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We report the case of a woman in her 30s who was referred to the ear, nose and throat department with sudden onset left-sided sensorineural hearing loss (SNHL), left anterior uveitis and erythematous lower limb lesions with bilateral pitting oedema. Based on her symptoms, an underlying inflammatory systemic disease was suspected. Autoantibodies were negative but an X-ray and high-resolution CT scan of the chest were suggestive of sarcoidosis, which was confirmed on endoscopic bronchial biopsy. Following treatment with a course of oral steroids, the patient’s hearing has improved but she still suffers from episodes of uveitis. While immune-mediated inner ear disorders are a recognised cause of SNHL, sarcoidosis is a very rare cause. This case demonstrates the importance of screening for systemic autoimmune aetiology in SNHL and highlights the importance of an effective multidisciplinary team in the diagnosis and management of these patients.

We describe two cases of giant cell arteritis where involvement of the superficial temporal artery and maxillary artery were demonstrated using colour doppler ultrasonography. Maxillary artery involvement is responsible for the symptoms of jaw claudication and toothache, and even headaches might be due to the involvement of the middle meningeal artery which is a branch of the maxillary artery. The maxillary artery has been difficult to visualise until now. There are international consensus definitions of ultrasonographic abnormalities seen in the superficial temporal artery affected by giant cell arteritis. We have used those definitions to demonstrate hypoechoic changes in the maxillary artery affected by giant cell arteritis. The maxillary artery can be visualised in the infratemporal fossa from an echo window between the condylar and coronoid processes of the mandible. This is the first proof of concept evidence that maxillary arteries can be visualised using bedside ultrasonography in giant cell arteritis.

Objective To estimate the current prevalence rates and decadal trends of gout and hyperuricemia in the US, as well as the prevalence of urate-lowering therapy (ULT) among gout patients, using 2007-2016 data from a nationally representative survey of American men and women (the National Health and Nutrition Examination Survey [NHANES]). Methods Using data from 5,467 participants in the NHANES 2015-2016, we estimated the most recent prevalence rates of gout and hyperuricemia. When the NHANES was conducted, all participants were asked about their history of gout (as diagnosed by a health professional) and medication use. Hyperuricemia was defined as having a serum urate level of >7.0 mg/dl in men and >5.7 mg/dl in women. We examined decadal trends in these estimates using data from the NHANES 2007-2016 and investigated ULT usage trends using the NHANES 2007-14 (the most recent data available to date). Results In 2015-2016, the prevalence of gout was 3.9% among adults in the US (9.2 million people), with 5.2% [5.9 million] in men and 2.7% [3.3 million] in women. Mean serum urate levels were 6.0 mg/dl in men and 4.8 mg/dl in women, and hyperuricemia prevalence rates were 20.2% and 20.0%, respectively. The prevalence rates of gout and hyperuricemia remained stable between 2007 and 2016 (P for trend > 0.05). The prevalence of ULT use among patients with gout was 33% in 2007-2014 and remained stable over time (P for trend > 0.05). Conclusion In this nationally representative survey sample of adults in the US, the prevalence rates of gout and hyperuricemia remained substantial, albeit unchanged, between 2007 and 2016. Despite these rates, only one-third of gout patients were receiving ULT.

Background/Aims Musculoskeletal ultrasound (MSUS) has utility in optimising the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs) in patients with inflammatory arthritis. However, it is unclear whether this is useful among patients with concomitant chronic pain and/or fibromyalgia, who often have elevated disease activity scores. We aimed to evaluate the impact of MSUS on inflammatory arthritis patients with concomitant chronic pain and/or fibromyalgia who met criteria for treatment escalation in a district general rheumatology service. Methods We conducted a retrospective audit of inflammatory arthritis patients with concomitant chronic pain and/or fibromyalgia who were eligible for DMARD escalation and underwent a MSUS since 2017. Scanning was performed by either a trained rheumatologist or musculoskeletal ultrasonographer. Synovitis was assessed following OMERACT guidelines. Results 43 patients with inflammatory arthritis and concomitant chronic pain and/or fibromyalgia who underwent MSUS were identified. The mean age was 57.0 years (SD 15.6), and 34 patients (79%) were female. Rheumatoid arthritis was the most frequent diagnosis with 32 patients (74%), with psoriatic arthritis in 5 (12%), undifferentiated inflammatory arthritis in 4 (9%) and axial spondylarthritis (axSpA) in 2 (5%). 20 patients (47%) had a concurrent diagnosis of fibromyalgia. The median tender joint count among non-axSpA patients was 10 (IQR 4-15) and 2 (IQR 0-4) for swollen joints. MSUS was requested for consideration of a bDMARD switch in 21 patients (49%), a new bDMARD in 15 (35%), and starting an adjunctive csDMARD among 7 (16%). 34 patients (79%) were already established on csDMARDs, with 15 patients (35%) being on one or more, and methotrexate being the most prescribed csDMARD in 26 (76%). 14 patients (33%) were already established on bDMARDs, 9 (21%) had been on them previously and 20 (47%) were bDMARD naïve. Among those on bDMARDs, anti-TNFs agents were the most prescribed (71%). Active synovitis was identified in 17 patients (40%). Greyscale synovitis, tenosynovitis and enthesitis were seen in 30 (70%), 10 (23%) and 2 patients (5%), respectively. Erosions were identified in 12 patients (28%), with 2 (17%) having new erosions. 27 patients (63%) had either a csDMARD started (n = 7, 33%), or a bDMARD started (n = 11, 31%) or switched (n = 9, 25%) after MSUS. Those with fibromyalgia were less likely to start or switch DMARDs (8/20 patients, 40%) than those without (19/23 patients, 82.6%), Pchi-squared = 0.004. Furthermore, active synovitis on MSUS was associated with DMARD escalation (14/17 patients [82.4%] with synovitis versus 13/26 patients [50%] without; Pchi-squared = 0.03). Conclusion MSUS avoided unnecessary DMARD escalation in a significant proportion of patients with inflammatory arthritis and features of concomitant chronic pain and/or fibromyalgia (n = 26, 37%), potentially resulting in reduced patient exposure to harmful DMARD side effects, and cost savings for the service. Disclosure M. Chen-Xu: None. D. Hyseni: None. K. Achilleos: None.

Case report - Introduction We present the case of a 70-year-old female with a background of anti-Ro positive Sjögren’s syndrome with difficult sicca symptoms who presented with worsening Raynaud’s, bilateral lower limb petechiae/purpura, fatigue, and progressive peripheral neuropathy. Blood tests revealed positive cryoglobulins with hypocomplementemia, and nerve conduction studies objectively confirmed the peripheral neuropathy. The patient was diagnosed with cryoglobulinaemic vasculitis and treated with pulsed intravenous cyclophosphamide and oral prednisolone, which resolved her rash and halted the progression of her symptoms. Cryoglobulinaemic vasculitis is a rare complication of Sjögren’s syndrome occurring in only 3–4% of patients with the disease. Case report - Case description A 70-year-old female with known Sjögren’s syndrome presented with a two-month history of an intermittent red, pin-prick rash affecting her lower legs, worsening fatigue and Raynaud’s, and a progression of longstanding symptoms of pins and needles from her ankles up to her knees, shortly after an acute Epstein-Barr virus infection. Her Sjögren’s syndrome was diagnosed after she presented with difficult sicca symptoms, fatigue and Raynaud’s phenomenon, and strongly positive ANA and anti-Ro antibodies (>240 u/mL). Past medical history was notable for microscopic colitis. On examination, she had bilateral pitting oedema with a purpuric rash affecting both legs. She had reduced sensation to both knees, but with normal power and downgoing plantars. Her joints examined normally. There were no ischaemic changes in her peripheries. Blood tests showed a positive cryoglobulin consisting of a monoclonal IgM paraprotein with polyclonal lambda light chains. She had a normal kappa: lambda ratio and Bence-Jones proteins. Inflammatory markers were raised (CRP 34mg/L, ESR 93mm/hour), with hypocomplementemia (C4 0.05g/L, normal C3). Otherwise, her full blood count, electrolytes, renal and liver function tests, chest X-ray, urine dipstick, hepatitis serology, ANCA profile, B12, folate and ferritin were unremarkable. Nerve conduction studies showed a length-dependent, moderately severe sensory motor axonal peripheral neuropathy, which Neurology agreed was due to a vasculitic process. The patient was diagnosed with a cryoglobulinaemic vasculitis with peripheral nerve involvement secondary to her Sjögren’s syndrome. This was initially treated with prednisolone 40mg daily, intravenous pulsed cyclophosphamide, which resolved her rash and halted the progression of her peripheral neuropathy. Pregabalin was prescribed for pain relief. After completing six cycles of cyclophosphamide, the patient was commenced on azathioprine. This was then replaced with mycophenolate due to leukopenia. She was gradually weaned off steroids, and her vasculitis to date remains biochemically and clinically stable. Case report - Discussion The presence of the combination of a petechial/purpuric rash on her lower limbs, worsening fatigue and Raynaud’s, and symptoms consistent with a progressive peripheral neuropathy raised the suspicion of a vasculitic process in this patient, which warranted urgent investigation. She had a type II mixed cryoglobulinemia which is the most common type of cryoglobulinemia found in Sjögren’s syndrome, evidenced by the presence of a monoclonal IgM paraprotein with polyclonal lambda light chains. Cryoglobulinaemic vasculitis is a systemic vasculitis characterised by the deposition of immune complexes into small vessels, commonly affecting the peripheral nerves, skin, and joints. Clinically, this can manifest with arthralgias/arthritis; constitutional symptoms, such as fatigue and fever; neurologically, with peripheral neuropathies, cranial nerve and central nervous system involvement; and with vascular symptoms, such as petechiae/purpura, skin ulcers, hyperviscosity syndrome, and Raynaud’s. Laboratory features consistent with a diagnosis of cryoglobulinaemic vasculitis aside from the sine qua non of positive cryoglobulins include hypocomplementemia (especially complement C4), positive rheumatoid factor, and a positive serum monoclonal component. We suspect that her cryoglobulinaemic vasculitis was most likely due to Sjögren’s syndrome, although it could have been triggered by the preceding Epstein-Barr virus infection, as this can be associated with cryoglobulinemia also. The decision to treat aggressively with pulsed intravenous cyclophosphamide and prednisolone was made given the severity of the patient’s symptoms, especially her progressive peripheral neuropathy. Given the paucity of data in the literature on the management of cryoglobulinaemic vasculitis secondary to rheumatological conditions, cyclophosphamide and prednisolone were chosen as these are proven in the other small vessel vasculitides, such as ANCA-associated vasculitis. This case is of interest as cryoglobulins are found in approximately 7–16% of patients with Sjögren’s syndrome, with cryoglobulinaemic vasculitis seen in only 3–4% of patients with the disease. Case report - Key learning points Cryoglobulins are uncommon in Sjögren’s syndrome, occurring in 7–16% of those with the disease. Symptomatic cryoglobulinaemic vasculitis among those with Sjögren’s syndrome is rare, seen in only 3–4% of cases. The presence of cryoglobulins in Sjögren’s syndrome is of clinical significance, as it is associated with higher global systemic disease activity and extra glandular involvement. Compared to non-cryoglobulinaemic patients with Sjögren’s syndrome, those with cryoglobulinemia are more likely to have lymphadenopathy, constitutional symptoms, peripheral nervous system and pulmonary involvement, and glandular, articular, and cutaneous features of the disease. The type of cryoglobulinemia found in Sjögren’s syndrome is the mixed type, which are either formed from a monoclonal immunoglobulin (usually IgM) and a polyclonal immunoglobulin (type II), or two polyclonal immunoglobulins (type III). Other conditions associated with mixed cryoglobulinemia include rheumatoid arthritis and systemic lupus erythematosus (SLE), although the most common cause of these is chronic hepatitis C (80–90% of cases). Other causes of mixed cryoglobulinemia include other viral infections, including Epstein-Barr virus and hepatitis B, and certain bacterial and parasitic infections. Most of the literature on the management of cryoglobulinaemic vasculitis is in the context of patients with this due to chronic hepatitis C and revolves around treating this with the appropriate antiviral therapy. Consequently, the current treatment options for moderate-to-severe cryoglobulinaemic vasculitis secondary to rheumatological conditions are the same as those for the other small vessel vasculitides, using a combination of cyclophosphamide and glucocorticoids to induce remission, and azathioprine as maintenance therapy. In severe cases, plasma exchange and rituximab can also be considered as agents to induce remission in cryoglobulinaemic vasculitis.

Background: Gout is associated with many metabolic and cardiorenal comorbidities. Several previous studies investigated the comorbidity patterns by cluster analysis; however, no such study has been based on the entire general population. As such, the generalizability, which is essential to these pattern analyses, remains unknown. Objectives: We used cluster analysis on a large, representative general population sample of the United States to identify discrete phenotype patterns comorbidities observed in gout patients. Methods: We used data from 8,607,137 participants in the 2007-2016 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of adults in the United States. Diagnosis of gout was based on survey of physician- or health professional-diagnosed gout. We used cluster analysis to identify subgroups among participants with gout with distinct comorbidity subgroups based on 9 variables: obesity, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, coronary heart disease (CHD), heart failure (HF), chronic kidney disease (CKD), and liver disease. Results: Cluster analysis identified 5 different subgroups (C1-C5) (Table 2). C1 had the highest proportion of patients with CKD (97%). C2 consisted of patients with gout but few other comorbidities. All patients in C3 had diabetes, but no HF, CHD, or CKD. C4 consisted primarily of patients with liver disease (85%), with high prevalences of lipid abnormalities and obesity. C5 had the highest proportion of patients with CHD and HF. Conclusion: These findings from a nationally representative data of US adults indicate that gout comorbidities have 5 distinctive phenotypic patterns. These subgroups may have implications in pathogenesis of gout and/or for personalized care in the management of gout and comorbidities. Disclosure of Interests: None declared

Background Although African-Americans (AAs) have a higher prevalence of risk factors for gout and hyperuricemia (e.g., hypertension, obesity, and chronic kidney disease [CKD]) than Whites, data on their disease burden of gout and hyperuricemia remains scarce. Objectives To examine potential racial/ethnic disparities in the prevalence of gout and hyperuricemia, using a nationally-representative sample of United States (US) adults over the past 10 years (The National Health and Nutrition Examination Survey [NHANES] 2007–16). Methods Using data from 26 332 participants aged ≥20 years (13 539 females and 12 793 males) from NHANES 2007–16, we calculated the age-standardised prevalence of gout and hyperuricemia by race/ethnicity. Gout was defined by report of a diagnosis by a health professional, and hyperuricemia as a serum urate >7.0 mg/dL (0.42 mmol/L) from participants’ blood samples. Logistic regression was used to adjust for covariates, while taking into account clusters and strata of the complex survey design of NHANES. Results The age-standardised prevalence of gout was 3.7% for Whites and 4.7% for AAs, with the age-standardised prevalence of hyperuricemia being 12.7% and 14.9% for Whites and AAs, respectively. Compared to Whites, AAs had a 65% higher odds of gout among females (age-adjusted OR, 1.65; 95% CI, 1.14 to 2.38) and a 31% higher odds of gout among males (age-adjusted OR, 1.31; 95% CI, 1.05 to 1.63). Further adjustment by body-mass index (BMI) attenuated these associations to non-significance for both sexes (table 1). AA females had a higher odds of hyperuricemia than White females (age-adjusted OR, 2.17; 95% CI, 1.72 to 2.73), but not males (age-adjusted OR, 1.08; 95% CI, 0.95 to 1.22; P for interaction=0.002) (table 1). Among females, this association attenuated after further adjustment for BMI, hypertension, CKD, type 2 diabetes mellitus, household income, and education, but remained significant (adjusted OR, 1.52; 95% CI, 1.19 to 1.95). Conclusions These nationally-representative data indicate that AAs have a larger disease burden of gout and hyperuricemia than Whites, particularly among women. This burden appears to be at least partly due to a higher prevalence of risk factors for hyperuricemia in AAs. 1 Reference [1] Flegal KM, et al. JAMA2016Jun 7;315(21):2284–2291. Disclosure of Interest M. Chen-Xu: None declared, C. Yokose: None declared, H. Choi Grant/research support from: Ironwood and Ardea/AstraZeneca, Consultant for: Horizon and Selecta

The IL-23R region is associated with a number of non-infectious inflammatory conditions including inflammatory bowel disease, ankylosing spondylitis and psoriasis,1,–,3 and albeit with less consistent evidence, rheumatoid arthritis (RA).4,–,6 Association of rs1343151 (G→A) with RA, but not rs1004819/rs10489629/rs2201841 , has been reported in European and New Zealand sample sets;5 none of rs3212227/rs6887695/rs7530511 was associated in European and North American sample sets,6 and rs7517847 was not associated in meta-analysed European and New Zealand sample sets.4 Given the immunological evidence pointing to the importance of the Th17–IL-23 axis in inflammation and autoimmunity,7 and the unresolved question of whether or not IL-23R is associated with RA, we further investigated association of IL-23R with RA in white European Caucasian case–control sample sets (cases ascertained …

Introduction The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus. Methods A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA. Results No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR) = 0.95 (0.80 to 1.12), P = 0.54), or rs17388568 (OR = 1.03 (0.90 to 1.19), P = 0.65) or rs907715 (OR = 0.98 (0.86 to 1.12), P = 0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR = 0.86 (0.82 to 0.91), P = 8.8 × 10-8, P = 2.1 × 10-8 including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR = 1.03, (0.98 to 1.09); P = 0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR = 0.93 (0.87 to 1.00), P = 0.07). However, this trend was not independent of the association at rs6822844. Conclusions The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P ≤ 5 ×10-8) level of support for association with RA. As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association.