Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: A global cross-sectional survey.

BACKGROUND: A spectrum of skin disease severity exists in patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVE: To characterize the patient-reported outcomes and quality of life (QOL) in patients with RDEB. METHODS: A cross-sectional study of patients with RDEB surveyed through the global EBCare Registry. Patient-reported outcomes included skin disease severity, wound characteristics, pain, itch, extracutaneous symptoms, and medications. QOL was measured by using the validated Quality of Life in Epidermolysis Bullosa instrument. RESULTS: A total of 85 patients with RDEB reported 1226 wounds (937 recurrent wounds and 289 chronic open wounds). Overall skin disease severity was self-reported as mild (26%; 22/83), moderate (48%; 40/83), or severe (25%; 21/83). Worsening skin disease severity was significantly associated with larger wounds, increased opiate use, anemia, gastrostomy tube use, infections, osteoporosis, and squamous cell carcinoma. Larger wound size was associated with worse quality of life scores. LIMITATIONS: All data were self-reported from an online epidermolysis bullosa patient registry. CONCLUSIONS: This study shows a significant correlation between larger wound size with worsening skin disease severity and quality of life in participants with RDEB. Worsening skin disease severity significantly correlated with key clinical manifestations. These results show that patients with RDEB are able to self-report their skin disease severity and wounds.

Restrictions in oral functions caused by oral manifestations of epidermolysis bullosa.

Several forms of epidermolysis bullosa (EB) present oral manifestations. Blistering of the (peri)oral mucosa affects the opening of the mouth, the mobility of the tongue and lips, thereby restricting oral functions. We describe the prevalence and characteristics of oral manifestations of EB in relation to loss of oral functions in a cross-sectional study of different types of EB patients using standardized measurement techniques. Twenty-two patients were included. The mobility of the mandible, lips and tongue was measured, the mandibular function impairment questionnaire (MFIQ) was filled out and additional questions regarding hindrance of EB during oral hygiene and intelligibility of speech (being understood) were asked in structured interviews. The median age was 11.8 yrs. Mobility of the mandible, tongue and lip was restricted, oral hygiene procedures were hindered in most patients. A data comparison was made between the recessive dystrophic EB (RDEB) and junctional EB (JEB) groups. Mandibular function was impaired in both groups but more severely in the RDEB-population. Intelligibility in both groups was almost unaffected. Restrictions in mobility of the mouth, tongue and lips are frequently present in EB patients. These are most severe in the RDEB group and support the clinical relevance of optimizing symptomatic treatment.

Epidermolysis bullosa in Australia and New Zealand.

This article describes the clinical services for EB in Australia and New Zealand. The history and epidemiology of EB in Australia is described. Current treatment and research achievements are described.

The clinical spectrum of dystrophic epidermolysis bullosa.

BACKGROUND: 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. OBJECTIVES: To document the clinical spectrum of DEB within a defined complete population. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Identification of two splicing mutations in the collagen type VII gene (COL7A1) of a patient affected by the localisata variant of recessive dystrophic epidermolysis bullosa.

Collagen type VII gene (COL7A1) has been demonstrated to be altered in several variants of dystrophic epidermolysis bullosa (DEB), with either recessive or dominant mode of inheritance. We have identified two mutations in a patient affected by a localisata variant of recessive DEB (L-RDEB), which is characterized by the less severe phenotype of the syndrome. These mutations are the first splicing mutations so far described for COL7A1 in DEB. One mutation is a paternally inherited A-->G transition at position -2 of the donor splicing site of intron 3, which results in three aberrant mRNAs, depending on the skipping of exon 3, the usage of a cryptic donor site inside exon 3, or the maintenance of intron 3. The second mutation is a maternally inherited G-->A transition at position -1 of the donor splicing site of intron 95, which induces the activation of a cryptic donor site 7 nt upstream the normal site and gives rise to a deleted mRNA, in addition to the normal one. All aberrant mRNAs show a shift of the reading frame, thus generating premature termination codons of translation. Allele-specific analysis of the transcripts has shown that the maternal mutation does not completely abolish the correct splicing of COLVII pre-mRNA, thus allowing, in the patient, the synthesis of a certain level of a functional protein. This result is compatible with the mild clinical L-RDEB phenotype observed in our patient.

Squamous cell carcinoma developing in epidermolysis bullosa dystrophica.

Two patients with epidermolysis bullosa dystrophica recessiva who had squamous cell carcinoma are presented. Case 1 is a 40-year-old woman who had ulcers on her left lower leg. Case 2 is a 42-year-old man who had a tumor on his left first toe. Wide surgical excision with skin coverage by autograft was performed in case 1. Amputation of the toe in case 2 was performed. A review of the cases of epidermolysis bullosa dystrophica associated with cancer reported in Japan is also presented.