HLA-E-expressing macrophage polarization and increased NKG2A/CD94 expression in adult-onset Still's disease.

We investigated the phenotypic characteristics of human leukocyte antigen (HLA)-E-expressing macrophages, NKG2A/CD94 expression in T and natural killer (NK) cells, and their interactions in patients with adult-onset Still's disease (AOSD). Peripheral blood mononuclear cells from 22 patients with AOSD and 22 healthy controls (HC) were used. Isolated monocytes were cultured first with macrophage colony-stimulating factor to differentiate into M0 macrophages and subsequently with lipopolysaccharide/interferon-γ or interleukin-4 to differentiate into M1 or M2 macrophages, respectively. HLA-E and NKG2A/CD94 expression levels were evaluated using quantitative RT-PCR and flow cytometry. HLA-E expression in M0 and M2 macrophages was significantly higher in patients with AOSD than in HC, and was positively correlated with serum C-reactive protein levels and erythrocyte sedimentation rate. NKG2A/CD94 expression in CD4 + and CD8 + T cells was significantly higher in patients with AOSD than in HC, but that in NK cells was not significantly different. In patients with AOSD, NKG2A expression in CD4 + T cells positively correlated with HLA-E expression in M0, M1, and M2 macrophages. CD94 expression in CD8 + T cells inversely correlated with HLA-E expression in M1 and M2 macrophages. NKG2A and CD94 expression in NK cells inversely correlated with HLA-E expression in M0, M1, and M2 macrophages. No significant correlation was observed between HLA-E and NKG2A/CD94 expression in HC. Increased expression of HLA-E in macrophages and NKG2A/CD94 in T cells can be observed in the inflammatory condition of AOSD. HLA-E-expressing macrophages may be associated with NKG2A/CD94 expression in T and NK cells with different correlations.

Low serum complements in idiopathic inflammatory myositis: clinical features and impact on the prognosis.

This study investigated the clinical features and prognostic relevance of decreased serum complement levels in patients with idiopathic inflammatory myositis (IIM). The clinical information of IIM patients with less than normal serum complement levels (L-Com) and that of those with normal serum complement levels (N-Com) was compared. In patients with interstitial lung disease (ILD), regression analyses were used to investigate the implication of L-Com in their PaO2/FiO2 (P/F) ratio. Prognostic outcomes of ILD were evaluated using the log-rank test. Of 94 IIM patients, 26 with L-Com (median age, 56.0 years) and 68 with N-Com (56.5 years) were included. The prevalence of women was significantly higher in patients with L-Com (92.3%) than in those with N-Com (67.6%). ILD was observed in 17 (65.4%) patients with L-Com and in 46 (67.6%) with N-Com. Among patients with ILD, the P/F ratio was significantly lower in those with L-Com than in those with N-Com. Serum C3 levels were correlated with decreased P/F ratio. Inferior prognosis of ILD was significantly demonstrated in patients with L-Com, especially in those positive for anti-melanoma differentiation-associated protein 5 antibody. L-Com may be implicated in reduced arterial oxygen levels and a poorer prognosis in patients with IIM-related ILD.

Predictive validity of Lupus Patient-Reported Outcome for damage accrual in patients with systemic lupus erythematosus: the LUNA Registry.

OBJECTIVES: The predictive validity of disease-specific quality of life (QOL) remains unknown in patients with systemic lupus erythematosus (SLE), although disease-specific measures are equally or more responsive to changes than generic QOL. We aimed to examine the predictive validity of the Lupus patient-reported outcome (PRO) for damage accrual. METHODS: Patients with SLE and ≥2 measurements over time were included in Japanese nationwide multicentre registry (LUNA). The Lupus PRO questionnaire contains both health-related (HR) and non-HR-QOL measures. Damage accrual was evaluated using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We examined the association between the Lupus-PRO score at baseline and longitudinal SDI scores using mixed-effects models adjusted for prognostic factors. RESULTS: Among 1295 patients, those with higher HR-QOL of Lupus PRO at baseline demonstrated a significantly lower increase in SDI (-0.005/year, 95% confidence interval [CI]: -0.007 to - 0.004, p < 0.001). According to the categorisation of HR-QOL based on tertile, a similar dose-dependent effect of HR-QOL on longitudinal SDI was identified (second vs first tertile category: -0.101/year, 95% CI: -0.172 to - 0.030; third tertile category: -0.211/year, 95% CI: -0.281 to - 0.142). Non-HR-QOL was not significantly associated with the SDI scores. Among the HR-QOL domains, cognition, procreation, and physical health were significantly associated with the total SDI scores over time. HR-QOL was associated with corticosteroid-dependent and -independent SDI scores. CONCLUSION: A higher HR-QOL of Lupus PRO was associated with a lower increase in SDI scores. Our findings imply the importance of disease-specific HR-QOL measurements in assessing prognosis.

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.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

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

We report a case of eosinophilic granulomatosis with polyangiitis 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 necrotising vasculitis with perivascular eosinophil infiltration, resulting in eosinophilic granulomatosis with polyangiitis diagnosis. Additionally, abundant immunoglobulin (Ig) G4-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 has been defined as a distinct clinical category regardless of fulfilling IgG4-related disease classification criteria. However, some autoimmune diseases, including eosinophilic granulomatosis with polyangiitis, can develop lymphadenopathy pathologically similar to IgG4-related lymphadenopathy.

Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry-a historical cohort study.

BACKGROUND: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. METHODS: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. RESULTS: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). CONCLUSIONS: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.

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.

Optimal Dose of Intravenous Cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: a retrospective cohort study of J-CANVAS.

OBJECTIVES: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively assessed patients with AAV who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes were also evaluated. RESULTS: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. CONCLUSION: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).

Quantitative evaluation of the thickened dura mater impacting clinical signs in immune-mediated hypertrophic pachymeningitis.

OBJECTIVE: This study evaluated the volume of thickened dura mater lesions and their impact on clinical findings in immune-mediated hypertrophic pachymeningitis (HP). METHODS: The volume of contrast-enhanced dura mater on magnetic resonance imaging was evaluated using the imaging feature quantification system in 19 patients with immune-mediated HP, including 12 with antineutrophil cytoplasmic antibody-related, 4 with IgG4-related, and 3 with idiopathic HP, as well as 10 with multiple sclerosis (MS) as controls. The implications of HP volume on neurological manifestations and cerebrospinal fluid (CSF) laboratory markers were statistically analyzed in patients with immune-mediated HP. RESULTS: The volumes of the contrast-enhanced dura mater in the convexity, cranial fossa, and tentorium cerebelli were significantly higher in patients with immune-mediated HP than in those with MS. Among patients with immune-mediated HP, those with cranial nerve (CN) VIII neuropathy had a significantly higher volume of the contrast-enhanced dura mater in the cranial fossa than those without CN VIII neuropathy. The volume of the contrast-enhanced dura mater in the tentorium cerebelli was positively correlated with CSF protein levels. CONCLUSION: Quantification of the thickened dura mater is useful for elucidating the relationship with the clinical findings in immune-mediated HP. Thickened dura mater lesions in the cranial fossa may be implicated in the development of CN VIII neuropathy. The enlargement of HP lesions in the tentorium cerebelli can increase CSF protein levels.

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.

Protective effect of hydroxychloroquine on infections in patients with systemic lupus erythematosus: an observational study using the LUNA registry.

Objectives: Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Alt hough hydroxychloroquine (HCQ) has been reported to inhibit infection, evidence from Asian populations remains insufficient. We investigated this effect in Japanese SLE patients. Methods: Data from the Lupus Registry of Nationwide Institutions were used in this study. The patients were ≥20 years old and met the American College of Rheumatology (ACR) classification criteria revised in 1997. We defined "severe infections" as those requiring hospitalization. We analyzed the HCQ's effect on infection suppression using a generalized estimating equation (GEE) logistic regression model as the primary endpoint and performed a survival analysis for the duration until the first severe infection. Results: Data from 925 patients were used (median age, 45 [interquartile range 35-57] years; female, 88.1%). GEE analysis revealed that severe infections were significantly associated with glucocorticoid dose (odds ratio [OR] 1.968 [95% confidence interval, 1.379-2.810], p<0.001), immunosuppressants (OR 1.561 [1.025-2.380], p=0.038), and baseline age (OR 1.043 [1.027-1.060], p<0.001). HCQ tended to suppress severe infections, although not significantly (OR 0.590 [0.329-1.058], p=0.077). Survival time analysis revealed a lower incidence of severe infections in the HCQ group than in the non-HCQ group (p<0.001). In a Cox proportional hazards model, baseline age (hazard ratio [HR] 1.029 [1.009-1.050], p=0.005) and HCQ (HR 0.322 [0.142-0.728], p=0.006) were significantly related to incidence. Conclusion: HCQ may help extend the time until the occurrence of infection complications and tends to decrease infection rates.

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.

Seasonal Influence on Development of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study Conducted at Multiple Institutions in Japan (J-CANVAS).

OBJECTIVE: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. RESULTS: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. CONCLUSION: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.

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.

Hypertrophic pachymeningitis in ANCA-associated vasculitis: Clinical and immunopathological features and insights.

Hypertrophic pachymeningitis (HP) is an inflammatory disorder characterized by intracranial and spinal thickened dura mater, leading to several neurological manifestations including headaches, cranial neuropathies, seizures, and sensorimotor disorders. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a crucial disease that is implicated in the development of immune-mediated HP. HP is observed throughout the clinical course of AAV, and 3%-4% of patients with AAV experience HP as the initial clinical episode. However, patients with ANCA-related HP are unclassifiable in the classification criteria of AAV when HP is the only manifestation, suggesting that ANCA-related HP can be identified as a central nervous system-limited type of AAV. Among patients with AAV, those who develop HP have predominantly been classified as having granulomatosis with polyangiitis (GPA). Myeloperoxidase-ANCA positivity has been more frequently demonstrated than proteinase 3-ANCA positivity in patients with ANCA-related HP. The ear, nose, and throat manifestations, such as otitis media, sinusitis, and mastoiditis, as well as mucous membranes/eyes manifestations including sudden visual loss, are robustly associated with HP in AAV. The histology of thickened dura mater tissues includes fibrotic changes and infiltration of several immunocompetent cells, but the typical findings of GPA, such as granulomatous inflammation with necrotizing vasculitis, are not observed in all patients with ANCA-related HP. Corticosteroids are the first-line therapy for ANCA-related HP, while the concomitant use of immunosuppressive agents including cyclophosphamide, methotrexate, and mycophenolate mofetil, is an ideal strategy for achieving remission. Rituximab is a useful agent in refractory ANCA-related HP.