Yasuhiro Suyama

Acute Calcific Tendinitis of the Longus Colli Muscle

acteristics of the minor salivary gland infiltrates in Sj€ ogren’s syndrome. J Autoimmun 2010;34:400–7. 23. Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K, Mysler E, et al. Sifalimumab, a human anti–interferon-a monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum 2013;65:1011–21. 24. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D, et al. for the BLISS-76 Study Group. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 2011;63:3918–30. 25. Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, et al. Efficacy and safety of rituximab in moderatelyto-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 2010;62:222–33. 26. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012;13:25–32. 27. Solomon B, Varella-Garcia M, Camidge DR. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J Thorac Oncol 2009;4: 1450–4. 28. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507–16.

MRI findings of the shoulder and hip joint in patients with polymyalgia rheumatica

Abstract Objectives. The purpose of this study is to evaluate magnetic resonance imaging (MRI) findings of the shoulder and hip joint in patients with polymyalgia rheumatica (PMR). Methods. MR images of a total of 25 PMR patients (23 shoulders and 6 hips), 43 rheumatoid arthritis (RA) patients (22 shoulders and 22 hips), and 50 control patients (25 shoulders and 25 hips) were examined. The following MRI findings were evaluated: In the shoulder, thickness and abnormalities of the supraspinatus tendon, effusion around the glenohumeral joint, subacromial-subdeltoid bursa, and the biceps tendon; In the hip, effusion around the acetabulofemoral joint, iliopsoas bursa, and trochanteric bursa. Periarticular soft-tissue edema and bone findings were also analyzed. Results. The supraspinatus tendon was significantly thicker in PMR patients than in RA patients and control patients (p < 0.05). Severe rotator cuff tendinopathy was frequently observed in PMR patients (p = 0.002). The scores for the amount of effusions (joint, bursa, and tendon sheath in the shoulder and bursa in the hip) were much higher in PMR patients (p < 0.05). Periarticular soft tissue edema was detected more frequently in PMR patients than in RA patients and control patients (p < 0.05). Conclusions. Thick supraspinatus tendon, severe rotator cuff tendinopathy, effusion around the joints, and periarticular soft tissue edema can be good indicators for the diagnosis of PMR.

Clinical Images: Arytenoid Chondritis

1991;10:4025–31. 18. Bouta EM, Banik PD, Wood RW, Rahimi H, Ritchlin CT, Thiele RG, et al. Validation of power Doppler versus contrast enhanced magnetic resonance imaging quantification of joint inflammation in murine inflammatory arthritis. J Bone Miner Res 2015;30:690–4. 19. Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological diseasemodifying antirheumatic drugs. Ann Rheum Dis 2010;69:964–75. 20. Keystone EC, Smolen J, van Riel P. Developing an effective treatment algorithm for rheumatoid arthritis. Rheumatology (Oxford) 2012;51 Suppl 5:v48–54. 21. Rahimi H, Bell R, Bouta EM, Wood RW, Xing L, Ritchlin CT, et al. Lymphatic imaging to assess rheumatoid flare: mechanistic insights and biomarker potential. Arthritis Res Ther 2016;18:194. 22. Zawieja DC. Contractile physiology of lymphatics. Lymphat Res Biol 2009;7:87–96. 23. Mallick A, Bodenham AR. Disorders of the lymph circulation: their relevance to anaesthesia and intensive care. Br J Anaesth 2003;91:265–72. 24. Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003;423:356–61. 25. Zwerina J, Hayer S, Tohidast-Akrad M, Bergmeister H, Redlich K, Feige U, et al. Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor–induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum 2004;50:277–90. 26. Mould AW, Tonks ID, Cahill MM, Pettit AR, Thomas R, Hayward NK, et al. Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Arthritis Rheum 2003;48:2660–9. 27. Catrina AI, Trollmo C, af Klint E, Engstrom M, Lampa J, Hermansson Y, et al. Evidence that anti–tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report. Arthritis Rheum 2005;52:61–72. 28. Binder NB, Puchner A, Niederreiter B, Hayer S, Leiss H, Bluml S, et al. Tumor necrosis factor–inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor–driven model of rheumatoid arthritis. Arthritis Rheum 2013;65:608–17. 29. Hayer S, Redlich K, Korb A, Hermann S, Smolen J, Schett G. Tenosynovitis and osteoclast formation as the initial preclinical changes in a murine model of inflammatory arthritis. Arthritis Rheum 2007;56:79–88.

Safety and efficacy of upfront graded administration of trimethoprim-sulfamethoxazole in systemic lupus erythematosus: A retrospective cohort study.

Abstract Objectives: Trimethoprim–sulfamethoxazole (TMP/SMX) is effective as prophylaxis against many infections in immunocompromised patients. However, it is not commonly prescribed for patients with systemic lupus erythematous (SLE) due to the risk of adverse reactions (ADRs). An upfront graded administration protocol for TMP/SMX was adopted, and its safety and efficacy were assessed. Methods: Data from 59 patients with SLE patients who received prophylactic TMP/SMX were retrospectively analyzed. The incidence and risk factors for ADRs in patients who received TMP/SMX before and after the introduction of graded administration were assessed. Results: The incidence of ADRs was 41.9% in the non-graded administration group, vs. 10.7% in the graded administration group (p = 0.009). The rate of high fever, liver function test (LFT) abnormality, shortness of breath, and hospitalization were reduced in upfront graded administration group. In addition, a higher rate of anti-Ro/SS-A positivity was found in patients experienced ADRs (46.2% in reactors vs. 5.6% in non-reactors; p = 0.012) in the non-graded administration group. Conclusions: Upfront graded administration of TMP/SMX reduces the incidence and severity of ADRs in SLE patients. The high incidence of TMP/SMX ADRs in SLE patients was also confirmed, especially when anti-Ro/SS-A antibody is present.

Endomyocardial Biopsy and Magnetic Resonance Imaging of Acute Myocarditis with Adult-Onset Still's Disease.

A 36-year-old female with a high-grade fever and epigastric abdominal pain was prescribed antibiotics, but developed hypoxia and dyspnea. An echocardiography revealed diffuse hypokinesis and massive pericardial effusion, after which diagnostic cardiac catheterization and an endomyocardial biopsy (EMB) were peformed to reveal fibrosis and infiltration of inflammation cells composed primarily of neutrophils. Clinical manifestation of a spiking fever, leukocytosis, elevated ferritin levels, skin rash and EMB findings led to a diagnosis of adult-onset Stills disease (AOSD) with acute myocarditis. Pulse therapy of intravenous methylprednisolone was performed for three days, followed by a daily dose of prednisone (60 mg). After a course of steroid therapy for fever and pericardial effusion, and conducting a left ventricular ejection fraction, the patient showed improvement and was discharged asymptomatic within 32 days of admission. This study is the first to report on a case of myocarditis in AOSD diagnosed by neutrophil infiltration in the myocardium.

Cold-associated painful purple digits due to type I cryoglobulinemia.

A 65-year-old man presented to our clinic in autumn with a 5-year history of painful purple digits that recovered with rewarming (Panel A). His skin changes developed when the temperature was below 20°C. He had not smoked for 20 years, and annual health checkup results were unremarkable (these included normal blood sugar and cholesterol levels). Raynaud phenomenon was suspected. He was subsequently hospitalized in the winter due to ischemic digital gangrene (Panel B). Laboratory evaluation revealed renal failure, elevated serum immunoglobulin G (IgG), low IgM and IgA, low C4, and the presence of cryoglobulins and monoclonal IgG-κ. Results were negative for antibodies to hepatitis B and C virus, antinucleolar antibody, anti-Ro antibody, and anti-La antibody. A bone marrow biopsy was performed and he was diagnosed with type I cryoglobulinemia due to multiple myeloma. Treatment with conservative amputation and chemotherapy was initiated, and the ischemic skin changes completely resolved. The differential diagnoses of painful purple digits suggesting arterial thromboembolism can be divided into two groups: those associated with cold temperature exacerbation (malignancy, cryoglobulinemia, small-vessel vasculitis, secondary vasculitis, systemic sclerosis, antiphospholipid syndrome, and Buerger’s disease) and those independent of temperature (embolus of infectious or thrombotic material from endocarditis, paradoxical embolus through an intracardiac shunt, thrombotic thrombocytopenic purpura, heparininduced thrombocytopenia, and cholesterol emboli).1,2 These diseases can lead to ischemic digital gangrene; thus, prompt evaluation of patients with acrocyanosis or Raynaud phenomenon is essential to prevent further complications.

Clinical Images: Widening of Joint Spaces in Acromegaly

Arthritis Prospective Study (CAPS), UKRAG Consortium, BSPAR Study Group, et al. Association of the CCR5 gene with juvenile idiopathic arthritis. Genes Immun 2010;11:584–9. 40. Civatte M, Bartoli C, Schleinitz N, Chetaille B, Pellissier JF, Figarella-Branger D. Expression of the b chemokines CCL3, CCL4, CCL5 and their receptors in idiopathic inflammatory myopathies. Neuropathol Appl Neurobiol 2005;31:70–9. 41. De Paepe B, de Bleecker JL. b-chemokine receptor expression in idiopathic inflammatory myopathies. Muscle Nerve 2005;31:621–7. 42. Desmetz C, Lin YL, Mettling C, Portalès P, No€el D, Clot J, et al. Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid arthritis synoviocytes. Clin Immunol 2007;123:148–54.

Systemic Capillary Leak Syndrome Successfully Treated with a TNF-α Inhibitor

Yasuhiro Suyama1*, Mitsumasa Kishimoto1, Ryo Rokutanda1, Chisum Min1, Gautam A Deshpande2, Youichiro Haji1, Ken-ichi Yamaguchi1, Akira Takeda1, Yukio Matsui1 and Masato Okada1 1Immuno-Rheumatology Center, St. Luke’s International Hospital, St. Luke’s International University, 9-1 Akashi-cho Chuo-Ku, Tokyo 104-8560, Japan 2Center for Clinical Epidemiology, St Luke’s Life Science Institute, 10-1 Akashi-cho Chuo-Ku, Tokyo 104-0044, Japan *Corresponding author: Yasuhiro Suyama, Immuno-Rheumatology Center, St. Lukes International Hospital, St. Luke’s International University, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan, Tel: +81-3-3541-5151; Fax: +81-3-5550-6000; E-mail: suyamaya@luke.ac.jp

FRI0393 Efficacy and Safety of Multi-Target Therapy with Mizoribine and Tacrolimus for Lupus Nephritis: Analysis of 28 Cases

Background We previously reported successful use of multi-target therapy using tacrolimus (TAC), mizoribine (MZR), and prednisolone for systemic lupus erythematosus[1]. More data is needed to confirm usefulness of this combination therapy for severe disease forms such as lupus nephritis. Objectives To examine efficacy and safety of multi-target therapy for lupus nephritis. Methods Retrospective review of electric medical record was performed for all the 28 patients who received multi-target usingTAC, MZR and corticosteroids for induction or maintenance of lupus nephritis at St. Lukes International Hospital, Tokyo, Japan. For efficacy analysis, we extracted a series of change in serum creatinine, serum complement level, urine protein creatinine ratio (UPCR), dose of corticosteroid. Patients with induction therapy were separately analyzed from those with maintenance therapy. We further reviewed safety profile such as adverse events occurred during the use of multi-target therapy, drug survival rate, or reasons for discontinue multi-target therapy in all patients. Complete remission of lupus nephritis was defined as a value of proteinuria <0.4 g/gCr, normal urinary sediment, serum albumin 3.5 g/dl and a normal value of serum creatinine. Partial remission was defined as an at least 50 per cent improvement in proteinuria and haematuria, serum albumin 3.0 g/dl and a normal value of serum creatinine or no more than 15 per cent above baseline values. Results Fourteen patients (mean aged 36.4 years) were given multi-target therapy as induction therapy, while the other 14 patient (mean aged 34.9 years) were given as maintenance therapy. As for induction patients, their mean baseline parameters were as follows: UPCR 4.34 g/gCr, serum creatinine 0.74mg/dl, C3 47.4mg/dl, and C4 7.1mg/dl. Within 6 month, 13 out of 14 induction patients achieved remission. Their mean doses of prednisolone at baseline, 3 months, and at 6 months are 59.4mg/day, 12.3mg/day, and 8.1mg/day, respectively. In maintenance patients, mean doses of prednisolone at baseline and at 6 months were 16.6mg/day and 8.1mg/day, respectively. There was one disease flare within 12 months. There was one disease flare during induction therapy and 3 flares during maintenance therapy. There was one case of serious adverse event which required hospitalization due to pyelonephritis during induction therapy. Conclusions This study demonstrated efficacy and safety of multi-target therapy with TAC and MZR for induction and maintenance of lupus nephritis. References Nomura A, Shimizu H, Kishimoto M, et al. Efficacy and safety of multitarget therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis. Lupus. 2012 Nov;21(13):1444-9. doi: 10.1177/0961203312458468. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4851

SAT0087 Diagnostic Performance of Anti-Ccp Antibody at Annual Health CHECK Up

Background There have been little data regarding epidemiology and usefulness of autoantibodies in general population. Objectives The purpose of this study is to describe epidemiological data about rheumatoid factor (RF) and anti-CCP antibody (ACPA) in Japanese general population and evaluate the usefulness of ACPA for detecting undiagnosed RA at annual health checkup. Methods During the period from November 2013 to January 2014, we checked RF and ACPA in all the female who visited St. Lukes International Hospital Center for Preventive Medicine for annual health examinations. Patients who already had diagnosis of RA were excluded. Patients who had positive RF and/or ACPA are encouraged to visit our Rheumatology Clinic. First, we analyzed clinical characteristics of ACPA positive population. Then we divided seropositive referred patients into 3 groups; patients with positive RF and negative ACPA (Group A), patients with negative RF and positive ACPA (Group B), and patients who were positive for both of RF and ACPA (Group C). Rheumatology specialists examined all the referred patients and diagnosed them as either of RA, undifferentiated arthritis, or asymptomatic seropositive patient. Results During the study period, 3,610 consecutive Japanese female were checked RF and ACPA. The mean age was 49.9±24.5 yrs. The number of the seropositive patients for RF and ACPA are 397 (11.0%) and 53 (1.5%), respectively. Among them, 33 patients were positive for both of RF and ACPA. By multivariate analysis, ACPA positive population showed significant higher prevalence of positive RF (OR 11.7, 95% CI 6.35-21.69) and malignancy (OR 2.20, 95% CI 1.08-4.46) than those who with negative ACPA. Twenty-one of Group A, 3 of Group B, and 9 of Group C were referred to our Rheumatology Clinic. Among them, 4 (44.4%) of Group C are newly diagnosed as RA at first visit, while none of Group A and Group B were diagnosed as RA. In addition, 2 (9.5%) of Group A, 1 of Group B (33.3%), and 3 (33.3%) of Group C were diagnosed as undifferentiated arthritis. The specificities of RF and ACPA for detecting undiagnosed RA in referred patients were 10.3% and 72.4%, respectively. Conclusions In general population, non-RA ACPA positive female showed higher prevalence of positive RF and malignancy. In addition, ACPA showed high specificity for detecting undiagnosed RA in referred patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4783