Intermediate generalized junctional epidermolysis bullosa (ORPHA:79402)
A form of junctional epidermolysis bullosa (JEB) characterized by generalized skin blistering, atrophic scarring, nail dystrophy or nail absence, and enamel hypoplasia, with extracutaneous involvement.
Epidemiology
Prevalence of intermediate junctional epidermolysis bullosa (intermediate JEB) is unknown.
Clinical description
The condition is clinically apparent at birth. Skin blistering is generalized and healing can occur either with atrophic scars, sometimes accompanied by hypopigmentation or hyperpigmentation or, less commonly, with the formation of exuberant granulation tissue. Nail dystrophy or loss is a constant feature, and focal palmoplantar keratoderma can develop over time. Progressive and permanent hair loss is frequently present, affecting the scalp, eyelashes and eyebrows; pubic and axillary hair are scant or do not fully develop. Mucosal lesions mainly affect the oral and nasal cavity, although there is considerable individual variability. Ocular involvement has been reported in some patients and comprises corneal erosions and scars, and, rarely, ectropion. The teeth regularly show enamel hypoplasia, leading to severe caries. Chronic anemia of multifactorial etiology, although of varying severity, is frequent and may be associated with a growth delay.
Etiology
Intermediate JEB is caused by mutations in the COL17A1 (10q24.3), ITGB4 (17q25.1), LAMA3 (18q11.2), LAMB3 (1q32) and LAMC2 (1q25-q31) genes.
Diagnostic methods
Diagnosis is suspected on clinical presentation and confirmed by immunofluorescence mapping or transmission electron microscopy and genetic testing.
Differential diagnosis
The differential diagnosis includes other forms of EB. In the neonatal period, aplasia cutis congenita, herpes simplex infection, congenital erosive and vesicular dermatosis, epidermolytic ichthyosis, linear IgA bullous dermatosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis, bullous impetigo, and staphylococcal scalded skin syndrome may need to be considered.
Antenatal diagnosis
Antenatal diagnosis can be recommended in families with this subtype depending on the degree of severity.
Genetic counseling
The pattern of inheritance is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child at each pregnancy.
Management and treatment
Management is preventive: protective padding of the skin reduces blistering and careful wound care prevents secondary infection and reduces scarring. Oral hygiene is important for management of caries. A dietitian should evaluate nutritional requirements. Ocular, gastrointestinal, urinary and renal manifestations require specific treatment.
Prognosis
Although intermediate JEB is less severe than other forms of JEB, death can occur in infancy and childhood due to sepsis, failure to thrive and respiratory failure. Adult patients have an increased risk of developing squamous cell carcinomas in particular on the lower extremities, in areas of chronic blistering, long-standing erosions, or atrophic scarring.

                            Last update: 
                            June 2021


                            - Expert reviewer(s): 
                            Pr Cristina HAS | ERN-Skin*


                                * European Reference Network