Reliability and validity of the instrument for scoring clinical outcomes of research for epidermolysis bullosa (iscorEB).

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare and currently incurable genetic blistering disorders. As more pathogenic-driven therapies are being developed, there is an important need for EB-specific validated outcomes measures designed for use in clinical trials. OBJECTIVES: To test the reliability and construct validity of an instrument for scoring clinical outcomes of research for EB (iscorEB), a new combined clinician- and patient-reported outcomes tool. METHODS: We conducted an observational study consisting of independent 1-day assessments (six assessors) at two academic hospitals. The assessments consisted of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity (BEBS) and global severity assessment for physicians; and iscorEB patient (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's Dermatology Life Quality Index for patients. Construct validity and intraclass correlation coefficients (ICCs) for interobserver, intraobserver and test-retest reliability were calculated. RESULTS: Overall, 31 patients with a mean age of 19·5 years (1·8-45·2) were included. Disease severity was mild in 42% of cases, moderate in 29% and severe in 29%. The interobserver ICC was 0·96 for both the clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver reliability was 0·91 and 0·70 for the skin and mucosal domains of iscorEB-c, respectively. Cronbach's alpha for iscorEB-c was 0·89. The test-retest reliability of iscorEB-p was 0·97 and Cronbach's alpha was 0·84. The clinical score differentiated between subjects with mild, moderate and severe disease, and both clinical and patient subscores discriminated between recessive dystrophic EB and other EB subtypes. CONCLUSIONS: iscorEB has robust reliability and construct validity, including strong ability to distinguish EB types and severities. Further studies are planned to test its responsiveness to change.

Patterns of bone mineral acquisition in children with epidermolysis bullosa: a longitudinal study.

BACKGROUND: Reduced bone mass and fractures are known complications of generalized forms of epidermolysis bullosa (EB). However, the aetiology - inadequate bone acquisition, premature bone loss, or a combination - is unclear. OBJECTIVES: To determine patterns of bone mineral acquisition in children with EB and to identify clinical and laboratory correlates of change in areal bone mineral density (aBMD). METHODS: Seventeen subjects ≥ 6 years of age with generalized EB were studied at two visits at least 12 months apart with clinical and laboratory evaluations and dual energy X-ray absorptiometry scans of the lumbar spine. Wilcoxon signed-rank tests were used to determine if changes from baseline to follow-up were significant. Wilcoxon rank-sum tests were used to compare subjects with gains in aBMD Z-score with those who experienced no change or decreases to determine if baseline laboratory or clinical characteristics differed between the two groups. RESULTS: Subjects gained height and weight at follow-up, but there was no significant improvement in mean Z-scores for height, weight or body mass index. Laboratory values did not change significantly. Mean bone mineral content and aBMD of the lumbar spine increased significantly at follow-up, but mean aBMD Z-scores remained static. No differences in clinical characteristics or laboratory values were seen between subjects with increased aBMD Z-scores vs. those whose scores decreased or did not change. CONCLUSIONS: Low bone mass in children with generalized EB is due primarily to inadequate gains in aBMD. Interventions to improve overall health and to help build bone mass in this patient population are warranted.

Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart.

Desmoplakin is the major linker in desmosomes in epithelia and myocardium, anchoring intermediate filaments by the C-terminus to plakoglobin and plakophilin in the desmosomal plaque. Mutations in the gene DSP encoding desmoplakin have been associated with various phenotypes affecting skin and/or heart. One of these phenotypes, lethal acantholytic epidermolysis bullosa (LAEB), is characterized by extensive postnatal shedding of epidermis leading to early demise and is caused by recessive mutations in the gene DSP resulting in truncation of the desmoplakin C-terminus. Here we describe two infants born to the same consanguinous parents who suffered extensive epidermal dislodgment and died shortly after birth. In addition, universal alopecia, anonychia, malformed ears and cardiomyopathy were observed. As the clinical diagnosis was LAEB, DSP mutation analysis was performed. A homozygous deletion (c.2874del5) abrogating the donor splice site of exon 20 was found. The deletion is predicted to cause read-through in intron 20 with subsequent recognition of a premature termination codon, resulting in desmoplakin lacking its rod domain and C-terminus (p.Lys959MetfsX5). Electron microscopic analysis of skin biopsies showed absence of the desmosomal inner dense plaque and lack of tonofilament insertion. This is the second report of LAEB. These findings suggest DSP mutations as the aetiology of LAEB and cardiomyopathy as part of the phenotype. Furthermore, they indicate that in addition to the desmoplakin C-terminus, the rod domain is dispensable for intrauterine development but is essential for the inner dense plaque of desmosomes.

Treatment decision-making for patients with the Herlitz subtype of junctional epidermolysis bullosa.

The Herlitz subtype of junctional epidermolysis bullosa (JEB-H) is a lethal genetic disorder characterized by recurrent and persistent erosions of the epithelial surfaces that heal with exuberant granulation tissue. In addition, respiratory distress, refractory anemia and failure to thrive are often seen. Mortality in the first year of life approaches 90%. JEB-H is caused by mutations in the genes that encode the protein laminin 5, a structural molecule involved in the adhesion of epidermis to dermis. There is currently no cure for JEB-H. Medical interventions treat complications but do not ultimately limit mortality. Ethical principles contend that offering comfort and company to the patient and family, not aggressive therapies, should comprise the mainstay of care for affected infants.

Allergic contact dermatitis in children: a practical approach to management.

Allergic contact dermatitis (ACD) may account for at least 20% of all childhood dermatitis. Clinically, its morphology is identical to other forms of dermatitis in acute, subacute and chronic forms. A persistent or unusual and localized pattern is often the key to diagnosis. Treatment has centered around the use of corticosteroids, with the adjunct of antihistamines, wet dressings, and emollients for alleviation of symptoms. The newer topical immunosuppressives, tacrolimus and pimecrolimus, may also hold promise as alternative therapies, although they have not been well-studied in this regard. Allergen identification, sometimes through patch testing and allergen avoidance are the keys to preventing recurrences of this disease.

Does sensitization to contact allergens begin in infancy?

OBJECTIVE: Because previous studies have found allergic contact sensitization common in children by 5 years of age, our aim was to determine the prevalence of positive epicutaneous test results in children <5 years of age and to determine whether sensitization to contact allergens was as common in infancy. METHODS: We recruited 95 asymptomatic children 6 months to 5 years of age from well-child visits at Denver area pediatric practices for epicutaneous patch testing using the T.R.U.E. Test system. Allergens were placed on the skin for 48 hours, and at a later follow-up visit, positive reactions were evaluated. RESULTS: A total of 85 patients completed the study. Of these, 20 (24.5%) had 1 or more positive reactions to the tested allergens. Positive reactors ranged from 6 to 65.5 months of age, with an average of 30.4 months of age. Of the children, 16 reacted to 1 allergen, and 4 reacted to 2. Eleven positive reactions were observed to nickel, followed by 8 to thimerosal. Other positive reactions were to neomycin, cobalt, and kathon CG. CONCLUSIONS: Children as young as 6 months of age may be sensitized to contact allergens. Within this pediatric population, the prevalence of sensitization is 24.5%. Sensitization to contact allergens may occur in infants.