Infliximab in serpiginous choroiditis

Abstract

Editor, S erpiginous choroiditis (SC) is a chronic, recurrent, progressive inflammation of the choroid and choriocapillaris that involves the retina secondarily (Weiss et al. 1979). The disease has been presumed to be autoimmune; corticosteroids and immunosuppressants constitute the mainstay of its therapy. In this article, we describe a patient with refractory SC with a long-term and safe response to infliximab. In October 2005, a 43-year-old man presented sudden photopsias and paracentral scotoma affecting his right eye. Examination revealed a diminished visual acuity of 20 ⁄ 60 for his right eye. On ophthalmological examination, the anterior segment appeared quiet, whereas funduscopic examination and fluorescein and indocyanine green angiographies revealed clinical pictures, on both eyes, compatible with SC (Fig. 1). Imaging tests (including chest computed tomography scan), purified protein derivative skin test, quantiFERON testing and extensive laboratory investigations were performed with negative results. The diagnosis of SC was established, and methylprednisolone followed by prednisone (1 mg ⁄kg ⁄day) associated with three-drug antituberculous therapy was started with a relapse 1 month later. Intravenous cyclophosphamide was then initiated. A good clinical, funduscopic and angiographic response was observed after six cycles. Cyclophosphamide was then stopped while mycophenolate mofetyl (2 g ⁄ day) was started and prednisone was reduced gradually to 17.5 mg. One month later, the patient had a new relapse on his right eye that was treated successfully with high-dose intravenous steroid therapy. Cyclosporine A (5 mg ⁄kg ⁄day) was then started. Three months later, while on cyclosporine, prednisone 60 mg ⁄day, isoniazid and rifampicin, an ophtalmological examination angiography showed signs of active inflammation of his right eye. A three-dose of infliximab (days 0, 15 and 45) at 5 mg ⁄kg was then initiated while cyclosporine was stopped. A good clinical, funduscopic and angiographic response was observed as early as the first course (Fig. 2). Our patient then received infliximab every 8 weeks, and prednisone was reduced gradually to 5 mg. Isoniazid and rifampicin were stopped in November 2007. At December 2008, after 15 infliximab infusions, our patient was healthy, with no relapse of his ocular condition. There is evidence of the involvement of Mycobacterium tuberculosis (MT) in the pathogenesis of SC. Gupta et al. (2003) presented seven patients with serpiginous-like choroiditis who all were skin-test-positive and had chest x-ray abnormalities; polymerase chain reaction (PCR) for MT was positive from ocular fluids in five patients. In a more recent study, 21 patients with SC were tested with QuantiFERON, which is an approved, antigen-specific test that utilizes synthetic peptides representing MT proteins (Mackensen et al. 2008). Eleven of these patients were tested positive and three improved with antituberculous therapy. Tumour necrosis factor-a (TNF-a) blockade with monoclonal antibody, as infliximab or adalimumab, is very useful in the treatment of many cases of refractory uveitis (Theodossiadis et al. 2007). However, anti-TNF therapy may be associated with severe toxicities, foremost of which is tuberculosis reactivation (Lin et al. 2008). Given the possible association between SC and tuberculosis, the highly increased risk of tuberculosis with anti-TNF agents is critical in decision-making. Some authors recently described a patient suffering from presumed SC who died of disseminated tuberculosis after a four-dose course of infliximab therapy (Cordero-Coma et al. 2008). Several factors can explain the opposite evolution of our two patients. Firstly, in the case reported by Cordero-Coma et al. (2008), a tuberculous-specific gamma interferon test was performed in a patient receiving long-term immunosuppression whereas we applied quantiFERON at the initial presentation. Immunosuppressive treatments can reduce interferon-c responses and lead to false-negative results (Mackensen et al. 2008). Secondly, their patient did not receive antituberculous therapy before starting infliximab. In conclusion, our case report suggests that infliximab could be used, in a cautious way, in patients with refractory SC. Before using antiTNF therapy, we recommend an extremely low index of suspicion of tuberculosis and that patients previously receive antituberculous chemotherapy. Fig. 1. Active lesion of the right eye showing blocked fluorescein early (46 seconds) with indistinct margins. View of the fundus at presentation showing a large serpiginous lesion surrounding the optic disc and extending to the macular area.