Mechanistic immunological based classification of rheumatoid arthritis

The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly supported by immunogenetics suggesting follicular helper T-cell responses driving high titre specific autoantibodies that pre-dates disease onset. Using the immunological disease continuum model of inflammation against self with “pure” adaptive and innate immune disease at opposite boundaries, we propose a novel immune mechanistic classification describing the heterogeneity within RA. Mutations or SNPs in autoinflammatory genes including MEFV and NOD2 are linked to seronegative RA phenotypes including some so called palindromic RA cases. However, just as innate and adaptive immunity are closely functionally integrated, some ACPA+ RA cases have superimposed “autoinflammatory” features including abrupt onset attacks, severe attacks, self-limiting attacks, relevant autoinflammatory mutations or SNPs and therapeutic responses to autoinflammatory pathway therapies including colchicine and IL-1 pathway blockade. An emergent feature from this classification that non-destructive RA phenotypes, both innate and adaptive, have disease epicentres situated in the extracapsular tissues. This mixed innate and adaptive immunopathogenesis may be the key to understanding severe disease flares, resistant disease subsets that are unresponsive to standard therapy and for therapies that target the autoinflammatory component of disease that are not currently considered by expert therapeutic recommendations

Enthesitis: Much More Than Focal Insertion Point Inflammation

Purpose of Review Recognition of the importance of enthesitis as the pivotal pathological process underpinning spondyloarthropathies (SpA) has increased in recent years. Thus, we summarized the current knowledge on the pathogenic role of enthesitis on SpA shown by both animal models and human studies in vivo. Recent Findings Experimental models have shown several SpA-like diseases that commence at entheses and are linked to nail disease as well as dactylitis, two important entheseal-associated conditions in humans. Frequently, enthesitis is not the primary outcome measure in studies of peripheral PsA and SpA although arguably it is the key parameter being indirectly assessed in spinal disease in ankylosing spondylitis. The use of different agents including JAK, IL-17, and IL-23 inhibitors contributes significantly to our understanding of enthesitis in terms of involved immune pathways. Summary Enthesitis and enthesis organ inflammation may be the primary pathological process underlying SpA associated skeletal inflammation. Emergent studies are beginning to elucidate the molecular basis for this type of joint inflammatory response

The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man

Objective: The heterodimeric IL-12 family member cytokines including, IL-12, IL-23, IL-27, and IL-35 and have multiple roles in regulating innate and adaptive immunity with crucial functions in inflammatory disorders such as psoriasis. Chain pairing promiscuity is a feature of the IL-12 family. Recently, based on murine data, a new family member, IL-39, was proposed, consisting of IL23p19 (shared with IL-23) and EBI3 (shared with IL-27 and IL-35). IL-39 has subsequently been implicated in experimental murine lupus. Given the success of IL-23p19 therapeutic targeting in diseases including psoriasis, it is of great interest to confirm the presence of IL-39 in man. Human IL-39 is yet to be either detected or expressed, which has halted research in this area. Methods: Using a disulphide-linked human chimera protein composing of IL-23p19 and EBI3 human chains, we stimulated human leukocytes, and analysed cytokine secretion and STAT3 phosphorylation. Results and Conclusion: We report that this cytokine shows no activity in human cells. IL-39 chimera protein failed to induce either IL-6, IL-8, TNF, or IL-17A from leukocytes or STAT3 phosphorylation and thus, remains a ‘theoretical cytokine' in humans

The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study

Intermittent circadian fasting, namely Ramadan, is a common worldwide practice. Such fasting has a positive impact on psoriasis, but no data exist on its role in psoriatic arthritis (PsA)—a disease that is clearly linked to body mass index. We enrolled 37 patients (23 females and 14 males) with a mean age 43.32 ± 7.81 and they fasted for 17 h for one month in 2016. The baseline PsA characteristics were collected and 12 (32.4%) patients had peripheral arthritis, 13 (35.1%) had axial involvement, 24 (64.9%) had enthesitis, and 13 (35.1%) had dactylitis. Three patients (8.1%) were treated with methotrexate, 28 (75.7%) with TNF-α blockers, and 6 (16.2%) with IL-17 blockers. After a month of intermittent fasting, C-reactive protein (CRP) levels decreased from 14.08 ± 4.65 to 12.16 ± 4.46 (p < 0.0001), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 2.83 ± 1.03 to 2.08 ± 0.67 (p = 0.0078), Psoriasis Area Severity Index (PASI) decreased from 7.46 ± 2.43 to 5.86 ± 2.37 (p < 0.0001), and Disease Activity index for PSoriatic Arthritis (DAPSA) decreased from 28.11 ± 4.51 to 25.76 ± 4.48 (p < 0.0001). Similarly, enthesitis improved after fasting, with Leeds Enthesitis Index (LEI) decreasing from 2.25 ± 1.11 to 1.71 ± 0.86 (p < 0.0001) and dactylitis severity score (DSS) decreasing from 9.92 ± 2.93 to 8.54 ± 2.79 (p = 0.0001). Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting. These preliminary data may support the use of chronomedicine in the context of rheumatic diseases, namely PsA. Further studies are needed to support our findings

Discrepancies Between Classic and Digital Epidemiology in Searching for the Mayaro Virus: Preliminary Qualitative and Quantitative Analysis of Google Trends

Background: Mayaro virus (MAYV), first discovered in Trinidad in 1954, is spread by the Haemagogus mosquito. Small outbreaks have been described in the past in the Amazon jungles of Brazil and other parts of South America. Recently, a case was reported in rural Haiti. Objective: Given the emerging importance of MAYV, we aimed to explore the feasibility of exploiting a Web-based tool for monitoring and tracking MAYV cases. Methods: Google Trends is an online tracking system. A Google-based approach is particularly useful to monitor especially infectious diseases epidemics. We searched Google Trends from its inception (from January 2004 through to May 2017) for MAYV-related Web searches worldwide. Results: We noted a burst in search volumes in the period from July 2016 (relative search volume [RSV]=13%) to December 2016 (RSV=18%), with a peak in September 2016 (RSV=100%). Before this burst, the average search activity related to MAYV was very low (median 1%). MAYV-related queries were concentrated in the Caribbean. Scientific interest from the research community and media coverage affected digital seeking behavior. Conclusions: MAYV has always circulated in South America. Its recent appearance in the Caribbean has been a source of concern, which resulted in a burst of Internet queries. While Google Trends cannot be used to perform real-time epidemiological surveillance of MAYV, it can be exploited to capture the public’s reaction to outbreaks. Public health workers should be aware of this, in that information and communication technologies could be used to communicate with users, reassure them about their concerns, and to empower them in making decisions affecting their health

Computer vision syndrome among Al-Rayan Medical Colleges students, Madinah, Saudi Arabia

Background: Digital devices now become a part of university student’s life, and with prolonged use, they may experience some ocular problems like dryness, headache, eye strain, and pain. These symptoms and others constitute computer vision syndrome (CVS). Our study aimed to assess CVS among Al-Rayan medical college students and to evaluate students’ behaviors related to preventing CVS. Methods: A cross-sectional, questionnaire-based study was performed among the students of Alrayan Medical College from the period from November to December 2022, with a sample size of 270 cases. Data were collected using (CVS-Q) questionnaire. Results: Near half of the participants (53.7%) were suffering from CVS. The most reported symptoms included headache (43.3%), tearing (42.9%), burning (39.3%), and blurred vision (35.1%). The most significant measures applied to minimize the impact of electronic devices were putting the digital device at enough distance (p value=0.001) and adjusting the screen brightness of the digital device (p value=0.004). Conclusions: This study disclosed that CVS is a common problem among medical students. The manifestation of CVS was affected by the frequency and duration of electronic device use

Systemic Sclerosis is Linked to Psoriasis and May Impact on Patients' Survival: A Large Cohort Study.

Although skin manifestations are quite common in systemic sclerosis (SSc), a link between SSc and psoriasis (PsO) has been poorly investigated. We assessed the Clalit medical database in a cohort study to compare the prevalence of PsO between SSc-patients and SSc-free controls. We also evaluated the SSc-related autoantibodies' role in the co-existence of the two conditions. Survival analysis was performed using both univariate (Kaplan-Meier, log-rank test) and multivariate (Cox proportional-hazards technique) analyses. Our cohort of 2,431 SSc-patients was age- and gender-matched with 12,710 controls (case-control match 1:5.2). There were 150 (1.2%) cases of PsO among controls and 47 (1.9%) among SSc-patients (p = 0.0027). A SSc diagnosis was an independent risk factor for PsO with an odds ratio (OR) of 2.16 (95%CI 1.38-3.39, p = 0.0008). Among SSc-patients, 98.6% with PsO were antinuclear antibodies (ANA)-negative. In terms of survival, the mortality rate in SSc-patients with PsO was lower than SSc without PsO (14.9% vs. 26%, p < 0.0001). At the multivariate-analysis, SSc-patients with PsO compared to SSc-patients without PsO had an OR for death of 0.44 (95%CI 0.19-0.99, p < 0.05). SSc is independently associated with PsO. The cases with concurrent PsO and SSc are almost exclusively ANA-negative and may exhibit a better survival

Hidradenitis suppurativa associated with systemic lupus erythematosus: A case report

Rationale: Hidradenitis suppurativa (HS) is a chronic inflammatory condition characterized by recurrent swollen, deep, and painful abscesses. Several autoimmune conditions have been shown to be associated with HS including inflammatory bowel disease and spondyloarthropathies. Patient concerns: 40-year-old female with systemic lupus erythematous (SLE) presented with recurrent abscesses and nodules on her extremities. Diagnosis: Early considerations related the described dermatologic findings to the dermatologic manifestations of SLE, however findings from lesion biopsy were suggestive of HS. Interventions: Prednisone and antibiotic therapy with clindamycin were started. Subsequently upon discharge, the patient was also treated with rifampicin and azathioprine. Outcome: In this communication, we demonstrate a case of HS in a patient with SLE that significantly improved under antibiotic and immunosuppressant therapy. Lessons: HS can coexist in patients with SLE. Evidence pertinent to the etiology of HS and its association with other autoimmune conditions implies a possible denominator in the disease etiopathogenesis. Increased awareness of the co-occurrence of the two conditions calls for increased efforts to devise better treatment modalities