Showing papers in "Rheumatology in 2021"

Herpes zoster following BNT162b2 mRNA Covid-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series.

Abstract: OBJECTIVES: As global vaccination campaigns against COVID-19 disease commence, vaccine safety needs to be closely assessed. The safety profile of mRNA-based vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is unknown. The objective of this report is to raise awareness to reactivation of herpes zoster (HZ) following the BNT162b2 mRNA vaccination in patients with AIIRD. METHODS: The safety of the BNT162b2 mRNA vaccination was assessed in an observational study monitoring post-vaccination adverse effects in patients with AIIRD (n = 491) and controls (n = 99), conducted in two Rheumatology Departments in Israel. RESULTS: The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: rheumatoid arthritis (n = 4), Sjogren's syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in 5 cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects. CONCLUSION: Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster.

Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: an observational cohort study.

Abstract: OBJECTIVES: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. METHODS: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). RESULTS: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. CONCLUSIONS: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. TRIAL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).

Incidence and severeness of COVID-19 hospitalization in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark.

Abstract: Objectives To estimate the incidence of COVID-19 hospitalisation in patients with inflammatory rheumatic disease (IRD); in patients with rheumatoid arthritis (RA) treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalised patients with RA. Methods A nationwide cohort study from Denmark between 1 March to 12 August 2020. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals.Further, the incidence of COVID-19 hospitalisation was estimated for patients with RA treated respectively non-treated with TNF-inhibitors, hydroxychloroquine, or glucocorticoids.Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome, or death) among hospital-admitted patients was estimated for RA and non-IRD individudals. Results Patients with IRD (n = 58,052) had an increased partially adjusted incidence of hospitalisation with COVID-19 compared with the 4.5 million people in the general population (HR 1.46, 95%CI 1.15 to 1.86) with strongest associations for patients with RA (n = 29,440, HR 1.72, 95%CI 1.29 to 2.30) and vasculitides (n = 4072, HR 1.82, 95%CI 0.91 to 3.64). There was no increased incidence of COVID-19 hospitalisation associated with TNF-inhibitor, hydroxychloroquine nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI 0.80 to 2.53) for a severe outcome. Conclusion Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalisation.

COVID-19 vaccination and antirheumatic therapy.

Abstract: The COVID-19 vaccination will be the largest vaccination programme in the history of the NHS. Patients on immunosuppressive therapy will be amongst the earliest to be vaccinated. Some evidence indicates immunosuppressive therapy inhibits humoral response to the influenza, pneumococcal and hepatitis B vaccines. The degree to which this will translate to impaired COVID-19 vaccine responses is unclear. Other evidence suggests withholding methotrexate for two weeks post vaccination may improve responses. Rituximab has been shown to impair humoral responses for 6 months or longer post administration. Decisions on withholding or interrupting immunosuppressive therapy around COVID-19 vaccination will need to be made prior to the availability of data on specific COVID-19 vaccine response in these patients. With this in mind, this article outlines the existing data on the effect of antirheumatic therapy on vaccine responses in patients with inflammatory arthritis and formulates a possible pragmatic management strategy for COVID-19 vaccination.

Osteosarcopenia: where osteoporosis and sarcopenia collide.

Abstract: The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. Osteoporosis describes low bone mass and deterioration of the micro-architecture of the bone, whereas sarcopenia is the loss of muscle mass, strength and function. With an ageing population the prevalence of both conditions is likely to increase substantially over the coming decades and is associated with significant personal and societal burden. The sequelae for an individual suffering from both conditions together include a greater risk of falls, fractures, institutionalization and mortality. The aetiology of 'osteosarcopenia' is multifactorial with several factors linking muscle and bone function, including genetics, age, inflammation and obesity. Several biochemical pathways have been identified that are facilitating the development of several promising therapeutic agents, which target both muscle and bone. In the current review we outline the epidemiology, pathogenesis and clinical consequences of 'osteosarcopenia' and explore current and potential future management strategies.

Rituximab in the treatment of systemic sclerosis–related interstitial lung disease: a systematic review and meta-analysis

Abstract: Objectives To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. Methods PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. Results A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). Conclusions Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.

Genetics and epigenetics in primary Sjögren's syndrome.

Abstract: Primary Sjogren's syndrome (pSS) is considered to be a multifactorial disease, where underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to disease development. In the last 5 years, the first genome-wide association studies in pSS have been completed. The strongest signal of association lies within the HLA genes, whereas the non-HLA genes IRF5 and STAT4 show consistent associations in multiple ethnicities but with a smaller effect size. The majority of the genetic risk variants are found at intergenic regions and their functional impact has in most cases not been elucidated. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs play a role in the pathogenesis of pSS by their modulating effects on gene expression and may constitute a dynamic link between the genome and phenotypic manifestations. This article reviews the hitherto published genetic studies and our current understanding of epigenetic mechanisms in pSS.

Telemedicine in rheumatology: a reliable approach beyond the pandemic.

Abstract: OBJECTIVES: The SARS-CoV-2 outbreak has imposed considerable restrictions on people's mobility, which affects the referral of chronically ill patients to health care structures. The emerging need for alternative ways to follow these patients up is leading to a wide adoption of telemedicine. We aimed to evaluate the feasibility of this approach for our cohort of patients with CTDs, investigating their attitude to adopting telemedicine, even after the pandemic. METHODS: We conducted a telephonic survey among consecutive patients referred to our CTD outpatients' clinic, evaluating their capability and propensity for adopting telemedicine and whether they would prefer it over face-to-face evaluation. Demographical and occupational factors were also collected, and their influence on the answers has been evaluated by a multivariate analysis. RESULTS: A total of 175 patients answered our survey (M/F = 28/147), with a median age of 62.5 years [interquartile range (IQR) 53-73]. About 80% of patients owned a device allowing video-calls, and 86% would be able to perform a tele-visit, either alone (50%) or with the help of a relative (36%). Telemedicine was considered acceptable by 78% of patients and 61% would prefer it. Distance from the hospital and patient's educational level were the strongest predictive factors for the acceptance of telemedicine (P < 0.05), whereas age only affected the mastering of required skills (P < 0.001). CONCLUSION: Telemedicine is a viable approach to be considered for routine follow-up of chronic patients, even beyond the pandemic. Our data showed that older patients would be willing to use this approach, although a proper guide for them would be required.

A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies

Abstract: Objectives To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. Methods A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared to the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesised via narrative review. Results Sixty nine studies were included in the meta-analysis. Dermatomyositis subtype (RR 2.21), older age (WMD 11.19), male gender (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73), and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. Polymyositis (RR 0.49) and clinically amyopathic dermatomyositis (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. Computed tomography (CT) scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. Discussion Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.

The role of chest ct in deciphering interstitial lung involvement: systemic sclerosis versus covid-19.

Abstract: OBJECTIVE: To identify the main computed tomography (CT) features that may help distinguishing a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc) from COVID-19 pneumonia. METHODS: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. RESULTS: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p < 0.0001) and signs of fibrosis in GGO in the lower lobes (p < 0.0001) remained independently associated with COVID-19 pneumonia or SSc-ILD, respectively. A predictive score was created which resulted positively associated with the COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). CONCLUSION: The CT differential diagnosis between COVID-19 pneumonia and SSc-ILD is possible through the combination the proposed score and the radiologic expertise. The presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.

Difficult-to-treat rheumatoid arthritis: contributing factors and burden of disease.

Abstract: OBJECTIVES Treatment of difficult-to-treat (D2T) RA patients is generally based on trial-and-error and can be challenging due to a myriad of contributing factors. We aimed to identify risk factors at RA onset, contributing factors and the burden of disease. METHODS Consecutive RA patients were enrolled and categorized as D2T, according to the EULAR definition, or not (controls). Factors potentially contributing to D2T RA and burden of disease were assessed. Risk factors at RA onset and factors independently associated with D2T RA were identified by logistic regression. D2T RA subgroups were explored by cluster analysis. RESULTS Fifty-two RA patients were classified as D2T and 100 as non-D2T. Lower socioeconomic status at RA onset was found as an independent risk factor for developing D2T RA [odds ratio (OR) 1.97 (95%CI 1.08-3.61)]. Several contributing factors were independently associated with D2T RA, occurring more frequently in D2T than in non-D2T patients: limited drug options because of adverse events (94% vs 57%) or comorbidities (69% vs 37%), mismatch in patient's and rheumatologist's wish to intensify treatment (37% vs 6%), concomitant fibromyalgia (38% vs 9%) and poorer coping (worse levels). Burden of disease was significantly higher in D2T RA patients. Three subgroups of D2T RA patients were identified: (i) 'non-adherent dissatisfied patients'; (ii) patients with 'pain syndromes and obesity'; (iii) patients closest to the concept of 'true refractory RA'. CONCLUSIONS This comprehensive study on D2T RA shows multiple contributing factors, a high burden of disease and the heterogeneity of D2T RA. These findings suggest that these factors should be identified in daily practice in order to tailor therapeutic strategies further to the individual patient.

Diagnostic delay in axial spondyloarthritis: a systematic review and meta-analysis.

Abstract: Background . Delay to diagnosis in axial spondyloarthritis (axSpA) is longer than many other rheumatic diseases. Prolonged delay has been shown to associate with poorer outcomes including functional impairment and quality of life. Our aims were to describe 1) global variation in delay to diagnosis, 2) factors associated with delay, and 3) differences in diagnostic delay between axSpA and psoriatic arthritis (PsA). Methods . We searched Medline, PubMed, EMBASE and Web of Science using a predefined protocol in accordance with PRISMA guidelines. Delay to diagnosis was defined as years between age at symptom onset and age at diagnosis. We pooled mean diagnostic delay using random-effects inverse variance meta-analysis. We examined variations in pooled estimates using pre-specified subgroup analyses and sources of heterogeneity using meta-regression. Results. A total of 64 studies reported mean diagnostic delay in axSpA patients. The pooled mean delay was 6.7 years (95% confidence interval 6.2 to 7.2) with high levels of heterogeneity. Delay to diagnosis did not improve over time when stratifying results by year of publication. Studies from high-income countries (defined by the World Bank) reported longer delay than those from middle-income countries. Factors consistently reported to be associated with longer delay were: lower education levels, younger age at symptom onset and absence of extra-articular manifestations. Pooled estimate for diagnostic delay from 8 PsA studies was significantly shorter, at 2.6 years (95%CI 1.6 to 3.6). Conclusion. For axSpA patients, delay to diagnosis remains unacceptably prolonged in many parts of the world, although some countries have reported remarkable improvements. Patient factors (education) and disease presentation (age at onset and extra-articular manifestations) should inform awareness campaigns to improve delay. Targets for improvement should aim to resemble delays in other spondyloarthritis patients.

Treatment of Sjögren's syndrome: current therapy and future directions.

Abstract: SS is usually described as having severe fatigue, dryness, diffuse pain, glandular swelling, and various extraglandular (systemic) manifestations. Clinical trials have generally failed because the vast majority of enrolled patients had no extraglandular manifestations at the time of enrolment but suffered from fatigue, dryness and pain that did not significantly respond to the study medication. A number of hypotheses on the pathogenesis of pSS have been put forward, including disturbances of innate and adaptive immunity as well as abnormalities of the interface between immune disorders and the neuro-endocrine system related to lacrimal and secretory gland dysfunction. Thus, future therapies must be designed for improvement of the symptoms of dry eyes and dry mouth, extraglandular disease, and fatigue and cognitive deficits. Given the inadequacies and limitations of current treatment options, we suggest that innovative directions involving interactions with neuroscientists and neuropsychiatrists together or combined with new immune targeting may be hold promise for better treating pSS.

Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2).

Abstract: Objective: To evaluate the impact of anti-Tumour Necrosis Factor-α (anti-TNF) treatment on the occurrence of vasculitic ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2). Methods: A retrospective analysis of DADA2 patients referred from six centres to Great Ormond Street Hospital for Children was conducted. Ischaemic events, vasculitic disease activity, biochemical, immunological, and radiological features were compared, before and after anti-TNF treatment. Results: A total of 31 patients with genetically confirmed DADA2 were included in the study. The median duration of active disease activity prior to anti-TNF treatment was 73 months (inter-quartile range [IQR] 27.5–133.5 months). Twenty seven/31 patients received anti-TNF treatment for a median of 32 months (IQR 12.0–71.5 months). The median event rate of central nervous system (CNS) and non-CNS ischemic events before anti-TNF treatment was 2.37 per 100 patient-months (IQR 1.25–3.63); compared with 0.00 per 100 patient-months (IQR 0.0–0.0) post-treatment (p< 0.0001). Paediatric vasculitis activity score (PVAS) was also significantly reduced: median score of 20/63 (IQR 13.0–25.8/63) pre-treatment vs. 2/63 (IQR 0.0–3.8/63) following anti-TNF treatment (p< 0.0001), with mild livedoid rash being the main persisting feature. Anti-TNF treatment was not effective for severe immunodeficiency or bone marrow failure, which required haematopoietic stem cell transplantation (HSCT). Conclusion: Anti-TNF treatment significantly reduced the incidence of ischaemic events and other vasculitic manifestations of DADA2, but was not effective for immunodeficiency or bone marrow failure.

Risk of death among people with rare autoimmune diseases compared with the general population in England during the 2020 COVID-19 pandemic.

Abstract: OBJECTIVES To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. METHODS We conducted a cohort study in Hospital Episode Statistics for England from 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. RESULTS We included 168 691 people with a recorded diagnosis of RAIRD alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. A total of 1815 (1.1%) participants died during March and April 2020. The age-standardized mortality rate (ASMR) among people with RAIRD (3669.3; 95% CI: 3500.4, 3838.1 per 100 000 person-years) was 1.44 (95% CI: 1.42, 1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. CONCLUSION The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to health-care services.

Mortality, causes of death and influence of medication use in patients with systemic lupus erythematosus vs matched controls.

Abstract: Objectives We wanted to estimate the magnitude of the risk from all-cause, cause-specific and sex-specific mortality in patients with SLE and relative risks compared with matched controls and to evaluate the influence of exposure to medication on risk of mortality in SLE. Methods We conducted a population-based cohort study using the Clinical Practice Research Datalink, Hospital Episode Statistics and national death certificates (from 1987 to 2012). Each SLE patient (n = 4343) was matched with up to six controls (n = 21 780) by age and sex. Cox proportional hazards models were used to estimate overall and cause-specific mortality rate ratios. Results Patients with SLE had a 1.8-fold increased mortality rate for all-cause mortality compared with age- and sex-matched subjects [adjusted hazard ratio (HR) = 1.80, 95% CI: 1.57, 2.08]. The HR was highest in patients aged 18-39 years (adjusted HR = 4.87, 95% CI: 1.93, 12.3). Mortality rates were not significantly different between male and female patients. Cumulative glucocorticoid use raised the mortality rate, whereas the HR was reduced by 45% with cumulative low-dose HCQ use. Patients with SLE had increased cause-specific mortality rates for cardiovascular disease, infections, non-infectious respiratory disease and for death attributable to accidents or suicide, whereas the mortality rate for cancer was reduced in comparison to controls. Conclusion British patients with SLE had a 1.8-fold increased mortality rate compared with the general population. Glucocorticoid use and being diagnosed at a younger age were associated with an increased risk of mortality. HCQ use significantly reduced the mortality rate, but this association was found only in the lowest cumulative dosage exposure group.

A case of psoriatic arthritis triggered by SARS-CoV-2 infection.

Abstract: DEAR EDITOR, Several autoimmune/autoinflammatory phenomena have been described during the new coronavirus SARS-CoV-2 pandemic, including cytokine storm/ macrophage-activation syndrome (MAS), vasculopathy (Kawasaki-like disease, chill-blain lesions), haematological alterations (hemolytic anaemia, antiphospholipids), skin manifestations (urticaria, purpura), demyelinating syndromes (Guillan–Barrè syndrome) and arthritis. To date, a few cases of arthritis have been reported with SARS-CoV-2 infection. Their features partially resemble the three subgroups of arthritis possibly associated to viral infections: viral arthritis, reactive arthritis or chronic arthritis triggered by viral infection. Yokogawa and colleagues described a case of knee arthritis occurring during SARS-CoV-2 disease (COVID-19), resolving spontaneously, and then suspected for viral arthritis [1]. Four cases resembling reactive arthritis have been reported after COVID-19 resolution: polyarthritis involving lower limbs and developing 8 days after COVID-19 symptoms [2], elbow arthritis with skin psoriasis developing 10 days after COVID-19 symptoms [3], knee arthritis with balanitis [4], and bilateral ankle arthritis with mild enthesitis on day 21 after COVID-19 [5]. A few days before COVID-19 symptoms, two other patients developed polyarthritis with a chronic course and in one case with positive anti-citrullinated peptide antibodies, thus suggesting rheumatoid arthritis triggered by the virus [6, 7]. We report, herein, the case of a 27-year-old woman who developed spondyloarthritis concomitantly with SARS-CoV-2 infection. She had a personal history for irritable bowel disease and a family history for psoriasis but never showed skin/nail lesions or articular/axial involvement. At the end of February 2020, she developed acute arthritis of the left ankle followed 7 days later by anosmia and dysgeusia, without fever or cough. No specific assays were performed to detect SARS-CoV-2 and symptoms resolved spontaneously within 2 weeks. In May she developed left knee arthritis (Fig. 1A) and a skin lesion on lumbar region resembling psoriasis (Fig. 1A). Inflammatory markers were slightly increased, while rheumatoid factor, anti-citrullinated peptides, and anti-nucleus antibodies were negative. MRI was performed (Fig. 1A) and an arthrocentesis followed by intraarticular steroid injection of the left knee was assessed with evacuation of 80 ml of inflammatory synovial fluid. In July, the patient was admitted to Humanitas Research Hospital for diarrhoea, low back pain, and arthritis involving the left knee and the metatarsophalangeal joints. Colonoscopy showed erythematous lesions of the caecum and rectum, but histological examination was not specific for inflammatory bowel disease (Fig. 1B). Sacroiliac MRI showed mild bilateral sacroiliitis (Fig. 1C) and HLA-B27 was negative. She had no fever or respiratory symptoms, a nasopharyngeal swab proved negative for SARS-CoV-2, a chest CT scan was negative for COVID-19 pneumonia, anti-SARS-CoV-2 IgG were positive (28 U/ml; Elecsys, Roche Diagnostics International, Basel, Switzerland). Synovial fluid, previously collected and stored at 20 C, was negative for SARS-CoV-2 genome (Cobas 680/8800 SARS-CoV-2, Roche) and positive for anti-SARS-CoV-2 IgG (29 U/ml; Elecsys, Roche). Therefore, psoriatic spondyloarthritis triggered by SARS-CoV-2 infection in a genetically predisposed subject was diagnosed and this is the first case reported, to our knowledge. The clinical presentation and course excluded the diagnosis of viral arthritis, which generally manifests as an acute monophasic arthritis and has a self-limiting course. Moreover, virus genome was absent in the synovial fluid, while the presence of anti-SARSCoV-2 in the synovial fluid could be the result of blood immunoglobulins crossing the inflamed synovia, as immunoglobulin levels were very similar in the blood and synovial fluid, regardless of different sample collection time. A diagnosis of reactive arthritis was also appraised less likely considering the onset of arthritis before the clinical manifestations of viral infection, while reactive arthritis generally develops after 1–24 weeks from the infection. The mechanisms by which SARS-CoV-2 can trigger autoimmunity and autoinflammation remain unknown. A virus-induced hyper-inflammatory milieu has been evoked in the case of MAS, while a Th17-shift has been hypothesized in the case of reactive arthritis [3]. The cases of rheumatoid arthritis and our case of spondyloarthritis developing before COVID-19 symptoms and in mild/asymptomatic patients suggest alternative mechanisms, such as immune-surveillance escaping. This ability of SARS-CoV-2 can be explained by disruption of the type I IFN–plasmacytoid dendritic cell response, which is the basis of the immune system activation, and the possible impairment of antigen recognition due to lymphocytopenia and exhaustion status of immune cells together with the down-modulation of the HLA-system induced by SARS-CoV-2. All of these mechanisms are Rheumatology key message

Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis.

Abstract: Objectives: The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokines levels in patients with diffuse CPS (fibromyalgia) versus healthy controls (HC). Methods: Human studies published in English from the PubMed and MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO(CRD42020193774). Results: Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared to HC, while the chemokine eotaxin, was consistently raised in fibromyalgia . Meta-analysis showed significantly increased tumour necrosis factor alpha (TNF-α) (SMD=0.36, p = 0.0034, 95%CI=0.12-0.60; I2=71%, Q2 p = 0.0002), interleukin (IL)-6 (SMD=0.15, p = 0.045, %95CI=0.003-0.29; I2=39%, Q2 p = 0.059), IL- 8 (SMD=0.26, p = 0.01, 95%CI =0.05-0.47; I2=61%, Q2 p = 0.005) and IL-10 (SMD=0.61; %95 = 0.34-0.89, p < 0.001; I2 = 10%, Q2 p = 0.34) in fibromyalgia patients compared to HC. Conclusion: We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared to HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8), and anti-inflammatory cytokines (IL-10) in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.

Incidence and prevalence of systemic sclerosis globally: A comprehensive systematic review and meta-analysis

Abstract: Objectives: We aimed to conduct a systematic review and meta-analysis on the incidence and prevalence of SSc covering the entire literature. Methods: This study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement of 2009. We conducted a systematic search in MEDLINE, Web of Science and Embase to identify articles reporting incidence and/or prevalence of SSc. Two authors conducted the search, reviewed articles for inclusion and extracted relevant data. We used random-effects models to estimate the pooled prevalence and incidence of SSc and performed subgroup analyses by sex, case definition and region to investigate heterogeneity. We explored the association between calendar period and reported estimates using meta-regression. Results: Among 6983 unique records identified, we included 61 studies of prevalence and 39 studies of incidence in the systematic review. The overall pooled prevalence of SSc was 17.6 (95% CI 15.1, 20.5) per 100 000 and the overall pooled incidence rate of SSc was 1.4 (95% CI 1.1, 1.9) per 100 000 person-years. We observed significant regional variations in reported estimates; studies conducted in North America reported considerably higher estimates than other regions. The pooled incidence and prevalence in women were five times higher than in men. More recent studies reported higher estimates than older ones. Conclusion: In this comprehensive review of the incidence and prevalence of SSc across the world, there was large heterogeneity among estimates, which should be taken into consideration when interpreting the results. (Less)

COVID-19 and myositis - unique challenges for patients.

Abstract: Objective The COVID-19 pandemic and the subsequent effects on healthcare systems is having a significant effect on the management of long-term autoimmune conditions. The aim of this study was to assess the problems faced by patients with idiopathic inflammatory myopathies (IIM). Methods An anonymized eSurvey was carried out with a focus on effects on disease control, continuity of medical care, drug procurance and prevalent fears in the patient population. Results Of the 608 participants (81.1% female, median (s.d.) age 57 (13.9) years), dermatomyositis was the most frequent subtype (247, 40.6%). Patients reported health-related problems attributable to the COVID-19 pandemic (n = 195, 32.1%); specifically 102 (52.3%) required increase in medicines, and 35 (18%) required hospitalization for disease-related complications. Over half (52.7%) of the surveyed patients were receiving glucocorticoids and/or had underlying cardiovascular risk factors (53.8%), placing them at higher risk for severe COVID-19. Almost one in four patients faced hurdles in procuring medicines. Physiotherapy, critical in the management of IIM, was disrupted in 214 (35.2%). One quarter (159, 26.1%) experienced difficulty in contacting their specialist, and 30 (4.9%) were unable to do so. Most (69.6%) were supportive of the increased use of remote consultations to maintain continuity of medical care during the pandemic. Conclusion This large descriptive study suggests that the COVID-19 pandemic has incurred a detrimental effect on continuity of medical care for many patients with IIM. There is concern that delays and omissions in clinical care may potentially translate to poorer outcomes in the future.

Methotrexate and risk of interstitial lung disease and respiratory failure in rheumatoid arthritis: a nationwide population-based study

Abstract: Objectives MTX is the most commonly recommended DMARD for first-line treatment of RA, however, it has been hypothesized to cause lung disease as an adverse effect. We investigated the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in persons with RA treated with MTX and other medications. Methods From the Danish National Patient Register (NPR) and the DANBIO register for rheumatic diseases, we retrieved data on 30 512 persons with RA registered in 1997-2015. Information on ILD and respiratory failure was obtained from the NPR. Information on age and sex for all Danish citizens was obtained from the Danish Civil Registration System. MTX and other medication purchases were retrieved from the Danish Prescription Registry. Associations between MTX and lung disease outcomes were analysed in Cox regression models with adjustment for age, calendar time, sex and other medications. Standardized incidence ratios (SIRs) of lung disease were calculated to compare the RA population with the general population. Results There was no increased risk of lung disease with MTX treatment [one or more purchases compared with no purchases; HR 1.00 (95% CI 0.78, 1.27) for ILD and 0.54 (95% CI 0.43, 0.67) for respiratory failure] at the 5 year follow-up. The SIR was three to four times higher for ILD in MTX-treated persons with RA, but similar to the whole RA population compared with the background population. Conclusion Persons with RA had an increased risk of ILD compared with the general population, but there was no further increased risk associated with MTX treatment.

Rheumatoid arthritis related interstitial lung disease – improving outcomes over 25 years: a large multicentre UK study

Abstract: Objective: This study explores whether the prognosis of interstitial lung disease in rheumatoid arthritis (RA-ILD) has improved over time and assesses the potential influence of drug therapy in a large multicentre UK network. Methods: We analysed data from 18 UK centres on patients meeting criteria for both RA and ILD diagnosed over a 25-year period. Data included age, disease duration, outcome and cause of death. We compared all cause and respiratory mortality between RA controls and RA-ILD patients, assessing the influence of specific drugs on mortality in four quartiles based on year of diagnosis. Results: A total of 290 RA-ILD patients were identified. All cause (respiratory) mortality was increased at 30% (18%) compared with controls 21% (7%) (P =0.02). Overall, prognosis improved over quartiles with median age at death rising from 63 years to 78 years (P =0.01). No effect on mortality was detected as a result of DMARD use in RA-ILD. Relative risk (RR) of death from any cause was increased among patients who had received anti-TNF therapy [2.09 (1.1–4.0)] P =0.03, while RR was lower in those treated with rituximab [0.52(0.1–2.1)] or mycophenolate [0.65 (0.2–2.0)]. Patients receiving rituximab as their first biologic had longer three (92%), five (82%) and seven year (80%) survival than those whose first biologic was an anti-TNF agent (82%, 76% and 64%, respectively) (P =0.037). Discussion: This large retrospective multicentre study demonstrates survival of patients with RA-ILD has improved. This may relate to the increasing use of specific immunosuppressive and biologic agents.

The safety of JAK-1 inhibitors.

Abstract: As efficacy and safety data emerge, differences between JAK inhibitor subclasses are appearing. JAK1 selective drugs, upadacitinib and filgotinib, have broadly come with the same overarching safety recommendations as other immunosuppressive drugs for RA: caution is needed regarding infection risk; monitoring for laboratory abnormalities, including lipids and muscle enzymes, is indicated. A distinguishing feature of JAK inhibitors is a risk for zoster reactivation. Numerically, overall rates of serious infection are similar among JAK inhibitor classes. There are currently no signals for diverticular perforation. VTE incidence rates were similar across comparator groups for the JAK1 selective agents. These observations are not yet conclusive evidence for different safety profiles between JAK1 selective agents and other JAK inhibitors. Differences in study population, design, and concomitant steroid use are examples of potential confounders. It is too early to draw conclusions on long-term outcomes such as malignancy and cardiovascular risk. Post-marketing pharmacovigilance studies will be essential.

Innate immunity and interferons in the pathogenesis of Sjögren's syndrome.

Abstract: Primary SS (pSS) is a rheumatic disease characterized by an immune-mediated exocrinopathy, resulting in severe dryness of eyes and mouth. Systemic symptoms include fatigue and joint pain and a subset of patients develop more severe disease with multi-organ involvement. Accumulating evidence points to involvement of innate immunity and aberrant activity of the type I IFN system in both the initiation and propagation of this disease. Analysis of the activity of IFN-inducible genes has evidenced that more than half of pSS patients present with a so-called 'type I IFN signature'. In this review, we examine activation of the IFN system in pSS patients and how this may drive autoimmunity through various immune cells. We further discuss the clinical value of assessing IFN activity as a biomarker in pSS patients and review novel therapies targeting IFN signalling and their potential use in pSS.

Global, regional, and national burden of other musculoskeletal disorders 1990-2017: results from the Global Burden of Disease Study 2017.

Abstract: Objectives To describe the level and trends of point prevalence, deaths and disability-adjusted life years (DALYs) for other musculoskeletal (MSK) disorders, i.e. those not covered by specific estimates generated for RA, OA, low back pain, neck pain and gout, from 1990 to 2017 by age, sex and sociodemographic index. Methods Publicly available modelled estimates from the Global Burden of Disease (GBD) 2017 study were extracted and reported as counts and age-standardized rates per 100 000 population for 195 countries and territories between 1990 and 2017. Results Globally, the age-standardized point prevalence estimates and deaths rates of other MSK disorders in 2017 were 4151.1 and 1.0 per 100 000. This was an increase of 3.4% and 7.2%, respectively. The age-standardized DALY rate in 2017 was 380.2, an increase of 3.4%. The point prevalence estimate was higher among females and increased with age. This peaked in the 65-69 year age group for both females and males in 2017, followed by a decreasing trend for both sexes. At the national level, the highest age-standardized point prevalence estimates in 2017 were seen in Bangladesh, India and Nepal. The largest increases in age-standardized point prevalence estimates were observed in Romania, Croatia and Armenia. Conclusion The burden of other MSK disorders is proven to be substantial and increasing worldwide, with a notable intercountry variation. Data pertaining to specific diseases within this overarching category are required for future GBD MSK estimates. This would enable policymakers to better allocate resources and provide interventions appropriately.

Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis.

Abstract: Objective The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA). Methods A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs). Results Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks. Conclusions In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.

Clinical course of 602 patients with Takayasu's arteritis: comparison between Childhood-onset versus adult onset disease.

Abstract: Objectives To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK). Methods Data related to clinical features and response to treatment of patients with cTAK (age of onset Results Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P 5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression. Conclusion Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK.

Beneficial effect of Mediterranean diet on disease activity and cardiovascular risk in systemic lupus erythematosus patients: a cross-sectional study

Abstract: Objective To analyse the influence of the Mediterranean diet (Med Diet) on SLE activity, damage accrual and cardiovascular disease risk markers Methods A cross-sectional study was conducted on 280 patients with SLE [469 (1285) years] Med Diet adherence was assessed through a 14-item questionnaire on food consumption frequency and habits (total score from 0 to 14 points; higher score is greater adherence to the Med Diet) CRP, homocysteine, SLEDAI-2K (SLE disease activity), and SLICC/ACR and SDI (damage accrual) were measured Obesity, diabetes mellitus, hypertension and blood lipids, among others, were considered cardiovascular disease risk factors Results Greater adherence to the Med Diet was significantly associated with better anthropometric profiles, fewer cardiovascular disease risk factors, and lower disease activity and damage accrual scores (P ≤ 0001 for SLEDAI and SDI) An inverse relationship between the Med Diet score and SLEDAI (P ≥ 0001; β = -0380), SDI (P ≤ 0001; β = -0740) and hsCRP (P = 0039; β = -0055) was observed The odds ratio for having active SLE (SLEDAI ≥5) or the presence of damage (SDI ≥1) was lower among patients whose Med Diet score was higher (P ≤ 0001) Finally, greater consumption of Med Diet foods (olive oil, fruits, vegetables, fish, etc) and abstaining from red meat and meat products, sugars and pastries was associated with less SLE clinical activity and damage Conclusion Greater adherence to the Med Diet seems to exert a beneficial effect on disease activity and cardiovascular risk in SLE patients To confirm these findings, further longitudinal studies would be of interest

EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies.

Abstract: Objectives aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria ('criteria aPL') and at titres lower than thresholds considered by classification criteria ('low-titre aPL') on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). Methods Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. Results EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-β2-glycoprotein I (β2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-β2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-β2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-β2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. Conclusion EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.