Synovial fluid crystal analysis with compensated polarization using a gout analyser in clinical practice.

OBJECTIVE: To validate the gout analyzer as a clinical method of synovial fluid crystal analysis. METHODS: Thirty knee synovial fluid samples with suspected calcium pyrophosphate (CPP) crystals were analyzed. Within 48 hours after collection, each non-centrifuged sample was examined blindly and independently by one or more rheumatologists in the following order: 1) with an optical microscope under ordinary light, 2) with the same microscope under compensated polarization provided by a gout analyzer, and 3) with a fully equipped compensated polarized microscope with a rotating stage as the gold standard. As a reference, laboratory technicians analyzed fresh, centrifuged synovial fluid using a gout analyzer. RESULTS: Of the 30 samples analyzed, CPP and monosodium urate (MSU) crystals were detected in 11 and four, non-centrifuged samples, respectively, using a fully equipped compensated polarized microscope. The rheumatologists' detection rate of crystals in the non-centrifuged synovial fluid under ordinary light and with a gout analyzer was 73.3% and 80%, respectively. The laboratory technicians' detection rate in fresh centrifuged synovial fluid using a gout analyzer was 100%. CONCLUSION: A gout analyzer may be used to diagnose gout and calcium pyrophosphate deposition disease definitively if a fully equipped compensated polarized microscope is unavailable.

Pharmacokinetics of hydroxychloroquine in Japanese systemic lupus erythematosus patients with renal impairment.

OBJECTIVES: Reduction of the hydroxychloroquine (HCQ) dosage is recommended in systemic lupus erythematosus (SLE) patients with renal impairment, but a pharmacokinetics (PK) study of patients with renal impairment has not yet been performed. METHODS: We investigated the PK of both single and multiple doses of HCQ and its metabolites in SLE patients with renal impairment who newly started HCQ at a daily dose of 300 mg based on an ideal body weight dosage of 6.5 mg/kg. Population PK analysis was performed using a non-linear mixed-effects model. RESULTS: In total, 219 samples from 21 patients were analysed. The PK of HCQ in blood after single and multiple oral administrations followed the two-compartment model. At steady state, the concentration ratio of HCQ to each metabolite was HCQ:desethylhydroxychloroquine:desethylchloroquine:bisdesethylchloroquine = 1:0.28:0.1:0.06. The HCQ concentration correlated positively with that of each metabolite. The estimated values (relative standard error) of the population PK parameters were the total clearance at 110 l/h (31%) and a central volume of distribution of 398 l (19%). Co-administration of prednisolone and age, but not renal impairment, were factors affecting the total clearance of HCQ. CONCLUSIONS: From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.

Anti-glomerular basement membrane diseases and thrombotic microangiopathy treated with rituximab.

A 68-year-old male patient presented with a 2-week history of malaise and anuria. Renal replacement therapy with haemodialysis was begun for acute kidney injury. His anti-glomerular basement membrane (anti-GBM) antibody titre was 3060 U/ml. Based on this finding, anti-GBM disease was diagnosed. Plasmapheresis and high-dose glucocorticoid therapy were begun, but his haemolytic anaemia and thrombocytopenia progressed. A disintegrin and metalloprotease with thrombospondin type 1 motif, 13 (ADAMTS-13) activity decreased to 33%, but no inhibitor was detected. Secondary thrombotic microangiopathy was suspected, and rituximab therapy was begun. The addition of rituximab is thought to have further reduced the anti-GBM antibodies, prevented recurrence, stabilised the platelet count, and facilitated the patient's withdrawal from plasmapheresis and glucocorticoid therapy. Rituximab may be a viable therapeutic option for anti-GBM diseases complicated with thrombotic microangiopathy.

Utility of the neutrophil-to-lymphocyte ratio for predicting bacterial infection in patients with rheumatoid arthritis receiving Tocilizumab.

This study aimed to describe the utility of the neutrophil-to-lymphocyte ratio (NLR) for predicting bacterial infections in patients with rheumatoid arthritis (RA) treated with Tocilizumab (TCZ). We extracted RA patients treated with TCZ in whom an infection developed between April 2008 and March 2018 from our hospital database. We divided these patients into the bacterial infection and non-bacterial infection groups and compared their background, C-reactive protein (CRP) values, white blood cell count (WBC), the NLR at the time of infection diagnosis, and the ratio of the NLR at the time of infection diagnosis (post-NLR) to the NLR at baseline (pre-NLR). Of the 196 patients who received TCZ, 21 experienced a bacterial infection and 20 had a non-bacterial infection. The median CRP level, WBC count, post-NLR, and post-NLR/pre-NLR ratio in the bacterial infection group were significantly higher than in the non-bacterial infection group. In receiver operating characteristics (ROC) curve analysis for predicting bacterial infection, the area under the curve (AUC) for CRP, WBC, NLR, and the post-NLR/pre-NLR ratio were 0.787, 0.857, 0.887, and 0.975, respectively. The cut-off value of 2.25 for the post-NLR/pre-NLR ratio showed the greatest sensitivity (90.5%) and specificity (100%). The post-NLR/pre-NLR ratio may be a useful surrogate marker for predicting bacterial infections in patients with RA treated with TCZ.

Characteristics and risk factors of an emergency department visit in patients with systemic lupus erythematosus.

This study aimed to examine the characteristics of patients with systemic lupus erythematosus (SLE) visiting the emergency department (ED) and the risk factors of an ED visit by these patients. This 4-year retrospective study was performed at a tertiary care center in Japan. We included all 205 patients with SLE who were treated in our outpatient clinic between April 1, 2008 and March 31, 2012 and divided them into two groups: those who visited the ED (the ED-user group) and those who did not (the ED-non-user group). We statistically compared the patient backgrounds and characteristics of the groups and identified the risk factors of an ED visit. Of all the patients, 118 visited the ED during study period and 87 did not. In total, 269 events were identified in the ED-user group. Of these, 91 (33.8%) were cases of infection, 32 (11.9%) were orthopedic problems, 32 (11.9%) were cases of gastrointestinal disease, 31 (11.5%) were cases of neurological disease, and 25 (9.3%) were cardiovascular events. Twenty-four events (8.9%) were due to SLE flares, of which ten (41.7%) were cases of neuropsychiatric lupus (NPSLE). The glucocorticoid dosage and the presence of a psychiatric illness, NPSLE, and lupus nephritis were higher among the ED-user group. Multivariate logistic regression analysis demonstrated high glucocorticoid dosage to be a risk factor of an ED visit. Among SLE patients, infections were the principal reason for visiting the ED. The most common reasons for an ED visit were common diseases rather than flares.

Comparison of the clinical characteristics and severity of community-acquired pneumonia between patients with rheumatoid arthritis treated with tocilizumab and those treated with TNF inhibitor.

Objective: To examine the clinical characteristics and severity of community-acquired pneumonia (CAP) between patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) and those treated with TNF inhibitors. Methods: We extracted RA patients treated with biological DMARDs who developed CAP between 2003 and 2015 from our hospital database. We compared the patient backgrounds, duration from the onset of symptoms to diagnosis, and the severity of CAP between patients who developed CAP after treatment with TCZ or tumor necrosis factor (TNF) inhibitor. Results: Of 98 patients who received TCZ, seven developed CAP (IL-6 inhibitor group). Of 560 patients who received TNF inhibitors, 27 developed CAP (TNF inhibitor group). Between the two groups, there was no difference in the duration from the onset of symptoms to diagnosis (7 [4-21], 7 days [1-15]). The IL-6 inhibitor group had a lower body temperature (36.5 °C [36.4-36.8], 37.8 °C [35.9-40.5]) and CRP level (0.09 mg/dL [0.02-2.5], 6.76 mg/dL [0.63-15.2]) at diagnosis than the TNF inhibitor group. The CURB-65 score did not differ significantly between groups. Conclusion: There were no delays in the diagnosis of CAP or any difference in the severity of CAP between patients with RA treated with TCZ and those treated with TNF-inhibitors.

Severe Thrombocytopenia Induced by First Infliximab Administration for Rheumatoid Arthritis.

Thrombocytopenia due to antitumor necrosis factorα agents is very rare. A 68-year-old woman with rheumatoid arthritis on methotorexate received infliximab (IFX). Three days after the first IFX infusion, she developed gingival bleeding, petechia, and gross hematuria. Her platelet count fell to 2000/µL. We administered a platelet transfusion and intravenous methylprednisolone. Three days after admission, her platelet count was 7000/µL and her bleeding persisted. After double filtration plasmapheresis, her bleeding stopped and her platelet count recovered over 2 weeks. Thrombocytopenia is a rare but severe complication of IFX. Double filtration plasmapheresis may be useful for removing IFX or possible antibodies against platelets when IFX remaining in the patient's blood interferes with improvement of the patient's condition.

Validation of RAPID3 using a Japanese version of Multidimensional Health Assessment Questionnaire with Japanese rheumatoid arthritis patients: characteristics of RAPID3 compared to DAS28 and CDAI.

OBJECTIVES: To validate Routine Assessment of Patient Index Data 3 (RAPID3) using a Japanese version of Multidimensional Health Assessment Questionnaire (MDHAQ) with Japanese rheumatoid arthritis (RA) patients and to describe the characteristics of RAPID3 by comparison with Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI). METHODS: The original MDHAQ was translated into Japanese with minor cultural modifications and was translated back in English. Test-retest reliability was evaluated in 50 Japanese RA patients and further validation was performed in 350 Japanese RA patients recruited by seven rheumatologists. RAPID3, CDAI, and DAS28 were assessed on two consecutive visits. RESULTS: The test-retest reliability and the internal reliability of RAPID3 were excellent. Spearman's correlation coefficients between RAPID3 score versus CDAI score and DAS28 score were 0.761and 0.555. However, the agreement measured by kappa (weighted) for RAPID3 category versus CDAI category and for RAPID3 category versus DA28 category were 0.225 (0.382) and 0.187 (0.336). The sensitivity and specificity of "RAPID3 ≤ 3 and swollen joint ≤ 1" for predicting Boolean remission were 90.0% and 93.4%, respectively. CONCLUSIONS: RAPID3 obtained by Japanese MDHAQ was validated with Japanese RA patients and the remission criteria were found to have excellent clinical utility in usual care.