Genotype-Phenotype Correlation in Junctional Epidermolysis Bullosa: Signposts to Severity.

Junctional epidermolysis bullosa (JEB) is a rare autosomal recessive genodermatosis with a broad spectrum of phenotypes. Current genotype-phenotype paradigms are insufficient to accurately predict JEB subtype and characteristics from genotype, particularly for splice site variants, which account for over a fifth of disease-causing variants in JEB. This study evaluated the genetic and clinical findings from a JEB cohort, investigating genotype-phenotype correlations through bioinformatic analyses and comparison with previously reported variants.

In utero development of epidermolysis bullosa acquisita.

We report the case of an infant born with perioral vesicles that rapidly spread to involve his mouth and the majority of his body. Histopathology, immunofluorescence, and enzyme-linked immunohistochemistry assays confirmed a diagnosis of epidermolysis bullosa acquisita (EBA). His mother had no history of EBA, and serum indirect immunofluorescence was negative.

Drug-induced linear IgA bullous dermatosis in a patient with a vancomycin-impregnated cement spacer.

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering rash caused by IgA autoantibodies against the epidermal basement membrane zone. It commonly is drug induced, often in association with systemic vancomycin. We report a case of a previously healthy 77-year-old man who developed a diffuse macular rash and hemorrhagic bullae on the left leg 10 days after placement of a vancomycin-impregnated cement spacer (VICS) during a revision knee arthroplasty and initiation of postoperative treatment with intravenous (IV) vancomycin.

Erythematous plaques and papules on a premature infant.

A 2240 gram boy was born at 33.2 weeks gestation with nonblanching, deeply erythematous plaques and papules on the back, flanks, and scalp (Figure 1). His mother was GBS positive and on antibiotic suppression for prior cutaneous MRSA and urinary tract infections.

Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates From the National Epidermolysis Bullosa Registry.

Importance: Accurate estimation of the incidence and prevalence of each subtype of epidermolysis bullosa (EB) is essential before clinical trials can be designed and sufficient funding allocated by government agencies and third-party insurers for the care of these individuals.

Objective: To determine the incidence and prevalence of inherited EB stratified by subtype in the United States during a 16-year period.

Design, Setting, And Participants: Prospective cross-sectional and longitudinal study.

Autoimmune bullous diseases with skin and eye involvement: Cicatricial pemphigoid, pemphigus vulgaris, and pemphigus paraneoplastica.

Autoimmune blistering diseases are a heterogeneous group of disorders that mostly affect the skin and mucous membranes. Occasionally, other organ systems may be involved, depending on the unique pathophysiology of each disease. Cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus are distinct entities, but all have the potential to have cutaneous and ocular involvement.

Systemic granulocyte colony-stimulating factor (G-CSF) enhances wound healing in dystrophic epidermolysis bullosa (DEB): Results of a pilot trial.

Background: Chronic nonhealing wounds are the norm in patients with inherited epidermolysis bullosa (EB), especially those with dystrophic EB (DEB). A possible benefit in wound healing after subcutaneous treatment with granulocyte colony-stimulating factor (G-CSF) was suggested from an anecdotal report of a patient given this during stem cell mobilization before bone-marrow transplantation.

Objective: We sought to determine whether benefit in wound healing in DEB skin might result after 6 daily doses of G-CSF and to confirm its safety.

Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification.

Background: Several new targeted genes and clinical subtypes have been identified since publication in 2008 of the report of the last international consensus meeting on diagnosis and classification of epidermolysis bullosa (EB). As a correlate, new clinical manifestations have been seen in several subtypes previously described.

Objective: We sought to arrive at an updated consensus on the classification of EB subtypes, based on newer data, both clinical and molecular.

Cumulative life course impairment by epidermolysis bullosa.

Inherited epidermolysis bullosa, which encompasses at least 30 distinctive genetic diseases, may be associated with marked functional impairment, the result of the presence of severe cutaneous and extracutaneous manifestations or complications in some of its subtypes.

Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa.

Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples.

Inherited epidermolysis bullosa: recent basic and clinical advances.

Purpose Of Review: This review highlights key findings, both clinical and basic, that have been published in the field of inherited epidermolysis bullosa within the past few years.

Recent Findings: New epidermolysis bullosa phenotypes, genotypes and modes of transmission have been identified, resulting in a revised classification system. Detailed evidence-based data are now available on the risk of extracutaneous complications in each of the major epidermolysis bullosa subtypes.

Inherited epidermolysis bullosa: past, present, and future.

Inherited epidermolysis bullosa encompasses dozens of diseases characterized by mechanical fragility of the skin, blister formation, and abnormal wound healing. Most of the more severe subtypes are associated with clinically significant extracutaneous complications. Some subtypes may lead to death, even in early infancy.

Inherited epidermolysis bullosa.

Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs.

A mouse model of generalized non-Herlitz junctional epidermolysis bullosa.

Epidermolysis bullosa (EB) is a class of intractable, rare, genetic disorders characterized by fragile skin and blister formation as a result of dermal-epidermal mechanical instability. EB presents with considerable clinical and molecular heterogeneity. Viable animal models of junctional EB (JEB), that both mimic the human disease and survive beyond the neonatal period, are needed.

Nephrogenic systemic fibrosis: report of an additional case with granulomatous inflammation.

Nephrogenic systemic fibrosis (NSF) is a novel disease entity described over the past 10 years. NSF is a progressive systemic fibrosing disorder that occurs arguably exclusively in patients with impaired renal function who have been exposed to gadolinium-containing contrast agents. As no single clinical or histopathologic finding is diagnostic of NSF, a careful review of the cumulative characteristics of each case is essential in making a correct diagnosis.

Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs.

It is well known, primarily via case reports and limited case series, that nonepithelial tissues may become injured in patients with epidermolysis bullosa. Only recently, however, have there been data generated from large, well characterized cohorts. Our objective is to provide dermatologists with a comprehensive review of each of these major extracutaneous complications, with a summary of the pertinent literature and evidence-based recommendations for surveillance, evaluation, and management.

Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I. Epithelial associated tissues.

Based upon case reports and small case series, it has been known for many years that some types and subtypes of inherited epidermolysis bullosa (EB) may be at risk for developing one or more extracutaneous complications. Many of these are associated with considerable morbidity; some may result in death. Only over the past few years have there been data generated from large, well characterized cohorts.

Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006.

Background: Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although the magnitude of this risk is undefined.

Methods: Systematic case finding and data collection were performed throughout the continental United States (1986-2002) by the National EB Registry on 3280 EB patients to determine cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative risk of death from each tumor. Study design was cross-sectional, with a nested randomly sampled longitudinal subcohort (N = 450).

The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB.

Background: Since publication in 2000 of the Second International Consensus Report on Diagnosis and Classification of Epidermolysis Bullosa, many advances have been made to our understanding of this group of diseases, both clinically and molecularly. At the same time, new epidermolysis bullosa (EB) subtypes have been described and similarities with some other diseases have been identified.

Objective: We sought to arrive at a new consensus of the classification of EB subtypes.