［Introduction］
    The values of serum D-dimer (DD) in patients with rheumatoid arthritis (RA) were reported to be relatively high in several studies. We analyzed the distribution of the values of serum DD and the relationship between the values of DD and the presence of deep-vein thrombosis (DVT).
［Materials and Methods］
    The serum DD was measured in 106 cases (RA 47 cases, non-RA 59 cases). For cases in which DD values were above 1.0 (μg/ml), we performed additional venography or Doppler ultrasonography to find DVT.
［Result］
    We found 11 cases of DVT (RA 8 cases, non-RA 3 cases). The incidence rates of DVT in the cases of RA and non-RA were 17%, 5% respectively (P＜0.05). In cases of RA, the values of DD in DVT-positive and DVT-negative cases were 7.8 and 3.4 respectively (P＜0.05). Positive correlation was found in the relationship between CRP and DD values in RA (P＜0.05). When a DD of 2.6 (μg/ml) was decided upon as the cutoff value for DVT, receiver-operatingcharacteristic (ROC) analysis revealed 75% sensitivity and 59% specificity.
［Conclusions］
    The result shows that the DD values are useful as a screening test to find DVT for RA patients. If a DD value of more than 2.6 is detected, ROC analyses indicate that additional examination should be performed to find DVT and furthermore to prevent pulmonary embolism.

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    To investigate the effectiveness of high-dose intermittent additive administration of mizoribine (MZB), 36 outpatients with RA who had insufficient responses to methotrexate (MTX) were enrolled in this study. 25 patients received additional use of MZB 300 mg once or twice a week (Group A). 11 other patients were treated with 100 or 150 mg/day of MZB concomitantly (Group B). We compared Group A with Group B in DAS28 (CRP) as the primary efficacy endpoint of this study. The response rate (good＋moderate) of DAS28 (CRP) was 44.0% in group A and 18.2% in B group at 3-4 months after MZB treatment. Group A demonstrated a significantly higher rate of improving anemia. The frequency of adverse effects and the abnormal test values of the 2 groups was low rate and not different. In patients with a CRP improvement rate of over 30％ at 2-4 months after the start of treatment, the rate of continuation of MZB after 12 months was 64.7% in group A and 62.5% in group B, showing that high rates of continuation were maintained. Concomitant therapy of MZB 300 mg twice a week to RA patients who responded poorly to MTX is a useful treatment with minimal adverse effects.

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Background: The pathogenesis of fibromyalgia syndrome (FMS) has not been fully elucidated, but the relationship between FMS and multiple chemical sensitivity (MCS), determined by symptomatic sensitivity to common agents encountered in modern life, has been discussed.
Methods: To evaluate MCS among patients with primary FMS (pFMS) and various inflammatory diseases, the quick environment exposure and sensitivity inventory (QEESI) was examined in 124 patients: 29 with pFMS, 18 with Sjögren syndrome (SS), 13 with Behçet disease (BD), 33 with systemic lupus erythematosus (SLE), 14 with systemic sclerosis (SSc), and 17 with other diseases (OD; various inflammatory diseases without FMS). Secondary FMS were found in 9 patients with SS, 12 with BD, 23 with SLE, 8 with SSc.
Results: QEESI revealed higher scores among pFMS, SS, BD, SLE, and SSc than OD patients. The values for Symptom Severity were 51.1±18.6 (pFMS), 32.8±20.9 (SS), 45.5±21.2 (BD), 34.8±22.3 (SLE), and 25.6±14.4 (SSc), and were significantly higher as compared to that in OD (13.8±11.1). The scores of Chemical Inhalant Intolerance were 48.1±22.0 (pFMS), 27.0±26.6 (SS), 45.8±23.2 (BD), 39.7±28.1 (SLE), and 23.9±12.6 (SSc), and were significantly higher than that in OD (and 6.7±6.0). Patients with pFMS, SS, BD, SLE, and SSc had higher values of Other Intolerance and Life Impact than the OD patients. Among the groups, pFMS and BD patients had high scores. Most of the patients with BD had fibromyalgia symptoms. The patients with primary and secondary FMS had significantly higher scores of QEESI than patients without fibromyalgia symptoms.
Conclusion: MCS may be commonly involved in the pathogenesis of pFMS, SS, BD, SLE, and SSc, suggesting that chemical agent-free conditions may improve various symptoms of patients with FMS and MCS.

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    Pulmonary arterial hypertension (PAH) is a refractory condition associated with CTD. In addition to prostanoid, bosentan and sildenafil were approved in 2005 and 2008 respectively. Outcome has improved with these drugs. We investigated the efficacy of these drugs to refractory digital ulcer. Out of 59 SSc, 27 MCTD and 102 SLE under the treatment, 14 patients with PAH (8 SSc,4 MCTD and 2 SLE) aged from 12 to 83 (mean＝55.7) were studied. Chief complaints of these patients were breathlessness (5), digital ulcer (8), and planter ulcer (1). Bosentan was administered to all patients and sildenafil to 4 patients. IVCY was added to bosentan in pediatric SSc patient. TSS was significantly improved from 29 to 14 in pediatric SSc patient with combination of bosentan and IVCY. Bosentan seems effective not only for PAH but also for refractory digital ulcer and skin sclerosis.

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    Japanese Oriental (Kampo) medicine has been widely used to treat fibromyalgia. In Kampo medicine, the determination of therapy is based on “Sho” (diagnosis of Kampo medicine). However there have not been sufficient studies of the “Sho” in fibromyalgia. We therefore investigated the “Sho” in fibromyalgia by assessing the “Sho” in 27 patients with fibromyalgia: 20 females and 7 males, mean age 52.9±15.6 (27 to 89). The result showed 3 patients with “Jissho” (hyperfunction of body energy), 15 patients with “Kyojitsukansho” (medium of hyperfunction/hypofunction of body energy) and 9 patients with “Kyosho” (hypofunction of body energy). All patients showed “Kikyo” (deficiency of “Ki” (vital energy)), “Kiutsu” (insufficient circulation of “Ki” and “Ki” stasis in an organism)”, and “Oketsu” (insufficient blood-circulation and blood stasis). The “Oketsu” score of the 15 patients using Terasawa’s criteria were 27.0～67.0, mean score 43.5±10.1. Nine of the 15 patients showed severe “Oketsu”, which was indicated by a total score of more than 40 points. This finding indicated an intimate correlation with fibromyalgia and“Oketsu”.Several reports showed the presence of abnormal microcirculation in fibromyalgia. Abnormal microcirculation is considered to be related to “Oketsu”. Therefore, we considered that “Oketsu” is an important pathological condition to investigate and treat with fibromyalgia.

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    Autoantibodies to ribosomal P proteins (anti-P) are detected in 12-16% of patients with systemic lupus erythematosus (SLE), and have been found to be associated with neuropsychiatric manifestations of the disease. Moreover, recent studies have disclosed the association of anti-P with hepatitis and nephritis in SLE. The presence of an epitope that is antigenically related to the carboxyl terminus of ribosomal P proteins has been demonstrated on the surface of human hepatoma cells, neuroblastoma cells, and endothelial cells. Recent studies have shown that anti-P reacts with activated T cells, but not with B cells. However, the presence of the epitope recognized by anti-P on human monocytic cell lines has not been elucidated. In the current studies, we used affinity-purified IgG from anti-P positive lupus patients to explore whether anti-P reacts with human monocytic cell line THP-1 cells. Flow cytometry analysis demonstrated that THP-1 cells constitutively expressed the ribosomal P epitope. Of note, anti-P enhanced the production of vascular endothelial growth factor (VEGF) of THP-1 cells in a dose response manner. These results suggest that anti-P might promote vascular permeability and facilitate the entry of immunocompetent cells into the site of inflammation, including the central nervous system, through the induction of vascular endothelial growth factor on activated monocytelineage cells.

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    A 47-year-old woman presented at her family physician complaining mainly of dyspnea and was admitted to our hospital with a diagnosis of acute cardiac failure. Cardiac failure did not improve despite oxygen therapy, diuretics, and other treatment; her condition deteriorated rapidly and she entered a state of shock. She was placed on a respirator and received assisted circulation via intra-aortic balloon pumping. A diagnosis of systemic lupus erythematosus (SLE) was made, based on the presence of leukocytopenia, positive anti-nuclear antibody, positive anti-ds-DNA, and arthritis. As SLE-associated cardiac lesions were suspected, steroid pulse therapy and oral methylprednisolone administration (50 mg/day) were started, and her medical condition quickly recovered. Myocardial biopsy revealed marked fibrosis among the cardiac muscle cells with no inflammatory cell invasion of the myocardium, establishing a diagnosis of acute cardiomyopathy caused by SLE.
    Pericarditis, myocarditis, and cardiomyopathy are all recognized as SLE-associated cardiac lesions. We herein report this case, firstly because SLE rarely presents initially with the onset of acute severe cardiomyopathy, as occurred in this case, and secondly, in view of this rarity, we consider that this case is educational for both primarycare physicians and specialists alike.

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    A 30-year old female was admitted to our hospital because of a refractory oropharyngeal ulcer from Behcet’s disease. She had been suffering from Behcet’s disease since she was 16 years old. Salazosulfapyridine, azelastine hydrochloride, colchicine, azathioprine, predonisolone and methotorexate, were not effective. She was hard to eat and drink about six months.
    Furthermore, she developed pneumocystis pneumonia, drug eruption due to methotorexate and trimethoprim sulfa, weight loss (7 kg), and steroid psychosis. Leukocytapheresis was effective for treating the oropharyngeal ulcer. Inflammatory markers normalized and prednisolone was reduced in a stepwise fashion.
    The cause of Behcet’s disease is unknown but it is assumed that hyperactivation of leucocytes and platelets is deeply related to the condition. We report a case of Behcet’s disease complicated with refractory oropharyngeal ulcer successfully treated by leukocytapheresis.

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    We report a case of 79-year-old woman with an inflammatory aneurysm occurred in a thoracic aorta. The patient was admitted to our medical center because of continuous pyrexia of unknown origin. A marked elevation of serum C-reactive protein level was observed. Infections, collagen vascular diseases and neoplastic disease including malignant lymphoma were found to be unlikely by hematologic, serologic and radiographic examinations. Autoantibodies including antineutrophil antibodies were undetectable. Only enhanced-computed tomography revealed an abnormal finding, so-called mantle core sign, in thoracic aorta, which is specific for inflammatory aortic aneurysm. In general, the disease occurs in abdominal aorta, and the involvement of thoracic aorta like this case is rare. Usually, an aortic aneurysm occurs based on atherosclerotic change of blood vessels, and the aspects of an inflammation of large vessels have been focused recently at the pathological findings, the cytokine profiles and the immunological abnormalities. Thus, the differential diagnosis of the disease from Takayasu arteritis, a prototype of a large vessel vasculitis, is often difficult. The diagnostic procedure to differentiate from the other large vessel vasculitis, Takayasu arteritis and atherosclerotic diseases in abdominal aorta, is discussed.
    The patient was given oral prednisolone which lead to favorable outcome.

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    Hypertrophic pachymenigitis is a rare disease for which the pathogenesis is almost unknown. The following mechanisms have been blamed for causing hypertrophic pachymeningitis: infection, chronic inflammatory disease, trauma, medicine etc. In this case, hypertrophic pachymenigitis was complicated with MPO-ANCA positive Wegener’s granulomatosis. A 50-yearold woman presented with bilateral refractory otitis media and sinusitis. Histopathological examination of the operated specimen taken from otitis media revealed granulomatous inflammation with giant cell infiltration. Ga-DTPA-enhanced magnetic resonance imaging (MRI) revealed a thickening of dura mater in the frontal cranial fossa and tentorium cerebelli. We diagnosed pachymeningitis associated with MPO-ANCA positive Wegener’s granulomatosis. Cyclophosphamide combined with prednisolone effectively improved the symptoms. In the case of MPO-ANCA positive hypertrophic pachymeningitis, we have to consider the differential diagnosis including of Wegener’s granulomatosis.

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