Sir,
Wegener's granulomatosis (WG) is characterised as one of the ANCA-associated small vessel vasculitides and is not typically recognised as a disorder causing a cicatrising conjunctivitis.1 Mucous membrane pemphigoid (MMP) is a systemic autoimmune disease of progressive scarring of the mucous membranes. To our knowledge, occurrence of these two diseases, simultaneously, has been reported once previously2 with the indication that ocular involvement marked uncontrolled systemic autoimmune activity.
Case report
A 46-year-old African lady with a history of haemoptysis and atypical asthma complained of decreased vision in the left eye. Previous investigations for an underlying vasculitis had been negative. Multiple episodes of red sticky eyes had been noted by the physicians in the past and ophthalmic examination revealed bilateral giant conjunctival papillae with extensive ulceration, left lower conjunctival fornix shortening, and temporal anklyloblepharon with restriction of horizontal ocular movements (Figure 1a, b). Lid and lash position were normal and intraocular examination showed a cataract in the left eye. Clinical examination suggested MMP; however, there was no effacement of the caruncle. A conjunctival biopsy demonstrated no evidence of granulomatous inflammation, giant cells or vasculitis, however, autofluoresence study showed linear basement membrane immunoglobulin deposition (Figure 2a, b) consistent with MMP.
At the same time she had developed severe sinus congestion, recurrent heavy epistaxsis and dyspnoea and was under investigation by the otolaryngologists. Blood parameters revealed strongly positive serum cytoplasmic antineutrophil cytoplasmic antibody (cANCA) and nasal endoscopy showed active sinusitis with a small granuloma in left Little's area. She has a working diagnosis of limited WG with coexisting MMP.
She was pulsed with intravenous methyl prednisolone 1000 mg, started on cyclophosphamide 200 mg and oral steroids. She had immediate relief of nasal congestion and epistaxsis with gradual reduction of ocular surface inflammation with normalisation of cANCA levels.
Comment
Limited WG (which does not affect the major organs) has a strong and specific association with autoantibodies directed against proteinase 3 a constituent of neutrophil azurophilic granules.3 Previous identification of T cells in vessel walls points towards the pathogenesis being cell mediated.4 In all, 8–16% of new cases present with ocular involvement5 but overall orbital pseudotumors and scleral/corneal ulcerations are the most frequent presentations. Tarso-conjuctival disease is an uncommon clinical characteristic most commonly affecting the upper palpebral region,4 however, classic symblephara and fornix shortening has been described.4, 6
Clinically MMP is characterised by hyperaemia, acute inflammation, blisters, and ulceration (suggesting active, aggressive disease1) with the primary process not affecting the cornea but rather the conjunctiva. Auto-antibodies to the basement membrane zone at the epithelial–subepithelial junction of mucous membranes characterise this disease with laminin7 and integrin8 proposed as antigens, initiating a type II hypersensitivity reaction in the transmembrane hemidesmosomal area in the lamina lucida leading to subepithelial fibrosis, extensive xerosis and ultimately visual loss.
Both conditions involve the presence of circulating autoantibodies; however, the immunopathogenic mechanisms differ, suggesting that two disease processes are occurring in this patient. Fortunately in this case treatment of both conditions requires potent systemic immunosuppressive therapy but we stress, whenever possible, the importance of a tissue diagnosis.
References
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Shah, S., Larkin, G. Wegener's granulomatosis and mucous membrane pemphigoid: a diagnostic challenge of coexisting autoimmune disease. Eye 20, 856–858 (2006). https://doi.org/10.1038/sj.eye.6702030
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DOI: https://doi.org/10.1038/sj.eye.6702030