039. INTERFERON-ALFA USED TO TREAT A CHALLENGING CASE OF REFRACTORY PAEDIATRIC BEHÇETS DISEASE WITH SIGHT-THREATENING UVEITIS

Abstract

Background: Behçets disease (BD) is an idiopathic, multi-system disorder of a vasculitic nature, characterized by mouth and genital ulcers, rash, arthritis and uveitis. Ocular manifestations occur in up to 80% of patients with BD with 30% risk of blindness. We present a challenging paediatric case of BD-associated bilateral pan-uveitis and aggressive refractory uveitis affecting the left eye. Methods: An 11 year-old girl presented acutely with a three-day history of a painful red left eye and blurred vision. Examination revealed bilateral uveitis with optic disc swelling, cystic macular oedema (worse in left eye), 2+ and 3+ cells in her right and left eyes respectively (Standardization of Uveitis Nomenclature classification) with snowballs and reduced visual acuity. A two-year history of mouth and genital ulcers was given and at presentation mild peripheral-joint arthritis was detected. Initial treatment with intravenous methylprednisolone, intensive steroid eye drops and subcutaneously administered methotrexate (15mg/m2) was commenced. Infliximab (6 mg/kg intravenously 4-weekly) and mycophenolate mofetil (600mg/m2 orally twice-daily) were subsequently added for multi-focal chorioretinitis in the left temporal retina. Infliximab was changed to tocilizumab (8mg/kg intravenously 2-weekly) in response to uveitis flares and reduced vision as a result of persisting chronic cystoid macular oedema. Subsequently tocilizumab was changed to adalimumab (40mg subcutaneously fortnightly), however a pattern of repeated sight-threatening uveitis flare-ups and persisting cystic macular oedema. Fifteen months after initial presentation mycophenolate mofetil and adalimumab were substituted for pulsed intravenous cyclophosphamide (initially 500mg/m2 fortnightly, increasing to 1g/m2 3-weekly; total 6 doses) for pseudo-hypopyon, recurrent widespread multi-focal chorioretinitis and acute sight loss (6/60). Multiple pulses of intravenous methylprednisolone and oral prednisolone were given throughout the treatment course in response to repeated flare-ups of inflammation associated with reduced visual acuity due to macular oedema. Despite cyclophosphamide treatment further severe flare-ups of eye disease complicated by pseudo-hypopyon, optic-disc swelling, multi-focal choroiditis and pseudo-necrotizing retinitis occurred. Following cyclophosphamide, interferon-alfa-2A (3 million units subcutaneously daily) was commenced resulting in sustained and complete remission of eye inflammatory features including previously refractory cystic macular oedema; vision improved significantly to 6/9+. To date interferon-alfa has been well tolerated and demonstrated clinical effectiveness from the first week. Throughout the treatment pathway we collaborated with colleagues in national centres of expertise for paediatric BD and uveitis. Results: Interferon-alfa has controlled intraocular inflammation, led to reduced macular oedema and improved vision; to date the patient remains in remission from uveitis. In this case interferon-alfa has been well tolerated but other BD manifestations (mouth and genital ulcers and arthralgia) have worsened. Conclusion: Interferon-alfa was successful in treating this child's panuveitis and cystoid macular oedema, which previously had proved refractory to multiple immunosuppression agents. To the best of the authors' knowledge, this is the first UK case of paediatric BD-uveitis treated with interferon-alfa.