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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.

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.

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.

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.

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.

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.

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 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.

Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. Methods: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Findings: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p

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.

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.

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.

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.

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 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.

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 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.

Antiphospholipid antibodies (aPL) have been reported to occur in numerous viral infections. We report a 24-year-old Japanese woman, who developed multiple venous thrombosis associated with the elevation of anticardiolipin IgM after acute viral infection presenting a mononucleosis-like illness. Two months later, aPL and thromboses disappeared. In this case both parvovirus B19 and cytomegalovirus antibodies IgM were elevated, which indicated the possibility of cross-reaction.

Background We report a case of invasive sinus aspergillosis that extended to the orbital cavity and cavernous sinus and was improved by treatment with micafungin and itraconazole. Case report A 83-year-old woman was referred to our hospital because of headache and impaired of eye movement on the right side. Physical examination revealed impaired function of cranial nerves, II, II, IV, and VI on the right side. MRI showed evidence of inflammation of the right sphenoid sinus and ethmoidal sinus and an enhancing mass in the right cavernous sinus and orbit. Because a culture of a specimen from the right sphenoid sinus extracted during endoscopic sinus surgery, yielede Aspergillus fumigatus, a diagnosed of invasive sinus aspergillosis complicated by cavernous sinus symdrome and orbital apex symdrome was made. It was difficult to completely remove the mass in the sinuses surgically and drug therapy with micafungin was started and then itraconazole was added. The clinical manifestations and the impaired function of cranial nerves II, III, IV, and VI improved, and MRI showed regression of the mass in the sinuses temporary in response to drug therapy. Conclusion Invasive sinus aspergillosis often progresses rapidly in the absence of surgery. Our case is valuable, because invasive sinus aspergillosis was improved by drug therapy alone, and combined treatment with micafungin and itraconazole was effective.

A 61-year-old man with hypertension had developed exertional dyspnea for 2 years. His symptom got worse with fever and wet cough 4months prior to admission (PTA), and inspiratory pain on his right chest 3 months PTA. He was suspected of having an atypical pneumonia or a tuberculosis on CT. Enhanced chest CT showed large mural defects in right main pulmonary artery, clearly delineated by contrast medium.He was diagnosed as having a pulmonary embolism and received anticoagulation therapy with heparin followed by warfarin. Despite 1 week of warfarin therapy, he remained symptomatic with no change in the pulmonary artery filling defects on repeated enhanced CT.Pulmonary artery sarcoma, or a metastatic tumor were suspected of by its time course and accompanying symptoms and signs of fever, secondary anemia, and weight loss. Increased uptake of FDG in the affected pulmonary artery indicated that pulmonary artery sarcoma was most likely.Aspiration cytology and needle biopsy through pulmonary artery catheter revealed malignant cells with results of CD31(-), CD34(-), D2-40(+),α-Actin(-), and AE1/AE3(+), consistent with pulmonary artery sarcoma which was not able to be specified further.It was out of operative indication because of distant metastasis in his lungs. Therefore, he received weekly Paclitaxel(45mg/m2) + Carboplatin(AUC 2)concurrent with TRT 60Gy/30Fr in order to mainly control intra-arterial mass. However, we discontinued it at 6courses because of neutropenia(Gr3) and development and progression of non-tuberculosis mycobacterium infection. He was also intolerable to pazopanib due to many side effects of increasing in the liver enzymes(Gr1), hypertension(Gr3), anorexia(Gr3), diarrhea(Gr3), nausea(Gr3) and NTM exacerbation. On the other hand, his primary and metastatic lesions have a tendency to decrease in size in comparison with one before chemotherapy. We will report this case with literature review in terms of diagnostic difficulty of pulmonary artery sarcoma.

We present three cases of intracranial hemorrhage with metastasis of gastric cancer to the bone/bone marrow. Case1: A 62-year-old man with history of distal gastrectomy 15 years ago was pointed out to have elevated ALP level and diffuse increased uptake of bone scintigraphy, which turned out to be a recurrence of diffuse metastases to bone and bone marrow confirmed by bone marrow biopsy. After partially successful treatment of chemotherapy with 6 cycles of TS-1 + CDDP, he developed an acute subdural hematoma, complicated by DIC. Craniotomy for removal of hematoma was performed. However, he was died of brain bleeding 12 months after diagnosis of recurrence. Case2: A 60-year-old man underwent subtotal gastrectomy 9 years ago. Similarly, diffuse bone and bone marrow metastasis was confirmed by bone marrow biopsy with trigger of elevated ALP level and diffuse increased uptake of bone scintigraphy. After chemotherapy with TS-1 + CDDP as 1st line and DTX as 2nd line was performed, he also developed and died of subdural hematoma with DIC 22months after diagnosis of recurrence. Case3: A 65-year-old woman with rheumatoid arthritis was pointed out to have low platelet and elevation of LDH and ALP in her regular visits. Endoscope examinations and imaging studies showed gastric cancer with multiple metastases to bone and bone marrow complicated by DIC. Although chemotherapy with TS-1 and blood transfusion was performed, she developed an acute subdural hematoma and received craniotomy for removal of hematoma. However she died of brain rebleeding 4 months after initial diagnosis. The following things are quite interesting in these 3 cases. 1) The former 2cases recurred with bone and bone marrow metastasis after long interval. 2) All cases developed bone and bone marrow metastasis complicated by fatal intracranial hemorrhage without obvious bleeding tendencies in other parts of body. We will discuss those issues with literature review.

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.

A 57-year-old woman with Crow-Fukase syndrome presented thiamine deficiency and pulmonary hypertension of unknown etiology. After oral administration of prednisolone and thiamine, echocardiogram showed marked improvement of the pulmonary hypertension. To our knowledge, this is the first case of this syndrome associated with thiamine deficiency and precapillary pulmonary hypertension, which may play a role in the pathogenesis of polyneuropathy and heart failure of this syndrome.

Prosthetic graft infection is difficult to diagnose early, and hence, is associated with high mortality and morbidity rates. A 63-year-old man who had undergone surgical prosthetic replacement for an inflammatory thoracic aortic aneurysm 10 months previously visited our emergency room, complaining of chills, shivering, frequent vomiting, and back pain. He was diagnosed with severe sepsis, and a blood culture detected Streptococcus anginosus and Prevotella oralis. Repeated contrast-enhanced computed tomography (CT) scans of his chest revealed ectopic gas around the graft, and esophagogastroduodenoscopy revealed esophageal perforations at several sites. We therefore diagnosed him with aortic prosthetic graft infection accompanied with esophagomediastinal fistulas. He received medical treatment and three operations and recovered from the infection. This is a rare case of aortic prosthetic graft infection accompanied with esophagomediastinal fistulas, and we conclude that repeated CT is useful for identifying the primary infection site and invasion route in patients with suspected aortic prosthetic graft infection.