[Show abstract][Hide abstract] ABSTRACT: Objectives. To compare the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings in patients with elderly-onset rheumatoid arthritis (EORA) with those in patients with polymyalgia rheumatica (PMR), two conditions with similar clinical presentations. Methods. We retrospectively analyzed the FDG-PET/CT findings in 10 patients with EORA and 27 patients with PMR admitted to our department between 2006 and 2012. Results: No significant difference was observed in the median patient ages at the time of FDG-PET/CT scans in the EORA and PMR groups (73.5 vs. 78.0 years, respectively). Significant differences in both FDG uptake scores and standardized uptake values were observed between the two groups in the ischial tuberosities, spinous processes, and wrists. No significant differences were detected in the shoulders and hips. However, specific uptake patterns were observed in each group: circular and linear uptake patterns were observed around the humeral head in the EORA group, whereas focal and non-linear uptake patterns were observed in the PMR group. Moreover, focal uptake in front of the hip joint, indicating iliopectineal bursitis, tended to be limited to the PMR group. High sensitivity (92.6%) and specificity (90%) were observed for PMR diagnoses when at least three of the following five items were satisfied: characteristic findings of shoulder and iliopectineal bursitis, FDG uptake in ischial tuberosities and spinal spinous processes, and lack of FDG uptake in the wrists. Conclusion. The differences in the degree of uptake at each lesion and in uptake patterns at the shoulders and hips are potentially useful for obtaining a definitive diagnosis.
Modern rheumatology / the Japan Rheumatism Association. 11/2014;
[Show abstract][Hide abstract] ABSTRACT: Introduction: Pulmonary hypertension (PH) is characterized by increased pressure in the pulmonary artery and right ventricular hypertrophy (RVH). Recently, angiotensin-converting enzyme 2 (ACE2), which converts angiotensin (Ang) II into Ang-(1-7), was shown to inhibit experimental PH. Here we identified a novel ACE2 activator and investigated how the compound reduced monocrotaline (MCT)-induced PH. Methods: To induce PH, Sprague-Dawley rats were injected subcutaneously with MCT, followed by the continuous administration of NCP-2454, an ACE2 activator, using osmotic pumps. Pulmonary arterial compliance was monitored every week until 4 weeks post-injection (wpi). RVH and lung remodeling was evaluated using lung tissue at 4 wpi. Results: NCP-2454 upregulated the production of Ang-(1-7) when incubated with ACE2 and Ang II. Notably, a continuous infusion of NCP-2454 significantly improved pulmonary arterial compliance, right ventricular systolic pressure, and RVH in MCT-treated rats. Interestingly, NCP-2454 increased the relative expression of ACE2 and MAS mRNA in lung tissue, especially in MCT-treated rats. In addition, the compound inhibited the MCT-induced overexpression of transforming growth factor β, phosphorylation of signal transducer and activator of transcription-3 (STAT3), and interleukin-6 production. The compound also restored the expression of caveolin-1 (Cav-1), which negatively regulates the Janus kinase-STAT signaling cascade. Conclusions: NCP-2454 prevented MCT-induced PH by suppressing intracellular inflammatory cascades, an upstream molecular change of which is the disruption of Cav-1 expression.
Experimental Lung Research 10/2014; · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 48-year-old female with a past history of systemic lupus erythematosus had developed autoimmune hepatitis (AIH) at the age of 45 years, and administration of PSL 30 mg/day was initiated. However, AIH exacerbation was suspected based on elevation of hepatic and biliary tract enzymes such as ALP (1207U/L) with a fever of 38 degrees C after tapering off the steroids to PSL 7.5 mg daily, and she was thus hospitalized. A liver biopsy was recommended, but she refused. Thus, we suspected concomitant AIH and autoimmune cholangitis (AIC). Although high-dose steroid treatment including steroid pulse therapy was administered, there was no improvement. We performed a liver biopsy on the 66th hospital day, after obtaining the patient's consent. Epithelioid granuloma was detected in the liver leaflet as the background of the AIH and AIC findings. In addition, acid fast bacteria were detected with auramine and Ziehl-Neelsen staining, raising the possibility of tuberculosis. Additionally, granuloma was also seen in her bone marrow, and miliary tuberculosis was suspected. Anti-tuberculous therapy with isoniazid, rifampicin, ethambutol and pyrazinamide was initially administered, but the regimen was changed to levofloxacin, ethambutol, and streptomycin due to the side effects of the earlier medications. Liver functions improved and the inflammatory reaction became negative. The patient was discharged on the 138th hospital day. Ultimately, no acid fast bacteria were detected with culture, PCR of her bone marrow, or liver biopsy. However, miliary tuberculosis was definitively diagnosed from the pathological findings and her clinical course. AIH was an underlying disease, and the discrimination from AIH exacerbation was difficult. Consequently, the diagnosis was miliary tuberculosis without the lung involvement and the main lesion was in the liver. It is important to take account of miliary tuberculosis in the differential diagnosis of fevers of unknown origin with elevation of hepatic and biliary tract enzymes, and to make a definitive diagnosis with a liver biopsy.
Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases. 07/2014; 88(4):459-62.
[Show abstract][Hide abstract] ABSTRACT: We herein report on a 69-year-old male who developed lung nocardiosis and brain abscessation. In April 2011, he was diagnosed as having systemic lupus erythematosus complicated by peripheral neuropathy. Immunosuppressive therapy with high-dose prednisolone was begun. In November 2011, he developed cryptococcal pneumonia and meningitis, which was treated with liposomal amphotericin and flucytosine for 4 weeks and was maintained with fluconazole. In April 2012, consolidation and peripheral atelectasis in the right middle lobe appeared. Bronchoscopy revealed edematous mucosa in the right middle bronchus and occlusive change of the right B4 and B5, but biopsy and culture results provided no etiological information. In late June, he developed an intermittent fever, and obstructive pneumonia of the right middle lobe was suspected. Nocardia species were detected from the sputum culture and were thought to be the causative pathogen. Brain CT and MRI revealed a contrast-enhanced lesion in the right cerebellar hemisphere. The patient was diagnosed as having lung nocardiosis and brain abscessation. Considering that the nocardiosis had developed under prophylaxis for Pneumocystis jirovecii pneumonia using one tablet per day of a sulfamethoxazole-trimethoprim combination, meropenem and amikacin were administered in addition to the sulfamethoxazole-trimethoprim combination for 6 and 4 weeks, respectively. After N. elegans had been identified from the sputum, antibiotics were switched to a sulfamethoxazole-trimethoprim combination and clarithromycin based on the susceptibility results. The patient's clinical and radiological findings were improved and have been well sustained.
Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases. 05/2014; 88(3):282-7.
[Show abstract][Hide abstract] ABSTRACT: We report a case of interstitial cystitis (IC) associated with primary Sjögren's syndrome (SS) successfully controlled with combination therapy of tacrolimus and a corticosteroid. In 2011, a 69-year-old female, who had been diagnosed with primary SS 23 years ago, developed IC and was successfully treated with tacrolimus and prednisolone combination therapy. The mechanism of IC, including the involved autoimmunity, has not been elucidated. Clinical observation studies suggest a potential association between SS and IC. However, IC is currently thought to be underdiagnosed in patients with SS as well as in the general population. Based on our case and others reported previously, IC associated with SS responds well to immunosuppressive therapy. In particular, a combination of a calcineurin inhibitor (tacrolimus or cyclosporine) with a corticosteroid seems to be highly effective. The possibility of IC in patients with SS complaining of lower urinary tract symptoms without features of infection or other identifiable causes should be given attention.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of tocilizumab (TCZ) on adult-onset Still's disease (AOSD), we reviewed medical records of seven patients with refractory AOSD treated with TCZ at our institution. TCZ therapy might allow rapid corticosteroid tapering and help maintain remission status, that is, resolution of clinical symptoms and normalization of biomarkers such as CRP and ferritin. Patients, however, should be monitored for the development of macrophage activation syndrome when TCZ is administered for active AOSD.
[Show abstract][Hide abstract] ABSTRACT: Objective. Relapsing polychondritis (RPC) is relatively rare and early diagnosis is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for the diagnosis of RPC and evaluation of disease activity.Methods. Five RPC patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from a total of 13 patients were analysed.Results. Typical FDG accumulation was noted in the tracheobronchial trees of nine patients, the costal cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses of three, auricles of three, lymph nodes of three and the aorta of one. One patient showed nasal chondritis on a PET scan despite the absence of nasal changes on physical examination. Of five patients with costochondritis, four remained asymptomatic. Of nine patients with airway FDG accumulation, eight developed respiratory symptoms and all had CT abnormalities. In the other patient, airway FDG accumulation was evident despite the absence of airway symptoms and a lack of abnormalities in the respiratory function test and CT. PET also revealed bronchial chondritis in asymptomatic patients. The mean maximum standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d. 2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement.Conclusion. FDG-PET/CT is a potentially powerful tool for the early diagnosis of RPC, especially in patients without easily biopsied organ involvement. This modality also facilitates evaluation of disease extent and disease activity during treatment.
[Show abstract][Hide abstract] ABSTRACT: Large vessel vasculitis (LVV) is an often-reported cause of inflammation of unknown origin (IUO) in elderly people. The objective of this study was to describe the usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and contrast-enhanced CT in early diagnosis and treatment follow-up of patients with LVV presenting as elderly onset IUO. We retrospectively compared contrast-enhanced CT findings and FDG-PET/CT findings of the patients diagnosed with LVV and 11 controls; all subjects were 50 years of age or older. We evaluated maximum standardised uptake value (SUVmax) and PET score of the aortic wall for quantitative comparison of FDG-PET/CT findings. We measured the aortic wall thickness (W) and its ratio against the radius (W/R) for quantitative comparison of aortic wall thickening by contrast-enhanced CT. After steroid treatment, we compared these values with those pre-treatment. Of 124 patients who were hospitalised due to advanced age and IUO, 88 underwent FDG-PET/CT and contrast-enhanced CT. Abnormal findings were observed on images from 78 patients. The findings were indicative of LVV in 13 patients (10.5 %), of whom more than half had only non-specific symptoms. Patients with LVV had significantly higher aortic wall SUVmax (3.85 vs. 1.95), PET scores by FDG-PET/CT, and aortic wall thicknesses by contrast-enhanced CT (3.8 vs. 2.6 mm) than controls. Significant improvement in aortic wall thickening was evidenced by reduced PET scores and by contrast-enhanced CT findings in patients who were followed up after treatment. LVV is an important cause of IUO with non-specific symptoms in elderly patients. Imaging examination comprising contrast-enhanced CT and FDG-PET/CT is useful for early diagnosis and early treatment evaluation of LVV, allowing for amelioration of reversible aortic wall thickening.
Rheumatology International 03/2014; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms. We report a very rare case with autoimmune hepatitis (AIH) complicated by CAEBV. A 50-year-old woman with systemic lupus erythematosus (SLE) complicated by AIH began to suffer from acute respiratory failure and her clinical symptoms improved rapidly in response to steroid treatment. However, during the gradual tapering of the steroid dose, a steady increase of the serum hepatobiliary enzyme levels subsequently was observed and the patient began to have continuous fever. Moreover, upper gastrointestinal endoscopy revealed multiple intractable gastric ulcers. When EBER-ISH was performed on liver biopsy and gastric mucosal biopsy specimens, EBER-positive lymphocytes were observed. When peripheral blood was examined, 2.1 × 10(6) copies/µg of EBV-DNA were observed in the CD4-positive T cells, confirming the diagnosis of CAEBV. A cooling therapy was started by steroid and cyclosporine. Thereafter, despite the start of CHOP therapy, she developed a malignant lymphoma (PTCL-NOS) and died of hepatic failure. When treatment-resistant AIH patients are encountered, not only AIH exacerbation but also CAEBV should be considered in the differential diagnosis.
[Show abstract][Hide abstract] ABSTRACT: Objective. The gamma-aminobutyric acid type B receptors (GABARB) are G-protein coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. We identified GABARB subunits as candidate antigens in patients with SLE using a random peptide display library. The aim of this study was to investigate the possible link between anti-GABARB antibodies and disease activity and NPSLE.Methods. ELISA was performed with recombinant proteins of GABARB1b and GABARB2 on serum samples from patients with SLE (n = 88), scleroderma (n = 20), myositis (n = 20) or vasculitis (n = 20) as well as healthy subjects (n = 20). Cerebrospinal fluid (CSF) from 23 patients with SLE was also examined.Results. Autoantibodies to GABARBs were exclusive to patients with SLE (P < 0.001) and positively associated with SLEDAI (anti-GABARB1b, P = 0.001; anti-GABARB2, P < 0.001). Of note, autoantibodies were positively linked with NPSLE (anti-GABARB1b, P = 0.02; anti-GABARB2, P = 0.03). Moreover, anti-GABARBs was detected in 61.5% of CSF samples from patients with active NPSLE, a frequency that was significantly higher than that for patients with non-SLE syndromes.Conclusion. Anti-GABARB antibodies could represent novel candidate markers for disease activity and NPSLE.
[Show abstract][Hide abstract] ABSTRACT: Objective. To investigate the incidence and clinical features of methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPDs) in patients with rheumatoid arthritis (RA). Patients. In total, 589 RA outpatients were examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010. Results. MTX was used in 403 cases, and the duration of follow-up was 2379 person-years. Four patients developed MTX-LPDs; the incidence of MTX-LPDs was calculated as 0.00168/person-year and the standardized incidence as 8.21 (95% CI: 0.16-24.30). The mean total dosage of MTX was 1142 ± 871 mg, and the dosage at LPD onset was 7.4 ± 1.9 mg/week. The patients who developed MTX-LPDs had significantly shorter disease duration of RA compared with the patients who had not received MTX, but who had not progressed to LPDs (3.1 years vs. 12.5 years; P = 0.01). The following LPD subtypes were observed: diffuse large B-cell lymphoma (N = 2); Hodgkin's lymphoma (N = 1); and T-cell lymphoma (N = 1). After withdrawal of MTX, two of these patients showed spontaneous regression of the tumor, one did not have a recurrence, while the other patient relapsed and required chemotherapy. Conclusion. Our study revealed that MTX-LPDs are not rare complications of RA outpatients. The MTX-LPDs were associated with a relatively shorter RA duration, and half of them showed tumor regression after MTX withdrawal, which suggested an association with MTX. It is important to consider the possibility of MTX-LPD in RA patients who have received MTX.
[Show abstract][Hide abstract] ABSTRACT: Objective. The etiology of mixed connective tissue disease (MCTD) has not been elucidated in detail. Case control studies of MCTD and systemic lupus erythematosus (SLE) were conducted in order to compare factors related to these two diseases. Methods. We selected 48 MCTD and 54 SLE female patients throughout Japan from 2009 to 2010. Controls were 182 female patients who visited the clinics of general internal medicine during the study periods. Results. Smoking and walking a longer time showed an increased age-adjusted risk for MCTD as well as SLE. On the other hand, frequent intake of bread increased the risk of MCTD and high intake of green tea decreased the risk of MCTD. Even after an additional adjustment of smoking and drinking, frequent intake of bread increased the risk of MCTD, while walking increased the risk of SLE. Conclusion. The present study suggests that Westernization of dietary habits (i.e. frequent intake of bread and low intake of green tea) may increase the risk of MCTD, while walking may increase the risk of SLE (probably due to exposure to the sunlight) among Japanese females. Further studies are needed to confirm the result of the present study.
[Show abstract][Hide abstract] ABSTRACT: We herein report the case of a 72-year-old woman with diffuse cutaneous systemic sclerosis (SSc) complicated by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who exhibited honeycomb lung without volume loss. On admission, chest computed tomography (CT) revealed honeycomb lung without volume loss in addition to increased density of the partition walls. A renal biopsy revealed global sclerosis and cellular crescent formation. Mononeuritis multiple subsequently occurred, and steroid pulse therapy with cyclophosphamide was administered. Repeat chest CT showed that the honeycomb lung was unchanged; however, overall reduced density of the partition walls was observed. It is necessary to recognise that vasculitis may develop in SSc patients who exhibit honeycomb lung without volume loss.
Internal Medicine 01/2014; 53(7):801-4. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
This study aimed to evaluate the utility of imaging techniques, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), in immunoglobulin (IgG)4-related disease (IgG4-RD).
We reviewed eight IgG4-RD patients who were referred to our hospital between August 2006 and April 2012. All cases underwent FDG-PET/CT and brain magnetic resonance imaging (MRI) and endobronchial ultrasonography (EBUS) were also performed in five cases and one case, respectively.
Although nearly all patients with IgG4-RD in this study were negative for CRP (mean 0.22 mg/dL), various organ involvement sites were detected by FDG-PET/CT. In the active phase in two autoimmune pancreatitis (AIP) cases, FDG-PET/CT showed longitudinal and heterogeneous FDG accumulation in the pancreas with FDG uptake in the hilar or mediastinal lymph nodes. Follow-up FDG-PET/CT after therapy in one case revealed that the abnormal FDG uptake in all affected lesions had completely disappeared. In two cases, brain MRI revealed asymptomatic hypertrophic pachymeningitis. In one case, EBUS imaging of mediastinal lymph node swelling was consistent with tortuous vessels with high Doppler signals and hyperechoic strands between lymph nodes.
When FDG-PET/CT shows FDG accumulation, characteristic of IgG4-RD in organs, without evidence of an associated inflammatory reaction, a diagnosis of IgG4-RD can be made. Treatment effects can be assessed by the disappearance of FDG uptake. A routine brain MRI is useful for detecting asymptomatic hypertrophic pachymeningitis. EBUS may also be useful for differentiating among the etiologies of lymphadenopathy with characteristic sonographic imaging findings.
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder that primarily affects the synovial joints. Rheumatoid vasculitis (RV) is an extra-articular manifestation of RA, and its association with aortitis is rare and not widely recognised. Here, we report the case of a 69-year-old woman with RA-associated aortitis and review the literature on rheumatoid aortitis. The mean oral steroid dose administered to RA-associated aortitis patients was 46.3 mg/day prednisolone (PSL). In our patient, the aortitis was also thought to be due to RV because she had findings of RV, such as cutaneous ulceration and a high rheumatoid factor titre, and because a moderate PSL dose dramatically improved the clinical findings. RA-associated aortitis, if left untreated, can be fatal; therefore, early detection and treatment initiation is very important.
[Show abstract][Hide abstract] ABSTRACT: We experienced three patients with refractory or severe hemophagocytic syndrome associated with the activity of systemic lupus erythematosus, so-called acute lupus hemophagocytic syndrome (ALHS). All patients were successfully treated with intermittent intravenous injections of cyclophosphamide (IVCY). In each patient, hemophagocytosis was found during bone marrow examination, and infectious causes of hemophagocytic syndrome were carefully excluded. Patients 1 and 2 were refractory to combination therapy with a high-dose corticosteroid and rituximab or cyclosporine and were successfully treated with additive IVCY. Patient 3 had very severe ALHS that developed after cardiac surgery but was successfully treated with a high-dose corticosteroid and IVCY. We conducted a literature review of adult ALHS and analyzed 54 cases reported from 2006 to 2013. Although the clinical and laboratory features were diverse, fever, bicytopenia or pancytopenia, and hyperferritinemia were almost universal. Including our 3 patients, a total of 16 have reportedly been treated with IVCY-containing regimens, and ALHS was successfully controlled in most of them without switching or adding other therapies. We suggest that combination therapy with IVCY and corticosteroids may be useful to treat severe or refractory ALHS.
[Show abstract][Hide abstract] ABSTRACT: We herein report two cases of myelodysplastic syndrome with rheumatic manifestations. (Case 1) A 70-year-old man presented with fever, arthritis and bone pain and developed cranial nerve palsy caused by an epipharyngeal mass. Steroid therapy led to a prolonged remission of the febrile condition and mass lesion. (Case 2) An 82-year-old male was treated for intractable polyarthritis and fever with steroid therapy, and serious side effects resulted in lethal pneumonia. We herein describe the entire course of steroid therapy in these two cases. Various rheumatic manifestations in myelodyaplastic syndrome often require empirical steroid therapy. It was effective for the soft tissue mass in Case 1, in which indolent lymphoma could not be denied, and was only partially effective for Case 2 of the febrile and putatively benign conditions, suggesting heterogeneous nature of rheumatic complications in myelodysplastic syndrome.