[in Japanese]

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[in Japanese]

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[in Japanese]

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    In recent years, there has been remarkable progress in the field of rheumatoid arthritis (RA) treatment with the emergence of biologic disease modifying anti-rheumatic drugs such as infliximab, etanercept, adalimumab and tocilizumab in Japan.
    In rheumatology clinics like ours, the first visits of many patients with joint symptoms worrying about being RA are seen in everyday outpatient clinics. Most of these patients are classified as non RA, but they also include not only early RA but also even very early that will become RA in the near future.
    Since we have already had the strong and effective means to treat RA like biologic DMARDs, I think our duty is to perform early diagnosis and early treatment of RA.
    To find and diagnose early RA correctly as early as possible, we are utilizing the medical network system of clinical images established recently with Tonan Hospital. As a tool of clinical images to find and evaluate synovitis of inflamed joints, we have two methods: one is power doppler ultrasonography (PDUS) and the other is MRI of the joint. We use PDUS in our clinic and utilize MRI as a second diagnostic tool by way of medical network system stated above. For the time being, it is very effective system to diagnose early RA in the clinic like ours.

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    We report 2 patients with rheumatoid arthritis (RA) of recent onset treated with sulfasalazine (SSZ) alone in whom bone erosion was repaired and bone regeneration observed during treatment. In both patients, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) remained low throughout treatment. One of the patients, however, exhibited a slight, transient increase in these parameters during progression of bone destruction, and repair of the site of bone erosion and bone regeneration were observed in association with decrease in these parameters. These findings confirm that treatment of early RA with SSZ not only reduces the risk of serious side effects but also yields a good prognosis.

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Background and aim: Biological drugs such as adalimumab, infliximab and etanercept dramatically improved the treatment of rheumatoid arthritis. However, there are some patients who do not respond to these tumor necrosis factor (TNF) inhibitors. We investigated whether switching therapy to adalimumab from other TNF inhibitor is effective for those who do not respond infliximab or etanercept.
Method: Patients who did not respond to infliximab or etanercept were enrolled in the study (n＝55; male/female, 13/42; mean age, 59.7 y.o.; mean duration of disease,13 y. and 9 mo.). Patients received adalimumab every other week, and efficacy was assessed using EULAR criteria. Efficacy and safety were evaluated 24 weeks after initiation of adalimumab administration.
Results: Among patients enrolled in the study, 36 (65.5%) cases completed the 24-week administration. The number of patients showing moderate/good response was 30 (54.5%). Adalimumab had fast onset and improved DAS28-CRP and MMP-3 immediately four weeks after initiation of administration, and the efficacy remained after 24 weeks. Adverse events were reported from 32 (58.2%) cases. Major events were rash/itching (18/55, 32.7%) and erythema at injection site (12/55, 21.8%). Three serious events (thrombopenia, back abscess after acupuncture and wound infection after cervical surgery) were reported, but none of them was considered to be associated with adalimumab. Only seven cases were discontinued due to adverse events.

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    Tocilizmab (TCZ) was introduced to 35 cases from May 2008 to September 2009. Among the cases which could be observed for half a year after the introduction, there were 13 cases which were effective to the biological medicine (First group; Group F) and 14 cases which were TNF-α in effective cases (Second group; Group S) The values of DAS28-ESR, VAS, MMP-3 and the decreased amount of the concurrent drugs were compared and examined between Group F and S, and before and half a year after the introduction of TCZ or at the time of its termination. In Group F, DAS28-ESR dropped to 2.17 from the initial level of 4.63, and in Group S, it dropped to 2.51 from the initial level of 5.17. Both achieved the remission. In Group F, VAS dropped to 11 from the initial level of 41.5 mm, and in Group S, it dropped to 17.7 from the initial level of 43.4 mm. MTX, PSL, the number of people who were prescribed and the average dosage decreased for both groups. In Group F, MMP-3dropped to 100 ng/ml from the initial level of 172.1 ng/ml, and in Group S, it dropped to 103.9 ng/ml from the initial level of 246.7 ng/ml. After 24 weeks, there was an increased number of cases which shifted to the single-agent treatment for both cases. This examination suggests that it is appropriate to consider TCZ as one of the first options when introducing a biological agent.

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Object: The number of rheumatoid arthritis (RA) patients treated with anti-tumor necrosis-α (anti-TNF-α) is rapidly increasing. However, some cases show an inadequate response to anti-TNF-αor reduction in effectiveness during long-term treatment.
    This report describes the efficacy of tacrolimus combination therapy in RA patients that showed an inadequate response to infliximab.
Methods: Six RA patients (5 females, one male, mean age 61±6.44 yrs, mean disease duration 7.3±2.94 yrs) who had shown an inadequate responses to infliximab were treated with tacrolimus combination therapy. The effectiveness was evaluated based on the clinical joint symptoms, CRP, VAS, and DAS28CRP at 3 months later and at the final follow-up.
Results: The mean value of tender joint scores decreased from 9.2 to 5.0, that of swelling joint score decreased from 8.0 to 3.3, mean value of patient’s global assessment of disease status using visual analogue scale (VAS) decreased from 67.0 to 41.2, the mean CRP level decreased from 4.6 to 1.4 mg/dl, and the mean DAS28CRP decreased from 5.6 to 3.8. The results showed that1of 6 high activity patients was in remission, while 2 patients showed moderate activity at the last observation. No serious adverse events were observed during the follow-up periods in any of the patients.
Conclusion: These results suggest that tacrolimus combination therapy may therefore be a useful method for rheumatoid arthritis patients that show an inadequate response to infliximab.

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    To analyze functional outcome of arthroscopic synovectomy in effect attenuation cases of biologics for rheumatoid arthritis (RA), we investigated 17 cases, 30 joints, 3 male and14female, mean age of 54.8 (40-71) years old, mean disease duration of 9.9 (1-36), mean follow-up periods of 36.7 (12-60) months, mean MTX of 6.2 (4-8) mg/weeks, mean prednisolone of 4.3 (0-7.5) mg/day including 17 knee joints, 7 shoulder joints, 3 elbow joints and 3 wrist joints for arthroscopic synovectomy. We compared DAS28 (CRP) and HAQ before and after surgery, especially compared between knee joints synovectomy and shoulder or elbow joints synovectomy. We found DAS28 significant improvement from 5.17±0.56 to 3.14±0.44 and HAQ significant improvement 1.53±0.79 to 0.58±0.53 after 3 years. HAQ remission (＜0.05) was 47%. In shoulder and elbow arthroscopic synovectomy, standing and extension of HAQ improved significantly. On the other hand, in knee arthroscopic synovectomy, almost all items of HAQ improved significantly. The correlations between before and 3 years after arthroscopic synovectomy were recognized significantly. Therefore combination therapy of biologics and arthroscopic synovectomy is useful to improve function of RA patients.

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    We present a case of rheumatoid arthritis (RA) successfully treated with Kampo medicine. A 44-year-old man developed RA in 2003. Methotrexate (MTX), prednisolone (PSL) and salazosulfapyridine therapy did not improve his condition. After MTX therapy with PSL (15mg/day) in 2007, the CRP value decreased from 6.0 to 1.2 mg/dl, but recurrence of RA occurred after a decrease in the dosage of PSL to 5 mg/day. The patient visited our clinic in Dec. 2008. We used granulated Kampo extract first, but RA conditions did not improve. Even after administering etanercept and MTX with 5 mg/day of PSL since March 2009, his condition did not improve well, and the MMP-3 value increased. Since August 2009, decoction of Kampo medicine, Keishi-nieppi-itto-ka-ryojutubu was administered second. Thereafter, polyarthralgia decreased to10% of the peak level, and DAS28-CRP and MMP-3 values also decreased. These values have remained low for 3 months to date. Kampo medicine may be a useful additional and alternative agent for the treatment of RA.

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    The patient was a 74-year-old woman who had been diagnosed with rheumatoid arthritis in 1998 and started treatment at our outpatient clinic in 2001. She had been repeatedly hospitalized for aggravated arthritis and vertebral compression fracture, among other problems. In the beginning of April 2008, she first experienced exertional dyspnea. On April 25, she was transported to our hospital by ambulance due to worsening of exertional dyspnea and was hospitalized immediately. A chest radiograph showed marked cardiac enlargement, while a cardiac ultrasonographic study revealed impaired diastole due to massive hydropericardium, consistent with a diagnosis of cardiac tamponade. Purulent pericardial fluid was drained under fluoroscopy. The drained fluid was exudative, culture-negative for general or acid-fast bacteria, positive for rheumatoid factors, and showed low complement and high immune complex C1q levels.
    We diagnosed the cause of cardiac tamponade as rheumatoid pericarditis from these results and started her on 40 mg/day of methylprednisolone, which prevented recurrence of pericardial effusion, leading to her discharge on June 3. Cardiac tamponade caused by rheumatoid pericarditis is a relatively uncommon pathologic condition complicated by late-stage rheumatoid arthritis. In this case, the patient recovered from this acutely morbid state with pericardial drainage and steroid administration.

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    A 62 year-old-man had been receiving regular outpatient treatment because of hypertension and hyperlipidemia. He was admitted to the hospital because of cerebral infarction in September and October 2007. In each case, medication was changed. He was admitted the hospital again because of pleulitis in February 2008. In the hospital, he became complicated with cerebral infarction and the medication dose was increased. Later, antinuclear antibody showed 640X. Pleuritis associated collagen disease was suspected. Oral predonisolone (20 mg/day) was administered and pleuritis improved quickly. Then, occult blood in urine and uric protein were indicated and he visited the department of nephrology. In April 2008, he was admitted to the hospital for the fourth time because of cerebral infarction. We diagnosed systemic lupus erythematosus (SLE) from malar rash, pleuritis, leucopenia, renal disorder and positive antinuclear antibody. We performed renal biopsy and diagnosed lupus nephritis type IV-S (A/C). Gradually, renal function was decreasing. Steroid pulse therapy followed by oral predonisolone (55 mg/day) was administered as a diagnosis of rapidly progressive glomerulonephritis (RPGN). Urine protein decreased and his condition improved.

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    We describe here a 51-year-old man with polymyositis and interstitial pneumonia (IP) who developed pneumatosis cystoides intestinalis (PCI). The patient was diagnosed as PM associated with interstitial pneumonia when he was 43 years old. Methylprednisolone and cyclosporine treatment were started. His clinical symptoms including the serum data improved progressively. Cyclosporine was stopped and methylprednisolone was tapered to 2 mg/day. However, IP had become worse when he was 50-year-old. The dosage of methylprednisolone was increased. However, he was admitted to our hospital due to intramural gas in the intenstinal wall and free air in the bottom of diaphragm, which was detectable by follow up CT scan. His vital signs were almost normal, and physical examination showed only mild abdominal distention. Physical, laboratory and radiographic examination showed no evidence of infection or necrotizing enterocolitis. Based on these findings, a diagnosis of PCI was established. We selected conservative treatment, the patient was treated with high dosage oxygen (5 L/min via a face mask for 5h per day), and diet was discontinued for 14 days. High dose oxygen was effective, but the gas did not disappear completely, and recurred upon discontinuation of oxygen. When high dose oxygen was used in addition to oxygen at hyperbaric pressure for1hr per day, PCI disappeared by abdominal CT scan. This progress was monitored by colonoscopy.
    We reported this rare case of PCI with polymyositis compared with PCI associated with other rheumatic disorders.

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    A 57-year-old woman was admitted to our hospital because of CSS (Churg-Strauss syndrome) with widespread bloody bullae and leg skin ulcer. She had been treated for asthma since she was 45. From the middle of August, she had repeated low grade fever (37°C) podarthralgia and urticaria-like eruption on both lower limbs. From the end of August, she presented with high fever (39°C), purpura and bloody bullae on her hands and legs. Then, she was admitted to our hospital on September 9th. Laboratory findings revealed eosinophilia -(1100/mm³), high levels of serum CRP (10.7 mg/dl) and nonspecific IgE elevation (943 IU/ml). MPO-ANCA titer increased to 920 EU (normal range＜10 EU), and ulinalysis showed proteinuria and microhematuria. Skin biopsy of the leg purpura demonstrated leukocytoclastic vasculitis with increased eosionophil infiltration in dermis middle class. She was diagnosis as having Churg-Strauss syndrome and was treated with prednisolone including steroid-pulse therapy, Although the therapy improved fever and CRP level. Purpura and bloody bullae changed to widespread skin ulcers. We report as a rare case of MPO-ANCA positive Churg-Strauss syndrome with widespread bloody bullae and leg skin ulcer.

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    Here, we report a case of myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPOANCA)-related vasculitis. The patient had been treated with propylthiouracil for Basedow’s disease. Propylthiouracil administration was ceased 20 years ago following thyroid surgery.
    A 46-year-old woman with a 26-year history of Basedow’s disease and 12-year history of rheumatoid arthritis was admitted with high fever and pulmonary hemorrhage. Results of laboratory evaluation were: CRP 7.54 mg/dL, Cr 4.54 mg/dL, Hb 6.8 g/dL.
    A diagnosis of MPO-ANCA-associated vasculitis was strongly suggested by positivity for MPO-ANCA (352EU), pulmonary hemorrhage, acute nephritis, and scattered purpura on the limbs. However patient condition did not allow histological confirmation of the diagnosis.
    She was treated with methylprednisolone pulse therapy and prednisolone. Consolidation on chest X-ray and C-reactive protein levels improved rapidly. However, pulmonary hemorrhage was repeated four times with tapering of prednisolone. The titer of MPO-ANCA showed a linear decrease during the clinical course. The recurrence of pulmonary hemorrhage was correlated with the level of CRP.
    MPO-ANCA-associated vasculitis was caused by propylthiouracil. It was reported that serum ANCA may still remain positive in the majority of patients with propylthiouracil-induced MPO-ANCA positive for up to 5 years. This patient developed MPO-ANCA-associated vasculitis from taking propylthiouracil 20 years previously. ANCA was detected in more than 20% of patients treated with propylthiouracil, but only 6.5% of patients showed clinical evidence of vasculitis. Long-term follow-up may be necessary after discontinuation of propylthiouracil.

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    A 34 year-old man was admitted to our hospital because of arthralgia, hematuria and positive finding of MPO-ANCA. Basedow disease (BD) was diagnosed when he was30years old. Propylthiouracil (PTU) was administered because he had an allergy to thiamazole. PTU treatment was temporarily discontinued because his thyroid function was well-controlled. However, the exacerbation of BD brought the restart of PTU treatment. Just a month after treatment was restarted, fever, myalgia and arthralgia developed. The examination in hospital revealed hematuria and the positive detection of MPO-ANCA. Furthermore, renal biopsy and chest CT showed necrotizing glomerulonephritis and interstitial pneumonitis, respectively, which were consistent with MPO-ANCA associated vasculitis. The change of PTU for potassium iodide and the treatment of 0.5 mg/kg predonisone allowed us to control both hyperthyroidism and MPO-ANCA associated vasculitis. This case suggests that the booster effect induced by PTU treatment might promote the rapid progress of MPO-ANCA associated vasculitis. Analysis of 79 past cases with PTU-induced ANCA-associated vasculitis showed that this complication was caused by the restart of the treatment with PTU in about 10% of the patients. Therefore, attention should be paid to the possibility of inducing MPO-ANCA even in patients under therestart of the PTU treatment for hyperthyroidism.

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    The patient was a 59-year-old woman with a history of uveitis since 2004. In September, 2008, a rash emerged on her lower extremities, which necessitated a skin biopsy in January of the following year. Examination of the biopsy specimen revealed non-caseous epithelioid granulomas with multinucleated giant cells characteristic of sarcoidosis. She had malaise as well as discomfort in her lower extremities starting in March, 2009, and so was referred to our department in August. A physical examination revealed neither muscle weakness nor tenderness. Blood studies showed an elevated erythrocyte sedimentation rate and mild increases in myogenic and angiotensin converting enzymes. T2-weighted and STIR MR images showed a large region of highintensity signals with ambiguously defined borders in the thigh muscle, raising the suspicion of myositis. Biopsy of the same muscle disclosed degenerated muscle fibers, inter-muscle fiber infiltration of inflammatory cells, and granulomas in some areas, establishing a diagnosis of sarcoid myopathy. Immunostaining demonstrated that the majority of inflammatory cells were CD4-positive T lymphocytes, a finding compatible with sarcoidosis. Prednisolone at a dose of 25 mg/day gave the patient relief from her clinical symptoms.

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