Optic neuritis associated with adalimumab in the treatment of uveitis.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors such as adalimumab are increasingly used in the treatment of ocular inflammatory disease refractory to standard therapies. There is evidence that TNF inhibitors are associated with demyelinating neurologic events. OBJECTIVE: The authors report a case of optic neuritis and multiple sclerosis developing in association with the use of adalimumab for the treatment of bilateral chronic granulomatous iridocyclitis and multifocal choroiditis. They also review the available literature on cases of optic neuritis occurring in the setting of TNF inhibition. RESULTS: The authors identified 21 cases of optic neuritis associated with TNF inhibition; 36% of cases with available MRI results had evidence of other demyelinating lesions in the CNS. CONCLUSIONS: The strong association between TNF inhibitors and CNS demyelination may represent an adverse effect of these drugs. Ophthalmologists should recognize the relationship between TNF inhibitors and demyelinating disease, as it can present initially with visual symptoms.

Ocular toxicity by latex of Calotropis procera (Sodom apple).

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3-14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further.

Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients.

OBJECTIVE: To report adverse events (AEs) seen in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with tumour necrosis factor (TNF)alpha blockers (infliximab and etanercept). METHODS: All patients with JIA treated with infliximab or etanercept at the Paediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to February 2006, were enrolled in an open, single-centre, long-term prospective study RESULTS: In all, 163 patients (68 infliximab, 95 etanercept) were enrolled. Mean (SD) age of onset was 6.4 (4.8) years, mean age 17.1 (9.2) years, mean therapy duration 22.9 (17.6) months. A total of 45 patients (32 infliximab, 13 etanercept) failed to respond to or did not tolerate the first therapy and switched to a second one. In all, 208 treatments (81 infliximab, 127 etanercept) were performed. A total of 71 AEs occurred in 51 (62.9%) patients on infliximab and led to discontinuation in 26 (32.1%); 133 AEs occurred in 69 (54.3%) patients on etanercept and led to discontinuation in 18 (14.2%). Some AEs, such as thrombocytopoenia, neuropsychiatric disorders, new onset of Crohn disease and new onset or flare-up of chronic iridocyclitis (CIC), are unusual and have rarely been described before, yet proved to be significant in frequency and/or clinically noteworthy in the large population we followed. CONCLUSIONS: In our 6-year study, anti-TNFalpha agents infliximab and etanercept were well tolerated and safe, and were associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFalpha therapy as much as possible.

[Side effects of anti-TNFalpha therapy in juvenile idiopathic arthritis]. / Effetti collaterali del trattamento con inibitori del TNFalpha nell'artrite idiopatica giovanile.

OBJECTIVES: To report adverse events registered in our population affected by JIA and treated with anti-TNFalpha blockers. METHODS: Ninety-five patients were enrolled to be treated with Etanercept, median age 14 years (range 4-34); median duration of therapy 12 months (range 1-40). 19 patients were also treated with MTX (median dose 12.5 mg/week). Fifty-six patients were enrolled to be treated with Infliximab associated with MTX (median dose of MTX 8.8 mg/week), median age 23.2 years (range 7.8-34.9); median duration of therapy 20.1 months (range 1.4-60.4). All adverse events were divided in definitely, probably and possibly related to the biologic agent. RESULTS: Side effects definitely related to Infliximab were the reactions to infusions and the Anti-dsDNA positivity. Side effects definitely related to Etanercept were severe headache and thrombocytopenia. Side effects probably correlated to both the biological agents were behavioural modifications and pain amplification syndrome. Probably correlated to the treatment with Etanercept was the onset of Crohn's disease in 3 patients. Possibly correlated to the biological agents were the new onset or flare-up of Chronic Iridocyclitis and single cases of thyroideal cancer, hypoglossal nerve paralysis and a severe Cytomegalovirus pulmonary infection. No case of tuberculosis infection was registered during this study. CONCLUSIONS: Treatment with a TNFalpha antagonist seems to be associated with various adverse events. Some of them, like onset of Crohn's disease, behavioural modifications are unusual and others, like pain amplification syndrome were never described before. Children and young adults affected by JIA should be monitored very carefully so as to limit as much as possible the risk of serious side effects on anti-TNFalpha therapy.

[Heterochromia of the Iris after t-PA and Gas Injection of Sulfur Fluoride]. / Irisheterochromie nach rtPA- und Gasinjektion.

BACKGROUND: Are changes in iris colour and retinal pigment epithelium after t-PA and gas injection and subsequent vitreous haemorrhage caused by blood cells, or is this a toxic effect? CASE: A 81-year old female presented for vitrectomy with a persistent vitreous haemorrhage two months after t-PA and gas injection because of subretinal macular haemorrhage. Sonographic control revealed attached retina. The examination disclosed a new heterochromia of the iris with a change from blue to green-brown. A discrete anterior chamber flare and blood cells were found. Subsequent vitrectomy revealed a thick, rubber-like haemorrhage in the vitreous with suspect pigmentation. A change in retinal pigmentation was also evident. CONCLUSION: The cause for the heterochromia and the change in pigmentation of the retinal pigment epithelium remained unclear. It may have been a consequence of the persistent bleeding with iron apposition on the iris. A toxic effect of t-PA has to be discussed which led to the alteration in pigmentation.

Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin.

OBJECTIVE: Iridocyclitis has been identified as a dosage-dependent side effect in patients with the acquired immunodeficiency syndrome (AIDS) who are treated for Mycobacterium avium complex (MAC) infection with systemic rifabutin. We reviewed cases of acute hypopyon uveitis occurring in patients with AIDS to establish whether there was an association. DESIGN: Retrospective case series. SETTING: Outpatient clinic and inpatient hospital-based ophthalmology referral practice and infectious disease specialty service. PATIENTS: Seven patients with AIDS, aged 10 to 40 years, presenting with acute unilateral hypopyon mimicking infectious endophthalmitis. MAIN OUTCOME MEASURES: Findings from complete ophthalmological evaluation and ancillary laboratory testing. RESULTS: At the time of presentation, all seven patients were receiving treatment for MAC infection with rifabutin (dosage range, 300 to 600 mg/d) and clarithromycin. Results of microbiological investigations in five patients were negative. Iridocyclitis became bilateral in all seven patients, and hypopyon developed in the contralateral eye in five of seven patients. Hypopyon resolved rapidly with intensive topical corticosteroid therapy. Residual inflammation responded to topical corticosteroids with or without reduction of the rifabutin dosage. CONCLUSIONS: Concomitant use of rifabutin, clarithromycin, and fluconazole may precipitate hypopyon uveitis in patients with AIDS being treated for MAC infection.

Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate].

The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 micrograms/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6.

[Acute iridocyclitis with fever and liver involvement during quinidine therapy]. / Akut iridocyclitis med feber og leverpåvirkning ved kinidinbehandling.

Acute iridocyclitis is a rare hypersensitive reaction to quinidine treatment. The third case in the literature is reported here. A woman aged 80 years developed pyrexia, anorexia, nausea, skin rash and hepatic dysfunction after treatment with quinidine for two weeks. Four weeks later, while still receiving quinidine, she developed acute iridocyclitis. Quinidine treatment was withdrawn, the eye symptoms were treated and the patient recovered rapidly without complications. This case report draws attention to quinidine as a possible cause of iridocyclitis of unknown origin.