IOF position on scientists and societies operating in conflict zones.

This position paper of the International Osteoporosis Foundation reports the findings of an IOF Commission to consider to recommend rules of partnership with scientists belonging to a country which is currently responsible for an armed conflict, anywhere in the world. The findings and recommendations have been adopted unanimously by the Board of IOF.

Value of Hands Ultrasonography in the Differential Diagnosis Between Psoriatic Arthritis and Rheumatoid Arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) can mimic rheumatoid arthritis (RA) at an early stage, especially when psoriasis is lacking. In the absence of specific radiological and immunological markers, the differential diagnosis between these two diseases can be challenging. We aimed to determine whether hands ultrasonography (US) may be useful in the differential diagnosis between PsA and RA. METHODS: We conducted a cross-sectional study including patients with PsA and RA. All wrists and small joints of the hands were examined using gray-scale and Power Doppler US. The evaluated US lesions were: synovitis, tenosynovitis of extensor carpi ulnaris, extensor communis and flexor tendons, enthesitis of extensor tendons at distal interphalangeal joints, peritendon inflammation of extensor tendons, and soft tissue edema. RESULTS: Six hundred joints in 20 PsA patients and 900 joints in 30 RA patients were assessed. Extensor enthesitis was significantly more observed in PsA compared with RA (39.4 vs 26.3%, P = .006) with a significant higher frequency of enthesophytes and calcifications (P = .022 and P = .002, respectively). Peritendon inflammation of extensor digitorum tendons was observed in 13% of metacarpophalangeal joints in PsA patients versus 3% in RA patients with a significant difference (P < .001). Soft tissue edema was exclusively observed in PsA (1.5 vs 0%, P = .033). Power Doppler synovitis was significantly more frequent in RA (9.2 vs 5%, P = .002). Extensor carpi ulnaris tenosynovitis was significantly more frequent in RA (18.3 vs 2.5%, P = .017). CONCLUSION: Extrasynovial US findings may be helpful to distinguish PsA from RA especially in patients with immunonegative polyarthritis and no evidence of psoriasis.

Serum IL-33 levels and skin mRNA expression in Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is an autoimmune/inflammatory disease characterised by abnormal production of proinflammatory cytokines. Interleukin-33 (IL-33) is a novel cytokine of the IL-1 cytokine family that has been recently implicated in several inflammatory and autoimmune diseases and the association of IL-33 with BD has remained unknown. Here we document for the first time, IL-33 level and its association with BD. METHODS: Serum IL-33 levels were measured in 46 BD patients (20 patients in active stage) and compared to multiple sclerosis (MS), rheumatoid arthritis (RA) patients and to healthy controls. In parallel, the transcription factor NF-κB that mediates IL-33 transcription was also measured. IL-33 mRNA was also quantified in freshly isolated PBMCs and in skin biopsies by real-time RT-PCR analysis. IL-6 and IL-17 were measured by ELISA. RESULTS: Serum IL-33 level was significantly higher in active BD patients [159.65 ± 61.7 pg/mL] compared to inactive BD patients [85.57 ± 21.07 pg/mL] (p<0.0001) and healthy controls [70.03±25.95 pg/mL] (p<0.0001). Active BD patients expressed lower IL-33 levels than the control disease group, RA and MS patients [p=0.00021]. The serum IL-33 level in active BD patients was corroborated by IL-33 mRNA expression in fresh PBMC. Patients with active BD with retinal vasculitis showed the highest serum IL-33 level. We further stimulated cultured PBMCs with phorbol myristate acetate (PMA) and ionomycin and macrophages with LPS for 24 h. Following stimulation the levels of IL-33 were increased similarly in PBMC [92.35±24.81 pg/ml] and macrophages [93.10±21.58 pg/ml] in active BD patients compared to healthy controls. NF-κB DNA binding activity was significantly increased in PBMCs of active BD patients particularly in LPS-stimulated macrophages compared to healthy controls. IL-33 mRNA expression in the skin lesions of patients with active BD was significantly increased compared to that in healthy skin biopsies [p=0.00016]. A significant relationship was found between the levels of IL-33 and IL-17 [r=0.533; p=0.0024] and IL-33 and IL-6 [r=0.661, p=0.0015] in 20 active BD patients. CONCLUSIONS: Elevated IL-33 level in active BD patients was found to correlate with disease activity. Targeting IL-33 should be approached with caution.

Chronic inflammatory rheumatism associated with Takayasu disease.

Takayasu disease is rarely associated with other autoimmune diseases. Therefore, the cases discussued herein are uncommon because we are reporting Takayasu disease associated with rheumatoid polyarthritis and spondylarthropathy. The first case concerns a 40-year-old woman presenting with Takayasu disease 11 years after the diagnosis of erosive and seronegative rheumatoid polyarthritis. The upper limb arteries and 1 lower limb artery were affected. The second 41-year-old case presented with ankylosing spondylitis that had been evolving for 10 years. Human leukocyte antigen-B27 typing was negative. Takayasu disease was revealed by severe high blood pressure. In both cases, radiologic examination revealed a typical aspect of the aorta and its main collaterals. Rarely in the literature have these associations been reported, and the pathology remains unknown.

Effect of bariatric and metabolic surgery on rheumatoid arthritis outcomes: A systematic review.

INTRODUCTION: Obesity is a growing and debilitating epidemic worldwide that is associated with an increased inflammation. It is often linked to rheumatic diseases and may impact negatively their natural history. The use of bariatric and metabolic surgery (BMS) has increased thanks to its positive effect on major comorbidities like diabetes type 2. This systematic review provides the most up-to-date published literature regarding the effect of BMS on outcomes in rheumatoid arthritis. METHODS: This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed, Embase and Cochrane, published until June 16th 2023, and tackling the effect of BMS on disease outcomes in patients with RA were included. RESULTS: Three studies met the inclusion criteria. They were published between 2015 and 2022. The total number of RA patients was 33193 and 6700 of them underwent BMS. Compared to non-surgical patients, weight loss after BMS was associated with lower disease activity outcomes at 12 months (p<0.05). Similarly, prior BMS in RA patients was significantly associated with reduced odds ratios for all the morbidities and in-hospital mortality compared with no prior BMS (36.5% vs 54.6%, OR = 0.45, 95% CI (0.42, 0.48), p< 0.001) and (0.4% vs 0.9%, OR = 0.41, 95% CI (0.27-0.61), p < 0.001) respectively. CONCLUSION: To conclude, published data indicate that BMS seems a promising alternative in reducing RA disease activity as well as morbidity and mortality in patients with obesity.

Journey of rheumatoid arthritis patients in Tunisia: From symptoms to treatment.

Objectives: This study aims to assess the different delays of rheumatoid arthritis (RA) patients' journey from disease onset to treatment initiation and to identify possible influencing factors. Patients and methods: This cross-sectional study included a total of 100 patients (14 males, 86 females; mean age: 56.5±12.4 years; range, 26 to 82 years) who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA between January 2019 and January 2020. Demographic and clinical data and disease characteristics were collected from the patient interviews and medical files. Five different intervals were defined from symptom onset until the initiation of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Results: The mean age at RA onset was 46.6±12.4 years. Median delays from onset of symptoms until general practitioner (GP) and rheumatologist consultations were six (range, 0.25 to 240) months and 12 (range, 0 to 242) months, respectively. Median delays from onset of symptoms to RA diagnosis and treatment with csDMARDs were 15.7 (range, 2 to 252) months and 18 (range, 2 to 270) months, respectively. The mean number of consultations was 7.3±4.2 and the median number of physicians visited before the diagnosis was three (range, 1 to 8). The RA diagnosis delay was associated with rural geographic environment (p=0.02), lack of social insurance (p=0.027), progressive symptoms onset (p=0.006), morning stiffness (p=0.023), being initially examined by a GP (p=0.02), number of consultations (p<0.001; r=0.49), and number of physicians consulted before diagnosis (p=0.001; r=0.33) respectively. Based on the patients' self-perception, the main causes of this long delay were lack of financial means (33%), wait times until exploration results (31%), wait times until the first GP or rheumatologist visit (26%), and geographical difficulty in accessing healthcare services (18%). Conclusion: Our study results suggest that patients with RA experience a significant delay until diagnosis and initiation of treatment. Healthcare providers should urgently consider factors related to diagnosis delay to shorten RA patients' journey.

Validity of Remission Criteria in Rheumatoid Arthritis Compared to Ultrasound-Defined Remission.

Objectives: Remission is the ultimate purpose of treatment in rheumatoid arthritis (RA). However, even when the most stringent composite scores are used, structural damages can occur; hence, ultrasonography (US) appears to be the best way to assess real remission. This study aimed to investigate the validity of different RA remission scores using US as a reference. Methods: An analytic diagnostic study, of 30 RA patients in remission (according to the Disease Activity Score in 28 Joints [DAS28]) and a control group with active RA, was conducted between January and October 2018 at Mongi Slim Hospital in Tunis, Tunisia. Among them, patients in remission were identified according to their Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and the Boolean American College of Rheumatology/European League against Rheumatism activity index (ACR/EULAR) remission scores. The validity of each activity score for remission was calculated by considering the absence of power Doppler (PD) signals as a gold standard. Results: All patients were in remission according to the DAS28, with an average score of 2.03 (1.1-2.6). US examination showed PD signals in 57% of patients. A total of 26 patients were in remission according to the CDAI; a Doppler signal was detected in 58% of those cases. SDAI remission was accomplished in 19 patients, with PD activity in 53% of cases. Of the 14 patients in remission according to the Boolean ACR/EULAR criteria, synovial hyper-vascularisation was found in 64%. Considering true remission as the absence of PD signals, the most sensitive and specific score was the DAS28 (93% and 68%, respectively). Conclusion: Considering remission in RA as the absence of vascularised synovitis, the DAS28 is the most sensitive and most specific score.

Non-radiographic axial spondyloarthritis in Tunisia: main characteristics and detailed comparison with ankylosing spondylitis.

OBJECTIVES: The aim of the present study is to compare the clinical features, disease activity, and physical impairment between non-radiographic axial spondyloarthritis and ankylosing spondylitis in Tunisian patients. METHODS: This is a retrospective study conducted in a single rheumatology center in Tunisia. Patients with axial spondyloarthritis fulfilling the 2009 ASAS criteria were included. The various spondyloarthritis-related variables were compared between non-radiographic axial spondyloarthritis and ankylosing spondylitis. p Values below 0.05 were considered statistically significant. RESULTS: Among 200 patients with axial spondyloarthritis, 40 had non-radiographic axial spondyloarthritis and 160 had ankylosing spondylitis. The non-radiographic axial spondyloarthritis patients were more frequently female, were younger, and had shorter disease duration. Patients with non-radiographic axial spondyloarthritis experienced enthesitis more frequently compared with ankylosing spondylitis patients. Psoriasis was more frequent in non-radiographic axial spondyloarthritis group, while inflammatory bowel disease was more frequent in ankylosing spondylitis group. The C-reactive protein level and functional score were significantly higher in patients with ankylosing spondylitis compared with non-radiographic axial spondyloarthritis. Tumor necrosis factor inhibitors were offered significantly more often to the ankylosing spondylitis group. There was no statistically significant difference between the 2 groups in other spondyloarthritis parameters. CONCLUSION: The non-radiographic axial spondyloarthritis is characterized mainly by a marked female prevalence, a higher enthesitis prevalence, and a better physical function. KEY POINTS: • Patients with nr-axSpA in Tunisia are more frequently female and have shorter disease duration compared with those with AS. • Peripheral manifestations were similar between nr-axSpA and AS patients except for enthesitis which were more frequent within nr-axSpA patients. • The disease activity is similar between the 2 groups of axSpA but the physical function is better within nr-axSpA patients.

Adherence to biologic disease-modifying antirheumatic drugs in adult patients with rheumatic diseases.

INTRODUCTION: The emergence of biologics has revolutionized the management of refractory rheumatic diseases (RD) by improving clinical outcomes. Unfortunately, the impact of non-adherence to the emerging therapy can limit their potential benefit. The objective of our study was to evaluate biologics' adherence in Tunisian patients with RD and to assess the determinants of non-adherence. METHODS: We conducted a cross-sectional study involving patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with bDMARDs (biologic disease-modifying antirheumatic drugs) for at least three months. Socio-demographic, clinical and biological data were collected. Biologic adherence was assessed using the compliance questionnaire for rheumatology (CQR). RESULTS: One hundred patients with RD (45 RA and 55 SpA) were collected. Non-adherence to bDMARDs was found in 70% of cases. In univariate analysis, non-adherence to bDMARDs was statistically related to the absence of coxitis (P=0.003), to a low ASDAS-CRP (ankylosing spondylitis disease activity score) prior to the initiation of the bDMARDs (P=0.01), to a rate of administration of bDMARDs less than one injection per month (P=0.01), to the subcutaneous delivery route (P=0.02) as well as to non-adherence to csDMARDs (conventional disease-modifying antirheumatic drugs) (P=0.001). In multivariate analysis, the predictors of non-adherence were the absence of coxitis (OR=6.01; IC 95% [1.88-19.12]; P=0.002], and a rate of administration of bDMARDs less than one injection per month (OR=8.79; IC 95% [2.13-36.22]; P=0.003). CONCLUSION: This work has revealed the low rate of adherence to biological treatments in Tunisian patient with RD. Predictors of poor adherence were the absence of coxitis and a rate of administration of bDMARDs less than one injection per month. Detection of these factors could help us to adapt our strategies to improve adherence that are essentially based on therapeutic education program.

Association of small ubiquitin-like modifier 4 (SUMO4) polymorphisms in a Tunisian population with Behçet's disease.

OBJECTIVES: An association of SUMO4 gene, which has recently been shown to be a negative feedback regulator for nuclear factor NF-κB, has been reported in several autoimmune/inflammatory diseases. A case-control study was set up to investigate the contribution of SUMO4 locus to the genetic susceptibility to Behçet's disease (BD). METHODS: One hundred and thirty-five Tunisian BD patients and 167 healthy blood donors from the same geographical area were genotyped by polymerase chain reaction for the SUMO4 polymorphisms. RESULTS. The SUMO4+438 C allele frequency is significantly increased in BD patients (p=0.03; χ2=4.71; OR=1.44; 95% CI=1.02-2.04) and highly significantly increased in HLA-B51 positive BD patients (p=3 10-6; χ2=21.62; OR=4.44; 95% CI=2.21-8.98). Similarly, the SUMO4 -847 G allele frequency is significantly increased in BD patients (p=0.03; χ2=4.34; OR=1.41; 95% CI=1.01-1.97). The studied polymorphisms were also associated with disease severity, skin lesions and vascular involvement. CONCLUSIONS: SUMO4+438 C and -847 G alleles seem to be associated with susceptibility to BD in Tunisian population. We suggest that SUMO4 gene polymorphisms may be involved in the development of skin lesions, vascular BD, as well as the severity of the disease.