Albopapuloid Lesions Research Articles

Epidermolysis bullosa pruriginosa: A report of two cases

Epidermolysis bullosa (EB) pruriginosa is a very rare pattern of dystrophic EB caused by type VII collagen gene mutation, with distinctive clinico-pathological features. It is characterized by nodular prurigo-like lichenified lesions, nail dystrophy, and variable presence of albopapuloid lesions. We report two such cases.

Pretibial epidermolysis bullosa: is this case a new subtype with loss of types IV and VII collagen?

Pretibial epidermolysis bullosa (PEB) is an extremely rare subtype of dominant dystrophic epidermolysis bullosa (DDEB), in which recurrent blistering with scarring predominantly involves the pretibial skin. Nail dystrophy, albopapuloid lesions, and hypertrophic scars may also occur. In PEB, immunohistochemical and electron microscopic studies demonstrate the complete or partial loss of the anchoring fibril (AF) in the basement membrane zone, suggesting disturbed synthesis or excessive degradation of collagen VII, the main component of AF. Interestingly, we report a case of PEB with unusual results of joint loss of types IV and VII collagen.

Epidermolysis bullosa pruriginosa - Report of three cases

Epidermolysis bullosa pruriginosa, a genetic mechanobullous disease, is characterized by pruritus, lichenified or nodular prurigo-like lesions, occasional trauma-induced blistering, excoriations, milia, nail dystrophy and albopapuloid lesions, appearing at birth or later. Scarring and prurigo are most prominent on the shins. Treatment is unsatisfactory. We report three such cases: two of them first cousins, are described with history of blisters since childhood, followed by intensely pruritic lesions predominantly on the shins, and dystrophy of toenails, but no albopapuloid lesions or milia. Intact blisters were present in one case, and excoriations were seen in the other two. All of them showed encouraging response to cryotherapy.

The clinical spectrum of dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is a genodermatosis resulting from mutations in COL7A1, the gene encoding type VII collagen. The site and specific nature of the underlying mutation determine the clinical phenotype, which ranges widely from a severe mutilating condition to a relatively mild disorder. To document the clinical spectrum of DEB within a defined complete population. Since 1992, when compilation of the U.K. epidermolysis bullosa register began, an exhaustive search for DEB sufferers within the Scottish population has been undertaken and their clinical features comprehensively recorded. One hundred and twenty-eight DEB sufferers have been identified within the Scottish population. In descending order, the frequencies of the different forms of DEB were dominant DEB (DDEB) in 88 individuals (68%), DEB of uncertain inheritance in 24 (19%) and recessive DEB (RDEB) in 16 patients (13%). Within this latter group, nine (7%) had the mutilating Hallopeau-Siemens subtype (RDEB-HS), five (4%) had localized (RDEB-loc) and two (2%) had a predominantly flexural (inverse) form of RDEB. During the study, two patients with RDEB died from squamous cell carcinomas (SCCs), one originating in the skin and the second arising in the oesophagus. Gastrointestinal problems such as dysphagia, constipation and anal fissures, and restriction of mouth opening were experienced by the majority of patients with RDEB and by a significant minority of DDEB sufferers. Pseudosyndactyly was most severe in RDEB-HS, all those over 9 years of age having mitten deformities of the hands. Milder pseudosyndactyly or flexion contractures of the fingers were present in younger patients with this subtype, in most adults suffering from other subtypes of RDEB and in 6% of those with DDEB. External ear involvement, a feature not often reported in DEB, was common in RDEB and also occurred in a minority of those with DDEB. Pruriginous lesions and albopapuloid lesions were each present in both DDEB and RDEB. Most patients with DEB have relatively mild dominantly inherited disease, only a minority suffering from severe recessive subtypes. Scarring, gastrointestinal involvement, albopapuloid lesions and a pruriginosa-like pattern each occur in both DDEB and RDEB. With increasing age, SCC is a major cause of morbidity and mortality.

Dominant Dystrophic Epidermolysis Bullosa (Pasini) Caused by a Novel Glycine Substitution Mutation in the Type VII Collagen Gene (COL7A1)

A 12 y old girl with the albopapuloid variant (Pasini) of dominant dystrophic epidermolysis bullosa is studied. The albopapuloid lesions developed within the first year of life, contained milia and were associated with pruritus. Mutation detection of the COL7A1 gene revealed a G-->A transition at nucleotide position 6110 in the mutant allele converting a glycine to glutamic acid (G2037E). This report adds to the expanding database on COL7A1 mutations in dystrophic epidermolysis bullosa.

Novel Glycine Substitution Mutations in COL7A1 Reveal that the Pasini and Cockayne–Touraine Variants of Dominant Dystrophic Epidermolysis Bullosa Are Allelic

Mutations in the type VII collagen gene (COL7A1) have been shown to underlie dystrophic epidermolysis bullosa (DEB). The dominantly inherited forms of DEB have been divided into two clinical subcategories, the Pasini (DDEB-P) and the Cockayne-Touraine (DDEB-CT) variants, on the basis of the presence or absence of albopapuloid lesions. In this study, we have examined the molecular basis of DDEB in two Japanese families, one with DDEB-P and the other with DDEB-CT. Mutation detection strategy consisted of polymerase chain reaction amplification of COL7A1 from genomic DNA, followed by heteroduplex analysis and direct nucleotide sequencing. The results revealed heterozygous glycine substitution mutations, G2076D and G2034R, in these families, respectively. Thus, these two variants of DDEB are allelic, and subtle differences in the clinical presentation may reflect the precise position of the mutation along the type VII collagen molecule. Alternatively, the nature of the substituting amino acid (D versus R) may influence the clinical phenotype. This is the first demonstration of a COL7A1 mutation in DDEB-P, and brings the total number of dominant DEB variants with underlying glycine substitutions in COL7A1 to five, including the pretibial and localized variants as well as the Bart's syndrome, in addition to DDEB-P and DDEB-CT.

Bart's syndrome. Ultrastructure and genetic linkage.

Bart's syndrome, originally described in a large family in 1966, consists of congenital localized absence of skin, blistering, and associated nail abnormalities. Since then, several descriptions of patients with similar clinical findings have suggested that this syndrome may represent any of the three subtypes of epidermolysis bullosa: epidermal, junctional, or dermal. Because no histologic or ultrastructural studies were done in Bart's kindred, and neither immunohistologic nor genetic linkage technology was available at that time, classification of the syndrome has been unclear. We report the findings of clinical, ultrastructural, immunohistologic, and genetic linkage studies of the original kindred and their descendants. We contacted original family members and their descendants by telephone and questionnaire. Skin biopsy specimens adjacent to blisters were obtained for ultrastructural and immunochemical analysis. Blood samples were drawn from affected members and their spouses and children for genetic linkage studies. The clinical findings seen in the descendants of the original family with Bart's syndrome were similar to those described in 1966. We did, however, detect persistence of blistering into adult life and mild atrophic scarring and milia formation at sites of blistering in some family members, a finding not noted in the original study. Hypertrophic scarring and albopapuloid lesions were not detected. Ultrastructural analysis of skin from affected family members showed poorly formed anchoring fibrils and cleavage below the lamina densa. Immunohistochemical staining localized type IV collagen at the roof of blistered skin. Staining for type VII collagen was found to have a normal distribution in nonblistered skin. Genetic linkage studies mapped the gene for the disease in this family to chromosome 3p at or near the site of the gene encoding type VII collagen. Bart's syndrome is a subtype of dominantly inherited dystrophic epidermolysis bullosa.

Proteoglycans in Albo-Papuloid Lesions of the Pasini Form of Dominant Dystrophic Epidermolysis Bullosa.

Epidermolysis bullosa is a group of inherited blistering diseases classified into three main sub-groups on the basis of the level of cleavage within the skin. In dominant dystrophic epidermolysis bullosa, characterized by cleavage below the basal lamina, two variants can be distinguished by the presence (Pasini form) or absence (Cockayne-Touraine form) of albo-papuloid lesions. The present study was undertaken to investigate the glycosaminoglycan chains of proteoglycans in the albo-papuloid lesions of a patient with the Pasini form, using histochemical and immunohistochemical methods. Histological examination revealed no dermo-epidermal separation. In the dermis, the papillary and subpapillary layers were slightly homogeneous, and exhibited a strong affinity towards alcian blue, which was abolished by treatment with chondroitinase ABC or in the presence of MgCl2 0.3M, but was resistant to digestion with streptomyces hyaluronidase. The papillary and subpapillary layers were intensely stained with a monoclonal antibody against small size proteoglycan with dermatan sulfate. These results suggest the presence of degraded dermatan sulfate proteoglycan in the papillary and subpapillary dermis of albo-papuloid lesions in the Pasini form of dystrophic epidermolysis bullosa.

Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features

Summary We report a study of eight unrelated adult patients with a highly distinctive phenotype of dystrophic epidermolysis bullosa. It is characterized clinically by pruritus, lichenified or nodular prurigo-like lesions, violaceous linear scarring, occasional trauma-induced blistering, excoriations, milia, Nail dystrophy and, in some cases, albopapuloid lesions on the trunk, The scarring is most evident on the limbs, particularly on the shins, with relative sparing elsewhere. Intact blisters are rarely seen. Physical signs were present at birth in three patients, but in the others skin manifestations were first noticed between 6 months and 10 years of age. Five cases are sporadic, but three of the eight patients have a history of familial involvement, with autosomal dominant inheritance in two cases and recessive transmission in the other case. Studies of the dermal-epidermal junction showed alterations in the number and ultrastructure of anchoring fibrils in lesional, perilesional and non-lesional skin, consistent with a diagnosis of dominant or localized recessive dystrophic epidermolysis bullosa. These patients represent an unusual, poorly recognized form or expression of dystrophic epidermolysis bullosa which has features in common with a variety of acquired inflammatory dermatoses.

Glycosaminoglycans Production by Cultured Skin Fibroblasts from the Pasini and Cockayne-Touraine Forms of Dominant Dystrophic Epidermolysis Bullosa

Qualitative and quantitative comparisons of glycosaminoglycans e (GAG) production were made on fibroblast lines cultured from the skin of six patients with the Pasini (albopapuloid) form of dominant dystrophic epidermolysis bullosa, six with the non-albopapuloid form (Cockayne-Touraine), eight lines from patients with simplex or recessive dystrophic epidermolysis bullosa and eight lines from normal individuals. A reasonable match of donor age and gender, site, and passage number was achieved. Contrary to an earlier report, the lines from the Pasini group were unexceptional in the amount of GAG they secreted and the proportions of sulfated and nonsulfated GAG showed no consistent difference from the Cockayne-Touraine or control lines. The Pasini lines secreted 77 +/- 18 (SEM) microgram GAG-uronic acid per 10(7) cells and the Cockayne-Touraine lines 81 +/- 12 micrograms at equivalent cells densities. Sulfated GAG represented averages of 19 +/- 4+ in Pasini lines, 17 +/- 5% in Cockayne-Touraine, and 14 +/- 3% in controls. These findings are consistent with current views of albopapuloid lesions as an unreliable clinical sign in epidermolysis bullosa and bring into question the validity of the Pasini entity.

Epidermolysis Bullosa Dystrophica et Albo-Papuloidea

A 26-year-old Japanese woman had epidermolysis bullosa dystrophica et albopapuloidea. The eruptions consisted of nodules, blisters on the extremities, and ivory-white, firm papules, about 5 mm in diameter, on the trunk. Like those of her father and paternal uncles, all of the patient's nails were dystrophic. Urinalysis revealed an increased excretion of degraded chondroitin sulfates. Histologic examination of biopsy specimens obtained from the nodules and blisters showed separation at the dermoepidermal junctional zone; in specimens from albo-papuloid lesions, the papillary and subpapillary layers were slightly homogeneous. Histochemical examination of these lesions revealed an increased amount of degraded chondroitin sulfates in the papillary and subpapillary layers. These results suggest some disturbance in catabolism of acid mucopolysaccharides in the lesions of epidermolysis bullosa dystrophica et albo-papuloidea.