Although there have been many different mutations in 19 different genes demonstrated to cause epidermolysis bullosa (EB) , common denominators within most forms of EB are trauma-induced blistering followed by an inflammatory response and eventual wound healing. As this cycle of events is repeated frequently, with more inflammation and longer healing times dependent on the degree of trauma, the amount of adhesion protein loss and the location of the proteins affected, different complications arise in the skin, mucous membranes and internal organs.
Whilst specific targeted therapies, such as gene, protein and cell therapies are underway in trials or pre-clinical work for certain types of EB, another approach is to target the downstream common inflammation to reduce complications.
The enzyme matrix metalloproteinase 1 (MMP1) has an isoform in the population which results in overactivity, leading to increased degradation of collagen substrate in the dermis. Already variations in this unrelated gene have been shown to modify the phenotype in recessive dystrophic EB which had the same collagen 7 defects in 3 brothers, one with a severe phenotype and overactive MMP1 and another with a mild phenotype, with normal MMP1. The commonly used anti-inflammatory agent, doxycycline and minocycline, are MMP1 inhibitors. They have been used ad hoc in reducing inflammation in EB but not in a formal RCT.
Colonization with bacteria, both gram positive and gram negative, is very common in EB. The sulfa antibiotic, trimethoprim, can reduce bacterial load and thus, inflammation. It was trialled in an RCT vs placebo for EB simplex, finding that whislt taking it, the patients improved. Collaborative studies have shown that colonization of wounds with flagellated gram negative organisms, such as E Coli, are carcinogenic in RDEB patients, resulting in aggressive SCC. Thus, reducing carriage of this organism might reduce inflammation and SCC in thi s patient population.
Colchicine, which inhibits the mitotic spindle and reduces cell proliferation, has also been helpful in one of our severely ill Junctional EB patients. Likewise, thalidomide maintained the eyesight of another of our JEB patients and prolonged the life of another adult JEB patient.
There are current RCTs being conducted for new topical anti-inflammatory agents for EB, including an allantoin cream, and creams derived from the birch bark tree (oleogel) and the rhubarb plant, diacerein. Our group is conducing an RCT of topical sirolimus for EB simplex, since it can reduce overexpression of Keratin 5. It is still debatable whether low dose systemic steroids should be tried in EB since they have many long term side effects.