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Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active FMF and an inadequate response or intolerance to colchicine (crFMF). The physician’s global assessment of disease activity (PGA), based on a five-point scale for six symptoms, was used as a clinical score, which had to be >2 at screening, together with elevated c-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) levels, to be eligible for inclusion. Patients were randomized 1:1 to either receive monthly TCZ or a placebo over a period of 24 weeks. The primary endpoint was the number of patients achieving an adequate response to treatment at week 16, defined as a PGA of ≤2 and normalized ESR or CRP and normalized SAA. Results: We randomized 25 patients with a median age of 31 years. At week 16, an adequate treatment response was achieved by two patients in the TCZ and none of the patients in the placebo arm (p = 0.089). SAA levels normalized with TCZ, but not with the placebo (p = 0.015). Conclusion: In this first randomized, placebo-controlled study in patients with active crFMF, more patients in the TCZ arm experienced a response to treatment in comparison to those receiving the placebo. As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA in TCZ-treated patients is essential. These findings have to be confirmed in a larger trial.

Rationale and Objectives: To assess muscular abnormalities related to systemic sclerosis (SSc) using shear wave elastography and correlate results with those of clinical tests., Materials and Methods: We evaluated 55 patients (mean age: 50.4 years; range: 18-88; 34 female) with SSc before treatment and choose muscle groups based on cutaneous involvement and functional impairment [forearms (9); thighs (41); thenar/hypothenar (5)]. We performed shear wave elastography in two orientations to access heterogeneity using virtual touch IQ and mean shear wave velocity values (SWV) and measured skin and fascia thickness. We compared SWVs to the modified Rodnan skin score (mRSS). Twenty-two healthy controls (mean age: 52.0; range: 19-88; 7 female) underwent the same protocol., Results: SWV pattern analysis (homogeneous vs heterogeneous) detected SSc with sensitivity/specificity/negative predictive value/positive predictive value0.79/0.81/0.91/0.62 in transverse and 0.75/0.18/0.91/0.56 in longitudinal orientation. In patients we found poor correlation between SWVs and mRSS but a cutoff of mRSSE = 20 separated them significantly (p < 0.01). Skin and muscle fascia were significantly thicker in patients vs. controls (p < 0.001)., Conclusion: SSc involves more than increased skin and fascial thickness which is not fully represented by mRSS. Elasticity differs in muscles with and without SSc. The former shows higher SWV and increased heterogeneity in transversal planes of muscular fibers., Competing Interests: Funding Jan Fritz received institutional research support from Siemens Healthcare USA, DePuy, Zimmer. Micorsoft, and BTG International; is a scientific advisor of Siemens Healthcare USA, Alexion Pharmaceuticals, and BTG International; received speaker's honorarium from Siemens Healthcare USA' and has shared patents with Siemens Healthcare and Johns Hopkins University. Horger Marius received institutional research support from Siemens Healthineers Germany; he is a scientific advisor of Siemens Healthineers Germany and received speaker's honorarium from Siemens Healthineers Germany., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: To evaluate the role of perfusion CT for monitoring inflammatory activity in patients with aortitis and chronic periaortitis undergoing immunosuppressive therapy., Materials and Methods: Seventeen symptomatic patients (median age 68.5 years) who underwent perfusion-based computed tomography (CT) monitoring after diagnostic contrast-enhanced CT were retrospectively included in this study. Blood flow (BF), blood volume (BV), volume transfer constant (k-trans), time to peak, and mean transit time were determined by setting circular regions of interest in prominently thickened parts of the vessel wall or perfused surrounding tissue at sites where the perfusion CT color maps showed a maximum BF value. Differences in CT perfusion and, morphological parameters, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were tested for significance during therapy., Results: In all patients BF and BV dropped at second perfusion CT (P < 0.05). In aortitis patients, CRP dropped from 3.86 ± 5.31 mg/dL to 0.9 ± 1.37 mg/dL and in periaortitis patients from 1.78 ± 2.25 mg/dL to 0.79 ± 1.55 mg/dL, whereas ESR dropped from 45.71 ± 37.59 seconds to 8.57 ± 3.1 seconds and 36.78 ± 34.67 seconds to 17.22 ± 21.82 seconds in aortitis and in periaortitis, respectively., Conclusions: The course of perfusion CT parameters in aortitis and chronic periaortitis undergoing immunosuppressive therapy dropped at different extent after therapy., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent., Methods: Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches., Results: Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein-damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10(-4) and P = 5.16 × 10(-4) , respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni-corrected P = 5.63 × 10(-14) , P = 7.29 × 10(-6) , P = 1.15 × 10(-5) , and P = 6.40 × 10(-3) , respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant., Conclusion: We used whole exome sequencing in BD for the first time and identified 2 rare putative protein-damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD., (© 2016, American College of Rheumatology.)

Objective: Recent publications have shown a negative influence of SLE on female ovarian reserve. Other authors have not found a significant impact of Crohn's disease or early RA on anti-Müllerian hormone (AMH) levels. This study aimed to investigate the potential effect of Behçet's disease (BD), RA and SpA on ovarian reserve as reflected by serum AMH levels., Methods: Serum samples from 33 RA, 32 SpA and 30 BD patients without previous cytotoxic treatment were analysed and compared with age-matched, healthy controls. AMH was quantified using a standard ELISA with a standard value of 1-8 ng/ml; values <1 ng/ml defined a reduced ovarian reserve., Results: Median age was 26, 28.5 and 33 years and median disease duration was 6, 5.9 and 7 years for RA, SpA and BD patients, respectively. Compared with healthy controls, patients had significantly reduced AMH levels, with a median value for RA of 1.8 ng/ml (control 2.4 ng/ml; P = 0.009), for SpA of 1.5 ng/ml (control 2.3 ng/ml; P = 0.013) and for BD of 1.1 ng/ml (control 1.9 ng/ml; P = 0.007). HLA-B27 had a negative influence on ovarian reserve in SpA patients, whereas other serological parameters did not in the other diseases., Conclusion: This is the first study to show a reduced ovarian reserve in patients with RA, SpA or BD. Together with our findings in SLE, we conclude a negative influence of chronic rheumatic diseases on ovarian reserve., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)