Benign junctional epidermolysis bullosa in three related Moroccan families
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Fig 1 PedIgree of patIents affected WIth JunctIonal epIdermolySIS bullosa were used for Immunofluorescent antIgen mappmg Bullous pemphIgOId antzgen was found In the roof of the blIster cavIty, whereas type IV collagen and lammIn were present on the b!Jster floor The dIstnbutlOn of three antlgemc determInants mdlcated that the cleavage had occurred m the lamma lucIda These findmgs mdlcate JunctIonal bhster formatlOn Cases 2 (V·S) and 3 (V-I) Two boys, 5 and 12 years of age, had slmdar hIS tones PhySICal findmgs were SImIlar to those of the proband but were more pronounced because of their ages FamIly hlstones The pedIgree shows three male patIents affected by Junctional epidermolySIS bullosa m three related JeWIsh fanulIes of Moroccan origIn The proband (IV-5) be- longs to Family 3 HIS parents were first cousms and he had seven slbhngs, a brother and SIX sisters Two of hiS sisters (IV-9 and IV-IO) were affected Wlth cerebrotendmous xan- thomatosls 4 and another sister (lV-l1) was a quadnpleglc followmg cerebrospmal fracture HIS other four slblmgs were healthy The proband and Ius Wife were not related and had two healthy chIldren V-B, the second patient (Fanuly 2) was the nephew of the proband HIS parents were first COUSInS and had three other healthy chIldren V-I, the thIrd pattent (FamIly 3), was the offspnng of a first cousm once removed mamage, furthermore, he was related to the proband as a first cousm once removed and as a second cousm from two lmeages The common ancestors of all three patIents were 1-1 and 1-2 and II-I and 11-2 Comment Bemgn JunctIOnal epIdermolySIS bullosa IS conSIdered a dlstmct and well-defined entIty 56 It IS easIly dlstmgUlshed on a chmcal baSIS from the other generahzed forms of epIdermolySIS bullosa by contm- uous bhstenng SInce blrth, predommantly over the fin- gers and other areas, subject to trauma and healIng WIthout scars and mIlIa Postbullous erOSIOns heal rap- Idly, but repeated blIstenng on repeatedly traumatized skm leads to atrophy PatIents have been reported WIth Correspondence Bemgn JunctIonal epIdermolysIs bullosa 10 three related Moroccan famIlIes To the Edztor JunctIOnal epIdermolysIs bullosa IS a very rare bul- lous genodermatosIs first descnbed by Herhtz l In 1935 Pearson 2 In 1962 showed that the blister formatIOn In JunctIOnal epIdermolysIs bullosa occurred In the lamma lucida Smce then SIX other chmcal phenotypes ofJunc- tIonal epidermolySIS bullosa 3 were descnbed, all of them were mhented through an autosomal recessIve gene It IS now well known that not all types have the lethal prognOSIS of the HerlItz vanety ThIS study descnbes three related JeWIsh famIlies ongmally from Morocco wIth three male patIents af- fected wIth bemgn JunctlOnal epIdermolySIS bullosa In two generatIOns (FIg 1) Case I The proband (IV-5), a 30-year-old mamed man, employee, had suffered smce buth from generalized bhstenng that was tnggered by fnctIon and trauma The predilection sItes for bhster formatlOn were fingers, palms, soles, elbows, and knees, but bullae had also appeared on the trunk No hIstory of blIstenng 10 the oral mucous membrane area and gums and no dysphagIa were noted The number of bhsters Increased 10 warm seasons and tended to decrease by pro- gressIOn of age Skm exammatlon revealed several well-defined, tense or flaCCid bullae measunng 0 5 to 1 5 cm m dIameter and con- tammg serous or hemorrhagIC flUId The bullae were present on the palms, soles, dorsal aspects of the hands and feet, trunk, and predommantly over the fingers Some of the bullae were supennfected They healed m the fonn of hyperplg- mented atrophIC scars and WIthout milia On the elbows and knees, areas of fine wnnkled skm already were present (FIg 2) Male pattern baldness was the only scalp findIng NIkolskI's sIgn was posItive on normal-appearmg skIn Oral mucous membranes were free of leSIOns The teeth were nor- mal No syndactyly was found The fingernails were elther completely normal or thIckened, discolored, and dystrophiC AnonychIa and onychodystrophy were observed m the toe naIls Laboratory tests SedimentatIOn rate was 37/mm dUring the first hour The results of other routme tests, chest x-ray, banum enema, and upper gastromtestmal tract examlOatlOn were normal Skm histopathology Skm speCImens stamed WIth hema- toxyltn and eOSin from bullae showed basket weave hyper- keratOSIs of the epIdermIS and atrophy of rete ndges A sub- epidermal level of cleavage was apparent Skm specImens stamed WIth penodlc aCld-Schlff reagent showed subepider- mal bullae Cryostat sectIOns from blOpSy specImens of bullae 508 I II III IV v Family 1 Family 2
Transcript of Benign junctional epidermolysis bullosa in three related Moroccan families
Fig 1 PedIgree of patIents affected WIth JunctIonalepIdermolySIS bullosa
were used for Immunofluorescent antIgen mappmg BullouspemphIgOId antzgen was found In the roof of the blIster cavIty,whereas type IV collagen and lammIn were present on theb!Jster floor The dIstnbutlOn of three antlgemc determInantsmdlcated that the cleavage had occurred m the lamma lucIdaThese findmgs mdlcate JunctIonal bhster formatlOn
Cases 2 (V·S) and 3 (V-I) Two boys, 5 and 12 years ofage, had slmdar hIStones PhySICal findmgs were SImIlar tothose of the proband but were more pronounced because oftheir ages
FamIly hlstones The pedIgree shows three male patIentsaffected by Junctional epidermolySIS bullosa m three relatedJeWIsh fanulIes of Moroccan origIn The proband (IV-5) belongs to Family 3 HIS parents were first cousms and he hadseven slbhngs, a brother and SIX sisters Two of hiS sisters(IV-9 and IV-IO) were affected Wlth cerebrotendmous xanthomatosls4 and another sister (lV-l1) was a quadnpleglcfollowmg cerebrospmal fracture HIS other four slblmgs werehealthy The proband and Ius Wife were not related and hadtwo healthy chIldren V-B, the second patient (Fanuly 2) wasthe nephew of the proband HIS parents were first COUSInS andhad three other healthy chIldren V-I, the thIrd pattent (FamIly3), was the offspnng of a first cousm once removed mamage,furthermore, he was related to the proband as a first cousmonce removed and as a second cousm from two lmeages Thecommon ancestors of all three patIents were 1-1 and 1-2 andII-I and 11-2
Comment Bemgn JunctIOnal epIdermolySIS bullosaIS conSIdered a dlstmct and well-defined entIty 56 It ISeasIly dlstmgUlshed on a chmcal baSIS from the othergenerahzed forms of epIdermolySIS bullosa by contmuous bhstenng SInce blrth, predommantly over the fingers and other areas, subject to trauma and healIngWIthout scars and mIlIa Postbullous erOSIOns heal rapIdly, but repeated blIstenng on repeatedly traumatizedskm leads to atrophy PatIents have been reported WIth
Correspondence
Bemgn JunctIonal epIdermolysIs bullosa 10
three related Moroccan famIlIes
To the EdztorJunctIOnal epIdermolysIs bullosa IS a very rare bul
lous genodermatosIs first descnbed by Herhtz l In 1935Pearson2 In 1962 showed that the blister formatIOn In
JunctIOnal epIdermolysIs bullosa occurred In the lammalucida Smce then SIX other chmcal phenotypes ofJunctIonal epidermolySIS bullosa3 were descnbed, all ofthem were mhented through an autosomal recessIvegene It IS now well known that not all types have thelethal prognOSIS of the HerlItz vanety
ThIS study descnbes three related JeWIsh famIliesongmally from Morocco wIth three male patIents affected wIth bemgn JunctlOnal epIdermolySIS bullosa In
two generatIOns (FIg 1)
Case I The proband (IV-5), a 30-year-old mamed man,employee, had suffered smce buth from generalized bhstenngthat was tnggered by fnctIon and trauma The predilectionsItes for bhster formatlOn were fingers, palms, soles, elbows,and knees, but bullae had also appeared on the trunk NohIstory of blIstenng 10 the oral mucous membrane area andgums and no dysphagIa were noted The number of bhstersIncreased 10 warm seasons and tended to decrease by progressIOn of age
Skm exammatlon revealed several well-defined, tense orflaCCid bullae measunng 0 5 to 1 5 cm m dIameter and contammg serous or hemorrhagIC flUId The bullae were presenton the palms, soles, dorsal aspects of the hands and feet,trunk, and predommantly over the fingers Some of the bullaewere supennfected They healed m the fonn of hyperplgmented atrophIC scars and WIthout milia On the elbows andknees, areas of fine wnnkled skm already were present (FIg2) Male pattern baldness was the only scalp findIngNIkolskI's sIgn was posItive on normal-appearmg skIn Oralmucous membranes were free of leSIOns The teeth were normal No syndactyly was found The fingernails were elthercompletely normal or thIckened, discolored, and dystrophiCAnonychIa and onychodystrophy were observed m the toenaIls
Laboratory tests SedimentatIOn rate was 37/mm dUringthe first hour The results of other routme tests, chest x-ray,banum enema, and upper gastromtestmal tract examlOatlOnwere normal
Skm histopathology Skm speCImens stamed WIth hematoxyltn and eOSin from bullae showed basket weave hyperkeratOSIs of the epIdermIS and atrophy of rete ndges A subepidermal level of cleavage was apparent Skm specImensstamed WIth penodlc aCld-Schlff reagent showed subepidermal bullae Cryostat sectIOns from blOpSy specImens of bullae
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vFamily
1Family
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Volume 14Number 3March, 1986
Fig. 2. A and B, Flaccid bullae, erosions, and atrophiedskin of elbow and knees of the proband (lV-5).
respiratory, gastrointestinal, and genitourinary tract involvements. Progression of age is associated with improvement of skin condition.
Pathogenesis of junctional epidermolysis bullosa isnot well known. Bauer et aP demonstrated marked elevated levels of collagenase in the normal-appearingskin of patients with junctional epidermolysis bullosaand suggested a causative role of collagenase in production of blisters. Blistered skin of patients affectedwith junctional epidermolysis bullosa has elevated collagenase levels. Histologically, the blister exists at thedermoepidermal junction. Hemotoxylin-eosin and periodic acid-Schiff staining of sections from normal andblistered skin show dermoepidermal cleavage and supepidermal blister formation. The PAS-positive basement membrane found on the floor of the blister andelectron microscopy reveal the separation to be in thelamina lucida. Immunofluorescence antigen mappingwith the use of bullous pemphigoid antigen, laminin
Correspondence 509
antibody, and antibody to type IV collagen reveal theseparation in the upper portions of the lamina lucida injunctional epidermolysis bullosa. 8 The preceding findings explain the rapid healing of blistered areas, theabsence of marked scarring, and the formation of atrophy in repeated blistering sites.
The present study describes three affected personswith benign junctional epidermolysis bullosa from threefamilies with common ancestors, all showing similarclinical findings. Consanguinity of phenotypically normal parents and sharing of common ancestors stronglysuggest autosomal recessive inheritance. Cerebrotendinous xanthomatosis is another autosomal recessivedisease in this family. The association of junctionalepidermolysis bullosa and cerebrotendinous xanthomatosis in siblings has not been reported in the literature.
Shoshana Hacham-Zadeh, M.D.Department ofDermatology
Hadassah University Hospital, Jerusalem, Israel
REFERENCES1. Herlitz 0: Kongenitaler nieht syphilitischer pemphigus:
Sins ubersicht nebst beschereibung einer neuen krankheitsfonn. Acta Paediatr 17:315-371, 1935.
2. Pearson RW: Studies on the pathogenesis of epidermolysisbullosa. J Invest Dermatol 39:551-575, 1962.
3. Haber RM, Hanna W, Ramsay CA, Boxal1 LBH: Cicatricial junctional epidennolysis bullosa. J AM ACAD DERMATOL 12:836-844, 1985.
4. Berginer VM, Abeliovich D: Genetics of cerebrotendinousxanthomatosis (CTX): An autosomal recessive trait withhigh gene frequency in Sepharadim of Moroccan origin.Am J Med Genet 10:151-157, 1981.
5. Hashimoto J, Schnyder UW, Anton Lamprecht I: Epidermolysis bullosa hereditaria with junctional blistering in anadult. Dermatologica 152:72-86, 1976.
6. Hintner H, Wolff K: Generalized atrophic benign epidermolysis bullosa. Arch DermatoI118:375-384, 1982.
7. Bauer EA, Gedde-Dah1 T, Eizen AZ: The role of humanskin collagenase in epidermolysis buHosa. J Invest DermatoI68:119-124, 1977.
8. HintnerK. Stingl G, Schuler G, et al: Immunofluorescencemapping of antigenic determinants within the dermalepidermal junction in mechanobuHous diseases. J InvestDermatoI 76:113-118, 1981.
Keratosis punctata of the palmar creasesTo the Editor:
In their recent article, "Keratosis Punctata of thePalmar Creases," Ortega, Quintana, and Camacho (JAM ACAD DERMATOL 13:381-382, 1985) indicated thatkeratosis punctata of the palmar creases is an uncom-
