GIANT CELL ARTERITIS – AN OVERVIEW

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults over age of 50 years in Western countries, affecting aorta and its primary branches (1). Though detailed etiopathogenesis of GCA is not completely understood, studies point to the breakage of immune privilegence of vessel wall, resulting in predominantly TH1 and TH17 mediated vascular inflammation and damage (2). Symptoms and signs of GCA are heterogeneous and reflect tissue and organ ischemia due to vessel wall inflammation, stenosis and/or occlusion (eg. headache, jaw claudication, vision disturbances, arm claudication, etc.), and systemic inflammation (constitutional symptoms, increased inflammatory parameters, polymyalgia rheumatica, ect.) (3). Based on the location of inflamed arteries, GCA could be divided into “cranial limited” and “extracranial large vessel” GCA. Due to severe ischemic manifestations (such as an irreversible vision loss or stroke), GCA represents a medical emergency. Major improvements in the diagnostic approach were reached in the last years, with the implementation of fast track clinics and imaging (mainly ultrasonography) into daily practice (4). Besides, European League Against Rheumatism recently published recommendations on imaging in large vessel vasculitides, acknowledging imaging result in clinically suspected GCA as sufficient for diagnosing GCA and thus equivalent to the position of histology (i.e.b temporal artery biopsy) (5). Furthermore, advances in the treatment of GCA have been made. The treatment goals are the prevention of ischemic complications and the achievement of sustained remission, with the minimum treatment related adverse events. Glucocorticoids have been for decades the standard therapy in GCA6. As prolonged glucocorticoid therapy could be associated with significant adverse events, different medications have been evaluated for the steroid sparing effect (6). Methotrexate was the most common conventional immunosuppressive drug used until very recently, when tocilizumab was approved for the GCA treatment, based on GiACTA trial (7). But therapeutic armamentarium is rapidly evolving and new medications (i.e. biologic and conventional targeted) for GCA are expected in the future. References: 1. Pucelj NP, Hočevar A, Ješe R, et al. The incidence of giant cell arteritis in Slovenia. Clin Rheumatol. 2018 Jul 30. doi: 10.1007/s10067- 018-4236-6. 2. Terrades-Garcia N, Cid MC. Pathogenesis of giant-cell arteritis: how targeted therapies are influencing our understanding of the mechanisms involved. Rheumatology (Oxford) 2018; 57(suppl_2):ii51–62.. 3. Koster MJ, Matteson EL, Warrington KJ. Large-vessel giant cell arteritis: diagnosis, onitoring and management. Rheumatology (Oxford) 2018;57(suppl_2):ii32–42. 4. Hocevar A, Rotar Z, Jese R, et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A Prospective Longitudinal Study. Medicine (Baltimore). 2016 Apr;95(14):e3210 5. Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018; 77:636–6436. Kermani TA, Dasgupta B. Current and emerging therapies in large-vessel vasculitis. Rheumatology (Oxford). 2018 Sep 1;57(9):1513–1524 7. Hočevar A, Ješe R, Rotar Ž, et al. Does leflunomide have a role in giant cell arteritis? An open-label study. Clin Rheumatol. 2018 Aug 6. doi: 10.1007/s10067-018-4232-

COLOUR DOPPLER SONOGRAPHY OF FACIAL AND OCCIPITAL ARTERIES IN PATIENTS WITH GIANT CELL ARTERITIS

Background: Giant cell arteritis (GCA) is the most common systemic large and medium size artery vasculitis in Western countries. Colour Doppler Sonography (CDS) 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. Objectives: 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. We used a Philips IU22 with a 5–17.5 MHz multi-frequency linear probe from January 2014 to August 2016 and a Philips Epiq 7 with a 5–18 MHz multi-frequency linear probe from September 2016 to December 2016. 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 (66.7% female) patients. The patients’ median (IQR) age was 73.7 (66.1–79.1) years, and they had a median (IQR) symptom duration of 30 (21–90) days. We observed the halo-sign on the FaA, and OcA in 38 (40.9%), and 29 (31.2%) cases, respectively. The FaA, and OcA were simultaneously affected in 18/93 (19.4%) cases. Either 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. Patients with OcA involvement least commonly had extracranial large vessel disease. Conclusions: A fifth of patients with a negative CDS of the TAs had signs of vasculitis on the CDS of the FaA, or OcA. Th e 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. References: 1. Ješe R, Rotar Ž, Tomšič M, Hočevar A. Th e role of colour doppler ultrasonography of facial and occipital arteries in patients with giant cell arteritis: A prospective study. European Journal of Radiology. 2017;95:9–12

Short-term outcome of patients with adult IgA vasculitis: a single-center experience

BackgroundFollow-up data on IgA vasculitis (IgAV) in adults are scarce. We aimed to investigate the outcome of adult IgAV in a well-defined cohort.MethodsData from histologically proven patients diagnosed between January 2010 and July 2022 with at least a 3-month follow-up were analyzed. The frequency and type of relapses and information on kidney function were extracted. Risk factors for IgAV relapse and decline in renal function were studied using the Cox hazards regression analysis. Mortality in IgAV was assessed using the Kaplan–Meier analysis and the standardized mortality ratio (SMR).ResultsIn total, 265 patients were followed for a median of 24 months. At baseline, 38.9, 29.8, and 44.5% had articular, gastrointestinal, and renal involvement, respectively. Initially, 189 (71.3%) patients received systemic glucocorticoids, and 32 (12.1%) patients received an additional immunomodulator. During follow-up, 42 (15.8%) patients relapsed. Relapses were more common in younger patients (HR 1.03 [95%CI 1.01–1.05]) and those without baseline glucocorticoid treatment (HR 3.70 [95%CI 2.0–6.67]). Furthermore, 74 (27.9%) patients had persistent abnormal urinalysis and a substantial (≥20%) decline in glomerular filtration rate (eGFR) was recorded in 41 (15.5%) patients. The factors associated with persistent abnormal urinalysis were an absence of IgAV joint involvement and baseline immunomodulatory treatment. Pre-existent chronic kidney disease and heart failure were associated with eGFR decline. The overall SMR was 1.4 (95%CI 1.14–1.71) compared to the Slovenian general population.ConclusionIgAV relapses occurred in 15% of patients, with younger patients with symptomatically managed IgAV experiencing it more frequently. Heart failure emerged as a predictor of persistent abnormal urinalysis and a decline in eGFR. Adults with IgAV had increased mortality compared to the general population

Epidemiologija i dijagnostika primarnoga Sjögrenovog sindroma

This review paper contains selected aspects of Sjögren’s syndrome. It consists of epidemiology, ultrasound of salivary glands and antimuscarinic antibodies. The first part present studies aimed to determine the prevalence and the incidence of the disease with special emphasize on epidemiological studies performed in Slovenia. This is followed by the demonstration of the role of ultrasound of salivary glands in the diagnosis of Sjögren’s syndrome and the value of antimuscarinic antibodies in global assesment of the secretory failure.U preglednom su članku opisani epidemiologija, ultrazvučni nalaz slinovnica i antimuskarinska antitijela u Sjögrenovom syndromu. U prvomu su dijelu rada prikazani prevalencija i incidencija bolesti u odnosu na epidemiološke studije u Sloveniji. Prikazana je uloga ultrazvučne pretrage slinovnica u dijagnozi Sjögrenova sindroma i vrijednost antimuskarinskih antitijela u općoj procjeni sekrecijske poremetnje

Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis

In this study, we explored expression of microRNA (miR), miR-target genes and matrix remodelling molecules in temporal artery biopsies (TABs) from treatment-naïve patients with giant cell arteritis (GCA, n = 41) and integrated these analyses with clinical, laboratory, ultrasound and histological manifestations of GCA. NonGCA patients (n = 4) served as controls. GCA TABs exhibited deregulated expression of several miRs (miR-21-5p, -145-5p, -146a-5p, -146b-5p, -155-5p, 424-3p, -424-5p, -503-5p), putative miR-target genes (YAP1, PELI1, FGF2, VEGFA, KLF4) and matrix remodelling factors (MMP2, MMP9, TIMP1, TIPM2) with key roles in Toll-like receptor signaling, mechanotransduction and extracellular matrix biology. MiR-424-3p, -503-5p, KLF4, PELI1 and YAP1 were identified as new deregulated molecular factors in GCA TABs. Quantities of miR-146a-5p, YAP1, PELI1, FGF2, TIMP2 and MMP9 were particularly high in histologically positive GCA TABs with occluded temporal artery lumen. MiR-424-5p expression in TABs and the presence of facial or carotid arteritis on ultrasound were associated with vision disturbances in GCA patients. Correlative analysis of miR-mRNA quantities demonstrated a highly interrelated expression network of deregulated miRs and mRNAs in temporal arteries and identified KLF4 as a candidate target gene of deregulated miR-21-5p, -146a-5p and -155-5p network in GCA TABs. Meanwhile, arterial miR and mRNA expression did not correlate with constitutive symptoms and signs of GCA, elevated markers of systemic inflammation nor sonographic characteristics of GCA. Our study provides new insights into GCA pathophysiology and uncovers new candidate biomarkers of vision impairment in GCA

Laboratory Methodology Important in the Diagnosis and Prognosis of Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by thrombosis and pregnancy complications with persistently elevated levels of antiphospholipid antibodies (aPL). Recently, a unique mathematical calculation has been presented to assess the risk of thrombosis in patients with APS called antiphospholipid score or global antiphospholipid syndrome score (GAPSS). This new approach in the diagnosis of APS leads to the assessment of the risk of thrombosis considering the results of different aPL (lupus anticoagulants (LA), anticardiolipin antibodies (aCL), antibodies against β2GPI (anti-β2GPI), and phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) (isotypes IgG and IgM). This chapter provides an overview of the algorithm strategy for APS diagnosis with the aims of characterizing in detail the laboratory methodology of criteria aPL (LA, aCL, and anti-β2GPI) and noncriteria aPL, such as IgA aCL and IgA anti-β2GPI, anti-domain I β2GPI, and antiprothrombin antibodies. In order to improve APS diagnosis, several new approaches in aPL detection have recently been suggested, such as multiline immunodot assay, detection of aPL by flow cytometry using beads with particular surface properties, and the newly developed automated BioPlex system technology for parallel detection of aCL and anti-β2GPI antibodies of IgG, IgA, and IgM isotypes. A completely different and promising approach in future research lies in the potential of microRNAs as biomarkers for risk of thrombosis and/or obstetric complication

Mnenje posvetovalnega sestanka revmatologov in pulmologov glede obravnave bolnika s prizadetostjo pljučnega intersticija v sklopu vnetnih revmatičnih bolezni

Vnetne revmatične bolezni so heterogena skupina bolezni, ki lahko prizadenejo tudi pljučni intersticij. Tako kot je pogostnost intersticijske pljučne bolezni (IPB) v okviru vnetnih revmatičnih bolezni variabilna, je tudi klinična slika zelo raznolika: od omejene nenapredujoče prizadetosti pljučnega intersticija do fulminantno potekajoče življenje ogrožajoče bolezni. Podatki za diagnosticiranje in zdravljenje IPB v sklopu vnetnih revmatičnih bolezni so razmeroma skopi. Temeljno zdravljenje praviloma predstavljajo imunomodulacijska zdravila. Nedavno so se jim pri progresivni pljučni fibrozi pridružili še protifibrotiki. Odločitev pri kom, kdaj in kako intenzivno zdraviti IPB pogosto predstavlja izziv. V prispevku podajamo sklepe multidisciplinarnega posvetovalnega sestanka slovenskih revmatologov in pulmologov, ki po mnenju avtorjev glede na dostopne podatke pomenijo dobro prakso pri obravnavi tovrstnih bolnikov. Osredinjamo se na bolnike s sistemskimi vezivnotkivnimi boleznimi in revmatoidnim artritisom

Zgodnji gigantocelični arteritis

Gigantocelični arteritis (GCA) je najpogostejši primarni sistemski vaskulitis pri odraslih po 50. letu starosti v Evropi. Prizadene velike in srednje velike arterije in vnetni proces, ki zožuje ali popolnoma zapre svetlino žile, lahko dovede do hudih/trajnih ishemičnih zapletov kot so oslepitev, možganska kap ali miokardni infarkt. V zadnjem desetletju se je z vključitvijo slikovnih preiskav v diagnostični postopek pomembno skrajšal čas do prepoznave bolezni (t.i. zgodnji GCA). Pospešena obravnava bolnikov (ang. “fast track clinic”) je vodila v zmanjšanje pojavnosti najresnejših ishemičnih zapletov bolezni in znižanje stroškov zdravljenja. Vendar pa bolezen praviloma poteka kronično, s poslabšanji, kar skupaj s kroničnim glukokortikoidnem zdravljenjem vodi v kopičenje okvar organov in tkiv. Prav zato se intenzivno preučuje patogeneza bolezni, z možnostjo implementacije izsledkov kot so sodobne molekularno in celično usmerjene tarčne terapije. Glavni cilji našega preglednega članka so bili: a) analiza raziskav z navedenim časom trajanja od začetka simptomov do postavitve diagnoze, b) raziskava obetavnih molekularnih tarč za zdravljenje GCA in c) prepoznava klinično pomembnih celičnih podtipov. Najbolj obetavne tarčne molekule za tarčno zdravljenje so IL-6, IL-12/IL-23 in citototoksični z limfociti T povezan protein 4, medtem ko terapija z zaviralci TNF-α ni bila uspešna. Kliničnih raziskav z učinkovinami, usmerjenimi proti IL-17, še ni. V prispevku pa smo se dotaknili tudi drugih potencialnih terapevtskih tarč, vključno z molekulami, ki sodelujejujo v signalnih poteh

GIANT CELL ARTERITIS – AN OVERVIEW

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults over age of 50 years in Western countries, affecting aorta and its primary branches (1). Though detailed etiopathogenesis of GCA is not completely understood, studies point to the breakage of immune privilegence of vessel wall, resulting in predominantly TH1 and TH17 mediated vascular inflammation and damage (2). Symptoms and signs of GCA are heterogeneous and reflect tissue and organ ischemia due to vessel wall inflammation, stenosis and/or occlusion (eg. headache, jaw claudication, vision disturbances, arm claudication, etc.), and systemic inflammation (constitutional symptoms, increased inflammatory parameters, polymyalgia rheumatica, ect.) (3). Based on the location of inflamed arteries, GCA could be divided into “cranial limited” and “extracranial large vessel” GCA. Due to severe ischemic manifestations (such as an irreversible vision loss or stroke), GCA represents a medical emergency. Major improvements in the diagnostic approach were reached in the last years, with the implementation of fast track clinics and imaging (mainly ultrasonography) into daily practice (4). Besides, European League Against Rheumatism recently published recommendations on imaging in large vessel vasculitides, acknowledging imaging result in clinically suspected GCA as sufficient for diagnosing GCA and thus equivalent to the position of histology (i.e.b temporal artery biopsy) (5). Furthermore, advances in the treatment of GCA have been made. The treatment goals are the prevention of ischemic complications and the achievement of sustained remission, with the minimum treatment related adverse events. Glucocorticoids have been for decades the standard therapy in GCA6. As prolonged glucocorticoid therapy could be associated with significant adverse events, different medications have been evaluated for the steroid sparing effect (6). Methotrexate was the most common conventional immunosuppressive drug used until very recently, when tocilizumab was approved for the GCA treatment, based on GiACTA trial (7). But therapeutic armamentarium is rapidly evolving and new medications (i.e. biologic and conventional targeted) for GCA are expected in the future. References: 1. Pucelj NP, Hočevar A, Ješe R, et al. The incidence of giant cell arteritis in Slovenia. Clin Rheumatol. 2018 Jul 30. doi: 10.1007/s10067- 018-4236-6. 2. Terrades-Garcia N, Cid MC. Pathogenesis of giant-cell arteritis: how targeted therapies are influencing our understanding of the mechanisms involved. Rheumatology (Oxford) 2018; 57(suppl_2):ii51–62.. 3. Koster MJ, Matteson EL, Warrington KJ. Large-vessel giant cell arteritis: diagnosis, onitoring and management. Rheumatology (Oxford) 2018;57(suppl_2):ii32–42. 4. Hocevar A, Rotar Z, Jese R, et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A Prospective Longitudinal Study. Medicine (Baltimore). 2016 Apr;95(14):e3210 5. Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018; 77:636–6436. Kermani TA, Dasgupta B. Current and emerging therapies in large-vessel vasculitis. Rheumatology (Oxford). 2018 Sep 1;57(9):1513–1524 7. Hočevar A, Ješe R, Rotar Ž, et al. Does leflunomide have a role in giant cell arteritis? An open-label study. Clin Rheumatol. 2018 Aug 6. doi: 10.1007/s10067-018-4232-