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Epidermolysis Bullosa Pruriginosa: A Systematic Review Exploring Genotype–Phenotype Correlation

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Abstract

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.

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Disclosures

Funding:

No funding was received.

Conflicts of interest

W. Kim, A. Alavi, S. Walsh, S. Kim, and E. Pope declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Michael G. DeGroote School of Medicine, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada

    Whan B. Kim

  2. Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada

    Afsaneh Alavi, Scott Walsh & Elena Pope

  3. Women’s College Hospital, Toronto, ON, Canada

    Afsaneh Alavi

  4. Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Scott Walsh

  5. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Song Kim

  6. University of Toronto Hospital for Sick Children, Toronto, ON, Canada

    Elena Pope

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  1. Whan B. Kim
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Correspondence to Whan B. Kim.

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Kim, W.B., Alavi, A., Walsh, S. et al. Epidermolysis Bullosa Pruriginosa: A Systematic Review Exploring Genotype–Phenotype Correlation. Am J Clin Dermatol 16, 81–87 (2015). https://doi.org/10.1007/s40257-015-0119-7

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  • DOI: https://doi.org/10.1007/s40257-015-0119-7

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