Self‐initiated use of topical cannabidiol oil for epidermolysis bullosa

Epidermolysis bullosa is a rare blistering skin disorder that is challenging to manage because skin fragility and repeated wound healing cause itching, pain, limited mobility, and recurrent infections. Cannabidiol, an active cannabinoid found in cannabis, is postulated to have antiinflammatory and analgesic effects. We report 3 cases of self‐initiated topical cannabidiol use in patients with epidermolysis bullosa in an observational study. One patient was weaned completely off oral opioid analgesics. All 3 reported faster wound healing, less blistering, and amelioration of pain with cannabidiol use. Although these results demonstrate promise, further randomized, double‐blind clinical trials are necessary to provide scientific evidence of our observed benefits of cannabidiol for the treatment of epidermolysis bullosa.     

Impact of next generation sequencing on diagnostics in a genetic skin disease clinic

Individuals with inherited skin diseases often pose one of the most difficult diagnostic challenges in dermatology. The hunt for the underlying molecular pathology may involve candidate gene screening or linkage analysis, which is usually determined by the initial history, the physical findings and laboratory tests. Recent technical advances in DNA sequencing, however, are shifting the diagnostic paradigm. Notably, next‐generation sequencing allows a more comprehensive approach to diagnosing inherited diseases, with potential savings of both time and money. In the setting of a paediatric dermatology genetics clinic in Kuwait, we therefore performed whole‐exome sequencing on seven individuals without a priori detailed knowledge of the patients’ disorders: from these sequencing data, we diagnosed X‐linked hypohidrotic ectodermal dysplasia (two cases), acrodermatitis enteropathica, recessive erythropoietic protoporphyria (two siblings) and localized recessive dystrophic epidermolysis bullosa (two siblings). All these groups of disorders are clinically and genetically heterogeneous, but the sequencing data proved inherently useful in improving patient care and avoiding unnecessary investigations. Our observations highlight the value of whole‐exome sequencing, in combination with robust bioinformatics analysis, in determining the precise molecular pathology and clinical diagnosis in patients with genetic skin disorders, notably at an early stage in the clinical evaluation of these often complex disorders and thereby support a new paradigm for future diagnostics.     

Epidermolysis bullosa acquisita mit facettenreichem klinischen Bild und erfolgreicher Mycophenolatmofetiltherapie

A 60-year-old woman with epidermolysis bullosa acquisita (EBA) presented with a highly variable clinical picture. First she developed oral erosions and ulcers covered with shaggy epithelial rests. Later she developed pustular and target lesions as well as tense cutaneous blisters. Clinically the alterations were strongly suggestive of aphthae or a pustular dermatosis. Histological and immunological examinations revealed subepidermal blister formation, neutrophilic infiltration, linear deposition of IgG and C3 at the basement membrane in the direct immunofluorescence and the evidence of circulating IgG-antibodies against basement membrane (monkey esophagus) in the indirect immunofluorescence. Thus our working diagnosis was a pustular or nodular form of bullous pemphigoid, as a linear IgA dermatosis was excluded. Indirect immunofluorescence using NaCl-separated primate skin localized the basement membrane antibodies in the base of the artificial blister, while immunoblotting of dermal extracts disclosed binding of serum antibodies to a 290-kDa protein. Bullous systemic lupus erythematosus was excluded, leading to the definitive diagnosis of EBA. The clinical variability of this disease is well known; the polymorphic picture in our patient with erosions, pustules, target lesions and blisters is unique in the literature. The similarity in histology and immunofluorescence of the clinically quite different lesions is another unexpected event. Also the speedy response to therapy with the immunosuppressive agent mycophenolate mofetil has only been described once before. The patient remains in remission after 6 months. Because of the poor response to therapy in most cases, the significant skin lesions are a source of physical as well as emotional distress. Additional complications include stenosis of trachea or bronchi injure.     

Genome‐wide single nucleotide polymorphism‐based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome‐wide single nucleotide polymorphism (SNP) array‐based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB‐targeted next‐generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed genetically.     

Murine type VII collagen distorts outcome in human skin graft mouse model for dystrophic epidermolysis bullosa

Human skin graft mouse models are widely used to investigate and develop therapeutic strategies for the severe generalized form of recessive dystrophic epidermolysis bullosa (RDEB), which is caused by biallelic null mutations in COL7A1 and the complete absence of type VII collagen (C7). Most therapeutic approaches are focused on reintroducing C7. Therefore, C7 and anchoring fibrils are widely used as readouts in therapeutic research with skin graft models. In this study, we investigated the expression pattern of human and murine C7 in a grafting model, in which human skin is reconstituted out of in vitro cultured keratinocytes and fibroblasts. The model revealed that murine C7 was deposited in both human healthy control and RDEB skin grafts. Moreover, we found that murine C7 is able to form anchoring fibrils in human grafts. Therefore, we advocate the use of human‐specific antibodies when assessing the reintroduction of C7 using RDEB skin graft mouse models.     

Coexistence of acquired hemophilia A and epidermolysis bullosa acquisita: Two case reports and published work review

Epidermolysis bullosa acquisita (EBA) is a rare chronic subepidermal bullous autoimmune disease. The occurrence of acquired hemophilia A (AHA) is low and so the coexistence of EBA and AHA is extremely rare. We herein described a case of EBA coexisting with AHA and a case of EBA coexisting with AHA and hepatitis B. These EBA may be related to the pathogenesis of AHA. In this study, we analyzed the clinical features in the two Chinese cases of EBA coexisting with AHA, and found esophageal hemorrhage and hematemesis were the main symptoms of both patients. Cyclosporin, prednisone and lamivudine effectively control EBA with AHA and hepatitis B. The dose of cyclosporin should be more than 4 mg/kg per day and the period of treatment should be longer than 5 months to reduce the risk of EBA co‐occurring with AHA.     

Selected genodermatoses – Status quo and future prospects

Genodermatoses are monogenetic disorders, which may manifest with symptoms either exclusively on the skin or also involve other organs in the context of an associated syndrome. Over the past 30 years, numerous hereditary hair, tumor, blistering, and keratinization diseases have been characterized both clinically and genetically. This has resulted in the continuous development of disease-specific classifications as well as diagnostic algorithms and examination techniques, and has also led to new pathogenesis-based therapeutic approaches. While the deciphering of the underlying genetic defects of these diseases is already well advanced, there is still much room for the development of new translationally motivated treatment strategies.     

Prevalence of delayed puberty and low bone density in patients with epidermolysis bullosa: Insight from a large single center's experience

Background

Epidermolysis bullosa (EB) is a group of rare genetic skin conditions that result in skin fragility. EB can be quite severe with chronic inflammation and malnutrition impairing growth and pubertal development. These factors have potential consequences for skeletal health. We aimed to determine the prevalence of delayed puberty and low bone mineral density (BMD) for age in children and young adults with EB.

Methods

Electronic medical records (EMR) of patients with confirmed EB <30 years of age at time of initial encounter at Cincinnati Children's Hospital Medical Center between January 1, 2010 and September 30, 2020 were reviewed. Natural language processing software was used to categorize pubertal status of patients with EB as early, normal or delayed. BMD was measured by dual energy x-ray absorptiometry and categorized as low if height adjusted Z-score was <−2.0 using age, sex and race specific reference ranges.

Results

29% of individuals with EB had low BMD with most cases occurring prior to 10 years of age. Of patients who reached adolescence, 23% failed to develop any signs of puberty in the normal range (before age 13 in females or 14 in males) and BMD Z-scores further declined in these individuals.

Conclusion

Delayed puberty is an under-recognized comorbidity of individuals with EB, especially in those with recessive dystrophic EB, and can have a significant impact on BMD.