Abstract

Background

Mucous membrane pemphigoid and epidermolysis bullosa acquisita are rare acquired autoimmune blistering diseases of the skin. Both can result in scarring of mucous membranes which may lead to blindness and life threatening respiratory complications.

Objectives

To assess the effects of treatments for mucous membrane pemphigoid and epidermolysis bullosa acquisita.

Search methods

We searched the Cochrane Skin Group Specialised Register (7th April 2005), the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2005), MEDLINE / PubMed (from 1966 to April 2005), EMBASE (from 1980 to April 2005), www.controlled‐trials.com (7th April 2005) and www.clinicaltrials.gov (7th April 2005) and reference lists of articles.

Selection criteria

Randomised controlled trials of any treatments for mucous membrane pemphigoid or epidermolysis bullosa acquisita involving participants of any age with a diagnosis of either disease confirmed by immunofluorescence.

Data collection and analysis

The data was independently extracted by three authors and subsequently checked for discrepancies. Two authors evaluated the studies in terms of the inclusion criteria.

Main results

Two small randomised controlled trials of mucous membrane pemphigoid, both conducted in participants with severe eye involvement were identified.

In the first trial, involving 24 participants, cyclophosphamide 2 mg/kg/day in combination with prednisone starting at 1 mg/kg/day and tapering was superior to prednisone alone (1 mg/kg/day) after 6 months of treatment. All 12 participants responded well to cyclophosphamide plus prednisone versus a good response in only 5 of 12 participants treated with prednisone (relative risk 2.40, 95% confidence interval 1.23 to 4.69).

In the second trial, involving 40 participants, all 20 participants treated with cyclophosphamide (2 mg/kg/day) responded well after three months of treatment, but only 14 of 20 participants responded to treatment with dapsone (2 mg/kg/day) (relative risk 1.43, 95% confidence interval 1.07 to 1.90). All non‐responders had severe inflammatory activity. It was not explicitly stated whether these participants received prednisone in addition to dapsone or cyclophosphamide initially. Hair loss and suppression of the red and white blood cells were common adverse events in the cyclophosphamide groups.

No randomised controlled trials of treatments for epidermolysis bullosa acquisita were identified.

Authors' conclusions

There is limited evidence that mucous membrane pemphigoid involving the eyes responds best to treatment with cyclophosphamide combined with corticosteroids. However, mucous membrane pemphigoid with mild to modest inflammatory activity responds to dapsone in most participants and may therefore be best treated with dapsone due to its lower side effect profile compared to cyclophosphamide. Treatment with mycophenolate mofetil combined with topical steroids seems worth considering in a future randomised controlled trial for mucous membrane pemphigoid.

Author(s)

Gudula Kirtschig, Dedee F Murrell, Fenella Wojnarowska, Nonhlanhla P Khumalo

Abstract

Plain language summary

Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita (rare autoimmune blistering diseases of the skin, eyes and mouth)

Mucous membrane pemphigoid and epidermolysis bullosa acquisita are rare autoimmune blistering diseases of the skin and mucous membranes (eyes and mouth). They can result in scarring, which may lead to disabling and life threatening complications. Treatments include corticosteroids, mycophenolate mofetil and cyclophosphamide to suppress the immune system, and less toxic drugs such as antibiotics. These diseases often progress despite treatment. There is some evidence that mucous membrane pemphigoid involving the eyes may respond better to treatment with cyclophosphamide combined with corticosteroids, compared to treatment with corticosteroids alone. Cyclophosphamide is, however, associated with potentially severe adverse effects. Dapsone may help moderate disease. More research is needed to identify the most effective treatment options.There is not enough reliable evidence about treatments for the rare blistering diseases, mucous membrane pemphigoid and epidermolysis bullosa acquisita.

Author(s)

Gudula Kirtschig, Dedee F Murrell, Fenella Wojnarowska, Nonhlanhla P Khumalo

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Based on these two identified RCTs:- 1. In MMP involving the eyes, cyclophosphamide in combination with short term corticosteroids may be more effective in suppressing inflammation of the conjunctiva and progression of scarring than long‐term corticosteroids or dapsone; however, both cyclophosphamide and corticosteroids may have severe adverse effects in the long term.- 2. In MMP with mild to modest inflammation involving the eyes, dapsone may be an effective first choice treatment in most patients, because the adverse effect profile of dapsone is more tolerable for most patients compared to cyclophosphamide and long term corticosteroids. Serious adverse effects in dapsone are very rare; they are only reported in single case reports.- No reliable evidence‐based recommendation can be given for the treatment of EBA.

Implications for research 

More research is urgently required. As MMP and EBA are rare diseases, international multicentre RCTs involving larger numbers of participants may be necessary to assess the best treatment for these diseases. Also, collaborating to improve the collection of case data would be worthwhile in order to overcome the many deficiencies of case series due to the possibility of selection bias; comprehensive case detection alleviates this.- Treatments with anti‐inflammatory antibiotics such as tetracycline, minocycline, and newer medications like anti‐TNF alpha antibodies might be as effective as dapsone and have the benefit of fewer adverse effects, and are worthy of further investigation. For example a RCT for the treatment of bullous pemphigoid suggests some merit in the use of tetracycline and nicotinamide (Fivenson 1994).

Treatment with Mycophenolate mofetil (MMF) combined with topical steroids seems worth considering in a future RCT.

RCT suggestion: Mycophenolate mofetil plus topical corticosteroids versus dapsone plus topical corticosteroids (or versus cyclophosphamide plus topical steroids) in moderate and severe MMP.

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