Patients:
In this retrospective study we performed a chart review of patients with a confirmed diagnosis of BS who were followed at the Behçet’s syndrome outpatient clinic, Rheumatology Research Center, Shariati Hospital, Tehran, Iran, between 2015 and 2017. Of all cases, the medical records for 165 patients who had ocular manifestations of the disease were included in this study. All patients were examined and diagnosed by a team of BS experts, and BS was diagnosed according to the International Criteria for Behcet's Disease (ICBD) criteria. All patients with the history of AZA prescription during ocular involvement in BS were eligible for inclusion in the study.
The Iranian BD dynamic activity measure (IBDDAM) questionnaire outcomes were used only for investigational purposes and had no impact on clinical decision making or treatment decisions. The patients’ IBDDAM scores were obtained in two follow-up sessions, and the overall score was calculated by adding the scores from the two sessions and dividing the sum by the interval between the two sessions (in months). The IBDDAM score evaluates 11 clinical manifestations, including oral aphthae (1 point per five ulcers), genital ulceration (1 point per ulcer), pseudofolliculitis (1 point per ten lesions), erythema nodosum (1 point per five lesions), arthritis (arthralgia 1 point, monoarthritis 2 points, polyarthritis 3 points), venous involvement (thrombophlebitis 1 point, large vessel thrombosis 2 points), intestinal manifestations (3 points for mild manifestations, 6 points for moderate to severe manifestations), central nervous system (CNS) manifestations (1 point for mild headaches, 3 points for mild CNS involvement, 6 points for moderate to severe manifestation), epididymitis (2 points), and pathergy (1 point).
All data were collected retrospectively from the medical records.
Azathioprine dosage, duration of use, and previous history of medication use (such as immunosuppressants or corticosteroids) were recorded from the patients’ medical records. The side effects of AZA were confirmed by a specific expert in the areas of ophthalmology, rheumatology, gastroenterology, dermatology, or oncology.
The patients were also monitored for side effects of AZA each month. This follow-up continued until the eye condition became stable and reached the remote phase. Thereafter the follow-up period was lengthened to 3 months, and follow-up ended when the drug was discontinued. There were no losses to follow-up.
A single ophthalmologist and rheumatologist examined the eyes in each visit. The ophthalmologist scored inflammation in each part of the eye between + 1 and + 4 (anterior and posterior uvea and the retina). In addition, the rheumatologist scored the amount of vasculitis. The classification published by Douglas A Jabs et al. (8) was used to establish the anatomical pattern of uveitis as anterior and posterior.
Treatment approaches were guided by the updated EULAR (The European League Against Rheumatism) recommendations for the management of Behcet’s syndrome (9). The overarching principles can be summarized as follows:
► BS is a condition that typically runs a relapsing and remitting course, and the goal of treatment is to promptly suppress inflammatory exacerbations and recurrences to prevent irreversible organ damage.
► A multidisciplinary approach is necessary for optimal care.
► Treatment should be individualized according to age, gender, type and severity of organ involvement, and patient’s preferences.
► Ocular, vascular, neurological, and gastrointestinal involvement may be associated with a poor prognosis.
► Disease manifestations may ameliorate over time in many patients.
In addition, EULAR highlights different types of involvement and their treatment approaches:
Eye involvement: The management of uveitis in BS requires close collaboration with ophthalmologists with the ultimate aim of inducing and maintaining remission. Any patient with BS and inflammatory eye disease affecting the posterior segment should be on a treatment regime such as AZA (IB), cyclosporine-A (IB), interferon alpha (IIA) or monoclonal anti-TNF antibodies (IIA). Systemic glucocorticoids should be used only in combination with AZA or other systemic immunosuppressants (IIA). Patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab or interferon alpha. Intravitreal glucocorticoid injection is an option in patients with unilateral exacerbation as an adjunct to systemic treatment.
Isolated anterior uveitis: Systemic immunosuppressants can be considered for those with poor prognostic factors such as young age, male gender, and early disease onset.
Adverse events:
A record was maintained for every patient treated with AZA, detailing side effects of the drug such as fever, nausea, vomiting, infection, leukopenia, thrombocytopenia, anemia, fever, hepatotoxicity, and skin cancers. Any other reasons for terminating or adjusting the drug dose were also documented. Leukopenia was considered less than 4000 WBC. In this study, leukopenia was recorded as moderate (3.0–4.0 × 106/ml) or severe (less than 3.0 × 106/ml). Altered liver enzymes in this study were defined as three times as much as the normal range for aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Most of these adverse events presented after starting AZA. In addition, most of the patients during treatment took just AZA. Then, the adverse events confirmed by specialists and they told that these effects are specific to this drug.