Multidrug-resistant IgA Vasculitis with Gastrointestinal Symptoms Successfully Treated with Intravenous Cyclophosphamide and Maintained with Mycophenolate Mofetil.

We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.

Comparative analysis of low-field magnetic resonance imaging in patients with rheumatoid arthritis treated with certolizumab pegol or infliximab.

OBJECTIVES: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). METHODS: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. RESULTS: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. CONCLUSIONS: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.

Abatacept ameliorates both glandular and extraglandular involvements in patients with Sjögren's syndrome associated with rheumatoid arthritis: Findings from an open-label, multicentre, 1-year, prospective study: The ROSE (Rheumatoid Arthritis with Orencia Trial Toward Sjögren's Syndrome Endocrinopathy) and ROSE II trials.

OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.

Clinical features and serum cytokine profiles of elderly-onset adult-onset Still's disease.

Recent studies have suggested that the clinical features of elderly-onset adult-onset Still's disease (AOSD) differ from those of young and middle-aged-onset patients, whereas the details remain unclear, and cytokine profiles of elderly-onset AOSD have not been reported. To clarify the clinical features and cytokine profiles of elderly-onset AOSD, we examined patients with AOSD who developed the disease between January 2006 and September 2021. We divided the patients into the young and middle-aged-onset group (aged < 65 years) and the elderly-onset group (aged ≥ 65 years) and compared the groups in terms of patient characteristics, clinical symptoms, laboratory findings including serum interleukin (IL)-6 and IL-18, treatment, and prognosis. A total of 48 patients were examined (10 in the elderly-onset group). In the elderly-onset group, atypical rash was significantly more frequent, typical rash and splenomegaly were significantly less frequent, white blood cell count and neutrophil ratio were significantly higher and serum IL-6 levels were significantly lower. Serum IL-6 showed a significantly negative correlation with age at onset. Treatment and relapse were comparable between the 2 groups, whereas infections were significantly more frequent in the elderly-onset group. The clinical features and cytokine profiles of elderly-onset AOSD might differ from those of young and middle-aged-onset AOSD.

Activation mechanisms of monocytes/macrophages in adult-onset Still disease.

Adult onset Still disease (AOSD) is a systemic inflammatory disorder characterized by skin rash, spiking fever, arthritis, sore throat, lymphadenopathy, and hepatosplenomegaly. Although the etiology of this disease has not been fully clarified, both innate and acquired immune responses could contribute to its pathogenesis. Hyperactivation of macrophages and neutrophils along with low activation of natural killer (NK) cells in innate immunity, as well as hyperactivation of Th1 and Th17 cells, whereas low activation of regulatory T cells (Tregs) in acquired immunity are involved in the pathogenic process of AOSD. In innate immunity, activation of monocytes/macrophages might play central roles in the development of AOSD and macrophage activation syndrome (MAS), a severe life-threating complication of AOSD. Regarding the activation mechanisms of monocytes/macrophages in AOSD, in addition to type II interferon (IFN) stimulation, several pathways have recently been identified, such as the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)-pattern recognition receptors (PRRs) axis, and neutrophil extracellular traps (NETs)-DNA. These stimulations on monocytes/macrophages cause activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain (NLRP) 3 inflammasomes, which trigger capase-1 activation, resulting in conversion of pro-IL-1ß and pro-IL-18 into mature forms. Thereafter, IL-1ß and IL-18 produced by activated monocytes/macrophages contribute to various clinical features in AOSD. We identified placenta-specific 8 (PLAC8) as a specifically increased molecule in monocytes of active AOSD, which correlated with serum levels of CRP, ferritin, IL-1ß, and IL-18. Interestingly, PLAC8 could suppress the synthesis of pro-IL-1ß and pro-IL-18 via enhanced autophagy; thus, PLAC8 seems to be a regulatory molecule in AOSD. These findings for the activation mechanisms of monocytes/macrophages could shed light on the pathogenesis and development of a novel therapeutic strategy for AOSD.

Synovitis-acne-pustulosis-hyperostosis-osteitis Syndrome with Bilateral Pleural Effusion.

Pleural effusion is a rare manifestation in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, which is characterized by the presence of osteoarticular lesions and dermatological involvement. We herein report a 71-year-old man with pleural effusion resulting from SAPHO syndrome. He was successfully treated using corticosteroids and has experienced no recurrence for one year. We should consider SAPHO syndrome when encountering cases of anterior chest pain and pleural fluid.

Predictive Factors for Pneumomediastinum During Management of Connective Tissue Disease-related Interstitial Lung Disease: A Retrospective Study.

Objective To identify factors associated with pneumomediastinum during management of connective tissue disease (CTD)-related interstitial lung disease (ILD). Methods Patients diagnosed with pneumomediastinum after the initiation of corticosteroid therapy for their CTD-ILD were enrolled. The baseline characteristics of patients who developed pneumomediastinum after the initiation of corticosteroid therapy (n=13, all occurring within 120 days) were compared to those of patients who did not develop pneumomediastinum (n=49). A multivariate logistic regression analysis was performed to identify factors associated with pneumomediastinum. A receiver operating characteristic (ROC) curve analysis was also performed to assess the predictive performance. Results The body mass index (BMI) [odds ratio (OR) (95% confidence interval (CI)) 0.482 (0.272-0.853)] and serum lactate dehydrogenase (LDH) [OR (95% CI) 1.013 (1-1.025)] levels at baseline were identified as independent factors associated with pneumomediastinum after corticosteroid initiation. The optimal cut-off points of the BMI and LDH levels for predicting pneumomediastinum development, as estimated by the Youden index, were 20.2 kg/m2 and 378 U/L, respectively. LDH showed a sensitivity of 61.5% and the highest specificity of 87.8%. Importantly, combining these markers resulted in the highest sensitivity of 100% and a specificity of 71.4%. Conclusion A low BMI and high serum LDH levels at baseline are useful predictive factors for pneumomediastinum development in CTD-ILD patients.

QTc interval prolongation in patients with systemic lupus erythematosus treated with hydroxychloroquine.

OBJECTIVES: The primary objective is to reveal the effect of hydroxychloroquine (HCQ) treatment on corrected QT (QTc) interval in patients with systemic lupus erythematosus (SLE). The secondary objective is to investigate factors that affect QTc prolongation. METHODS: SLE patients who had electrocardiograms between 2015 and 2020 were recruited and assigned to two groups based on whether they were treated with HCQ (HCQ group) or not (control group). Change of QTc before and after HCQ administration in the HCQ group was measured and compared with the control group. Patients treated with HCQ were further divided into two groups based on presence or absence of QTc prolongation and the characteristics were compared. RESULTS: In total, 126 patients were recruited, of whom 42 were treated with HCQ. In the HCQ group, the mean QTc significantly increased (p < .001), while there was no significant difference of mean QTc in the control group. Moreover, those in the HCQ group with QTc prolongation showed a significantly higher proportion of hypertension and longer SLE duration compared to those without QTc prolongation. However, the multiple logistic regression analysis showed that there were no significant differences among them. CONCLUSION: HCQ could induce QTc prolongation in SLE patients. It might be better that the possibility of QTc prolongation was taken into consideration when HCQ was administered in the patients with longer disease duration of SLE and coincidence of hypertension.

Clinical features of large vessel vasculitis (LVV): Elderly-onset versus young-onset.

OBJECTIVES: We compared large vessel vasculitis (LVV) clinical features between age groups. METHODS: We retrospectively examined clinical features and therapies in 41 LVV patients at our hospital from January 2010 to March 2020. We compared two patient groups, elderly (≥50 years) and young (<50 years). RESULTS: Of all patients, 29 were elderly and 12 were young. In the younger group, upper extremity symptoms (p <.05), bruits (p <.01), and cardiovascular complications (p <.01) were more common. Of the elderly group, 7 (24%) met classification criteria for giant cell arteritis while none of the younger group met these criteria; however, 10 (83%) of the younger group and 3 (10%) of the elderly group met the ACR classification criteria for Takayasu arteritis (p <.01). In the elderly group, 16 patients (66%) met no criteria (p <.01). There were no significant differences in laboratory findings but imaging showed a significantly higher incidence of head and neck artery lesions in the younger group (p <.05). The younger group was more likely to receive additional tocilizumab (p <.01) and cardiovascular complications were more likely to occur in younger patients (p < .01). CONCLUSION: LVV clinical features differed between elderly- and young-age-onset groups.

Clinical features and prognosis of nocardiosis in patients with connective tissue diseases.

OBJECTIVES: To investigate the clinical features and prognosis of nocardiosis complicated by connective tissue diseases (CTDs). METHODS: We examined patients with CTDs who were diagnosed with nocardiosis from October 2004 to 2019. We retrospectively investigated patient characteristics and therapeutic outcomes. We then performed a comparison between survivors and non-survivors. RESULTS: Fourteen patients were examined. Underlying CTDs were systemic lupus erythematosus (28.6%), vasculitis syndrome (28.6%), rheumatoid arthritis (21.4%), adult Still disease (14.3%) and dermatomyositis (7.1%). Infected organs were lung (85.7%), brain (42.9%), skin/cutaneous lesions (28.6%) and muscle (7.1%). Disseminated infections were seen in nine patients (64.3%). At the onset of nocardiosis, all patients were given prednisolone (23.2 ± 11.9 mg/day). Only two patients (14.3%) were given TMP-SMX for prophylaxis of pneumocystis pneumonia. Relapse occurred in one patient (7.1%) and four patients (28.6%) died from nocardiosis for a cumulative survival rate at 52 weeks of 76.9%. In a comparison of survivors (71.4%) and non-survivors (28.6%), cutaneous lesions were significantly more frequent in the latter (10 vs 75%, p = .04) with an odds ratio of 27.0 (95% CI: 1.7-453.4). CONCLUSION: Cutaneous lesions as a result of dissemination might be a risk factor for nocardiosis mortality in patients with CTDs.

Therapeutic Plasma Exchange Improved Pregnancy-associated Thrombotic Microangiopathy but not the Pregnancy Outcome in Patient with Systemic Lupus Erythematosus.

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.

M3 muscarinic acetylcholine receptor-reactive Th17 cells in primary Sjögren's syndrome.

M3 muscarinic acetylcholine receptor (M3R) is one of the autoantigens associated with Sjögren's syndrome (SS) and is localized in exocrine glands where disease-specific inflammation occurs. The inflammatory lesion is characterized by infiltration of CD4+ T cells, including clonally expanded Th17 cells. We undertook this study to identify circulating M3R-specific Th17 cells and to determine functional properties of those cells. Using the enzyme-linked immunospot assay (ELISpot) method, we identified M3R-reactive Th17 cells in the peripheral blood of patients with primary SS (pSS). Among 10 examined pSS patients, 10 healthy subjects (HS), and 5 IgG4-related disease (IgG4-RD) patients, M3R-reactive IL-17 secreting cells were significantly increased in 5 pSS patients specifically. The most common T cell epitope, which was analyzed and confirmed by coculture of isolated CD4+ T cells with antigen presenting cells plus M3R peptides in vitro, was peptide 83-95 of M3R. Peptide recognition was partly in an HLA-DR-restricted manner, confirmed by blocking assay. M3R-reactive Th17 cells positivity correlated with higher titers of anti-M3R antibodies, whose systemic disease activity score tended to be higher. Our studies highlight the role of tissue-specific autoantigen-derived circulating Th17 cells in pSS, for which further work might lead to antigen-specific targeted therapy.

IgG4-related pleural disease with aortitis and submandibular glands involvement successfully treated with corticosteroid: case-based review.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by increased serum IgG4 level, infiltration of lymphocytes and IgG4-positive (IgG4+) plasma cells and fibrosis. It can occur in almost all organs, commonly affecting the pancreas, biliary tract, salivary and lacrimal glands and kidneys. However, reports of IgG4-RD accompanied by pathologically confirmed, IgG4-related pleural disease are scarce. Here, we present a case of a 64-year-old man with suspected malignant pleural mesothelioma based on imaging findings but finally diagnosed with IgG4-RD (including pleuritis, periaortitis and bilateral submandibular gland enlargement) based on a high serum IgG4 level and pleural histopathological findings such as lymphoplasmacytic infiltration including IgG4+ plasma cells and fibrosis. Systemic corticosteroid therapy was effective at reducing serum IgG4, improving bilateral submandibular gland enlargement, and regressing pleural thickening and periaortic soft tissue. We also discuss clinical characteristics and pleural pathological features of previously reported cases with IgG4-related pleural disease based on a comprehensive literature review. Our case of IgG4-RD with pleura, aorta and submandibular gland involvement, pathologically confirmed by pleural specimen might be unique and very rare.

Aortic Arch Aneurysm in Behçet Disease Successfully Treated with Infliximab.

Aortic arch aneurysm (AAA) is a rare involvement in Behçet disease (BD). It is often life-threatening, yet few reports related to the treatment of AAA have been published. We herein report a 27-year-old woman with AAA caused by vascular BD. She was initially treated with prednisolone 1 mg/kg/d. However, the inflammation had not subsided after three weeks, so infliximab (IFX) was added for relief. After IFX administration, the C-reactive protein level normalized, and computed tomography at three months after therapeutic intervention revealed that the aneurysm had disappeared. This case suggests that early induction of IFX might be effective for aortic aneurysm in BD.

Association of anti-cyclic citrullinated peptide antibody with clinical features in patients with psoriatic arthritis.

Background: Although anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is reported to be found in 5-20% of patients with psoriatic arthritis (PsA), its clinical significance has not been elucidated.Objective: To clarify the association of anti-CCP Ab with clinical features in PsA.Methods: Patients were enrolled who fulfilled the classification criteria for psoriatic arthritis (CASPAR) criteria and visited our hospital. We retrospectively compared clinical characteristics between those who were positive and negative for anti-CCP Ab and further compared changes in disease activity in the patients treated with biological disease-modifying anti-rheumatic drugs (DMARDs).Results: We examined 41 patients (11 females), seven were anti-CCP Ab-positive and 34 were negative. Age (55.0 ± 15.1 years old) and frequency of lung involvements (71.4%) in the anti-CCP Ab-positive group were significantly higher than those (40.0 ± 16.0 and 0%, respectively) in the negative group (p < .05). Rheumatoid factor (RF) titer (749.4 ± 860.7 U/mL) and MMP-3 (604.8 ± 1060.6) in the anti-CCP Ab-positive group was significantly higher than that (3.6 ± 4.4 U/mL and 111.2 ± 77.4, respectively) in the negative group (p < .05). Five patients were treated with tumor necrosis factor (TNF) inhibitors (infliximab (IFX): 3 and adalimumab (ADA): 2) in the anti-CCP Ab-positive group, while in the negative group there were 11 (IFX: 6, ADA: 4, and etanercept (ETN): 1). Within 6 months of treatment, arthritis did not improve with TNF inhibitors in the anti-CCP Ab-positive group, whereas it improved significantly in the negative group.Conclusion: In patients with PsA, anti-CCP Ab might be related to lung involvements, elderly onset, RF and MMP-3 titers, and resistance to TNF inhibitor.