The complications caused by EBA include secondary skin infections, usually due to Staphylococcus or Streptococcus, because the blisters and erosions compromise the skin's barrier. Scarring and milia formation are naturally occurring complications or sequelae of the deep blistering process. Severe EBA patients may develop significant fibrosis of the hands with decreased range of motion of the palm and digits. Because of wounds and fibrosis of the soles of the feet and toes, some EBA patients have difficulty walking. Many patients with EBA lose their fingernails. EBA patients with significant mucosal involvement may develop esophageal strictures and even laryngeal scarring.
EBA usually responds poorly to treatment. Supportive therapy is warranted in all patients with EBA. This includes instruction in open wound care and strategies for avoiding trauma. Patients should be warned not to over wash or overuse hot water or harsh soaps and to avoid prolonged or vigorous rubbing of their skin with a washcloth or towel. In some patients, it appears that prolonged sun exposure may aggravate or promote new lesions on the dorsal hands and knuckles. Thus, avoidance of prolonged sun exposure and the use of sunscreens are helpful. The patient should be educated to recognize localized skin infections and to seek medical care and antibiotic therapy promptly when they occur.
EBA patients are often refractory to high doses of systemic glucocorticoids, azathioprine, methotrexate, and cyclophosphamide, especially when they have the classic mechanobullous form of the disease. These agents may be somewhat helpful in controlling EBA when it appears as an inflammatory BP-like disease. Some EBA patients improve on dapsone, especially when neutrophils are present in their dermal infiltrate.
Cyclosporine has been shown to be beneficial in EBA.27 However, the long-term toxicity of this drug limits its use.
There are also independent reports of EBA patients responding to high doses of colchicine.28 This is often used as a first-line drug because its side effects are relatively benign compared with other therapeutic choices. However, diarrhea is a common side effect of colchicine, which makes it difficult for many patients to achieve a high enough dose to control the disease. Moreover, because of this side effect, we are hesitant to use colchicine in EBA patients who also have inflammatory bowel disease. In addition, there are patients who do not respond to colchicine. Colchicine is a well-known microtubule inhibitor, but it also appears to have properties that have the potential to inhibit antigen presentation to T cells, which could downregulate autoimmunity.
Photopheresis has been used in Sézary syndrome, mycosis fungoides, and a variety of autoimmune bullous diseases (see Chapter 238). Photopheresis improves the clinical features of EBA and remarkably lengthens the suction blistering times of the patients, suggesting an improvement in their epidermal–dermal adherence.29
In addition to photopheresis, plasmapheresis and removal of the antibodies to type VII collagen in an EBA patient's plasma is useful for gaining control of EBA patients similar to pemphigus patients. Given that the autoantibodies are pathogenic, this is not surprising, but when plasmapheresis is performed it is necessary to have the patient also treated with a chemotherapy agent (such as azathiaprine, cyclophosphamide, mycotile mofelate, methotrexate).
Intravenous Ig has been used in dermatomyositis, an entity in which autoimmunity may play a role. Intravenous Ig has been reported to be effective in some patients with EBA.30 The mechanism by which γ globulin may invoke a positive response in EBA is unknown.
The anti-TNF-α biologics (such as infliximab; see Chapter 234) and anti-CD antibodies against B cells have been tried in EBA with some success in limited open trials. Box 60-2 outlines treatment options in EBA that have some support in the medical literature.
Box 60-2 Treatments for Epidermolysis Bullosa Acquisita (EBA) ||Download (.pdf)
Box 60-2 Treatments for Epidermolysis Bullosa Acquisita (EBA)
3 g/kg divided over 5 days
5 mg/kg at 0, 2, 4, and 6 week
Recently, anecdotal reports have also shown that, riuximab, a monoclonal antibody to the CD20 receptor on B lymphocytes is effective in treating recalcitrant patients with EBA.