Risk of tuberculosis is increased in Behçet's disease compared to other rheumatological disorders after anti-TNFα treatments: a case series and review of the literature

Background/aim: Tumor necrosis factor-alfa (TNF-a) antagonists are extensively utilized in the treatment of inflammatory rheumatic diseases and also shown to be effective in Behçet's disease (BD) patients with major organ involvement. In this study, we aimed to re- evaluate the incidence of tuberculosis (TB) infection after anti-TNFa treatments and to reveal the risk of TB in BD. Methods: Data of patients who received anti-TNFa treatment between 2005 and 2018 were assessed retrospectively. Demographic features, TNF-a antagonist type/treatment time, tuberculosis skin test (TST) and QuantiFERON results, isoniazid prophylaxis status, and concomitant corticosteroid (CS) treatments were collected. Results: A total of 1277 (male/female = 597/680; median age = 49 years) patients were treated with TNF-a antagonist for a median of 33 months (Q1:12, Q3:62). Thirteen (1%) patients developed TB during the follow-up period. Within 13 TB-positive patients, 7 of them had pulmonary, and 7 had extrapulmonary TB. Although, the median time of (month) TNF-a antagonist treatment was higher in TB-positive patients than negative ones, the difference was not statistically significant (48 and 33 months, respectively, p = 0.47). Similarly, TB-positive patients were treated with CSs more than TB-negative patients (80% vs. 60%). Time from the initiation of TNF-a antagonist treatment to the diagnosis of TB had a median of 40 months (Q1-Q3: 22-56). There was a statistically significant increase of TB development in BD patients than non-BD patients after TNF-a antagonists (7.5% vs. 0.8%, respectively, p = 0.007). When we combined our patients with the other series from Turkey, among 12928 patients who received TNF-a antagonists, TB was positive in 12 (3.9%) of 305 BD patients compared to 112 (0.9%) of 12623 non-BD patients (p < 0.00001). Conclusion: Our results suggest a higher frequency of TB infections in BD patients with TNF-a antagonists. As biologic agents are increasingly used for major organ involvement in current practice for BD, screening mechanisms should be carefully implemented.

Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects

Psoriatic arthritis (PsA) is an underdiagnosed entity with a broad impact on the quality of life. Although the pathogenesis is largely unknown, autoimmune footprints of the inflammation in PsA have increasingly been recognized. Most of the genetic variation predisposing to PsA is mapped to the class I major histocompatibility complex (MHC) region and shared by a variety of autoimmune diseases. Polymorphisms in the genes IL12B, IL23R, IL13, TNIP1, TRAF3IP2, TYK2, and many others explain the non- HLA genetic risk with little known functional consequences. Entheseal and synovial cellular infiltrate with oligoclonal CD8+ T cells and occasional germinal centers, loss of regulatory T cell function, and specific autoantibodies such as anti-PsA peptide, anti-LL-37, and anti-ADAMTSL5 are the immunopathological findings suggestive of autoimmunity. These were supported by clinical observations of autoimmune multimorbidity and treatment response to calcineurin/mTOR and co-stimulation inhibition.

Decreasing incidence and severity of Behçet's disease: a changing trend in epidemiological spectrum possibly associated with oral health

Behçet's disease (BD) is a systemic and inflammatory disorder that is mainly present along the ancient Silk Road, from the Mediterranean Sea to East Asia. A wide range of prevalence figures (0.1­420/100,000) have been reported for BD, also among Turkish populations of similar genetic background living in different countries. Recently, a decline in the incidence of BD and a change of the disease spectrum to less-severe manifestations have been reported from Japan and Korea, two genetically homogenous, affluent populations with limited immigration. It was hypothesized that a decline in infectious diseases, especially dental/periodontal infections, associated with the improvement in oral health, could be a part of these changes in the disease expression. Further epidemiological studies in other populations might demonstrate whether there is a worldwide similar trend and may provide a better understanding of the triggering factors for the onset and course of BD.

IFN-γ stimulated dental follicle mesenchymal stem cells regulate activated lymphocyte response in rheumatoid arthritis patients in vitro.

BACKGROUND: Multipotent mesenchymal stem cells (MSCs) have been investigated in autoimmune diseases such as rheumatoid arthritis (RA) due to their immunomodulatory and regenerative properties. In this study, their immunosuppressive effects on peripheral blood mononuclear cells (PBMC) of RA patients were studied. METHODS: Dental follicle stem cells (DFSCs) were isolated from follicle tissue in the orofacial region. Characterization and multipotency analyses were performed. Lymphocytes were isolated from peripheral venous blood of RA patients (n = 5) and healthy individuals (n = 5). DFSCs were preincubated with IFN-γ for 48 h. PBMCs of RA patients and healthy individuals were separately cultured with or without DFSCs for 72 h. After culture period, lymphocyte proliferation and viability, the frequency of CD4+ CD25+FoxP3+ T regulatory cells, IL-10 and TNF-α levels in the culture supernatants were measured via flow cytometry. RESULTS: Our results demonstrated that DFSCs suppressed proliferation of T lymphocytes by increasing the number of FoxP3 expressing CD4+CD25+ T regulatory cells and suppressed lymphocyte apoptosis in RA patients. Also, DFSCs reduced TNF-α cytokine secretion and upregulated IL-10 secreting cells. DISCUSSION: Such cells could potentially be a source for future immunomodulatory treatments of RA patients.

The assessment of work productivity and activity impairment in Behçet's disease.

BACKGROUND/AIM: The aim of this study was to assess the relationships between the course of Behçet's disease (BD), disease-specific fears, and work productivity and activity impairment. MATERIALS AND METHODS: In this cross-sectional study, 110 consecutive BD patients were included. The Work Productivity and Activity Impairment questionnaire was used. RESULTS: In the group of employed patients, 30.41% had missed work during the previous week. The mean percentages of daily activity impairment were higher in patients with musculoskeletal involvement (39.81 ± 33.61%) compared to those without (23.48 ± 32.45%) (P = 0.008). A greater decrease in working hours was observed in patients with eye involvement (45.52 ± 15.29 h) compared to those without (54.15 ± 15.29 h) (P = 0.007). More of the male patients (67.8%) were afraid of losing their jobs compared to females (30%) (P = 0.000). CONCLUSION: The highest levels of lost productivity and the most severe effects on daily life are consequences of eye and musculoskeletal involvement in the study population. More effective therapeutic approaches are required to improve the working lives of patients with BD. Moreover, male patients had a higher fear of losing their jobs, suggesting a match between the expected clinical course and the predictions of BD patients.

Flip-flop phenomenon in systemic sclerosis on fluorodeoxyglucose positron emission tomography/computed tomography.

Systemic sclerosis (SSc) is a rare autoimmune disease, which may affect multiple organ systems. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) can demonstrate the degree and anatomical extent of involvement in the entire body and coexisting malignancies in connective tissue diseases. We present a case of SSc with an increased 18F-FDG uptake in the cutaneous and subcutaneous tissues even higher than the neighboring skeletal muscles ("flip-flop phenomenon," that is, an increased 18F-FDG uptake in the skin but a decreased 18F-FDG uptake in the skeletal muscles).