Madeline Weiner

Epidermolysis bullosa and the risk of life-threatening cancers : The National EB Registry experience, 1986-2006

BACKGROUND Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although the magnitude of this risk is undefined. METHODS Systematic case finding and data collection were performed throughout the continental United States (1986-2002) by the National EB Registry on 3280 EB patients to determine cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative risk of death from each tumor. Study design was cross-sectional, with a nested randomly sampled longitudinal subcohort (N = 450). RESULTS SCCs arose primarily in RDEB, especially the Hallopeau-Siemens subtype (RDEB-HS), first beginning in adolescence. Less frequently, SCCs occurred in junctional EB (JEB). Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively. In Herlitz JEB, the risk was 18.2% by age 25. SCC deaths occurred only in RDEB, with cumulative risks in RDEB-HS of 38.7%, 70.0%, and 78.7% by ages 35, 45, and 55, respectively. MM arose in RDEB-HS, with a cumulative risk of 2.5% by age 12. BCCs arose almost exclusively in the most severe EB simplex subtype (Dowling-Meara) (cumulative risk = 43.6% by age 55). LIMITATIONS Mutational analyses were performed on only a minority of enrollees in the National EB Registry, preventing evaluation of the possible influence of specific genotypes on the risk of developing or dying from cutaneous SCCs. CONCLUSIONS SCC is the most serious complication of EB within adults, especially those with RDEB-HS. By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection. When compared with SCCs arising within the normal population, the remarkably high risk of occurrence of and then death from SCCs among RDEB patients suggests likely differences in pathogenesis. Additional studies of EB-derived tumors and SCC cell lines may not only provide new insights into the mechanisms of carcinogenesis but also means whereby these particular tumors may be prevented or more effectively treated.

Cause-Specific Risks of Childhood Death in Inherited Epidermolysis Bullosa

OBJECTIVE To determine the cause-specific risks of death in children with epidermolysis bullosa (EB). STUDY DESIGN Data were collected throughout the continental United States between 1986 and 2002 by the National EB Registry. The study design is cross-sectional (n = 3280), containing within it a nested randomly sampled longitudinal subcohort (n = 450). RESULTS The risk of death during infancy and childhood was greatest in junctional EB (JEB), with cumulative and conditional risks of 40% to 44.7% by age 1 in both JEB subtypes, rising to 61.8% in children with JEB, Herlitz subtype and 48.2% in those with JEB, non-Herlitz subtype (JEB-nH) by age 15. In decreasing order, sepsis, failure to thrive, and respiratory failure were the major causes of death in children with JEB, plateauing by age 2 to 6. A small minority of children with epidermolysis bullosa simplex, Dowling-Meara subtype was at risk for death by age 1 (cumulative risk, 2.8%), with sepsis and respiratory failure accounting for cumulative risks of 1.9% and 0.9%. Only a minority of children with recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens subtype was at risk of death (cumulative risk = 8% by age 15). Renal failure also rarely accounted for death in children with JEB-nH. CONCLUSIONS Infants and children with inherited EB, particularly those with JEB, are at significant risk of death as a result of disease complications.

Gastrointestinal Complications of Inherited Epidermolysis Bullosa : Cumulative Experience of the National Epidermolysis Bullosa Registry

Background: Portions of the gastrointestinal (GI) tract may be severely involved in patients with inherited epidermolysis bullosa (EB). Evidence-based data are lacking as to the frequency and time of onset of these complications. Patients and Methods: Cross-sectional and longitudinal data were analyzed on 3,280 and 450 patients with EB, respectively, who were followed from 1986–2002 as part of the National EB Registry, an epidemiological study that attempted to identify, enroll, and collect data on every EB patient residing within the continental United States. Frequencies of abnormalities arising within the esophagus, stomach, small and large intestines, rectum, and anus were determined for each major EB subtype. Cumulative risks were similarly calculated for esophageal stenoses or strictures, and for severe growth retardation. Results: Esophageal strictures and growth retardation were commonly seen among the more severe EB subtypes, most notably Hallopeau-Siemens recessive dystrophic EB, and occurred as early as within the first year of life. EB subtype-specific differences were also observed in the frequency of occurrence of other GI complications. Discussion: A variety of GI complications arise in patients with inherited EB, varying across the major EB subtypes in their relative severity, frequency, and time of onset. Conclusions: Data generated by the National EB Registry should provide a sound basis whereby evidence-based strategies can be implemented for more effective surveillance and treatment of specific GI complications.

Impact of inherited epidermolysis bullosa on parental interpersonal relationships, marital status and family size.

Background  The presence in a family of a child or children with epidermolysis bullosa (EB) may have profound psychological implications for other family members.

Tracheolaryngeal Complications of Inherited Epidermolysis Bullosa: Cumulative Experience of the National Epidermolysis Bullosa Registry†

Objectives/Hypothesis: To accurately determine the frequency with which complications arise in the ears, noses, and throats of patients with inherited epidermolysis bullosa (EB) as well as the cumulative risk of tracheolaryngeal stenosis or stricture.

The risk of cardiomyopathy in inherited epidermolysis bullosa

Background  Case reports have suggested that cardiomyopathy may be a complication of recessive dystrophic epidermolysis bullosa (RDEB).