The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term “hyperferritinemic syndromes” and including macrophage activation syndrome (MAS), ...adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and “hyperferritinemic syndromes” are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and “hyperferritinemic syndromes” which would allow considering severe COVID-19 as a fifth member of this spectrum of inflammatory conditions.
•COVID-19 infection share clinical/laboratory features with “hyperferritinemic syndromes”.•A cytokine storm is responsible for COVID-19 systemic inflammatory response.•COVID-19 severe infection benefit from b-DMARDs targeting specific cytokines.
Six months following the beginning of Covid-19 pandemic in China, data on the risk of SARS-CoV-2 infection among patients with autoimmune rheumatic diseases are now available. However, the rapid ...spread of the pandemic has not allowed proper design of prospective studies, thus evidence came mostly from case series and observational studies.The early enthusiasm on hydroxychloroquine (HCQ) anti-viral properties should not suggest that patients who are long-term treated with antimalarials, such as patients with systemic lupus erythematosus (SLE), are protected against SARS-CoV-2 infection. Indeed, a French report on 17 HCQ-treated SLE patients dampened the enthusiasm.1 A recent report from Covid-19 Global Rheumatology Alliance has described 80 SLE patients with Covid-19, mostly females under 65 years of age, 64% of whom were already taking HCQ before the infection: the rate of hospitalisation and the need for intensive care did not differ between patients who were and those who were not taking HCQ.2 A study group from Northern Italy – the Italian epicentre of the pandemic – reported an incidence of 2.5% of Covid-19 (higher compared to the general population of the same region) in 165 patients with SLE.3 Patients with SLE are possibly at risk of developing symptomatic or severe Covid-19, not only because of their disease or treatment but as a consequence of associated comorbidities known to worsen the outcome of SARS-COv-2 infection.4 5 What do we know so far? SLE patients should not withdraw their medication. Before drawing any other conclusion, large registry data are needed to clarify the incidence and the outcome of Covid-19 in patients with SLE.Learning ObjectivesDescribe the current evidence for risk of SARS-CoV-2 infection among patients with autoimmune rheumatic diseases, notably SLEExplain why it is important to ensure robust evidence are available to clarify the outcome of Covid-19 in patients with SLEReferencesMathian A, Mahevas M, Rohmer J, et al. Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Ann Rheum Dis 2020;79(6):837–39.Konig MF, Kim AH, Scheetz MH, et al. Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19. Ann Rheum Dis 2020 doi: 10.1136/annrheumdis-2020-217690 published Online First: 2020/05/10.Bozzalla Cassione E, Zanframundo G, Biglia A, et al. COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine. Ann Rheum Dis 2020 doi: 10.1136/annrheumdis-2020-217717 published Online First: 2020/05/14.Wallace B, Waher L, Correspondence regarding Research Letter to the Editor by Mathian A, et al. ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus under long-term treatment with hydroxychloroquine’. Ann Rheum Dis 2020. doi:10.1136/annrheumdis-2020-217794.Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis 2020;79(7):859–66.
Witchcraft is a varied historical phenomenon with changing sociocultural aspects according to the times and the places considered. Nonetheless, it is possible to trace the different cultural ...substrata giving shape to witch-beliefs in order to shed light on their process of amalgamation. The aim of this study is to show how the folkloric and the Classical literary motives were intertwined in the fifteenth century by figures lauded as the high intellectuals of the time, Franciscan and Dominican preachers and inquisitors, to produce a coherent and multifaceted picture of witchcraft-related beliefs. By putting some of the most significant sources that I have analyzed in my monograph Witchcraft, Superstition, and Observant Franciscan Preachers in relation to others that I have not considered before composed by the same or different authors, my aim is to show how this process of combination of various cultural traditions gave shape to the creation and the understanding of the witchcraft phenomenon. Furthermore, I also intend to highlight how the at times contradictory views concerning witch-beliefs, pointing either to realistic or to skeptical stances, are related to specific declensions of those different traditions on the part of the friars.
Little is known about the safety of SARS-CoV-2 vaccination in patients with rheumatic musculoskeletal disease (RMD). We evaluated the occurrence of adverse events following immunization (AEFI) in RMD ...patients and heathy subjects who received anti-SARS-CoV-2 mRNA vaccine.
We performed a telephone interview collecting any adverse event (AE) following immunization (AEFI) that occurred in RMD patients and healthy controls after the two doses of mRNA vaccine including common local reactogenicity and systemic events (for example, fever, fatigue/malaise, joint and muscle pain). We also investigated the onset of new signs or symptoms of the RMD after the vaccination.
We evaluated 126 patients with RMDs 105 females and 19 males, median age 51(IQR 17) and 85 controls 62 females and 23 males, (median age 49 (20). Seventy patients (55.6%) were taking immunosuppressants, conventional synthetic (n=31, 43.3%) and/or biological TNF inhibitors (n=49, 68.6%), and 30 (23.8%) were taking hydroxychloroquine; treatment remained unchanged in 77% of patients. Eleven out of 126 patients and none of the 85 controls previously contracted COVID-19. The median follow-up from the completion of vaccination was 15 (3) weeks both in patients and controls. We reviewed 5 suspected cases confirming mild articular flares in 3 women (2.8) with inflammatory arthritis (2 psoriatic arthritis and 1 rheumatoid arthritis) while no disease reactivation was recorded in patients with connective tissue diseases; the incidence rate of RMD reactivation was 0.007 person/month. Multivariable logistic regression analysis showed similar frequencies of local and systemic AEFI in patients and controls with no effect of therapies or previous COVID-19. Local reaction-pain in the injection site-was the most frequently reported AEFI both in RMD and controls (71% and 75% of all the AEFI, respectively) after the first dose. Overall, up to 66% of patients experienced at least one AEFI at the second dose and up to 62% in the control group. Most of AEFI occurred within 2 days of vaccine administration. Two RMD patients developed pauci-symptomatic COVID-19 after the first dose of vaccine.
The low incidence rate of disease reactivation and the similar AEFI occurrence compared to controls should reassure on mRNA vaccine safety in RMD patients.
In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated ...worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, we feel a duty to share our experience and our knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.
Abstract
Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The ...2022 update of EUALR recommendations for the management of patients with RA suggests to reduce and discontinue oral GCs as quickly as possible. Considering GCs as a "bridging therapy" to promptly reduce symptoms and control inflammation, fast-acting drugs such as tofacitinib could allow faster and safer tapering of GCs. The purpose of this pilot study was to evaluate the steroid-sparing effect of adding tofacitinib in patients with RA inadequately responsive to methotrexate taking concomitant GCs. In this open-label pilot study, we enrolled patients with moderate to severe RA on a stable dose of prednisone (5–12.5 mg/day) who started treatment with tofacitinib. After 1 month, in patients who achieved at least a moderate EULAR response (decrease of > 1.2 in DAS28_CRP), GCs was tapered according to a predetermined schedule until complete discontinuation at week 12. Disease activity was assessed after 4, 12, 24 and 48 weeks of treatment. The primary endpoint was the percentage of patients discontinuing GCs after 12 weeks of tofacitinib treatment. We enrolled 30 patients (26 F: 4 M, mean age 60 ± 13 years, mean disease duration 13.2 ± 7.8 years). The primary endpoint was achieved: 9 patients (30%) discontinued GCs at week-12. At week-24, other 12 patients (46%) withdrew GCs. The median prednisone dose decreased from 5 mg/day (interquartile range 5–10 mg) to 2.5 (0–5) mg/day at week 12 and 48 (p < 0.00001 vs baseline). At week 48, 12 out of 30 patients (40%) had discontinued prednisone. The percentage of patients achieving remission or low disease activity increased throughout the follow-up without any difference between patients who discontinued or not the GC. In this cohort of long-standing RA patients treated with tofacitinib, the discontinuation of glucocorticoids was achievable in up to 30% of patients. These results should encourage rheumatologists to consider GCs tapering and discontinuation of GCs, as suggested by the 2022 EULAR recommendations, an achievable goal.
To explore the pathogenic association between periodontal disease and rheumatoid arthritis focusing on the role of Porphyromonas gingivalis.
In the last decades our knowledge about the pathogenesis ...of rheumatoid arthritis substantially changed. Several evidences demonstrated that the initial production of autoantibodies is not localized in the joint, rather in other immunological-active sites. A central role seems to be played by periodontal disease, in particular because of the ability of P. gingivalis to induce citrullination, the posttranslational modification leading to the production of anticitrullinated protein/peptide antibodies, the most sensitive and specific rheumatoid arthritis biomarker.
The pathogenic role of P. gingivalis has been demonstrated in mouse models in which arthritis was either triggered or worsened in infected animals. P. gingivalis showed its detrimental role not only by inducing citrullination but also by means of other key mechanisms including induction of NETosis, osteoclastogenesis, and Th17 proinflammatory response leading to bone damage and systemic inflammation.
Autophagy is a degradation mechanism by which cells recycle cytoplasmic components to generate energy. By influencing lymphocyte development, survival, and proliferation, autophagy regulates the ...immune responses against self and non-self antigens. Deregulation of autophagic pathway has recently been implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Indeed, autophagy seems to be involved in the generation of citrullinated peptides, and also in apoptosis resistance in RA. In this review, we summarize the current knowledge on the role of autophagy in RA and discuss the possibility of a clinical application of autophagy modulation in this disease.
Phosphodiesterases (PDEs) are a heterogeneous superfamily of enzymes which catalyze the degradation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine ...monophosphate (cGMP). Among PDEs, PDE4 is the most widely studied and characterized isoenzyme. PDE4 blocking can lead to increased levels of intracellular cAMP, which results in down-regulation of inflammatory responses by reducing the expression of tumor necrosis factor (TNF), interleukin (IL)-23, IL-17, interferon-γ, while increasing regulatory cytokines, such as IL-10. Therefore, PDE4 has been explored as a therapeutic target for the treatment of different chronic inflammatory conditions such as psoriatic arthritis (PsA) and inflammatory bowel disease (IBD). PsA shares clinical, genetic, and pathogenic features with IBD such as ulcerative colitis (UC) and Crohn's disease (CD), and enteropathic spondyloarthritis (eSpA) represent a frequent clinical evidence of the overlap between gut and joint diseases. Current therapeutic options in PsA patients and underlying UC are limited to synthetic immunosuppressants and anti-TNF. Apremilast is an oral PDE4 inhibitor approved for the treatment of active PsA patients with inadequate response to synthetic immunosuppressants. The efficacy and a good safety profile observed in randomized clinical trials with apremilast in PsA patients have been confirmed by few studies in a real-life scenario. In addition, apremilast led to significant improvement in clinical and endoscopic features in UC patients in a phase II RCT. By now there are no available data regarding its role in eSpA patients. In view of the above, the use of apremilast in eSpA patients is a route that deserves to be deepened.
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease and is extremely heterogeneous in terms of immunological features and clinical manifestations. This complexity could result in a ...delay in the diagnosis and treatment introduction, with impacts on long-term outcomes. In this view, the application of innovative tools, such as machine learning models (MLMs), could be useful. Thus, the purpose of the present review is to provide the reader with information about the possible application of artificial intelligence in SLE patients from a medical perspective. To summarize, several studies have applied MLMs in large cohorts in different disease-related fields. In particular, the majority of studies focused on diagnosis and pathogenesis, disease-related manifestations, in particular Lupus Nephritis, outcomes and treatment. Nonetheless, some studies focused on peculiar features, such as pregnancy and quality of life. The review of published data demonstrated the proposal of several models with good performance, suggesting the possible application of MLMs in the SLE scenario.
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