Headache in systemic lupus erythematosus: The LUNA registry cross-sectional study.

OBJECTIVES: This study investigated the clinically relevant factors for headaches in patients with systemic lupus erythematosus (SLE) using a registry from a Japanese multicenter cohort. METHODS: This cross-sectional study analysed the clinical information of patients with SLE who experienced headache episodes using the Migraine Disability Assessment (MIDAS) questionnaire. Significant findings in the comparisons between patients with headache (HA patients) and those without headache (non-HA patients) and in the comparisons depending on the grades of headache-induced disability in daily life based on the MIDAS scores were evaluated. Multivariate logistic regression analyses were performed to identify the relevant factors for headache. RESULTS: We analyzed 369 patients (median age, 45 years; female, 90.8%), including 113 HA patients who were significantly younger than non-HA patients (p < .005). HA patients had significantly higher frequencies of photosensitivity, rashes, and mucosal ulcers than non-HA patients (p < .05). Age and photosensitivity were significantly associated with headache (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.95-0.99; OR 2.11, 95% CI 1.29-3.49, respectively). In the HA patients, hypocomplementemia was significantly associated with a disability of more than mild grade (OR 2.89, 95% CI 1.14-7.74), while rash was significantly observed in those presenting with moderate and severe disability. CONCLUSION: This study suggests that photosensitivity is a relevant manifestation of headache in patients with SLE. Persistent hypocomplementemia can contribute to headache-induced disability in daily life, whereas a rash may be a dominant manifestation in patients presenting with moderate/severe headache-induced disability.

Impact of multiple MEFV variants of unknown significance on the diagnosis and clinical presentation of familial Mediterranean fever.

The detection of variants of unknown significance (VUS) in familial Mediterranean fever (FMF) is common; however, their diagnostic value remains elusive, and the interpretation of multiple VUS remains difficult. Therefore, we examined FMF diagnosis-associated factors 1-year post-genetic testing in patients with only VUS and assessed the impact of multiple VUS on diagnosis and clinical features. A 1-year follow-up was conducted on patients clinically suspected of having FMF without confirmatory diagnosis owing to the presence of only VUS. Clinical features were compared between patients with a single VUS and those with multiple VUS among patients diagnosed with FMF. Among 261 patients followed up, 202 were diagnosed with FMF based on clinical judgment. No specific clinical symptoms or variant patterns at genetic testing were associated with diagnosis at 1 year. Multiple VUS was significantly and independently associated with a lower response to colchicine than single VUS among patients diagnosed with FMF. However, clinical symptoms showed no correlation with the number of VUS. In conclusion, predicting FMF diagnosis 1-year post-genetic testing in patients with only VUS remains challenging. Moreover, the impact of multiple VUS on FMF may be limited owing to the lack of correlation with clinical features, except colchicine response.

Multiple lymphadenopathies in eosinophilic granulomatosis with polyangiitis: differentiating from IgG4-related lymphadenopathy.

We report a case of eosinophilic granulomatosis with polyangiitis (EGPA) in a 75-year-old man who developed mononeuritis multiplex and purpura in the lower legs concomitantly presenting with lymphadenopathies. Biopsied lymph node tissue pathologically demonstrated fibrinoid necrotizing vasculitis with perivascular eosinophil infiltration, resulting in EGPA diagnosis. Additionally, abundant IgG4-positive plasma cell infiltration exhibiting >70% IgG4/IgG ratio, without storiform pattern fibrosis and obliterative phlebitis, was observed in the biopsied lymph node. Clinical improvement was observed after corticosteroid therapy. IgG4-related lymphadenopathy (IgG4-LAD) has been defined as a distinct clinical category regardless of fulfilling IgG4-related disease classification criteria. However, some autoimmune diseases, including EGPA, can develop lymphadenopathy pathologically similar to IgG4-LAD.

Immune-mediated necrotizing myopathy with concomitant development of Kikuchi-Fujimoto disease.

Immune-mediated necrotizing myopathy (IMNM) is a distinct type of idiopathic inflammatory myositis, pathologically characterized by myofiber necrosis and degeneration in the absence of lymphocyte infiltration. Herein, we present a case of IMNM with concomitant development of Kikuchi-Fujimoto disease (KFD), characterized by histiocytic necrotizing lymphadenitis, in a 36-year-old woman who had a treatment history for rheumatoid arthritis (RA). Treatment with oral prednisolone and tacrolimus as immunosuppressants resulted in the remission of the skeletomuscular involvement and lymphadenopathy. To the best of our knowledge, this is the first report of IMNM and KFD developing concomitantly during the clinical course of RA.

Effect of Attending Rheumatologists' Big 5 Personality Traits on Patient Trust in Patients With Systemic Lupus Erythematosus: The TRUMP2-SLE Project.

OBJECTIVE: Differences in communication styles based on physicians' personality traits have been identified, particularly in primary care, and these physician-related factors can be important in building patient-physician trust. This study examined the effects of rheumatologists' personality traits on patients' trust in their attending rheumatologists. METHODS: This cross-sectional study included adult Japanese patients with systemic lupus erythematosus (SLE) at 5 academic medical centers between June 2020 and August 2021. The exposures were the Big 5 personality traits (ie, extraversion, agreeableness, openness, conscientiousness, and emotional stability) of attending rheumatologists using the Japanese version of the 10-Item Personality Inventory scale (1-7 points each). The outcome was the patients' trust in their attending rheumatologist using the Japanese version of the 5-item Wake Forest Physician Trust Scale (0-100 points). A general linear model was fitted. RESULTS: The study included 505 patients with a mean age of 46.8 years; 88.1% were women. Forty-three attending rheumatologists (mean age: 39.6 years; 23.3% female) were identified. After multivariable adjustment, higher extraversion and agreeableness were associated with higher trust (per 1-point increase, 3.76 points [95% CI 1.07-6.45] and 4.49 points [95% CI 1.74-7.24], respectively), and higher conscientiousness was associated with lower trust (per 1-point increase, -2.17 points [95% CI -3.31 to -1.03]). CONCLUSION: Whereas higher extraversion and agreeableness of attending rheumatologists led to higher patient trust in their rheumatologist, overly high conscientiousness may lead to lower trust resulting from the physicians' demand of responsibility and adherence to instructions from patients with SLE.

Immunopathological features of myopathy associated with small-to-medium-sized vessel vasculitis and differences from autoimmune myositis.

OBJECTIVES: Patients with systemic vasculitis may develop myalgia as an initial symptom. However, the immunopathology of vasculitic myopathy remains unclear. We investigated the immunopathological features of skeletal muscle in small-to-medium-sized vessel vasculitis. METHODS: We analysed muscle tissue biopsies from 15 patients with vasculitis, including antineutrophil cytoplasmic antibodyassociated vasculitis and polyarteritis nodosa, and 15 patients with autoimmune myositis (AIM), including polymyositis and immune-mediated necrotising myopathy, as comparison disease controls. Immunohistochemical staining for CD56/neural cell adhesion molecule (NCAM), major histocompatibility complex class I, C5b-9/membrane attack complex (MAC), and CD31 was performed. The vascularity score was defined as the total number of CD31-expressing blood vessels. The association between CD56/NCAM-expressing myofibers and clinical findings was evaluated in patients with vasculitis. RESULTS: Patients with vasculitis had a significantly lower frequency of CD56/NCAM-expressing myofibers than those with AIM and a positive correlation between the frequency of CD56/NCAM-expressing myofibers and serum aldolase levels. Patients with vasculitis had significantly fewer major histocompatibility complex class I-expressing myofibers and C5b-9/MAC deposits on the sarcolemma than those with AIM. C5b-9/MAC deposits in blood vessels were observed in >70% of patients with vasculitis. Patients with vasculitis had significantly higher vascularity scores in the endomysium than those with AIM. CONCLUSIONS: Patients with vasculitis demonstrated mild myofiber damage based on the lower involvement of CD56/NCAM-expressing myofibers compared to those with AIM. Complement component deposits on the vessel walls and hypervascularity in the endomysium areas may be immunopathological features of vasculitic myopathy.

Impact of online health information-seeking behavior on shared decision-making in patients with systemic lupus erythematosus: The TRUMP2-SLE project.

OBJECTIVE: Providing appropriate health information to patients with systemic lupus erythematosus (SLE) is advantageous in the treatment decision-making process. We aimed to investigate how online health information-seeking behaviors affect shared decision-making (SDM) in patients with SLE. METHODS: This cross-sectional study included 464 patients with SLE from five institutions. The main exposure was time spent on the internet per day, divided into four categories (none, <1 h, 1- < 2 h, ≥2 h). Participants categorized their preferred first source of health information as physicians, the internet, or other media. The outcome was the degree of SDM measured via the 9-item Shared Decision-Making Questionnaire (SDM-Q-9). A general linear model was applied. RESULTS: Compared to no internet use, longer internet use was associated with a higher SDM-Q-9 score: <1 h, 6.9 points (95% confidence interval [CI] 0.32 to 13.6) and ≥2 h, 8.75 points, (95% CI 0.61 to 16.9). The SDM-Q-9 did not differ between the individuals who chose physicians and those who chose the Internet as their preferred first source of health information (-2.1 points, 95% CI -6.7 to 2.6). Individuals who chose other media had significantly lower SDM-Q-9 scores than those who chose physicians (-7.6 points, 95% CI -13.2 to -1.9). CONCLUSIONS: The present study suggests that SDM between physicians and patients is positively associated with online information-seeking behavior, with no negative influence associated with accessing the Internet before clinical consultations. Rheumatologists may need to introduce their patients to websites offering high-quality health information to establish a good physician-patient relationship for SDM.

Variables for differential diagnosis of familial Mediterranean fever: multiple correspondence analysis of a large Japanese cohort.

OBJECTIVES: We investigated differential diagnoses that should be noted with familial Mediterranean fever (FMF) and useful variables for differentiation in a large Japanese cohort. METHODS: Patients aged ≥13 years who were clinically suspected of having FMF by Livneh criteria were studied 1 year after MEFV genetic testing. Patients ultimately diagnosed with other diseases were studied, and the association among each disease, patient characteristics, and clinical variables were analyzed using multiple correspondence analysis. RESULTS: In total, 504 patients were included in this study; 34 (6.7%) were diagnosed with a disease other than FMF. The most common diagnosis was Behçet's disease, followed by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, inflammatory bowel disease, myelodysplastic syndromes (MDS), and infectious diseases. Although none of the non-FMF patients had exon 10 variants, some responded to colchicine treatment. Multiple correspondence analysis suggested that atypical symptoms such as stomatitis were associated with Behçet's disease and PFAPA syndrome, whereas characteristic situations such as disease onset ≥40 years were associated with MDS and infectious diseases. CONCLUSION: Careful follow-ups and reanalysis of the diagnosis should be performed for patients with atypical findings and no exon 10 variants, even if their symptoms meet the clinical criteria for FMF.

The Association of Grit With Burnout Components (Professional Efficacy, Exhaustion, and Cynicism) Among Academic Rheumatologists: The TRUMP 2 -SLE Study.

OBJECTIVES: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists. METHODS: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [assistant professor or higher vs lower], marital status, and having children). RESULTS: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04). CONCLUSIONS: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit.

Features of BAFF and APRIL receptors on circulating B cells in antineutrophil cytoplasmic antibody-associated vasculitis.

To investigate the features of circulating B cells, their expressing receptors, serum levels of B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Blood samples from 24 patients with active AAV (a-AAV), 13 with inactive AAV (i-AAV), and 19 healthy controls (HC) were included in this study. The proportion of B cells and their expressing BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen were analyzed via flow cytometry. Serum levels of BAFF, APRIL, and interleukin (IL)-4, IL-6, IL-10, and IL-13 were also evaluated using an enzyme-linked immunosorbent assay. The proportion of plasmablasts (PB)/plasma cells (PC) and serum levels of BAFF, APRIL, IL-4, and IL-6 were significantly higher in a-AAV than in HC. Higher serum levels of BAFF, APRIL, and IL-4 were observed in i-AAV than in HC. Lower expression of BAFF-R on memory B cells and higher expression of TACI on CD19+ cells, immature B cells, and PB/PC were demonstrated in a-AAV and i-AAV than in HC. The population of memory B cells was positively associated with serum APRIL levels and BAFF-R expression in a-AAV. In conclusion, decreased expression of BAFF-R on memory B cells and increased expression of TACI on CD19+ cells, immature B cells, and PB/PC, as well as increased serum levels of BAFF and APRIL, were sustained even in the remission phase of AAV. Persistent aberrant signaling of BAFF/APRIL may contribute to disease relapse.

Testicular vasculitis in eosinophilic granulomatosis with polyangiitis: a case-based review.

Testicular vasculitis (TV) develops when an organ is involved in systemic vasculitis. A 47-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA) developed TV as the first clinical episode. The patient had bronchial asthma for 8 years and developed left testicular pain before developing arthralgia, abdominal involvement, and sensory polyneuropathy, which led to the diagnosis of EGPA. The induration of the affected testicle persisted even after initiating immunosuppressive therapy with corticosteroids and cyclophosphamide, raising concern for testicular neoplasm, while testicular pain and other symptoms resolved. The patient underwent inguinal orchiectomy, and a histology examination of the resected testicle revealed fibrinoid necrotizing vasculitis. Only three cases of biopsy-proven TV in patients with EGPA have been reported in our review of published English-language articles. Two of the three patients in the reviewed cases developed TV before being diagnosed with EGPA. Moreover, all patients underwent extirpation of the affected testicle, leading to a pathological diagnosis of TV. This report suggests that TV may develop and be the presenting condition in EGPA, although urogenital involvement is rare.

Effect of Communicative and Critical Health Literacy on Trust in Physicians Among Patients With Systemic Lupus Erythematosus (SLE): The TRUMP2-SLE Project.

OBJECTIVE: Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one's physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit. RESULTS: A total of 362 patients with SLE were included. Trust in one's physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference -6.88, 95% CI -11.72 to -2.04, respectively). Longer internet use was associated with both higher communicative and critical HL. CONCLUSION: The findings suggest that rheumatologists need to improve their communication to match each patient's HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.

Grit personality of physicians and achievement of treatment goals in patients with system lupus erythematosus.

OBJECTIVES: Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. METHODS: This cross-sectional study was conducted at five referral hospitals. The main exposure was 'consistency of interest' and 'perseverance of effort' of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders. RESULTS: The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8) and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question 'I often set a goal but later choose to pursue a different one' was significantly higher in patients achieving LLDAS. CONCLUSIONS: Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.

Hypertrophic Pachymeningitis Associated with Myeloperoxidase-anti-neutrophil Cytoplasmic Antibodies Induced by Propylthiouracil.

A 71-year-old man with hyperthyroidism complained of headache lasting two months. He had been using propylthiouracil (PTU) for 14 years. Treatment intensification did not improve the symptoms. Blood tests detected a positive myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA). Diffuse dural thickening was identified by magnetic resonance imaging. The patient was diagnosed with hypertrophic pachymeningitis (HP) due to ANCA-associated vasculitis (AAV). He received methylprednisolone pulse therapy followed by prednisolone and methotrexate, which improved his headache. PTU-induced AAV-related HP is a rare and indiscernible disease. Therefore, the possibility of the disease should be proactively considered when a PTU user experiences refractory headaches.

Trust in the attending rheumatologist, health-related hope and medication adherence among Japanese systemic lupus erythematosus patients.

OBJECTIVE: Poor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one's physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians. METHODS: This cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one's physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications. RESULTS: Altogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one's physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence. CONCLUSIONS: This study demonstrated that patients' health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE.

The impact of normal serum complement levels on the disease classification and clinical characteristics in systemic lupus erythematosus.

BACKGROUND: Some patients have normal levels of complement during the diagnosis of systemic lupus erythematosus (SLE), although decreased serum levels of complement are a hallmark of the active phase of the disease. This study investigated the clinical characteristics, impact on the classification of SLE, and the prognosis of patients with SLE who had normal serum complement levels at initial diagnosis (N-com). METHODS: We evaluated 21 patients with N-com and 96 patients with hypocomplementemia at the initial diagnosis of SLE (H-com). The classification rates among the American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, European League Against Rheumatism (EULAR)/ACR 2019 criteria, and clinical and immunological involvements were compared between SLE patients with N-com and H-com. Relapse and organ damage based on the SLICC/ACR damage index were also evaluated. RESULTS: The classification rates of SLE were not significantly different in the ACR, SLICC, and EULAR/ACR criteria between the N-com and H-com groups. Patients with N-com had no significant differences in the classification rates among the three criteria, whereas patients with H-com had lower classification rates in the ACR criteria than in the SLICC criteria. A lower incidence of renal manifestation, less positivity for anti-dsDNA antibody, and a higher incidence of fever were observed in patients with N-com than in those with H-com. The occurrence of relapse and organ damage was not significantly different between patients with N-com and H-com. CONCLUSION: Patients with N-com were less involved in renal manifestation and anti-dsDNA antibody positivity but had a higher incidence of fever than those with H-com, while having no disadvantage in SLE classification processes. Serum complement levels at the initial diagnosis of SLE may not predict prognosis.

Hypertrophic pachymeningitis in ANCA-associated vasculitis: a cross-sectional and multi-institutional study in Japan (J-CANVAS).

BACKGROUND: This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan. METHODS: We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed. RESULTS: Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03-2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59-13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51-29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24-85.03, p < 0.0001). CONCLUSION: GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.

Clinical characteristics and treatment of elderly onset adult-onset Still's disease.

Adult-onset Still's disease (AOSD)-a systemic inflammatory disease-often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008-December 2020. Patients were divided into two groups according to age at disease onset: younger-onset (≤ 64 years) and elderly onset (≥ 65 years). Clinical symptoms, complications, laboratory findings, treatment, and outcomes were compared. Twenty-six (41.9%) patients developed AOSD at age ≥ 65 years. The elderly onset group had a lower frequency of sore throat (53.8% vs. 86.1%), higher frequency of pleuritis (46.2% vs. 16.7%), and higher complication rates of disseminated intravascular coagulation (30.8% vs. 8.3%) and macrophage activation syndrome (19.2% vs. 2.8%) than the younger onset group. Cytomegalovirus infections were frequent in elderly onset patients (38.5% vs. 13.9%) but decreased with early glucocorticoid dose reduction and increased immunosuppressant and tocilizumab use. Elderly AOSD is not uncommon; these patients have different characteristics than younger-onset patients. Devising a way to control disease activity quickly while managing infections may be an important goal in elderly AOSD.

Oxidative Stress Promotes Instability of Regulatory T Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

We investigated the characteristics of regulatory T cells (Tregs), focusing on the relationship between their stability and reactive oxygen species (ROS), in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Intracellular expressions of effector cytokines, forkhead box protein 3 (FoxP3), ROS, phosphorylated mammalian target of rapamycin (mTOR), and sirtuin 1 (SIRT1) in Tregs from peripheral blood mononuclear cells (PBMCs) of patients with AAV and healthy controls (HC) were analyzed. The alterations in and functional ability of Tregs were compared before and after resveratrol (RVL) treatment of PBMCs in patients with AAV. Significantly higher expressions of interferon (IFN)-γ, interleukin (IL)-17, IL-4, ROS, and phosphorylated mTOR (pho-mTOR) and lower expression of SIRT1 in CD4+CD25+FoxP3+ cells were found in patients with AAV than in the HC. FoxP3 expression in CD4+CD25+ cells and suppressive function of Tregs were significantly lower in patients with AAV than in the HC. Tregs after RVL treatment demonstrated significant decreases in IFN-γ, ROS, and pho-mTOR levels and increases in FoxP3, SIRT1 levels, and functional activity. Conversely, the direct activation of SIRT1 by SRT1720 resulted in decreased FoxP3 expression, with no reduction in ROS levels. The pho-mTOR levels were significantly higher in Tregs after activation by SRT1720 than in those after RVL treatment. This study suggested that imbalanced changes in Tregs could be attributed to mTOR activation, in which ROS overproduction was predominantly implicated. Therefore, ROS is a key mediator for promoting Tregs instability in AAV.