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ID PMID Title PublicationDate abstract
28828323 Survey of False-positive Reactivity of Latex Agglutination Test for Kala-azar (Katex) with 2017 Jun BACKGROUND: Latex agglutination test for Kala-azar (KAtex) is an easy, inexpensive, and field-applicable antigen detection test. However, the main drawback of this method is the boiling step applied to remove false positivity of the test. This study was conducted to survey false positivity results of latex agglutination test for KAtex without boiling process in urine of some autoimmune patients. METHODS: Ninety-two urine samples from autoimmune patients including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, autoimmune vasculitis, vitiligo, pemphigus and Wagner cases and 20 urine samples from healthy individuals were collected from Kerman Province in Southeastern Iran in 2010-2011. All urine samples were checked by KAtex after boiling for 5 min false positivity rate of the test was surveyed in different healthy and patients groups while boiling process was removed. Rheumatoid factor (RF) then was checked in sera of all cases to evaluate the relationship between RF and KAtex false positivity. RESULTS: All samples represented negative results with KAtex when boiling was performed (100% specificity). Then, 20% positivity was evident in healthy cases. False-positive reactivity was more prominent observed in patient groups than healthy individuals, except in vitiligo. However, a significant difference was only observed in RA group (P<0.05). RF was related to KAtex false positivity. CONCLUSION: RA was described as the autoimmune disease in which KAtex false positivity was higher than normal population. RF or its metabolic products may have role in false positivity of KAtex but this finding needs to be confirmed by more reliable and improved experiments. Overall, immune system products should be considered in attempts for modification of KAtex for boiling process removal.
29286020 A case of Candida septic arthritis with rice body formation in a 2-month-old infant. 2017 Dec 1 We present a case of rice body formation in the left knee joint of a 2-month-old infant affected by Candida albicans septic arthritis which has never been reported before. Rice body formation has been described in association with rheumatoid or tuberculous arthritis and is very rare in Candida arthritis. After three weeks of therapy with amphotericin B administered intravenously, the infant recovered fully from infection. Septic arthritis is a serious cause of morbidity and for proper evaluation and treatment fungal septic arthritis should be included in the differential diagnosis.
28690517 Erythema Gyratum Repens-Like Purpura in a Patient with Sjögren Syndrome. 2017 May The etiology of purpura in Sjögren syndrome (SS) includes cryoglobulinemia, hypergammaglobulinemia, and leukocytoclastic vasculitis (LCV). The clinical symptoms of LCV associated with SS comprise palpable or nonpalpable purpura and urticarial vasculitis. Here, we report a case of LCV presenting as erythema gyratum repens (EGR)-like purpura in a 62-year-old woman with rheumatoid arthritis and SS. EGR-like skin lesions, characterized by annular lesions with expanding concentric pattern and coalescing to form a zebra-like pattern or grain of wood pattern, can appear in various autoimmune conditions; however, EGR-like eruption in SS is extremely rare. On the basis of the expansion pattern, we considered that the EGR-like purpura in this case was elicited by urticarial vasculitis accompanied by SS.
28735613 Does Treatment of Psoriasis Reduce Cardiovascular Comorbidities? 2017 Aug Psoriasis has been associated with an increase in myocardial infarctions. Several registries have shown reductions in major adverse cardiovascular events in psoriasis patients and rheumatoid arthritis patients treated with tumor necrosis factor-α antagonists. Many assume that the reduction in cardiovascular events can be attributed to the anti-inflammatory effect of tumor necrosis factor blockers, but a 52-week study conducted by Bissonnette and coworkers failed to show a reduction in cardiovascular inflammation in psoriasis patients treated with adalimumab. Longer and larger studies are needed to explain why tumor necrosis factor-α blockade appears to reduce cardiovascular events in patients with severe psoriasis.
28556615 Characteristics of germinal center-like structures in patients with Sjögren's syndrome. 2017 Feb AIM: To analyze the relationship between ectopic germinal centers (GCs) in the salivary glands and the clinical/laboratory characteristics of patients with Sjögren's syndrome (SS). METHODS: Retrospectively, 126 patients with primary SS (pSS) and 16 patients with secondary SS (sSS) were analyzed. Minor salivary gland biopsies were evaluated for the presence of GC-like morphology by hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining for CD21. Clinical and serological data were obtained from medical records. RESULTS: GC-like structures were observed in 36/126 (28.6%) pSS patients and 4/16 (25.0%) sSS patients. The mean inflammatory focus score of the gland was significantly higher in GC-positive samples than in GC-negative ones in both pSS and sSS patients (P = 0.007 and 0.024, respectively). In pSS, significantly elevated titers of rheumatoid factor (RF)-IgM (P = 0.023) and antinuclear antibodies (ANA) (P = 0.036), increased levels of IgA (P = 0.012) and IgG (P = 0.017) were encountered in GC-positive patients. The GC-positive group also presented higher prevalence of anti-SSA antibodies, lower levels of white blood cells, higher levels of erythrocyte sedimentation rate and γ-globulin, although not statistically significant. In sSS patients with ectopic GC formation, ANA titers were remarkably elevated. The anticyclic citrullinated peptide (anti-CCP)-IgG titers and the prevalence of antikeratin antibody (AKA)-IgG, antiperinuclear factor (APF)-IgG were also increased, yet not significantly. GCs were found to be associated with antibody and immunoglobulin production. CONCLUSION: This study indicates that SS patients with ectopic GCs have distinct features. Ectopic GC structures were particularly noted in patients with higher focus scores, and might play an essential role in sustaining antibody production as well as B cell activation.
28424097 Unusual course of generalized lymph node primary plasmacytoma in a patient with Sjögren's 2017 Apr 20 BACKGROUND: Primary lymph node plasmacytoma is a rare disease that typically involves lymph nodes of the neck. In only 15% of cases is the disease generalized. Here, we present a case of generalized lymph node plasmacytoma in a patient with Sjögren's syndrome with an unusual course. CASE PRESENTATION: A 48-year-old white woman presented to our hospital with enlargement of groups of lymph nodes, liver, and spleen. Her medical history was consistent with a 12-year course of Sjögren's syndrome. Blood and urine immunochemistry showed a massive (72 g/l) M-gradient formed from immunoglobulin Aκ in the serum and monoclonal free κ-type light chains in her urine. A skeletal X-ray revealed no bone destruction. Cytological and histological bone marrow assays showed no signs of plasma cell infiltration. The microarchitecture of her neck and inguinal lymph nodes was destroyed. Only small remnants of B cell follicles were found, while the interfollicular areas were expanded and infiltrated by CD138, MuM1, CD43, and IgAκ-positive plasma cells. After nine cycles of doxorubicin, cyclophosphamide, vincristine, and prednisolone chemotherapy, complete remission was achieved. However, the lymphoma relapsed 3 months later, with histological verification in her femoral lymph node. Despite the absence of subsequent adequate therapy, she gradually achieved complete remission of plasmacytoma with the disappearance of paraproteins. CONCLUSIONS: Currently, primary lymph node plasmacytoma is generally considered a nodal marginal zone lymphoma with an extensive plasmacytic differentiation. In our case, despite the critical histological and immunohistochemical evaluation of three lymph node biopsies from different anatomical areas at different times, no signs of nodal marginal zone lymphoma were found. An 18-year follow-up of our patient with primary lymph node plasmacytoma demonstrated an extremely unusual clinical course. Initially, primary lymph node plasmacytoma was refractory to chemotherapy. However, subsequently, she underwent a complete spontaneous remission of plasmacytoma.
28339495 MicroRNA expression profiles identify disease-specific alterations in systemic lupus eryth 2017 The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.
27890174 Immune-Related Adverse Effects of Cancer Immunotherapy- Implications for Rheumatology. 2017 Feb Immune checkpoint inhibitors (ICIs) are increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAEs). Some IRAEs, including inflammatory arthritis, sicca syndrome, myositis, and vasculitis, are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important. In this review, the current literature on rheumatic and musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and treatment considerations are highlighted.
28877615 Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorders, wit 2018 May Although recent accumulative data reveal the clinicopathogenesis of regression in methotrexate-induced lymphoproliferative disorders (MTX-LPDs), the precise understanding including this category remains controversial. In this study, we analyzed 62 patients with MTX-LPD. Forty-three patients showed regression (Reg group), with high rates of Hodgkin lymphoma (HL) and LPD (90 and 88%, respectively). Among the 43 patients of the Reg group, 14 patients (33%) relapsed. The median duration before relapse in the Reg group was 10.6 months. Although the difference of OS between the Reg and Non-Reg groups was not significantly different, relapse-free patients in the Reg group had a superior overall survival (OS). MTX duration had a significant impact on Epstein-Barr virus (EBV) infection (p = .00131). Furthermore, EBV infection was significantly related to clinical manifestations, including spleen invasion, in the regression phenomenon. Some human leukocyte antigens (HLA) alleles might affect MTX-LPD development via EBV infection, although A*2402 and DRB1*0405 might be affected as fundamental factors.
28223750 Tumor Necrosis Factor Alpha Blocker-Induced Erythrodermic Sarcoidosis in with Juvenile Rhe 2017 Feb The development of cutaneous sarcoidosis as a paradoxical adverse event of tumor necrosis factor alpha (TNF-α) blockers has been reported in the literature; however, an erythrodermic form of cutaneous sarcoidosis during anti-TNF-α therapy has not yet been reported. Herein, we report the first case of an erythrodermic form of cutaneous sarcoidosis during anti-TNF-α therapy and review previous studies of cutaneous sarcoidosis. A 6-year-old Korean girl who had been suffering from juvenile rheumatoid arthritis presented with generalized erythematous skin eruption involving more than about 90% of her body surface area. After 14 months of etanercept treatment, the new erythematous skin eruption had developed and progressed into generalized erythroderma. Exclusion of suspected co-medication had been performed based on medication history. She had no other systemic symptoms, and ophthalmologic and neurologic examinations were normal. Histopathologic findings of the skin lesion revealed diffuse non-caseating granulomatous infiltrates composed of epithelioid histiocytes with sparse lymphocytes involving the entire dermis. Periodic-acid-Schiff and acid-fast stains were negative, and acid-fast bacilli was not detected by polymerase chain reaction of the skin biopsy. Based on clinicopathologic findings, she was diagnosed with etanercept-induced sarcoidal granuloma. After discontinuation of the suspected agent, the lesions spontaneously disappeared.
28322470 Anti-Inflammatory and Antioxidant Actions of Copaiba Oil Are Related to Liver Cell Modific 2017 Oct The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · kg(-1) , arthritic rats, and arthritic rats treated with copaiba oil (0.58 and 1.15 g · kg(-1) ). The oil was administrated orally once a day during 18 days after arthritis induction. Both doses of copaiba oil improved the paw edema and the dose of 0.58 mg · kg(-1) improved the swollen adrenals and lymph nodes besides decreasing the plasmatic myeloperoxidase activity (-30%) of arthritic rats. Copaiba oil (1.15 g · kg(-1) ) abolished the increases of protein carbonyl groups and reactive oxygen species in the liver and both doses increased the liver GSH content and the catalase activity in arthritic rats. Copaiba oil (1.15 g · kg(-1) ) decreased glycolysis (-65%), glycogenolysis (-58%), and gluconeogenesis (-30%) in the liver of arthritic animals. However, gluconeogenesis was also diminished by the treatment of control rats, which presented lower body weight gain (-45%) and diminished number of hepatocytes per liver area (-20%) associated to higher liver weight (+29%) and increased hepatocyte area (+13%). The results reveal that copaiba oil presented systemic anti-inflammatory and antioxidant actions in arthritic rats. These beneficial effects, however, were counterbalanced by harmful modifications in the liver cell metabolism and morphology of healthy control rats. J. Cell. Biochem. 118: 3409-3423, 2017. © 2017 Wiley Periodicals, Inc.
29242717 Prevalence, treatments and medical cost of multiple sclerosis in Japan based on analysis o 2017 Nov OBJECTIVE: To understand, through an analysis of health insurance claims data, the current treatment status and medical cost of multiple sclerosis (MS) in Japan. METHODS: We analyzed claims data (January 2005-January 2016) from the Japan Medical Data Center Co., Ltd., identifying MS patients, except those with neuromyelitis optica, using an algorithm based on diagnosis codes. Prescription drug usage and medical costs for MS patients were analyzed. RESULTS: A total of 713 MS patients were identified in the database. Between 2011 and 2015, the age-adjusted prevalence of MS in the database increased from 0.015% to 0.019%, and the female-to-male ratio increased from 1.70 to 2.03. The prescription rate for disease-modifying therapy drugs was higher in larger care settings. Prescriptions for fingolimod increased from 2011, with a concomitant decrease in prescriptions for interferon. The per patient per month cost for MS was ¥124 337 (US$1190 or €1084, as of October 2016). This was higher than the costs for Parkinson's disease (¥84 410), myasthenia gravis (¥82 944) and rheumatoid arthritis (¥53 843). However, the total per member per month cost for MS, which represents the population-based economic impact, was ¥25.2, which was lower than the parallel costs for Parkinson's disease (¥123.0) and rheumatoid arthritis (¥311.6) because of the low prevalence of MS in Japan. CONCLUSIONS: Using real-world data, we obtained up-to-date prevalence, treatment status and medical cost information for MS in Japan. The present results showed the efficacy of a real-world database to obtain the latest national trends for rare diseases, such as MS; this could have important implications for clinicians and policymakers.
29055558 Pelvic fractures after definitive and postoperative radiotherapy for cervical cancer: A re 2017 Dec OBJECTIVES: This study clarified the incidence of and identified the risk factors for post-radiation pelvic insufficiency fractures (PIFs) in women who received postoperative definitive or adjuvant radiotherapy (RT) for cervical cancer. PATIENTS AND METHODS: The medical records and data of imaging studies, including computed tomography scan and magnetic resonance imaging, of women with cervical cancer who received external-beam RT for the entire pelvic area between January 2003 and December 2012 at our institution were reviewed. RESULTS: A total of 533 patients with histologically diagnosed cervical cancer who received RT (298: definitive RT, 235: adjuvant RT) were included in this study. Eighty-four patients (15.8%) developed PIF in the irradiated field. Median age at onset of PIF was 72.5years (range: 54-95years), and 82 of them (98%) were postmenopausal women. Sixty-nine patients (80%) developed PIF within 3years from the completion of RT. The median time for the development of PIF was 14months (range: 1-81months). The most commonly involved fracture site was the sacral bone. Postmenopausal state, coexistence of rheumatoid arthritis, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) use were significant predisposing factors for the development of PIF, according to multivariate analysis. CONCLUSIONS: The incidence rate of PIF among patients who received RT for locally advanced cervical cancer was 15.8%. The principal predisposing factors for post-radiation PIF were postmenopausal state, rheumatoid arthritis, and HDR-ICBT use. Active interventions, including bone density screening followed by medication, should be considered during the early stage of RT for women with high-risk factors of PIF.
28455712 Macrophages' Role in Tissue Disease and Regeneration. 2017 Inflammation is an essential component of the normal mammalian host tissue response and plays an important role during cardiovascular and musculoskeletal diseases. Given the important role of inflammation on the host tissue response after injury, understanding this process represents essential aspects of biomedical research, tissue engineering, and regenerative medicine. Macrophages are central players during the inflammatory response with an extensive role during wound healing. These cells exhibit a spectrum of activation states that span from pro-inflammatory to pro-healing phenotypes. The phenotype of the macrophages can have profound influences on the progression of disease or injury. As such, understanding and subsequent modulation of macrophage phenotype represents an exciting target area for regenerative medicine therapies. In this chapter, we describe the role of macrophages in specific cases of injury and disease. After myocardial infarction, a biphasic response of pro- and anti-inflammatory macrophages are involved in the remodeling process. In volumetric muscle loss, there is an intricate communication between inflammatory cells and progenitor cells affecting repair processes. Osteoarthritis is characterized by increased levels of pro-inflammatory macrophages over an extended period of time with significant impact on the progression of the disease. By harnessing the complex role of macrophages, enhanced therapeutic treatments can be developed that enhance the normal healing response as well as help the survival of therapeutic cells delivered to the site of injury.
29263487 [A Sjögren's syndrome patient with prominent aortic valve involvement: a case report]. 2017 Dec 18 Sjögren's syndrome is a systemic autoimmune disease which is characterized by xerosis, and multiple organs can be affected, causing interstitial lung disease, renal tubular acidosis, blood system involvement, peripheral neuropathy, and liver damage, but cardiac involvement is rare. Here we report a case of Sjögren's syndrome with prominent aortic valve involvement. A 66-year-old woman was admitted for exertional dyspnea, and the ultrasonic cardiogram showed severe aortic stenosis with moderate regurgitation. Preoperative examination for valve replacement found that the patient had elevated erythrocyte sedimentation rate and positive rheumatoid factor, so she was referred to the rheumatology outpatient department for further examination and treatment. Further questions about medical history found that the patient had dry eyes and dry mouth for more than ten years, and had obvious caries. Further laboratory examination showed elevated serum immunoglobulin levels and positive anti-nuclear antibody. The findings of ophthalmologic examination and labial gland biopsy also supported the diagnosis of Sjögren's syndrome. After treatment of glucocorticoids and hydroxychloroquine for ten months, her dyspnea symptoms were obviously improved in the patient, and the rheumatoid factor had become negative while her erythrocyte sedimentation rate normal. Repeated ultrasonic cardiogram examination showed that her aortic stenosis was also improved. The patient has been followed up for four years, and her condition kept stable. Cardiac involvement in Sjögren's syndrome can affect all parts of the heart, but valve involvement is relatively rare. The specific relationship between cardiac involvement and Sjögren's syndrome and the mechanisms behind these associations both need further research.
28013357 Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome. 2017 Apr The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.
27866757 Differential diagnosis of IgG4-related sialadenitis, primary Sjögren syndrome, and chroni 2017 Feb Our aim was to differentiate IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjögren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p<0.001 in all cases. Sialography showed enlargement of the gland, dilatation of the duct, and slightly decreased secretory function in IgG4-related disease; obvious sialectasia and decreased secretory function in Sjögren syndrome; and dilatation of Wharton's duct and filling defects in obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic infiltration with storiform fibrosis, lymphoplasmacytic inflammation and lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia in the three groups, respectively. The number of IgG4-positive plasma cells was 123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p<0.001). The three conditions have different clinical, radiographic, and pathological features that provide important clues to the differential diagnosis. Serological and histological tests are important, and comprehensive consideration is necessary.
27307501 Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. 2017 Jan OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. METHODS: We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours. RESULTS: We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis. CONCLUSIONS: As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.
28913747 Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy. 2017 Nov The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi(2) test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.
28231589 Ultrasound Elastography in Diffuse and Focal Parotid Gland Lesions. 2017 In Europe, ultrasound (US) is the diagnostic gold standard for the visualisation of parotid gland disorders. While high-resolution B-mode US reliably visualises focal lesions, its diagnostic capacity to distinguish tumour entities or to characterise diffuse lesions remains poor. Strain elastography (SE) and shear wave elastography (SWE) are novel imaging techniques that provide additional information about tissue elasticity. SE analyses the strain or displacement in response to force or compression and, therefore, shows the relative tissue elasticity within a selected region of interest (ROI). Recent studies suggest that SE might be able to predict parotid gland malignancy. In SWE, push pulses generate localised displacements within an ROI that describes mechanical tissue properties expressed in absolute values. Recent studies indicate that SWE can predict tissue fibrosis in different organs. This review article highlights the current role of SE and SWE modalities in diffuse and focal changes of the parotid gland.