Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

The value of inquiring patients about local discomfort during blood pressure measurement for fibromyalgia detection. A cross-sectional study.

BACKGROUND: Fibromyalgia overlaps and/or mimics other rheumatic diseases and may be a confounding factor in the clinimetric assessment of these illnesses. Allodynia is a distinctive fibromyalgia feature that can be elicited during routine blood pressure measurement. For epidemiological purposes fibromyalgia can be diagnosed using the 2016 Wolfe et al. criteria questionnaire. No physical examination is required. OBJECTIVE: To evaluate the role of a straightforward question formulated during routine blood pressure measurement for fibromyalgia detection in a rheumatology outpatient clinic. PATIENTS AND METHODS: All adult patients attending our Rheumatology outpatient clinic were invited to participate. While awaiting their medical consultation, they filled-out the 2016 Wolfe et al. FM diagnostic criteria questionnaire. During the ensuing routine physical examination, the physician advanced the following guideline: "I am going to take your blood pressure; tell me if the cuff's pressure causes pain". Then, blood pressure cuff was inflated to 170 mm/Hg. Sphygmomanometry induced allodynia was defined as any local discomfort caused by blood pressure measurement. If a patient voiced any uneasiness, a follow-up dichotomic question was formulated "did it hurt much or little". Sphygmomanometry-induced allodynia was correlated with the presence of fibromyalgia according to the 2016 Wolfe diagnostic criteria. RESULTS: Four hundred and ninety-one patients were included in the study; most of them (84%) were female. The female cohort displayed the following features: Twenty five percent had fibromyalgia. Twenty seven percent had sphygmomanometry-induced allodynia. In women, sphygmomanometry-evoked allodynia had 63% sensitivity and 84% specificity for fibromyalgia diagnosis. The area under curve was 0.751. Moreover, having "much" local pain elicitation during blood pressure testing had 23% sensitivity and 96% specificity for fibromyalgia diagnosis. Men behaved differently; 15% fulfilled the fibromyalgia diagnostic criteria, but only 2% had sphygmomanometry induced allodynia. CONCLUSIONS: Inquiring female patients about local discomfort during routine blood pressure measurement is a simple and efficient procedure for fibromyalgia detection. This undemanding approach could be implemented in all clinical settings. There is marked sexual dimorphism in the link between sphygmomanometry-induced allodynia and fibromyalgia diagnosis. The presence of fibromyalgia is almost certain in those individuals having substantial pain elicitation during blood pressure measurement.

lncRNAs dysregulation in monocytes from primary antiphospholipid syndrome patients: a bioinformatic and an experimental proof-of-concept approach.

BACKGROUND: Antiphospholipid syndrome (APS) is the main cause of acquired thrombophilia where peripheral circulating cells such as monocytes have a key role. Currently, several studies have linked long non-coding RNAs (lncRNAs) in different inflammatory and autoimmune processes, including lupus. However, the role of lncRNAs in antiphospholipid syndrome is unknown, therefore, we aimed to select and measure expression levels of three lncRNAs based on its abundance in monocytes from APS patients. METHODS: Selection of lncRNAs candidates were carried out based on its abundance in monocytes and their relationship with Perez-Sanchez miRNA signature by using miRNet 2.0 bioinformatic tool, then lncRNAs expression levels was measured in monocytes by RT-qPCR. RESULTS: This is the first study to report that lncRNAs: FGD5-AS1, OIP5-AS1 and GAS5 are promising candidates for play a role on APS monocytes and they are expressed differently between patients and controls. CONCLUSIONS: OIP5-AS1, FGD5-AS1 and GAS5 are downregulated on monocytes from APS patients.

Interferon-alpha regulates expression of lncRNA MALAT1 and interferon-stimulated genes, as well as chemokine production, in primary Sjögren's syndrome.

OBJECTIVES: This study aimed to explore the contribution of interferon-alpha (IFN-α) to MALAT1 expression in primary Sjögren's syndrome (pSS). METHODS: Peripheral blood mononuclear cells (PBMC) from pSS patients and healthy blood donors were stimulated with recombinant human IFN-α, and the expression levels of MALAT1 and several interferon-stimulated genes (ISGs) were measured by RT-PCR, while supernatant levels of interferon-regulated chemokines were measured using multiplex cytokine immunobead assay. RESULTS: In this work, we found that MALAT1 expression levels were increased in IFN-α-stimulated PBMC from pSS patients and healthy controls. As expected, ISG expression levels and interferon-regulated chemokine secretion levels were higher after IFN-α stimulation. However, the fold-change values for ISG15, Ly6E, OAS1, and OASL expression levels were higher in cells from pSS patients than in controls. Similarly, PBMC from pSS patients produced higher concentrations of chemokines than those from healthy controls after IFN-α stimulation. CONCLUSIONS: Our data provide insights into the abnormal IFN-α-mediated regulation of the lncRNA MALAT1 in pSS. Based on an unusually high capacity of PBMC to express ISG and to produce interferon-responsive chemokines, it is likely that targeted therapies to block these molecules may be of benefit to patients with pSS.

Clinical overlap between fibromyalgia and myalgic encephalomyelitis. A systematic review and meta-analysis.

Myalgic encephalomyelitis is an illness characterized by profound malaise after mental or physical effort occurring in patients already suffering from constant fatigue. On the other hand, widespread pain and widespread allodynia are the core fibromyalgia clinical features. There is controversy on these two syndromes alikeness. Through the years, different diagnostic and/or classification criteria have been put forward to appraise both fibromyalgia and myalgic encephalomyelitis. The epidemiology of these two illnesses, and their overlap, may vary accordingly to the used definition. The most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria incorporates three myalgic encephalomyelitis features including fatigue, waking unrefreshed and dyscognition. The objective of this meta-analysis was to define the clinical overlap between fibromyalgia and myalgic encephalomyelitis based on a systematic literature review. METHODS: PubMed, Embase, Lilacs, and Cochrane data bases were searched on January 25, 2021 linking the medical subject heading "Fibromyalgia" to the following terms "chronic fatigue syndrome", "myalgic encephalomyelitis" and "systemic exertion intolerance disease". Our review included all original articles in which the clinical overlap between fibromyalgia and myalgic encephalomyelitis could be quantified based on recognized diagnostic or classification criteria. Articles scrutiny and selection followed the PRISMA guidelines. Each study quality was assessed according to GRADE recommendations. The global clinical overlap was calculated using a fixed effect model with inverse variance-weighted average method. RESULTS: Twenty one publications were included in the meta-analysis. Reviewed studies were highly dissimilar in their design, objectives, sample size, diagnostic criteria, and/or outcomes yielding a 98% heterogeneity index. Nevertheless, the clinical overlap between fibromyalgia and myalgic encephalomyelitis was a well defined outcome that could be reliably calculated despite the high heterogeneity value. All reviewed publications had moderate GRADE evidence level. Most evaluated articles used the old 1990 Wolfe et al. fibromyalgia diagnostic criteria. Myalgic encephalomyelitis and fibromyalgia diagnoses overlapped in 47.3% (95% CI: 45.97-48.63) of the reported cases. CONCLUSION: This meta-analysis found prominent clinical overlap between fibromyalgia and myalgic encephalomyelitis. It seems likely that this concordance would be even higher when using the most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria.

Interferon Lambda 3/4 (IFNλ3/4) rs12979860 Polymorphisms Is Not Associated With Susceptibility to Systemic Lupus Erythematosus, Although It Regulates OASL Expression in Patients With SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex etiology. Various genetic factors are associated with susceptibility to developing SLE and contribute to its onset and progression. Different single-nucleotide polymorphisms (SNPs) have been associated with SLE in several populations. The rs12979860 SNP in interferon lambda 3/4 (IFNλ3/4) is significantly associated with SLE susceptibility in patients negative for nephritis in Taiwanese people, and interferon-stimulated genes (ISGs) are differentially expressed in normal liver by the rs12979860 genotype. This study aimed to investigate whether rs12979860 is associated with the presence of SLE and lupus nephritis in Mexican individuals as well as with the expression of several ISGs in SLE patients. In total, 439 SLE patients and 358 healthy donors were genotyped for rs12979860 using real-time PCR, and allelic discrimination plots were constructed. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated from the venous blood of SLE patients by centrifugation (n = 78). The mRNA levels of 2'-5'-oligoadenylate synthetase like (OASL), myxovirus resistance 1 (MX1), 2'5'-oligoadenylate synthetase 1 (OAS1), interferon-stimulated gene 15 (ISG15) and lymphocyte antigen 6 complex, locus E (LY6E) were determined using real-time PCR. The distributions of rs12979860 genotypes and allele frequencies were compared between SLE patients and healthy donors; case-control analysis revealed that rs12979860 was not associated with SLE susceptibility (OR 1.18, 95% CI 0.97-1.45, p = 0.08) or with the risk for lupus nephritis (OR 0.913, 95% CI 0.590-1.411, p = 0.682). However, OASL expression levels in PBMCs were significantly different between rs12979860 genotypes in SLE patients: median OASL mRNA levels were significantly higher in patients carrying the CC genotype (197.10, IQR 71.10-411.17) than in those with CT/TT genotypes (173.75, IQR 58.80-278.75, p = 0.016). Our results suggest that the SNP rs12979860 does not play a relevant role in susceptibility to SLE in Mexican individuals. However, IFNλ3/4 genotypes appear to be associated with OASL expression in PBMCs from patients with SLE.

Assessment of inflammatory activity in Takayasu's arteritis: performance of clinical scores and common biomarkers versus 18F-FDG PET/CT.

OBJECTIVES: There is no consensus on how to evaluate inflammatory activity in Takayasu's arteritis (TAK). Here we compare biochemical tests and three clinical scores, which evaluate inflammatory activity (IA) in TAK, versus quantitative 18F-FDG PET/CT as the gold standard. METHODS: This prospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria. IA was assessed through laboratory tests, clinical scores of the National Institute of Health (NIH), Dabague-Reyes (DR) and the Indian Takayasu Clinical Activity Score 2010 (ITAS2010), and the result of these assessments was compared against 18F-FDG PET/CT Standardised Uptake Values (SUVmax). RESULTS: A total of 35 patients were studied, 86% were women. SUVmax had positive correlations with acute phase reactants and DR and NIH. Agreement of 18F-FDG PET/CT was significant with erythrocyte sedimentation rate (ESR) and DR score. Receiver Operating Characteristic (ROC) curve analysis showed diagnostic value for inflammatory activity in ESR, DR and NIH scores, which had higher specificity when they were estimated with new cut-off points for the Mexican population. CONCLUSIONS: ESR and other phase reactants have good sensitivity but low specificity to evaluate IA in TAK when compared against 18F-FDG PET/CT. Among all the clinical scores, DR had the best diagnostic value, with strong potential as a clinical tool to define the inflammatory status in TAK patients when the study image is not available. However, in complex TAK cases with doubtful diagnosis after assessment by clinical scores or laboratory, 18F-FDG PET/CT remains mandatory.

Multifractal Analysis Reveals Decreased Non-linearity and Stronger Anticorrelations in Heart Period Fluctuations of Fibromyalgia Patients.

Objective: To characterize the multifractal behavior of the beat to beat heart-period or RR fluctuations in fibromyalgia patients (FM) in comparison with healthy-matched subjects. Methods: Multifractral detrended fluctuation analysis (MDFA) was used to study multifractality in heartbeat times-series from 30 female healthy subjects and 30 female patients with fibromyalgia during day and night periods.The multifractal changes as derived from the magnitude and sign analysis of these RR fluctuations were also assessed. Results: The RR fluctuations dynamics of healthy subjects showed a broad multifractal spectrum. By contrast, a noticeable decrease in multifractality and non-linearity was observed for patients with fibromyalgia. In addition, the spectra corresponding to FM subjects were located on the average to the right of the spectra of healthy individuals, indicating that the local scaling exponents reflect a smoother behavior compared to healthy dynamics. Moreover, the multifractal analysis as applied to the magnitude and sign heartbeat series confirmed that, in addition to a decreased nonlinearity, fibromyalgia patients presented stronger anticorrelation in directionality, which did not remain invariant for small or rather larger fluctuations as it occurred in healthy subjects. Conclusion: When compared to healthy controls, fibromyalgia patients display decreased nonlinearity and stronger anticorrelations in heart period fluctuations. These findings reinforce the hypothesis of the potential role of the dysfunctional autonomic nervous system in the pathogenesis of fibromyalgia.

Ambroxol for fibromyalgia: one group pretest-posttest open-label pilot study.

A consistent line of investigation proposes that fibromyalgia is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia sodium channels may play a major role in fibromyalgia pain transmission. Ambroxol is a secretolytic agent used in the treatment of various airway disorders. Recently, it was discovered that this compound is also an efficient sodium channel blocker with potent anti-neuropathic pain properties. We evaluated the add-on effect of ambroxol to the treatment of fibromyalgia. We studied 25 patients with fibromyalgia. Ambroxol was prescribed at the usual clinical dose of 30 mg PO 3 times a day × 1 month. At the beginning and at the end of the study, all participants filled out the Revised Fibromyalgia Impact Questionnaire (FIQ-R) and the 2010 ACR diagnostic criteria including the widespread pain index (WPI). At the end of the study, FIQ-R decreased from a baseline value of 62 ± 15 to 51 ± 19 (p = 0.013). Pain visual analogue scale decreased from 77 ± 14 to 56 ± 30 (p = 0.018). WPI diminished from 14.6 ± 3.1 to 10.4 ± 5.3 (p = 0.001). Side effects were minor. In this pilot study, the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms. The open nature of our study does not allow extracting the placebo effect from the positive results. The drug was well tolerated. Ambroxol newly recognized pharmacological properties could theoretically interfere with fibromyalgia pain pathways. Dose escalating-controlled studies seem warranted.

HPV vaccination syndrome. A questionnaire-based study.

Isolated cases and small series have described the development of complex regional pain syndrome, postural orthostatic tachycardia, and fibromyalgia after human papillomavirus (HPV) vaccination. These illnesses are difficult to diagnose and have overlapping clinical features. Small fiber neuropathy and dysautonomia may play a major role in the pathogenesis of these entities. We used the following validated questionnaires to appraise the chronic illness that might appear after HPV vaccination: The 2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria, COMPASS 31 dysautonomia questionnaire, and S-LANSS neuropathic pain form. These questionnaires and a "present illness" survey were e-mailed to persons who had the onset of a chronic ailment soon after HPV vaccination. Forty-five filled questionnaires from individuals living in 13 different countries were collected in a month's period. Mean (±SD) age at vaccination time was 14 ± 5 years. Twenty-nine percent of the cases had immediate (within 24 h) post-vaccination illness onset. The most common presenting complaints were musculoskeletal pain (66%), fatigue (57%), headache (57%), dizziness/vertigo (43%), and paresthesias/allodynia (36%). Fifty-three percent of affected individuals fulfill the fibromyalgia criteria. COMPASS-31 score was 43 ± 21, implying advanced autonomic dysfunction. Eighty-three percent of the patients who had ongoing pain displayed S-LANSS values >12, suggesting a neuropathic component in their pain experience. After a mean period of 4.2 ± 2.5 years post-vaccination, 93% of patients continue to have incapacitating symptoms and remain unable to attend school or work. In conclusion, a disabling syndrome of chronic neuropathic pain, fatigue, and autonomic dysfunction may appear after HPV vaccination.

Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies.

BACKGROUND: Fibromyalgia often coexists and overlaps with other syndromes such as chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Chronic stress has been implicated in the pathogenesis of these illnesses. The sympathetic nervous system is a key element of the stress response system. Sympathetic dysfunction has been reported in these syndromes, raising the possibility that such dysautonomia could be their common clustering underlying pathogenesis. OBJECTIVE: The objective of this study was to carry out a review of all published comparative case-control studies investigating sympathetic nervous system performance in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. METHODS: Online databases PubMed and EMBASE were accessed using the following key words: autonomic (OR) sympathetic (AND) fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. All entries up to December 10th 2012 were reviewed by 2 independent investigators searching for case-control studies in humans. The Method for Evaluating Research and Guidelines Evidence adapted to the Scottish Intercollegiate Guidelines Network was used to rank the level of evidence contained in the selected articles. RESULTS: A total of 196 articles are included in this review. The most often used methods to assess sympathetic functionality were heart rate variability analysis, sympathetic skin response, tilt table testing, and genetic studies. The majority of studies (65%) described sympathetic nervous system predominance in these overlapping syndromes. In contrast, 7% of the studies found parasympathetic predominance. CONCLUSIONS: This review demonstrates that sympathetic nervous system predominance is common in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. This concordance raises the possibility that sympathetic dysfunction could be their common underlying pathogenesis that brings on overlapping clinical features. The recognition of sympathetic predominance in these 4 syndromes may have potential clinical implications. It may be worth exploring the use of nonpharmacological measures as well as drug therapies aimed to regain autonomic balance.

Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis.

BACKGROUND: The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system. OBJECTIVE: To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012. METHODS: The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis. RESULTS: During the conformation of this document, each working group settled the existing evidence from the different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables. CONCLUSIONS: This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system.