A 40-year-old woman who had bilateral swelling in the eyelids and submandibular region was admitted. Clinical findings suggested she had primary Sjögren’s syndrome. Laboratory data showed glucosuria, positive CRP (0.50 mg/dl), liver dysfunction (AST 53 U/l, ALT 101 U/l, γ-GTP 241 U/l, ALP 914 U/l, LAP 496 U/l), hyperglycemia, hypergammaglobulinemia (IgG 3450 mg/dl, IgA 91 mg/dl, IgM 80 mg/dl), hypocomplementemia (C3 73 mg/dl, C4 2 mg/dl, CH50 < 19.0 U/ml), renal tubular dysfunction (urine N-acetyl-β-d-glucosaminidase 8.6 U/l, urine β2-microglobulin 83 μg/l), and urinary concentration defect. Ammonium chloride loading test was normal. Gallium-67 scintigram indicated abnormal uptake in bilateral lacrimal glands, submandibular glands, and kidneys. A diagnosis of Mikulicz’s disease and interstitial nephritis was made, since biopsy specimens of her lacrimal gland and minor salivary gland showed diffuse infiltration of lymphocytes. Renal biopsy specimens also showed severe interstitial infiltration of lymphocytes. Symptoms and laboratory data normalized in response to methylprednisolone pulse therapy and prednisolone 60 mg/day. This case of Mikulicz’s disease complicated with interstitial nephritis was successfully treated by high-dose corticosteroid.
Abstract Objectives Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid‐induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. Methods Twenty‐five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density ( BMD ) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. Results Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. Conclusions Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid‐induced osteoporosis.
Individuals with rheumatoid arthritis (RA) are at a 2-fold increased risk of sudden death compared with age- and gender-matched controls without RA. Although mechanisms underlying the increased risk are yet unclear, evidence indicates effects of systemic inflammation on ventricular repolarization. Accordingly, corrected QT (QTc) interval prolongation is more frequent in patients with RA than in those without RA. A previous pilot study reported that tocilizumab (TCZ) normalizes the QTc interval by dampening systemic inflammation.
Objectives
Our study prospectively evaluates TCZ treatment effects on the QTc interval of patients with RA without cardiac symptoms and explores the association between this QTc interval and RA disease activity and severity measures.
Methods
This prospective interventional study was conducted between March 2012 and August 2015 at the Itabashi Chuo Medical center. Patients who fulfilled the American College of Rheumatology (ACR) RA classification criteria or the 2010 ACR/ European League against Rheumatism RA criteria were included. Exclusion criteria included diabetes, history of cardiovascular events, hypertension (systolic blood pressure (BP) >140 mm Hg and/or diastolic BP >90 mm Hg), dyslipidemia (LDL cholesterol levels >140 mg/dL, HDL cholesterol level <40 mg/dL, or triglyceride level >150 mg/dL), cardiomyopathy, renal disease, and current atrial fibrillation. Age- and gender-matched healthy controls without any cardiac symptoms were selected. Patients with active RA with inadequate clinical response to methotrexate (MTX) were administered tocilizumab (TCZ 8 mg/kg IV every 4 weeks or 162 mg SC biweekly). Electrocardiography and clinical and biological monitoring were performed at baseline and 24 weeks after TCZ treatment in patients with RA.
Results
Ninety patients with RA (mean age: 56.4±10.4 yers; 85% female) and 40 age and gender matched healthy controls (mean age 55.6±3.4 years; 86% female) were included, of which 20% and 13% of RA patients received antihypertensive and antihyperlipidemia therapy, respectively. No significant differences were observed in mean Framingham 10 scores between healthy controls and patients with RA at baseline. The 24-week Simplified Disease Activity Index scores were significantly lower than those at baseline. Using previously established cutoffs (440 ms), we identified 8 (10%) patients with abnormal QTc interval prolongation. However, QTc intervals at baseline were higher in patients with RA than in controls (mean SD 420.3 ± 35.8 msec, mean SD 411 ± 31.2 msec; p=0.04). The QTc interval decreased by 20.9 msec from baseline to 24 weeks (p=0.001) following TCZ treatment. QTc interval prolongation at baseline was significantly correlated with the anticyclic citrullinated peptide antibody (ACPA) at baseline (p=0.003). ACPA at baseline (p=0.001) was associated with %change in QTc interval. Furthermore, no significant associations between QTc interval and RA activity were observed.
Conclusions
Tocilizmab treatment in patients with RA decreases QTc interval. Furthermore, anti-arrhythmic potential of TCZ treatment may have beneficial effects in patients with RA. Our results provide further evidence regarding the close association between ACPA degree and QTc intervals.
A 64-year-old woman, who had been treated for gastric diffuse large B-cell lymphoma (DLBCL) by total gastrectomy and received 3 courses of CHOP therapy at 61 years of age, was diagnosed with recurrence of DLBCL in the small intestine. After the small intestinal tumor was resected, multiple metastases were found in the liver. Because intensive chemotherapy was difficult for her poor performance status, 50 mg of etoposide daily by oral was administered for 21 consecutive days. After one course of chemotherapy, liver metastases and lymph node swelling almost disappeared without severe adverse effects, and after five courses she achieved complete remission. Though DLBCL invaded the central nervous system, the abdominal regions had been free from recurrence for 12 months. This case report suggests that oral etoposide therapy is useful for gastrointestinal DLBCL which has metastasized to the liver.
Systemic sclerosis (SSc) has an increased prevalence of cardiac involvement despite often being clinically silent. When clinically evident, cardiac involvement decreased the 70% 5-year mortality of SSc. Cardiac magnetic resonance imaging (CMR) is useful in SSc beause it focuses on late gadolinium enhancement (LGE) abnormalities and ventricular morphology and function.
Objectives
We aimed to assess the prevalence of subclinical myocardial involvement by left ventricular (LV) function and structure on CMR. We evaluated the relation between myocardial abnormalities and LV geometry.
Methods
This study compared consecutive female SSc patients without cardiac symptoms and healthy female controls with no history or clinical findings of systemic and pulmonary hypertension by echocardiography, coronary artery disease, valvular heart disease, atrial fibrillation, diabetes mellitus, and dyslipidemia. All underwent non-contrast or contrast CMR on a 3.0-T scanner. LV function was measured using ejection fraction (EF), end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and cardiac output (CO). LV hypertrophy was measured by absolute LV mass (LVM) and LVM index (LVMI) determined by LVM/body surface area. LGE was obtained to assess myocardial fibrosis. Myocardial inflammation was assessed by black- blood T2WI. Serum BNP concentrations were measured simultaneously.
Results
There were 44 SSc patients with a mean age of 57.1±8.7 years; 20 had diffuse type and 24 had limited type. There were 20 healthy controls with a mean age of 56.9±3.1 years. There were no significant differences in terms of age, gender, and cardiovascular risk factors. Compared with the control, SSc patients had a significantly higher EDV with tendency towards a high LVMI. There was no difference in EF. LGE (+) was detected in 25 of 44 (57%) SSc patients; LGE was in a linear pattern without coronary distribution in 13 (52%) SSc patients. T2WI was observed in 11 of 44 (25%) SSc patients. There were no differences in LGE and T2WI between the diffuse and limited type. The BNP level of the SSc group was significantly higher than that of the control group (P=0.04). The mean BNP level of SSc patients with LGE was significantly higher than that of SSc patients without LGE (P<0.0001). BNP level in SSc patients was significantly correlated with LVMI (P<0.0001) but not correlated with EF. Eccentric hypertrophy was observed in 52% of LGE (+) patients. LGE (+) was correlated with (+) anti Scl-70 antibody (P=0.004). After adjustment for age, disease duration, anti Scl-70 antibody, and BNP, SSc with LGE did not have a modified association with LVMI.
Conclusions
SSc patients without cardiac symptoms have a high prevalence of cardiac abnormalities. Our data suggest that SSc-specific autoimmunity against Scl-70 mediates these changes. SSc patients with LGE had cardiac abnormalities associated with LVMI and serum BNP, leading to cardiac remodeling and possible development of cardiac involvement, even with a normal EF.
A 40-year-old woman who had bilateral swelling in the eyelids and submandibular region was admitted. Clinical findings suggested she had primary Sjögren's syndrome. Laboratory data showed glucosuria, positive CRP (0.50 mg/dl), liver dysfunction (AST 53 U/l, ALT 101 U/l, γ-GTP 241 U/l, ALP 914 U/l, LAP 496 U/l), hyperglycemia, hypergammaglobulinemia (IgG 3450 mg/dl, IgA 91 mg/dl, IgM 80 mg/dl), hypocomplementemia (C3 73 mg/dl, C4 2 mg/dl, CH50 < 19.0 U/ml), renal tubular dysfunction (urine N-acetyl-β-d-glucosaminidase 8.6 U/l, urine β2-microglobulin 83 μg/l), and urinary concentration defect. Ammonium chloride loading test was normal. Gallium-67 scintigram indicated abnormal uptake in bilateral lacrimal glands, submandibular glands, and kidneys. A diagnosis of Mikulicz's disease and interstitial nephritis was made, since biopsy specimens of her lacrimal gland and minor salivary gland showed diffuse infiltration of lymphocytes. Renal biopsy specimens also showed severe interstitial infiltration of lymphocytes. Symptoms and laboratory data normalized in response to methylprednisolone pulse therapy and prednisolone 60 mg/day. This case of Mikulicz's disease complicated with interstitial nephritis was successfully treated by high-dose corticosteroid.
Polymyositis (PM) and dermatomyositis (DM) are inflammatory diseases; up to 70% affected patients (pts) show cardiac involvement, which may be fatal. However, the diagnosis, based on electrocardiogram, laboratory, and imaging investigations, is difficult because of nonspecific clinical presentation and the lack of standardized criteria. Cardiac magnetic resonance (CMR) is currently the best technique for diagnosing cardiac fibrosis and inflammation.
Objectives
To evaluate cardiac involvement in PM/DM pts without cardiac manifestations by using CMR.
Methods
Sixteen consecutive female PM/DM pts (age, 51.9±11.0 years; 7 DM, 9 PM) and 16 gender/age-matched healthy controls without cardiac symptoms (age, 52.6±5.3 years) underwent CMR. Pts and control subjects had no history and/or clinical findings of systemic/pulmonary hypertension, coronary artery disease, valvular heart disease, atrial fibrillation, diabetes mellitus, and dyslipidemia. Late gadolinium enhancement (LGE) was considered to indicate myocardial fibrosis, and black-blood T2WI was used for assessing myocardial inflammation. Left ventricular geometry was classified into concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal. We compared the pts and controls regarding prevalence of CMR abnormalities, and explored the possible associations between CMR abnormalities and PM/DM disease characteristics. Group comparisons were made using the Wilcoxon chi-square test, Tukey–Kramer test, and Fisher exact test.
Results
PM/DM pts had normal inflammatory indices (erythrocyte sedimentation rate, C-reactive protein level), muscle enzyme assays, and improved muscle strength tests. LGE and T2WI were similar between PM and DM. LGE was seen in 8 pts (50%). Three of these 8 pts also had positive T2WI. Enhancement patterns observed were linear in middle layer, linear in subepicardial layer, nodular in middle layer, and patchy in middle layer (3, 1, 3, 1 pts, respectively). T2WI was observed in the same areas with LGE. No difference LGE positivity and T2WI findings was observed between PM (56% and 11%, respectively) and DM (43% and 29%, respectively) pts. Ejection fraction (EF) was similar between pts and controls (p=0.23). Of note, 7 pts showed concentric remodeling, and 75% of these pats showed LGE. PM/DM pts had higher NT-proBNP levels than controls. LGE was significantly correlated with concentric remodeling in PM/DM pts (p=0.04). Anti-Jo1 Ab positivity was correlated with LGE (p=0.03). However, T2WI was not associated with disease characteristics. Adjustment for disease duration, anti-Jo1 Ab, and LGE did not modify the association with concentric remodeling.
Conclusions
PM/DM pts without cardiac symptoms have a high prevalence of cardiac abnormalities. PM/DM pts with LGE are associated with abnormal morphology even with normal EF. Moreover, anti-Jo1 Ab positivity may be associated with LGE. Further studies are needed to determine whether CMR abnormalities affect prognosis or treatment strategy.
Individuals with rheumatoid arthritis (RA) have a twofold higher risk of developing sudden death than age and gender matched controls without RA. The underlying mechanisms have not yet been clarified.
Objectives
The aim of this study was to prospectively investigate the association of myocardial involvement assessed by a cardiac magnetic resonance imaging (CMR) and the QTc interval in RA without cardiac symptoms.
Methods
RA patients and control subjects with no history and/or clinical findings of systemic and pulmonary hypertension, coronary artery disease, valvular heart disease, atrial fibrillation, diabetes mellitus, and dyslipidemia were enrolled and underwent CMR. RA patients received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Late gadolinium enhancement (LGE) was obtained for the assessment of myocardial fibrosis. Using a black-blood T2-weighted image (T2-WI), myocardial inflammation could be assessed. The QTc intervals were manually measured on a 12-lead electrocardiogram, according to standard criteria. The QTc interval of 440 ms was considered to be prolonged in this study. We compared the patients and controls in terms of prevalence of CMR abnormalities and the QTc interval, and explored possible associations between CMR abnormalities and the QTc interval.
Results
Sixty-seven patients (mean age, 54.2 ± 1.7 years; 89% female) and 30 controls (mean age 53.6 ± 2.5 years; 87% female) were enrolled. Thirty-one RA patients received csDMARDs [25, methotrexate (MTX) (9.7±2.1 mg); 7, other drugs)] and 36 RA patients received bDMARDs [(15, infliximab; 15, tocilizumab; 6, abatacept, plus MTX respectively. (9.6±1.4 mg)]. The control group showed no myocardial abnormalities. Twenty seven RA patients (40%) demonstrated myocardial abnormalities. T2-WI was seen in seven RA patients (10%). LGE-positive was found in 20 RA patients (30%), six of whom also demonstrated T2-WI. All RA patients and control patients displayed a normal QTc interval. However, there was significant difference in the QTc interval between the control and LGE-positive (p=0.013). Also LGE-positive was significant higher in the QTc interval than LGE -negative. LGE-positive was associated with the QTc interval. The use of bDMARDs was significantly associated with LGE-negative findings (p=0.001) and the QTc interval. (p=0.001). High titer of anticitrullinated protein antibodies was associated with the QTc interval (p=0.04). Receiver operating characteristic analysis showed the QTc interval reliably detected myocardial abnormalities (area under the curve 0.898; 95% confidence interval, 0.830–0.900). Considering patients with RA and a normal QTc interval and using a cutoff of 420 ms, sensitivity and specificity were 91% and 70% in the detection of myocardial abnormalities.
Conclusions
Subclinical myocardial inflammation and fibrosis are common in active RA patients without cardiac manifestation. Abnormal CMR findings were associated with a QTc interval. Even if the QTc interval is normal, we should keep in mind the possibility of subclinical myocardial involvement in RA.
Three cases of myelodysplastic syndrome (MDS) complicated with inflammatory intestinal ulcers all had cytogenetic abnormalities with trisomy 8. The first two patients were diagnosed with intestinal Behçets disease and were successfully treated with salazosulphapiridine, and the third patient died after leukemic transformation. We review the reported cases of MDS complicated with Behçets disease. Most of these cases are Japanese, having intestinal involvement as well as cytogenetic abnormalities with trisomy 8. We discuss the significance of trisomy 8 in intestinal involvement in MDS.
