Pain catastrophizing in rheumatic diseases: prevalence, origin, and implications.

Pain is a crucial factor in rheumatic disorders, and reducing it is a primary goal of successful treatment. Adaptive pain-coping strategies can enhance this improvement, but maladaptive approaches such as pain catastrophizing may worsen overall patient well-being. This narrative review aims to provide a concise overview of the existing knowledge on pain catastrophizing in the most prevalent specific rheumatic disorders. The objective of this study was to improve understanding of this phenomenon and its implications, as well as to pinpoint potential directions for future research. We conducted searches in the MEDLINE/PubMed, SCOPUS, and DOAJ bibliography databases to identify articles related to pain catastrophizing in rheumatoid arthritis, psoriatic arthritis, axial spondylarthritis, systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, juvenile idiopathic arthritis, and osteoarthritis (non-surgical treatment). Data extraction was performed on November 1, 2023. The investigators screened the identified articles to determine their relevance and whether they met the inclusion criteria. Following a bibliography search, which was further expanded by screening of citations and references, we included 156 records in the current review. The full-text analysis centred on pain catastrophizing, encompassing its prevalence, pathogenesis, and impact. The review established the role of catastrophizing in amplifying pain and diminishing various aspects of general well-being. Also, potential treatment approaches were discussed and summarised across the examined disorders. Pain catastrophizing is as a significant factor in rheumatic disorders. Its impact warrants further exploration through prospective controlled trials to enhance global patient outcomes.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Factors Associated With an Electronic Health Record-Based Definition of Postacute Sequelae of COVID-19 in Patients With Systemic Autoimmune Rheumatic Disease.

OBJECTIVE: Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition. METHODS: We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk. RESULTS: Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC. CONCLUSION: Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.

Paxlovid use is associated with lower risk of cardiovascular diseases in COVID-19 patients with autoimmune rheumatic diseases: a retrospective cohort study.

BACKGROUND: Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). METHODS: TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2-5 days of COVID-19 diagnosis were performed. RESULTS: Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47-0.88]), arrhythmia outcomes (HR = 0.81 [0.68-0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35-0.74]) naming heart failure (HR = 0.41 [0.26-0.63]) and deep vein thrombosis (HR = 0.46 [0.24-0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44-0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66-0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11-0.40]), admission (HR = 0.68 [0.60-0.76]), and ICU admission rates (HR = 0.52 [0.33-0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. CONCLUSIONS: Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Is There a Link between the Molecular Basis of Juvenile Idiopathic Arthritis and Autoimmune Diseases? Systematic Review.

Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of diagnoses. Under-diagnosis is a barrier to early treatment and reduced complications of the disease. Other immune-mediated diseases may coexist in the same patient, making research in this area relevant. The main objective was to analyse whether links could be established between the molecular basis of JIA and other immune-mediated diseases. Early diagnosis may benefit patients with JIA, which in most cases goes undetected, leading to under-diagnosis, which can have a negative impact on children affected by the disease as they grow up. METHODS: We performed a PRISMA systematic review focusing on immune molecules present in different autoimmune diseases. RESULTS: A total of 13 papers from different countries dealing with the molecular basis of JIA and other immune diseases were evaluated and reviewed. CONCLUSIONS: Most of the autoimmune diseases analysed responded to the same group of drugs. Unfortunately, the reason for the under-diagnosis of these diseases remains unknown, as no evidence has been found to correlate the immunomolecular basis with the under-diagnosis of these immune-mediated diseases. The lack of information in this area means that further research is needed in order to provide a sound basis for preventing the development of immune-mediated diseases, especially in children, and to improve their quality of life through early diagnosis and treatment.

Impact of preeclampsia on infant and maternal health among women with rheumatic diseases.

OBJECTIVES: We sought to identify the impact of preeclampsia on infant and maternal health among women with rheumatic diseases. METHODS: A retrospective single-center cohort study was conducted to describe pregnancy and infant outcomes among women with systemic lupus erythematosus (SLE) with and without preeclampsia as compared to women with other rheumatic diseases with and without preeclampsia. RESULTS: We identified 263 singleton deliveries born to 226 individual mothers (mean age 31 years, 35% non-Hispanic Black). Overall, 14% of women had preeclampsia; preeclampsia was more common among women with SLE than other rheumatic diseases (27% vs 8%). Women with preeclampsia had a longer hospital stay post-delivery. Infants born to mothers with preeclampsia were delivered an average of 3.3 weeks earlier than those without preeclampsia, were 4 times more likely to be born preterm, and twice as likely to be admitted to the neonatal intensive care unit. The large majority of women with SLE in this cohort were prescribed hydroxychloroquine and aspirin, with no clear association of these medications with preeclampsia. CONCLUSIONS: We found preeclampsia was an important driver of adverse infant and maternal outcomes. While preeclampsia was particularly common among women with SLE in this cohort, the impact of preeclampsia on the infants of all women with rheumatic diseases was similarly severe. In order to improve infant outcomes for women with rheumatic diseases, attention must be paid to preventing, identifying, and managing preeclampsia.

Association between sinusitis and incident rheumatic diseases: a population-based study.

OBJECTIVES: To determine whether antecedent sinusitis is associated with incident rheumatic disease. METHODS: This population-based case-control study included all individuals meeting classification criteria for rheumatic diseases between 1995 and 2014. We matched three controls to each case on age, sex and length of prior electronic health record history. The primary exposure was presence of sinusitis, ascertained by diagnosis codes (positive predictive value 96%). We fit logistic regression models to estimate ORs for incident rheumatic diseases and disease groups, adjusted for confounders. RESULTS: We identified 1729 incident rheumatic disease cases and 5187 matched controls (mean age 63, 67% women, median 14 years electronic health record history). After adjustment, preceding sinusitis was associated with increased risk of several rheumatic diseases, including antiphospholipid syndrome (OR 7.0, 95% CI 1.8 to 27), Sjögren's disease (OR 2.4, 95% CI 1.1 to 5.3), vasculitis (OR 1.4, 95% CI 1.1 to 1.9) and polymyalgia rheumatica (OR 1.4, 95% CI 1.0 to 2.0). Acute sinusitis was also associated with increased risk of seronegative rheumatoid arthritis (OR 1.8, 95% CI 1.1 to 3.1). Sinusitis was most associated with any rheumatic disease in the 5-10 years before disease onset (OR 1.7, 95% CI 1.3 to 2.3). Individuals with seven or more codes for sinusitis had the highest risk for rheumatic disease (OR 1.7, 95% CI 1.3 to 2.4). In addition, the association between sinusitis and incident rheumatic diseases showed the highest point estimates for never smokers (OR 1.7, 95% CI 1.3 to 2.2). CONCLUSIONS: Preceding sinusitis is associated with increased incidence of rheumatic diseases, suggesting a possible role for sinus inflammation in their pathogenesis.

A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Rehabilitation of patients with inflammatory rheumatic diseases and comorbidities: unmet needs.

Comorbidities may contribute to inadequate response to therapy and accelerate disability in various rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriatic arthritis (PsA). Cardiovascular, oncological, and infectious comorbidities are common in rheumatic patients. The rehabilitation of patients with inflammatory rheumatic diseases (IRDs) with comorbidities requires a multidisciplinary approach to improving patients' functional mobility, slowing down the disease progression and minimizing the risks of complications. The evidence suggests that cardiac rehabilitation can be implemented in daily practice in patients with IRDs to reduce mortality for those with established risk factors. Physical exercises reduce the severity, improve the clinical course, and reduce hospitalization rates in patients with rheumatic diseases. A rehabilitation program with focused physical therapy can lead to functional improvements and reduction of disease activity in patients with lowered quality of life (QoL). Health professionals should provide evidence-based recommendations for patients with rheumatic diseases and comorbidities to initiate the self-management of their diseases and prevent complications.

The Link Between Dysregulated Immunometabolism and Vascular Damage: Implications for the Development of Atherosclerosis in Systemic Lupus Erythematosus and Other Rheumatic Diseases.

A bimodal pattern of mortality in systemic lupus erythematosus (SLE) exists. Early-stage deaths are predominantly caused by infection, whereas later-stage deaths are mainly caused by atherosclerotic disease. Further, although SLE-related mortality has reduced considerably in recent years, cardiovascular (CV) events remain one of the leading causes of death in people with SLE. Accelerated atherosclerosis in SLE is attributed to both an increase in traditional CV risk factors and the inflammatory effects of SLE itself. Many of these changes occur within the microenvironment of the vascular-immune interface, the site of atherosclerotic plaque development. Here, an intimate interaction between endothelial cells, vascular smooth muscle cells, and immune cells dictates physiological vs pathological responses to a chronic type 1 interferon environment. Low-density neutrophils (LDNs) have also been implicated in eliciting vasculature-damaging effects at such lesion sites. These changes are thought to be governed by dysfunctional metabolism of immune cells in this niche due at least in part to the chronic induction of type 1 interferons. Understanding these novel pathophysiological mechanisms and metabolic pathways may unveil potential innovative pharmacological targets and therapeutic opportunities for atherosclerosis, as well as shed light on the development of premature atherosclerosis in patients with SLE who develop CV events.

The effect of COVID-19 infection on patients with rheumatic diseases in China.

OBJECTIVES: At the end of 2022, the COVID-19 outbreak erupted in China, and BA.5.2 or BF.7 subtypes of Omicron novel variations were implicated in more than 90% of the cases. We created a real-world questionnaire survey to better understand how this new variant pandemic was affecting rheumatic patients in China. METHODS: During the COVID-19 outbreak in China, the subjects of this study were rheumatic patients and non-rheumatic individuals (control group), who were matched for sex and age. Professional physicians carefully questioned the participants before administering a questionnaire as part of the study. This study focused on the general baseline characteristics, clinical symptoms and treatment after COVID-19 infection, and the target populations' awareness of COVID-19. RESULTS: The study included 1130 participants, of whom 572 were assigned to the rheumatic group and 558 to the control group. The percentage of vaccinated controls was significantly higher than that of rheumatic patients (90.1% vs. 62.8%, p < 0.001), while the rate of COVID-19 infection was not significantly different between the two groups (82.3% vs. 86.6%, p = 0.051). Patients with rheumatic disease experienced substantially more days of fever following infection (2.87 ± 3.42 vs. 2.18 ± 1.65, p = 0.002) compared to individuals in the control group. The rheumatic patients had a greater prevalence of cough (67.1% vs. 54.0%, p < 0.001), somnipathy (13.8% vs. 6.0%, p < 0.001), and conjunctivitis/ophthalmodynia (5.3% vs. 2.1%, p = 0.008), while dry throat/throat pain/weakness (49.9% vs. 59.4%, p = 0.003), myalgia/osteodynia (33.3% vs. 41.8%, p = 0.003), and dyspnea (14.0% vs. 25.3%, p < 0.001) were more likely to occur in non-rheumatic group after infection. Human immunoglobulin (2.1% vs. 0.2%, p = 0.006), glucocorticoids (19.5% vs. 1.6%, p < 0.001), oxygen support (6.8% vs. 2.1%, p < 0.001), and traditional Chinese medicine (21.9% vs. 16.6%, p = 0.037) were all more frequently used by rheumatic patients with COVID-19 infection. People in the control group were more confused about whether to use masks in following social activities after contracting COVID-19 (14.7% vs. 7.6%, p = 0.001). In the control group, more individuals than patients with rheumatic disease (25.1% vs. 13.4%, p < 0.001) expressed an interest to receive the vaccine again. After being exposed to COVID-19, the majority of rheumatic patients (66.9%) reported no discernible change, only 29.1% reported a worsening of their symptoms, and the remaining 4% indicated an improvement. CONCLUSIONS: After the COVID-19 outbreak in China, the proportion of patients with rheumatic diseases infected with the virus was similar to that of normal individuals. But the clinical symptoms, follow-up treatment requirements, and awareness of the COVID-19 among rheumatic patients were distinct from those among non-rheumatic patients, necessitating the use of individualized diagnosis and treatment plans as well as health advice by medical professionals in clinical work. Key Points • Despite there were different comorbidities and vaccination rates, the rate of COVID-19 infection in patients with rheumatic disease was similar to that of normal individuals. • After COVID-19 infection, rheumatic patients and normal controls had different clinical symptoms and drug usage. • After being exposed to COVID-19, the majority of rheumatic patients felt no significant change in the primary disease, while the normal controls was more likely to accept a new vaccine injection and confused about whether to use masks in following social activities.

Primary cardiac rhabdomyosarcoma in a mitral valve involved with rheumatic disease.

A 51-year-old female underwent emergency mitral valve replacement for mitral stenosis with an undetermined mass which was attached to the anterior mitral leaflet. Histopathological testing of the excised specimen confirmed the diagnosis of rheumatic mitral disease in combination with a primary rhabdomyosarcoma. Postoperative adjuvant chemotherapy with pazopanib hydrochloride was given. At 10 months of follow-up, repeated computed tomographic screening has not shown any signs of local recurrence or secondary metastases. The potential for the existence of primary rhabdomyosarcomas should be borne in mind when faced with undetermined masses on mitral leaflets, even in the presence of rheumatic disease.

Respiratory involvement in connective tissue diseases.

Pulmonary involvement is doubtless one the most fatal organ manifestations of the autoimmune rheumatic diseases (ARD) and involves the parenchyma, the vessels, the respiratory system itself, but also the muscles and the pleura. Close and regular screening assessments, identification of risk factors, clinical signs associated with the existence of lung disease should alarm the involved physicians treating these patients. The accurate classification is essential, as different treatment options are nowadays available. Pulmonary manifestations of ARD will be analyzed in this review article with special emphasis on interstitial lung disease and pulmonary hypertension.

Breakthrough COVID-19 After Tixagevimab/Cilgavimab Among Patients With Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: To determine the incidence and baseline factors associated with breakthrough coronavirus disease 2019 (COVID-19) after preexposure prophylaxis (PrEP) with tixagevimab/cilgavimab among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: We performed a retrospective cohort study among patients with SARDs who received tixagevimab/cilgavimab between January 2, 2022, and November 16, 2022. The primary outcome was breakthrough COVID-19 after tixagevimab/cilgavimab. We performed multivariable Cox regression models adjusted for baseline factors to identify risk factors for breakthrough COVID-19. RESULTS: We identified 444 patients with SARDs who received tixagevimab/cilgavimab (mean age 62.0 years, 78.2% female). There were 83 (18.7%) breakthrough COVID-19 cases (incidence rate 31.5/1000 person-months, 95% CI 24.70-38.24), 7 (1.6%) hospitalizations, and 1 (0.2%) death. Older age was inversely associated with breakthrough COVID-19 (adjusted hazard ratio [aHR] 0.86/10 years, 95% CI 0.75-0.99). Higher baseline spike antibody levels were associated with lower risk of breakthrough COVID-19 (aHR 0.42, 95% CI 0.18-0.99 for spike antibody levels > 200 vs < 0.4 units). CD20 inhibitor users had a similar risk of breakthrough COVID-19 (aHR 1.05, 95% CI 0.44-2.49) compared to conventional synthetic disease-modifying antirheumatic drug (DMARD) users. CONCLUSION: We found that patients with SARDs had frequent breakthrough COVID-19, but the proportion experiencing severe COVID-19 was low. DMARD type, including CD20 inhibitors, did not significantly affect risk of breakthrough COVID-19. Evidence of prior humoral immunity was protective against breakthrough infection, highlighting the continued need for a multimodal approach to prevent severe COVID-19 as novel PrEP therapies are being developed.