Epidermolysis Bullosa Simplex

Watchlist

(log in to enable)

Retrieved

2021-01-23

Source

Orphanet

Trials

—

Genes

KRT5, KRT14, EXPH5, DST, PLEC, ITGB4, NAT9, COL17A1, KLHL24, KRT1, VIM, TNF, MMP9, PLOD3, MAPK8, TGM5, CPSF4, ACTB, KRT10, KRT17, KRT9, IVL, CXCL8, IL6, IL2, HSP90AA1, GFAP, FN1, DES, BHLHE23

Drugs

Allantoin, Allogeneic adipose-derived adult mesenchymal stem cells contained in a fibrin-based bioengineered dermis, Allogeneic human dermal fibroblasts

Allantoin, Allogeneic adipose-derived adult mesenchymal stem cells contained in a fibrin-based bioengineered dermis, Allogeneic human dermal fibroblasts, Allogeneic skin-derived ABCB5-positive mesenchymal stem cells, Bilayer engineered skin composed of keratinocytes (patient autologous) and fibroblasts (donor allogeneic) in a plasma matrix, Diacerein, Dry extract from Betulae cortex (birch bark), Ex-vivo-expanded autologous fibroblasts transduced with lentiviral vector containing the COL7A1 gene, Ex-vivo-expanded autologous keratinocytes transduced with retroviral vector containing the COL7A1 gene, Human dermal fibroblasts cultured on a bioresorbable polyglactin mesh, Losartan, ex-vivo-expanded autologous human keratinocytes containing epidermal stem cells transduced with a COL7A1-encoding retroviral vector, genetically modified replication-incompetent herpes simplex virus-1 expressing collagen VII

Interested in hearing about new therapies?

Epidermolysis bullosa simplex (EBS) is a group of hereditary epidermolysis bullosa (HEB) disorders characterized by skin fragility resulting in intraepidermal blisters and erosions that occur either spontaneously or after physical trauma.

Epidemiology

Reported prevalence ranges from 1/215,000 in the USA to 1/35,000 in Scotland.

Clinical description

Onset is usually at or shortly after birth, although blistering in localized EBS may not develop until late childhood or early adulthood. Along with localized or generalized blistering and erosions, sometimes showing characteristic patterns (herpetiform grouping), cutaneous features may include nail shedding and dystrophy, and, rarely, milia formation. Scarring is mostly absent or minimal (mild atrophic wrinkling and dyspigmentation). Other findings may include congenital absence of the skin, and localized or confluent keratoderma of the palms and soles. The commonest extracutaneous manifestation is blistering of the oral cavity. A variety of additional extracutaneous complications may occur and are age-dependent, with time of onset and cumulative risk of occurrence highly dependent on the EB subtype. Several subtypes exist based on the intraepidermal localization of blisters. In most, blisters occur in the basal layer of the epidermis (autosomal recessive EBS; Dowling-Meara type; Köbner type; EBS - muscular dystrophy; Ogna type; EBS - pyloric atresia; localized EBS; EBS with migratory circinate erythema; EBS with mottled pigmentation). However, 3 subtypes involve suprabasal blistering (EBS due to plakophilin deficiency, EBS superficialis, lethal acantholytic EB; see these terms).

Etiology

EBS is caused by genetic mutations in specific genes depending on the subtype.

Diagnostic methods

Diagnosis is based on determination of the epidermal level within which blisters develop following minor skin traction. Recommended techniques are immunofluorescence antigen mapping (IFM) and transmission electron microscopy (TEM) performed on a skin biopsy sample. Subtypes are then defined on the basis of the mode of transmission, IFM and TEM, and clinical presentation. Cutaneous findings are not reliable diagnostic markers.

Differential diagnosis

Diagnosis is usually straightforward with little need for extensive differential diagnosis. However, in the neonatal period, in utero herpes simplex infection may be considered, especially if there is no family history of blistering disease or if clinical findings are atypical for EB. The differential diagnosis in neonates and small children may include congenital aplasia cutis, neonatal pemphigus, neonatal herpes gestationis, staphylococcal scalded skin syndrome, as well as incontinentia pigmenti, epidermolytic ichthyosis, linear IgA dermatosis, bullous pemphigoid, and bullous impetigo (see these terms).

Antenatal diagnosis

Prenatal testing using fetal DNA from chorionic villi or amniotic fluid cells is possible if the causative gene is known and the pathogenetic mutation(s) identified.

Genetic counseling

Inheritance is either autosomal dominant or autosomal recessive, depending on the subtype. Correct diagnosis of EBS subtype is crucial to proper genetic counseling.

Management and treatment

Management is based on the avoidance of blistering by meticulous protective skin padding and appropriate life-style to avoid trauma, and prevention of secondary infection by careful wound care. Air-conditioning may help in preventing disease worsening in warm weather. Patients with EB subtypes with the highest risk of specific extracutaneous complications need to be monitored closely and appropriate measures implemented to prevent the affected tissues from becoming severely injured.

Prognosis

Prognosis is highly dependent on the subtype. Most patients have a normal life expectancy but significant morbidity and even early death may occur in some subtypes.