Current Rheumatology Reviews - Volume 17, Issue 3, 2021

A review of the available literature was performed in order to summarize the pathogenic and clinical connections between HIV infection and rheumatological syndromes. The increasing life expectancy during human immunodeficiency virus (HIV) infection has led to the observation of many rheumatological manifestations over the years in these types of patients. Although the pathological mechanisms are still not fully understood, several rheumatological diseases have been more commonly observed in the general population, especially after the advent of highly active antiretroviral therapy (HAART), and sometimes clinical and serological findings are influenced by the underlying condition which defines a characteristic onset or development of the disease. Autoimmune diseases occur during specific stages of the HIV infection, depending on the underlying pathogenic mechanism being mainly influenced by the CD4+ cells count. Several rheumatological diseases show peculiar clinical manifestations influenced by the underlying HIV infection leading to specific features less commonly observed in the healthy population. Conversely to pathological findings, broadly, HIV-1-neutralizing antibodies (BnAb) observed in several autoimmune diseases, such as SLE, could play a protective role in HIV infection. It is important to evaluate the onset of autoimmune diseases in HIV patients in order to start the appropriate treatment to avoid harmful events. More studies are needed to enlighten the trend of autoimmune diseases during HIV infection. Pathogenic mechanisms and clinical manifestations of rheumatological diseases during HIV infection are discussed in this review.

Objective: This study aims to provide consolidation of current research findings as well as the most important concepts regarding neutrophil extracellular traps (NETs) in rheumatoid arthritis. Data Sources: Relevant publications from 2004 to 2018 were identified using PubMed, Web of Science, Scopus, and eLibrary databases. Primary search terms used were “neutrophil extracellular traps” or “NETs” in combination with “rheumatoid arthritis”. Data Synthesis: NETs are distinctive structures promoting capture and non-phagocytic cleavage of foreign substances. NETs usually consist of thin chromatin fibers decorated with various molecules of granular, cytosolic, and cytoskeletal origin. NETosis can develop in two ways: either with neutrophil death or when the viability of the cell prolongs. ROS generation and pronounced protein citrullination are essential during the initial phase of NETs formation. NETosis is considered to have certain immunological consequences, including DAMPs-mediated signalling, proinflammatory cytokine secretion, and contact of extensively modified self and foreign epitopes with antigen-presenting cells. There are several putative pathogenetic links between NETosis, citrullination, neoepitope formation, and production of anticitrullined autoantibodies that can strongly influence rheumatoid arthritis progression. NET-induced vascular injury in rheumatoid arthritis can arise directly from NETs and indirectly through enhanced thrombosis and atherosclerosis. Conclusion: NETs are currently estimated as a possible influential factor of rheumatoid arthritis initiation and/or progression, especially in the context of vascular involvement. NETs can also serve as a source of novel antigenic biomarkers for the diagnosis of rheumatoid arthritis.

Objectives: To determine the effect of intra-articular injection of platelet-rich plasma (PRP) in patients with primary knee osteoarthritis (OA) by clinical evaluation and ultrasonographic (US) assessment of cartilage thickness. Patients and Methods: A total of 100 patients with mild to severe primary knee OA using the Kellgren- Lawrence (K-L) grading scale were included and divided into two groups. Group I included 50 patients who were given two intra-articular knee injections of PRP, 1 week apart; Group II included 50 patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and chondroprotective drugs. Functional assessment of all OA patients was done using the basal WOMAC score, at 2 and 6 months. US assessment of femoral condylar cartilage thickness was conducted basally and at 6 months. Results: Improvement of WOMAC score was observed at 2 and 6 months in Group I following PRP injection compared to Group II (p values < 0.001), The improvement of WOMAC in Group I occurred in all severity degrees of OA (p < 0.001). Moreover, a significant increase in cartilage thickness was found at the intercondylar area (ICA) at 6 months relative to baseline assessment by US in Group I (p = 0.041). Conclusion: Treatment with PRP injections can reduce pain and improve knee function in patients with various degrees of articular degeneration. Further studies are needed to clarify the anabolic effect of PRP on the articular cartilage.

Background: Patients with rheumatic diseases are more likely to suffer from anxiety, depression and insomnia. Yet, little is known about mental health status during COVID-19 pandemic. Objective: This study aims to measure the prevalence of mental health disorders among patients with rheumatic diseases in the era of COVID-19 pandemic and to determine potential risk factors for major symptoms of depression, anxiety, and insomnia in participants. Methods: Participants with rheumatic diseases were asked to complete a questionnaire using a telephonic interview. Sociodemographic and rheumatic disease characteristics were recorded. Mental health status was assessed by the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder (GAD)-7, and insomnia severity index (ISI) questionnaires to detect depression, anxiety and insomnia symptoms, respectively. Results: We included 307 patients in the survey. Rheumatoid arthritis was the most frequent diagnosis (55%). Of all participants, 7.5% had known depression and 5.5% known anxiety. Mental health disorders were insomnia (34.9%), anxiety (33.2%), and depression (24.4%). Major symptoms of insomnia, anxiety, and depression were noted in respectively, 19.9%, 12.4%, and 7.8% of participants. Risk factors for major insomnia were male gender (OR= 4.36, 95% CI 2.06 to 9.25; p<0.0001), low socioeconomic status (OR= 2.64, 95% CI 1.44 - 4.83; p<0.002) and having rheumatoid arthritis (OR= 2.00, 95% CI 1.04 to 3.84; p<0.036). Major anxiety was associated with low monthly income (OR=1.79, 95% CI 1.07 to 3.01; p<0.026), and higher Numerical Rating Scale (NRS) of pain (OR=1.795, 95% CI 1.074 to 2.994 ; p<0.026). Major depression was associated with the worsening of rheumatic disease (OR=1.86, 95% CI 1.06 to 3.26; p<0.03). Conclusion: A high frequency of undiagnosed depression, anxiety and insomnia symptoms was found in rheumatic patients. Rheumatologists should be aware of these comorbidities, especially in the era of COVID-19 pandemic.

Background: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are routinely used to assess disease activity in spondyloarthritis. New biomarkers have been reported, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), CRP to albumin ratio (CAR), and albumin to fibrinogen ratio (AFR). Aims: Our study aimed to assess these ratios in spondyloarthritis and to determine the relationship between these ratios and the disease activity. Methods: We conducted a cross-sectional study, including patients with spondyloarthritis. The following ratios were calculated: PLR, NLR, AFR, and CAR. Pearson correlation analysis was carried out to test the correlation of the data. Receiver operating characteristic curves were evaluated for each ratio using ASDASCRP as the gold standard for disease activity. Results: Eighty-five patients were included. The sex ratio was 60 males to 25 females. The mean age was 42.58 ± 11.75 years. There was a positive correlation between the PLR and the following parameters: CAR, CRP, and ESR. A negative correlation was found between AFR and the following ratios: PLR, NLR, CRP, and ESR. The ASDAS correlated negatively with AFR and positively with both PLR and CAR. The cutoff values of CAR and PLR to distinguish patients with very high disease activity (ASDASCRP>3.5) were 0.442 and 173.64, respectively. Conclusions: Given their good correlation with ESR and CRP, we suggest that PLR, CAR, and AFR can be used as potential indicators of inflammation in spondyloarthritis. The CAR and PLR are useful to identify patients with very high disease activity.

Background: People with rheumatic disease may be at higher risk for more severe course with COVID- 19, and the adverse effects of drugs used to treat rheumatic diseases is a major concern. Objective: We conducted this survey to learn about the real impact of COVID-19 pandemic on patients with rheumatic diseases. Methods: Participants were asked to complete a questionnaire using a telephonic interview conducted by two rheumatologists. Rheumatic disease characteristics, knowledge and attitude toward COVID-19, and impacts of pandemic on rheumatology care and patient’s compliance were assessed. Results: We included 307 patients in the survey, and rheumatoid arthris was the main rheumatic disease. Patients had mostly moderate level of knowledge about COVID-19, and patients with higher level of education were more likely to have better knowledge. Participants respected mainly recommended preventive measures. The pandemic and sanitary containment impacted strongly the rheumatology care. Over quarter of patients noted worsening of their rheumatic disease, two-thirds reported postponed or canceled medical apointments and more than three quarters postponed their laboratory tests. Patients with higher disease activity were more likely to have lack of follow-up. Medication change was noted in more than third of cases. It was mostly stopped, and DMARDs were mainly affected. Patients living in rural areas and who had canceled, or postponed their appointments were more likely to change their treatment. Conclusion: Our data are useful to better manage rheumatic patients. Physicians are encouraged to renew contact with their patients to insure medication compliance.

Background: Granulomatosis with polyangiitis is a systemic anti-neutrophil cytoplasmic antibody-associated vasculitides (AAVs), mainly involving the respiratory tract and renal system. Treatment by Rituximab as a next-generation therapy in ANCA-associated vasculitis is associated with promising outcomes in GPA patients. Despite symptoms improvements, disease recurrence and drug reaction are a challenging topic nowadays. Objectives: In this study, we examined six GPA patients who were confirmed to have paradoxical reactions to rituximab and then described how to control their symptoms. Methods: In this study, all the systemic GPA patients (diagnosed based on ACR/EULAR criteria) who received RTX in Amir-Allam hospital were monitored for any sign of disease exacerbation up to 3 months after RTX exposure. Results: From 78 GPA-diagnosed patients, six, including one man and five women with the mean age of 37.3 ± 13.8, were identified for exacerbation after RTX administration. Conclusion: According to our observation, it could be recommended not to deprive the patient of the benefits of RTX treatment due to the early patient's possible complications.

Background: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disease that specifically affects the spine and sacroiliac joint. AS diagnosis is often delayed in the clinical practice and this delay may cause the patients to miss the chance of early treatment. Fibromyalgia (FM) is a frequently encountered clinical syndrome, fibromyalgianess is a term used when patients who are diagnosed with inflammatory arthropathies meet the criteria for FM syndrome as shown in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome, and AS. Objectives: We aimed primarily to assess the frequency of concomitant diagnosis of FM syndrome in AS patients and study its impact on clinical disease aspects. Secondary, our aim extended as a preliminary pilot study to assess the Plasma Pentraxin-3(PTX-3) as a potential marker for the diagnosis of FM syndrome in AS patients. Methods: Plasma PTX-3 in 61 AS patients was compared to 60 matched controls. FM was diagnosed by FM Rapid Screening Tool. Bath AS disease activity index (BASDAI) and AS disease assessment score using C- reactive protein (ASDAS-CRP), Bath AS functional impairment index (BASFI), Bath AS metrology index (BASMI), AS quality of life (ASQoL) scale, Beck Depression Inventory, and Bath AS Radiology Index (BASRI) were assessed. Results: The patients were categorized into two groups according to the concomitant diagnosis of FM syndrome. Group I included 14 (22.9%) AS patients who fulfilled the clinical diagnosis of FM syndrome. Group II included 47 (77.1%) AS patients without FM syndrome. AS patients with FM (Group I) had significantly(p<0.001) increased an average of ages, disease duration, diagnostic delay of AS, switching of bDMARDs, morning stiffness duration, ASDAS-CRP, BASFI, ASQoL score, BASDAI (p=0.008), and BDI score (p=0.005) compared to AS patients without FM (Group II). PTX-3 levels were significantly (p<0.001) higher in Group I (p<0.001) (median, 0.23; IQR, 0.15-0.41 ng/ml) than Group II (median, 0.13; IQR, 0.035-0.21ng/ml) which showed no significant differences (p>0.05) compared to the controls. PTX-3 levels had significant positive correlations (p<0.05) with disease duration, BASFI, and ASQOl. Age, female sex, switch of biologic, ASDAS - CRP, and PTX-3 were significant predictors of FM in AS patients. Conclusion: These results indicate that concomitant FM is a significant problem in patients with AS and its presence is associated with higher disease activity, impaired function as well as an overall negative impact on QoL. Easy scanning of suspicious cases of FM with FiRST questionnaire can be done in daily practice. PTX-3 is more or less accurate as the clinical features to improve the diagnostic certainty of FM in the presence of AS with a proven sensitivity of 62.3%, a specificity of 90%, a positive predictive value of 82.75%, and a negative predictive value of 73.9%.

Objectives: Early diagnosis and management of rheumatoid arthritis (RA) have improved the outcome of patients. In the last decade, musculoskeletal Ultrasonography (MSUS) had demonstrated its superiority over clinical examination in detecting synovitis in RA. We conducted this present study in order to assess the added value of MSUS in diagnosing early RA. Methods: A cross-sectional study was conducted, including one hundred patients diagnosed RA based on the physician's opinion and presenting with inflammatory arthralgia or swollen joints for more than 6 weeks and less than 2 years. Patients underwent clinical, laboratory, and radiographic examination. MSUS was performed by a radiologist blinded to clinical findings assessing 22 joints of hands. A US ACR/EULAR 2010 score was calculated by replacing the swollen joints of hands with those expressing synovitis in Greyscale US. Agreement between clinical and US ACR/EULAR score was assessed. Results: Among the 2200 joints scanned by the US, synovitis was detected in 81% of patients, an intra-articular effusion in 36% patients, and PD signals in 51% of patients. Flexor tenosynovitis was present in 55% of patients and extensor tenosynovitis in 59% of patients. Synovitis and PD signals were more often detected in wrists. PD mode was found to be correlated with CRP results (r=0,302, p=0,023). The MSUS assessment has demonstrated synovitis on 71% (N=22) patients who were free of swollen joints on clinical examination. Through 13 patients expressing monoarthritis at clinical examination, 69% (N=9) patients were reclassified with oligo or polyarthritis. By adding US data, a further 13 patients accomplished the ACR/EULAR score. A good level of agreement was found between clinical and US ACR/EULAR criteria (k=0,684, p=0,001). Conclusion: MSUS is an inexpensive and accessible examination tool, which should be considered in patients in the onset of an inflammatory rheumatic disease in order to benefit of the window of opportunity and reach remission.

Objective: For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease-modifying anti-rheumatic drugs (cs- DMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. Methods: Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for all patients and those initiating their first bDMARD/tsDMARD. All TNFi therapies were included. Non-TNFi included Abatacept, Rituximab, Tocilizumab, and Tofacitinib. Results: A total of 1,057 patients were included, of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/ts- DMARD-naïve patients. In 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. Conclusion: This descriptive analysis of data from the OBRI cohort reveals that TNFi are still used in the majority of cases; however, there has been an increase in the use of non-TNFi therapies both overall and as first-line advanced therapy. This trend towards non-TNFi therapies as first-line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line to any of the advanced therapeutics.

Background: Beh’s disease (BD) is a rare systemic vasculitis of unknown etiology with relapsing and remitting course, characterized by triple-symptom complex of recurrent attacks of oral aphthous ulcers, genital ulcers and ocular lesions and other clinical features that include dermatological, cardiovascular, gastrointestinal, and neurological manifestations. The main goal of management is to prevent relapses and suppress inflammation rapidly for major organ involvement that may cause damage and even be fatal. Case Presentation: We hereby describe a case of a patient with Beh’s disease followed in our rheumatology consultation over the course of 15 years with multi-organ involvement resistant to several treatments and showed partial results with IL-1 inhibitors, particularly anakinra and canakinumab, while also discussing the current treatments of refractory BD and how early implementation of treatments could make a difference.