Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.

Infrared Thermography and Ultrasonography of the Hands in Rheumatoid Arthritis Patients.

Ultrasonography (US) and power Doppler US (PDUS) are used worldwide for diagnosing rheumatoid arthritis (RA). Superb microvascular imaging (SMI) is a good tool for evaluating inflammatory activity. Thermal imaging is a noncontact, noninvasive procedure using skin temperature measurement. We report a case wherein the thermal and ultrasound images of the hand are compared and evaluated for inflammatory activity in patients with RA. Case: US imaging of the left hand of a 75-year-old woman with RA revealed a hypoechoic lesion of the left wrist joint. PDUS and SMI evaluated blood flow according to the blood flow at Grade 2. The temperature of the hypoechoic lesion with high blood flow was higher than that of the same location on the opposite side. This study shows that combining thermal and blood flow images may be useful for detecting inflammatory activity levels in RA patients.

Association of higher arterial ketone body ratio (acetoacetate/ß-hydroxybutyrate) with relevant nutritional marker in hemodialysis patients.

BACKGROUND: An association of higher levels of ß-hydroxybutyrate (ß-HB) in serum with greater mortality in hemodialysis (HD) patients has been reported. This study examined the significance of arterial ketone body ratio (AcAc/ß-HB), a relevant marker of energy state, in HD patients. METHODS: The levels of arterial AcAc and ß-HB, and AcAc/ß-HB ratio were determined in 49 HD patients just before undergoing an HD session. Additionally, changes in those levels during the session were examined to investigate their associations with clinical nutritional markers. RESULTS: Arterial ß-HB, but not AcAc, was significantly higher at the baseline in 25 patients with type 2 diabetes mellitus (T2DM) as compared to 24 non-DM patients, with a significant reduction in arterial AcAc/ß-HB ratio seen in those with DM. Although the arterial AcAc/ß-HB ratio before the HD session was significantly higher in the non-DM group, it did not differ significantly after the session between the groups, indicating a faster rate of ß-HB disappearance from circulation in non-DM HD patients during the interdialytic period. Multiple regression analysis, which included age, gender, presence/absence of DM, log HD duration, log ß-HB, and log AcAc/ß-HB ratio as independent variables, revealed an independent and significant association of log AcAc/ ß-HB ratio, but not log ß-HB, with serum albumin and uric acid. CONCLUSION: We found that a decreased AcAc/ß-HB ratio resulting from increased ß-HB, but not increased ß-HB itself, was a significant factor independently associated with decreased levels of serum albumin and uric acid, known to be related to higher mortality in HD patients. Furthermore, it is possible that higher mortality in DM HD patients can be explained by reduced arterial AcAc/ß-HB ratio.

Acute pericarditis as the first manifestation of familial Mediterranean fever: a possible relationship with idiopathic recurrent pericarditis.

A 56-year-old man was admitted to our hospital due to periodic episodes of acute pericarditis. These episodes occurred monthly along with a high fever and elevation of the C-reactive protein (CRP) level. The patient became afebrile and his CRP level decreased following the administration of a non-steroidal anti-inflammatory drug. A mutation analysis revealed the heterozygote of the familial Mediterranean fever (FMF) gene (E84K, G304R). This finding confirmed our diagnosis, and we treated the patient with colchicine. He responded to treatment and has been visiting our hospital without disease recurrence. FMF should be included in the differential diagnosis of repeated episodes of pericarditis.

Clinical experiences of bixalomer usage at our hospital.

In 2012, bixalomer was launched as new non-calcium (Ca) containing phosphorus (P) binder, increasing the choices available for the treatment of hyperphosphatemia. In this study, among the maintenance dialysis patients at our hospital, we newly administered bixalomer to 21 patients who were not receiving any P binders, and switched to bixalomer for 13 patients who had been receiving sevelamer hydrochloride and 23 patients who had been receiving lanthanum carbonate. The initial dosage of bixalomer was set as 1500 mg/day for new administration patients and dosage equivalent to that of the previously-used P binder for patients who were switched to bixalomer. The dosage of bixalomer was increased if the effects were insufficient. The serum P, Ca and intact parathyroid hormone concentrations as well as serum pH, HCO3 concentration and base excess were evaluated prior to administering bixalomer, 3 months and 6 months after administering bixalomer. For the group who were newly administered bixalomer, significant reductions in serum P concentrations were seen (P<0.01) and no significant changes were seen in clinical test items that serve as indices for acidosis. For the group who were switched from sevelamer hydrochloride to bixalomer, significant reductions in serum P concentrations were seen (P<0.01) together with significant improvements in acidosis (P<0.01). For the group who were switched from lanthanum carbonate to bixalomer, by increasing the dosage of bixalomer to approximately three times the dosage of lanthanum carbonate, it was possible to maintain post-switch serum P concentrations at almost the same levels as before the switch. Furthermore, there were minor, yet significant improvements in acidosis (P<0.01). From these results, it was shown that bixalomer can be useful treatment alternative in dialysis patients for whom it is necessary to change the P binder due to insufficient management of serum P concentrations or development of acidosis.

Beneficial effect of risedronate on arterial thickening and stiffening with a reciprocal relationship to its effect on bone mass in female osteoporosis patients: a longitudinal study.

AIMS: A longitudinal study was performed to examine the effect of risedronate on arterial thickening and stiffening in postmenopausal female osteoporosis patients. MAIN METHODS: Patients treated with risedronate (2.5mg/day) (n=33) and those that did not receive risedronate (n=30, control group) were monitored over a 1-year period. Bone metabolic markers, bone mineral density (BMD) of the femur neck (FN), brachial-ankle pulse wave velocity (baPWV), and intima-media thickness at the carotid artery (CA-IMT) were measured. KEY FINDINGS: At baseline, there was no significant difference in blood pressure, serum lipid profiles, FN BMD, baPWV and CA-IMT between the risedronate-treated patients and the controls. Baseline levels of FN BMD were significantly negatively correlated with those of CA-IMT and baPWV. During the study, FN BMD increased significantly in the risedronate group (p=0.0097), but decreased significantly in the control group (p=0.0013). BaPWV and CA-IMT did not change significantly in the risedronate group, but both increased significantly in the control group. The percentage change in FN BMD over the study period showed a significant negative correlation with those for baPWV (r=-0.294, p=0.0262) and CA-IMT (r=-0.305, p=0.0234) in all subjects (risedronate-treated patients and controls). SIGNIFICANCE: In addition to increasing BMD, risedronate significantly suppressed the progression of arterial thickening and stiffening in postmenopausal osteoporotic patients over one year. These changes may indirectly be due to the effect of risedronate on bone.

Time-course of health status in patients with rheumatoid arthritis during the first year of treatment with infliximab.

OBJECTIVES: A longitudinal study was performed to examine changes in health status in comparison with rheumatoid arthritis (RA) inflammation in patients with RA during the first 54 weeks of infliximab (IFX) treatment. METHODS: Health status in active RA patients (n=13) was assessed monthly using the Arthritis Impact Measurement Scale 2 (AIMS2) and the VAS-GH during the first year of IFX treatment. Simultaneously, RA activity was assessed using inflammation markers, MMP-3 and the Disease Activity Score in 28 joints (DAS-28) based on CRP [DAS-28(CRP)] and ESR[DAS-28(ESR)]. RESULTS: Serum CRP and ESR decreased significantly from 2.14+/-0.52mg/dL and 56.9+/-6.96mm/h, respectively, at baseline to 0.24+/-0.11mg/dL and 31.6+/-4.39mm/h, respectively, at 2 weeks after initiation of IFX. Other inflammatory markers and MMP-3 were also suppressed significantly after 2 weeks of IFX treatment. DAS-28(CRP) and DAS-28(ESR) were also significantly decreased after 2 weeks and suppression of both DAS values remained significant until 54 weeks of IFX treatment. After initiation of IFX, patient-reported general health also showed a significant improvement based on the changes in the six summary component scores on the AIMS2 (physical, affect, symptom, role, social interaction, and patient satisfaction). These scores all improved progressively until 14-18 weeks after initiation of IFX treatment, and then exhibited a temporary but insignificant exacerbation. The six components of the physical score also improved in a time-dependent manner until 14-18 weeks, but the scores for walking and bending, hand and finger function, arm function, self-care, and household tasks showed significant exacerbation at 22-30 weeks. The score for mobility level did not show this change. CONCLUSION: IFX treatment significantly improved both RA disease activity and health status in active RA patients. Time-dependent improvement of ADL until 14-18 weeks after initiation of IFX treatment, as reflected in the six components of the physical score, might have contributed to the temporary exacerbation of health status thereafter in these patients.

Effects of pravastatin on serum osteoprotegerin levels in patients with hypercholesterolemia and type 2 diabetes.

Osteoprotegerin is a secretory glycoprotein. Recent experimental findings have suggested that osteoprotegerin may protect against vascular calcification and/or atherosclerosis. In humans, osteoprotegerin levels are positively correlated with the presence and severity of coronary artery disease and the progression of atherosclerosis. However, it is unclear how osteoprotegerin levels are regulated. Statins are known to have beneficial pleiotropic effects against atherosclerosis beyond their lipid-lowering effects. In this study, we examined whether treatment with pravastatin can alter osteoprotegerin levels in patients with hypercholesterolemia and type 2 diabetes. Osteoprotegerin levels were significantly increased from 6.64 +/- 2.18 pmol/L at baseline to 7.08 +/- 2.29 pmol/L (P = .024) after 3-month treatment with pravastatin. These increases in osteoprotegerin levels remained after 6 months of treatment (7.05 +/- 2.22 pmol/L, P = .026). These findings suggest that pravastatin may exert its pleiotropic effects in part through alteration of osteoprotegerin levels.

Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis.

OBJECTIVE: We recently reported that rheumatoid arthritis (RA) patients had increased intima-media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes. METHODS: We studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high-resolution B-mode ultrasonography. The second examination was performed 18-36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium-to-creatinine ratio). RESULTS: RA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C-reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium-to-creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium-to-creatinine ratio were significantly and independently associated with the increase in IMT of the CCA. CONCLUSION: Patients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes.

[Depressive tendency in patients with RA].

OBJECTIVES: To determine if depression scores are higher in patients with RA and to identify risk factors for depression. METHOD: The subjects were 287 RA in-patients and outpatients. We investigated the tendency of depression by SDS of Zung and whether SDS is correlated with age, face scale, VAS (visual analog scale), MHAQ, class, BSG and CRP. We compared the frequency of depression tendency between those who took steroid and those who did not. Among 238 cases that we studied, 131 patients took steroid hormone and the rest did not. RESULTS: It was found that 113 out of 287 patients (about 39%) showed depression tendency. SDS was correlated with face scale (r = 0.55198 P = 0.0001) followed by VAS (r = 0.40772 P = 0.0001). However, SDS was not correlated with BSG, CRP, age and duration range. For the group who took steroid hormone, the average score of SDS was 38.63 (+/- 8.37). The average score for the other group who did not take steroid was 35.98 (+/- 7.97). As a result, it was measured by T-value that the group who took steroid hormone had higher SDS than the other group who did not take steroid.

Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis.

OBJECTIVE: To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA. METHODS: We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). IMT was measured on digitized still images of the common carotid and femoral arteries obtained by high-resolution ultrasonography (10-MHz in-line Sectascanner). Laboratory variables relevant to RA activity were measured by routine methods. The degree of RA progression was assessed by scoring (Larsen method) metacarpophalangeal (MCP) joints on hand radiographs. Activities of daily living were determined by a modified Health Assessment Questionnaire (M-HAQ) score, and physical activity levels were assessed by ultrasound measurement of the calcaneus (expressed as the osteo-sono assessment index [OSI] Z score). RESULTS: Common carotid and femoral artery IMTs were significantly higher (P < 0.05) in RA patients (mean +/- SD 0.641 +/- 0.127 and 0.632 +/- 0.125 mm, respectively) compared with controls (0.576 +/- 0.115 and 0.593 +/- 0.141 mm, respectively). Multiple regression analysis revealed a significant association between RA and the common carotid artery IMT. Moreover, the common carotid artery IMT in RA patients was positively associated with disease duration, the MCP joint Larsen score, and the M-HAQ score, and was negatively associated with the calcaneus OSI Z score. No significant association was found between corticosteroid treatment and common carotid artery IMT. CONCLUSION: RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.