Sir,

Ocular mucous membrane pemphigoid (MMP) is a rare and challenging condition due to lack of a comprehensive therapeutic evidence base. We describe successful treatment of severe ocular MMP with anti-tumour necrosis factor-α (TNF-α).

Case report

A 55-year-old gentleman, with transitional-cell bladder cancer 8 years previously, presented with bilateral painful, red, and watery eyes. Examination revealed bilateral inferior fornix symblepharon with active subconjunctival vascular leading edge and progressive loss of inferior fornices. Conjunctival biopsy showed lymphocytes, plasma cells, and leukocytes infiltration with goblet cell depletion consistent with MMP. Immunofluorescence studies were not performed. Cyclosporine eye drops were given for lid margin inflammation. Systemic treatment commenced with dapsone, at which point there was 25% loss of fornix depth. Despite courses of 20–40 mg oral prednisolone with azathioprine and then mycophenalate mofetil, the acute flare continued. Loss of fornices progressed to 50% (Figure 1a). Cyclophosphamide was contraindicated (its metabolite acrolein causes haemorrhagic cystitis and increased risk of bladder cancer). Etanercept anti-TNF-α was commenced (50 mg weekly self-administered subcutaneously). Both eyes responded allowing immediate decrease of the 20 mg prednisolone (Figure 1b). He remains on long-term etanercept; the prednisolone dose decreasing by 1 mg/month. Eighteen months later there have been no flares.

Figure 1
figure 1

(a) Active ocular MMP. (b) Resolving disease activity 8 weeks after commencing anti-TNF-α treatment.

Full size image

Comment

MMP is a heterogeneous group of autoimmune, inflammatory, subepithelial blistering diseases affecting mucous membranes that heal with scarring.1 Ocular MMP presents with conjunctival inflammation, symblepharon, and (in one-third of patients) visual impairment. The visual prognosis is poor; corneal scarring and keratinisation may cause blindness.1, 2

Mild disease is observed. Moderate disease may be suppressed by dapsone.2 More extensive and progressive scarring disease requires systemic therapy (prednisolone and immunosuppressants). There is evidence for azathioprine, methotrexate, leflunomide, mycophenolate mofetil, and intravenous immunoglobulin.1, 2 However, for severe/rapidly progressive disease (particularly eye or larynx where inadequately treated disease may be devastating), cyclophosphamide with corticosteroids is recommended as first-line treatment.1, 2

Advances in other autoimmune inflammatory conditions have shown biologic treatments to be effective. A systematic review of biologic therapies for inflammatory eye disease highlighted dramatic remissions in ocular inflammation.3 Most literature relates to uveitis; inflammatory eye diseases are heterogeneous and research is required to establish which subtypes are responsive.3 Research in MMP characterising its autoantibody profile supports the potential use of monoclonal antibodies. There are reports describing the successful use of anti-TNF-α therapies4, 5 and daclizumab (reviewed in Lim et al3).

With rare conditions where treatment is challenging, collating reports of success with novel biological agents is important. We support the development of a patient database1 for longitudinal follow-up to monitor efficacy and side effects of such treatments.