The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent ...changes in the medical environment in Japan. This article is a digest version of the guidance.
We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members.
We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach.
The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations.
To update and revise the diagnostic criteria for mixed connective tissue disease (MCTD) issued by the Japan Research Committee of the Ministry of Health, Labor, and Welfare (MHLW), a round table ...discussion by experts from rheumatology, dermatology, and pediatric medicine was conducted in multiple occasions.
The definition of MCTD, and items included in the diagnostic criteria were generated by consensus method and evaluation using clinical data of typical and borderline cases of MCTD, by applying to the diagnostic criteria for MCTD proposed in 1996 and 2004 by the Research Committee of MHLW.
To the end, all committee members reached consensus. Then, the criteria were assessed in an independent validation cohort and tested against preexisting criteria. The revised criteria facilitate an understanding of the overall picture of this disease by describing the concept of MCTD, common manifestations, immunological manifestation and characteristic organ involvement. Conditions with characteristic organ involvement include pulmonary arterial hypertension, aseptic meningitis and trigeminal neuropathy. Even if the overlapping manifestations are absent, MCTD can be diagnosed based on the presence of the characteristic organ involvement. Furthermore, the criteria were validated for applicability in actual clinical cases, and public comments were solicited from the Japan College of Rheumatology and other associated societies.
After being reviewed through public comments, the revised diagnostic criteria have been finalized.
Abstract
Background
Porphyromonas gingivalis
(Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria ...(i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease. Therefore, this study investigated dysbiosis-mediated arthritis by Pg oral inoculation in an experimental arthritis model mouse.
Methods
Pg inoculation in the oral cavity twice a week for 6 weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in serum as well as periodontal, intestinal, and joint tissues were measured by ELISA. Gut microbiota composition was determined by pyrosequencing the 16 s ribosomal RNA genes after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-LA-derived feces to normal SKG mice. The effects of Pg peptidylarginine deiminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using a PgPAD knockout mutant.
Results
Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and both IL-6 and CP productions in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingiva, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice reproduced donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The average AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores and ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild-type inoculation.
Conclusion
Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.
To compare the efficacy and safety between tocilizumab added to methotrexate and tocilizumab switched from methotrexate in patients with active rheumatoid arthritis (RA).
This is a 2-year randomised, ...controlled study. RA patients with moderate or high disease activity despite methotrexate were randomly assigned either to tocilizumab added to methotrexate (add-on) or tocilizumab switched from methotrexate (switch). The primary endpoint was the DAS28 remission rate at week 24. Secondary objectives included other clinical efficacy indices, radiological outcomes assessed with the van der Heijde-modified total Sharp scoring system (mTSS), and safety.
Of 223 randomised patients, 83% completed 52 weeks. DAS28 remission rates at week 24 were 70% for add-on and 55% for switch (p=0.02), but they became comparable at week 52 (72% vs 70%, p=0.86). Structural remission rates (mTSS≤0.5) at week 52 were not different (66% vs 64%, p=0.92). However, clinically relevant radiographic progression rates (CRRP; mTSS≥3) tended to be higher with the switch than with the add-on (15% vs 7%, p=0.07). Radiographic progression in the CRRP patients was larger with the switch than with the add-on (9.0/year vs 5.0/year, p=0.04). The difference in the mean C-reactive protein of the CRRP patients was significant for the first 24 weeks (1.56 vs 0.49, p=0.001) but not for the following 28 weeks (0.10 vs 0.04, p=0.1). Overall safety was preferable in the switch group.
In RA patients with inadequate response to methotrexate, tocilizumab added to methotrexate more rapidly suppressed inflammation than tocilizumab switched from methotrexate, leading to superior clinical efficacy and prevention of joint destruction.
NCT01120366.
Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of ...patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.
We herein report the case of a 78-year-old woman who was diagnosed as having disseminated herpes zoster (DHZ) complicated with probable varicella-zoster pneumonia during maintenance therapy for ...microscopic polyangiitis. Because the patient had severe renal dysfunction, amenamevir administration was started to avoid any neurotoxicity of acyclovir, which is suggested to be optimal for treatment. It ameliorated her symptoms without any adverse events. This is the first report suggesting the efficacy of amenamevir in the treatment of severe herpes zoster infection with coexisting DHZ and probable varicella-zoster pneumonia. Amenamevir could thus be a treatment option for severe varicella zoster virus infections.
Dermatomyositis (DM) with rapidly progressive interstitial lung disease (DM RP-ILD) is a life-threatening condition. Serum cytokine levels are potentially suitable biomarkers for DM RP-ILD. However, ...the relationships among cytokine levels, lung imaging findings, and lung pathology have not been investigated. The aim of the present retrospective study was to determine the association between hypercytokinemia and lung inflammation in patients with DM RP-ILD.
The study subjects were nine patients with life-threatening DM RP-ILD and severe hypoxemia (partial arterial oxygen pressure (PaO
)/fraction of inspired oxygen (FiO
) ratio ≤ 200) before receiving intensive care management, who were admitted to our hospital between 2006 and 2015. The controls included 10 patients with DM without RP-ILD and 19 healthy subjects. We assessed the association between serum cytokine levels and computed tomography (CT) scores of the lung (ground glass opacity-score, G-score; fibrosis-score, F-score). Lung, hilar lymph nodes, and spleen from two autopsies were examined by hematoxylin-eosin (H&E) staining and immunostaining.
Serum interferon (IFN)-γ, interleukin (IL)-1β and IL-12 levels were significantly higher in patients with DM RP-ILD than in the other two groups, whereas serum IL-6 levels were elevated in the two patient groups but not in the healthy subjects. Serum levels of IL-2, IL-4, IL-8, IL-10, IFN-α, and TNF (tumor necrosis factor)-α were not characteristically elevated in the DM RP-ILD group. Serum IFN-γ levels correlated with G-scores in patients with DM RP-ILD, while IL-1β was negatively correlation with F-scores. Immunohistochemical staining showed infiltration of numerous IFN-γ-positive histiocytes in the lung and hilar lymph nodes; but not in the spleen. Serum IL-6 levels did not correlate with the CT scores. Numerous IL-6-positive plasma cells were found in hilar lymph nodes, but not in the lungs or spleen.
Our results suggest strong IFN-γ-related immune reaction in the lungs and hilar lymph nodes of patients with life-threatening DM RP-ILD, and potential IFN-γ involvement in the pathogenesis of DM, specifically in the pulmonary lesions of RP-ILD.
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