Yuko Takahashi

Benefit and a possible risk of tocilizumab therapy for adult-onset Still’s disease accompanied by macrophage-activation syndrome

We report a 57-year-old female case of intractable adult-onset Still’s disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage-activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease.

FDG PET for rheumatoid arthritis: basic considerations and whole-body PET/CT

[18F]Fluorodeoxyglucose (FDG) is a tracer for glucose metabolism. Its distribution is not specific to cancer cells but is also observed in inflammatory tissue, including macrophages, capillaries, and fibroblasts. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. The disease is characterized by fibrovascular proliferation leading to the formation of a pannus and causing high FDG uptake. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between uptake and various clinical parameters having been noted. Furthermore, the use of FDG PET for the sensitive detection and monitoring of the response to RA therapy has been reported. FDG PET/computed tomography (CT) enables the detailed evaluation of disease in large joints throughout the whole body, which is a unique advantage of PET/CT. FDG PET/CT can also be used to detect high‐risk disease complications, such as atlanto‐axial joint involvement, at an early stage. The possible contribution of FDG PET to the management of patients with RA remains to be studied in detail.

Similarities and differences in fluorodeoxyglucose positron emission tomography/computed tomography findings in spondyloarthropathy, polymyalgia rheumatica and rheumatoid arthritis

OBJECTIVES We assessed fluorine-18 ((18)F)-labelled fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with seronegative spondyloarthritis (SpA), polymyalgia rheumatica (PMR), and rheumatoid arthritis (RA). METHODS We studied 53 patients with SpA (n=21), PMR (n=16), or RA (n=16) admitted to our hospital between 2006 and 2011. Disease activity in the ischial tuberosities, greater trochanters, spinous processes, vertebral bodies, and sacroiliac joints (SIJ) were evaluated by determining FDG accumulation using maximum standardized uptake values (SUV(max)) and FDG scores. RESULTS SUV(max) for ischial tuberosities was significantly higher in PMR than SpA or RA. SUV(max) for greater trochanters and spinous processes was significantly higher in PMR than RA (P<0.001) and significantly higher in SpA than in PMR or RA for SIJ (P=0.01). No significant difference in vertebral scores was observed among groups (P=0.488). FDG scores yielded similar results. X-ray findings were consistent with PET/CT findings in 3/15 (20%) patients with sacroiliitis, whereas magnetic resonance imaging findings were consistent with PET/CT findings in 4/7 (57.1%) patients. CONCLUSIONS PET/CT detection of inflammation in the ischial tuberosities, greater trochanters, and spinous processes discriminated between PMR and RA, but not between SpA and PMR. PET/CT findings can distinguish SpA from RA and PMR and are useful for the early diagnosis of sacroiliitis.

Utility of fluorodeoxyglucose positron emission tomography/computed tomography for early diagnosis and evaluation of disease activity of relapsing polychondritis: a case series and literature review

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.

Autoantibodies to angiotensin-converting enzyme 2 in patients with connective tissue diseases

IntroductionAngiotensin-converting enzyme (ACE) 2, a homolog of ACE, converts angiotensin (Ang) II into Ang(1-7), and the vasoprotective effects of Ang(1-7) have been documented. We explored the hypothesis that serum autoantibodies to ACE2 predispose patients with connective tissue diseases to constrictive vasculopathy, pulmonary arterial hypertension (PAH), or persistent digital ischemia.MethodsSerum was examined from 42 patients with systemic lupus erythematosus (SLE), scleroderma, or mixed connective tissue disease. Eighteen vasculopathy patients with PAH (five cases) and/or persistent digital ischemia (16 cases) were compared with 24 patients without these vasculopathies (control patients) for serum reactivity to purified recombinant human ACE2, using an ELISA.ResultsThe sera from 17 of the 18 (94%) vasculopathy patients had ELISA scores above the baseline level determined using control sera from 28 healthy subjects, and the mean ELISA score in the vasculopathy patients was significantly higher than that in the control patients (P < 0.0005). The relative activity of serum ACE2, which was defined using a reference serum, correlated inversely with the ELISA scores for serum anti-ACE2 antibodies in the 18 vasculopathy patients (R2 = 0.6872). The IgG fraction from vasculopathy patients, but not from healthy subjects, inhibited ACE2 activities in vitro. Consistent with this, immunosuppressive therapy given to one SLE patient with digital necrosis markedly decreased the anti-ACE2 antibody titer and restored serum ACE2 activity.ConclusionsAutoantibodies to ACE2 may be associated with constrictive vasculopathies.

The utility of FDG-PET/CT and other imaging techniques in the evaluation of IgG4-related disease.

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). METHODS 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. RESULTS 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. CONCLUSIONS 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.

Differences in fluorodeoxyglucose positron emission tomography/computed tomography findings between elderly onset rheumatoid arthritis and polymyalgia rheumatica

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.

Intravascular large B-cell lymphoma with diffuse FDG uptake in the lung by 18FDG-PET/CT without chest CT findings

We report a rare case of intravascular large B-cell lymphoma (IVLBCL) with diffuse fluorodeoxyglucose (FDG) uptake in the lung by 18FDG-positron emission tomography/computed tomography (PET/CT). CT showed nodular shadow, whereas diffuse FDG uptake in PET/CT suggested IVLBCL in the lung. A random skin biopsy provided histological evidence of IVLBCL. The patient responded well to combination chemotherapy. Only two cases of IVLBCL in which diffuse pulmonary FDG uptake was demonstrated have been reported previously. FDG-PET/CT plus random skin biopsy may be useful for the early diagnosis of IVLBCL with pulmonary involvement even without convincing radiological findings in the lung.

Systemic lupus erythematosus complicated by Crohn’s disease: a case report and literature review

BackgroundAlthough patients with systemic lupus erythematosus (SLE) may experience various gastrointestinal disorders, SLE and Crohn’s disease (CD) rarely coexist. The diseases may have gastrointestinal (GI) manifestations, laboratory results, and radiographic findings that appear similar and consequently differentiating between GI involvement in CD and in SLE may be difficult. We present the case of a patient with SLE and CD who developed continuous GI bleeding and diarrhea that was initially treated as SLE-related colitis to little effect.Case presentationA 55-year-old Japanese woman with systemic lupus erythematosus (SLE) developed continuous gastrointestinal bleeding and diarrhea since the patient was aged 30 years that was initially treated as SLE-related colitis. Although a longitudinal ulcer and aphthous ulcers in the colon were observed every examination, biopsy showed only mild inflammation and revealed neither granuloma nor crypt abscess. The patient underwent surgery for anal fistulas twice at 50 and 54 years of age and her symptoms were atypical of lupus enteritis. Colonoscopy was performed again when the patient was 55 years of age because we suspected she had some type of inflammatory bowel disease (IBD). Cobblestone-like inflammatory polyps and many longitudinal ulcers were detected between the descending colon and the cecum. Macroscopic examination strongly suggested CD. Histopathological examination revealed non-caseating granuloma and no evidence of vasculitis, consistent with CD. Introduction of infliximab dramatically relieved the patient’s melena and abdominal symptoms.ConclusionDiagnostic criteria for CD and SLE overlap, making them difficult to diagnose correctly. It is important to consider CD for patients who have SLE with gastrointestinal manifestations. The pathology of lupus enteritis should be clarified through the accumulation of cases of SLE combined with CD.

Skin conductance activity after intraventricular administration of 6-hydroxydopa in rats

Absence of skin conductance response (SCR) and failure of its habituation are psychophysiological signs observed in most schizophrenics. In the present experiments, skin conductance activity was studied in rats before and after intraventricular administration of 6-hydroxydopa (6-OHdopa), a neurotoxin that selectively destroys noradrenaline nerve terminals and induces denervation supersensitivity at the synapse. All intact rats studied (n = 32) showed SCR and its habituation to repeated auditory stimuli (500 Hz, 90 dB, 1 sec, 20 times). They also showed some spontaneous fluctuation (SF) of the skin conductance. In the early stage following the 6-OHdopa (100 micrograms) administration (n = 16), it was noted that the SCR disappeared and the SF were markedly reduced in frequency (p less than 0.001). From the third day to the fourth week after this treatment, there was some recovery of the SF rate, and the SCR tended to reappear with a marked slowing down of its habituation. Eight weeks after the treatment, the majority (11/16) of the 6-OHdopa rats showed habituation failure of the SCR (p less than 0.005); vehicle-treated rats (n = 16) did not show these alterations. Estimation of catecholamine concentration after the experiment confirmed the selective depletion of brain noradrenaline. These results suggest that destruction of the noradrenergic fibers after the 6-OHdopa treatment and denervation supersensitivity which developed later are the cause of the nonresponding and nonhabituating changes of SCR, respectively.