Clinical Guidance

RDEB

• Severe RDEB is typically caused by biallelic pathogenic variants in COL7A1 that result in null or out-of-frame insertions/deletions and splice site variants resulting in no functional protein. Recent analysis of 236 individuals with RDEB showed correlation with types of pathogenic variants and disease severity .

• Intermediate RDEB generally results from glycine substitution within the triple helical domain on one allele and a premature stop codon on the other allele; only a small amount of partially functional protein is made.

• Less severe forms generally result from other (non-glycine) amino acid substitutions and splice site variants

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"

Penetrance

Penetrance for DDEB is reduced; unaffected individuals have been identified .

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"

Diagnostic Criteria

Suggestive Findings

Dystrophic epidermolysis bullosa (DEB) should be suspected in individuals with the following clinical findings:

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"

Differential Diagnosis

Blistering, especially in the neonatal period, should prompt consideration of acquired conditions and congenital genetic disorders.

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"

Management Guidelines

International clinical practice guidelines for dystrophic epidermolysis bullosa (DEB) have been published by DEBRA International. These include guidelines for treatment of anemia, foot care, occupational therapy, palliative and end-of-life care, psychosocial care, neonatal care, cancer management, hand surgery and hand therapy, oral health care, physical therapy, skin and wound care, constipation management, pain care, pregnancy, childbirth, and aftercare, and supporting sexuality.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with DEB, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 5.

Dystrophic Epidermolysis Bullosa: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Skin | • Thorough eval of skin surface for blisters, erosions, infections

• Eval of crusted, non-healing, or painful lesions in older persons for SCC

| Difficult for some persons to fully undress in clinic; may need to rely on photos

Oral mucosa

| • Dental consult

• Exam of mouth incl mucosal blistering erosions

• Assessment for dental caries crowding

Clinical Guidance

Nasogastric tubes are discouraged because of oral and esophageal fragility . Poorly fitting or coarse-textured clothing and footwear should be avoided, as they can cause trauma. In general, activities that traumatize the skin (e.g., hiking, mountain biking, contact sports) should be avoided; affected individuals who are committed to participation in such activities should be encouraged to devise ways of protecting the skin. Most persons with DEB cannot tolerate the use of ordinary medical tape or Band-Aids®.

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"

Therapies Under Investigation

There are several promising therapies currently being studied, including various stem cell therapies including bone marrow transplant, mesenchymal stem cells, stromal cells, induced pluripotent stem (IPS) cells , and gene-corrected fibroblasts . Stop codon read-through, exon skipping, COL7A1 protein therapy, and revertant mosaicism are being investigated. There are many new approaches to therapy currently in trial. Clinical trials evaluating antifibrotic, anti-inflammatory, and antipruritic medications are in progress . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 8. Dystrophic Epidermolysis Bullosa: Recommended Surveillance

Source: GeneReviews — "Dystrophic Epidermolysis Bullosa"