Junctional epidermolysis bullosa in children:an overview

Epidermolysis bullosa consist of a pattern of diseases which is mainly associated with genetic defects in the integrity of structures that cause the adhesion of the epidermis with the dermis,primarily called as the Basement Membrane Zone.If the defect is associated with the lamina lucida of the basement membrane zone,it is called junctional epidermolysis bullosa(JEB).JEB is mainly inherited in an autosomal recessive manner.The characteristic feature of all the JEB subtypes is enamel hypoplasia.This article is aimed at identifying the main features of JEB in children.Fifty articles which were published between 2000 and 2022 were reviewed and the types,investigations and management of JEB are explained based on the existing literature.

Identification of a Novel COL17A1 Compound Heterozygous Mutation in a Chinese Girl with Non-Herlitz Junctional Epidermolysis Bullosa

Summary:Non-Herlitz junctional epidermolysis bullosa(JEB-nH),an autosomal recessive bullous genodermatosis,is characterized by generalized skin blistering from birth onward,dental anomalies,universal alopecia and nail dystrophy.The underlying defect is mutation of the COLI7AI gene encoding the type XVⅡcollagen,resulting in losing structure for attachment of basal epithelial cells to the matrix.In present study,we described one case of congenitally affected female child aged 10 years,with skin blistering.Dermatologic examination revealed sparse,mild blisters on the face and hand,with profound enamel pitting of the teeth.Skin biopsy from proband's bullous skin displayed subepidermal bulla formation without acantholysis.The immunofluorescence of anti-type XVⅡcollagen antibody staining showed loss of type XVⅡcollagen staining at the basement membrane zone.A combination of whole exome sequencing(WES)and Sanger sequencing revealed the novel heterozygous mutations(C.4324C>T;p.Q1442^*and C.I 834G>C;p.G612R)in COLI7AI gene,which could be associated with the observed JEB-nH.One allele had a novel nonsense mutation(c.4324C>T;p.Q1442^*),resulting in nonsense-mediated mRNA decay and truncated collagen XVⅡ;the other allelc had a novel misscnse mutation of c.1834G>C;p.G612R in exon 22,causing a glycine-to-arginine substitution in the Gly-X-Y triple helical repeating motifs and decreasing the thermal stability of collagen XVⅡ.Our findings indicate that the genetic test based on WES can be useful in diagnosing JEB-nH patients.The novel pathogenic mutations identified would further expand our understanding of the mutation spectrum of COLI7AI gene in association with the inherited blistering diseases.

Natural Nanoskin ACT Management of the Rare Disease as Burnt Patient with Epidermolysis Bullosa and Stevens-Johnson

Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, which is characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. Sufferers of EB have compared the sores to third-degree burns. Stevens-Johnson syndrome is a rare but very serious skin problem, which causes the appearance of reddish lesions throughout the body and other changes, such as difficulty in breathing and fever, which can endanger the life of the affected person. The aim of this study was to show efficacy of a NANOSKIN ACT, AND NANOSKIN ACT SOFT wound dressing on the wound care management in patients with EB AND Stevens-Johnson syndrome (SJS).

Misdiagnosed dystrophic epidermolysis bullosa pruriginosa:A case report

BACKGROUND Dystrophic epidermolysis bullosa pruriginosa(DEB-Pr)is a rare subtype of DEB,characterized by recurrent pruritus of the extremities,pruritus papules,nodules,and mossy-like plaques.To date,fewer than 100 cases have been reported.We report a misdiagnosed 30-year-old man with sporadic late-onset DEB-Pr who responded well to tacrolimus treatment,thereby serving as a guide to correct diagnosis and treatment.CASE SUMMARY A 30-year-old man presented with recurrent itching plaques of 1-year duration in the left tibia that aggravated and involved both legs and the back.Examination revealed multiple symmetrical,purple,and hyperpigmented papules and nodules with surface exfoliation involving the tibia and dorsum of the neck with negative Nissl's sign,no abnormalities in the skin,mucosa,hair,or fingernail,and no local lymph node enlargement.Blisters were never reported prior to presentation.Serum immunoglobulin E level was 636 IU/mL.Clinical manifestations suggested DEB-Pr.Histological examination showed subepidermal fissure,scar tissue,and milia.Direct immunofluorescence showed no obvious abnormalities.However,we were unable to perform electron microscopy or genetic research following his choice.We treated him with topical tacrolimus.After 2 wk,the itching alleviated,and the skin lesions began to subside.No adverse reactions were observed during treatment.CONCLUSION Topical tacrolimus is a safe treatment option for patients with DEB-Pr and can achieve continuous relief of severe itching.

Haemolytic Anaemia Following High Dose Intravenous Immunoglobulin Treatment for Epidermolysis Bullosa Acquisita

Background: Epidermolysis bullosa aquisita (EBA) is a severe acquired blistering skin disease that is often resistant to prednisolone but can respond well to intravenous immunoglobulin infusion (IVIg). Main Observations: We describe the case of a 35 years old male patient with EBA who developed clinically significant haemolytic anaemia with a drop in Hb from 15.3 g/dL to a nadir of 8.4 g/dL within 5 days post IVIg infusion. The patient was blood group A and the IVIg batch was found to have a high titre of anti-A immunoglobulin. Conclusions: IVIg is an effective treatment for EBA. Haemolysis associated with IVIg has not previously been reported in the dermatology literature but review of data from other specialties shows that the problem is well recognised. Dermatologists using IVIg should be aware of this potential complication and patients should be consented appropriately and warned about this potential side effect.

End Stage Renal Disease in a Child with Epidermolysis Bullosa

Epidermolysis bullosa (EB) is an inherited connective tissue disease causing blisters in the skin and mucosal membranes. In severe cases, EB may be associated with renal damage through several mechanisms, mainly immunological ones. The present case described a young male with dystrophic recessive EB who developed an advanced chronic renal damage secondary to tubulointerstitial nephritis that was demonstrated by a renal biopsy. Unpublished previously, this complication should be considered among the possible causes of renal damage in EB. Also it is recommended a protocoled surveillance of renal and urinary tract complications in children with EB.

AB078.Ocular involvement in epidermolysis bullosa

Background:Epidermolysis bullosa(EB)is a heterogynous group of skin disorders characterized by formation of blisters and erosions of the skin in response to minor trauma.Subtypes include EB simplex(EBS),junctional EB(JEB),dystrophic form of EB(DEB)and finally Kindler syndrome(KS).In addition to dermal manifestation,patients can present with various ophthalmic pathologies.Methods:We reviewed the pathobiology,epidemiology and management of ocular manifestations as well as current and future innovative therapies for EB.Results:The severity and incidence of ocular involvement were the highest in the recessive DEB-generalized severe and JEB-generalized severe subtypes.Recurrent corneal erosions and blisters were the most common finding and seem to correlate with skin disease.Other manifestations include corneal scaring,blepharitis,ectropion,symblepharon,infantile cataracts,lacrimal duct obstruction as well as meibomian gland deficiency.Conclusions:Ophthalmology consult as well as regular follow-up are essential in the multi-disciplinary approach of this disease.Indeed,parents’and patients’education as well as early diagnosis and treatment are crucial to prevent permanent and long-term visual disabilities.

Epidermolysis Bullosa Pruriginosa in Two Siblings:A Case Report

Introduction:Epidermolysis bullosa pruriginosa(EBP)is a rare clinical subtype of inherited dystrophic epidermolysis bullosa(DEB)caused by type VII collagen mutations.The onset of EBP is variable and may present in late adulthood.The clinical features of EBP include prurigo-like papules,plaques,nodules,or linear configuration on the lower extremities.Here,we reported two sisters with EBP.Case presentation:We identified two Thai sisters with mild to moderate form of EBP,which resulted from a shared glycine substitution(Gly2287Val)in COL7A1 identified by genomic sequencing.Discussion:The histology and molecular findings of both cases supported a diagnosis of dystrophic EBP,however,the clinical manifestations differ between both cases.Conclusion:Molecular testing is the key for the diagnosis of EBP due to nonspecific clinical manifestation and histologic findings,however,there is no clear genotype-phenotype correlation in EBP.

单纯型大疱性表皮松解症患儿的角蛋白5基因突变研究

目的:对1例单纯型大疱性表皮松解症(EBS)患儿及其家系进行基因突变检测和致病性分析。方法:应用高通量二代测序技术捕获目标序列,对患儿进行全外显子组测序。发现致病位点后,应用Sanger测序法进行家系验证,查阅人类基因突变数据库(HGMD),运用生物信息学蛋白功能预测软件,分析变异位点的致病性。结果:患儿角蛋白5(KRT5)基因的第一外显子检出杂合变异c.536T>C(p.F179S),该变异造成KRT5蛋白的第179位氨基酸改变,患儿父母均未检测到相同突变。结论:患儿KRT5基因的杂合变异c.536T>C(p.F179S)为新发致病性变异,导致患儿KRT5缺陷,进而引发疱疹样型EBS(DM-EBS)。该变异位点在国内未见报道,扩大了我国人群KRT5的基因突变谱,为家系的遗传咨询和产前诊断提供依据。

透视下球囊扩张在大疱性表皮松解症伴食管狭窄中的应用疗效

目的探索透视引导下食管球囊扩张治疗在大疱性表皮松解症(epidermolysis bullosa,EB)伴食管狭窄中应用的疗效及安全性。方法回顾性收集我院2020年5月至2023年5月因食管狭窄行透视引导下食管球囊扩张治疗的EB患者相关临床资料及随访数据,分析该治疗方法的治疗效果及预后情况。结论共计有17例EB患者因食管狭窄所致吞咽困难于我院行透视引导下食管球囊扩张治疗。食管狭窄多为单处狭窄(13/17,76.5%),且常见于食道颈段(12/17,70.6%)和胸段上段(8/17,47.1%)。2例患者在扩张后出现食管出血,无需特殊治疗,未观察到其他治疗后并发症。大部分患者(15/17,88.2%)仅行单次扩张后即可获得持久的改善,截止随访时大部分患者(15/17,88.2%)体重较治疗前增长,平均增长2.97 kg。结论EB是引起食管狭窄的一种罕见病因,其食管狭窄的特点以食管上段的单处狭窄多见。透视引导下食管球囊扩张是治疗这类食管狭窄有效且安全的方法。

遗传性大疱性表皮松解症患者主要照护者生活质量现况及其影响因素

目的调查遗传性大疱性表皮松解症患者(epidermolysis bullosa,EB)主要照护者生活质量现况及其影响因素。方法采用一般情况调查表、SF-36健康调查量表和照护者负担量表对166名EB患者主要照护者进行调查。结果EB患者主要照护者SF-36总分为(57.40±17.42)分,其中:躯体健康方面得分为(64.05±18.30)分、心理健康方面得分为(50.98±20.39)分。照护负担与生活质量呈负相关(P<0.01)。多元线性回归分析显示,伤口护理材料获取便利性、家庭年收入、患者伤口面积占比、每日照护时长和照护负担程度是EB患者主要照护者生活质量的影响因素(均P<0.05)。结论EB患者的主要照护者生活质量处于低水平,尤其是伤口护理材料获取不便利、家庭年收入低、EB患者伤口面积较大、照护时长长、照护负担重的照护者,需要医护人员重点关注。

基因编辑技术在皮肤再生中的研究进展

基因编辑是对特定基因进行精确修改从而改变生物体遗传信息和表现型特征的技术,在皮肤再生领域应用前景巨大,为皮肤结构破坏而产生的难治性疾病带来全新的应对思路。本文阐述了基因编辑技术的研究现状并重点阐述其在皮肤再生疗法治疗大疱性表皮松解症、常染色体隐性先天性鱼鳞病及促进创面愈合的研究进展。

右美托咪定滴鼻麻醉在大疱表皮松解症患儿手术中效果的研究

目的评价右美托咪定滴鼻麻醉用于大疱表皮松解症(EB)矫形手术的效果。方法择期行双手假性并指矫形手术EB患儿41例,按照随机数字表法分为右美托咪定组(D组,21例)和对照组(N组,20例)。D组于入手术室前30 min经鼻滴注2 ug/kg右美托咪定,N组给予等量生理盐水经鼻滴注。记录患儿入室前与家长分离时的Ramsay评分,记录患儿术中追加氯胺酮次数、手术时间、苏醒时间及术后24 h FLACC疼痛评分。统计患儿术中呼吸抑制、苏醒期躁动发生例数和新发大疱数。结果D组患儿的Ramsay评分高于N组,氯胺酮追加次数和术后苏醒期躁动例数均少于N组,差异有统计学意义(P<0.05)。2组患儿呼吸抑制发生次数、术后苏醒时间、FLACC评分、新发大疱数的差异均无统计学意义(P>0.05)。结论右美托咪定滴鼻麻醉用于大疱表皮松解症患儿矫形手术,可有效减轻患儿与家长分离障碍,与麻醉药物起协同作用,减少术中氯胺酮追加次数、苏醒期躁动次数,而且对患儿苏醒时间及术后疼痛程度均无影响。

多技术联合治愈化疗致大疱性表皮松解型药疹1例报告

给予2022年4月重庆市铜梁区中医院收治的1例直肠癌术后复发行保守化疗联合免疫治疗致大疱性表皮松解型药疹患者在地塞米松及人免疫球蛋白抗过敏、盐酸莫西沙星氯化钠抗感染等对症支持治疗的基础上,会阴及阴囊创面均匀涂抹夫西地酸乳膏并覆盖湿润烧伤膏药纱治疗,其余皮肤破溃创面均匀涂抹湿润烧伤膏与重组牛碱性成纤维细胞生长因子凝胶混合剂治疗、未破损创面均匀涂抹湿润烧伤膏治疗,并于创面有新生表皮生长后,均改为单纯应用湿润烧伤膏治疗。治疗12 d,患者明显好转出院,于家中自行应用湿润烧伤膏换药治疗14 d后,创面完全愈合。

临床药师参与1例大疱性表皮松解型药疹的治疗实践

目的探讨临床药师在大疱性表皮松解型药疹[又称中毒性表皮松解症(TEN)]治疗中的作用。方法回顾临床药师参与的1例TEN的治疗全程,通过协助医师整理患者既往用药史及查询相关文献和指南,为医师筛选引起该药疹的可疑药物,并建议医师在后续治疗中应避免选用头孢菌素类药物和非甾体抗炎药,选用物理降温及其他交叉过敏反应发生率低的抗感染药物治疗。结果医师采纳药师的建议并执行后,患者皮疹明显改善,感染指标恢复正常。后续也及时阻止了含非甾体抗炎成分的滴眼液使用,保障了疗效。结论临床药师可帮助医师筛选出引起TEN的可疑药物,并提供合理的治疗建议,保障治疗的有效性和安全性。

Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in five Chinese families

Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.

新生儿遗传性营养不良性大疱性表皮松解症基因诊断1例

目的:探讨临床表现、皮肤活检病理诊断和基因诊断在遗传性营养不良性大疱性表皮松解症的诊断意义。方法:分析1例新生儿起病的遗传性营养不良性大疱性表皮松解症的临床和病理特点和基因诊断结果。结果:1例生后10 h入院新生儿,出生后即发现下肢有大片皮肤破损和糜烂,病变延伸至左侧踝关节和足底,住院后发现口腔内有血疱和水疱,住院期间皮肤受压和摩擦处多处出现新的大疱和皮肤脱落及皮肤糜烂。皮肤糜烂处分泌物和口腔分泌物细菌涂片和培养均未见细菌。取患儿皮肤做病理检查,结果光镜下可见真皮内有少量疏松结缔组织。电子显微镜下真皮层仅见少量纤维母细胞和胶原纤维,基质结构不清。大部分区域未见基底层,张力丝零散分布在真皮组织,部分区域有基底膜,但锚纤维结构不清,致密层变薄,符合遗传性营养不良性大疱性表皮松解症诊断标准。取患儿及其父母静脉血进行COL7A1基因检测,其母在COL7A1基因第13个外显子500上插入AGGG片段,其父在第98个外显子序列后剪切位点有一个G突变为A。患儿COL7A1基因出现复合杂合突变;突变位点分别与父亲和母亲位点一致,证实患儿遗传了来自父、母亲双方的突变基因,因此发病,其父母为表型正常的致病基因携带者。结论:对于临床怀疑遗传性大疱性表皮松解症患儿应先做皮肤病理检查,特别是通过电子显微镜超微结构观察做出初步分型,再根据病理类型进一步做相应基因检测确诊,如能对父母同时进行基因检测对今后优生可能有很大帮助。

痒疹样营养不良型大疱性表皮松解症一家系的基因突变检测

目的研究一中国汉族人痒疹样营养不良型大疱性表皮松解症家系的基因突变。方法采用聚合酶链反应及直接测序的方法对家系中11例患者进行COL7A1基因突变检测,以家系中的16例健康者和100例无亲缘关系的正常人作对照。结果该家系11名患者的COL7A1基因的87号外显子第6859位碱基鸟嘌呤G被腺嘌呤A替代,家系中健康对照及无亲缘关系的正常人均未发现该突变。结论甘氨酸替代突变c.6859G>A(p.G2287R)引起该痒疹样营养不良型大疱性表皮松解症家系发病。

白色丘疹样大疱性表皮松解症──附6例报告

报告６例白色丘疹样大疱性表皮松解症，临床上均具有典型的象牙白色丘疹，部位以小腿最多，一般无自觉症状。取水疱作组织病理显示表皮下疱或裂隙，真皮浅层轻度纤维母细胞增生；丘疹的病理表现为真皮浅层结缔组织轻度增生；取１例患者外观正常皮肤作透射电镜发现锚状纤维明显减少。我们认为本病的确诊需同时具有ＥＢ典型表现和特征性的白色丘疹，治疗以对症处理为主，预后较好。