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Objectives The role of musculoskeletal US (MSUS) in routine care for diagnosing arthritis is not fully elucidated, but US is more sensitive than clinical joint examination for detecting synovitis. Therefore, the use of US may facilitate diagnosis of arthritis. The aim of the study was to assess whether MSUS examination of hands and feet in relation to the first clinical visit had an impact on the time to reach a final diagnosis and the number of clinical follow-up visits needed after first consultation. Methods Two cohorts referred to the outpatient arthritis clinic with suspected arthritis were compared with each other, (i) MSUS (October 2017 to June 2018) of hands and feet performed prior to the first clinical visit and (ii) MSUS (November 2016 to June 2017) was performed ad hoc, for the following aspects: time to clinical diagnosis, number of clinical visits needed, and number of US examinations. Results In total, 163 and 109 patients were included in the MSUS and comparative cohorts, respectively. Adding MSUS to the first clinical visit reduced the time to diagnosis from mean 31 (32.2) days to 12 (17.3) days (P Conclusion In patients referred for suspected arthritis, routine MSUS in relation to the first clinical visit significantly reduces time to diagnosis and number of clinical visits needed to reach a final diagnosis.

Objective To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. Methods Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0–3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. Results Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10–0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. Conclusion Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up—the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

ObjectiveTo identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs).MethodsSustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses.ResultsOf 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007).ConclusionThe majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.

Background:All patients referred to our Rheumatology department suspected of having arthritis are scheduled for a visit in the out-patient fast track clinic (FTC) for arthritis. Routine blood samples including C-reactive protein (CRP), anti-CCP, IgM RF, and x-ray of hands and feet are available at the first clinical visit where the medical history and clinical examination is obtained by rheumatologists or rheumatologists-in-training under supervision. The role of ultrasound (US) in routine care for diagnosing arthritis is not fully elucidated but US is more sensitive than clinical joint examination for detecting synovitis. Therefore, US may facilitate diagnosis of arthritis.Objectives:To assess whether US examinations of hands and feet in relation to the first clinical visit impact the time to diagnosis and number of clinical visits needed.Methods:From Oct. 2017 to June 2018, US examination of hands and feet (wrist, metacarpophalangeal and proximal interphalangeal joints, ankle, and metatarsophalangeal joints) were performed prior to the first clinical visit by ultrasound-experienced rheumatologists. Using the OMERACT scoring system for grey-scale (GS) and Doppler, synovitis was defined as GS score >1 with or without Doppler score ≥1. Examination time was 20 minutes.Time from the first clinical visit to the final clinical diagnosis and the number of clinical visits needed in the FTC was assessed and compared to a similar patient cohort the previous year (Nov. 2016 to June 2017) where ultrasound was performed ad hoc. Number of revised diagnoses and the number of patients re-referred after 12 months was noted. Local ethics committee ruled that approval was not needed.Results:From 2017- 2018, 163 referred patients had US prior to first clinical visit. 76(47%) were diagnosed with inflammatory arthritis (IA), 12(7%) with crystal-related arthritis, 39(24%) with other Rheumatic Diseases (RMDs) and 36(22%) with no RMD diagnosis. The comparative cohort comprised of 109 patients of whom 29(27%) were diagnosed with IA, 16 (15%) with crystal-related arthritis, 31(28%) with other RMDs and 33 (30%) with no RMD diagnosis. Adding US to the first clinical visit reduced the time to diagnosis from mean 31 (standard deviation(SD) ±32.2) days to mean 12 (±17.3) days. The number of clinical visits needed was reduced from mean 2.8(±1.1) to 2.1 (±1.3) corresponding to a reduction of 114 visits in the period from 2017–2018. The mean number of all US examinations in the FTC was 1.1 (±0.3) in the US cohort versus 0.8(±0.7) in the comparative cohort. In the US cohort vs. comparative cohort 8 (4.9%) vs. 17 (15.7%) patients had a revised diagnosis at 1 year-follow-up, and 7 (4%) vs. 12 (11%) were re-referred, respectively. For demographics, clinical, US, and laboratory characteristics see Table 1 where median values and inter-quartile range (IQR) for all parameters.Conclusion:Adding routine US examination to the first clinical visit reduces time to diagnosis markedly, lowers the number of clinical visits needed thereby reducing the time patients spent away from work, and freeing time for visits in the FTC to be used for other patientsTable 1.Comparative cohortUS cohortP(n=109)(n=163)AgeMedian [IQR]55.5[42;69]53[40;67]0.44Mean ±SD54.7±16.153.2±17.2Time to diagnosis daysMedian [IQR]12.4[10;42]0[0;25]Mean ±SD30.6±32.212.4±17.3Visits in FTCMedian [IQR]3[2;3]2[1;2]Mean ± SD2.8±1.12.1±1.3US assessments in the FTCMedian [IQR]1[0;1]1[1;1]Mean ±SD0.8±0.71.1±0.27Swollen joint count (0-28)Median [IQR]0[0;1]0[0;2]0.19Mean ±SD1.1±2.11.8±3.1Tender joint count (0-28)Median [IQR]1[0;5]1[0;5]0.06Mean ±SD3.1±3.73.1±5.2Grey-scale US sum score (0-72)*Median [IQR]1[0;3]4[1;8]Mean ± SD2.8±5.96.3±7.9Colour Doppler US sum score (0-36)*Median [IQR]0[0;0]0[0;2]Mean ±SD1.2±4.02.8±5.9CRP (mg/l)Median [IQR]4[1;16.5]3[1.75;12]0.42Mean ± SD13.4±23.19.6±14.6P, p-value for Mann-Whitney U test for comparing independent data.* US sum score for both hands and feet.Disclosure of Interests:Mads Ammitzbøll_Danielsen: None declared, Uffe Møller Døhn Speakers bureau: Roche, Lilly, Novartis, Viktoria Fana: None declared, Torsten Møller: None declared, Sin Ngai Ng: None declared, Anne Emilie Secher: None declared, Jens Jørgen Lykkegaard: None declared, Lene Terslev Speakers bureau: Novartis, Pfizer, Roche

Background:Giant Cell Arteritis (GCA) is a vasculitis predominantly affecting the large vessels from aorta and its proximal branches and extra-cranial arteries. Precise and fast diagnosis is important in order to initiate proper treatment and avoid ischaemic events, e.g. irreversible visual loss. Unnecessary and prolonged glucocorticoid treatment is also unwanted due to its significant side effects. Therefore, immediate diagnosis of GCA is recommended, and the primary diagnostic tool, according to EULAR recommendation, is vascular ultrasound (US)1. In 2018, a GCA Fast-Track Clinic (FTC) was implemented in our department covering a population of approximately 900.000. Patients even with a low á-priori suspicion of GCA were accepted. It is the aim to have patients seen within one office day.Objectives:In this retrospective study, to describe clinical data from patients seen in the FTC in a 1-year period from September 1st, 2018 and to investigate the time required for making a diagnosis, and to which extent US as the primary diagnostic tool was adequate for making the final diagnosis.Methods:All patients, irrespective of clinical presentation, had US of bilateral temporal-, facial-, axillary and common carotid arteries done (exam time 30 min.). All US were done by ultrasonographers with experience and training in vascular US. Immediately after the initial US, patients were seen by a senior registrar in rheumatology at our out-patient clinic. The senior registrar was aware of the conclusion of the US. Decisions on further diagnostic procedures were solely up to this rheumatologist. From electronic patient report files, all patients’ clinical- and US-findings as well as results from other diagnostic procedures (temporal artery biopsy (TAB) and positron emission tomography computed tomography (PET-CT)) were evaluated. Furthermore, final diagnosis and fulfilment of ACR1990 classification criteria for temporal arteritis at three months was noted, as was the number of days required for diagnosis.Results:A total of 120 patients were seen in the FTC and had a vascular US done. Demographic and clinical data are seen in table 1. Of 120 patients, 42 (35%) had a clinical diagnosis of GCA at three months and 42% fulfilled ACR1990 criteria for temporal arteritis. Based on US alone, 36% of patients had GCA. A diagnosis or exclusion of GCA were done on median 1 day (in 55% of patients). However, in cases where further diagnostics (TAB and PET-CT) were necessary, the time for diagnosis increased substantially. See table 2 for data on waiting time from referral, diagnoses and time required for diagnosis.Table 1Demographic and clinical data (n=120)Females72%Age (years)74 (46-98)Symptom duration (days)16 (1-180)New onset headache72%Jaw claudication21%Temporal artery abnormality33%Visual symptoms42%Visual loss (permanent visual loss)18% (19%)Constitutional symptoms32%Fever11%Weight loss18%Polymyalgia symptoms33%Glucocorticoid therapy68%Duration of glucocorticoid (days)3 (1->365)Haemoglobin (mmol/L)8.0 (5.0-10.0)C-reactive protein (mg/L)22 (0-290)Sedimentation rate (mm/hr)38 (2-146)Values are percentage, median (range)Table 2Office days from referral to visit1 (0-20)Days for diagnosis/exclusion of GCA1 (1-46)GCA clinical diagnosis35%GCA ACR1990 criteria42%Nr. of US (% w. GCA)120 (36%)Nr. of PET-CT (% w. GCA)44 (23%)Nr. of TAB (% w. GCA)34 (21%)Polymyalgia diagnosis17%Arthritis diagnosis5%Other diagnosis17%Conclusion:In this newly established GCA FTC, fast and precise diagnosis of GCA or exclusion of this was possible in majority of patients referred, even though referral criteria were liberal. In 55% of patients, further diagnostic procedures were considered unnecessary, and a diagnosis on day 1 could be established based on US, clinical findings and existing paraclinical data.References:[1]Dejaco C et al.: Ann Rheum Dis 2018;77:636-643.Disclosure of Interests:Uffe Møller Døhn Consultant of: Roche, Lilly, Novartis, Speakers bureau: Roche, Novartis, Abbvie, Pfizer, Viktoria Fana: None declared, Torsten Møller: None declared, Jens Jørgen Lykkegaard: None declared, Lene Terslev Speakers bureau: LT declares speakers fees from Roche, MSD, BMS, Pfizer, AbbVie, Novartis, and Janssen.

In Sudan, post kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined the immunological response in lesions of PKDL patients by immunohistochemistry and compared the findings with results obtained using peripheral blood mononuclear cells (PBMCs). In all lesions, parasites or parasite antigen were present and provoked the formation of an inflammatory infiltrate consisting of a mixture of macrophages, lymphocytes, and plasma cells. In patients who had high interferon-gamma (IFNgamma) responses to Leishmania antigen in vitro, compact epithelioid granulomas were formed. The inflammatory cells were mainly CD3(+) and interleukin-10 (IL10) was the most prominent cytokine in the lesions. However, IFNgamma was found in all and IL4 in most lesions, in varying amounts. PBMCs from all patients responded to Leishmania antigen by IFNgamma production or proliferation. The results indicate that PKDL develops as a result of an influx of immunocompetent cells into skin, which harbours parasites. The inflammatory response to the parasites is complex. It involves several cell types and cytokines, of which some are antagonistic. It is conceivable that the balance between these cytokines determines the outcome of the disease.

Low mean concentrations of serum immunoglobulin A (IgA) and an increased frequency of overt IgA deficiency (IgAD) in certain dog breeds raises the question whether it is a breeding-enriched phenomenon or a legacy from the dog's ancestor, the gray wolf (Canis lupus). The IgA concentration in 99 serum samples from 58 free-ranging and 13 captive Scandinavian wolves, was therefore measured by capture ELISA. The concentrations were markedly lower in the wolf serum samples than in the dog controls. Potential differences in the IgA molecule between dogs and wolves were addressed by sequencing the wolf IgA heavy chain constant region encoding gene (IGHA). Complete amino acid sequence homology was found. Detection of wolf and dog IgA was ascertained by showing identity using double immunodiffusion. We suggest that the vast majority of wolves, the ancestor of the dog, are IgA deficient.

Summary The calcium lowering hormone, calcitonin, also affects the immune system. The effect of nasal salmon calcitonin on lymphocyte transformation tests and on serum-ionised calcium was investigated in a randomised, double-blind and placebo-controlled study including 24 healthy adult volunteers. The participants received a single dose of either 200 IU of nasal salmon calcitonin or nasal placebo in the morning and measurements were done before and 3 h after administration of the spray. Nasal salmon calcitonin exerted a significant hypocalcemic effect, but did not interfere with antigen- or mitogen-induced expansion of T-lymphocytes. It is unlikely that nasal salmon calcitonin affects cell-mediated immunity in healthy subjects.