[in Japanese]

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[in Japanese]

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    The purpose of this study was to examine the relationships between depression and demographics, disease activity, physical disability, and negative emotional suppression in patients with rheumatoid arthritis. A total of 113 patients who visited the outpatient clinic of the Department of Internal Medicine at Kitasato University Hospital agreed to participate in the study. Of these patients, 26 failed to complete the questionnaire. Therefore, data from the remaining 87 patients (18 men and 69 women; mean age±SD, 60.7±11.7 years) were analyzed. Patients were asked to provide demographics and respond to the Modified Health Assessment Questionnaire (mHAQ), Negative Emotional Suppression Scale (NESS), and Beck Depression Inventory-Second Edition (BDI-II). The attending physician evaluated disease activity with the Disease Activity Score 28-CRP (DAS28-CRP). The average BDI-II score was 12.1 (SD＝8.7),and 14.9% of patients felt depression. BDI-II was positively correlated with gender(r＝0.243, p＜0.05), DAS28-CRP(r＝0.341, p＜0.01), mHAQ (r＝0.464, p＜0.01), and suppression of anxiety (r＝0.201, p＜0.10). In the present study, approximately one-fifth of patients reported moderate or severe depression. Depressed patients had severe rheumatoid arthritis and physical disability, and were more likely to suppress their anxiety. Medical staff members and health care professionals need to manage disease activity and maintain physical activity of patients. This study also suggests the importance of depression management by medical staff members and health care professionals, particularly with respect to psychological characteristics.

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Purpose: To investigate the factors related to serum TNF-α and IL-6 in patients with MTX treatment, we assessed clinical factors related to TNF-α and IL-6.
Methods: Serum TNF-αand IL-6 concentration were analyzed in 24 patients of RA, comprising 3 males and 21 females, with mean age of 56.6 years, mean disease duration of 13.3 years, mean MTX dose of 5.48 mg/weeks, mean prednisolone dose of 3.98 mg/day.
Results: The mean TNF-αwas 3.63±2.72 pg/ml and IL-6 was 30.0±26.0 pg/ml in total number of patients. TNF-αwas 1.3 times the normal level, showing positive changes in 46% (11/24) of the cases, and IL-6 was 7.5 times showing positive changes in 100% (24/24) of the cases. The relationship between TNF-α and CRP, IL-6 and age IL-6 and MMP-3 showed significant correlation respectively.IL-6 and the dose of MTX had a significant negative correlation.
Conclusion: Serum IL-6 tended to be high rather than TNF-αin MTX treatment. The serum IL-6 was low in the high dose of MTX. It was useful to use the marker of CRP correlated with TNF-α and MMP-3 correlated with IL-6 in the treatment of MTX.

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    Purpose: To verify the usefulness of aggressive treatment of early-onset rheumatoid arthritis with combination therapy of oral disease-modifying antirheumatic drugs (DMARDs). Patients and treatment: We retrospectively analyzed up 5-year therapeutic process in 27 rheumatoid arthritis (RA) patients with disease duration of 2 years or less, who consented to aggressive treatment with oral DMARDs in order to achieve remission. These patients were selected from among those who visited Tokorozawa Central Hospital between July 1997 and January 2006. When the treatment was started, tender joint count, swollen joint count, and C-reactive protein level were monitored weekly or biweekly. After the disease activity of RA fully decreased, these parameters were monitored monthly or bimonthly. If any of these indicators did not improve, the dose of the DMARD(s) was increased and/or additional DMARDs were prescribed. Results: Follow-up showed that 19 (70%) of the 27 patients achieved clinical remission within1year.The remission status remained almost unchanged during 5 years of follow-up, and in the 5th year of observation, 21 (84%) of the 25 patients who were followed up showed clinical remission. The health assessment questionnaire (HAQ) score for the 5th year was evaluated in 23 patients (median HAQ score, 0.125), and 65% of them achieved functional remission with HAQ scores of less than 0.5, the levels at which the patients’ quality of life was relatively high. Conclusion: The usefulness of aggressive treatment with oral DMARDs was confirmed.

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Objective: To examine whether to continue treatment with TNF inhibitor or switch to biological agent with a different target of action in outpatients with RA refractory to TNF inhibitor as the 1st biologic.
Subjects and methods: Since four biologics became available for our use in July 2008, we have examined 22 RA patients for at least 1 year of observation who were administered 2nd biologics: a TNF inhibitor in 11 subjects (T group) or an anti-IL-6 agent in 11 subjects (I group).
Results: All subjects received previous treatment of a single TNF inhibitor. The ratios of MTX combination as 2nd biologics were 36.3% and 18.2% in the T and I group (P＝0.635), and the ratios of PSL combination were 90.9% and 81.8% in the T and I group, respectively (P＝1.000). Mean DAS28-CRP values before the start and after 48 weeks (final observation) were 4.87±1. 16 and 4.62±1.27 in the T group, and 4.87±1.47 and 1.93±0.91 in the I group, respectively. The 48-week treatment completion rates were 36.4% (4/11) in the T group and 81.8% (9/11) in the I group. The numbers of subjects who discontinued the treatment due to inadequate response were 4 and 1 in the T and I groups, respectively, and the numbers of failures due to adverse events were 3 in the T group and 1 in the I groups.
Conclusion: Switching to an anti-IL-6 agent with a different mechanism of action may have a beneficial effect on patients with RA refractory to TNF inhibitor as the 1st biologic.

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    Mizoribine (MZR) was administered at a dose of 150 mg once daily to 21 patients with rheumatoid arthritis (RA) associated with dry mouth who had not responded well to diseasemodifying anti-rheumatic drugs or methotrexate. We evaluated the usefulness of MZR for treatment of RA, its effect on dry mouth, and the association between these effects and the blood MZR concentration. Significant differences in the tender joint count and swollen joint count were noted at 1 and 3 months, and 3 months after MZR treatment, respectively. There were no significant differences in VAS and CRP between before and after the treatment. Significant differences in DAS28-CRP were noted at 3 months after the treatment. According to the EULAR criteria, the clinical response was good in 3 patients and moderate in 5 patients, with 8 of 18 patients (44.4%) showing a moderate or greater response at 3 months after treatment. The Saxon test showed a significant improvement in saliva production after 3 months. There was no association between blood MZR concentration and RA response or the improvement in saliva production. The results suggest once-daily administration of MZR at a dose of 150 mg to be a potential method of treating RA associated with dry mouth.

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Objective: We tried to use an ultrasound-Doppler guided technique for visualization of needle placement within the temporomandibular joint in patients with rheumatoid arthritis (RA).
Methods: The efficacy of temporomandibular joint corticosteroid injection and a liniment as a positive control were compared. Randomization was performed and 14 outpatients with RA were treated with their respective treatment. The mouth opening length at 4 weeks was compared with those at baseline in each treatment group.
Results: At the 4 week assessment, participants in the temporomandibular joint injection group (n＝8) demonstrated significantly increased mouth opening length (P＜0.0001) in comparison with their baseline assessments. The significant differences were not found in the group with the liniment (n＝6), (P＝0.61).
Conclusion: The ultrasound-Doppler guided technique for temporomandibular joint injection with corticosteroid is suitable for patients with RA who have complained of severe pain in their jaws when chewing.

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    A 45 year-old woman with rheumatoid arthritis (RA) showed symptoms at the age of 41.She was treated with disease modifying antirheumatic drugs (DMARDs). Blood examination data showed gradual improvement, but the patient’s knee joint destruction developed. The attending doctor (physician) said “You need a total knee arthroplasty (TKA) operation”. The patient said “I’ve always complained of knee joint pain, but the doctor didn’t conduct X-ray examination. I can’t consent any more”. The attending doctor had not recorded knee joint pain. Then, she changed hospitals, and consulted our hospital. Her knee joints were destructed (Stage 4). We tried hyaluronic acid injection in knee joints, but her knee joint pain did not improve. Finally, we enforced TKA. She, and her family demanded clinical record be presented to the previous hospital. However, even if her previous doctor did make joint injections, knee joint destruction was not prevented. Although RA therapy is advanced, it is not perfect. If the patient experienced any falls, the previous doctor did not record the details in medical reports. In the future, there is a possibility that lawyers could file a medical lawsuit. This report suggests, that recording detailed medical reports (complaints, physical examinations, operations and so on) as soon as possible is important.

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    A 78 year-old woman was admitted into our hospital due to recurrent abdominal pain. She was diagnosed with Sjögren syndrome when she was 66 years old. Dietary restriction transiently improved her abdominal pain. However, with the resumption of diet, her abdominal pain was exacerbated again. The recurrent abdominal pain was resistant to gastrointestinal medicines. The elevation of soluble interleukin-2 receptor was recognized but not significant. While ⁶⁷Gascintigraphy showed positive accumulation in the right lower quadrant of the abdomen, the diagnosis could not be defined through either colonoscopy or capsule endoscopy. During these examinations, she presented the symptom of acute abdomen. An emergency operation revealed that the acute abdominal symptom was caused by the perforation of the small intestine pathologically diagnosed as a localized diffuse large B cell lymphoma. Sjögren syndrome often combines malignant lymphomas. However, the incidence of primary lymphoma from small intestine is rare. Furthermore, in this case, the titer of soluble interleukin-2 receptor, ⁶⁷Gascintigraphy and capsule endoscopy were not useful for the diagnosis or identification of the lymphoma. These results might suggest that screening tests including exploratory laparotomy for malignancy in the gastrointestinal tract should be intensively performed if patients with Sjögren syndrome have unexplained complaints in the abdomen.

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    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multisystem involvement, and mainly occurs in young women. In contrast, late onset SLE, which is diagnosed at or above 50 years of age, accounts for about 12％-18％ of all patients with SLE. In this group, the occurrence of serositis and lung involvement is higher, but skin manifestations, photosensitivity, arthralgia, and nephritis are less frequent in comparison to early onset lupus patients. Moreover, there are 3 case reports with very late onset SLE which was diagnosed at or above the age of 80.Here, we report an 83-year-old man presenting with fever, polyarthralgia, and massive pericardial effusion. Infection and malignancy were ruled out, and positive anti-nuclear antibody, anti-DNA antibody, and lymphopenia led to the diagnosis of SLE. One week after initiation of prednisolone, however, he died suddenly. In the autopsy, visceral pericardium and parietal pericardium were tightly adhered and pericardial space was nearly obliterated. Pericardial effusion was bloody, but scarcely observed. Diffuse deposition of IgG at the site of pericarditis was also observed. The cause of his death was due to fibrinofibrous pericarditis. To date, this is the first case of very late onset male SLE with fibrinofibrous pericarditis and suggests that fibrous organization of pericardial effusion in lupus patients is more progressive than we had thought.

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    A 66-year-old man visited with the chief complaints of proximal muscle pain and fatigue. He was diagnosed with dermatomyositis (DM) by further evaluation. We started the administration of prednisolone (PSL) 70 mg/day (1 mg/kg/day). After a short time of PSL administration, black stool, hemoglobin reduction and thrombocytopenia were observed. Esophagogastroduodenoscopy (EGD) revealed multiple shallow ulcers in the gastric antrum and duodenum. Cytomegalovirus (CMV) antigen (C7-HRP) was slightly positive, but no giant cells or inclusion bodies were detected in the biopsy tissue from the ulcer. However, CMV gastroenteritis was strongly suspected, which led to the start of ganciclovir and γ-globulin administration. Later, CMV DNA-PCR in the peripheral and bone marrow blood at the time of the first gastrointestinal bleeding turned out to be positive. The CMV antigen, CMV DNA-PCR, and endoscopic findings improved. He was discharged but thrombocytopenia and hemoglobin reduction were prolonged. So, we retried bone marrow puncture in clinic. There was dysplasia in multiple lineages and fewer than 5% blast cells in the bone-marrow aspiration sample. He was diagnosed with myelodysplastic syndrome (MDS). Although many case reports of autoimmune diseases associated with MDS have been reported, dermatomyositis associated with MDS is very rare. We report the case of dermatomyositis associated with myelodysplastic syndrome, accompanying intractable gastrointestinal bleeding due to cytomegalovirus gastroenteritis.

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