The clinical efficacy and safety of anti-IgE therapy in recessive dystrophic epidermolysis bullosa.

The treatment of recessive dystrophic epidermolysis bullosa (RDEB) remains challenging. Elevated IgE levels have previously been reported in several RDEB patients. In this prospective, single-centre, open intervention study, elevated IgE levels were seen in 11 out of 12 patients with intense pruritus, and the patients with elevated IgE levels received anti-IgE therapy every 4 weeks for at least three cycles. Compared with the baseline, 10 patients with RDEB had good clinical outcomes with enhanced wound healing, a reduction in Birmingham (epidermolysis bullosa) EB severity score by 15%, a reduction in affected body surface area by 23.3%, amelioration of skin inflammation, and an increase in type VII collagen deposition by 13.1-fold. All the patients had a good tolerance to anti-IgE therapy. Furthermore, patients with higher IgE levels tended to have higher disease severity and more favorable clinical outcomes. Our report also suggested the potential role of IgE in the pathogenesis of inflammatory conditions associated with RDEB. (ChiCTR1900021437).

Leg amputation and dystrophic epidermolysis bullosa: A case report with 15 years of follow-up.

OBJECTIVE: Dystrophic epidermolysis bullosa is a rare disease characterized by widespread blistering of the skin and mucous membranes, which may ultimately prompt limb amputation. In this context, the outcome of fitting a prosthesis to a chronically wounded stump is not well known. Our patient's experience (with 15 years of follow-up) should contribute to better knowledge of this topic. CASE REPORT: A 37-year-old man presented with severe dystrophic epidermolysis bullosa. Recurrent skin carcinoma had led to an amputation below the knee. Despite incessant development of blisters on the stump and the need for wound dressing and padding, the patient has been able to walk freely with a prosthesis and a cane. A large number of skin sarcomas were excised over the 15-year period of prosthesis use. Two falls have resulted in limb fractures. A new sarcoma on the stump marked the end of the use of the prosthesis. DISCUSSION: Despite the constant presence of wounds on the stump, amputees with dystrophic epidermolysis bullosa can successfully be fitted with a prosthesis.

Recessive dystrophic epidermolysis bullosa caused by COL7A1 hemizygosity and a missense mutation with complex effects on splicing.

Loss-of-function mutations in the gene encoding type VII collagen, COL7A1, are the molecular basis of the blistering skin disorder, recessive dystrophic epidermolysis bullosa (RDEB). COL7A1 maps to a region of the short arm of chromosome 3 that has been found to be deleted in many types of malignancies. We have characterized the first case of a large genomic deletion in chromosome 3p21.31 that removes COL7A1 entirely in an RDEB patient. This interstitial deletion spans 255 to 520 kb and encompasses 9 to 15 genes, but seems to have no pathological consequences other than RDEB. We show that the second, hemizygous allele of COL7A1 in this patient bears a base substitution within exon 94, c.7245G>A. This translates into an amino acid substitution, p.M2415I, and leads to a complex splicing abnormality that allows marginal levels of functional mRNA and protein to be synthesized. We propose that the leakiness of the splicing defect enables the partial rescue of collagen VII deficiency. This is consistent with the diagnosis of the moderately severe form of RDEB in the proband, at variance with the most severe form, RDEB Hallopeau-Siemens, that would arise from complete collagen VII deficiency.

Epidermólisis bulosa distrófica recesiva: caso clínico / Recessive dystrophic epidermolysis bullosa: report of one case

We report a female newborn with a dystrophic epidermolysis bullosa. The diagnosis was made by electron microscopy of a bullous skin lesion. The importance of reaching a specific diagnosis is underscored. Close relatives can therefore be informed and educated about prognosis, etiology and the possibility of having new affected offspring. An accurate diagnosis can be reached through electronic microscopy or modern immunohistochemical techniques. Further complementary information given by conventional histology is required. A complete study is recommended to minimize errors in the intepretation of morphology (Rev MÚd Chile 2004; 132: 614-8).

Epidermolysis bullosa pruriginosa.

Epidermolysis bullosa (EB) pruriginosa is a rare clinical subset of dystrophic EB, characterized by marked itching and presence of prurigo-like or lichenoid features. In order to further delineate the phenotype and understand the pathogenesis of this disorder, the clinical, histological and ultrastructural findings of a 19-year-old patient presenting a typical form of EB pruriginosa are described. The prevalence of papular itchy lichenoid lesions, signs of scratching and paucity of blisters at the time of clinical examination may result in incorrect diagnosis and treatment. Microscopic studies of the lesions show the typical findings of dystrophic EB associated with an unusually high density of collagen bundles and absence of elastic fibres in the upper dermis. Itching lichenoid lesions of EB pruriginosa could represent an abnormal dermal reactivity of some patients to their inherited bullous disorder.

Constitutive activation of the collagenase promoter in recessive dystrophic epidermolysis bullosa fibroblasts: role of endogenously activated AP-1.

Recessive dystrophic epidermolysis bullosa (RDEB) is a mutilating disease of the skin characterized by recurrent blistering and erosions that result from compromised integrity of the basement membrane zone. In this study, fibroblasts derived from the skin of RDEB patients were characterized for expression of the major metalloproteinases, particularly interstitial collagenase. Consistent with previous reports on increased collagenase protein levels in fibroblasts from some RDEB patients, we found that steady-state levels of collagenase mRNA were significantly increased in fibroblast strains derived from three of five RDEB patients compared to fibroblasts obtained from normal donors. Stromelysin mRNA was elevated in the same three fibroblast strains, whereas expression of neither the 72- nor the 92-kDa type IV collagenases was different from that of controls. Tissue inhibitor of metalloproteinases was expressed in RDEB fibroblasts at levels similar to those observed in normal fibroblasts. To investigate the mechanism behind the steady-state elevation in collagenase and stromelysin expression, AP-1 expression and activation were studied. Although levels of Jun expression were not different from those seen in normal fibroblasts, AP-1 activity, as assessed by ability to bind to a TPA response element-containing oligonucleotide, was endogenously elevated in RDEB fibroblasts compared to normal fibroblasts. Transfection studies using a plasmid construct containing the collagenase promoter linked to a CAT reporter gene demonstrated that RDEB fibroblasts were able to support active transcription of the promoter compared to normal fibroblasts. These studies support the hypothesis that RDEB fibroblasts contain chronically activated AP-1, and perhaps other transactivating factors, that contribute to the cellular phenotype of collagenase and stromelysin overexpression.