[Show abstract][Hide abstract] ABSTRACT: A 69-year-old woman with rheumatoid arthritis and pleuritis presented with dyspnea. On admission, she was afebrile and had an oxygen saturation of 97% on ambient air. Chest radiography and CT revealed only subtle ground-glass opacities. However, FDG PET revealed pathological uptake in both lungs. A diagnosis of Pneumocystis pneumonia was made based on a positive β-D-glucan assay and polymerase chain reaction amplification of Pneumocystis jirovecii from the sputum. Posttreatment FDG PET revealed resolution of the previously noted uptake. This case illustrates that FDG PET can be used to diagnose Pneumocystis pneumonia when the CT findings are equivocal.
Clinical nuclear medicine 05/2015; DOI:10.1097/RLU.0000000000000831 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We herein report a rare case of microscopic polyangiitis with primary biliary cirrhosis (PBC) and a literature review of six previously reported cases of PBC complicated by anti-neutrophil cytoplasmic antibody-associated vasculitis. Due to the scarcity of similar reports, it was not possible to establish a true overlap syndrome or casual association. When the biliary enzyme levels are elevated in patients with vasculitis, physicians should thus be mindful of the possible coexistence of these diseases.
Internal Medicine 01/2015; 54(10):1303-8. DOI:10.2169/internalmedicine.54.3678. · 0.97 Impact Factor
[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 11/2014; DOI:10.3109/14397595.2014.978936 · 2.21 Impact Factor
[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; 41(1). DOI:10.3109/01902148.2014.959141 · 1.75 Impact Factor
[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: Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of 18 F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia rheumatica, adult-onset Still's disease, relapsing polychondritis, immunoglobulin G4-related disease, large-vessel vasculitis, Wegener's granulomatosis, polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.
[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: 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.
[Show abstract][Hide abstract] ABSTRACT: Background Relapsing polychondritis (RPC) is relatively rare, and early diagnosis is difficult.
Objectives We investigated the utility of FDG-PET/CT for the diagnoses of RPC and evaluation of disease activity.
Methods Five RPC patients undergoing FDG-PET/CT hospitalized in our hospital between 2006 and 2013 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from 13 patients total were analyzed.
Results Typical FDG accumulation was noted in tracheobronchial trees of 9 patients, costal cartilage of 5, joints of 5, larynx of 4, nasal cavity/paranasal sinuses of 3, auricles of 3, lymph nodes of 3, and the aorta of 1. One patient showed nasal chondritis on PET scan despite absence of nasal changes on physical examination. Of 5 patients with costochondritis, 4 remained asymptomatic. Of 9 patients with airway FDG accumulation, 8 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.In 5 patients with PET post-treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement.
Conclusions 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 the evaluation of extent of disease and disease activity during treatment.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):1120-1121. DOI:10.1136/annrheumdis-2014-eular.1039 · 10.38 Impact Factor
[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.
[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.
Modern Rheumatology 04/2014; DOI:10.3109/14397595.2014.895283 · 2.21 Impact Factor
[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.
Modern Rheumatology 04/2014; DOI:10.3109/14397595.2014.899178 · 2.21 Impact Factor
[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; 34(11). DOI:10.1007/s00296-014-2985-3 · 1.63 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.