Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

AIM: To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. METHOD: Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. RESULTS: A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). CONCLUSION: Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Successful treatment for eosinophilic granulomatosis with polyangiitis causing severe myocarditis followed by cardiac magnetic resonance.

A 38-year-old woman had a history of asthma for 20 years. Bullous lesions had appeared on her left side of the back. Two months before admission, the biopsy revealed eosinophilic cellulitis. One month later, she experienced numbness in both legs. She was admitted to our hospital for emergency treatment due to chest pain and loss of consciousness. Emergency coronary angiography revealed triple-vessel vasospasm. She had cardiac arrest for 4 min during the examination. We suspected eosinophilic granulomatosis with polyangiitis due to pulmonary infiltrate, eosinophilia, and a history of illness. We, therefore, started methylprednisolone pulse therapy. Although her condition and laboratory findings improved, cardiac magnetic resonance (CMR) imaging performed on day 16 showed myocardial oedema and myocardial fibrosis on late gadolinium enhancement. Coronary angiography on day 35 revealed no spasm, and myocardial biopsy showed the absence of vasculitis. There was no improvement in myocardial oedema. CMR showed enlargement of late gadolinium enhancement and formation of a ventricular aneurysm. As myocarditis did not improve sufficiently, five courses of intravenous cyclophosphamide pulse therapy were administered. CMR on day 152 showed the disappearance of myocardial oedema. We report a unique case of successful treatment of severe myocarditis and the usefulness of follow-up CMR.

Involvement of Epstein-Barr virus in the development and spontaneous regression of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis.

OBJECTIVES: Conventionally, some patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) undergo spontaneous tumour regression after cessation of MTX. Although the involvement of Epstein-Barr virus (EBV) in the development and spontaneous regression has been suggested, the underlying mechanism remains unknown. In this study, we analysed patients who had developed MTX-LPD to evaluate the association between the development and spontaneous regression of MTX-LPD with EBV. METHODS: We analysed the age, stage, disease activity, MTX dose, lymphocyte count, EBV real-time polymerase chain reaction (PCR) test value, and EBV-encoded small RNA (EBER) positivity rate in patients with MTX-LPD at our hospital. Moreover, we investigated the factors related to spontaneous regression, which is a characteristic of MTX-LPD. RESULTS: Thirty-four patients were enrolled in this study. The MTX dose at LPD onset was 8.3±2.0 mg/week, and the total dose of MTX was 1,530.3±779.2 mg. The EBV load in the peripheral blood was 270.4±431.8 copy/µL, and the pathological tissues of 17 of 34 (50%) patients tested positive for EBER. Twenty-one patients had spontaneous regression after discontinuation of MTX. The factors related to spontaneous regression were examined using a univariate analysis, and the EBV real-time PCR test value in the peripheral blood, EBER in pathological tissues, and improvement rate of lymphocyte count were considered significant factors. The EBV real-time PCR test value in the peripheral blood was defined as an independent factor of spontaneous regression using a multivariate analysis of related factors. CONCLUSIONS: EBV may be involved in the development of MTX-LPD and its spontaneous regression.

Successful early introduction of mepolizumab for peripheral neuropathy with a peripheral circulatory disorder in a patient with myeloperoxidase anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

A 26-year-old woman presented with abdominal pain, diarrhoea, vomiting, fever, and progressive paralysis in the lower limbs. She had a history of bronchial asthma and experienced sinusitis, progressive peripheral neuropathy, polyarthritis, and leukocytosis with prominent eosinophilia. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Abdominal pain was considered to be an ischaemic enteritis associated with EGPA. She was administered 1,000 mg/day of methylprednisolone for 3 days and intravenous immunoglobulin (400 mg/kg/day of γ-globulin for 5 days) followed by 50 mg (1 mg/kg)/day of oral prednisolone due to rapidly progressing peripheral neuropathy. Her symptoms temporarily improved; however, peripheral neuropathy recurred after a week, and the eosinophil count increased. Eighteen days after following the resumed treatment, 300 mg of mepolizumab, a humanised monoclonal antibody, was administered. Subjective symptoms, nerve conduction velocity, and skin perfusion pressure (an index of peripheral circulation in the lower extremities) improved after 4 weeks. Although mepolizumab has been approved for EGPA, there is no evidence of its efficacy against peripheral neuropathy. Early introduction of mepolizumab may contribute to an the early improved progressive peripheral neuropathy with eosinophilia.

Salivary Gland Focus Score Is Associated With Myocardial Fibrosis in Primary Sjögren Syndrome Assessed by a Cardiac Magnetic Resonance Approach.

OBJECTIVE: The risk of clinically manifested major cardiovascular (CV) events in primary Sjögren syndrome (pSS) remains unclear. This study aimed to assess myocardial fibrosis in pSS and investigate the associated disease characteristics by cardiac magnetic resonance imaging (cMRI). METHODS: We performed a cross-sectional study of patients with pSS without cardiac symptoms. Labial gland biopsy was documented in 44 patients (85%). Patients without CV risk factors underwent contrast-enhanced cMRI. Late gadolinium enhancement (LGE) was used to assess myocardial fibrosis. Myocardial edema was assessed using T2-weighted imaging (T2WI). We compared the left ventricular (LV) geometry and function between the groups with and without LGE. Further, we explored the associations of cMRI abnormalities with pSS characteristics. RESULTS: Fifty-two women with pSS (median age 55, IQR 47.0-65.7 yrs) were enrolled in the study. LGE was observed in 10 patients (19%), two of whom showed high intensity on T2WI. High intensity on T2WI was observed in 3 patients (5.8%). LV mass index and LV mass/end-diastolic volume tended to be higher in the LGE-positive group than in the LGE-negative group (P = 0.078 and 0.093, respectively). Salivary gland focus score (FS) ≥ 3 was independently associated with LGE-positive in the multivariable analysis (OR 11.21, 95% CI 1.18-106.80). CONCLUSION: Subclinical myocardial fibrosis, as detected by cMRI, was frequent in patients with pSS without cardiac symptoms. Abnormal cMRI findings were associated with salivary gland FS ≥ 3.

Impact of biological treatment on left ventricular dysfunction determined by global circumferential, longitudinal and radial strain values using cardiac magnetic resonance imaging in patients with rheumatoid arthritis.

AIM: To evaluate left ventricular (LV) dysfunction in patients with rheumatoid arthritis (RA) and to determine the impact of biological treatment on LV function in these patients using global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) values assessed by feature tracking cardiac magnetic resonance (FT-CMR) imaging. METHODS: Eighty patients with RA and 20 controls without cardiovascular disease underwent non-contrast CMR imaging. Patients with RA received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Global strains were calculated in 16 LV segments. RESULTS: No significant differences in cardiovascular risk factors were found between the RA group and controls. GCS was 21% lower in the RA group compared with controls (P < 0.001) and was 14% lower in the csDMARDs group compared with the bDMARDs group (P = 0.002), whereas, there was no significant difference in GLS and GRS between the RA group and the controls. In regard to strain rates, diastolic GCS and GRS rates were significantly lower in the RA group (P < 0.001, 0.011, respectively). In univariate analyses, GCS was significantly associated with the Simplified Disease Activity Index, bDMARDs, swollen joint count, anti-cyclic citrullinated peptides antibodies and matrix metalloproteinase-3, but in multivariable analysis, only bDMARDs was significantly associated with GCS (P = 0.021). CONCLUSION: Global circumferential strain, GLS and GRS assessed by FT-CMR can reveal subclinical LV dysfunction in patients with RA. Furthermore, they can be used to determine the normalization of LV regional dysfunction induced by bDMARDs possibly related to disease activity reduction.

Association of cardiac magnetic resonance-detected myocardial abnormalities with disease characteristics and brain natriuretic peptide levels in systemic sclerosis without cardiac symptoms.

AIM: This study aimed to evaluate the association between myocardial abnormalities and left ventricular (LV) geometry as assessed using cardiac magnetic resonance imaging (CMRI) in systemic sclerosis (SSc) patients without cardiac symptoms. METHODS: SSc patients without cardiac symptoms or cardiovascular risk factors underwent contrast CMRI. CMRI were assessed for structural and functional LV parameters and myocardial fibrosis based on myocardial late gadolinium enhancement (LGE). The correlation between brain natriuretic peptide (BNP) levels and LGE status was evaluated. RESULTS: Among 49 patients, 27 (55%) showed LGE positivity. The most common identified LGE pattern was a linear pattern. LGE was not consistent with coronary artery distribution. There was no difference in ejection fraction between those with and without LGE. LV morphological changes were observed in 29% of SSc patients. An abnormal LV structure was detected in 44% and 14% of patients in the LGE+ and LGE- groups, respectively. The BNP levels were higher by 57% in the LGE+ group than in the LGE-group. Receiver operating characteristic analysis showed that BNP levels reliably detected myocardial abnormalities (area under the curve, 0.72; 95% confidence interval 0.58-0.88). CONCLUSIONS: Myocardial abnormalities were common in SSc patients without cardiac symptoms. We suggest that LV morphological changes may have resulted from myocardial abnormalities. BNP may be useful as a screening tool for the detection of myocardial abnormalities in SSc patients.

Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporosis.

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.

[Diagnostic value of brain biopsy in intravascular large B-cell lymphoma mimicking progressive multifocal leukoencephalopathy: case report].

We report a 68-years-old woman with systemic sclerosis and interstitial pneumonia (IP). She had developed subacute progressively encephalopathy and dementia while treated with oral cyclophosphamide and prednisolone. She admitted to our hospital because of syncope. Laboratory tests indicated slight elevated cerebrospinal fluid protein, and levels of serum C-reactive protein (CRP), levels of soluble IL-2 receptor was normal. But, magnetic resonance imaging (MRI) of the brain showed multiple infarct-like lesions mainly in the white matter, which mimics progressive multiple leukoencephalopathy (PML). Twenty days after admission, the retested MRI of the brain disclosed initial lesions progressively enlarged and numbers of the lesions were increased. The polymerase chain reaction (PCR) for JC virus of cerebrospinal fluid was negative. To make diagnosis, brain biopsy was performed. Microscopic examination revealed that small vessels were filled with lymphoma cells (CD20+, CD79+, CD3-), and intravascular lymphoma (IVL) was diagnosed. She treated with regimens of R-CHOP. After chemotherapy her consciousness and dementia were gradually improved. IVL of central nerve system (CNS) is a rare disease, and its common symptoms are ischemia, infarction and dementia. Diagnosis of IVL of CNS is difficult when the lesion mimics PML, and patient with similar laboratory examinations and radiographic findings of PML should undergo brain biopsy detected malignant cell in small vessels, which is a value of diagnosis.