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.

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.

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.

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.

Rare case of dysphagia, skin blistering, missing nails in a young boy

Epidermolysis bullosa is a group of genetic disorders with an autosomal dominant or an autosomal recessive mode of inheritance and more than 300 mutations. The disorder is characterized by blistering mucocutaneous lesions and has several varying phenotypes due toanchoring defect between the epidermis and dermis. The variation in phenotypic expression depends on the involved structural protein that mediates cell adherence between different layers of the skin. Epidermolysis bullosa can also involve extra-cutaneous sites including eye, nose, ear, upper airway, genitourinary tract and gastrointestinal tract. The most prominent feature of the gastrointestinal tract involvement is development of esophageal stricture. The stricture results from recurrent esophageal mucosal blistering with consequent scarring and most commonly involves the upper esophagus. Here we present a case of a young boy with dominant subtype of dystrophic epidermolysis bullosa who presented with dysphagia, extensive skin blistering and missing nails. Management of an esophageal stricture eventually requires dilatation of the stricture or placement of a gastrostomy tube to keep up with the nutritional requirements. Gastrostomy tube also provides access for esophageal stricture dilatation in cases where antegrade approach through the mouth has failed.

Clinical management of gastrointestinal amyloidosis

Amyloidosis is characterized by extracellular deposition of abnormal protein, consisting of primary, secondary, hemodialysis-related, hereditary, senile and localized type. Primary amyloidosis is associated with monoclonal light chains. Secondary amyloidosis is associated with inflammatory, infectious, and neoplastic diseases. Amyloid deposition in the gastrointestinal tract can manifest the symptoms including diarrhea, steatorrhea, or constipation. For diagnosis, one should obtain an immunofixation of serum or urine as well as biopsy sampling of gastrointestinal mucosa stained specifically. While most gastrointestinal complications are managed symptomatically, treatment depends upon the type of amyloidosis. Causal therapy is reserved for a select few from various subtypes of this disorder.

Application of topical gentamicin-a new era in the treatment of genodermatosis

Background The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic.However,in the past decade,there were considerable interests in therapeutic approaches in treating hereditary diseases.Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins.Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins.We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases.Data sources We search the MEDLINE through PubMed,EMBASE databases,and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms"gentamicin,topical gentamicin,genodermatosis,genetic skin diseases".Results The application of gentamicin in genodermatosis yielded promising results,both in vivo and in vitro,including Nagashima-type palmoplantar keratosis,epidermolysis bullosa,Hailey-Hailey disease,hereditary hypotrichosis simplex of the scalp,etc.Conclusions Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.