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Background/Aims A 72-year-old lady presented in primary care with complaints of generalised body aches, bilateral leg weakness and constitutional symptoms following a first dose of COVID-19 vaccine. Blood tests showed slightly raised inflammatory markers. She was initially diagnosed with polymyalgia rheumatica and was started on 40mg prednisolone with minimal improvement. Methods The examination in the rheumatology clinic was unremarkable. Investigations revealed raised white cell count, consistent with high dose steroid treatment, and elevated monocytes. There was mild improvement in inflammatory markers. The working diagnosis was of self-limiting viral illness. Further testing discovered strongly positive MPO ANCA (115 IU/ml), and the patient received three pulses of 500mg methylprednisolone for suspected vasculitis arranged by the medical team. There was no evidence of renal involvement. The diagnosis made at this point was autoimmune inflammatory disorder with unclear aetiology. At the subsequent clinic visit she reported mild shortness of breath, but no other symptoms suggestive of either vasculitis or connective tissue disease. Repeat ANCA showed significant reduction in MPO titre following pulse steroid treatment. CT of chest, abdomen and pelvis demonstrated a localised lobular/ nodular deformity of the liver. Viral hepatitis screen was negative. CA19-9 was raised at 100 U/ml. Liver biopsy was reported as poorly differentiated carcinoma without specific localising immunohistochemical features. Results The patient underwent hemi-hepatectomy for histologically confirmed pT2pNXM0R0 liver cholangiocarcinoma in a tertiary centre followed by adjuvant chemotherapy with capecitabine. With treatment, her MPO ANCA and CA19-9 levels declined. An interval CT scan of chest, abdomen and pelvis performed ten months after the surgery, showed no recurrence of malignancy. Given the fact that the patient's MPO ANCA fell following the treatment of cholangiocarcinoma, it is likely that positive MPO ANCA is associated with underlying malignancy rather than an active vasculitis. Conclusion This unusual case describes an evolution of the diagnostic process guided by non-specific symptoms and ANCA positivity, arriving at an unexpected diagnosis of malignancy. Although ANCA is a sensitive and specific marker of vasculitides, it can be positive in other conditions particularly hepatitis B, inflammatory bowel disease and autoimmune liver disorders. Malignancy can also be associated with ANCA in the absence of vasculitis. In one study, of 118 ANCA positive patients without ANCA-associated vasculitis, four were found to have malignancy. In a study of 1024 patients who had ANCA tested, 61 patients were found to have malignancy, predominantly haematological and lung cancers. However, after adjustment for sex, age and time of blood draw, no association was found between ANCA status and incidence of cancer. Interestingly, paraneoplastic vasculitis such as polyarteritis nodosa (PAN) has been described in the context of underlying cholangiocarcinoma, and is associated with ANCA rise. Moreover, patients with raised ANCA and PAN also have raised CA 19- 9.
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Background/Aims There are sporadic reports about the development of new rheumatic immune-mediated inflammatory diseases (R-IMIDs) in adults after receiving SARS-CoV-2 vaccines. This systematic review (SR) aimed to critically review and summarize the clinical profile, patient demographics, treatment, and prognosis of new-onset R-IMIDs following SARS-CoV-2 vaccination. Methods We retrieved English-language articles (Case reports and series and observational studies) on new-onset R-IMIDs following SARS-CoV-2 vaccination, published until June 2022, from standard databases (MEDLINE, Embase, Cochrane). The search strings used during the literature search incorporated 'SARS-CoV-2 vaccination' (along with related MeSH terms) and various key terms for R-IMIDs [which included (but was not limited to) inflammatory arthritis, connective tissue disease (CTD), vasculitis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, systemic sclerosis, idiopathic inflammatory myositis, anti-synthetase syndrome, Adult-onset Stills disease (AOSD), giant cell arteritis (GCA), and polymyalgia rheumatica (PMR)]. The protocol was registered in PROSPERO (CRD42022318561). Results Of the total 2179 articles retrieved, 1986 articles were excluded following the title- screening, and 107 articles that did not meet inclusion criteria. We included the remaining 86 articles (130 cases) upon full-text screening. Furthermore, we added four articles (six cases) based on a manual search, comprising 90 articles (136 cases) for final analysis. These 136 new R-IMID cases were reported from 27 different countries. Of these, more than one-third of the cases were reported from three countries (viz., Italy, Japan, and the USA). The patients had a mean age of 57 (range:17-90) years, and the majority were females (63.0%). Most patients developed R-IMIDs after receiving Pfizer-BioNTech vaccine (76;55%), followed by Oxford AstraZeneca vaccine (35;25%). The mean duration between SARSCoV- 2 vaccination and R-IMIDs development was 9.2 (range:1-90) days. The second dose of the vaccine resulted in more R-IMIDs (74;54%) than the first (53;39%). CTDs (34;25%) and small vessel vasculitis (33;24%) were the commonest R-IMID manifestations, followed by inflammatory arthritis and AOSD, each in 13 (9.5%) cases. Nearly half of the patients with CTDs had Idiopathic Inflammatory Myositis. PMR and GCA accounted for 16 (11.7%) and 5 (3.6%) cases, respectively. However, no cases of axial spondylarthritis were reported. Most (118;86%) R-IMID patients were treated with corticosteroids, with a small number receiving steroid-sparing drugs, such as methotrexate, rituximab and cyclophosphamide. Most (125;91%) went into either disease remission or improvement following the treatment. Only three patients were admitted to the intensive care unit (ICU) to manage their disease;One of them died due to fatal myositis and rhabdomyolysis;two surviving ICU patients had ANCA-associated vasculitis with lung involvement. Conclusion Although rare, this SR highlights the emergence of de novo R-IMIDs following SARS-CoV-2 vaccination. We cannot confirm the causality between the vaccination and the onset of R-IMID. However, further research is warranted in this area.
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Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs. The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice. Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records. Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjogren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases. Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.Copyright © Team of Authors, 2022.
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Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs. The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice. Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records. Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjögren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases. Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.
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Objectives Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinflammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, methotrexate, leflunomide and tocilizumab. In this study, we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases (based on humoral and cellular immunity). Methods Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks after the second dose (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-vaccination and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared with age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specific T-cells was assessed by IFN-gammaELIspot assay, and side effects and disease activity were recorded. Results GCA/PMR patients did not have reduced antibody concentrations compared with controls. However, linear regression analysis revealed a significant association of methotrexate and >10 mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients. Patients using >10 mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to significant side effects or changes in disease activity. Conclusions SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10 mg/day prednisolone did show lower vaccine responses, which corroborates findings in other autoinflammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection. Copyright ©
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Background: In recent times, safety and potential adverse effects (AEs) of Sars-CoV-2 vaccines have gained great relevance and have been a central topic in Scientific discussion. Objectives: The aim of this study was to evaluate the incidence of AEs after Sars-CoV-2 vaccine administration in patients affected by Connective Tissue Disease, Vasculitis or Polymyalgia Rheumatica. Moreover, we assessed patients' adherence to the American College of Rheumatology (ACR)1 or Italian Rheumatology Society (SIR)2 recommendations. Methods: 139 patients affected by Connective Tissue Disease, Vasculitis or Polymyalgia Rheumatica were enrolled at the Rheumatology Units of University Hospitals of Bari and Foggia. All patients were given a questionnaire to evaluate vaccine type and dose number, AEs, potential pre-vaccine prophylaxis, immuno-suppressive therapy and its possible suspension according to the clinical guidance summary proposed by ACR or SIR. Results: Among the 139 enrolled patients (120 females and 19 males, mean age 54 ± 14,7 year, mean disease duration 8,6 ± 7, 4 years), 31 subjects (19%) received anti Sars-CoV-2 vaccination. 5 patients received the Astra-Zeneca COVID-19 vaccine, 23 the BioNTech-Pfzer COVID-19 vaccine and 3 the Moderna vaccine. Only 48% of subjects received two doses. 42% of patients reported non-severe AEs after the frst dose of vaccine, specifcally 45% of patients who received the BioNTech-Pfzer COVID-19 vaccine, 40% of those who were administered the AstraZeneca vaccine and 33% of those who received the Moderna vaccine. Most frequent AEs were site injection pain (19%), fatigue (13%), headache (13%), myalgia (6%), fever (6%), nausea (3%), rheumatic disease fare (3%) (the latest was reported only among the Polymyalgia Rheumatica patients). Considering the different diseases, the highest trend of AEs was observed in Polymialgya Rheumatica (66%), Systemic Sclerosis (57%), Sjogren Syndrome (40%) and undifferentiated connective tissue disease (23%) patients. 30% of patients who received the second vaccine dose reported AEs. All of them were administered the BioNTech-Pfzer COVID-19 vaccine. Most reported AEs after the second vaccine dose were site injection pain (6%), headache (3%), myalgia (6%), fever (6%). The highest trend of AEs was observed in undifferentiated connective tissue disease (60%) and Sjogren Syndrome (33%) patients. Only 13 % of subjects who reported AEs after the frst vaccine administration, reported AEs also after the second dose. Only 9,7% of patients did not comply with the COVID-19 vaccine clinical guidance prosed by ACR or SIR regarding immunosuppressive treatment management before and after immunization. Conclusion: Patients enrolled in this study developed mild AEs. Only among Polymyalgia Rheumatica patients were described disease fares and higher trend of AEs. Although patients affected by Systemic Lupus Erythematosus, Antiphospholipid Syndrome and Vasculitis were enrolled, none of them reported severe AEs, included the extensively discussed post-vaccine thrombosis. We found no signifcant dissimilarity of AEs relating to different types of vaccine and good patient compliance to physician recommendations about treatment management.
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Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.
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Background: During the COVID-19 pandemic, the patients with rheumatic disease in the biopsychosocial perspective have been adversely affected by social isolation, uncertainty, and the thought that their chronic disease will worsen and increase in their symptoms. ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) defnes recommendations about continuing current pharmacotherapy and the signifcance of the biopsychosocial approach and exercise for patients with rheumatic diseases during a COVID-19 infection 1, 2. Objectives: This study aims to investigate the effectiveness of the biopsychoso-cial exercise performed by telerehabilitation on biopsychosocial status, general health status, and anxiety-depression levels in the patients with infammatory and non-infammatory rheumatic diseases. Methods: Fourteen patients with infammatory rheumatic diseases (rheumatoid arthritis: 4;ankylosing spondylitis: 4;sjogren's syndrome: 3;polymyalgia rheumatica: 2;and vasculitis: 1) and eight patients with non-infammatory rheumatic diseases (fbromyalgia: 6;and osteoarthritis: 2) performed a biopsychoso-cial-based exercise model (named as 'Bilişsel Egzersiz Terapi Yaklaşimi'-(BETY) in original;'Cognitive Exercise Therapy Approach' in English) via telerehabilita-tion continued for three sessions per week for 12 months 3. Outcome measures were Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS), and BETY-Biopsychosocial Questionnaire (BETY-BQ) 4. All outcomes were measured baseline and at the 12th month. The Wilcoxon's test was used for statistical analysis. Results: All of the 22 patients were female. The mean age was 57.4 and 55.8 years in the infammatory and non-infammatory rheumatic diseases groups respectively, and they had a mean BMI of 25.9 and 25.3 kg/m2. There was no signifcant difference by time for HAQ score (p = 0.125), HADS anxiety and depression (p = 0.916 and p = 0.663, respectively), and BETY-BQ score (p = 0.753) between the baseline and at the 12th month follow-up in the patients with infammatory rheumatic diseases. Similarly, in the patients with non-in-fammatory rheumatic diseases, there was no signifcant difference by time for HAQ score (p = 0.546), HADS anxiety and depression (p = 0.343 and p = 0.527, respectively), and BETY-BQ score (p = 0.068) between the baseline and at the 12th month follow-up. Conclusion: This study showed that biopsychosocial-based exercise through real-time telerehabilitation was able to maintain their conditions before pandemic in biopsychosocial status, general health, and anxiety-depression levels on the patients with infammatory and non-infammatory rheumatic diseases during COVID-19 pandemic period in one-year follow-up.
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Background: Interleukin-6 (IL-6) is elevated in patients with active polymyalgia rheumatica (PMR) and is associated with disease activity, relapse and severity. Clinical trials with IL-6 receptor (IL-6R) inhibitors in PMR showed higher remission rates and reduced glucocorticoid (GC) use vs GC alone.1-4 Objectives: The SAPHYR study (NCT03600818) assessed the efficacy and safety of sarilumab (SAR), a fully human anti IL-6Rα monoclonal antibody, with a 14 week (wk) GC taper in patients with steroid resistant active PMR who fared on ≥7.5 mg/day prednisone or equivalent. Methods: Patients were randomized (1:1) to 52 wks of treatment with SAR 200 mg every 2 wks (Q2W) + 14 wk GC tapered regimen (SAR arm) OR placebo Q2W + 52 wk GC tapered regimen (comparator arm). The primary endpoint was the proportion of patients achieving sustained remission at wk 52, defned as disease remission by wk 12, absence of disease fare, CRP normalization from wks 12 to 52 and adherence to the per protocol GC taper from wks 12 to 52. Results: The study was terminated early due to protracted recruitment timelines during the COVID-19 pandemic, resulting in 118 of the intended 280 patients recruited between Oct 2018 and Jul 2020, and 117 were treated (SAR n=59, comparator n=58). The demographics were balanced;patients were primarily female, Caucasian, and a median age of ~70 years (Table 1). Overall, 78 patients completed the treatment (SAR n=42;comparator n=36). Primary reasons for treatment discontinuation were adverse events (AEs;SAR n=7, comparator n=4) and lack of efficacy (SAR n=4, comparator n=9). Sustained remission rate was signifcantly higher in the SAR arm vs the comparator arm (28.3% vs 10.3%;P=0.0193). Results of a sensitivity analysis excluding CRP from the sustained remission defnition was consistent with the primary analysis (31.7% vs 13.8%;P=0.0280). All sustained remission components favored SAR (Figure 1). Patients in the SAR arm were 44% less likely to have a fare after achieving clinical remission vs the comparator arm (16.7% vs 29.3%;HR 0.56;95% CI 0.35-0.90;P=0.0158). The comparator arm required more additional GCs vs the SAR arm, mainly due to PMR fare (median difference in actual and expected cumulative dose 199.5 mg vs 0.0 mg;P=0.0189). The cumulative GC toxicity index scores numerically favored SAR but the difference was not statistically signifcant. PMR activity scores improved in the SAR arm vs the comparator arm (LS mean-15.57 vs-10.27, nominal P=0.0002). Patient reported outcomes (eg, physical and mental health component scores, disability index, etc) favored SAR (Figure 1). Incidence of treatment-emergent AEs (TEAEs) was numerically higher in the SAR arm vs the comparator arm (94.9% vs 84.5%) and included neutropenia (15.3%) and arthralgia (15.3%) in the SAR arm, and insomnia (15.5%) in the comparator arm. Conversely, the frequency of serious AEs was higher in the comparator arm vs the SAR arm (20.7% vs 13.6%). No deaths were reported. Conclusion: SAR + 14 wk GC taper demonstrated signifcant efficacy vs the comparator arm in steroid refractory PMR patients, including clinically meaningful improvement in quality of life. Safety was consistent with the known safety profile of SAR.
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Background: COVID-19 has become a common disease in patients with rheumatic immune-mediated diseases (R-IMID). A risk stratifcation of the patients at COVID-19 onset is important to predict possible unfavorable results. Objectives: To identify predictive severity factors in patients with COVID-19 with R-IMID. Methods: Cross-sectional study in a single University Hospital. We included all consecutive patients with a R-IMID and COVID-19 up to November 6th, 2020. Confrmed infection was defned if the patient had a positive nasopharyngeal swab for SARS-CoV-2. COVID-19 case severity was divided into mild, moderate, severe and critical according to the United States National Institute of Health (NIH) COVID-19 guidelines (1). We performed a multivariable analysis and calculated de odds ratio of critical COVID in patients with R-IMID, adjusting by age, sex and comorbidities. Results: We included 274 patients with R-IMID complicated with COVID-19. At COVID-19 onset, the main comorbidities, analytical values, underlying R-IMID and treatments received are shown in Table 1. According to COVID-19 severity, patients were mild (n=209;76.3%), moderate (n=35;12.8%), severe (n=9;3.3%) and critical (n=21;7.7%). The predictive variables at COVID-19 onset related statistically to critical COVID were older patients, hypertension, dyslipidemia, previous cardiovascular disease, cancer, chronic kidney disease, and chronic liver disease. The only underlying R-IMID and treatment was polymyalgia rheumatica and Rituximab, respectively. Regarding analytical values were higher values of C-reactive protein, LDH, platelets and lymphopenia (Figure 1). Conclusion: We identifed various factors associated with a worse prognosis of COVID-19 in patients with R-IMID. This can help to identify which patients can present a worse course of the disease at the moment of the diagnosis.
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Background: COVID19 may present different degrees of severity. It is generally thought that viral infections in patients with rheumatic infammatory diseases (R-IMID) or receiving immunosuppressive treatment tend to present more severe disease. However, data comparing the severity of the disease between R-IMID and the general population are scarce. Objectives: To assess the predisposing factors, clinical-analytical features and severity of COVID-19 infection in R-IMID compare to patients without R-IMID. Methods: Case-control study in a single University Hospital. We included all consecutive patients with a diagnosis of a R-IMID and a positive test for COVID-19 up to March 31st, 2021. A total of 274 controls were selected for each case, and matched by sex, age (± 5 years), and without previous diagnosis of R-IMID or use of immunosuppresive therapy. Confrmed infection was defned if the patient had a positive nasopharyngeal swab for SARS-CoV-2. COVID-19 case severity was divided into mild, moderate, severe and critical according to the United States National Institute of Health (NIH) COVID-19 guidelines (1). Mild/moderate COVID19 was compared with critical. Results: We included 274 patients (185 women/89 men), mean age 59.1 18 years. More frequent R-IMID were: Rheumatoid arthritis (RA) (n=87, 31.8%), Axial spondylarthritis/Psoriatic arthritis (SpA/PsA) (n=90, 32.8%), Polymyalgia Rheumatica (PMR) (n=22, 8%) and Systemic Lupus Erythematosus (SLE) (n=22, 8%) We also included 274 age and matched controls. Main characteristics of patients with R-IMID and controls are shown in Table 1. Concerning comorbidities, hypertension and dyslipidemia were more frequent in patients with R-IMID (p< 0.05). COVID-19 symptoms' distribution is shown in Figure 1. Cough and dyspnoea were more frequent and headache, odynophagia and diarrhea were less frequent in the R-IMID group. The only analytical difference was D-Dimer that was signifcantly higher in patients with R-IMID. Although most of the cases were mild, critical cases and deaths were more frequent in R-IMID (p <0.05). Conclusion: Most of the patients present a mild COVID-19. However, a more severe syndrome was observed in R-IMID.
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Background: In Korea, it has been reported that the incidence of some respiratory diseases and Kawasaki diseases has decreased compared to the previous year along with active non-pharmaceutical interventions in the early stages of the COVID-19 pandemic. Autoimmune infammatory rheumatic disease (AIIRD) is mainly affected musculoskeletal organs and connective tissues due to impaired immune regulation. Although gout and osteoarthritis are rheumatic diseases, they are not a disease of the immune system, and are not included in the AIIRD. Objectives: In this study, we investigated the change and difference in the incidence rate of various rheumatic diseases during the COVID-19 pandemic after 2020. Methods: The number of patients for each disease from January 2016 to December 2020 was obtained from the Korea Health Insurance Review and Assessment Service database. We compared the incidence of 9 rheumatic diseases [systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), Sjogren syndrome (SJS), Behcet's disease (BD), infammatory myositis (IIM), scleroderma, polymyalgia rheumatica (PMR), and gout] and hypertension before and after the COVID-19 outbreak. The incidence rates of patients before and after the COVID-19 outbreak were compared using the Poisson test. Results: From 2016 to 2019, the prevalence of rheumatic diseases showed gradually increased. In 2020, the incidence of SLE, AS, SJS, BD, and IIM were signif-cantly decreased compared to the previous 4 years. In contrast, the incidences of gout and hypertension during the COVID-19 pandemic period were signifcantly increased from the predicted values. Conclusion: In conclusion, we found that the incidence of many AIIRDs, including SLE, AS, SJS, BD, and IIM decreased despite the increased incidence of hypertension and gout during the COVID-19 pandemic.
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Background: Even with the use of tocilizumab (TCZ), signifcant glucocorticoid exposure (usually ≥ 6 months) continues to be an important problem in giant cell arteritis (GCA). Objectives: We aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in combination with 2 months of prednisone in a group of patients with GCA. Methods: We conducted a prospective, single arm, open-label study of TCZ in combination with 2 months of prednisone for new-onset and relapsing GCA patients with active disease (ClinicalTrials.gov Identifer NCT03726749). GCA diagnosis required confrmation by temporal artery biopsy or vascular imaging. Active disease was defned as presence of cranial or polymyalgia rheumat-ica symptoms necessitating treatment within 6 weeks of baseline. All patients received TCZ 162 mg subcutaneously every week for 12 months and an 8-week prednisone taper starting between 20 mg and 60 mg daily (Figure 1). The primary endpoint, sustained prednisone-free remission, was defned as absence of relapse from induction of remission up to week 52 while adhering to the prednisone taper. Relapse was defned as the recurrence of symptoms of GCA requiring treatment intensifcation regardless of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Safety was also evaluated. 8-week prednisone taper starting between 20 mg and 60 mg Primary endpoint Prednisone-free remission at week 52 Figure 1. Clinical Trial Schema Results: Between 11/2018 and 11/2020 we enrolled 30 patients (mean age 74 years, 60% females, 50% new-onset disease, 77% temporal artery biopsy-proven, 47% imaging-proven). The mean ESR and CRP at screening were 45 mm/hour and 48 mg/L, respectively. The initial prednisone dose was 60 mg (n = 7), 50 mg (n = 1), 40 mg (n = 7), 30 mg (n = 6) and 20 mg (n = 9). All patients entered remission within 4 weeks of baseline. The primary endpoint was achieved by 23 (77%) patients (Table 1). The mean (SD) cumulative prednisone dose in these 23 patients was 1052 (390) mg. After a mean period of 16 weeks, 7 (23%) patients relapsed (Table 1). All relapses but one occurred after the completion of the study prednisone taper. Overall, 6 of the 7 patients with relapse received a second prednisone taper over 8 weeks. Of these 6 patients, 4 achieved and maintained remission for the remainder of the trial period, and 2 withdrew from the study after having a second relapse. One patient with relapse received a second prednisone taper over 26 weeks and stayed in remission until the end of the study. The mean (SD) cumulative prednisone dose in the 7 patients with relapse was 1883 (699) mg (Table 1). Overall, 4 (13%) participants developed a serious adverse event (Table 1). No cases of ischemia-related visual symptoms including permanent vision loss occurred during the study. Table 1. Efficacy and Safety Outcomes GCA patients (n = 30) Efficacy Sustained, prednisone-free remission by week 52 23.0 (76.7) Cumulative prednisone dose (mg) at week 52, mean (SD) 1051.5 (390.3) Relapse 70 (23.3) Time to relapse, weeks: mean (SD) 15.8 (14.7) Prednisone dose (mg/day) at relapse, mean (SD) 2.1 (5.2) Cumulative prednisone dose (mg), mean (SD) 1883.1 (699.2) Clinical manifestations at relapse Cranial symptoms 4 out of 7 patients schemic visual symptoms 0 out of 7 patients PMR symptoms 4 out of 7 patients Safety Serious adverse events 4.0 (13.3) Cellulitis 1 COVID-19 1 Fragility fracture 1 Cholecystitis 1 Values represent number and (%) unless otherwise specifed. SD, standard deviation;PMR, polymyalgia rheumatica Conclusion: These results suggest that 12 months of TCZ in combination with 8 weeks of prednisone could be efficacious for inducing and maintaining disease remission in patients with GCA. Confrmation of these fndings in a randomized controlled trial is required.
ABSTRACT
Background: The EPISER study is the frst Spanish epidemiological study that has confrmed the great burden of rheumatic diseases in the general population: they consume a large quantity of health resources (doctor visits, medical products) and imply a high social impact in terms of work absenteeism. Rheumatic diseases represent almost 30% of Primary Care medical consultations in Spain1,2. Electronic consultation could be an alternative response to the increase of this demand, both to make an early diagnosis and derivation and to improve communication with Primary Care physicians3,4. Objectives: To analyze the demand of Primary Care and its resolution through the electronic consultation system of the Rheumatology Department of a tertiary hospital. Methods: Retrospective descriptive study of the data collected in the request and information system (Sistema de Peticiones Electrónicas, SIPE) that supports electronic consultation between primary care physicians of the health area and the Rheumatology Department of a tertiary hospital, between July 2020 and May 2021.The following variables were collected: age, sex, reason for consultation, response time in days and destination (primary care/outpatient follow-up). Descriptive statistics were used to present the results. Results: The last 500 consecutive electronic consultations registered in the system, referring to 496 patients, were collected. Mean age was 59.5±17.7 years;74.2% women. Mean response time was 2 days, median response time 1 day and range 0-45. The reasons for consultation (see Graph 1) were: osteoporosis assessment 55 (11%), treatment adjustment 50 (10%), appointment request 49 (9.8%), loss to follow-up 43 (8.6%), local-regional pathology assessment 39 (7.8%), infltration request 28 (5, 6%), suspected rheumatoid arthritis 19 (3.8%), fare 18 (3.6%), suspected polymyalgia rheumatica or giant cell arteri-tis 16 (3.2%), COVID vaccine consultation 14 (2.8%), Raynaud's phenomenon 13 (2.6%), monoarthritis assessment 12 (2.4%), assessment of polyarthritis 11 (2.2%), adverse effects of treatment 11 (2.2%), suspected spondyloarthritis 11 (2.2%), suspected psoriatic arthritis 8 (1, 6%), generalized pain 7 (1.4%), suspected Sjögren's syndrome 5 (1%), suspected systemic lupus erythematosus 1 (0.2%), suspected other systemic autoimmune diseases 9 (1.8%), others 81 (16.2%). Fifty-seven and four % (287) of the patients required an appointment at the Rheumatology outpatient clinic and in 42.6% of the patients (213) the electronic consultation was successful, so it was not necessary to refer the patient to the hospital. Conclusion: Forty-two and six percent of the queries were resolved thanks to the electronic consultation system in an average of two days, otherwise that patients would have been referred to specialized care. The main reasons for consultation were osteoporosis assessment and clarifcation of doubts about the treatment of patients who were already being followed up by the Rheumatology Department.
ABSTRACT
Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinfammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, metho-trexate, lefunomide and tocilizumab. Even though GCA and PMR patients have a substantially higher risk for infections, little is known about humoral and cellular immune responses after vaccination in these patients. Objectives: In this study we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases. Methods: Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks post-vaccination (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared to age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specifc T-cells was assessed by IFN-γ ELIspot assay, and side-effects and disease activity were recorded. Results: The GCA/PMR patients, as a group, did not have reduced antibody concentrations compared to controls. However, linear regression analysis revealed a signifcant association of methotrexate and >10mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients, and was correlated with humoral immunity (Figure 1). Patients using >10mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to signifcant side-effects or changes in disease activity. Conclusion: SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10mg/day prednisolone did show lower vaccine responses, which corroborates fndings in other autoinfammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection.
ABSTRACT
Background/Aims Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undoubtedly changed the course of the pandemic and lessened hospital admissions and death as a result of the aforementioned virus. Reactive arthritis has been reported with other vaccinations, for example influenza, and now it seems patients are presenting with similar symptoms post SARS-CoV-2 vaccination, the first human mRNA vaccine to be used against a virus. There are occasional case reports in the literature of patients developing various rheumatological conditions post COVID-19 vaccination including reactive arthritis and polymyalgia rheumatica. Currently the Summary of Product Characteristics (SmPC) for Pfizer BioNTech, Moderna and AstraZenica vaccinations only list myalgia and arthralgia as side effects in the musculoskeletal and connective tissue disorders section. Our aim was to collect data in a prospective manner on patients who presented to clinic with a new rheumatological condition which was believed to have been triggered by receiving a COVID-19 vaccination and their progress was followed over time. Methods Data have been collected prospectively from patients who have presented to the West Suffolk NHS Foundation Trust rheumatology department with symptoms which are thought to be attributable to COVID-19 vaccination over the last five months. Results Nineteen patients had a new inflammatory condition that appeared to have been triggered by the COVID-19 vaccination. The mean age of onset of symptoms is 65.2 years (range 22-85 years) with the mean number of days between vaccine and symptom onset of 9.6 days. 89% presented within 14 days of vaccination. Eleven patients received the Pfizer BioNTech vaccine and 6 the AstraZeneca vaccine. Seven patients presented after their first vaccine and seven after their second. Three had symptoms after both. The most common presentation was a small joint polyarthritis (8 patients) and polymyalgia rheumatica type symptoms (5). All but one were seronegative. So far, outcomes have varied between self-resolution or conservative management (6 patients), short- and long-term prednisolone requirement (6) and initiation of disease modifying anti-rheumatic drugs (5). Conclusion The emergence of post-COVID-19 vaccine inflammatory arthritis appears to be a new condition which rheumatologists will be required to treat. With the introduction of booster vaccinations and third doses this phenomenon is likely to be seen in clinic for the foreseeable future. Further data are required in order to guide best treatment options and enable better prognostic indicators.
ABSTRACT
Background/Aims Vaccination against coronavirus is a cornerstone in the fight against the COVID-19 pandemic. Although the safety and efficacy of vaccines was established prior to roll out, long-term data and reports of rare adverse reactions remain inadequate. Literature reviews revealed two cases of PMR-like syndrome, left elbow arthritis and a case of rheumatoid arthritis (RA) flare following COVID-19 vaccination. Additionally, a case of new onset RA and case of reactive arthritis was reported with COVID infection. Methods We present four patients with polymyalgia rheumatica (PMR) following COVID-19 vaccination. The clinical details of the four patients are outlined in the table: Ultrasound (US) revealed typical finding of bilateral sub deltoid bursitis and biceps tendonitis in the first patient and there was severe right sub deltoid bursitis with biceps tendonitis in the second patient. None of the patients had features to suggest malignancy, giant cell arteritis, seronegative spondyloarthropathies or connective tissue disease. Results After exclusion of other inflammatory causes of shoulder pain, they were diagnosed with PMR based on clinical judgement and high inflammatory marker at time of presentations, ultrasound findings and significant improvement with prednisolone. Conclusion PMR following COVID-19 vaccination is exceptional and cannot be proven. In these patients post vaccination chronology of events favours this diagnosis. It is known that immunological illness may start after viral infection or vaccination (hapten or immune stimulation). The patients have responded well to the prednisolone similar to typical PMR cases. We need further studies to look at possible link between COVID-19 vaccination and PMR.