Recessive dystrophic EB (RDEB) is divided into several subtypes. The most severe subtype is generalized RDEB, also known as Hallopeau-Siemens, which presents at birth with widespread blistering and is a chronic, progressive disorder. Milia, scarring, alopecia and other scalp abnormalities are common. Nail dystrophy with permanent loss of nails also is common. Severe blistering of the mouth may occur, and as the blisters on the oral mucosa heal, scars form and contribute to microstomia (small mouth opening) and ankyloglossia (tongue scarred to the floor of the mouth). Another contributing factor of microstomia is the scarring that develops on the outside of the mouth, further reducing the size of the mouth opening. Although dental enamel is normal, excessive dental caries occur. Fragile oral mucosa and microstomia make it difficult and painful to perform oral hygiene, and reduced production of saliva due to the injured mucous membranes creates dryness that leads to further decay; thus, regular dental cleanings and fluoride applications may be required every three months for severely affected individuals. Poor growth, anemia, and blistering and other problems involving the intestines/gastrointestinal tract and eyes cause significant problems.
The etiology of anemia in RDEB is complex, and includes iron deficiency anemia, chronic inflammatory anemia and nutritional anemia. Chronic blood and iron loss from skin; poor absorption of iron and other nutrients due to chronic inflammation in the intestines; chronic infection; bone marrow suppression; deficiency of B-complex vitamins, vitamin C, vitamin E and selenium; and decreased red blood cell survival contribute to chronic anemia, which often is refractory to treatment. Growth retardation largely is due to the increased need for calories and protein required for healing wounds, the mechanical difficulties of eating created by the oral and esophageal scarring and the absorption problems created by the interruption in the integrity of the small intestine. Placement of gastrostomy feeding tubes often is indicated. Painful blisters and erosions may develop on the conjunctiva of the eye.
Symblepharon (adherence of the eyeball to the eyelid) also may occur. Involvement of the genitourinary tract is uncommon, and involvement of the trachea/respiratory tract does not occur. Pseudosyndactyly leads to mitten deformity of the hands and feet.
Generalized RDEB is associated with an increased risk of squamous cell carcinoma of the skin cancer and, less commonly, of malignant melanoma by 30 years of age; therefore, individuals with JEB should be evaluated annually by a dermatologist. Renal (kidney) problems may occur, including glomerulonephritis, renal amyloidosis, IgA nephropathy and chronic renal failure. Other reported complications include cardiomyopathy, delayed puberty and osteopenia/osteoporosis, the latter of which may be due to malnutrition and malabsorption problems as well as a decrease in mobility and weight-bearing activities.