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76-Year-Old Man With New Bilateral Shoulder Pain

FRI0200 TIME TO FLARE IN GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA AND REVIEW OF THE LITERATURE

AIMTo investigate whether immune mediated diseases (IMD) are more frequent in patients with inflammatory bowel disease (IBD).METHODSIn this population based registry study, a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16, 2013. Controls were randomly selected from the Danish Civil Registration System (CRS) and matched for sex, age, and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis (UC), Crohn’s disease (CD) and Both the latter referring to those registered with both diagnoses. Subsequently, odds-ratios (OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher’s exact test.RESULTSThere were significantly more women than men in the registry, and a greater percentage of comorbidity in the IBD groups (P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased (P < 0.00125) for primary sclerosing cholangitis (PSC), celiac disease, type 1 diabetes (T1D), sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis. Restricted to UC (P < 0.00125) were autoimmune hepatitis, primary biliary cholangitis, Grave’s disease, polymyalgia rheumatica, temporal arteritis , and atrophic gastritis. Restricted to CD (P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC (P < 0.00125) were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica. Restricted to women with CD were episcleritis, rheumatoid arthritis, and psoriatic arthritis. The only disease restricted to men (P < 0.00125) was sarcoidosis.CONCLUSIONImmune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

SP0036 Where Does Polymyalgia Rheumatica Fit in the Spectrum of Inflammatory Rheumatic Disease?

Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.

Survive an innate immune response through XBP1

Polymyalgia Rheumatica (PMR) is an inflammatory disease which does not have specific diagnostic tests or pathological symptoms and is identified based on clinical characteristics. Among acute phase reactants (APR), the erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP) are laboratory findings used in diagnosis and follow-up. In this study, it was aimed to determine the incidence of normal ESH and CRP in patients diagnosed with PMR and identify the distinguishing characteristics of these patients. PMR patients who were clinically diagnosed at a single center were reviewed. After the presence of bursitis was demonstrated with ultrasonography in patients with normal ESR and CRP rates, they were accepted to have PMR. Among all 54 patients (63% female), ESR and CRP values were normal in 8 patients (14%), and serum amyloid A (SAA) was determined to be elevated in all these patients. In the comparisons of the groups with normal and high levels of ESR and CRP, it was found that the group with normal ESR and CRP values had a younger age of diagnosis (P = .027), a longer symptom duration (P < .001), and a lower comorbidity rate (P = .010). PMR patients can have normal ESR and CRP values at the time of their diagnosis. While bursitis can be demonstrated with ultrasonography in patients who are clinically evaluated to have PMR, APRs such as SAA other than ESR and CRP can also be used.

Small intestinal epithelial cells (IEC) show apoptosis in physiological turnover of cells and in certain inflammatory diseases. To investigate the role of caspases in the progression of IEC apoptosis in vivo. IEC were separated along the villus-crypt axis from the jejunum of normal and Nippostrongylus brasiliensis infected rats at 4 degrees C. Caspases were examined by a fluorometric assay method, histochemistry, and immunoblotting. Villus cell rich IEC from normal rats exhibited a high level of caspase-3-like activity whereas activities of caspase-1, -8, and -9 were negligible. Immunoblotting analysis of villus cell rich IEC revealed partial cleavage of procaspase-3 into a 17 kDa molecule as well as cleavage of a caspase-3 substrate, poly(ADP-ribose) polymerase (PARP), whereas in crypt cell rich IEC, caspase-3 cleavage was less significant. Caspase-3 activity was also observed histochemically in villus epithelium on frozen sections of the normal small intestine. IEC prepared at 4 degrees C did not reveal nuclear degradation whereas subsequent incubation in a suspension at 37 degrees C induced intense nuclear degradation within one hour in accordance with increases in active caspase-3. This apoptosis was partially suppressed by the caspase inhibitor Z-VAD-fmk. Nematode infected animals showed villus atrophy together with significant increases in levels of caspase-3 in IEC but not of caspase-1, -8, or -9. Caspase-3 may have an important role in the physiological replacement of IEC as well as in progression of IEC apoptosis induced by nematode infection.

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease in the elderly. Glucocorticoids (GCs) remain the mainstay of treatment. GC therapy usually dramatically improves the clinical picture, but approximately one-third of patients experience disease recurrence when the dose is reduced. Moreover, long-term use of GCs causes adverse reactions. Macrolide antibiotics have anti-inflammatory action. Several recent studies have reported the successful treatment of rheumatoid arthritis (RA) and PMR treated using clarithromycin (CAM), a macrolide, because of its anti-inflammatory action. Tacrolimus (TAC) has been indicated as a treatment for RA in patients who failed to respond to methotrexate. Recently, a case of RA was successfully treated using CAM and TAC according to one report. Reported here are two cases of PMR treated using CAM and/or TAC. Case 1: A 73-year-old man suffering from PMR was successfully treated with prednisolone (PSL) and CAM. Because his muscle pain disappeared, CAM was discontinued. However, the pain returned after that discontinuation, so CAM was successfully administered again. Case 2: An 83-year-old man suffering from PMR was successfully treated with PSL and CAM. Because muscle pain disappeared, the CAM dosage was halved. The pain returned after the dosage was reduced, so the CAM dosage was successfully resumed and the PSL dosage was reduced. When the PSL dosage was reduced, muscle pain recurred. Because the PSL and CAM dosages were not successfully increased, TAC was also administered and was found to be effective at treating muscle pain. These two cases suggest that CAM and/or TAC are effective at treating PMR.

4. Gastrointestinal mucosal immunity

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 ± 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment.

An immunoglobulin-independent deposition of the complement (C) components C4 and C3 occurs on rat kidney medullary structures, when sera of patients with various inflammatory diseases are studied by indirect immunofluorescence. The diagnostic value of this new test (C4-C3-IFT) for polymyalgia rheumatica (PMR) is stressed, since all sera from patients with active disease yielded positive reactions. Though highly sensitive with respect to PMR, C4/C3-IFT is not specific for this syndrome. Examples of positive reactions in systemic inflammatory diseases other than PMR are documented. Besides the clinical studies, C4/C3-IFT reactivity was analyzed with regard to the mechanisms of the reaction. Experimental data are presented which suggest that C-reactive protein (CRP) binds to rat kidney structures, thereby activating the classical C cascade. As a result of CRP-C interaction, C4 and C3 components are fixed to distinct renal medullary structures. Because of its technical simplicity, C4/C3-IFT can routinely be used to screen patients' sera for CRP-mediated C activation. This ex vivo test system may contribute to a better understanding of pathophysiological functions of serum CRP in various inflammatory diseases.

SP0040 The Immune/Inflammatory Response Follows Circadian Rhythms

Macrophages regulate inflammatory and fibrotic processes in several autoimmune and inflammatory rheumatic diseases. They are highly plastic cells, shifting within a range of pro-inflammatory and anti-inflammatory or pro-fibrotic phenotypes in response to dynamic interactions with other cells, environmental factors and cytokine signatures. The terms 'M1 macrophages', or classically activated, and 'M2 macrophages', or alternatively activated, were previously used to denote pro- and anti-inflammatory macrophage subsets, respectively, but this classification system has been outdated by in vivo evidence of a continuum of macrophage phenotypes that includes M1-like, M2-like and hybrid phenotypes. Deciphering the specific mechanisms that drive macrophage plasticity and function during the progression of rheumatoid arthritis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematosus, and in synovitis and large vessel vasculitis in polymyalgia rheumatica and giant-cell arteritis, can improve our understanding of disease pathophysiology. Macrophage plasticity is enhanced in synovial tissue in rheumatoid arthritis, fibrotic skin and lung in systemic sclerosis, damaged kidney in systemic lupus erythematosus, and the bursal tissues or large vessels in polymyalgia rheumatica and giant-cell arteritis. Sophisticated transcriptomic analyses have revealed various phenotypic clusters of macrophages in biopsies of affected organs. Moreover, macrophage plasticity seems to be targeted by some standardized drugs used to treat the aforementioned conditions.

Introduction:Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions. The diagnosis of PMR/GCA poses many challenges since there are no specific diagnostic tests. Recent literature emphasizes the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to assess global disease activity in inflammatory diseases. 18F-FDG PET/CT may lead to the diagnosis at an earlier stage than conventional imaging and may also assess response to therapy. With respect to the management of PMR/GCA, there are 3 significant areas of concern as follows: vasculitis process/vascular stiffness, malignancy, and osteoporosis.Methods and analysis:All patients with suspected PMR/GCR referred to the Rheumatology section of Medicine Department at Svendborg Hospital, Denmark. The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients.Ethics and dissemination:The study has been approved by the Regional Ethics Committee of the Region of Southern Denmark (identification number: S-20160098) and Danish Data Protection Agency (J.nr 16/40522). Results of the study will be disseminated via publications in peer-reviewed journals, and presentation at national and international conferences.