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Objectives We aimed to investigate the vaccination coverage and the factors associated with non-vaccination for vaccine-preventable diseases among patients with rheumatoid arthritis. Methods This single-centre, cross-sectional study was conducted in a 715-bed regional tertiary-care teaching hospital in Japan from 1 September to 30 November 2020. Vaccination status and the factors and reasons for not receiving the influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), and varicella vaccine live (VVL) were investigated. Results Among 991 patients, the vaccination coverage for the influenza vaccine, PPSV23, PCV13, and VVL was 62%, 46%, 14%, and 3%, respectively. The most common reasons for vaccine hesitancy were efficacy concerns for the influenza vaccine, safety concerns for the PPSV23 and PCV13, and both efficacy and safety concerns for the VVL. Younger age, no use of biologics or other hospital visits, and public assistance were factors significantly associated with non-vaccination for the influenza vaccine; younger age, short disease duration, and no visits to other hospitals for PPSV23; younger age, no hospitalisation, more experienced doctor, and no medical immunodeficiency for PCV13. Conclusions We found that the factors associated with non-vaccination varied by vaccine type; therefore, vaccinations should be promoted with individualised strategies.

Objectives This study aimed to clarify the vaccination coverage of vaccine-preventable diseases and the factors and reasons for non-vaccination among patients with systemic lupus erythematosus (SLE). Methods/Patients This single-centre, cross-sectional study was conducted from 1 September to 30 November 2020 in a 715-bed regional tertiary-care teaching hospital in Japan. A questionnaire survey was undertaken to investigate the vaccination status of patients with SLE, and the factors and reasons for not receiving the influenza vaccine, 23-valent-pneumococcal-polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), varicella vaccine live (VVL), and recombinant zoster vaccine (RZV). Results The vaccination coverage for the influenza vaccine, PPSV23, PCV13, VVL, and RZV was 61%, 22%, 19%, 3.4%, and 0%, respectively, among 261 patients. The most common reason for vaccine hesitancy was 'efficacy concerns about vaccines' for the influenza vaccine and 'cost' for PPSV23 and PCV13. The factors significantly associated with non-vaccination were prescription of high-dose glucocorticoids and no history of visits to other internal medicine clinics for the influenza vaccine; a younger age and prescription of high-dose glucocorticoids for PPSV23; and a younger age, no medication with hydroxychloroquine, no history of hospitalisation in internal medicine, and extensive clinical experience of the doctor for PCV13. Conclusion These findings, which demonstrated that the factors and reasons for non-vaccination varied by vaccine type, suggest that individualised strategies should be used to promote vaccination in this population.

Objectives This study aimed to clarify factors associated with polypharmacy among patients with systemic lupus erythematosus. Methods This single-centre cross-sectional study was conducted by reviewing the medical records and questionnaire data of 261 systemic lupus erythematosus patients at a teaching hospital in Japan from 1 September to 30 November 2020. Polypharmacy was defined as the regular administration of five or more oral medications; excessive polypharmacy consisted of the regular use of 10 or more oral medications. This study investigated (1) the prevalence of polypharmacy and excessive polypharmacy, (2) the distribution of medication types, and (3) the factors associated with polypharmacy and excessive polypharmacy. Results The proportions of patients who exhibited polypharmacy and excessive polypharmacy were 70% and 19%, respectively. Polypharmacy was associated with older age, long duration of systemic lupus erythematosus, high disease activity, and administration of glucocorticoids or immunosuppressive agents. Excessive polypharmacy was associated with a higher updated Charlson comorbidity index, history of visits to multiple internal medicine clinics, and presence of public assistance. Conclusions Polypharmacy and excessive polypharmacy in patients with systemic lupus erythematosus are related to medical aspects such as disease severity and comorbidities in addition to social aspects such as hospital visitation patterns and economic status.

We encountered a case of refractory adult-onset Still's disease (AOSD) with two relapses. Prednisolone and methotrexate were begun as induction therapy, resulting in the patient's first relapse during tapering of prednisolone. After the introduction of tocilizumab, she achieved remission. However, she experienced a second relapse following prednisolone tapering. While lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts increased in both relapses, interleukin-6 (IL-6) suppression resulted in stable C-reactive protein and ferritin levels in the second relapse. A comparison of the two relapses indicated that increases in both WBC counts and LDH levels can aid in the diagnosis of AOSD relapse.

Objectives Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM. Methods Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups. Results Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%). Conclusions RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA.

TAFRO syndrome is a rare disorder that manifests as thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Although this disease often follows a severe clinical course, the cause remains unknown. The coronavirus disease 2019 (COVID-19) pandemic is a major global problem. Vaccination against COVID-19 has been successful; however, there are concerns about severe adverse events. Herein, we report a rare presentation of TAFRO syndrome triggered by the COVID-19 vaccine with a fatal clinical course. A 42-year-old Japanese man presented to our hospital complaining of fever lasting for 2 weeks that occurred a day after receiving the BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccine. The patient had a low platelet count, ascites, reticulin myelofibrosis, renal failure, and lymphadenopathy and was diagnosed with TAFRO syndrome. Despite administering several immunosuppressive drugs, the condition did not improve. The patient repetitively developed and eventually died of bacteremia caused by multidrug-resistant Klebsiella pneumoniae. We highlight the first reported case of TAFRO syndrome after COVID-19 vaccination.

ObjectivesThe aim of this study is to determine whether the ‘programmed’ infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year.MethodsIn this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106.ResultsA total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI −6.6% to 11.0%; p=0.631). Baseline SDAI ConclusionProgrammed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

The histology of skin lesions of TAFRO (thrombocytopenia, anasarca, reticulin fibrosis/renal failure, and organomegaly) syndrome has rarely been reported. We report herein two cases of TAFRO syndrome with characteristic vascular skin lesions. The lesions resembled a tufted angioma, although those of case 1 partially resembled a glomeruloid hemangioma, which was known as a specific lesion in POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes), a variant of multicentric Castleman disease (MCD). The high titer of serum vascular endothelial growth factor and interleukin-6 could explain common characteristic vascular lesions in both TAFRO syndrome and POEMS syndrome/MCD.

Lupus aortitis is a rare and potentially life-threatening disorder. Previous studies have reported the utility of high-dose systemic glucocorticoids or surgery as the treatment, although there have been no related controlled trials. We herein report a 49-year-old woman with a 35-year history of systemic lupus erythematosus who was diagnosed with aortitis. Her symptoms and laboratory and imaging abnormalities rapidly resolved upon the administration of moderate-dose glucocorticoids. We subsequently performed a literature review of similar cases to identify the appropriate treatment and discuss these cases. A study of further cases will be needed to identify the characteristics of patients who would benefit from moderate-dose glucocorticoid therapy.

Summary Background Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X. Methods COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0–10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov , number NCT02757352 . Findings Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified. Interpretation Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy. Funding Eli Lilly and Company.

Background Takayasu’s arteritis is extremely rare in children aged below 6 years. At the onset of Takayasu’s arteritis in children, symptoms are varied but differ from those in adults. Corticosteroids are the mainstay of treatment for preventing irreversible vascular damage but there is no standard treatment for progressive vascular stenosis. Case presentation A Japanese 11-month-old baby boy presented with Takayasu’s arteritis and heart failure, possibly due to afterload mismatch caused by high blood pressure. Computed tomography was performed and revealed thoracic and abdominal aortic aneurysms. It also revealed severe celiac artery stenosis and bilateral renal artery stenosis. Prednisolone was initiated as first-line therapy. The fever resolved, and C-reactive protein levels returned to normal. Although his general condition improved, deterioration of vascular lesions was evident. Celiac artery occlusion, severe right renal artery stenosis, and new superior mesenteric artery stenosis were observed. We decided to use a continuous infusion of lipo-prostaglandin E1 for prevention of branch stenosis of his abdominal aorta. The progression of vascular stenosis was stopped and our patient’s cardiac function gradually improved. Conclusions A differential diagnosis of heart failure with high blood pressure should be considered in babies. The progression of vascular stenosis may be suppressed by lipo-prostaglandin E1.

Background:Rheumatoid pleural effusion (RPE) is a common extra-articular complication in patients with rheumatoid arthritis (RA). Previous studies have shown that RPE usually occurs in middle-aged men with rheumatoid factor (RF)-positive RA. RPE usually has features of pleural fluid acidosis, high lactate dehydrogenase (LDH) levels, and very low glucose levels(1). However, to the best of our knowledge, these findings were based on very few case series and reports, and most of these reports were published by the early 2000s(1, 2).Objectives:To investigate the clinical and laboratory characteristics and typical clinical courses of patients with RPE in a single centre of Japan since the beginning of the 21st century.Methods:Medical records of RPE patients were retrospectively reviewed between May 2006 and September 2020. RPE was identified by fulfilling these five conditions: (1) confirmation of the RA diagnosis; (2) having an exudative pleural effusion according to Light’s criteria; (3) negative results of pleural fluid culture; (4) negative results of pleural fluid cytology; and (5) exclusion of a parapneumonic effusion or empyema defined as no antibiotic use or ineffectiveness of antibiotics during the clinical course. Patients were divided into two groups according to their age at diagnosis: Results:A total of 30 cases of RPE were included in the study. The median age was 71 years (interquartile range [IQR], 66–78 years). Of these patients, 16 (53%) were women. The median disease duration of RA was 98 months (IQR, 8–162 months). The two groups comprised six patients aged vs. 3 months, p=0.008). Compared with Group A, Group B had fewer patients with fever (14% vs. 83%, p=0.003), and had lower serum C-reactive protein levels (3.3 vs. 11.1 mg/dL, p=0.03). Moreover, Group B was more likely to show mild inflammatory pleural fluids with higher pH (7.5 vs. 7.2, p=0.005) and lower LDH levels (155 vs. 1810 IU/L, p=0.046). Corticosteroids were started or increased in five (83%) and nine (38%) patients, and biologic disease-modifying anti-rheumatic drugs were started in one (17%) and two (8%) patients in groups A and B, respectively. One patient (16%) died within 5-years in Group A, and seven patients (29%) died in Group B.Conclusion:In contrast to previous studies, RPE was seen in older patients as well as middle-aged adults, and the pleural fluid analysis in older patients with RPE showed milder inflammation than the middle-aged patients.References:[1]Balbir-Gurman A, et al. Semin Arthritis Rheum. 2006 Jun; 35(6): 368-78.[2]Faurschou P, et al. Thorax. 1985 May; 40(5): 371-5.Table 1.Comparison of clinical and laboratory findings between Group A and Group B.Group A (n=6)Group B (n=24)P valueAge (years)54 [49-56]74 [69-78]Female2 (n=6, 33.3)14 (n=24, 58.3)0.38Disease duration of RA (months)3 [1-9]132 [44-199]0.008Fever ≥37.0°C5 (n=6, 83.3)3 (n=22, 13.6)0.003SerumCRP (mg/dL)11.1 [5.6-1.4]3.3 [0.9-10.5]0.03 RF (IU/mL)100 [19-816]63 [23-193]0.95 Anti-CCP ab positive5 (n=6, 83.3)12 (n=15, 80)1.00Pleural fluid analysispH7.2 [7.2-7.2]7.5 [7.4-7.5]0.005LDH (IU/L)1810 [594-2932]155 [123-346]0.046Glu (mg/dL)59 [10-123]105 [91-122]0.42Tp (g/dL)5.1 [4.9-5.6]4.6 [3.6-5.2]0.21Number of cells (/μL)5235 [3353-9300]3300 [1490-5008]0.27 Glu/serum Glu0.41 [0.09-0.99]1.05 [0.85-1.15]0.71Started or increased CS5 (n=6, 83.3)9 (n=24, 37.5)0.18Started bDMARDs1 (n=6, 16.6)2 (n=24, 8.3)0.50Died within 5 years1 (n=6, 16.6)7 (n=24, 29.1)1.00Data are median [interquartile range], or number (total number, percent).Abbreviations: RA, rheumatoid arthritis; CRP, C-reactive protein; RF, rheumatoid factor; Anti-CCP ab, anti-cyclic citrullinated peptide antibodies; LDH, lactate dehydrogenase; Glu, glucose; Tp, total protein; CS, corticosteroid; bDMARDs, biologic disease-modifying anti-rheumatic drugsDisclosure of Interests:None declared

We had encountered the case of membranous glomerulonephritis (MGN) with dilated cardiomyopathy due to LMNA gene mutation. LMNA mutation was known as a cause of ‘laminopathy’ such as dilated cardiomyopathy, muscular dystrophy, neuropathy and so on. LMNA gene might be a candidate of genetic basis in cryptogenic MGN.

OBJECTIVE Interstitial lung disease (ILD) accompanied by anti-melanoma differentiation-associated gene 5 (anti-MDA-5)-positive dermatomyositis (DM) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti-MDA-5-positive DM patients with ILD. METHODS Adult Japanese patients with new-onset anti-MDA-5-positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high-dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IV CYC). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6-month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti-MDA-5-positive DM patients with ILD who received step-up treatment (high-dose GC and stepwise addition of immunosuppressant). Secondary end points were 12-month survival rate, adverse events, and changes in laboratory data. RESULTS The combined immunosuppressive regimen group showed significantly higher 6-month survival rates than the step-up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti-MDA-5 titers, serum ferritin levels, vital capacity, and chest high-resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step-up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks. CONCLUSION A combined immunosuppressive regimen is effective for anti-MDA-5-positive DM patients with ILD. Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.

Objective We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). Methods We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. Results Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. Conclusion Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.

Rationale Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. Objectives To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. Methods A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. Measurements and main results During the observational period (median 49 months; range, 1–114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. Conclusions The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

Summary Background Polymyositis and dermatomyositis-associated interstitial lung disease (PM/DM-ILD) can have variable courses. We evaluated the prognostic value of high-resolution computed tomography (HRCT) in PM/DM-ILD. Methods The cases of 51 patients newly diagnosed with PM/DM-ILD were retrospectively reviewed. HRCT images at diagnosis were categorized into four radiological patterns based on the major findings and distributions of these abnormalities, and the disease extent on HRCT was scored. The impact of HRCT findings and other clinical parameters on day 90 and overall mortality were analyzed. Results Of the 51 patients (11 with polymyositis and 40 with dermatomyositis), the lower consolidation/ground-glass attenuation (GGA) pattern was observed in 21 patients (41%), lower reticulation was observed in 23 patients (45%), random GGA was observed in four patients (8%), and other patterns were observed in three patients (6%). Twenty-one patients (42%) were positive for anti-CADM-140. The lower consolidation/GGA pattern, clinically amyopathic dermatomyositis, fever (≥38.0 °C), ferritin levels >500 ng/mL, and the presence of anti-CADM-140 were significantly associated with 90-day mortality in univariate analysis. Multivariate analysis revealed that the lower consolidation/GGA pattern (odds ratio, 23.1; P = 0.02) and the presence of anti-CADM-140 (odds ratio, 14.1; P = 0.03) were independent predictors of 90-day mortality. This HRCT pattern was also associated with a higher 90-day morality rate among anti-CADM-140-positive patients. The lower consolidation/GGA pattern was also associated with overall mortality in univariate analysis, whereas only the presence of anti-CADM-140 was an independent determinant of overall mortality in multivariate analysis. Conclusion HRCT patterns at diagnosis can help predict the prognosis of patients with PM/DM-ILD as well as the presence of anti-CADM-140.

We performed renal biopsy in three cases complicated by myeloproliferative neoplasms (MPN). Although several cases of glomerulonephritis associated with MPN have been reported, the etiologies of the renal disorders were not established (Plomley et al., Aust NZ J Med, 13:125-129, 1983; Sharma et al., Nephron, 69:361, 1995; Kanauchi et al., Intern Med, 33:36-40, 1994; Kasuno et al., Nephrol Dial Transplant, 12:212-215, 1997; Au et al., Am J Kid Dis, 34:889-893, 1999; Kosch et al., Nephrol Dial Transplant, 15:1710-1711, 2000; Oymak et al., Nephron, 86:346-347, 2000; Chun et al., Am J Nephrol, 20:344-346, 2000; Chung et al., Am J Nephrol, 22:397-401, 2002; Asaba et al., Clin Exp Nephrol, 7:296-300, 2003; Haraguchi et al., Clin Exp Nephrol, 10:74-77, 2006; Saigusa et al., J Nephrol, 19:656-658, 2006; Okuyama et al., Clin Nephrol, 6:412-415, 2007; Nishi et al., Clin Nephrol, 5:393-398, 2010; Ulusoy et al., Intern Med, 49:2477, 2010). A review of previous reports of renal biopsy cases with MPN in the English literature suggested that circulation control is important for the treatment of renal disorders that mimic glomerulonephritis in MPN.

We report a case of acquired generalized anhidrosis successfully treated with cyclosporine. A skin biopsy showed T cell infiltration around the sweat glands and labial biopsy revealed lymphoplasmacytic infiltration around the minor salivary gland, suggesting an underlying autoimmune disease such as Sjögren's syndrome. Administration of cyclosporine markedly improved the patient's condition and sympathetic skin response; thus cyclosporine may be effective for treating anhidrosis in patients with autoimmune disorders.

Objective This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). Methods We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. Results Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients. Conclusion CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.

Objective Acute-onset diffuse interstitial lung disease (AoDILD) in patients with rheumatoid arthritis (RA) has been a serious concern, especially for those under treatment with biological agents which may affect the presentation and outcome of AoDILD, including Pneumocystis pneumonia (PCP). Therefore, we conducted a retrospective, multi-center study of AoDILD in RA patients receiving biological agents. Methods Patients who developed AoDILD while receiving biological agents (infliximab, etanercept, adalimumab and tocilizumab) were enrolled in the study. Definite PCP was defined as patients who showed either P. jirovecii organisms in their respiratory samples by microscopic examination, or positive tests for both P. jirovicii DNA-PCR with respiratory samples and an elevated serum 1,3-β-D-glucan level above the cut-off value. Probable PCP was defined as either a positive test for P. jirovicii PCR or an elevated serum β-D-glucan level. Chest HRCT findings were evaluated and scored by two board-certified radiologists. Results The final diagnoses for 26 patients examined were definite PCP for 13 patients, probable PCP for 11, and methotrexate-associated pneumonitis in 2 patients. Definite and probable PCP cases were clinically indistinguishable. Generalized, diffuse ground-glass opacity (GGO) is the characteristic HRCT finding in patients with definite or probable PCP, which was different from our previous findings in RA patients, mostly without biologics, showing GGO distributed in a panlobular or multilobular manner. The clinical outcome was favorable by treatment with trimethoprim-sulfamethoxazole and glucocorticoids. Conclusion The possibility of PCP should be intensively investigated in RA patients developing AoDILD while receiving biological agents.

The safety and efficacy of rituximab were examined in a multicenter open-label pilot study in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan.Patients with refractory AAV were administered a rituximab infusion at a weekly dose of 375 mg/m(2) for 4 weeks. All patients also received oral daily prednisolone. The primary outcome was complete remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 or 1.The mean age of the 7 patients was 57 (range, 34-71) years. The mean follow-up period after rituximab treatment was 62.9 (range, 4.8-81) months. The mean BVAS at entry was 16.7 (range, 2-34). Complete remission occurred in all cases, except in 1 case in which the patient died, with a significant decline in BVAS from baseline at 12 months after initiation of rituximab. Rituximab reduced granulomatous orbital involvement in a patient with granulomatosis with polyangiitis. Relapse occurred in five patients. Adverse events included de novo hepatitis B in one patient, cancer (hepatocellular carcinoma and prostate cancer) in two patients, and transient visual disturbance, atypical mycobacterial infection, urinary tract infection, sepsis, and cytomegalovirus infection. Two patients died due to recurrent infections and airway obstruction, caused by an AAV lesion.Rituximab had a beneficial effect on refractory AAV in Japanese patients, but several adverse effects occurred during rituximab treatment.

Herein we present two cases of hypereosinophilic syndrome with a unique clinical presentation. One patient showed severe systemic thrombosis with splenic rupture and the other patient showed finger gangrene with various systemic symptoms. Both patients were examined histologically, and several characteristics were noted. First, fresh or organized thrombosis with marked eosinophilic infiltration was observed in the cavity and walls of the thrombosed vessels. Second, many eosinophils showed degranulation and were positive for eosinophilic cationic protein on immunohistological examination. Third, the structures of thrombosed vessels were well preserved, which is not observed in systemic vasculitis. These patients exhibited no neoplastic features and were treated with prednisolone with excellent therapeutic results.

A 49-year-old man presented with fever and uremic symptoms such as general malaise, leg edema and decreased urine output. He was diagnosed as having infective endocarditis (IE) accompanied by renal failure. Although he had been receiving hemodialysis for a long time, renal function dramatically improved after heart valve replacement. This case suggests that uremia can develop as an initial manifestation of IE and removal of an infected heart valve can improve renal function despite persistent renal failure. From the perspective of recovery of renal function, early surgery should be considered in patients with renal failure following IE.

A 68-year-old female, suffering from rheumatoid arthritis, was admitted to our institution for right heart failure with massive pericardial effusion. Her pericardial effusion had increased after starting infliximab, tumor necrosis factor (TNF)-inhibitor therapy, despite improvement in arthralgia. Hemodynamic findings demonstrated effusive–constrictive pericarditis. Because association between exacerbation of pericarditis and infliximab was highly suspected through her clinical course, its administration was stopped. We should pay much attention to pericardial effusion and symptoms of right heart failure after starting TNF-inhibitor therapy in patients with rheumatoid arthritis.

Thrombotic thrombocytopenic purpura (TTP) is an unusual complication of systemic lupus erythematosus (SLE). Although the reported association between SLE and TTP is increasing, a few cases do improve without plasmatherapy. We report a case of TTP which was successfully treated without plasmatherapy, which might be underestimated as an etiology of thrombocytopenia in SLE. TTP should always be considered as a concomitant disease when Coombs' negative hemolytic anemia or thrombocytopenia is seen in SLE patients.

In 1986, a 45-year-old man, who had a past medical history of swollen submandibular lymph nodes and colon cancer, was admitted for an evaluation of eyelid swelling and generalized edema. On admission, in addition to massive proteinuria, increased total protein (9.2 g/dL) and low albumin (2.7 g/dL) were noted. By several radiological and endoscopic examinations, a diagnosis of chronic pancreatitis was made. And the finding of multiple peritoneal lymph nodes raised the possibility of a cancer recurrence. An open biopsy of several involved organs was performed. The diagnostic conclusions in 1986 were as follows: (1) reactive follicular hyperplasia (lymph node); (2) reactive hepatitis; (3) chronic pancreatitis; and (4) idiopathic membranous nephropathy (MN). These findings were considered to represent a state of hyperimmune reactivity, but no precipitating factor could be identified at that time. When the diagnosis was revisited 25 years later, reinterpretation of the histology, performance of IgG4 staining, and recognition of the features of IgG4-RD in other organs led to reclassification of the patient’s diagnosis as IgG4-related MN without tubulointerstitial nephritis.

A 13-years-old girl was admitted to our hospital with high levels of serum IgM, thrombocytopenia and splenomegaly. Not only IgG but also IgM were found on the surface of platelets by flow-cytometry. Direct Coombs' test was positive, and IgG was also found on the surface of red blood cells. After splenectomy, platelet count was increased and serum IgM was decreased. The biopsy of salivary glands showed infiltration of lymphocytes around the ducts, and Shirmer test revealed slightly decreased secretion of tears, suggesting subclinical Sjögren syndrome.

This is the first report on effective leukocytapheresis (LCAP) in an acquired infliximab (IFM) resistant patient with rheumatoid arthritis (RA). A 44-year-old Japanese woman with RA was treated with prednisolone, cyclosporine A, and methotrexate, which failed to stabilize the disease. Infliximab was then administered and the disease activity was controlled on December 2003. However, RA became active again on June 2004 so that LCAP was administered weekly for 5 weeks. After the LCAP treatment, the ACR20% response was obtained again and IFM has regained its efficacy.

A 20-year-old man with ulcerative colitis was admitted because of fever, eruption and lymphadenopathy. He had started taking salazosulfapyridine one month previously. Lymph node biopsy revealed angioimmunoblastic lymphadenopathy. Autoantibody titers were all negative, and viral antibody titers were not increased retrospectively. Rearrangement of T-cell receptor beta and chromosomal aberration were not seen on the lymph node. This case is considered not to be a peripheral T-cell lymphoma but rather salazosulfapyridine-induced angioimmunoblastic lymphadenopathy (AIL), which is the second case in English language literature.

Acute-onset diffuse interstitial lung disease (AoDILD) in patients with rheumatoid arthritis (RA) has been a serious concern, especially for those under treatment with biological agents which may affect the presentation and outcome of AoDILD, including Pneumocystis pneumonia (PCP). Therefore, we conducted a retrospective, multi-center study of AoDILD in RA patients receiving biological agents.Patients who developed AoDILD while receiving biological agents (infliximab, etanercept, adalimumab and tocilizumab) were enrolled in the study. Definite PCP was defined as patients who showed either P. jirovecii organisms in their respiratory samples by microscopic examination, or positive tests for both P. jirovicii DNA-PCR with respiratory samples and an elevated serum 1,3-β-D-glucan level above the cut-off value. Probable PCP was defined as either a positive test for P. jirovicii PCR or an elevated serum β-D-glucan level. Chest HRCT findings were evaluated and scored by two board-certified radiologists.The final diagnoses for 26 patients examined were definite PCP for 13 patients, probable PCP for 11, and methotrexate-associated pneumonitis in 2 patients. Definite and probable PCP cases were clinically indistinguishable. Generalized, diffuse ground-glass opacity (GGO) is the characteristic HRCT finding in patients with definite or probable PCP, which was different from our previous findings in RA patients, mostly without biologics, showing GGO distributed in a panlobular or multilobular manner. The clinical outcome was favorable by treatment with trimethoprim-sulfamethoxazole and glucocorticoids.The possibility of PCP should be intensively investigated in RA patients developing AoDILD while receiving biological agents.