Dystrophic epidermolysis bullosa (DEB) is a group of rare inherited diseases that cause skin fragility and blistering. A recent classification includes 3 subtypes: severe generalized recessive DEB (RDEB-sev gen), generalized other recessive DEB (RDEB-O), and dominant DEB (DDEB). DEB occurs because of a type VII collagen defect in the anchoring fibrils in the epidermal-dermal junction (in the lamina densa of the cutaneous basement membrane). Both the recessive and dominant variants stem from a mutation in the type VII collagen gene COL7A1. The recessive variant, RDEB-sev gen, is perhaps the most catastrophic and tragic. There is some literature that indicates an occasional de novo mutation, but generally it is inherited.

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RDEB-sev gen, once called Hallopeau-Siemens type RDEB or (RDEB-HS), is the most severe form of DEB, with symptoms presenting at birth. The skin is extremely fragile and painful; milia formations are common (tiny white cysts). Simple trauma such as a slight bump or even an abrupt change in temperature can cause blistering, and patients are pruritic (excessively itchy), which presents further complications. The mucosal membranes are not spared from this fate—the linings of their mouths, noses, and intestines also blister regularly. On the bodies of RDEB-sev gen individuals, extensive scarring and deformities trace the disease’s progression and serve as an indelible record of the pain they have endured.

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Because of the constant blistering and scarring, pseudosyndactyly, or “mitten deformities,” are a horrific reality for these individuals. Essentially, they may develop webbed fingers or toes; or worse, their digits may fuse into a single mass. Scarring may cause the opening of their mouths to become smaller (microstomia) and their oral vestibule (the space between the cheeks/lips) to be obliterated. They may develop tongue abnormalities, and in some instances, their tongues may fuse to the floor of their mouths. Because of oral complications and scarring within the esophagus, creating webs and strictures, dysphagia (difficulty in swallowing) has been reported. As a result, severe nutritional deficiencies are a secondary hazard in RDEB-sev gen. Progressive blindness due to corneal erosions has been reported, and rapid tooth decay may occur because of thinning tooth enamel and cementum problems. Nail deformities and hair loss are also common. The most troubling aspect of RDEB-sev gen is an increased lifetime risk (over 90%) of developing aggressive squamous cell carcinoma.

Watch this short clip from the documentary The Boy Whose Skin Fell Off. It is about Jonny Kennedy, a 36 year old who suffered from this horrific condition all his life. He died on September 26, 2003, a year before the documentary aired in the UK.

Presently there is no treatment for this horrific disease. Prevention and management are typically the only options. Aggressive wound treatment is the standard of care and includes constantly cleaning and dressing wounds as well as employing antibiotics to prevent infections. There is some literature that discusses immunomyeloablative chemotherapy and allogeneic stem cell transplantation as offering some measure of relief. A small study followed 6 patients and describes improved wound healing and reduced blistering between 30 and 130 days after the procedure. Increased deposits of collagen type VII and a sustained presence of donor cells were also observed. One patient died after 183 days because of graft-vs-host issues. The future may hold some promise. Gene therapy and the use of retroviral vectors (RVs), lentiviral vectors (LVs), and non-viral vectors may eventually offer a cure. Currently, research into RVs has demonstrated that COL7A1 cDNA may be transferred into keratinocytes of RDEB and have a corrective effect on the genetic defect. Research into LVs has also demonstrated similar promise, as has cell therapies. With a little bit of luck, perhaps one day there will be no other stories like that of Jonny Kennedy.

Reference

  1. Dang N, Murrell DF. Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa. Exp Dermatol. 2008;17(7):553-568. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2008.00723.x/pdf.
  2. Das BB, Sahoo S. Dystrophic epidermolysis bullosa. J Perinatol. 2004;24(1):41-47.
  3. Dystrophic epidermolysis bullosa. Genetics Home Reference Web site. Reviewed January 2008. http://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa.
  4. Dystrophic epidermolysis bullosa. Orphaned Web site. Updated March 2013. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=303.0.
  5. Pfendner EG, Lucky AW. Dystrophic epidermolysis bullosa. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, eds. SourceGeneReviews. Seattle, WA: University of Washington, Seattle. Published August 21, 2006; updated November 4, 2010. http://www.ncbi.nlm.nih.gov/books/NBK1304/.
  6. Wagner JE, Ishida-Yamamoto, McGrath JA. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010;363:629-639. http://www.nejm.org/doi/pdf/10.1056/NEJMoa0910501.

Topics:

General Dermatology Rare Conditions Rare Disease