Clinical trial Serum GDF-15 level in Behc ß et’s disease: relationships between disease activity and clinical parameters Mustafa Akif Sarıyıldız 1 , Assoc. Prof. MD, Levent Yazmalar 1 , MD, _ Ibrahim Batmaz 1 , MD, Mahmut Alpaycı 2 , MD, Yahya Kemal Burkan 3 , MD, Bilal Sula 4 , MD, _ Ibrahim Kaplan 5 , MD, Mehmet Yıldız 1 , MD, Zeynel Abidin Akar 1 , MD, and Mehtap Bozkurt 1 , MD 1 Department of Physical Medicine and Rehabilitation, Dicle University, Diyarbakır, Turkey, 2 Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Y€ uz€ unc€ u Yıl University, Van, Turkey, 3 Department of Physical Medicine and Rehabilitation, Memorial Hospital, Diyarbakır, Turkey, 4 Department of Dermatology, Dicle University, Diyarbakır, Turkey, and 5 Department of Biochemistry, Faculty of Medicine, Dicle University, Diyarbakır, Turkey Correspondence Mustafa Akif Sariyildiz, MD Department of Physical Medicine and Rehabilitation Faculty of Medicine Dicle University Diyarbakır 21282, Turkey Tel: + 90 412 248 8001, + 90 5057 673521 Fax: + 90 412 248 8523 E-mail: makifsariyildiz@hotmail.com Conflicts of interest: None. doi: 10.1111/ijd.13309 Abstract Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-b superfamily of cytokines, plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate serum GDF-15 levels and their relationships with disease-related variables in patients with Behc ßet’s disease (BD). Forty- six patients diagnosed with BD and 30 demographically matched healthy control subjects participated in the study. GDF-15 levels were measured in blood samples from patients and controls. The Behc ßet’s Disease Current Activity Form (BDCAF) was used to evaluate the disease activity of BD. There were no significant differences between the two groups in C-reactive protein (CRP) level, mean erythrocyte sedimentation rate (ESR), age, body mass index, and mean GDF-15 levels (P > 0.05). Serum GDF-15 levels were positively correlated with findings for peripheral arthritis and CRP, and with BDCAF erythema nodosum, BDCAF arthralgia, and BDCAF arthritis scores. Patients with BD were divided into two groups according to the presence of peripheral arthritis; nine subjects (20%) were positive for peripheral arthritis. Serum ESR, CRP, white blood cell counts, and GDF-15 levels were significantly higher in the group that was positive for peripheral arthritis (P < 0.05). GDF-15 may play a role in the progression and pathway of Behc ßet’s joint involvement and erythema nodosum that is independent of classic inflammatory response measures. Introduction Behc ßet’s disease (BD) is a systemic inflammatory disorder characterized by recurrent oral and genital ulcers, uveitis, and skin lesions such as erythema nodosum and pustules. 1–3 Although our understanding of the causes and pathogene- sis of BD remains incomplete, the features of BD as an inflammatory multi-system disease with spontaneous remissions and relapses are similar to those of other autoimmune diseases. 2 Approximately 50% of patients with BD also display musculoskeletal involvement. Joint involvement is usually non-erosive, non-deforming, mono- oligoarticular, and intermittent, and most frequently affects the knees or ankles. Less common musculoskeletal features are enthesitis, spondylitis, and sacroiliitis. 4,5 Behc ßet’s disease is a neutrophil-mediated disease char- acterized by neutrophil hyperactivity. Inflamed rheuma- toid synovium is characterized by the presence of many proinflammatory cytokines that eventually induce joint destruction. Joint repair may proceed via transforming growth factor-b (TGF-b) expressed in the synovium and subsynovial macrophages. 5–7 Another TGF-b superfamily cytokine, growth differentiation factor-15 (GDF-15) (or macrophage inhibitory cytokine-1), has been implicated in chronic inflammatory pathways similar to those seen in rheumatoid arthritis (RA). 6,8 GDF-15 was originally iden- tified as a factor secreted by activated macrophages and plays an important role in cell growth and differentia- tion. 7 Expression of GDF-15 is usually low in resting tis- sues but may be increased following an adaptive stress response to diverse cellular stress signals such as hypoxia, inflammation, and tissue injuries. 9 The relationship of macrophage activation to GDF-15 gene expression sug- gests that GDF-15 may be an autocrine regulator of ª 2016 The International Society of Dermatology International Journal of Dermatology 2016 1