British Jourtiai of Dertnatology (1992) 127, 318-321.
Epidermolysis bullosa in Northern Ireland K.E.McKENNA, M.Y.WALSH* AND E.A.BINGHAM Departments of Dermatology and *Pathology. Royal Victoria Hospital. Belfast. Northern Ireland Accepted for publication 1 June 1992
Summary
Cases of epidermolysis bullosa (EB) diagnosed in Northern Ireland during a 23-year period (1962-84) were identified from dermatology clinic files, paediatric hospital notes and cases known by general practitioners, A total of 48 confirmed new cases ofEB were diagnosed during the screening period. This involved 31 families, with identification of 36 further cases. The distribution of incident EB subtypes was: simplex 31 (65%), junctional 1 (2%). dystrophic 12 (25%) and acquisita 4 (8%). The incidence rate of new cases of EB diagnosed per year is 1-4/million and prevalence of all forms estimated at 32/miIlion. The prevalence of simplex, junctional and dystrophic forms is 28, 0-7 and 3/miUion, respectively.
Epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders characterized by marked skin fragility, blister formation, and in some cases by significant scarring. There are three major types of hereditary EB— simplex, junctional and dystrophic. Each type has certain characteristic clinical features and a specific site of cleavage within or adjacent to the epidermal basement membrane,^"* In addition, there is an acquired type of EB with characteristic immune deposition in the sublamina densa zone.^ Few studies have been performed regarding the epidemiology of EB.*"^^ We have performed an epidemiological study of the incidence and distribution of types and subtypes ofEB occurring in Northern Ireland during a 2 3-year period.
Methods Patients
Cases of EB diagnosed in Northern Ireland (NI) during the period 1962-84 inclusive were identified from dermatology clinic notes. This time interval was selected because records were complete for all clinics during this period. This included four Belfast hospital-based clinics, including the Royal Belfast Hospital for Sick Children, and 18 other clinics distributed throughout NI. Cases recorded in paediatric hospital notes were also noted. Patients were contacted to attend for review. In addition, general practitioners were contacted to assist in tracking cases. Correspondence: Dr K.E.McKenna, Department of Dermatology, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland.
318
Classification of EB cases
Diagnostic criteria for EB were similar to those used by Gedde-Dahl,^ supplemented by electron microscopy and immunofluorescence antigen mapping 'i* to determine the level of blister formation. The skin was examined for blister distribution, scarring, milia, pigmentary abnormalities, acral hyperkeratosis and cutaneous neoplasia. Involvement of mucous membranes, nails, teeth, eyes and hair was recorded. A family pedigree of each affected family was constructed. Further affected members or secondary cases were identified and interviewed if possible. Skin biopsy
The clinical diagnosis was confirmed when possible by skin biopsy. Two 4-mm punch biopsies were taken from recent blisters, or rubbed skin, using local anaesthesia with 1% Iignocaine. The samples were examined by EM and IAM. Antibodies used included those against bullous pemphigoid antigen, laminin, type IV and type VII collagen.
Results A total of 72 new cases of EB were recorded during the screening period. Of these, 10 were not EB, and in 14 the notes had either been destroyed or lost. The remaining 48 cases had EB, and from these index cases or probands a further 36 secondary cases were identified from pedigree studies. This involved 32 families with one or more affected members.
EB IN NORTHERN IRELAND
Table 1. Distribution of EB simplex subtypes. Skin biopsies examined by electron microscopy (EM) and immunofluorescence antigen mapping (IAM)
Koebner Weber-Cockayne Dowling-Meara Mottled pigmentation Ogna Bart
Simplex types EB simplex (EBS) was diagnosed in 31 probands (Table 1), The most common variety was Weber-Cockayne (EBS-WC), witb blistering affecting tbe palms and soles. Tbis occurred in 26 patients, and a furtber 3 5 secondary cases were identified. The majority of EBS-WC cases occurred in two large families with 14 and 11 living affected members, respectively. Three patients had the Koebner form (EBS-K) in which disseminated blistering occurs. One also had dystrophic nails. Two cases of the Dowling-Meara form (EBS-DM) were recorded. Clinical features of EBS-DM included generalized blistering at birth witb erosions and crusting. Blistering showed grouping and was non-scarring. Palmoplantar keratoderma developed in later life. Electron microscopic findings included basal cell cytolysis and clumping of tonofilaments. One patient is still resident in NI, the other lives abroad, and his son is affected. No cases with mottled pigmentation, and no Bart or Ogna forms of EBS were discovered.^'-^^ A total of 30 affected individuals were examined and skin biopsy was performed in six patients. Junctional types Six main types of junctional EB (JEB) are recognized, and include the gravis, mitis, cicatricial, inversa, minimus and progressiva variants,^'^ During our screening period Table 2, Distribution of dystrophic EB cases. Skin biopsies examined by electron microscopy (EM) and immunofluorescence antigen mapping (IAM)
Recessive Hailopeau-Siemens Inversa Localized Dominant Cockayne-Touraine Pasini Pretibial
Probands
Secondary cases
Families
3 26 2 — — —
0 34 1 — — —
3 17 2 — — —
319
EM/IAM
4 2
one case of JEB of the inversa type was diagnosed in a male patient, who is still alive. The patient had a history of axillary and groin blistering since birth. Corneal involvement and nail dystropby were also present.
Dystrophic types A total of 12 dystrophic EB (DEB) index cases were identified (Table 2). These were represented by six dominant and six recessive cases. The four cases of Hailopeau-Siemens recessive DEB were related, and had died following the development of squamous carcinoma of the skin. Two other unaffected sibs had ichthyosis vulgaris. Interestingly, Gedde Dabl* reported tbree unaffected members in the family of a case of lethal DEB who had ichthyosis vulgaris. The two cases with localized recessive disease were brotber and sister. Blistering mainly affected the limbs, and nails were dystrophic. Both patients complained of dysphagia, and upper oesophageal webs were demonstrated. Patients with autosomal dominant Cockayne-Touraine DEB* had blistering, and atrophic scarring with milia, occurring mainly over knees, elbows, fingers and toes. Nail dystrophy was present in three patients. Three of these cases were not traced and a secondary case had died of an unrelated illness. There was one case of Pasini DEB. with atrophy and scarring affecting mainly the limbs, with occasional truncal lesions. In addition, lumbar
Probands
Secondary cases
Families
4
0
1
2
0
1
1
5 1
1 0
4 1
2 1
EM/IAM
320
K.E.McKENNA et al.
albopapuloid lesions were present. No cases of inversa or pretibial DEB were recorded. A total of five cases of DEB were traced, and are resident in Nortbern Ireland. Four of tbese patients bad skin biopsies performed. Acquisita
Four patients witb EB acquisita were diagnosed during tbe screening period. Unfortunately tbree of tbese patients are now dead, and tbe fourtb cannot be traced. Tbese patients were cbaracterized by late onset of mainly acral blistering witb milia formation. Tbere was a negative family bistory of EB. Tbe patients were not taking any systemic medications, Porpbyria bad been excluded by appropriate biocbemical tests. Unfortunately tbese patients were diagnosed at a time wben electron microscopy was not available in tbe province. Incidence and prevalence
Tbe incidence of newly diagnosed cases of EB occurring in Nortbern Ireland was calculated for tbe 2 3-year screening period. Tbe population of Nortbern Ireland is approximately 1 • 5 million, Tbe incidence rate of new cases of all types of EB is 1-4/million/annum. Tbe incidence rate for EBS is 0-9, JEB 0-03 and DEB 0-3/ million/annum. Of tbe 50 patients wbose vital status could be ascertained on tbe 31 January 1991, 41 (82%) were alive and resident in Nortbern Ireland, In addition, a furtber seven cases (all simplex) were discovered after tbe screening period for wbicb records are complete. A minimum estimate of tbe prevalence of all forms ofEB in Nortbern Ireland is 32/million. Tbe approximate prevalence of bereditary EB subtypes is EBS 28, JEB 0-7 and DEB 3/million. Tbese figures are undoubtedly an underestimate as not all recorded cases were identified, and many cases witb mild involvement go unreported.
Discussion Several studies of tbe epidemiology of EB bave been carried out. In Norway, Gedde-Dabl* estimated tbe minimum prevalence of all congenital types of EBS to be 24/million of population—EBS-K 1-1, EBS-WC 9 and EBS-Ogna 14-2/million of population. Tbe prevalence of dominant DEB was 1-4 and recessive DEB 6-6/million. In Finland, Kero'' identified cases ofEB diagnosed over a period of 10 years. At tbe time of bis study patients still alive included a total of 74 witb EBS, one junctional EB, 41 dominant DEB, two recessive DEB and one EB
acquisita. Kero concluded tbat tbe most significant difference compared witb tbe Norwegian data was tbe mucb lower frequency of recessive dystropbic EB, GeddeDabl did not use ultrastructural criteria, bence junctional and dystropbic forms were classified in tbe same group. In tbe Oxford area of England, Davison^ estimated tbe minimal frequency of all types of dominant EB togetber as 1/50,000 and for tbe recessive forms as 1/ 300,000. Winsbip' estimated tbe prevalence of EB in Soutb Africa to be 1 in 354,195, Inaba et a/,"' estimated tbe prevalence ofEB subtypes in Japan to be EBS 2-9-4, JEB 0-15-0-2, dominant DEB 1-1-1-5 and recessive DEB 1-5-2-1/million of population. Pavicic et aV^ retrospectively analysed 27 years of records in Croatia. Fifty-eigbt patients witb EB were discovered, 35 of wbom were believed to bave severe generalized DEB of tbe Hailopeau-Siemens variety. Seven patients were defined as baving JEB, two dominant DEB, and only two EBS. Tbe prevalence of EB in Croatia is estimated to be 0-956/ 100,000. Tbe prevalence of all types ofEB in Nortbern Ireland is comparable witb tbe disease prevalence in Norway. EBS and dominant DEB are more prevalent in Nortbern Ireland, but recessive DEB is less common. It is interesting to note tbe low prevalence of EB in Japan and Croatia, particularly tbe simplex form. Recessive DEB in Croatia appears to bave a bigb incidence, and EBS to occur only rarely. Epidemiological studies of EB are important, as patients can be located and tbeir disease type classified accurately. Tbis not only yields important statistical information, but can also serve as a data bank for continuing researcb into tbe patbogenesis of tbis beterogeneous group of disorders.
Acknowledgments We tbank Dr C.Patterson for statistical advice, Mrs J.Smitb-Davidson and Miss E.King for assistance witb tracing patients.
References 1 Gedde-Dahl T Jr. Classiflcation of epidermolysis bullosa. In: Padiatrische Dermatologie (Herzberg, JJ, ed). Stuttgart: F.K. Schattauer Verlag, 1978: 65. 2 Haber RM, Hanna W, Ramsay CA, Boxall LB. Hereditary epidermolysis bullosa. ; Am Acad Dermatol 1985: 13: 252-78. 3 Gedde-Dahl T Jr. Sixteen types of epidermolysis bullosa. On the clinical discrimination, therapy and prenatal diagnosis. Acta Derm Venereol (Stockh) 1981: 95 (SuppI.): 74-87. 4 Gedde-Dahl T Jr, Anton-Lamprecht I. In: Principles and Practice of
EB IN NORTHERN IRELAND
5
6
7 8 9
10
11
Medical Genetics (Emery AEH, Rimoin EL, eds). Vol. 1. New York: Churchill Uvingstone, 1983: 672-87. Medenica-Moisilovic L, Fenske NA, Espinoza CG. Epidermolysis bullosa acquisita. Direct immunofluorescence and ultrastructural studies. Am J Dermatopathol 1987: 9: 324-33. Gedde-Dahl T Jr. Epidermotysis Bullosa. A Clinical. Genetic and Epidemiological Study. Oslo, Bergen-Tromso: Universitetsforiaget 1970. Baltimore: Johns Hopkins Press, 1971. Kero M. Occurrence ofepidermolysis bullosa in Finland. Acta Derm Venereol (Stockh) 1984: 64: 57-62. Davison BC. Epidermolysis bullosa./Med Genet 1965: 2: 233-42. Winship I. Epidermolysis bullosa in South Africa. In: Epidermolysis Bullosa: A Comprehensive Review of Classification. Management and Laboratory Studies (Priestley GC, Tidman MJ, Weiss JB, Eady RAJ, eds). Crowthorne, Berkshire: DEBRA, 1990: 134-6. Inaba Y, Kitamura K, Ogawa H et al. A study on the prevalence of epidermolysis bullosa in Japan. Nippon Hifuka Gakkai Zasshi 1989: 99: 1021-6. Pavicic Z, Kmet-Vizintin P, Kansky A, Dobric I. Occurrence of
12 13
14
15
16 17
321
hereditary bullous epidermolyses in Croatia. Pediatr Dermatol 1990: 7: 108-10. Pearson RW. Studies on the pathogenesis ofepidermolysis bullosa. / Invest Dermatol 1962: 39: 551-75. Hintner H, Stingl G, Schuler G et al. Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in mechanobullous diseases. / Invest Dermatol 1981: 76: 113-18. Kero M, Peltonen L, Foidart JM, Savolainen ER. Immunohistological localization of three basement membrane components in various forms ofepidermolysis bullosa. / Cutan Pathology 1982: 9: 316-28. Medenica-Mojsilovic L, Fenske NA, Espinoza CG. Epidermolysis bullosa herpetiformis with mottled pigmentation and an unusual punctate keratoderma. Arch Dermatol 1986: 122: 900-8. Bart Bj. Epidermolysis bullosa and congenital localized absence of skin. Arch Dermatol 1970: 101: 78-81. Fin,e JD, Bauer EA, Briggaman RA et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. / Am Acad Dermatol 1991: 24: 119-35.
Epidermolysis bullosa in Northern Ireland K.E.McKENNA, M.Y.WALSH* AND E.A.BINGHAM Departments of Dermatology and *Pathology. Royal Victoria Hospital. Belfast. Northern Ireland Accepted for publication 1 June 1992
Summary
Cases of epidermolysis bullosa (EB) diagnosed in Northern Ireland during a 23-year period (1962-84) were identified from dermatology clinic files, paediatric hospital notes and cases known by general practitioners, A total of 48 confirmed new cases ofEB were diagnosed during the screening period. This involved 31 families, with identification of 36 further cases. The distribution of incident EB subtypes was: simplex 31 (65%), junctional 1 (2%). dystrophic 12 (25%) and acquisita 4 (8%). The incidence rate of new cases of EB diagnosed per year is 1-4/million and prevalence of all forms estimated at 32/miIlion. The prevalence of simplex, junctional and dystrophic forms is 28, 0-7 and 3/miUion, respectively.
Epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders characterized by marked skin fragility, blister formation, and in some cases by significant scarring. There are three major types of hereditary EB— simplex, junctional and dystrophic. Each type has certain characteristic clinical features and a specific site of cleavage within or adjacent to the epidermal basement membrane,^"* In addition, there is an acquired type of EB with characteristic immune deposition in the sublamina densa zone.^ Few studies have been performed regarding the epidemiology of EB.*"^^ We have performed an epidemiological study of the incidence and distribution of types and subtypes ofEB occurring in Northern Ireland during a 2 3-year period.
Methods Patients
Cases of EB diagnosed in Northern Ireland (NI) during the period 1962-84 inclusive were identified from dermatology clinic notes. This time interval was selected because records were complete for all clinics during this period. This included four Belfast hospital-based clinics, including the Royal Belfast Hospital for Sick Children, and 18 other clinics distributed throughout NI. Cases recorded in paediatric hospital notes were also noted. Patients were contacted to attend for review. In addition, general practitioners were contacted to assist in tracking cases. Correspondence: Dr K.E.McKenna, Department of Dermatology, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland.
318
Classification of EB cases
Diagnostic criteria for EB were similar to those used by Gedde-Dahl,^ supplemented by electron microscopy and immunofluorescence antigen mapping 'i* to determine the level of blister formation. The skin was examined for blister distribution, scarring, milia, pigmentary abnormalities, acral hyperkeratosis and cutaneous neoplasia. Involvement of mucous membranes, nails, teeth, eyes and hair was recorded. A family pedigree of each affected family was constructed. Further affected members or secondary cases were identified and interviewed if possible. Skin biopsy
The clinical diagnosis was confirmed when possible by skin biopsy. Two 4-mm punch biopsies were taken from recent blisters, or rubbed skin, using local anaesthesia with 1% Iignocaine. The samples were examined by EM and IAM. Antibodies used included those against bullous pemphigoid antigen, laminin, type IV and type VII collagen.
Results A total of 72 new cases of EB were recorded during the screening period. Of these, 10 were not EB, and in 14 the notes had either been destroyed or lost. The remaining 48 cases had EB, and from these index cases or probands a further 36 secondary cases were identified from pedigree studies. This involved 32 families with one or more affected members.
EB IN NORTHERN IRELAND
Table 1. Distribution of EB simplex subtypes. Skin biopsies examined by electron microscopy (EM) and immunofluorescence antigen mapping (IAM)
Koebner Weber-Cockayne Dowling-Meara Mottled pigmentation Ogna Bart
Simplex types EB simplex (EBS) was diagnosed in 31 probands (Table 1), The most common variety was Weber-Cockayne (EBS-WC), witb blistering affecting tbe palms and soles. Tbis occurred in 26 patients, and a furtber 3 5 secondary cases were identified. The majority of EBS-WC cases occurred in two large families with 14 and 11 living affected members, respectively. Three patients had the Koebner form (EBS-K) in which disseminated blistering occurs. One also had dystrophic nails. Two cases of the Dowling-Meara form (EBS-DM) were recorded. Clinical features of EBS-DM included generalized blistering at birth witb erosions and crusting. Blistering showed grouping and was non-scarring. Palmoplantar keratoderma developed in later life. Electron microscopic findings included basal cell cytolysis and clumping of tonofilaments. One patient is still resident in NI, the other lives abroad, and his son is affected. No cases with mottled pigmentation, and no Bart or Ogna forms of EBS were discovered.^'-^^ A total of 30 affected individuals were examined and skin biopsy was performed in six patients. Junctional types Six main types of junctional EB (JEB) are recognized, and include the gravis, mitis, cicatricial, inversa, minimus and progressiva variants,^'^ During our screening period Table 2, Distribution of dystrophic EB cases. Skin biopsies examined by electron microscopy (EM) and immunofluorescence antigen mapping (IAM)
Recessive Hailopeau-Siemens Inversa Localized Dominant Cockayne-Touraine Pasini Pretibial
Probands
Secondary cases
Families
3 26 2 — — —
0 34 1 — — —
3 17 2 — — —
319
EM/IAM
4 2
one case of JEB of the inversa type was diagnosed in a male patient, who is still alive. The patient had a history of axillary and groin blistering since birth. Corneal involvement and nail dystropby were also present.
Dystrophic types A total of 12 dystrophic EB (DEB) index cases were identified (Table 2). These were represented by six dominant and six recessive cases. The four cases of Hailopeau-Siemens recessive DEB were related, and had died following the development of squamous carcinoma of the skin. Two other unaffected sibs had ichthyosis vulgaris. Interestingly, Gedde Dabl* reported tbree unaffected members in the family of a case of lethal DEB who had ichthyosis vulgaris. The two cases with localized recessive disease were brotber and sister. Blistering mainly affected the limbs, and nails were dystrophic. Both patients complained of dysphagia, and upper oesophageal webs were demonstrated. Patients with autosomal dominant Cockayne-Touraine DEB* had blistering, and atrophic scarring with milia, occurring mainly over knees, elbows, fingers and toes. Nail dystrophy was present in three patients. Three of these cases were not traced and a secondary case had died of an unrelated illness. There was one case of Pasini DEB. with atrophy and scarring affecting mainly the limbs, with occasional truncal lesions. In addition, lumbar
Probands
Secondary cases
Families
4
0
1
2
0
1
1
5 1
1 0
4 1
2 1
EM/IAM
320
K.E.McKENNA et al.
albopapuloid lesions were present. No cases of inversa or pretibial DEB were recorded. A total of five cases of DEB were traced, and are resident in Nortbern Ireland. Four of tbese patients bad skin biopsies performed. Acquisita
Four patients witb EB acquisita were diagnosed during tbe screening period. Unfortunately tbree of tbese patients are now dead, and tbe fourtb cannot be traced. Tbese patients were cbaracterized by late onset of mainly acral blistering witb milia formation. Tbere was a negative family bistory of EB. Tbe patients were not taking any systemic medications, Porpbyria bad been excluded by appropriate biocbemical tests. Unfortunately tbese patients were diagnosed at a time wben electron microscopy was not available in tbe province. Incidence and prevalence
Tbe incidence of newly diagnosed cases of EB occurring in Nortbern Ireland was calculated for tbe 2 3-year screening period. Tbe population of Nortbern Ireland is approximately 1 • 5 million, Tbe incidence rate of new cases of all types of EB is 1-4/million/annum. Tbe incidence rate for EBS is 0-9, JEB 0-03 and DEB 0-3/ million/annum. Of tbe 50 patients wbose vital status could be ascertained on tbe 31 January 1991, 41 (82%) were alive and resident in Nortbern Ireland, In addition, a furtber seven cases (all simplex) were discovered after tbe screening period for wbicb records are complete. A minimum estimate of tbe prevalence of all forms ofEB in Nortbern Ireland is 32/million. Tbe approximate prevalence of bereditary EB subtypes is EBS 28, JEB 0-7 and DEB 3/million. Tbese figures are undoubtedly an underestimate as not all recorded cases were identified, and many cases witb mild involvement go unreported.
Discussion Several studies of tbe epidemiology of EB bave been carried out. In Norway, Gedde-Dabl* estimated tbe minimum prevalence of all congenital types of EBS to be 24/million of population—EBS-K 1-1, EBS-WC 9 and EBS-Ogna 14-2/million of population. Tbe prevalence of dominant DEB was 1-4 and recessive DEB 6-6/million. In Finland, Kero'' identified cases ofEB diagnosed over a period of 10 years. At tbe time of bis study patients still alive included a total of 74 witb EBS, one junctional EB, 41 dominant DEB, two recessive DEB and one EB
acquisita. Kero concluded tbat tbe most significant difference compared witb tbe Norwegian data was tbe mucb lower frequency of recessive dystropbic EB, GeddeDabl did not use ultrastructural criteria, bence junctional and dystropbic forms were classified in tbe same group. In tbe Oxford area of England, Davison^ estimated tbe minimal frequency of all types of dominant EB togetber as 1/50,000 and for tbe recessive forms as 1/ 300,000. Winsbip' estimated tbe prevalence of EB in Soutb Africa to be 1 in 354,195, Inaba et a/,"' estimated tbe prevalence ofEB subtypes in Japan to be EBS 2-9-4, JEB 0-15-0-2, dominant DEB 1-1-1-5 and recessive DEB 1-5-2-1/million of population. Pavicic et aV^ retrospectively analysed 27 years of records in Croatia. Fifty-eigbt patients witb EB were discovered, 35 of wbom were believed to bave severe generalized DEB of tbe Hailopeau-Siemens variety. Seven patients were defined as baving JEB, two dominant DEB, and only two EBS. Tbe prevalence of EB in Croatia is estimated to be 0-956/ 100,000. Tbe prevalence of all types ofEB in Nortbern Ireland is comparable witb tbe disease prevalence in Norway. EBS and dominant DEB are more prevalent in Nortbern Ireland, but recessive DEB is less common. It is interesting to note tbe low prevalence of EB in Japan and Croatia, particularly tbe simplex form. Recessive DEB in Croatia appears to bave a bigb incidence, and EBS to occur only rarely. Epidemiological studies of EB are important, as patients can be located and tbeir disease type classified accurately. Tbis not only yields important statistical information, but can also serve as a data bank for continuing researcb into tbe patbogenesis of tbis beterogeneous group of disorders.
Acknowledgments We tbank Dr C.Patterson for statistical advice, Mrs J.Smitb-Davidson and Miss E.King for assistance witb tracing patients.
References 1 Gedde-Dahl T Jr. Classiflcation of epidermolysis bullosa. In: Padiatrische Dermatologie (Herzberg, JJ, ed). Stuttgart: F.K. Schattauer Verlag, 1978: 65. 2 Haber RM, Hanna W, Ramsay CA, Boxall LB. Hereditary epidermolysis bullosa. ; Am Acad Dermatol 1985: 13: 252-78. 3 Gedde-Dahl T Jr. Sixteen types of epidermolysis bullosa. On the clinical discrimination, therapy and prenatal diagnosis. Acta Derm Venereol (Stockh) 1981: 95 (SuppI.): 74-87. 4 Gedde-Dahl T Jr, Anton-Lamprecht I. In: Principles and Practice of
EB IN NORTHERN IRELAND
5
6
7 8 9
10
11
Medical Genetics (Emery AEH, Rimoin EL, eds). Vol. 1. New York: Churchill Uvingstone, 1983: 672-87. Medenica-Moisilovic L, Fenske NA, Espinoza CG. Epidermolysis bullosa acquisita. Direct immunofluorescence and ultrastructural studies. Am J Dermatopathol 1987: 9: 324-33. Gedde-Dahl T Jr. Epidermotysis Bullosa. A Clinical. Genetic and Epidemiological Study. Oslo, Bergen-Tromso: Universitetsforiaget 1970. Baltimore: Johns Hopkins Press, 1971. Kero M. Occurrence ofepidermolysis bullosa in Finland. Acta Derm Venereol (Stockh) 1984: 64: 57-62. Davison BC. Epidermolysis bullosa./Med Genet 1965: 2: 233-42. Winship I. Epidermolysis bullosa in South Africa. In: Epidermolysis Bullosa: A Comprehensive Review of Classification. Management and Laboratory Studies (Priestley GC, Tidman MJ, Weiss JB, Eady RAJ, eds). Crowthorne, Berkshire: DEBRA, 1990: 134-6. Inaba Y, Kitamura K, Ogawa H et al. A study on the prevalence of epidermolysis bullosa in Japan. Nippon Hifuka Gakkai Zasshi 1989: 99: 1021-6. Pavicic Z, Kmet-Vizintin P, Kansky A, Dobric I. Occurrence of
12 13
14
15
16 17
321
hereditary bullous epidermolyses in Croatia. Pediatr Dermatol 1990: 7: 108-10. Pearson RW. Studies on the pathogenesis ofepidermolysis bullosa. / Invest Dermatol 1962: 39: 551-75. Hintner H, Stingl G, Schuler G et al. Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in mechanobullous diseases. / Invest Dermatol 1981: 76: 113-18. Kero M, Peltonen L, Foidart JM, Savolainen ER. Immunohistological localization of three basement membrane components in various forms ofepidermolysis bullosa. / Cutan Pathology 1982: 9: 316-28. Medenica-Mojsilovic L, Fenske NA, Espinoza CG. Epidermolysis bullosa herpetiformis with mottled pigmentation and an unusual punctate keratoderma. Arch Dermatol 1986: 122: 900-8. Bart Bj. Epidermolysis bullosa and congenital localized absence of skin. Arch Dermatol 1970: 101: 78-81. Fin,e JD, Bauer EA, Briggaman RA et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. / Am Acad Dermatol 1991: 24: 119-35.
