Epidermolysis bullosa pruriginosa: a systematic review exploring genotype-phenotype correlation.

Introduction: Epidermolysis bullosa pruriginosa (EBP) is a clinical variant of dystrophic epidermolysis bullosa (DEB), characterized by intense pruritus and hypertrophic, lichenified, prurigo-like papules, plaques, and nodules secondary to scratching. These clinical findings have been attributed to various mutations in the COL7A1 gene. Previous reports have yielded inconsistent findings regarding a possible genotype-phenotype relationship in EBP.

Objective: Our aim was to conduct a systematic review aimed at assessing the genotype-phenotype correlation in EBP.

Methods: A systematic review was conducted using PubMed, Medline, EMBASE, and Cochrane databases for all reports of mutation-verified EBP, published from 1946 to September 2014. Statistical comparison of clinical findings between mutation types was performed using logistic regression analysis.

Results: The review included a total of 28 articles with 74 individuals, which consisted of level 4 non-controlled case series (grade C) and level 5 case reports (grade D). Previous reported mutation types included glycine substitution (GS, 52.7%), in-frame skipping (IFS, 33.8%), non-glycine substitution (NGS, 8.1%), and premature termination codon (PTC, 5.4%). The most common clinical findings were extremities involvement, linear configuration, and nail dystrophy. In comparison with GS mutation carriers, IFS carriers had a higher likelihood of (1) being male (OR 2.99; p = 0.043; 95% CI 1.27-11.4) and (2) presenting with blisters (OR 4.10; p = 0.013; 95% CI 1.34-12.5).

Conclusions: To our knowledge, this study is the first systematic review examining the relationship between mutation type and clinical presentation in EBP. The findings in this review (1) identify common clinical characteristics of EBP that may help in the assessment of patients with possible EBP; and (2) indicate that certain mutation carriers may have a higher likelihood of exhibiting particular phenotypes. In the case of potential diagnostic challenge, assessment for presence of common clinical findings as well as molecular testing may facilitate correct identification and prognostication.