Prediction of relapses and determining patients who also require aggressive treatment is more challenging. management strategies according to clinical phenotypes. Keywords: Beh?et syndrome, treatment, management, biologic brokers, TNF inhibitor Introduction Beh?et syndrome (BS) is a relapsing, multisystem inflammatory vasculitis characterized by oral (OU) and genital ulcers (GU), as well as involvement of the joints, ocular, vascular, nervous, and gastrointestinal AG-1478 (Tyrphostin AG-1478) systems. For many years, BS was thought to be an autoimmune disease. However, there are certain clinically significant differences between BS and other autoimmune diseases, such as sex differences in disease manifestations, lack of autoantibodies, and comorbidities (eg, premature atherosclerosis).1,2 In recent years, AG-1478 (Tyrphostin AG-1478) BS has begun to be considered as an autoinflammatory disease. Just as in autoimmune diseases, AG-1478 (Tyrphostin AG-1478) there are some differences between BS and autoinflammatory diseases. Autoinflammatory disorders are typically seen in children with recurrent fever syndromes; however, BS is quite rare in the pediatric age group, and recurrent fever is not a part of the BS clinical feature.1 Also, vasculitis is an important feature of BS, which is not the case in autoinflammatory diseases. Moreover, IL1 inhibition, which has been shown to be effective in the treatment of autoinflammatory illnesses, has only a limited effect on some subgroups of BS patients. The basic principles in BS treatment are to suppress inflammation promptly and prevent damage AG-1478 (Tyrphostin AG-1478) and relapses. Since the disease has a heterogeneous nature, its treatment varies according to the type of involvement. Mucocutaneous and joint involvement in BS patients may reduce the quality of life (QoL) but do not result in permanent damage. Standard treatment is the first choice in these patients. On the other hand, immunosuppressive treatment is usually mandatory in patients with major organ involvement. Otherwise, it can cause morbidity or mortality. Male gender and young age are other important prognostic factors and affect the choice of treatment. In this review, we aimed to give an overview of the studies with standard and biological drugs with proven efficacy in the treatment of BS, as well as promising drugs and current management strategies according to clinical phenotypes. For this purpose, studies retrieved during the systematic reviews for the 2018 update of the EULAR recommendations for the management of BS, as well as more recent studies that were published since then were examined.3C5 Conventional Treatment Modalities Colchicine The efficacy of colchicine was evaluated in 3 different randomized controlled trials (RCT) with different conclusions (Table 1). In the first RCT (n=28), no beneficial effect of colchicine was found in BS patients with AG-1478 (Tyrphostin AG-1478) mucocutaneous and ocular involvement during 6 months.6 On the other hand, the authors reported that colchicine might still have some efficacy on erythema nodosum (EN) and arthralgia. In the second and larger RCT RPS6KA6 (n=116) led by the same group, colchicine was found effective on EN and GUs in women and arthritis in both genders during 2 years.7 On the other hand, the third RCT (n=169) reported significant improvement in OUs, pseudofolliculitis, as well as GUs and EN during the 4-months trial.8 In all 3 trials colchicine was generally well tolerated and did not cause any serious adverse effects (AEs). Table 1 The Effect of Drugs According to the Types of Involvement in Beh?et Syndrome

Drugs Type of Study Type of Organ Involvement Skin and Mucosa Joint Uveitis Vascular Involvement CNS Involvement GI Involvement

ColchicineRCT???OSApremilastRCT?OS?AzathioprineRCT???OS????Cyclosporine-ARCT?OS??CyclophosphamideOS?Interferon-alphaRCT???OS????TNF-inhibitorsRCT??OS??????IL-1 inhibitorsRCT?OS???IL-6 inhibitorsOS?????IL-17 inhibitorsRCT?OS?IL-23 inhibitorsOS?ThalidomideRCT??OS?Mycophenolic acidOS???TofacitinibOS??? Open in a separate window Notes: ?: Effective, ?: Not Effective, : Not Evaluated, : Controversial/Inconclusive, ?: Reported to cause relapses. Abbreviations: RCT, randomized controlled trial; OS, observational study. Long-term prognosis of patients who took part in the second RCT were evaluated after about 17 years.9 Among 90 (78%) patients who could be contacted, 28 (31%) experienced to receive immunosuppressives during the.