The advent of anti-tumor necrosis factor (TNF)-α agents, specifically remedies for rheumatoid arthritis, sometimes make patients with rheumatoid arthritis go into remission. But, occasionally, it also brings an ancient scourge, tuberculosis. Japan is a country with a middle incidence rate of tuberculosis. So, it is important to make a vernacular solution suitable for tuberculosis-problems in Japan.
    The problems concerning tuberculosis following therapy with anti-TNF-α agents in Japan as follows:
1. It is difficult to select RA patients infected with tuberculosis.
2. Prophylaxis of tuberculosis for the rheumatoid arthritis patients infected with tuberculosis is sometimes more difficult than usual.
3. Diagnosis of tuberculosis is more difficult than the usual because of the non-specific nature of tuberculosis following after the anti-TNF-α agents.
4. Tuberculosis following therapy with the agents may be refractory to anti-tuberculosis therapy.
5. Rheumatoid arthritis following the cessation of the agents may be refractory.
6. There are few good medical facilities to treat both tuberculosis and rheumatoid arthritis.
    The most important lesson to be noted is stopping short at administration of anti-TNF-α agents when something is wrong or is expected is to happen.

View full abstract

    A six-month, double-blind, controlled study to compare mizoribine (MZR) with lobenzarit disodium was conducted in Japan, and this is the first Japanese study that has demonstrated an inhibitory effect of MZR on joint destruction. In order to observe this effect over a longer period, we performed a two-year, open-label study using MZR and an oral gold compound, auranofin (AUF), as a comparator from September 1993 to July 1997. Thirty-five medical institutions in Japan participated in this study. A total of 166 patients were enrolled in the study, and of these participants, 87 and 79 received MZR and AUF, respectively. The joints were assessed in 31 MZR patients and 28 AUF patients who met the joint evaluation criteria. In AUF patients, damage scores for the hands showed significant increases of 104.55±11.13%, 107.57±17.96%, and 107.03±15.07% at 6 months, 1 year, and 2 years, respectively. However, MZR patients had a score increase only at two years (104.05±18.26%). One of the characteristics of this effect is found in the fact that MZR has inhibited joint destruction in patients with or without clinical improvement, whereas AUF exerts such an effect only in symptomatically improved patients.

View full abstract

    Various kinds of factors contribute to osteoporosis by rheumatoid arthritis (RA) compare with post-menopausal osteoporosis. In this study, we analyzed the influence for bone metabolism administration with leflunomid for RA patient. A subject is the 19 RA patients after menopause older than 48 years old that do not take administration of bisphosphonate previously. These patients were given leflunomid as a treatment purpose of RA, and measured urine-NTX, serum -NTX, BAP, OC and bone mineral density (BMD), in the period of before administration with leflunomid, six months and one year of later. NTX value in the urine was significantly decreased in the period of administration six months compared with before administration. Serum-NTX, BAP and OC were observed decreasing tendency in the period of administration six months compared with before administration, but not significantly. However, as for these values, appearing came back to before administration and an approximately equal value administration one year later. On the other hand, BMD and %YAM value increased an average of 3.6% and 2.2%, respectively, and these effects were maintained to the annual back for administration 1 year. In this study, we observed that leflunomid has the ability to return osteoporosis of high turn type to normal turn.

View full abstract

    We studied the anxiety about medications of 33 patients who were taking corticosteroids (CS) orally for more than two weeks, including 17 patients with rheumatoid arthritis (RA), and 16 patients with the other autoimmune diseases, bronchial asthma, or toxicoderma, and so on. The mean age was 59.5 years in the RA group and 63.8 years in the non-RA group. The mean dosage of CS was 7.4 mg/day (prednisolone equivalent) in the RA group, and 17.8 mg/day in the non-RA group. The mean duration of CS medication was 9.9 years in the RA group, and 1.2 years in the non-RA group.
    Ninety-nine percent of patients in both groups thought that the medication was necessary for their treatment, however more than 50% patients were scared by medication and 18-25% patients felt stress from taking medicine. Eighty-eight percent of RA patients were concerned about the adverse effects of CS and 65% of them answered that they felt more than one adverse effect.
    Patients of both groups were concerned about osteoporosis caused by CS. It was reported that anxiety for the adverse effects diminished adherence of medication. Strategies to improve adherence could include reducing fear of adverse effects and the adoption of a patient-oriented team approach.

View full abstract

    Psoriasis is an autoimmune and chronic skin disease. There are about 100, 000 patients with psoriasis in Japan. Six percent of these patients suffer arthralgia. Rheumatologists have to discriminate between the complicated cases with rheumatoid arthritis and psoriatic arthritis because rheumatoid arthritis is rapid and severe joint destructive disease and is coupled with systemic complications such as rheumatoid nodule, interstitial pneumonia and vasculitis.
    We examined the utility of the anti-CCP antibodies in eleven patients with psoriasis complicated by arthritis. Clinical diagnosis followed for psoriatic arthritis by the definition reported by Moll and Wright (1973) and rheumatoid arthritis by the criteria of American College of Rheumatology (1987). All was diagnosed as psoriatic arthritis and three patients with rheumatoid arthritis. It was disclosed that the sensitivity of anti-CCP antibodies in rheumatoid arthritis was 66.7%, and the specificity was 100.0% in this study.
    We also analyzed the clinical characteristics in the anti-CCP antibodies-positive and negative group. The values of CRP and MMP-3 in the anti-CCP antibodies positive-cases were revealed to be higher than in the negative group. The anti-CCP antibodies positive group showed multiple bone erosions.
    It is possible that an anti-CCP antibody was one of the factors in predicting joint destruction, irrespective of complication by rheumatoid arthritis.

View full abstract

    A 79-year-old woman had been suffering from rheumatoid arthritis with polyarthritis and morning stiffness since the age of 25 in 1951. Her disease displayed progressive deformity involving proximal interphalangeal, metacarpophalangeal, wrist and knee joints. She had been treated with 5 mg/day of prednisolone and the joint pain had been controlled. Her disease was classified as stage IV and class III. In April, 2003, she complained of dyspnea. She was admitted to the local hospital and transfferred to our hospital. Her disease was progressed with rheumatoid pleuritis and interstitial pneumonia. She was treated with 20 mg/day of prednisolone and 500 mg/day of sulphasalazine. She was discharged and controlled activity of her disease. In January, 2004, she had atrial tachycardia and was admitted to the department of cardiology in our hospital and was treated with catheter ablation. She was transferred to the department of rheumatology for control of RA. She had influenza pneumonia and was treated with Oseltamivir. When she had almost recovered from influenza pneumonia, she was suddenly developed an acute lung injury. Her symptoms were not improved with steroid pulse, antibiotics and antifungal drug. She died on the 53rd day of hospitalization. Autopsy findings revealed diffuse alveolar damage (DAD). This DAD might be caused by rheumatoid arthritis without infection or drug-induced.

View full abstract

    Objective: The object of this study is to investigate the visualization capabilities of X-ray refraction contrast imaging with in-line configuration when assessing the early form of osteoarthritis (OA).
    Methods: We prepared resected human femoral bone with known OA as well as with OAmodel rat induced by anterior cruciate ligament transaction. X-ray refraction contrast imaging was conducted at the Japan Synchrotron Radiation Research Institute (SPring8: Super Photon ring 8GeV Hyogo, Japan) with in-line configuration and compared to X-ray absorption contrast imaging scanned by a conventional X-ray source.
    Results: Refraction contrast imaging revealed articular cartilage and microstructure of bone trabecula with remarkable edge effects that could not be detected solely with absorption contrast imaging methods.
    Conclusion: We think these findings are particular to refraction contrast imaging with in-line configuration. When evaluating bony lesion and cartilage detail from early osteoarthritic disease, this method might have future potential.

View full abstract

    Fibromyalgia syndrome (FMS) is the most commonly encountered disorder among the extraarticular rheumatic diseases, and is characterized by long-lasting generalized pain of the fibromuscular tissue and various unidentified symptoms. However, diagnosis and treatment of FMS have not been discussed seriously in Japan, because disease-specific laboratory test findings are difficult to collect on its pathological state. Since the onset and clinical course of Fibromyalgia Syndrome (FMS) involves many psychosocial factors, its diagnosis and treatment crucially require the understanding of FMS from a psychosomatic perspective. In the past study, we reported that the experience of physical trauma or excessive stress underlay in the background of chronic pain in FMS. It is considered that chronic pain, numerous indefinite complaints and autonomic nervous symptoms are developed from physical and/or mental exhaustion, when anxiety, fear, obsession, depression, sorrow, anger or other psychosocial stresses, as well as physical or mental fatigue are combined with the above background. As for medication, NSAIDs were effective, especially in its early period of FMS treatment. However, in the chronic stage of FMS, tricyclic antidepressants, SSRI, SNRI and other antidepressants, and anticonvulsive agents such as clonazepam are sometimes effective, which may improve the serotonin-and noradrenalinmediated descending analgesic system, contraction of muscular and vascular systems, and/or bloodstream disorders. As a matter of fact, the largest number of physicians selected SSRI, SNRI as first-line drugs, indicating the standpoint of psychosomatic specialists to take into account the significance of psychotherapy. We tried to investigate the efficacy of Milnacipran, especially early effect for chronic pain, and discussed the application and indication of Milnacipran for FMS. Psychosomatic specialists often incorporates certain psychotherapy into treatment. Several psychotherapies are applied for treatment of FMS such as cognitive behavioral therapy (CBT), autogenic training, brief psychotherapy and general counseling. CBT is one of the most commonly used therapeutic methods in psychosomatic medicine, which seeks to develop the healthy conditions by the recovery of healthy way of thinking and behavior.

View full abstract

    Fibromyalgia (FN) is a common rheumatic disorder in American and European populations. In Japan, however, FM is not a well-accepted concept because it is a poorly recognized disorder. Epidemiological findings of Japanese patients with FM are still unclear due to a lack of nationwide epidemiological surveys. We conducted the first nationwide epidemiological survey for FM in Japan. The estimated annual number of patients diagnosed and treated in hospitals was 2,670 (95% confidence interval (CI) 1,850-3,490), and the number of patients treated by Japanese rheumatologists was 3,930 (95% CI 3, 220-4,640). Only 31.7% (734/2,313) of Japanese rheumatologists could diagnose the patient as having FM. The age distribution was from 11 to 84, with an average age of 52.3±16.2 years of age and 3.6% of them were in their childhood. The estimated onset ages were 44.0±16.1 (9-76) years, and the time elapsed from onset to the survey date was 4.7±6.7 (0-50) years. The male to female ratio was 1: 4.8, and primary FM to secondary FM ratio was 3.1: 1. Among secondary FM cases, underling disorders were as follows: rheumatoid arthritis (35.5%), other rheumatic disorders (44.1%) and others (20.4%). The Japanese patients were treated by rheumatology clinics and physicians. Most of the patients were outpatients, and only 12.5% were hospitalized. For one year, the rate of recovery from FM was only 1.5%, and a half of the patients had poor activity in daily life. These findings show that only a small portion of FM patients would be received medical management in Japan.

View full abstract