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Rheumatoid and psoriatic arthritis (RA and PsA) are inflammatory rheumatic disorders characterised by a multifactorial etiology. To date, the genetic contributions to the disease onset, severity and drug response are not clearly defined, and despite the development of novel targeted therapies, ~10% of patients still display poor treatment responses. We characterised a selected cohort of eleven non-responder patients aiming to define the genetic contribution to drug resistance. An accurate clinical examination of the patients was coupled with several high-throughput genetic testing, including HLA typing, SNPs-array and Whole Exome Sequencing (WES). The analyses revealed that all the subjects carry very rare HLA phenotypes which contain HLA alleles associated with RA development (e.g., HLA-DRB1*04, DRB1*10:01 and DRB1*01). Additionally, six patients also carry PsA risk alleles (e.g., HLA-B*27:02 and B*38:01). WES analysis and SNPs-array revealed 23 damaging variants with 18 novel “drug-resistance” RA/PsA candidate genes. Eight patients carry likely pathogenic variants within common genes (CYP21A2, DVL1, PRKDC, ORAI1, UGT2B17, MSR1). Furthermore, “private” damaging variants were identified within 12 additional genes (WNT10A, ABCB7, SERPING1, GNRHR, NCAPD3, CLCF1, HACE1, NCAPD2, ESR1, SAMHD1, CYP27A1, CCDC88C). This multistep approach highlighted novel RA/PsA candidate genes and genotype-phenotype correlations potentially useful for clinicians in selecting the best therapeutic strategy.

Introduction The most serious COVID‐19 deriving from severe acute respiratory syndrome coronavirus 2 causes cytokine release storm and it is associated with worse outcomes. In COVID‐19 patients, Interleukin (IL)‐6 levels are significantly elevated. Blocking IL‐6 preliminary resulted in the improvement of this hyperinflammatory state. It is unknown which patients could require higher doses of tocilizumab to get out of the cytokine storm. Materials and Methods Twenty‐four patients affected by COVID‐19 pneumonia were included. All the patients underwent tocilizumab 8 mg/kg intravenously and were tested for serum IL‐6 24‐48 hours before and 12‐48 hours after tocilizumab infusion. Comparisons between survivors and non‐survivors were performed. Results Eighteen patients were discharged, while six patients died, with no clinical or laboratory differences between the two groups at baseline. IL‐6 was not different at baseline (p=0.41), while 24‐48h post‐tocilizumab IL‐6 serum levels were significantly higher in non‐survivors than in survivors [2398.5 (430.5‐9372) pg/mL vs 290.5 (58.5‐1305.5) pg/mL, p=0.022)]. Serum IL‐6 post‐tocilizumab showed a good predictive ability to discriminate survivors from non‐survivors (AUC 0.815 95%CI 0.63‐0.99, p=0.02). Conclusion Repeated measurement of serum level of IL‐6 early after tocilizumab may distinguish non‐survivors from survivors and support the choice of deeper targeting IL‐6 in COVID‐19 pneumonia. This article is protected by copyright. All rights reserved.

Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background.

Background Patients infected by SARS-CoV-2 can develop interstitial pneumonia, requiring hospitalisation or mechanical ventilation. Increased levels of inflammatory biomarkers are associated with development of acute respiratory distress syndrome (ARDS). The aim of the present study was to determine which cytokines are associated with respiratory insufficiency in patients hospitalised for COVID-19. Patients and methods Data on 67 consecutive patients were collected between March 8 and March 30, 2020. PaO2/FiO2 ratio (P/F) was calculated at hospital admission. The following cytokines were analysed: interleukin (IL)-6, IL-1α, IL-18, tumour necrosis factor (TNF)-β, macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), soluble IL-2 receptor alpha (sIL-2Rα; CD25), IL-12β, IL-3, interferon (IFN) α2a, monokine induced by gamma interferon (MIG), monocyte-chemotactic protein 3 (MCP3) and hepatocyte growth factor (HGF). Results P/F lower than 300 was recorded in 22 out of 67 patients (32.8%). P/F strongly correlated with IL-6 (r = −0.62, P

Highlights • There is an urgent need for markers of prognosis in COVID-19. • Higher inflammatory markers best select tocilizumab treatment. • The ward based tocilizumab group showed better responses and less infections than ICU tocilizumab group. • The former group may be the best for evaluating the impact of anti-cytokine therapy in COVID-19. • The known poor risk factors for COVID-19 infection were present in the TOCI treated rather than in the good prognosis standard of care group., Objective Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or “cytokine storm”. Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Methods Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Results In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p

Background:Anti-3-hydroxy-3-methylglutaryl-coenzime A reductase (HMGCR) myopathy is a new entity, which has been clearly associated to statin use, even if it can be diagnosed in patients without a history of exposure to statin or even in the childhood (1).Objectives:The aim of the study is to describe the efficacy of a triple therapy regimen consisting in high-doses of intravenous immunoglobulins (IVIG), methotrexate (MTX), and glucocorticoids (GC) in 16 patients with Anti-HMGCR myopathy enrolled in 6 specialized centres.Methods:A total of 16 patients with anti-HMGCR myopathy (7 females; 9 males) were collected. Mean (±standard deviation) age at the onset of disease was 72.4±10.3 years old. All patients were diagnosed having anti-HMGCR myopathy [anti-HMGCR antibodies were measured by chemiluminescence assay (BioFlash, Inova, CA)] (2). Median follow-up was 29.5 months (interquartile range: 15.75-60 months). Anti-HMGCR antibodies were available in the follow-up in 8/16 patients.Results:Thirteen out of 16 patients (81.3%) had been exposed to statin (1/13 to red rice), 3/16 (18.7%) were not exposed. As induction therapy, 11/16 patients have been treated with triple therapy (high-dose IVIG, MTX and GC), 2/16 with double therapy (high-dose IVIG and GC), 2/16 have been treated with GC alone, the patient exposed to red rice resolved only with red rice suspension. Clinical remission and normalization of CPK values within month +24 were obtained in all the patients. All the patients were in remission at the last follow-up. Gradual improvement started soon from the first month, and among the 13 patients treated with an aggressive immunosuppresssive therapy including IVIG (13/13), GC (13/13) and methotrexate (11/13), 9/13 normalized the CPK value within 6 months. Clinical and laboratory response was accompanied by significant decrease or normalization of the anti-HMGCR antibody titer. All the patients were either not taking GC (56.3%), or were taking low doses of GC (43.7%) at the last follow-up. Four patients had stopped GC within 6 months. No serious side effects were recorded. After persistent remission, a maintenance immunosuppressive therapy was then administered. Only 3 relapses in 3 different cases were recorded, all of them during drug-free remission in long-term follow-up. Reinduction was again effective in all.Conclusion:Anti-HMGCR myopathy is a rare and serious myopathy which usually affects older people during statin treatment. After statin suspension, a rapid and sustained remission can be achieved by induction with a triple aggressive therapy consisting in medium-to high doses of GC, high-dose IVIG, and MTX (3). GC should be tapered as soon as possible. Relapse appears infrequent during maintenance treatment. Monitoring anti-HMGCR antibody titer may be clinically relevant.References:[1]AL Mammen et al. N Engl J Med. 2016;374:664-9[2]Musset L et al. Autoimmun Rev. 2016;15:983-93.[3]Aggarwal A et al. Scand J Rheumatol. 2019; 1-7.Acknowledgments:We thank MD Francesca Grosso and MD Valentina Mecheri from the University of Florence, MD Angela Zuppa and MD Chiara De Michelis, from San Martino Hospital, Genova, for their valued collaboration in data collectionDisclosure of Interests:Elena Treppo: None declared, Maria Infantino: None declared, Maurizio Benucci: None declared, Viviana Ravagnani: None declared, Boaz Palterer: None declared, Marina Grandis: None declared, Martina Fabris: None declared, Paola Tomietto: None declared, Mariangela Manfredi: None declared, Arianna Sonaglia: None declared, Maria Grazia Giudizi: None declared, Francesca Ligobbi: None declared, Daniele Cammelli: None declared, Paola Parronchi: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer