Shuzo Yoshida

Differentiation between Polymyalgia Rheumatica (PMR) and Elderly-Onset Rheumatoid Arthritis Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Is Enthesitis a New Pathological Lesion in PMR?

Background It is difficult to differentiate polymyalgia rheumatica (PMR) from elderly-onset rheumatoid arthritis (EORA) in clinical practice. We compared FDG-PET/CT findings between patients with PMR and those with EORA and extracted factors useful for differentiating the two disorders. Methods We compared abnormal FDG accumulation sites and maximum standardized uptake value (SUVmax) between 15 patients with PMR and 7 with EORA in whom FDG-PET/CT was performed. Results The proportion of patients in the PMR group with abnormal FDG accumulation at the following 9 sites on FDG-PET/CT was significantly higher than that in the EORA group: periarticular region of the scapulohumeral joint, enthesis of the pectineus muscle, vicinity of the enthesis of the rectus femoris muscle, lateral side of the greater trochanter, ischial tuberosity, hip joint, spinous process of the lower cervical vertebra, intervertebral joint of the lumbar vertebra, and spinous process of the lumbar vertebra. The PET/CT score was evaluated at 9 sites consisting of the abovementioned sites. The median score in the PMR group was 8, which was significantly higher than that of 0 in the EORA group (P = 0.0003). ROC curve analysis was performed with the PET/CT scores, and a score of 5 was shown to maximize the area under the ROC curve (sensitivity: 86.7%, specificity: 86.7%). Conclusions FDG-PET/CT is useful for differentiating PMR from EORA. In patients with PMR, abnormal FDG accumulation was observed at the entheses, suggesting the presence of enthesitis in addition to bursitis and synovitis.

Pre-Treatment Ferritin Level and Alveolar-Arterial Oxygen Gradient Can Predict Mortality Rate Due to Acute/Subacute Interstitial Pneumonia in Dermatomyositis Treated by Cyclosporine A/Glucocorticosteroid Combination Therapy: A Case Control Study

Background Acute/subacute interstitial pneumonia in dermatomyositis (DM-A/SIP) is a disease associated with a poor prognosis that resists treatment with glucocorticosteroids (GC) and progresses rapidly in a period of weeks to months to death. We retrospectively studied outcomes, prognostic factors, and their relations with survival rate in patients with DM-A/SIP treated with early cyclosporine A (CSA)/GC combination therapy and 2-hour postdose blood concentration monitoring. Methods This study comprised 32 DM-A/SIP patients who were simultaneously treated with CSA and prednisolone. Clinical and laboratory findings were compared between those who died due to DM-A/SIP and those surviving 24 weeks after beginning of therapy. Prognostic factors were extracted, and their relations with the survival rate were evaluated. Results Of the 32 DM-A/SIP patients, 25 survived, 5 died of DM-A/SIP, and 2 died of infections. In those who died due to DM-A/SIP, ferritin level and the alveolar-arterial oxygen gradient were significantly increased compared with the survivors (P<0.001 and P = 0.002, respectively). Multivariate analyses showed that ferritin and alveolar-arterial oxygen gradient were independent prognostic factors of poor outcome. The survival rate 24 weeks after beginning of treatment was significantly lower in those with a ferritin level of ≥600 ng/ml and alveolar-arterial oxygen gradient of ≥45 Torr (P<0.001 and P<0.001, respectively). All patients with both prognostic factors died, and the outcome was significantly poorer in these patients than in those with one or neither of the prognostic factors (P<0.001). Conclusions We identified pre-treatment high serum ferritin level and high alveolar-arterial oxygen gradient as poor prognostic factors in DM-A/SIP patients undergoing early CSA/GC combination therapy and showed that the outcomes were poor in patients with both factors.

Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients.

Abstract Objectives: We retrospectively investigated clinical prognostic factors for interstitial pneumonia (IP) in anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM) patients. Methods: Subjects comprised 18 patients with anti-MDA5 Ab-positive DM-IP (9 survivors; 9 deaths). Results: Initial serum albumin levels, ferritin levels, and ground-glass opacity (GGO) scores in the right middle lobes were significantly higher in the death group than in the survivor group (p = .033, .013, and .005, respectively). Initial alveolar-arterial oxygen gradient (P[A-a]O2) was also higher in the death group than in the survivor group (p = .064). Initial serum ferritin, P[A-a]O2, and right middle lobe GGO score were found to significantly relate to death. Survival rates after 24 weeks were significantly lower among patients with an initial ferritin level of ≥450 ng/mL (25%), P[A-a]O2 of ≥30 mmHg (31%), and a right middle lobe GGO score of ≥2 (11%) than each of the others (p = .006, .020, and .002, respectively). Conclusions: An initial serum ferritin level of ≥450 ng/mL, P[A-a]O2 of ≥30 mmHg, and right middle lobe GGO score of ≥2 (GGO ≥5% of the lobe) were identified as poor prognostic factors for anti-MDA5 Ab-positive DM-IP patients.

Periodontal pathogens participate in synovitis in patients with rheumatoid arthritis in clinical remission: a retrospective case–control study

OBJECTIVE The objective of this study was to investigate the role of periodontal pathogens in RA in remission. METHODS Twenty-one patients with active RA and 70 patients in clinical remission, including 48 patients with synovitis [US power Doppler (USPD)(+) group] and 22 patients without synovitis [USPD(-) group] were clinically assessed by US. CRP, ESR, haemoglobin, MMP-3, RF and ACPA were measured. Antibody titres against four types of periodontal pathogen [Aggregatibacter actinomycetemcomitans, Eikenella corrodens (Ec), Porphyromonas gingivalis and Prevotella intermedia (Pi)] were analysed using ELISA. RESULTS Musculoskeletal US examination showed that 68.6% of patients with RA in clinical remission exhibited synovitis. CRP, ESR, haemoglobin, MMP-3 and RF levels in both the USPD(+) and USPD(-) groups were clearly lower compared with the RA group in non-remission. The IgG serum antibody titre against Ec in the non-remission RA(+) group was significantly greater than that in the USPD(+) group, and the IgG antibody titre against Pi in the non-remission RA and USPD(+) groups was greater than in the USPD(-) group. CONCLUSION More than half of RA patients in remission showed persistent synovitis. This synovitis may be associated with periodontal disease-causing Pi. Thus, treating periodontal disease should also be considered in order to achieve more profound remission of RA.

Successful treatment with tocilizumab of pericarditis associated with rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) is a systemic inflammatory disease often complicated by vasculitis. Pericarditis is a serious complication caused by vasculitis, resulting in retention of pericardial effusion that sometimes induces cardiac tamponade. We report a patient with RA in whom pericarditis improved after tocilizumab administration. A male patient was diagnosed with RA and chronic renal failure in 1980 and was treated with salazosulfapyridine, but disease activity remained high. In January 2012, at the age of 73 years, he developed organizing pneumonia as a complication and was admitted to our hospital. Treatment with prednisolone 30 mg/day was initiated. However, 20 days after initiation of treatment, chest pain and palpitation developed, and chest computed tomography (CT) and echocardiography (ECG) revealed retention of pericardial effusion without cardiac tamponade. Rheumatoid nodules and interstitial pneumonia were also observed, and serum C3 level was decreased. A diagnosis of pericarditis caused by vasculitis was made based on these findings, and tocilizumab 8 mg/kg was administered. His symptoms improved gradually, and chest CT and ECG showed no pericardial effusion after about 3 weeks. No adverse effects of tocilizumab were observed during the clinical course. Although there are only a few reports of the effects of tocilizumab on vasculitis associated with RA, tocilizumab administration appears worthwhile in RA patients with vasculitis who do not respond to conventional treatment.

Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study-

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.

Gastrointestinal involvement at the onset of granulomatosis with polyangiitis: A case report

A 30-year-old man had developed fever, bloody stools, and oral aphtha. Proteinase 3-antineutrophil cytoplasmic antibody level was 31 EU. Lower intestinal endoscopy revealed edematous mucosa with hemorrhage in the transverse colon. Biopsies of oral aphtha showed necrotizing angiitis with granuloma. Based on these findings, he was diagnosed with granulomatosis with polyangiitis (GPA). Digestive symptoms were remitted by treatment with prednisolone and azathioprine. GPA with digestive symptoms as the initial development is rare.

Successful multi-target therapy including rituximab and mycophenolate mofetil in anti-melanoma differentiation-associated gene 5 antibody-positive rapidly progressive interstitial lung disease with clinically amyopathic dermatomyositis

Dear Editor, Interstitial lung disease (ILD) in dermatomyositis (DM) is a serious complication that affects patient prognosis. ILD associated with clinically amyopathic DM (CADM) is more refractory and rapidly progressive than classical DM. Sato et al. identified anti-melanoma differentiation-associated gene 5 (MDA5) antibody and reported that about half of the patients with CADM positive for this antibody developed rapidly progressive ILD (RP-ILD). The cumulative 6month survival rate is reported to be approximately 50% for RP-ILD with anti-MDA5 antibody. In classic DM patients, ILD can progress rapidly when they are anti-MDA5 antibody positive. Here, we present a case of worsening RP-ILD despite treatment with high-dose prednisolone (PSL) combined with cyclosporine (CSA) and intravenous cyclophosphamide (IVCY) in a patient with anti-MDA5 antibody-positive CADM. The addition of polymyxin-B direct hemoperfusion (PMXDHP), mycophenolate mofetil (MMF), intravenous immunoglobulin (IVIG), and rituximab (RTX) led to remission of the disease.

Add-on iguratimod as a therapeutic strategy to achieve remission in patients with rheumatoid arthritis inadequately responding to biological DMARDs: A retrospective study

Abstract Objectives: In this study, iguratimod (IGU) was added to rheumatoid arthritis (RA) patients inadequately responding to 24-week or longer treatment with biological disease-modifying antirheumatic drug (bDMARDs), its effectiveness was assessed, and factors contributing to remission were evaluated. Methods: RA patients who fulfilled the following criteria were included: (i) ≥ 24-week of bDMARDs; (ii) 2.6 < disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) < 5.1 or the presence of synovitis with a power Doppler (PD) score ≥2 in at least 1 of the 28 joints on joint ultrasonography. Disease activity and joint ultrasound findings were evaluated at baseline and at 12 and 24 weeks. Results: DAS assessing 28 joints with ESR (DAS28-ESR) decreased significantly from 3.45 ± 0.92 at baseline to 2.85 ± 1.13 at 24 weeks (p < .001). Overall, 38.3% achieved clinical remission (c-remission). The total PD score decreased significantly from 8.7 ± 6.1 at baseline to 5.5 ± 5.0 at 24 weeks (p < .001). A lower baseline DAS28-ESR was related to c-remission after 24 weeks (p =.002). Shorter duration of disease (p =.020) was related to ultrasound remission, in addition to a lower baseline DAS28-ESR (p < .001). Conclusions: IGU add-on therapy can be a therapeutic strategy to achieve remission in RA patients inadequately responding to ≥24-week treatment with bDMARDs.

Chemokine profiles of interstitial pneumonia in patients with dermatomyositis: a case control study

Chemokines play an important role in the pathophysiology of dermatomyositis (DM) with interstitial pneumonia (IP). However, the relation between chemokines and the disease activity or prognosis of DM-IP has not been elucidated. We evaluated the serum C-C motif chemokine ligand (CCL) 2, Th1 chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11), and Th2 chemokine (CCL17) profiles of 30 patients, and examined the relation between these chemokines and the disease activity or prognosis of DM-IP. Initial serum CCL2 level was higher in the death group (P = 0.007). To determine the cut-off points effective as poor prognostic factors of DM-IP, ROC curve analysis was carried out on initial serum CCL2 level. The value that maximized the area under the ROC curve was 894 pg/mL (sensitivity: 100%, specificity: 70.8%). Serum CCL2, CXCL9, CXCL10, and CXCL11 levels were lower at 2 weeks after treatment initiation than before treatment. Serum CCL2, CXCL10, and CXCL11 levels at 2 weeks after treatment initiation were higher in the death group. Serum levels of chemokines such as CCL2, CXCL10, and CXCL11 may be possible biomarkers of disease activity and prognosis in DM-IP, and serum CCL2 level may be useful when deciding initial treatment.