026. Cyclophosphamide, A Sight for Sore Eyes: A Case of Refractory Uveitis Successfully Treated with Cyclophosphamide

Abstract

Background: Anterior uveitis is the commonest manifestation occurring in a quarter to half of paediatric uveitis(3). Uveitis can lead to devastating disability if left untreated and requires quick and aggressive management. Sarcoidosis is a multisystem granulomatous disorder with an unknown aetiology. Paediatric sarcoidosis has a varied presentation(1). As with most chronic inflammatory diseases the key cytokines involved in the process are tumour necrosis factor-alpha (TNF-), interferon gamma and interleukin (IL)-2 and IL-12(3). In sarcoidosis these cytokines are thought to be secondary to CD4+ and CD8+ activity resulting in granuloma periphery(4). Older children present with similar features to that of adult onset sarcoidosis while patients < 4yrs present have a triad of uveitis, symmetrical arthritis and rash(2). Of note within the presenting features, uveitis or ocular involvement is common in childhood sarcoidosis. This is a case presentation of a ten year old boy (AO) who had been diagnsoed with Sarcoidosis at the age of 2 years. AO developed anterior uveitis, early, which persisted despite the use of two different anti-TNF agents. Methotrexate was started at diagnosis and continued throughout. AO also continued to have troublesome skin with intermittent episodes of nodules and abscesses. This childs eyesight was becoming significantly affected, with loss of central vision, due to macular oedema. Cyclophosphamide was introduced in view of the failure of response to anti-TNF agents, Infliximab and Adalimumab (in this respective order) and the concern regarding sight loss. The response was almost immediate with resolution of skin exacerbations and the uveitis. AO did not suffer any of the side effects associated with cyclophophamide. Our patient is registered partially sighted (acuity 0.84 left, 0.78 right eye, with good peripheral vision), but it is clear the use of cyclophosphamide at the right time has preserved his overall sight allowing him to do well academically and grow, as the inflammation in the eye was effectively arrested. Aims: Paediatric Sarcoidosis treatment methods might be complicated by refractory uveitis, despite good control of other elements of disease such as rash. We aim to present a case of refractory uveitis in sarcoidosis which was successfully treated with cyclophosphamide. The choice to use cyclphosphamide was mde based on the poor response to conventional treatment with adalimumab and infliximab and with concern for the patient's vision. This child had already undergone a lensectomy for bilateral cataract and had lost central vision. We wish to present this unique case to explore the option of cyclophosophamide use in uveitis earlier in the patients journey, to prevent further vision loss. Methods: Electronic and physical patient notes were reviewed. Collaboration occured with the ophthalmology team to collate accurate information about treatment pathway and reasoning behind management decisions. A literature search on current practice and use of cyclophophamide in the treatment of uveitis in sarcoidosis was carried out. There are very few examples of successful use of cyclophosphamide in refractory uveitis in sarcoidosis. Results: This is a unique case of a 10 year old bangladeshi boy (AO), where cyclophosphamide was used for the treatment of refractory uveitis with sarcoidosis, at a point of sight threatening disease. The patient had a very good response without the anticipated side effects, related to cyclophophamide. This was preceded by a difficult journey to control his uveitis activity and rash. AO's overall vision has been preserved and his rash has much improved following the introduction of the quicker acting cyclophosphamide and continues to do well on a maintenance of 10 weekly infliximab. Conclusions: Although there are warranted concerns regarding use of cyclophosphamide in young patients there seems to be benefit in the quick clinical response gained. The response of this patient presents a real possiblity for cyclophosphamide to be used in refractory uveitis, where anti-TNF has failed. This has preserved vision and bought time to restart the safer long term treatment with infliximab or adalimumab. Patient AO is currently enjoying a successful school career at a prestigious grammar school, following effective treatment with cyclophosphamide.