus (1, 2) is chrcterized by clefts or bulle between the bsl epiderml lyer nd the corium. Both the reduced cohesion between bsl nd prickle cells nd the loss of foothold of the bsl cells in the connective tissue constitute the pthologicl bsis of the Nikoisky phenomenon. This clinicl test is vluble sign to llow differentition of pemphigus from other bullous skin diseses. t is not, however, specific for the pemphigus group of diseses, nd, in pemphigus vulgris, the sign my be present only in certin stges or res, or be lcking completely, even in infiltrted nd erythemtous res where intrepiderml blisters re observed microscopiclly. f histopthologic dignosis is to be mde, fresh bull should be excised nd the tissue fixed in tolo. n older bulle, epithelil regenertion my hve tken plce covering the floor of the bull, thus disturbing the dignosis (2). The phenomenon described below offers higher dignostic vlue to the histopthologist, s well s, s it seems, n lmost pthognomonic feture t disposl for the clinicin in his efforts to distinguish pemphigus from other severe bullous dermtoses. MATERAL The bullous skin diseses observed were the following: Pemphigus vulgris (cutus) (6); pemphigus foliceus (3); pemphigus vegetns (2); bullous pemphigoid (pemphigus vulgris chronicus) (6); benign mucous membrne pemphigoid (2); fmilil benign chronic pemphigus (Hiley nd GUSTAV ASBOE-HANSEN, M.D. * From the Deprtment of Dermtology nd Venereology, University Hospitl (Rigshospitlet), Copenhgen, Denmrk. Received for publiction My 12, 1959. 5 Hiley) (2); dermtitis herpetiformis (11); epidermolysis bullos hereditri (3); urticri bullos (1); urticri pigmentos bullos (2); bullous erythem multiforme (8); bullous drug eruption (2); bullous contct dermtitis (6); bullous epidermophytid (3); bullous lichen plnus (2); impetigo (4); pemphigus neontorum (3); erysipels (1); herpes simplex (8); Kposi's vricelliform eruption (2); herpes zoster (5); vricelle (2); bullous kertogenous nd pigmentry dermtitis (2); trumtic bull (7); embolic hemorrhgic bull (1); hemorrhgic bull in uremi (1); rtificil congeltion (C02) (4); mustrd gs corrosion (1); burn (6). TECJNCS AND RESULTS 1. Clinicl Dignosis A bull is pressed by finger pulp from bove verticlly down. By slight to moderte pressure, pemphigus bull cn be brought to spred in one or more directions depending on the min direction of the pressure (Figs. 1, 2). Thus, it is possible to expnd the blister severl centimeters, the only limit being the mount of fluid. The phenomenon my be produced in res where no Nikoisky sign cn be produced, nd where, to the nked eye, the surfce revels no disese. The phenomenon reflects reduced cohesion between the epiderml cells or between the bsl epiderml cells nd the derml connective tissue. The sign hs been found positive in pemphigus vulgris (eutus), pemphigus foliceus, pemphigus vegetns nd bullous pemphigoid (pemphigus vulgris chronicus). n one cse of embolic gngrene in foot nd one of bullous drug eruption, spred of bulle could be produced by exertion of strong pressure. n dermtitis herpetiformis, benign mucous membrne pemphigoid, epidermolysis bullos, erythem multiforme, nd ll other mentioned bullous diseses the blebs could not be moved before bursting. Two cses of fmilil benign chronic pemphigus (Hiley nd Hiley) did not present bulle of size nd chrcter tht could be used for these studies.
6 THE JOURNAL OP NYTGSTVE DZRM&TOLOGT 'Pt S. Pm. 1. Right hnd of ptient with bullous peniipbigid (pemphigus nigeri ehronieue). 1 nd 2 indicte spontneous nd untouched bulle. J! 2 9 'PC. w Pm. t Seine res s Pig. 1. The "blister.spred" ph.nonwmon is shown to the right, where blister 1 is being trnsported. Bllster2hs been spred; the dotted line indicting the expns1m. Note the wrin- Medsurfce of the spred blister in comprison to the tense bulls 2 of Fig. 1.
BLSTER SPREADNG N PEMPHGTJS 7 2. Histoplhologic Dignosis described bove, nd to remove the specimen nsted of choosing fresh bull for totl for biopsy from the new, dvnced border. excision, it is preferble to move spontneous t cn now be seen which lyer is the site of bull, young or old, into the surroundings s most pronounced brekdown of the resistnce F FG. 3. Microphotogrph of the new, dvnced edge of n rtificlly spred pemphigus vulgris blister produced by finger pressure. Note the shrp intrepiderml edge to tbe right, nd the single lyer of bsl epiderml cells covering the bottom. >< indictes cntholytic cells. Mgn. X600. Stining: Hemtoxylin-eosin. A. S 4 Si.'. 'p t. S. 0 c,. pp p ' 'A 4.%_.'pp t' Fin. 4. Microphotogrph of n rtificilly spred pcmphigus vulgris (cutus) blister. Note the extensive lysis of epiderml cells. X cntholytic cell cluster. Mgn. X350. Stining: Hemtoxylincosin.
8 THE JOURNAL OF NVESTGATVE DERMATOLOGY ginst spred, i.e. is the site of the most dvnced physicl nd/or chemicl dmge to intercellulr bridges or to the derml-epiderrnl junction. n pemphigus vulgris (cutus) the displcement of the fluid tkes plce in the suprbsl re, usully leving single lyer of epiderml cells ttched to the corium. The new-formed ngle _. C 'i r" 4l 'it. - 7.. 'i_s p 4 FG. 5. Microphotogrph of n rtificilly spred bullous pemphigoid (chronic pemphigus vulgris) blister. Note the lysis in the derml-epiderml junction. To the left the dvnced edge is rounded. No cntholytic cells. Mgn. X350. Stining: Hemtoxylin-eosin. SW-' 0 2. '% '._c.. t':. :.i:'.4. 1, FG. 6. Microphotogrph of n rtificilly produced derml-epidcrml lysis in bullous pemphigoid. The most dvnced border is to the left. No cntholytic cells. Mgn. X160. Stining: llcmtoxylineosin.
BLSTER SPREADNG N PEMPHGUS 9 into the surrounding epidermis is shrp, nd the bull extends into cleft-like edge zone. There is detchment (cntholysis) of single cells or clusters of cells of the epidermis nd the hir follicles (Fig. 3). The intercellulr lysis nd fluid invsion long verticl or horizontl clefts (Fig. 4) re constnt findings, s in spontneous bullc, nd the totl picture is replic of pemphigus vulgris blister, except for the bsence of nucler chnges in the cntholytic cells. Like in pemphigus vulgris, blisters of pemphigus vegetns my be moved intrepidcrmlly in the suprbsl re. n pemphigus follceus blisters rc esily moved. The trnsport tkes plce in the upper Mlpighin lyer or in the re immeditely below the strtum corneum. n bullous pemphi gold (pemphigus eulgris chronicus) the bull my be trnsported by slight pressure between the epidermis nd the corium (Fig. 5). n some cses, intrcpiderml displcement hs occsionlly been noted; but in such cses the dvnced border is rounded like in the pressure bull (2), nd true cntholysis hs not been observed. t is possible to rtificilly detch the epidermis from the connective tissue in wide res, depending on the mount of blister fluid (Fig. 6). DscussoN n this reltively smll mteril, it ppers tht the blister spred, lthough not bsolutely specific, is chrcteristic phenomenon belonging to the pemphigus group of diseses. n the present study the term dermtitis herpetiformis hs been scribed to cses comptible with the description of Brocq's "dermtite polymorphe doulourcuse." Cses without herpetiform grouping, polymorphism, itching or pins, exhibiting low blood lbumin levels, nd lrge subepiderml blisters hve been designted bullous pemphigoid nd considered synonymous with pemphigus vulgris chronicus. Like cute pemphigus vulgris, this disese is chrcterized by positive Nikolsky nd "blister spred" signs; nd by these phenomen oriented to the pemphigus group. The microscopic studies of the morphologic bckground of the blister spred suggest tht either cntholysis or derml-epidcrml lysis occur in skin where the sign cn be produced. The phenomenon is of dignostic vlue to the histopthologist, reproducing the microscopic picture of spontneous fresh blister. Compred to spontneous bulle, the rtificilly expnded blister does not crry the risk of misinterprettion of the site of bull, becuse there cn be no secondry epithelil regenertion. SUMMARY A spreding of blisters cn be rtificilly induced by slight to moderte externl finger pressure in pemphigus vulgris (cutus), pemphigus foliceus, pemphigus vegetns nd bullous pcmphigoid (pcmphigus vulgris chronicus). The sign is chrcteristic, lthough possibly not bsolutely specific, of the pemphigus group of diseses. t reflects reduction or loss of intercellulr bridges between cpiderml cells or dermlcpidcrml lysis. n the new re of the expnded blister, the microscopic picture of spontneous fresh blister is reproduced. The blister spred sign is of dignostic vlue to the clinicin s well s to the histopthologist. REFERENCES 1. LEvER, W.: Pemphigus. Arch. dcrmt. syph., 64: 727, 1951. 2. LEVER, W.: Femphigus. Medicine, 32: 1, 1953.