Yoko Fujita

Retrospective analysis of 95 patients with large vessel vasculitis: a single center experience

Although Takayasu arteritis (TAK) and giant cell arteritis (GCA) have been considered as distinct disease entities, similarities of these diseases have been recently reported. However, little data is available regarding this issue in Japanese patients with TAK and GCA. In addition, the classification criteria for TAK established in 1990 by the American College of Rheumatology (ACR) have been criticized due to the age restriction for disease onset (≤ 40 years). Thus, we aimed to compare the clinical characteristics of Japanese patients with TAK and those with GCA and to clarify whether clinical differences existed between patients with early‐onset (≤ 40 years) and late‐onset (> 40 years) TAK.

Extracorporeal Shock Wave Therapy for Digital Ulcers of Systemic Sclerosis: A Phase 2 Pilot Study

Patients with systemic sclerosis (SSc) often display Raynauds phenomenon and digital skin ulcers. As these ulcers are not associated with autoimmune factors or abnormal coagulation, conventional immunosuppressive therapies, vasodilators, and anticoagulants are often ineffective. Here, we used extracorporeal shock wave therapy (ESWT) to treat these ulcers. Nine SSc patients with new digital ulcers, previously treated with at least one currently available vasodilator or anticoagulant were enrolled. One ESWT session consisted of 100 pulses at 0.08-0.25 mJ/mm(2) in 20 areas on both hands and 15 areas on both feet, totaling 7,000 pulses. Treatment was performed once per week for 9 weeks with observations over 20 weeks. Outcomes were evaluated according to the number and diameter of ulcers, Rodnan skin score, Health Assessment Questionnaire (HAQ), EuroQol 5 dimensions (EQ-5D), visual analog scale for pain, and the PainVision system. The surface skin temperature of all the fingers was measured using thermography. Ulcers showed signs of healing after one session, and their mean number decreased from 5.4 to 1.1 at 9 weeks. In particular, of the 18 large ulcers (> 5 mm) observed in 7 patients before the treatment, 10 disappeared and the rest became smaller; namely, the mean size decreased from 10.9 mm to 2.5 mm at 20 weeks. The average scores on the HAQ, EQ-5D, and PainVision system also improved. Treatment was minimally invasive and could be repeated without any adverse effects. ESWT may be added to standard treatments for indolent digital ulcers of SSc, as an effective and safe method.

Successful multi-target therapy using corticosteroid, tacrolimus, cyclophosphamide, and rituximab for rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis

administered (IVCY, 750 mg) every 3 weeks, but GGO of the left lobe continued to progress (Figure 1D). We persevered by adding four weekly infusions of rituximab (375 mg/m 2 , 500 mg per body) with concomitant use of steroid pulse therapy (mPSL pulse), intravenous immunoglobulin, and polymyxin B hemoperfusion treatment (PMX). After infusions of rituximab, the population of B-cells decreased to an undetectable level. Since then, radiographical progression dramatically stopped, and the patient has been in clinical remission for the last 6 months, although fi brosis and traction bronchiectasis persist in the left lobe (Figure 1E – G). The KL-6 level peaked out (maximum; 4185 U/mL, at the last visit; 2756 U/mL), and respiratory function has relatively been maintained (%vital capacity; 75.9%, forced expiratory volume 1.0%; 104.5%). Rituximab has recently been demonstrated to be eff ective in treatment-refractory myositis or ILD in patients with dermatomyositis [2,5]; however, to our knowledge, there is no reported case of a patient with CADM and RP-ILD who was successfully treated with a combination therapy including rituximab. In patients with CADM, serum anti-MDA5 antibody level closely correlated with the severity of ILD, and it decreased after treatment [6], which suggested that autoreactive B-cells may play a role in the pathogenesis of ILD associated with CADM. Our case demonstrates that multi-target therapy including rituximab is a new therapeutic option for RP-ILD in patients with CADM.

Long-term follow-up of 124 patients with polymyositis and dermatomyositis: Statistical analysis of prognostic factors.

Objectives. The aims of this study were to clarify the long-term outcome of patients with polymyositis and dermatomyositis (PM/DM) and to elucidate prognostic factors using statistical analysis. Methods. We enrolled patients with PM/DM who visited our department between 1990 and 2014. Diagnoses of PM/DM and clinically amyopathic DM were based on the definitions of Bohan and Peter, and Sontheimer, respectively. We also obtained clinical data, such as age of onset, sex, medications, and presence of interstitial lung disease and malignancies, as well as laboratory tests, including the values of creatine kinase, KL-6, and ferritin. The follow-up was conducted until June 2014. Results. A total of 124 patients (PM: 46, DM: 78) were enrolled. The mean age of onset was 53.5 years, and females were predominant (64.5%). Overall survival rates were 93%, 86%, and 78% for 1, 5, and 10 years, respectively. The survival rates were significantly lower in patients with higher age of onset, with malignancies, and with hyperferritinemia in univariate analysis; however, multivariate analysis identified age of onset and serum ferritin as the most significant prognostic factors. Conclusions. Our study indicates that when age of onset and serum ferritin are used in combination, we can predict prognosis of patients with PM/DM.

High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by extensive fibrosis and autoantibodies. Its clinical manifestations are diverse and include Raynauds phenomenon, gastrointestinal dysmotility, interstitial lung disease (ILD), pulmonary hypertension, and renal crisis. Among these, ILD is the primary cause of SSc-related death. It has been considered that acute exacerbation of ILD (AE-ILD) is not common in patients with SSc; however, little is known about the prevalence of AE-ILD in Japanese patients with SSc. In this study, we aimed to clarify the prevalence, clinical characteristics, and prognosis of patients with SSc who developed AE-ILD and to identify predictive factors for AE-ILD in our Japanese cohorts. Clinical data of patients who visited our department from 1990 to 2014 and fulfilled the 2013 classification criteria for SSc were retrospectively reviewed. A total of 139 patients were enrolled. The mean age of onset was 49.1 years, and 113 (81.3%) patients were female; 116 (83.5%) had limited cutaneous involvement, and the overall 10-year survival rate was 92.0%. Among 66 (47.5%) patients with ILD, 13 (9.4%) developed AE-ILD. Patients with AE-ILD had a significantly higher incidence of overlap with polymyositis (PM) or dermatomyositis (DM) and lower prevalence of anticentromere antibodies with higher mortality rate compared with those without AE-ILD. Multivariate Cox regression analysis identified that an overlap with PM or DM was the most significant predictive factor for AE-ILD. Our study results suggest that Japanese patients with SSc, particularly patients overlapped with PM or DM, have a high risk of AE-ILD.

Synovitis in a Patient with IgG4-related Disease

A 71-year-old man was admitted to our department due to arthralgia and renal dysfunction. A physical examination disclosed swelling of the right shoulder and left wrist joints. Laboratory tests showed elevated serum IgG4 and creatinine levels, and magnetic resonance imaging of the wrist revealed bone erosion and synovitis. In addition, fluorodeoxyglucose positron emission tomography showed uptake in the submandibular glands, pancreas, kidneys, and affected joints and a renal biopsy revealed tubulointerstitial nephritis with the infiltration of IgG4+ plasma cells. The patient was subsequently diagnosed with IgG4-related disease (IgG4-RD) and successfully treated with corticosteroid therapy. This case suggests that erosive arthritis may occur in patients with IgG4-RD.

Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus

Abstract Objectives: The objective of this study is to evaluate the efficacy and safety of bortezomib for treating systemic lupus erythematosus (SLE), in patients whose disease activity could not be controlled. Methods: Fourteen SLE patients with persistent disease activity were selected, who required prednisolone doses of >10 mg/d despite concomitant immunosuppressive therapy. Patients were randomly administered either bortezomib or a placebo, eight times. The primary and secondary end-points were a change in anti-dsDNA antibody titer at week 24 and the SLE Responder Index (SRI), respectively. Results: In the bortezomib group, four out of eight patients discontinued the trial; three others failed to complete the minimum protocol treatment due to adverse reactions. The changes in anti-dsDNA antibody titers at week 24 were 4.24% and −1.96%, for the bortezomib and placebo groups, respectively, disconfirming bortezomib’s efficacy. In contrast, the corresponding SRI at week 12 was 75% and 40%. Conclusions: As bortezomib therapy for SLE is associated with many adverse reactions, treatment indications should be selected carefully, and protocols should aim to prevent these occurrences. Although the change in anti-dsDNA antibody titer did not support the efficacy of bortezomib as a treatment for SLE, high SRI in the treatment group suggests bortezomib may utilize mechanisms other than inhibition of anti-dsDNA antibody production.

Takayasu Arteritis Coexisting with Sclerosing Osteomyelitis

We report a rare case of a 27-year-old woman with Takayasu arteritis (TAK) complicated by diffuse sclerosing osteomyelitis. She first presented with sclerosing osteomyelitis of the right mandible without evidence of arteritis in the carotid arteries. Eight months later, she complained of left neck pain, and imaging studies revealed the presence of arteritis in the left carotid artery. She was diagnosed with TAK, and immunosuppressive treatment was initiated, which was effective for both the arteritis and the osteomyelitis. Osteomyelitis is an important complication of TAK and bone scintigraphy is useful for its detection.

Pseudothrombocytosis caused by cryoglobulin crystals in a patient with primary Sjögren's syndrome

because of high titers of platelet-associated immunoglobulin G (212 ng/10 7 cells) and exclusion of other diseases. In rare cases, cryoglobulin-induced laboratory artifacts, such as pseudoleukocytosis and pseudothrombocytosis, impacts laboratory test results, which diff er from clinical symptoms [2 – 4]. Therefore, we rheumatologists should realize that the electrical resistance method, which is the conventional method for counting platelets, is aff ected by the formation of cryoglobulin crystals and that such artifacts may lead to a wrong decision of blood transfusion, potentially resulting in fatal consequences.