Žiga Rotar

The role of colour doppler ultrasonography of facial and occipital arteries in patients with giant cell arteritis: A prospective study

OBJECTIVE Colour Doppler Sonography (CDS) in giant cell arteritis (GCA) allows the study of involvement of cranial arteries other than the temporal arteries, which are inconvenient to biopsy, such as the facial (FaA), and occipital (OcA) arteries. We aimed to estimate the frequency of the FaA, and OcA involvement in GCA; and to explore the clinical characteristics of these subgroups of patients. METHODS From 1 January 2014 to 31 December 2016 we prospectively performed a CDS of the FaA, and OcA in addition to the temporal (TA), and the extracranial supra-aortic arteries in all newly diagnosed patients suspected of having GCA. All the arteries were evaluated in two planes for the highly specific halo sign. RESULTS During the 36-month observation period we performed a CDS of the cranial and extra-cranial arteries in 93 GCA patients. We observed the halo sign on the FaA, and OcA in 38 (40.9%), and 29 (31.2%) cases, respectively. The FaA, or OcA were affected in 4/22 (18.2%) patients with a negative TA CDS. FaA involvement significantly correlated with jaw claudication and with severe visual manifestations, including permanent visual loss. CONCLUSIONS A fifth of patients with a negative CDS of the TAs had signs of vasculitis on the CDS of the FaA, or OcA. The addition of FaA and OcA CDS to the routine CDS of the TAs could identify 4.3% more patients and thus further improve the sensitivity of the CDS in the suspected GCA.

A concise review of significantly modified serological biomarkers in giant cell arteritis, as detected by different methods

Giant cell arteritis (GCA) is a primary systemic vasculitis present in subjects older than 50years with involvement of large- and medium-sized arteries. Early diagnosis for GCA is essential to prevent serious complications, such as permanent vision loss and/or cerebrovascular events. Elevated inflammatory cytokines, with acute phase and other proteins dominate large- and medium-sized arteries leading to stenosis or occlusion of arterial lumen. To date, there are no reliable serological markers for monitoring GCA. The review aims to provide concise overview of published GCA studies in order to: a) identify significantly changed serological biomarkers in GCA and compare the influences of techniques for marker evaluation and b) investigate most promising markers in GCA using analyte frequency and meta-analysis.

Tumour necrosis factor-alpha inhibitor-induced hepatic injury in patients with rheumatoid arthritis: two case reports and an analysis of the laboratory data from the Slovenian national biologicals registry

Tumour necrosis factor-alpha (TNF-α) inhibitors are widely used in the management of patients with rheumatoid arthritis (RA) and spondylarthritides. However, TNF-α inhibition may lead to adverse events, including liver injury. The RA patients are frequently treated with several potentially hepatotoxic drugs concomitantly; hence, a causative link between TNF-α inhibitors and liver injury is usually difficult to establish. We report two cases of RA patients who developed histologically manifest liver injury shortly after the introduction of treatment with two different TNF-α inhibitors. Furthermore, we present the analysis of the laboratory data from the BioRx.si registry (the Slovenian national registry of rheumatologic patients treated with biologicals) and provide evidence that elevated levels of serum aminotransferase can be observed in patients treated with TNF-α inhibitors. Additionally, our analysis suggests no significant differences between the impact of adalimumab and etanercept on aminotransferase levels. Although the use of TNF-alpha inhibitors is safe and efficient, we suggest that continuous careful monitoring of aminotransferase levels in patients treated with these agents is probably warranted.

Survivin polymorphism is associated with disease activity in rheumatoid arthritis patients

AIM Survivin expression was associated with unfavorable and erosive course of rheumatoid arthritis (RA). This is the first study investigating association between BIRC5 polymorphisms, survivin plasma levels and disease activity in RA. PATIENTS & METHODS A testing group of 123 and validation group of 150 RA patients initially treated with methotrexate monotherapy were genotyped for three BIRC5 promoter polymorphisms. Survivin plasma levels were determined in testing group. RESULTS BIRC5 c.-31G>C was marginally associated with treatment response after 6 months of methotrexate treatment (p = 0.046) and with DAS28 at the time of inclusion in testing (p = 0.052) and in validation group (p = 0.057). Survivin plasma levels were not associated with BIRC5 polymorphisms or DAS28. CONCLUSION BIRC5 -31C>G polymorphism could be useful pharmacogenetic marker for methotrexate treatment response in RA.

THU0268 Visual Complications in Giant Cell Arteritis – Beyond Inflammation

Background Permanent visual loss, one of the most severe ischemic complications of giant cell arteritis (GCA), affects 6% of patients at our secondary/tertiary rheumatology center despite a fast track GCA diagnostic procedure. Objectives To determine potential clinical and laboratory markers forecasting visual complications in GCA. Methods We performed a paper chart review of GCA cases diagnosed between 01.09.2011 and 31.12.2014. Descriptive statistics was used to describe our cohort and appropriate post hoc tests to compare characteristics of patients with/without visual complications. Results During the 40-month observation period, 83 new GCA cases (70% female) were identified. The median (interquartile range (IQR), range) symptom duration at presentation was 30 days (IQR 14-78 days, range 2-880). 28 patients (33.7%) reported of visual symptoms: blurred vision (16), diplopia (8), amaurosis fugax (5); permanent visual loss (5; all unilateral; in 1 patient after glucocorticoids), and ptosis (1). Conventional cardiovascular risk factors: obesity, arterial hypertension, hyperlipidemia, diabetes mellitus were not associated with visual complications in our cohort. Visual manifestations were significantly more common in patients with permanent atrial fibrillation (AF) (p=0.027). 80% of patients with AF were on anticoagulants. The mean erythrocyte sedimentation rate (69 vs 85 mm/h; p=0.007), C reactive protein (31 vs 93 mg/l, p=0.011) and platelet count (372 vs 405×109/l, p=0.001) were lower in patients with visual symptoms than in those without them. Antiphospholipid antibodies were not associated with visual symptoms.Table 1. Clinical and laboratory features of GCA patients with and without visual symptoms Feature With visual symptoms Without visual symptoms P value Feature With visual symptoms Without visual symptoms P value (N=28) (N=55) (N=28) (N=55) Female, % 71.4 69.1 ns Jaw claudication, % 53.6 30.9 0.059 Age (years), median (IQR) 75.4 (72.9-79.8) 72.2 (66.3-76.6) ns Dry cough, % 7.1 23.6 ns Symptom duration, median (IQR) 30 (14-79) 30 (14-84) ns Clin. changed TA % 71.4 54.5 0.016 BMI, median (IQR) 24.3 (22.4-27.3) 25.0 (22.9-27.4) ns LVV (US) % 23.1 34.7 ns Smokers, % 25.0 45.5 ns ESR (mm/h), mean (SD) 69 (19) 85 (30) 0.007 Diabetes, % 21.4 12.7 ns CRP (mg/l), mean (SD) 61 (54) 93 (64) 0.011 Arterial hypertension, % 64.3 50.9 ns Albumin (g/l), mean (SD)) 33 (5) 32 (4) ns Hyperlipidemia, % 39.3 30.9 ns Ferritin (μg/l), mean (SD) 409 (341) 398 (416) ns PAOD, % 0 1.8 ns SAA (mg/l), mean (SD) 189 (192) 381 (385) 0.049 Low dose aspirin, % 32.1 21.8 ns Hb (g/L), mean (SD) 118 (14) 115 (13) ns Atrial fibrillation, % 25.0% 5.5% 0.027 PLT (109/l), mean (SD) 327 (167) 405 (126) 0.001 General symptom, % 78.6 69.1 ns aCL IgG, % 35.7 46.2 ns PMR, % 17.9 20.0 ns anti-β2 GPI IgG, % 3.6 15.1 ns New headache, % 89.3 65.5 0.034 LA, % 19.9 42.2 ns Legend: BMI, body mass index; PAOD, peripheral arterial occlusive disease; PMR, polymyalgia rheumatica; TA, temporal arteries; US, ultrasonography; LVV, large vessel vasculitis; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; SAA, serum amyloid A; Hb, hemoglobin; aCL, anticardiolipin antibody; LA, lupus anticoagulants; NS, non significant, PLT, platelet count. Conclusions Visual complications were significantly more common in patients with AF which has so far not been reported. The presence of the conventional cardiovascular risk factors, antiphospholipid antibodies seem not to contribute to visual complications. Disclosure of Interest None declared

SAT0283 The Incidence of GIANT Cell Arteritis in Slovenia

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in adults aged 50 years or above. Annual incidence rates vary widely from 6.9–76.6 per 105 of adults in this age group, depending on the region.1 Objectives To determine the incidence rate of GCA in our population. Methods We prospectively collected incident cases of GCA from January 1st 2011 to December 31st 2012 at our department of rheumatology which is a part of an integrated secondary/tertiary university teaching hospital that is the only referral center serving a region representing approximately a quarter of the national adult population. Additionally, newly diagnosed cases of GCA between January 1st 2009 and December 31st 2010 were retrospectively identified by searching the electronic patient records for ICD-10 codes M31.5 and M31.6 at our department. The retrospective approach and search strategy was also applied on electronic medical records at the departments of infectious diseases and ophthalmology between January 1st 2009 and December 31st 2012. To further reduce possibility of underreporting, the attached medical facultys Institute of Pathology provided a list of all temporal artery biopsies examined during the observation period which were then cross-referenced with the hospitals electronic medical records. Annual incidence rate for GCA was then calculated. Results During the four year observation period we identified 97 new cases of GCA (68% female; mean (SD) age 75.6 (8.1) years) from a well-defined adult white Caucasian population of 232,041 inhabitants aged 50 or above. The temporal artery biopsy was consistent with GCA, negative or not performed in 75.3%, 18.6, and 6.2% of cases, respectively. Thus, the annual incidence of GCA in our population is 10.5 (95% CI 8.5–12.7), and 4.7 (95% CI 3.8–5.7) per 105 adults aged 50, and 20 years or above, respectively. Conclusions The annual incidence rate of 10.5 per 105 adults aged 50 or above makes GCA the most common systemic vasculitis in this age group of our population. Although the GCA almost exclusively affects adults over 50 years of age, the incidence rate of 4.7 per 105 adults aged 20 and above, also makes it the most common systemic vasculitis in the adult population overall, with IgA vasculitis coming a close second with 3.7 per 105 adults aged 20 years or above. References Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ et al. Epidemiology of Giant Cell Arteritis and Polymyalgia Rheumatica. Arthritis Rheum 2009;61:1454-61. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1968

The frequency of tuberculosis chemoprophylaxis prior to TNF-α inhibitor treatment, and the incidence tuberculosis infection using a two-step screening algorithm for latent tuberculosis infection: data from the BioRx.si registry

Due to the well-established risk of latent tuberculosis infection (LTBI) reactivation, and its potentially devastating consequences in patients treated with tumour necrosis factor (TNF)-α inhibitors (anti-TNF), a low threshold for TB chemoprophylaxis is usually recommended.1 ,2 Conversely, TB chemoprophylaxis is time consuming, delays the initiation of required treatment, adds to the overall cost of treatment, and carries risk of adverse events in its own right.3 A screening algorithm able to safely reduce the frequency of TB chemoprophylaxis would be of great value. Recently, Mariette et al 4 showed that replacing the tuberculin skin test (TST) with interferon-γ release assays in their LTBI screening algorithm reduced the requirement for TB chemoprophylaxis from 45.2% to 27.3%, while there were no new cases of TB during the 1-year observation period. In Slovenia, since 2002, a two-step LTBI screening algorithm is being used for all rheumatological patients who are candidates for anti-TNF. The LTBI screening is not repeated on a regular …

Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements

The international classification criteria for definite antiphospholipid syndrome (APS) include three laboratory measurements: lupus anticoagulant (LA), IgG and IgM isotypes of anti-cardiolipin (aCL) and anti-β2glycoprotein I antibodies (anti-β2GPI). When persistently elevated, they are specific for APS; however, many patients that fulfil clinical criteria may exhibit negative serological results. These “seronegative” APS (SN-APS) are exposed to an increased thrombotic risk. The aims of our cross-sectional, retrospective study of consecutive autoimmune patients’ samples were to evaluate the association of non-criteria antiphospholipid antibodies (aPL) with thrombosis and obstetric events, to calculate the risk score for adverse events and to assess the specific contribution of single aPL positivity in SN-APS. LA, aCL, anti-β2GPI and anti-phosphatidylserine/prothrombin antibodies (aPS/PT) of IgG, IgM, and IgA isotypes were determined in sera of 323 patients with autoimmune disorders. Medical records of all patients were carefully analyzed. aCL, anti-β2GPI and aPS/PT of IgG and IgA isotypes were significantly associated with thrombosis while none of the IgM aPL showed such association. aPS/PT of all isotypes, aCL and anti-β2GPI of IgG and IgA isotype showed significant correlation to obstetric events. When considering results of aPS/PT ELISA, we could additionally identify 3% of thrombotic patients and 2% of obstetric patients. Thrombotic and obstetric risk scores were calculated showing significantly higher association to clinical events, as compared to evaluating individual risk factors. aPS/PT could represent an additional biomarker in SN-APS patients. IgA aPL are associated with thrombosis and obstetric complications. Risk scores accounting different aPL and conventional risk factors, better assesses risk for adverse event, as compared to evaluating individual factors alone.

The incidence of idiopathic inflammatory myopathies in the adult Slovenian population

Idiopathic Inflammatory myopathies (IIM) are rare disorders. The aim of our study was to determine the incidence of IIM in a well-defined Slovenian region. This retrospective study was conducted at the Department of Rheumatology, University Medical Centre Ljubljana, the only secondary/tertiary rheumatology center in a region with a population of 704,342 adults. We identified potential IIM cases by searching the electronic patient records for ICD-10 codes M33, M35.1, M35.8, M60, G72, G73, and J84. We included incipient IIM cases between January 2010 and December 2017, who were at the time of the diagnosis, residents of the inspected region. To avoid under-reporting due to miscoded cases, we obtained a list of the patients who had histological patterns consistent with IIM on muscle biopsy from the Institute of Pathology. The annual incidence rate for IIM was calculated. During the eight-year observation period, we identified 65 IIM cases (72.3% female, median (IQR) patient age 64.8 (54.8–73.2) years). The estimated annual incidence of IIM in the studied population was 11.5 (95% CI 9.0–14.6) per 106 adults, in females 16.2 (95% CI 12.1–21.4), and in males 6.6 (95% CI 4.0–10.2) per 106 adults. The incidence rate of IIM in Slovenia is consistent with data from the literature.

Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients.

Early diagnosis and treatment of giant cell arteritis (GCA) is crucial for preventing ischemic complications. Multiple serological markers have been identified; however, there is a distinct lack of predicting markers for GCA relapse and complications. Our main objective was to identify serological parameters in a large cohort of treatment-naïve GCA patients, which could support clinicians in evaluating the course of the disease. Clinical data was gathered, along with analyte detection using Luminex technology, ELISA, and nephelometry, among others. Unsupervised hierarchical clustering and principal component analysis of analyte profiles were performed to determine delineation of GCA patients and healthy blood donors (HBDs). Highest, significantly elevated analytes in GCA patients were SAA (83-fold > HBDs median values), IL-23 (58-fold), and IL-6 (11-fold). Importantly, we show for the first time significantly changed levels of MARCO, alpha-fetoprotein, protein C, resistin, TNC, TNF RI, M-CSF, IL-18, and IL-31 in GCA versus HBDs. Changes in levels of SAA, CRP, haptoglobin, ESR, MMP-1 and MMP-2, and TNF-alpha were found associated with relapse and visual disturbances. aCL IgG was associated with limb artery involvement, even following adjustment for multiple testing. Principal component analysis revealed clear delineation between HBDs and GCA patients. Our study reveals biomarker clusters in a large cohort of patients with GCA and emphasizes the importance of using groups of serological biomarkers, such as acute phase proteins, MMPs, and cytokines (e.g. TNF-alpha) that could provide crucial insight into GCA complications and progression, leading to a more personalized disease management.