The Many faces of vasculitis: diagnostic challenges and economic burden

The systemic vasculitides are characterized by inflammation of the blood vessel walls. Most vasculitides are idiopathic but sometimes a triggering event, e.g., medication, can be identified. Vessels of any type and size can be affected, resulting in a wide spectrum of symptoms ranging from mild to multisystemic life-threatening disorders. The rarity of vasculitides and the heterogeneous nature of the diseases present a diagnostic challenge causing diagnostic delay and numerous examinations. Imaging, including positron emission tomography with computed tomography (PET/CT), has an increasing role in the diagnostic work-up. The aim of this study was to evaluate the performance of PET/CT prospectively, in a real-life cohort of patients with suspected vasculitis, to assess the diagnostic delay and total costs of the diagnostic process of systemic vasculitis and to explore the rare association between large vessel vasculitis (LVV), chemotherapy and granulocyte-colony stimulating factor (G-CSF). PET/CT was found effective in diagnosing vasculitis in a cohort of 82 patients. Lower dose and shorter duration of glucocorticoid medication were significantly associated with positive PET/CT vasculitis finding. Overall, PET/CT revealed clinically significant information in 56% of the patients. Among systemic vasculitides, the diagnostic delay was substantial with great individual variability. Diagnostic delay was correlated with higher total costs, but PET/CT was not a significant contributor. LVV and neutropenic infections might present with similar clinical symptoms. We identified six patients with breast cancer who unexpectedly developed acute, non-infectious LVV during chemotherapy. This patient series and a systematic literature review support the previous reports of a rare causal association between LVV, chemotherapy and G-CSF.Vaskuliitin monet kasvot: diagnoosivaiheen haasteet ja taloudellinen taakka Vaskuliitit ovat verisuonen seinämän tulehduksia, jotka immunologisella mekanismilla vaurioittavat suonen seinämää. Vaskuliitin syy on usein tuntematon, mutta joissain harvoissa tapauksissa laukaiseva tekijä, kuten lääkeaine, voidaan tunnistaa. Sairastuneen suonen koko ja sijainti vaikuttavat taudinkuvaan, joka vaihtelee lievistä paikallisoireista vaikeisiin elinvaurioihin. Vaskuliittien harvinaisuus ja oireiden epämääräisyys aiheuttavat diagnoosiviivettä ja laaja-alaisia tutkimuksia. Kuvantamistutkimuksilla, kuten positroniemissiotomografia-tietokonetomografialla (PET/TT), on lisääntyvä merkitys vaskuliittien diagnostiikassa. Tämän tutkimuksen tarkoituksena oli selvittää PET/TT-kuvantamisen merkitystä vaskuliittiepäilyssä, systeemistä vaskuliittia sairastavien potilaiden diagnoosivaiheen viivettä ja kustannuksia sekä tutkia harvinaista yhteyttä suurten suonten vaskuliitin (SSV), kemoterapian ja valkosolukasvutekijähoidon välillä. PET/TT osoittautui hyödylliseksi vaskuliittidiagnostiikassa. Glukokortikoidilääkityksen matalampi annos ja lyhyempi käyttöaika olivat merkitsevästi yhteydessä positiiviseen PET/TT-vaskuliittilöydökseen. PET/TT-kuvantamisessa 56 %:lla potilaista todettiin kliinisesti merkitsevä löydös. Potilailla, joilla oli systeeminen vaskuliitti, diagnoosiviive oli huomattava ja viiveen yksilöllinen vaihtelu suurta. Diagnoosiviiveen ja korkeampien kustannusten välillä oli merkittävä yhteys. Sen sijaan PET/TT ei ollut yksinään merkittävä kustannustekijä. SSV ja neutropeeniset infektiot voivat olla taudinkuvaltaan samankaltaisia. Tunnistimme kuusi rintasyöpää sairastavaa potilasta, joille kehittyi yllättäen akuutti, ei-infektiivinen SSV kemoterapiahoidon aikana. Tämä potilassarja ja aiheesta laadittu systemaattinen kirjallisuuskatsaus puoltavat harvinaista syy-yhteyttä SSV:n, kemoterapian ja valkosolukasvutekijän välillä

INFLUENCE OF MEDITERRANEAN DIET ON INCIDENCE AND COURSE OF INFLAMMATORY RHEUMATIC DISEASES

Th e Greek “Father of Medicine” and physician Hippocrates, said around 400 B.C. “Let thy food be thy medicine and thy medicine be thy food” (Nikiphorou et al. 2018) Therefore, over the last decades we become increasingly aware and concerned about how nutrition affects our health and the field of nutrition have meet unprecedented interest and expansion. On the other hands, a number of dietary factors might act as environmental triggers in rheumatic and muskuloskeletal diseases (RMDs) development. Overall, a ‘Western’ type diet rich in energy intake, total and saturated fat, an unbalanced ratio of n-3 to n-6 fatty acids, high in sugar and low in fiber and antioxidants might increase the risk of RMDs both directly through increasing inflammation (Minihane et al. 2015) and indirectly through increasing insulin resistance, obesity and associated co-morbidities, with obesity being a known risk factor for RMDs (Qin et al. 2015). In detail, high consumption of foods characteristic of the ‘Western-type’ diet such as red meat, meat and meat products combined, or total protein have been shown to increase the risk of inflammatory polyarthritis suggesting a role of advanced glycation end products (AGEs) (Pattison et al. 2004). This is supported by findings of regular consumption of sugar-sweetened soda, but not diet soda, being associated with an increased risk of seropositive rheumatoid arthritis (RA) in women (Hu et al. 2014), and of high fructose corn-syrup sweetened soft drinks, fruit drinks and apple juice being associated with arthritis in young US adults (DeChristopher et al. 2016). It is hypothesized that regular consumption of excess free fructose and HFCS contributes to fructose reactivity in the gastrointestinal tract and intestinal in situ formation of enFruAGEs, which once absorbed, travel beyond the intestinal boundaries to other tissues and promote inflammation (DeChristopher et al. 2016). Individual biomarkers of antioxidant intake have also been previously investigated in relation to RA with some evidence that low serum levels of selenium and alpha tocopherol (Knekt et al. 2000) and beta carotene (Comstock et al. 1997) are associated with an increased disease risk. Interestingly, a meta-analysis also suggests that coffee consumption of ≥ four cups per day is associated with an elevated risk of seropositive RA but not seronegative RA (Lee et al. 2014). However, the results should be interpreted with caution due to other potential confounders. The same meta-analysis found no association between tea consumption and risk of RA (Lee et al. 2014). On the contrary, consumption of longchain omega-3 polyunsaturated fatty acids, derived from fish and fish oil, is associated with a reduced risk of inflammatory RMD like RA (Di et al. 2014) probably due to their anti-inflammatory properties. The Mediterranean diet (MD), rich in plant-based foods such as wholegrains, legumes, fruit, vegetables, extravirgin olive oil and low in red meat consumption, might have the potential to reduce the risk of RA. It has been shown that greater adherence to the MD is associated with lower concentrations of inflammatory biomarkers (Fung et al. 2005), while daily consumption of monounsaturated fatty acids from olive oil is thought to be the key factor in suppressing RA disease activity (Matsumoto et al. 2017). Other nutritional approaches like vegan, elemental or elimination diets did not showed any superiority to the MD (Ciccia et al 2018, Philippou et al. 2018) regarding the interference on RMDs. In addition, recent evidences suggest the diet pattern, by modifying the composition of intestinal microbiome, might influence the activation of innate immune pathways such as inflammasome and autophagy directly involved in the production of pro-inflammatory cytokines such as IL-1b and IL-18 with effects on RMDs Based on current research evidence, it is concluded that adherence to the MD with an increased consumption of fatty fish, reduced consumption of sugar-sweetened drinks and maintenance of a normal body weight, contributes to reducing the risk of RA. Interestingly, looking at the “chrononutrition” following the body circadian rhythms (Nobel Prize for Medicine 2017) it has been assessed that circadian misalignment, behavioral processes such as food intake or sleep occurring at inappropriate endogenous circadian times, commonly occurs during shift work (i.e. night shift workers) are associated with serious health problems over the time including RMDs (Cutolo 2018). In conclusion, both correct quality and timing in nutrition, are essential in prevention and/or co-management of RMD-

THE OCCURRENCE OF PARANEOPLASTIC SYNDROMES IN PATIENTS WITH POLYMYALGIA RHEUMATICA TREATED AT THE UNIVERSITY HOSPITAL CENTER OSIJEK

Background: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that occurs in an elderly person, usually over fifty years of age. Disease is characterized by pain, discomfort, and tenderness of shoulder, throat and hip muscles, elevated erythrocyte sedimentation values, and a fast and effective therapeutic response to the applied glucocorticoid therapy. Clinical image of PMR may resemble the presentation of many malignant diseases, given that it is of great importance to do extensive diagnostic treatment of the patient. Objectives: Th e aim of this study was to investigate the occurrence of paraneoplastic syndromes in patients with PMR, treated at the Department of Rheumatology, Clinical Immunology and Allergology of the University Hospital Center of Osijek (UHCO). Methods: Th e study included PMR patients treated at the UHCO in the period from 1/2013. to 10/2018. A study was conducted using data from the General Practice Research Database of the UHCO. Results: In 46 patients with PMR the occurrence of paraneoplastic syndrome was 8.7% (N=4) with a 95% confidence interval of 2.42%–20.79%. Th e median age of the detection of the paraneoplastic syndrome was 73 (65–85) years, and the mean time of detection of the syndrome since the diagnosis of PMR was 1± 1 years. In total number of diagnosed, there is an equal number of male and female patients (N=2, p>0.999). Among males, the occurrence of paraneoplastic syndrome was 15.38%, and among women 6.02% (p = 0.585). The mean age of discovery of male paraneoplastic syndrome was 75±14.14, and in women 64±7.07 godina (p=0.699). Th ere was no statistically significant difference in the age of PMR patients (76.17±6.93) compared to those with paraneoplastic syndrome (71.5±9.11), p=0.213. Conclusions: According to the results of our research the time to diagnose paraneoplastic syndrome is approximately one year after the diagnosis of PMR. Therefore, more extensive diagnostic processing and disease control during the first year from the diagnosis of the PMR will reduce the risk of non-recognition of malignant disease disguised as a clinical image of PMR. In addition, the occurrence of paraneoplastic syndromes was 8.7% in the population of PMR patients included in this fi ve-year study. References: 1. Muller, Sara, et al. Is cancer associated with polymyalgia rheumatica? A cohort study in the General Practice Research Database. Ann Rheum Dis. 2014;73(10): 1769–73. 2. Muller, S., et al. Th e real evidence for polymyalgia rheumatica as a paraneoplastic syndrome. Reumatismo. 2018; 70(1): 23–34. 3. Ji, Jianguang, et al. Cancer risk in patients hospitalized with polymyalgia rheumatica and giant cell arteritis: a follow-up study in Sweden. Rheumatology.2010; 49(6): 1158–63. 4. Myklebust, Geirmund, et al. No increased frequency of malignant neoplasms in polymyalgia rheumatica and temporal arteritis. A prospective longitudinal study of 398 cases and matched population controls. J Rheum.2002; 29(10): 2143–7. 5. Mayer, Miroslav, and Branimir Anić. Paraneoplastički sindromi u reumatologiji. Reumatizam.2015; 62(Suppl. 1): 0–0