Medication Summary
In epidermolysis bullosa acquisita (EBA), as in other autoimmune blistering diseases, treatment is directed at decreasing the development of new blisters, promoting healing, and preventing scarring and the sequelae of scarring.
The main goal of treatment is to modify or reduce the autoimmune response and decrease the production of autoantibodies. To date, only non–target-specific immunosuppressive and anti-inflammatory agents are available. There have been no randomized controlled trials to assess epidermolysis bullosa acquisita treatments. Most treatments are based on case reports and retrospective case series. Corticosteroids remain a mainstay of treatment, although many patients do not respond well and require various other immunosuppressants.
Prednisone doses commonly range from 0.5-1.5 mg/kg/day. [44] A retrospective analysis of 30 epidermolysis bullosa acquisita patients demonstrated that high-dose methylprednisolone (>8 mg/day) for at least 1 month achieved remission in 3 months as compared with remission in 12 months in those treated with a low dose (< 8 mg/day) methylprednisolone. [21]
Dapsone is an antibiotic as well as an anti-inflammatory agent used to treat non‒pathogen-related inflammatory diseases. It can be used as an adjunctive therapy to systemic corticosteroids, or as monotherapy. A review in 2011 summarized the treatment of 18 patients who received dapsone at doses of 25-100 mg/day or 1-2 mg/kg/day in conjunction with prednisone. Clinical improvement was noted in all 18 patients, of which half were able to discontinue steroid use. [45] A retrospective review in 2014 documented seven patients treated with dapsone (50-150 mg/day) in conjunction with corticosteroids. Two patients achieved complete remission and two patients achieved partial remission. Of note, adverse effects occurred in two patients, both at doses greater than 100 mg. [18]
Colchicine administration at a dose of 0.5-2.0 mg/day has been reported in 15 patients, both as a sole agent and in combination with other treatments. Some form of remission occurred in 13 of 15 patients, with a majority requiring maintenance therapy. [18, 45] Diarrhea is a common adverse effect. Colchicine may have an improved overall adverse effect profile compared with other agents, particularly if they have limited efficacy. As such, it can be considered a first-line agent for mild cases. [46]
Immunosuppressives are used in patients with severe disease. Azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, and cyclosporine have all been described as treatments in small case reports and case series. Immunosuppressive agents can be used in combination with steroids or other anti-inflammatory treatments. [44, 45]
Azathioprine is the most commonly used adjunctive agent. However, its documented efficacy is limited, and, owing to multiple adverse effects such as hepatitis, leukopenia, and pancreatitis, it may be a suboptimal choice. [47]
Methotrexate has not been studied directly in patients with epidermolysis bullosa acquisita, but its efficacy for bullous pemphigoid suggests that it could be incorporated into a treatment regimen. A dose of 20-25 mg weekly would be suggested when used in conjunction with other immunosuppressives. The adverse effect profile of anemia, nausea, and potential infection is documented. [48]
Mycophenolate mofetil may be an effective adjunct, or as a steroid-sparing monotherapy. Randomized clinical trials for adjuvant therapy used in patients with bullous pemphigoid suggest a moderate adverse effect profile, but not of significant difference from that of azathioprine when used in conjunction with systemic corticosteroids. [47] However, in one case-series study, some patients were effectively treated with mycophenolate mofetil as a steroid-sparing approach. [49]
Extracorporeal photochemotherapy (photophoresis) has been shown to be effective in three of four patients after three to six cycles of treatment. [45]
Rituximab is an anti-CD20 monoclonal antibody that has resulted in complete resolution in a 2018 retrospective analysis. [47] Most commonly, it was used as 375 mg/m2 weekly for a total of 4 weeks. This is a promising agent that has also shown efficacy in reduced development of antigen-specific CD4+ T cells in animal models. [50] In one study of seven patients with refractory disease, rituximab resulted in clinical improvement in five of seven patients. [18]
Intravenous immunoglobulin (IVIg) may be an option in severe disease. A 2011 review documented 15 cases of IVIg use in patients mostly with severe widespread refractory disease. Clinical improvement was noted in 14 of 15 patients. Thirteen of 15 patients remained on IVIg for maintenance treatment. [45] A 2012 retrospective case series demonstrated similar clinical response rates, but suggested IVIg may induce a more sustained remission. [51] Ten patients, all nonresponsive to conventional treatments, were started on 2 g/kg/cycle of IVIg for a mean of 23 cycles over 39 months. All 10 demonstrated clinical response and were able to completely withdraw their previous therapy; no recurrence was observed during a mean follow-up period of 54 months after cessation of treatment.
Anti-inflammatory agents
Class Summary
In the inflammatory form of epidermolysis bullosa acquisita (EBA), there may be an inflammatory cell infiltration near the basement membrane zone. Theoretically, anti-inflammatory agents would block the inflammatory process and improve the disease. Prednisone, dapsone, and colchicine all have been reported to induce clinical improvement.
Prednisone (Deltasone)
Prednisone is used as a sole agent or in conjunction with other medications (eg, immunosuppressives) to treat epidermolysis bullosa acquisita (EBA). It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Dapsone (Avlosulfon)
Dapsone is bactericidal and bacteriostatic against mycobacteria; its mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent the formation of folic acid, inhibiting bacterial growth. It is used in conjunction with other anti-inflammatory medications and immunosuppressives. In children, physicians should consult the patient's pediatrician before prescribing this medication.
Colchicine (Colcrys, Mitigare)
Colchicine is an anti-inflammatory agent that disrupts cytoskeletal functions by inhibiting B-tubulin polymerization, preventing neutrophil activation, degranulation, and migration.
Photophoresis agents
Class Summary
Extracorporeal photochemotherapy (photophoresis) a therapeutic method that uses ultraviolet-sensitizing medication (psoralen) and extracorporeal ultraviolet A irradiation of the sensitized WBCs. The photoinactivated cells are reinfused into the patient.
Methoxsalen (8-MOP, Oxsoralen)
Methoxsalen inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by ultraviolet A.
Biological response modulators
Rituximab (Rituxan)
Rituximab is a monoclonal antibody that specifically targets the immune cell surface marker CD20, which is primarily expressed by B lymphocytes.
Immune Globulins
Immune globulin IV (IGIV) (Bivigam, Carimune, Carimune NF)
IVIg is a purified preparation of gamma globulin. It is derived from large pools of human plasma with four subclasses of antibodies, approximating the distribution of human serum. They may decrease autoantibody production and increase solubilization and removal of immune complexes.
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Direct immunofluorescence performed on perilesional skin biopsy specimen from a patient with epidermolysis bullosa acquisita detects a linear band of immunoglobulin G deposit along the dermoepidermal junction.
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Indirect immunofluorescence performed on salt-split normal human skin substrate using serum from a patient affected with epidermolysis bullosa acquisita detects immunoglobulin G class circulating autoantibodies that bind to the dermal (base) side of the basement membrane.
