Kim Whan B, Alavi Afsaneh, Walsh Scott, Kim Song, Pope Elena
Michael G. DeGroote School of Medicine, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada,
Am J Clin Dermatol. 2015 Apr;16(2):81-7. doi: 10.1007/s40257-015-0119-7.
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.
Our aim was to conduct a systematic review aimed at assessing the genotype-phenotype correlation in EBP.
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.
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).
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.
痒疹性大疱性表皮松解症（EBP）是营养不良性大疱性表皮松解症（DEB）的一种临床变异型，其特征为剧烈瘙痒以及搔抓后继发的肥厚性、苔藓化、痒疹样丘疹、斑块和结节。这些临床发现归因于COL7A1基因的各种突变。先前的报告对于EBP中可能存在的基因型-表型关系得出了不一致的结果。
我们的目的是进行一项系统评价，旨在评估EBP中的基因型-表型相关性。
使用PubMed、Medline、EMBASE和Cochrane数据库对1946年至2014年9月发表的所有经突变验证的EBP报告进行系统评价。使用逻辑回归分析对突变类型之间的临床发现进行统计学比较。
该评价共纳入28篇文章，涉及74例个体，包括4级非对照病例系列（C级）和5级病例报告（D级）。先前报告的突变类型包括甘氨酸替代（GS，52.7%）、框内缺失（IFS，33.8%）、非甘氨酸替代（NGS，8.1%）和提前终止密码子（PTC，5.4%）。最常见的临床发现是四肢受累、线状形态和甲营养不良。与GS突变携带者相比，IFS携带者更有可能：（1）为男性（比值比[OR]2.99；p = 0.043；95%置信区间[CI]1.27 - 11.4），以及（2）出现水疱（OR 4.10；p = 0.013；95% CI 1.34 - 12.5）。
据我们所知，本研究是首次对EBP中突变类型与临床表现之间的关系进行系统评价。本评价中的发现：（1）确定了EBP的常见临床特征，这可能有助于评估可能患有EBP的患者；（2）表明某些突变携带者可能更有可能表现出特定的表型。在面临潜在诊断挑战的情况下，评估常见临床发现的存在以及进行分子检测可能有助于正确识别和预后判断。
