Clinical characteristics: Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; renal and/or ureteral anomalies; and protein-losing enteropathy. The course of EB-PA is usually severe and most often lethal in the neonatal period. Those who survive may have severe blistering with formation of granulation tissue on the skin around the mouth, nose, diaper area, fingers, and toes, and internally around the trachea. However, some affected individuals have little or no blistering later in life. Additional features shared by EB-PA and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita) affecting the extremities and/or head, milia, nail dystrophy, scarring alopecia, hypotrichosis, and corneal abnormalities.
Diagnosis/testing: The diagnosis of EB-PA is established in a proband with characteristic clinical findings by identification of biallelic pathogenic variants in ITGA6, ITGB4, or PLEC. Skin biopsy using transmission electron microscopy and/or immunofluorescent antibody/antigen mapping can be considered in those with inconclusive molecular genetic testing.
Management: Treatment of manifestations: Tracheostomy when indicated for respiratory failure; nutrition consult to address oral intake and nutritional needs; minimization of new blister formation by teaching caretakers proper handling of infants and children to protect skin from shearing forces, wrapping and padding of extremities, and use of soft and properly fitted clothing and footwear; lance and drain new blisters and dress with three layers (primary: nonadherent; secondary: for stability and protection; tertiary: elastic properties to insure integrity); antibiotics and antiseptics to treat and prevent wound infections; surgical intervention to correct pyloric atresia; gastrostomy if indicated; treatment of protein-losing enteropathy by gastroenterologist; referral to urologist and/or nephrologist for renal anomalies, abnormal voiding, and/or abnormal renal function; calcium, vitamin D, vitamin A, zinc, carnitine, selenium, and iron supplements as indicated by laboratory studies; treatment of corneal abnormalities by ophthalmologist; psychosocial support; palliative care consultation.
Surveillance: Assessment of oral mucosa, feeding, and nutritional status at each visit; assessment of tracheal involvement at each visit; assessment of skin for blisters and infection at each visit; assessment of renal function per nephrologist; assessment for gastrointestinal involvement at each visit; assessment of urinary involvement per urologist; annual CBC, iron studies, zinc, vitamin D, selenium, carnitine, and vitamin A; periodic DXA scan for risk of osteopenia; assessment for corneal abnormalities at each visit; assessment of family needs at each visit.
Agents/circumstances to avoid: Ordinary medical tape or Band-Aids®; EKG leads with adhesive; poorly fitting or coarse-textured clothing and footwear; activities that traumatize the skin.
Pregnancy management: Consider cesarean section to reduce trauma to the skin of an affected fetus during delivery.
Genetic counseling: EB-PA is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an EB-PA-related pathogenic variant, each sib of an affected individual has at conception 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. Once the EB-PA-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing for EB-PA are possible.
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