False-positive semiquantitative immunochromatography assays for procalcitonin in three patients with rheumatoid arthritis-A case series.

We report three rheumatoid arthritis (RA) patients with false-positive procalcitonin (PCT) based on semiquantitative immunochromatography assays without infection, but who had negative PCT assay results based on quantitative methods. Immunochromatography was useful for screening; however, other heterophilic antibodies rather than rheumatoid factor were possible to affect, especially in RA flare.

An adult case of atypical familial Mediterranean fever (pyrin-associated autoinflammatory disease) similar to adult-onset Still's disease.

We present a 55-year-old woman with periodic fever and symptoms similar to adult-onset Still's disease (AOSD). She had a heterogeneous mutation of the MEFV gene and colchicine was effective. Atypical familial Mediterranean fever (pyrin-associated autoinflammatory disease) should be considered in patients with periodic fever accompanied by symptoms similar to AOSD.

Utility of estimated glomerular filtration rate using cystatin C and its interpretation in patients with rheumatoid arthritis under glucocorticoid therapy.

BACKGROUND: Patients with rheumatoid arthritis (RA) often have reduced muscle mass. Estimated glomerular filtration ratio using the serum cystatin C concentration (eGFRcys) is more accurate than eGFR using the serum creatinine (eGFRcreat) because cystatin C is not influenced by muscle mass, but glucocorticoid therapy may affect serum cystatin C concentration. METHODS: Fifty patients with RA were included in this study. Renal inulin clearance (Cin) was measured and compared with eGFRcreat, eGFRcys, or the mean of eGFRcreat and eGFRcys (eGFRavg). RESULTS: The mean creatine kinase (CK) concentration was low (36.8 ±â€¯24.4 U/l).The eGFRcreat and eGFRcys regression lines were significantly different from y = x. The mean eGFRcreat value was significantly higher than Cin and that of eGFRcys was lower than Cin. The difference between eGFRcys and Cin was negatively correlated with daily PSL dose. The mean eGFRcys value of patients taking <10 mg PSL was not different from Cin and the eGFRcys regression line was not different from y = x. CONCLUSION: eGFRcys of patients taking a daily PSL dose ≥10 mg was inaccurate, while eGFRcys was underestimated. eGFRcys was more accurate than eGFRcreat or eGFRavg for patients taking a daily PSL dose of <10 mg.

Adult-onset Chronic Recurrent Multifocal Osteomyelitis with High Intensity of Muscles Detected by Magnetic Resonance Imaging, Successfully Controlled with Tocilizumab.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder that generally occurs in children and predominantly affects the long bones with marginal sclerosis. We herein report two cases of adult-onset CRMO involving the tibial diaphysis bilaterally, accompanied by polyarthritis. Magnetic resonance imaging (MRI) showed both tibial osteomyelitis and high intensity of the extensive lower leg muscles. Anti-interleukin-6 therapy with tocilizumab (TCZ) effectively controlled symptoms and inflammatory markers in both patients. High intensity of the lower leg muscles detected by MRI also improved. These cases demonstrate that CRMO should be included in the differential diagnosis of adult patients with bone pain, inflammation, and high intensity of the muscles detected by MRI. TCZ may therefore be an effective therapy for muscle inflammation of CRMO.

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log10%amyloid). The results of sex-, age-, and Log10%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis.

Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. Results Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). Conclusion Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis.

Acute exacerbation of interstitial pneumonia associated with rheumatoid arthritis during the course of treatment for Pneumocystis jirovecii pneumonia: a case report.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is potentially fatal infectious complication in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. Hospital survival due to human immunodeficiency virus-unrelated PCP reaches to 60%. The high mortality rate results from difficulties in establishing an early diagnosis, concurrent use of prophylactic drugs, possible bacterial coinfection. We herein report a case of PCP in RA patients who developed the architectural distortions of lung in spite of combined modality therapy. CASE PRESENTATION: A 73-year-old Japanese woman with RA was admitted with shortness of breath. Five weeks previously, she had been started on etanercept in addition to methotrexate (MTX). Chest computed tomography (CT) demonstrated diffuse ground glass opacities distributed throughout the bilateral middle to lower lung fields, and serum ß-D-glucan was elevated. Bronchoalveolar lavage fluid revealed no P. jirovecii, but the organism was detected by polymerase chain reaction method. Trimethoprim/sulfamethoxazole was administered with methylprednisolone pulse therapy. However, the follow-up chest X-ray and chest CT demonstrated aggravation of the pneumonia with architectural distortions. Additional direct hemoperfusion with polymyxin B-immobilized fibers and intravenous cyclophosphamide therapy were insufficiently effective, and the patient died on day 25. CONCLUSION: The architectural distortions of lung should be considered as a cause of death of PCP. For this reason, a high suspicion of this infectious complication must be kept in mind in order to establish an early diagnosis and treatment in patients with RA managed with MTX and biologics.

Local delivery of a direct renin inhibitor into the kidney ameliorates progression of experimental glomerulonephritis.

BACKGROUND: Increasing evidence indicates that locally blocking renin-angiotensin system activity exerts a beneficial effect on glomerulonephritis (GN) progression leading to irreversible glomerulosclerosis. This is the first study on the pharmacological effect of the renal delivery of aliskiren, a direct renin inhibitor, in a progressive model of anti-Thy-1 GN. METHODS: Local blockade of renin activity was accomplished by subrenal capsular implantation of a collagen sponge with aliskiren. The pharmacological effect was evaluated by semiquantitative and quantitative analysis of immunohistological findings and by analysis of glomerular microcirculation using an intravital microscope system. RESULTS: Quantitative mesangial matrix analysis showed that local treatment with aliskiren significantly suppressed mesangial matrix expansion and ameliorated the glomerular sclerotic index in the progressive model of ATS GN. Immunofluorescent studies revealed that renin expression at the juxtaglomerular region was enhanced in the ATS + aliskiren group, and pathological expressions of α-smooth muscle cell actin and type I collagen in ATS GN were remarkably decreased by local treatment with aliskiren. Furthermore, local delivery of aliskiren significantly improved glomerular blood flow levels. CONCLUSION: This study revealed that renally delivered aliskiren has a renoprotective effect on potentially progressive glomerulosclerosis.

The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I2 analog on the progression of sclerotic glomerulonephritis in rats.

BACKGROUND AND METHODS: There is increasing evidence that a change in glomerular hemodynamics may promote the development of glomerulosclerosis. In this study, we focused on the pharmacological effects of 2 contrasting agents, etodolac, a preferential cyclooxygenase-2 inhibitor, and beraprost sodium (BPS), a prostaglandin I(2) analog, delivered renally, on the disease course of progressive anti-Thy-1 (ATS) glomerulonephritis. RESULTS: Intravital microscopic analysis showed that the diameters of glomerular capillaries and glomerular blood flow in unilaterally nephrectomized (Nx) rats treated locally with BPS were significantly increased, as compared to those of Nx rats treated locally with normal saline (NS) or etodolac. We then examined the effects of BPS and etodolac on the course of progressive glomerulosclerosis. Mesangial cell proliferation, adhesion of glomerular capillary tufts and crescent formation in the BPS-treated group appeared to be more severe compared to the ATS + NS and the ATS + etodolac groups. Scoring of mesangial proliferation and glomerulosclerosis revealed that local BPS treatment significantly worsened glomerular pathology. At day 28, there were significant differences in blood flow between the ATS + etodolac group and both the ATS + NS and ATS + BPS groups, indicating that local treatment with etodolac enhanced the recovery of glomerular circulation. CONCLUSION: This study provides hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulonephritis.

Effects of connexin-mimetic peptides on perfusion pressure in response to phenylephrine in isolated, perfused rat kidneys.

BACKGROUND: Gap junction intercellular communication plays a fundamental role in various tissues and organs. Gap junctions transfer ions and molecules between adjacent cells and are formed by connexins (Cx). It is supposed that vascular conducted responses, which most likely spread through gap junctions in vascular beds, regulate microcirculatory blood flow and maintain vascular resistance. This study provides functional evidence supporting the critical role of gap junctions in a physiological setting and in phenylephrine (PE)-induced vasoconstriction using an ex vivo kidney perfusion technique. METHODS: Using the isolated, perfused kidney model, infusion of gap junction inhibitors and PE, we examined the local effect of gap junction communication. Additionally, gap junction proteins Cx37, Cx40 and Cx43 were detected by immunofluorescence. RESULTS: First, changes in the perfusion pressure were analyzed by infusing the nonselective gap junction uncoupler, 18α-glycyrrhetinic acid (18α-GA), and specific connexin-mimetic peptide inhibitors, (37,43)Gap27, (40)Gap27 and (43)Gap26. Administration of 18α-GA and (43)Gap26 significantly elevated perfusion pressure while infusion of (40)Gap27 and (37,43)Gap27 had no effect. Second, we examined the effect of infusing gap junction inhibitors on PE-induced vasoconstriction. Infusion of 18α-GA and (40)Gap27 significantly suppressed the increase in perfusion pressure induced by PE, while (43)Gap26 and (37,43)Gap27 had no effect. Third, we confirmed by immunofluorescence that Cx37, Cx40 and Cx43 were found in the endothelial cells of interstitial microvessels and that Cx40 was localized in glomerular mesangial cells as well as in smooth muscle cells of the juxtaglomerular area. CONCLUSIONS: This study showed that Cx43 plays a pivotal role in regulating renal vascular resistance and that Cx40 attenuates PE-induced vasoconstriction. These results provide new evidence that gap junctions may control renal circulation and vascular responses.

Clinical aspects of invasive infection with Streptococcus dysgalactiae subsp. equisimilis in elderly patients.

The number of patients with severe invasive infections (mainly exhibiting bacteremia) with Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been increasing worldwide. We herein report the clinical aspects of invasive infections (cellulitis, pneumonia, and urosepsis) occurring with SDSE in 13 elderly patients (mean age 84 years, range 69-99 years) diagnosed at a hospital for elderly individuals during the period January 2005-June 2009. Ten subjects had underlying diseases, including neurologic disorders, diabetes mellitus, and others. Eleven patients presented to the hospital emergency department, and the most common symptom was high fever or respiratory distress. Primary care and emergency department doctors treating elderly patients with high fever should keep in mind invasive SDSE infection as a differential diagnosis, especially when an elderly person has underlying illnesses. To detect SDSE in elderly subjects, blood cultures should be obtained before the administration of antimicrobials because, as we found, the patients' symptoms were limited.