Katsuya Nagatani

Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs

To examine the incidence of hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving biological disease‐modifying antirheumatic drugs (DMARDs).

Low level of seroconversion after a novel influenza A/H1N1/2009 vaccination in Japanese patients with rheumatoid arthritis in the 2009 season

We examined change in the antibody titre against pandemic influenza A/H1N1/2009 before and after vaccination in Japanese patients with rheumatoid arthritis. This observational study was conducted with the participation of five hospitals in Japan. A total of 89 patients with rheumatoid arthritis were included in this study. The seroprotection and seroresponse rates to vaccination with the pandemic influenza A/H1N1/2009 vaccine were analysed. The seroprotection rates prior to the vaccination were 5.6% in the Japanese patients with rheumatoid arthritis. The seroprotection rates after subcutaneous vaccination were 55.1%. The seroresponse rate after subcutaneous vaccination was 50.6% in the patients with rheumatoid arthritis. Both the seroprotection and seroresponse rates obtained after the vaccination with the pandemic influenza A/H1N1/2009 vaccine were low in Japanese patients with rheumatoid arthritis. We should realise that a vaccination against this newly emerged influenza virus may protect only half of the Japanese patients with rheumatoid arthritis in a real world.

Difference in relapse-rate and clinical phenotype by autoantibody-subtype in Japanese patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract Objective: To correlate the serotype specificity to myeloperoxidase (MPO) and proteinase-3 (PR3) with clinical characteristics in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: Clinical characteristics and outcomes of patients with AAV in our division from 2005 to 2014 were retrospectively compared on the basis of ANCA subtype. Results: We collected the data from 88 patients with MPO–ANCA vasculitis, and 17 with PR3-ANCA vasculitis. Patients with PR3-ANCA vasculitis were younger, and had higher involvement-rates in the eye, nose, and ear. In both MPO- and PR3-ANCA vasculitis, the most frequently involved organ was the respiratory system. Interstitial pneumonia was more frequent in MPO-ANCA vasculitis (52.3% versus 5.9%, p < 0.01), whereas nodular shadow was more frequent in PR3-ANCA vasculitis (9.1% versus 58.8%, p < 0.01). Multivariable Cox proportional hazard regression analysis showed that the hazard ratio of PR3-ANCA for relapse was 2.48 (95% confidence interval 1.14–5.42, p = 0.02). There was no difference in the survival and the progression to end-stage kidney disease and respiratory failure between the two vasculitides. Conclusion: MPO-ANCA vasculitis was a predominant form of AAV in Japan. Classification based on ANCA subtype would be clinically relevant in the prediction of organ involvement and relapse.

Prediction of the therapeutic response to methotrexate at 24 weeks by methotrexate–polyglutamates concentration in erythrocytes at 8 weeks in patients with rheumatoid arthritis

Abstract Objectives: The objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of methotrexate–polyglutamates (MTX-PGs) in erythrocytes in patients with rheumatoid arthritis and correlate them with the efficacy. Methods: MTX-PG concentrations in erythrocytes were measured in 42 MTX-naïve patients repeatedly for 24 weeks by high-performance liquid chromatography. In 56 patients receiving stable MTX doses for at least 12 weeks, the correlation between MTX doses and MTX-PG concentrations was examined. The efficacy was measured by the change of DAS28CRP (ΔDAS28CRP). Results: There were moderate correlations between MTX dose and MTX-PG 3, 4, and 5. At 24 weeks, MTX-PG2, 3, 4, and 1–5 were higher in patients with ΔDAS28CRP >1.2 than in those with ≤1.2. The cutoff value of MTX-PG1-5 to discriminate ΔDAS28CRP >1.2 from ≤1.2 at 24 weeks was 68.7 nM. Among 20 patients with MTX-PG1-5 > 50.6 nM at 8 weeks, seven already improved at 8 weeks and additional 11 improved at 24 weeks (p < 0.001). On the contrary, among the nine patients with MTX-PG1-5 ≤ 50.6 nM at 8 weeks, none improved at 8 weeks and only one improved at 24 weeks (p = 0.500). Conclusions: Erythrocyte MTX-PGs might be a potential indicator and predictor of MTX efficacy.

A Case of Raoultella planticola Bacteremia in a Patient with Early Gastric Cancer

The patient was an 81-year-old man who was found to have bacteremia due to Raoultella planticola, which might have entered the circulation through the bile duct during the passing of a gallbladder stone. In the present case, we screened for malignancies because most cases of R. planticola bacteremia occur after trauma, invasive procedures, or in patients with malignancy (70.6%). Early gastric cancer was detected. Although the association between R. planticola bacteremia and malignancy remains speculative in the present case, it may be useful to scrutinize similar cases involving low-virulence bacteremia for possible malignancies or immune conditions.

Unaffected reaction level in tuberculin skin test by long-term therapy with tumor necrosis factor inhibitors for rheumatoid arthritis

The tuberculin skin test (TST) is used to diagnose tuberculosis; however, the influence of tumor necrosis factor (TNF) inhibitors on the test is unclear. This study investigated whether therapy with TNF inhibitors suppresses the TST reaction due to immunosuppression or whether the TST reaction increases due to reactivation of latent Mycobacterium tuberculosis infection.

Pseudorheumatoid Arthritis Caused by Calcium Pyrophosphate Dihydrate Deposition

An 80-year-old woman was referred to our department with recurrent episodes of symmetric polyarthritis, which were resistant to nonsteroidal anti-inflammatory drugs. Laboratory tests revealed a C-reactive protein (CRP) level of 0.82 mg/dL, and rheumatoid factor and antibodies against cyclic citrullinated peptides were negative. Radiography revealed chondrocalcinosis of the affected joints, including the metacarpophalangeal and wrist joints (Picture 1, arrows) and the metatarsophalangeal joints (Picture 2, arrows). According to these findings, the patient was diagnosed with pseudorheumatoid arthritis, a form of chronic inflammatory arthritis due to calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (1). Low-dose colchicine (0.5 mg/day) completely eliminated her symptoms, and her CRP level decreased to 0.03 mg/dL. Pseudorheumatoid arthritis occurs in 5% or fewer patients with symptomatic CPPD crystal deposition disease. Pseudorheumatoid arthritis due to CPPD crystal deposition disease should be included in the differential diagnosis if a patient demonstrates radiographic signs similar to those observed in our patient.

SAT0269 The Clinical Features of Sapho Syndrome in Japanese Patients: A Single Center Cohort Study

Background SAPHO syndrome is a rare syndrome characterized by osteoarticular and cutaneous involvements. Some drugs including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, antibiotics, synthetic disease modifying antirheumatic drugs (sDMARDs) and bisphosphonates have been used for the treatment of SAPHO syndrome, but there are no randomized trials about the treatment. Recently, some cases who responded to anti-TNF agents have been reported. Objectives We investigated the clinical features and treatment courses of SAPHO syndrome in our division. Methods We retrospectively reviewed the clinical data of patients with the diagnosis of SAPHO syndrome who were hospitalized in our division from 2003 to 2014. We used Hayems criteria as the diagnostic criteria. Results Twenty patients (6 males and 14 females) were included in this study. The median age at the time of diagnosis was 53 years (22-64 years). Thirteen patients (65%) had palmoplantar pustulosis (PPP), one (5%) had sterile pustulosis, and six (30%) had no sign of cutaneous manifestation. Osteoarticular lesions involved the anterior chest wall (65%), the spine (45%), sacroiliac joint (30%), and osteitis (20%). Axial arthritis, peripheral arthritis, and enthesitis developed in 80%, 45%, and 20% of the patients, respectively. Although PPP developed at the same time of bone involvement in five patients (25%), five patients (25%) had PPP after the onset of bone symptoms and four patients (20%) had PPP before bone symptoms. There was no association with PPP and peripheral arthritis, sternoclavicular arthritis, or spondylitis. Comorbidities included metabolic syndrome in 25% of the patients and autoimmune diseases in 20%. Rheumatoid factor examined in 19 patients was positive in 2 patients and one of them was also positive for anti-citrullinated protein antibody. The elevation of C-reactive protein or erythrocyte sedimentation rate was observed in 15 of 19 patients. None of 10 patients tested for HLA was positive for HLA-B27. Various kinds of drugs were used in these patients. NSAIDs were medicated in all the patients. NSAIDs, glucocorticoids, sDMARDs, bisphosphonates, or anti-TNF agents were administered as monotherapy, or combination therapy with two or more drugs. Among five patients who received anti-TNF agent, two patients (40%) responded to the treatment. Finally, the results of the treatments were partial or complete response in 17 patients and no response in 3 patients. Conclusions In our experience, the frequency of osteitis and axial involvements was higher compared with past studies. The effect of anti-TNF agents was reported in some case series, but the effect was dependent on the patients in our study. Since there are several patients refractory to treatment, the treatment for SAPHO syndrome needs further exploration. References Hayem G et al. Semin Arthritis Rheum 1999;29:159-171 Jurik AG, et al. J Pediatr Orthop 1998;8:49-58 Colia M, et al. Arthritis Rheum 2009;61:813-821 Grosjean C, et al. J Rheumatol 2010;37:639-643 Hurtado-Nedelec M, et al. J Rheumatol 2010;37:401-409 Sueli C, et al. Rheum Dis Clin 2013;39:401-418 Disclosure of Interest None declared

An unusual cause of hemichorea-hemiballism in a patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) can present with various neuropsychiatric manifestations [1]. One of these, chorea, is rarely seen and has been possibly associated with antiphospholipid antibodies [2–4]. Along with connective tissue disorders, many other diseases are also associated with the symptom of chorea [5]. Although rare, chorea has occasionally been found to be a presenting symptom of hyperglycemia [6]. Here we report on a patient with SLE who presented with unilateral involuntary movement in her upper and lower extremities, which was eventually diagnosed as diabetic hemichorea–hemiballism (HC–HB). A 55-year-old woman with SLE presented with involuntary movements in her left upper and lower extremities, and general malaise which had developed 8 days previously. Her SLE had been diagnosed 4 months earlier, and the initial laboratory findings were as follows: leukocyte count, 2,600/ll with 37% lymphocytes; hemoglobin, 10.0 g/dl; platelet count, 18.9 9 10/ll; complement C3, 82 mg/dl (normal 86–160); and C4, 13 mg/dl (normal 18–25). Antinuclear antibody (1:1,280 with speckled pattern), anti-SSA antibody (1:64), anti-RNP antibody (1:64), and anti-double-stranded DNA antibody (18.9 IU/ml, normal \9.5) were positive, but anti-Sm antibody was negative. Urinary protein was 1.26 g/day with no hematuria. Renal histology was not obtained. She had been treated with prednisolone 30 mg/day, which had been reduced to 20 mg/day by the time of presentation. She was admitted to our hospital because of the involuntary movement. On examination, she was alert and oriented. Involuntary movement—chorea and ballism—was observed in her left arm and leg. Laboratory testing showed a leukocyte count of 13,000/ll, hemoglobin 12.7 g/dl, and platelet count 20 9 10/ll. Serum sodium and potassium were 129 mmol/l and 5.4 mmol/l, respectively. Blood glucose was significantly elevated at 700 mg/dl, and hemoglobin A1c level, which had been 6.0% 4 months ago, was now 15.2% (normal\5.8). Complement C3 was low (81 mg/dl), but C4 and C-reactive protein were within normal range, and lupus anticoagulant was negative. Urine dipstick showed 1 ? ketone, 4 ? sugar, and no protein. Cerebrospinal fluid examination showed a normal number of cells, protein 50 mg/dl (normal \40), and glucose 352 mg/dl. Although computed tomography of the brain was unremarkable, magnetic resonance imaging (MRI) showed a bilateral hyperintensity in the putamen on fluid-attenuated inversion recovery image. We speculated that the impaired glycemic control might have induced this condition. After intensive glycemic control with insulin and hydration, the involuntary movement quickly resolved within a day. Both anti-doublestranded DNA antibody and anti-phospholipid antibodies were negative. Because the response to glycemic control was very rapid, the diagnosis of hyperglycemia-induced HC–HB was highly probable. HC–HB is characterized by unilateral, continuous, proximal and distal involuntary movements [7]. HC–HB due to hyperglycemia mainly affects elderly women, often Asian, who have uncontrolled diabetes or recent-onset hyperglycemia [6]. Most cases are associated with nonketotic hyperglycemia, although HC–HB with ketoacidosis has also been reported [8]. High signal intensity in the A. Maruyama T. Nagashima (&) Y. Kamata K. Nagatani T. Murosaki T. Yoshio S. Minota Division of Rheumatology and Clinical Immunology, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan e-mail: naga4ma@jichi.ac.jp