Clinical phenotype and cytokine profile of adult IgA vasculitis with joint involvement.

OBJECTIVE: Joint involvement can be observed during the course of adult IgA vasculitis (IgAV). However, clinical picture, prognosis, or pathophysiological data associated with this condition have been overlooked. We aimed to describe the clinical characteristics and outcome of IgAV patients with joint involvement and look to a specific cytokine profile. METHODS: We analyzed clinical and biological data from a nationwide study that included adult IgAV patients. Presentation and outcomes of patients with or without joint involvement were compared at baseline and during follow-up. Plasma cytokine measurements of IgAV patients included in a prospective study were also analyzed using multiplex assays. RESULTS: Among 260 patients, 62% had joint involvement. Among them, rheumatological manifestations included arthralgia (100%) or arthritis (16%), mostly involving the knees and ankles. In multivariate analysis, patients with joint involvement, compared to those without, were younger (p = 0.002; OR 0.87; 95% CI 0.80-0.95) and showed more frequent gastrointestinal tract involvement (p = 0.012; OR = 2.08; 95% CI 1.18-3.67). However, no difference in terms of clinical response, relapse, end-stage renal disease, or death was observed between groups. Among 13 cytokines measured, plasma interleukin (IL)-1ß level was higher in patients with joint involvement compared to those without (mean ± SEM IL-1ß, 3.5 ± 1.2 vs. 0.47 ± 0.1 pg/ml; p = 0.024) or healthy controls (vs. 1.2 ± 0.5 pg/ml; p = 0.076). CONCLUSION: Joint involvement is frequent in adult IgAV and is associated with more frequent gastrointestinal involvement. Increased plasma IL-1ß levels raise the question of targeting this cytokine in patients with chronic and/or refractory joint involvement. Key Points • Joint involvement in adult IgAV is a frequent manifestation. • Joint involvement is associated with more frequent gastrointestinal manifestations. • Interleukin-1ß (IL-1ß) might orchestrate joint inflammation in adult IgAV. • IL-1ß might be a therapeutic target in patients with chronic and/or refractory joint involvement.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

OBJECTIVES: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. METHODS: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. RESULTS: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. CONCLUSION: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Calcium pyrophosphate deposition disease revealing a hypersensitivity to vitamin D.

OBJECTIVE: Hypersensitivity to vitamin D (HVD) due to a loss of function mutation of the CYP24A1 gene, which encodes vitamin D catabolizing enzyme was initially described as a cause of acute hypercalcemia in children and chronic renal diseases in adults. METHODS: We describe the first case of a patient presenting a calcium pyrophosphate deposition disease (CPDD) revealing a HVD. RESULTS: An abnormality of phospho-calcic metabolism was discovered during the course of an etiological workup for CPDD in a 52-year-old patient. Laboratory tests revealed a blood calcium level at the upper limit of normal range, a markedly low parathormone level, a 25-hydroxyvitamin D level within the upper level of normal, an elevated 1,25-dihydroxyvitamin D level and an elevated urine calcium level. CYP24A1 gene sequencing analysis revealed two mutations in a heterozygous state. The study of the 25-hydroxyvitamin D3: 24,25-dihydroxyvitamin D3 ratio, two metabolites of vitamin D confirmed the enzyme deficiency in vivo. Our observation suggests that this disease could correspond to a rare cause of CPDD. CONCLUSION: In cases of CPDD associated with calcium values within the upper limit of normal range (or hypercalcemia) with an abnormally low PTH, one could suggest searching for HVD.

Association between osteoarthritis and dyslipidaemia: a systematic literature review and meta-analysis.

OBJECTIVES: We aimed to investigate the prevalence of dyslipidemia in patients with osteoarthritis (OA) and whether OA and dyslipidemia are associated. METHODS: We performed a systematic literature review and a meta-analysis, including cross-sectional, cohort and case-control studies, to assess the number of patients with OA and/or dyslipidemia. We calculated the mean (±SD) prevalence of dyslipidemia in patients with and without OA and the risk of dyslipidemia (OR, 95% CI) among patients with OA. RESULTS: From 605 articles screened, 48 were included in the analysis (describing 29 cross-sectional, 10 cohort and 9 case-control studies). The mean prevalence of dyslipidemia was 30.2%±0.6% among 14 843 patients with OA and 8.0%±0.1% among 196 168 without OA. The risk of dyslipidemia was greater with than without OA overall (OR 1.98,95% CI 1.43 to 2.75, p<0.0001) and with knee OA (OR 2.27, 1.33 to 3.89, p=0.003) and hand OA (OR 2.12, 1.46 to 3.07), p<0.0001). CONCLUSION: The risk of dyslipidemia was twofold greater with than without OA, so lipid disturbances could be a risk factor for OA. Such a result supports the individualisation of the metabolic syndrome-associated OA phenotype.