Junctional Epidermolysis Bullosa

Clinical characteristics: Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures.

Diagnosis/testing: The diagnosis of JEB is established in a proband with characteristic clinical findings by molecular genetic testing that identifies biallelic pathogenic variants in one of the genes associated with JEB: COL17A1, ITGB4, LAMA3, LAMB3, or LAMC2. Skin biopsy using transmission electron microscopy (TEM) and/or immunofluorescent antibody/antigen mapping can be performed but is no longer the preferred method of diagnosis.

Management: Treatment of manifestations: Lance and drain new blisters and dress with three layers (primary: non-adherent; secondary: for stability and protection; third: elastic properties to ensure integrity); protect skin from shearing forces; teach caretakers proper handling of infants and children; treatment of granulation tissue with high-potency topical steroids, silver nitrate, electrocautery, or autologous skin grafts; antibiotics and antiseptics as needed for wound care and infection; dilation of esophageal strictures (rare); tracheostomy if appropriate; gastrostomy tube if needed; standard treatment of gastroesophageal disease; appropriate footwear and physical therapy to promote/preserve ambulation; psychosocial support, including social services and psychological counseling; appropriate management of chronic pain; regular dental care; treatment of urologic and renal disease using standard treatments.

Prevention of secondary complications: Attention to fluid and electrolyte balance in severely affected infants (especially sodium levels); nutritional support including feeding gastrostomy when necessary; calcium, vitamin D, zinc, and iron supplements.

Surveillance: Annual screening for iron-deficiency anemia, zinc deficiency, vitamin D deficiency; periodic bone mineral density scanning for osteopenia and/or osteoporosis; periodic echocardiograms to evaluate for dilated cardiomyopathy; in the second decade of life, surveillance for squamous cell carcinoma is appropriate.

Agents/circumstances to avoid: Ordinary medical tape or Band-Aids^®, poorly fitting or coarse-textured clothing and footwear, activities that can traumatize the skin (e.g., hiking, mountain biking, contact sports).

Pregnancy management: Consider cesarean section delivery to reduce trauma to the skin of an affected fetus.

Genetic counseling: JEB is inherited in an autosomal recessive manner. The parents of an affected child are usually obligate heterozygotes (i.e., carriers). Because germline mosaicism and uniparental isodisomy have been reported, carrier status of parents needs to be confirmed with molecular genetic testing. At conception, each sib of an affected individual whose parents are both carriers has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. The offspring of an individual with autosomal recessive JEB are obligate heterozygotes (carriers) for a pathogenic variant. Carrier testing for family members at increased risk and prenatal testing for a pregnancy at increased risk are possible if both pathogenic variants have been identified in the family.