Epidermolysis bullosa acquisita (EBA) is an autoimmune mucocutaneous blistering disease.1, 2 Cutaneous involvement presents with blisters primarily on trauma-prone areas healing with milia.1, 2 Mucosal involvement can lead to irreversible scarring. The treatment of EBA is based on anecdotal reports in the literature with systemic therapies.3, 4, 5, 6, 7 Mycophenolate mofetil (MMF) is an immune-suppressing agent that has been reported to be effective in the treatment of autoimmune mucocutaneous blistering diseases.3, 4, 8, 9, 10, 11 This report describes the successful treatment of 4 patients with EBA using MMF as a steroid-sparing agent at our center along with a long term follow-up.
Case series
This retrospective study consisted of 4 patients with EBA treated with MMF, and was conducted with the approval of the institutional review board of the University of Alabama at Birmingham. The diagnosis was confirmed in all 4 patients with a skin biopsy specimen, immunopathology, and serology.1, 2 Skin biopsy specimens demonstrated a subepidermal split with a mixed inflammatory infiltrate on routine histology, and IgG binding along the basement membrane zone on direct immunofluorescence. Serological studies with indirect immunofluorescence demonstrated antibasement membrane zone antibodies using monkey esophagus as substrate and autoantibody binding to the dermal side of the salt-split skin. The response to MMF treatment was assessed based on the following criteria: (1) healing of involvement of the initial presentation; and (2) absence of new lesions. Complete control was defined as patients meeting both response criteria 1 and 2 and discontinuing systemic corticosteroids. Partial control was defined as patients meeting only criteria 1 and being unable to discontinue steroids.
Two patients were male and 2 were female. The age at onset ranged from 48 to 86 (mean 61) years. All patients had both mucosal and cutaneous involvement. The most common areas of mucosal involvement included oral (4), nasal (4), pharyngeal (2), and laryngeal (1). The patient with laryngeal involvement required a tracheostomy. Cutaneous involvement was present on the extremities and acral surfaces and amount of body surface area involvement is presented in Table I.
Table I.
Clinical features, prior treatments, and mycophenolate mofetil treatment of epidermolysis bullosa acquisita
| Age at onset, y/gender | Clinical features (mucosal/cutaneous BSA) | Prior treatments to MMF | Duration of prior treatments, mo | MMF (maximum) dosage for control, g/d | Response |
|---|---|---|---|---|---|
| 48/F | Oral, nasal, pharyngeal, laryngeal 20% BSA |
Prednisone (40 mg/d) | N/A | 2 | Complete control |
| 53/F | Oral, nasal, pharyngeal 20% BSA |
Prednisone (40 mg/d) Dapsone (100 mg/d) Azathioprine (100 mg/d) |
16 | 3 | Complete control |
| 56/M | Oral, nasal 20% BSA |
Prednisone (60 mg/d) Tetracycline (2 g/d) Dapsone (200 mg/d) Colchicine (1.2 mg/d) Azathioprine (200 mg/d) |
24 | 3 | Partial control |
| 86/M | Oral, nasal 30% BSA |
Prednisone (60 mg/d) Dapsone (100 mg/d) Colchicine (1.2 mg/d) |
26 | 2 | Complete control |
BSA, Body surface area involved (cutaneous); F, female; M, male; MMF, mycophenolate mofetil; N/A, MMF was started with prednisone.
All patients were initially treated with prednisone with dosages ranging between 40 and 60 mg/d. Steroid-sparing agents before MMF included the following with their dosages: azathioprine (100-200 mg/d), dapsone (100-200 mg/d), colchicine (0.6-1.2 mg/d), and tetracycline (2 g/d). The duration of systemic treatments before starting MMF ranged between 16 and 26 (mean 22) months. All 4 patients received MMF with a dosage ranging between 2 and 3 g/d. An effective response to MMF was observed after 4 to 12 (mean 7) months and the dosage of prednisone was gradually reduced. Three patients achieved complete control and 1 patient had partial control because he was unable to taper below 10 mg/d of prednisone. However, this was the lowest dosage he was able to achieve after failing to respond to previous treatments. The details of each patient are presented in Table I. Local supportive care was also recommended including avoiding trauma and infection, and the use of the following topical corticosteroid creams to affected areas to facilitate healing: triamcinolone 0.1%, betamethasone diproprionate 0.05%, and halobetasol propionate 0.05%. After a mean follow-up period of 9 years (range 4-12 years) only 1 of the 4 patients was able to discontinue MMF.
Discussion
MMF is an immune-suppressing agent that has been used in the treatment of autoimmune mucocutaneous blistering disease.3, 4 However, there are very few case reports that have described its use in EBA.8, 9, 10, 11
This study described 4 patients who were successfully treated with MMF for extensive involvement with EBA. MMF was instituted as a steroid-sparing agent after failure of response was observed to multiple conventional treatments. Three of the 4 patients were able to completely discontinue systemic corticosteroids and establish complete control of their disease with just MMF as monotherapy. This included 1 patient with laryngeal involvement requiring a tracheostomy who is currently only taking MMF at 500 mg/d as monotherapy while maintaining complete control. She has also underwent successful removal of her T-tube and repair of the open anterior tracheal wall with no further issues with breathing or swallowing and her voice has remained stable.
Although the precise mechanism of action of MMF in EBA is unclear, MMF is an immune suppressant that has been shown to inhibit the proliferation of B and T lymphocytes.4 This could lead to a decrease in the production of autoantibodies, specifically to collagen VII, resulting in clinical control of the disease.
MMF has been reported to have multiple side effects including gastrointestinal, genitourinary, infectious, and neurologic.3 Two of our patients reported gastrointestinal side effects when they were taking dosages greater than 2.5 g/d and resolved in both patients when the dosage was reduced to 2 g/d.
Because EBA is a chronic disease, the length of therapy can vary widely. We have been unsuccessful in discontinuing MMF as monotherapy in 2 of the 3 patients in the complete control group. An attempt to slowly taper the MMF in 1 patient when she had been stable at 2 g/d for 2 years resulted in an exacerbation with nasal involvement and localized scarring after reaching a dosage of 500 mg/d. Complete control of the disease was re-established in this patient by increasing the dosage of MMF to 2 g/d. Hence, MMF may be necessary as long-term maintenance treatment in some patients.
There are several limitations to this study including a very small cohort of patients and lack of a control group. The use of MMF is also limited by the higher cost of the medication compared with other oral conventional alternative agents. Because treatment choices are limited, MMF could still be a viable alternative for patients with EBA who have contraindications to or failed other systemic therapies. Larger multicenter randomized controlled trials are needed to evaluate the efficacy and role of MMF for the treatment of EBA.
Footnotes
Funding sources: None.
Conflicts of interest: None declared.
References
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