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Background and Aims: To determine salivary flow rate, oral and periodontal status, OHRQoL, objective (ESSDAI) and subjective (ESSPRI, 6- items-VAS-SS, Profile of Fatigue) indexes, and serum antibody reactivity in patients with primary Sjögren's Disease (pSD). Methods: Thirty-one patients with pSD and 31 control subjects participated in this cross- sectional, single-center study. The unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index, periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, OHRQoL, objective (ESSDAI) and subjective (ESSPRI, 6-items-VAS-SS, Profile of Fatigue) indexes were analyzed. Biochemical analysis of serum from a blood sample was performed. Results: The mean DMFT index of pSD patients was 23.74 ± 7.28 compared with control subjects (20.77 ± 5.73), without statistical significance (p=0.08, T-test). The prevalence of periodontitis was the same in pSD patients and control subjects (83.87% vs. 77.42%), without statistical significance (p=0.348, λ2 test). ESSDAI correlated positively with UWSFR (p

Objectives: The objective of this study was to examine the differences in clinical manifestations and comorbidities in men and women with Sjögren’s syndrome (SS) treated at the University Hospital Centre Split. Methods: The data were collected from outpatient clinics, inpatient facilities and the day hospital of the Department of Rheumatology and Clinical Immunology of the Department for Internal Medicine of the University Hospital Centre Split. By inspecting the protocol and archive of the medical history of the disease, we have collected various data such as the demographic characteristics and the accompanying clinical manifestations and comorbidities. The SPSS 20 software for Windows (IBM, New York, USA), χ2 test, Fisher’s test, Fisher-Freeman-Halton test, univariate logistic regression, Firth univariate logistic regression and multivariate logistic regression were used in the statistical analysis. Results: Out of a total of 317 patients with SS, there were 17 (5.4%) men and 300 (94.6%) women. The median age of the patients was 64 (min-max: 19–89 years of age, Q1- Q3: 54–2 years of age). We have obtained a statistically significantly higher chance of developing lung diseases, vasculitis and lymphoma in men, and a statistically significantly higher chance of developing hypothyroidism in women. By using the Fisher-Freeman-Halton test we have proved a statistically significant association of the younger age group with thrombocytopenia and APS. In multivariate logistic regression in which age and gender were taken as independent variables, we have confirmed the association of the primary SS (pSS) with the male gender and the younger age group. Conclusion: Our study showed that men with Sjögren’s disease had a higher incidence of lymphoma, vasculitis and lung involvement, while women had a higher incidence of hypothyroidism. Furthermore, thrombocytopenia and APS were more common in younger patients. In contrast, cardiovascular diseases, hypertension, diabetes, dyslipidemia, osteoporosis, rheumatoid arthritis (RA ), systemic sclerosis (SSc) and secondary SS (sSS) were characteristically more common in elderly patients. Despite the fact that men are less likely to develop pSS, our research shows that at the time of diagnosis, male patients have a more serious form of the disease than women. Nevertheless, in order to draw precise conclusions on this issue, it is necessary to include the wider population in this research and perform its follow-up over a longer time period., Cilj istraživanja: Cilj istraživanja bio je ispitati razlike u kliničkim manifestacijama i komorbiditetima između muškaraca i žena oboljelih od Sjögrenova sindroma (SS) liječenih u KBC-u Split. Materijali i metode: Podatci su prikupljeni iz ambulanta, stacionara i dnevne bolnice Zavoda za reumatologiju i kliničku imunologiju Klinike za unutarnje bolesti KBC-a Split. Iz arhive medicinske dokumentacije prikupljena su demografska obilježja te popratne kliničke manifestacije i komorbiditeti. U statističkoj analizi korišten je paket SPSS 20 for Windows (IBM, New York, SAD), χ2 test, Fisherov test, Fisher-Freeman-Haltonov test, univarijantna logistička regresija, Firth univarijantna logistička regresija i multivarijantna logistička regresija. Rezultati: Istraživanje je obuhvatilo 317 ispitanika s dijagnozom SS-a: 17 (5,4%) muškaraca i 300 (94,6%) žena. Medijan životne dobi ispitanika iznosio je 64 godine (min-maks: 19 – 89 god., Q1-Q3: 54 – 72 god.). Dobili smo statistički značajno veće izglede za nastanak plućnih bolesti, vaskulitisa i limfoma u muškaraca te statistički značajno veće izglede za pojavnost hipotireoze u žena. Fisher-Freeman-Haltonovim testom dokazali smo statistički značajnu povezanost mlađe dobne skupine s trombocitopenijom i antifosfolipidnim sindromom (APS). Multivarijantnom logističkom regresijom u kojoj smo kao nezavisne varijable uzeli dob i spol, potvrdili smo povezanost primarnog SS-a (pSS) s muškim spolom i mlađom dobnom skupinom. Zaključci: Istraživanje je pokazalo da je u muškaraca sa SS-om bila veća pojavnost limfoma, vaskulitisa i zahvaćenosti pluća, dok je u žena bila veća učestalost hipotireoze. Trombocitopenija i APS češće su se javljali u bolesnika mlađe životne dobi. Nasuprot tomu, kardiovaskularne bolesti, hipertenzija, šećerna bolest, dislipidemija, osteoporoza, reumatoidni artritis (RA ), sistemska skleroza (SSc) i sekundarni SS (sSS) karakteristično su bili češći u bolesnika starije životne dobi. Unatoč činjenici da su muškarci manje skloni razvoju pSS-a, naše istraživanje pokazuje da muškarci imaju veći izgled za ozbiljniji oblik bolesti naspram žena. Ipak, za preciznije zaključke potrebno bi bilo obuhvatiti širu populaciju i pratiti je tijekom duljeg razdoblja.

Introduction. The most common types of vasculitis that involve the gastrointestinal tract (GIV) are immune complex- mediated in systemic lupus erythematosus (SLE ), Sjögren’s syndrome (SS), mixed connective tissue disease (MCTD ), and IgA vasculitis (IgAV). GI manifestations are rarely the leading symptom of systemic vasculitis. Only 1 – 5% of rheumatoid arthritis (RA ) patients develop symptoms of gastrointestinal tract vasculitis (GIV), while up to 40% of them have GI symptoms. GIV is a rare but life-threatening complication in patients with SLE with a prevalence of up to 2.5%. The leading symptoms in patients with GIV include abdominal pain, nausea, vomiting, diarrhoea, small bowel obstruction, and profuse GI bleeding. The objective of this study was to describe the incidence and clinical manifestations of GIV in patients with various systemic autoimmune (AI) diseases who were treated at Split University Hospital Centre over a 10-year period. Materials and methods. A retrospective study was conducted by analysing medical records of patients diagnosed with GIV and treated for SLE , SS, MCTD , vasculitis syndrome, IgAV, and RA between January 2009 and December 2018. Only patients with anamnestic data in relation to abdominal pain or endoscopic and/or radiographic findings of GIV were included in the study. Results. Out of a total number of 12 patients with a confirmed diagnosis of GIV, 9 were male. Eight of them had vasculitis with gastrointestinal involvement (GIV) in IgAV, 2 patients had GIV in SLE , 1 patient had microscopic polyangiitis (MPA ), and one patient had primary SS. In 6 cases, GIV was diagnosed by an MSCT of the abdomen, in one case it was diagnosed by a PET -CT scan, in another case it was diagnosed through histopathological findings, and in 4 cases it was diagnosed through endoscopic findings. The leading symptom in 4 patients was abdominal pain with nausea and vomiting, 2 had profuse GI bleeding, 1 had fatigue without GI symptoms, and the remaining patients’ clinical features included acute abdomen with visible radiographic thickening of the bowel wall with oedema and stratification with ascites. GIV was the cause of death of one patient with SLE . Others had a good or moderate response to treatment with glucocorticoids and immunosuppressants. Conclusion. In conclusion, GIV is a rare manifestation of systemic AI diseases, but the clinical features can be very severe and lead to a fatal outcome, especially if it is not diagnosed at an early stage and treated with aggressive immunosuppressive therapy., Uvod. Najčešći vaskulitisi gastrointestinalnog trakta (GIV) su oni posredovani imuno-kompleksima u sistemskom eritemskom lupusu, Sjögrenovoj bolesti, miješanoj bolesti vezivnog tkiva, IgA-vaskulitisu (IgAV). Gastrointestinalne (GI) manifestacije rijetko su vodeći simptom sustavnih vaskulitisa. Samo 1–5% bolesnika s reumatoidnim artritisom razvija kliničku sliku vaskulitisa gastrointestinalnoga trakta (GIV), dok ih do 40% ima GI simptome. GIV je rijetka, ali životno ugrožavajuća komplikacija u bolesnika sa sistemskim eritemskim lupusom (SLE ), s prevalencijom do 2,5%. Vodeći simptomi u bolesnika s GIV-om su bol u trbuhu, mučnina, povraćanje, proljev, opstrukcija tankog crijeva i obilno GI krvarenje. Cilj ovog rada bio je ispitati učestalost i klinička očitovanja GIV-a u bolesnika s različitim sustavnim autoimunim (AI) bolestima liječenih u KBC -u Split u desetogodišnjem razdoblju. Materijali i metode. R etrospektivno su analizirani podatci iz medicinske dokumentacije bolesnika koji su se liječili od SLE -a, Sjögrenovog sindroma (SjS), miješane bolesti vezivnog tkiva (MCTD ), sindroma vaskulitisa, IgA-vaskulitisa (IgAV) i i RA , a imali su anamnestičke podatke o boli u trbuhu ili endoskopske ili/i radiografske znakove GIV-a, u razdoblju od 1/2009. do 12/2018. Rezultati. Od ukupno 12 bolesnika s potvrđenom dijagnozom GIV-a, 9 su bili muškarci. Osam ih je imalo GIV u sklopu IgAV-a, dvije bolesnice u sklopu SLE -a, MPA jedna bolesnica, primarnog SS-a jedan bolesnik. U 6 slučajeva GIV je dokazan MSCT-om trbuha, u jednom PET -CT-om, u jednom patohistološki, a u 4 slučaja endoskopski. Vodeći simptom u četvoro bolesnika bila je bol u trbuhu s mučninom i povraćanjem, dva su imala su obilno GI krvarenje, jedna bolesnica je imala umor bez GI simptoma, a preostali kliničku sliku akutnog abdomena s radiološki verificiranim edemom i raslojavanjem stijenke crijeva uz ascites. GIV je bio uzrok smrti jedne bolesnice sa SLE -om. Ostali su imali dobar ili umjeren odgovor na liječenje glukokortikoidima i imunosupresivima. Zaključak. Zaključno, GIV je rijetka manifestacija sustavnih AI bolesti, ali klinička slika može biti vrlo teška i dovesti do fatalnog ishoda te je nužna brza dijagnoza i agresivno imunosupresivno liječenje.

Chronic inflammation plays a role in all stages of atherosclerosis leading to coronary artery disease (CAD), with elevated inflammatory markers being associated with the worse clinical outcome. The goal of the current study was to examine possible association between pro-inflammatory/pro-coagulant factors ; anticardiolipin (aCL) autoantibodies, complement C3, C4 and leptin, and the severity of CAD expressed as SYNTAX score. Patients with symptoms of cardiac ischemia undergoing coronary angiography were recruited, and their blood levels of aCL-IgG, aCL-IgM, complement C3, C4 and leptin were assessed. Their association with the SYNTAX score, calculated based on coronary angiography findings, was analyzed. All patients had aCL antibody titer within the normal range. A significant positive association was found for aCL-IgG and SYNTAX score. Male patients had higher average aCL-IgG concentration and SYNTAX score than female patients. No association was found between SYNTAX score and C3 and C4. On the other hand, leptin was negatively associated with SYNTAX score. Our study demonstrates an association between the extent of CAD and aCL-IgG even in the absence of systemic autoimmune disease and at the aCL-IgG levels that are within the normal range. Also, association of lower leptin levels with more severe CAD suggests that its pro-inflammatory effects might not contribute to the pathogenesis of CAD, and that leptin might even exert protective effects on coronary vasculature.

Aim: Systemic sclerosis (SSc) is a rare chronic disease characterized by pathologic collagen deposits in the skin and internal organs. Although it is considered to be an autoimmune disease, immunosuppressants have a limited effect on severe SSc. Intravenous immunoglobulins (IVIG) have shown favorable effects in patients with SSc by suppressing the action of profibrotic cytokines, so they could have additional effect on standard treatment such as cyclophosphamide (CYC). This article presents the immunomodulatory effect of low- dose IVIG in addition to CYC in the treatment of severe SSc in this center during the last 9 years. Methods: This retrospective observational study analyzed the medical documentation of nine patients with SSc treated with low-dose IVIG (0.4 g/kg and month) together with intravenous CYC (600 mg/m2 and month). The therapeutic effect on lung and skin manifestations was assessed. Results: Of the patients one had interstitial lung diseases (ILD), two had progressive skin diseases, and six had a combination of skin and lung involvement. The best results were achieved in skin changes, where complete healing of digital ulcers (DU) was recorded in every reported case. A decrease in the modified Rodnan skin score (mRSS) was noted in three patients and increased diffusion capacity of the lungs for carbon monoxide in another three patients. Conclusion: The results of the study suggest that IVIG may be an additional treatment option together with CYC for patients for whom other therapies have failed, but further studies on the exact role of IVIG in the treatment of severe SSc are required.

The primary mRSS endpoint was not met ; however, TCZ Tx resulted in clinically relevant differences in FVC with preservation of LFS and improvement in fibrosis, measured by HRCT, in SSc pts.

Background: Fibromyalgia (FM) is very common clinical problem in inflammatory rheumatic diseases. Concomitant fibromyalgia may influence on disease activity, functional status and quality of life, and its recognition is important for the management of these diseases.Objectives: The aim of this study was to determine the frequency of FM in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) and to evaluate the effect of fibromyalgia on the outcome measures of these diseases.Methods: This two-center cross-sectional study included patients aged≥18 years, who were diagnosed with axSpA, PsA and FM by the rheumatologist. Patients with axial form of psoriatic arthritis were excluded. Clinical assessments included BASDAI and BASFI for axSpA group, HAQ-DI and DAS28 for PsA group. VAS and the Beck Anxiety Inventory (BAI) were performed for both group.Results: The study included 22 axSpA patients and 22 PsA patients. Out of 44 patients, 20 (45, 5%) were males and 24 (54, 5%) were females , with a mean age of 51±11, 7. Fibromyalgia was present in 18, 18% of axSpA patients and in 22, 73% of PsA patients (p=0, 500). No difference in the prevalence of FM was found between male and female (p=0, 332). BASDAI and DAS28 scores were higher in patients with coexisting FM (p=0, 001). Patients with FM had higher values of BASFI (p=0, 001) and HAQ-DI indexes (p=0, 003), higher VAS pain score (p=0, 001) and higher BAI anxiety score (p=0, 007). Conclusion: Patients with axSpA and PsA with concomitant FM had higher disease activity, a worse functional status, more severe pain and higher levels of anxiety.

Polimiozitis (PM) autoimunosna je bolest koja primarno zahvaća poprečnoprugastu muskulaturu. U mlađoj životnoj dobi najčešće se radi o idiopatskom obliku povezanom sa specifi čnim autoprotutijelima (anti Jo), dok je u zreloj dobi češće povezana s novotvorinama. PM može biti udružen s drugim autoimunosnim bolestima kao što je sistemska skleroza (SSc), rijetka progresivna bolest kojoj je glavno obilježje patološka fi broza tkiva i organa. 65-godišnji bolesnik, dugogodišnji pušač, primljen je u bolnicu zbog bolnog edema podlaktica i potkoljenica te izražene slabosti proksimalnih mišića udova. Iako mišićni enzimi nisu bili povišeni, dijagnoza PM-a postavljena je na osnovi karakterističnoga patohistološkog nalaza. Na trupu su uočene kožne promjene koje bi mogle odgovarati SSc-u, ali nije bilo pozitivnih autoprotutijela ni drugih dijagnostičkih kriterija SSc-a. Nakon iscrpne obrade zbog moguće maligne bolesti započeta je terapija glukokortikoidima (GK) koja je dovela do jenjavanja edema i jačanja mišićne snage. Već nakon četiri tjedna bolesnik se javlja sa simptomima koji upućuju na SSc: Raynaudov sindrom, disfagija i izrazito zadebljanje kože prethodno otečenih dijelova udova. PM je nerijetko pridružen SSc-u. U ovom slučaju nije jasno je li egzacerbacija latentnog SSc-a potaknuta višim terapijskim dozama GK ili se radi o jednostavnom preklapanju dviju bolesti s različitim početkom. Premda ne postoje terapijske smjernice za liječenje preklapanja PM-a i SSc-a, nužna je oprezna primjena GK već i kod diskretnih naznaka SSc-a zbog poznatog učinka viših doza GK na razvoj i tijek bolesti., Polymyositis (PM) is an autoimmune disease which aff ects skeletal muscles. In young age, it usually occurs as an idiopathic disorder associated with specifi c autoantibodies (anti-Jo), while in older age it is oft en associated with neoplasms. It can present with symptoms of other autoimmune diseases, such as systemic sclerosis (SSc), a rare progresive disease characterized by collagen deposits in various tissues and organs. A 65-year-old patient, long-time smoker, came to the ER because of painful edema in the distal parts of his limbs and proximal muscle weakness of his arms and legs. Although his muscle enzymes were not increased, PM was confi rmed by the characteristic pathohistological fi nding. Th e patient had sclerodermal skin lesions on his back, but he did not have other typical SSc symptoms, and the specifi c autoantibodies were negative. He received glucocorticoid therapy (GC) aft er we had fi nished screening for malignant tumors. He felt better, his muscle strength returned, and the limb edema disappeared. Four weeks later, he developed symptoms which are more typical of SSc, such as dysphagia, Raynaud’s phenomenon, and skin thickening of the limbs that had been swollen. PM is oft en associated with SSc. It is not clear if the exacerbation of latent SSc was stimulated by GC, or if it was just a simple overlap of the two diseases with diff erent onsets. Th ere are no therapy guidelines for the treatment of this combination of diseases. Careful use of GC is necessary even if SSc symptoms are discreet, because of the well-known eff ects of GC in SSc.

Serotonin: The New Marker of Skin and Lung Involvement in Systemic Sclerosis

Reumatoidni artritis sustavna je upalna reumatska bolest koja, osim zglobova, zahvaća i unutarnje organe, kožu, osjetilni i živčani sustav, a znatno povisuje i rizik od kardiovaskularnih bolesti. Posljednjih godina znatno se promijenio pristup u dijagnostici i liječenju bolesnika s reumatoidnim artritisom. Rana dijagnoza i pravodobno započinjanje liječenja sintetskim i biološkim lijekovima iznimno su važni da bi se spriječile ireverzibilne posljedice ove teške bolesti. Hrvatsko reumatološko društvo Hrvatskoga liječničkog zbora u skladu s novijim spoznajama u reumatologiji obnovilo je preporuke za liječenje reumatoidnog artritisa.

Spondiloartritisi (SpA) grupa su upalnih reumatskih bolesti koje dijele zajednička etiopatogenetska, radiološka i klinička obilježja. Te su bolesti znatan teret za bolesnika i za društvo. Posljednjih godina dogodile su se velike novosti u klasifi kaciji, dijagnostici i liječenju SpA. Stoga je Hrvatsko reumatološko društvo Hrvatskoga liječničkog zbora ažuriralo prijedlog primjene bioloških lijekova (referentnih ili biosličnih) i novouvedenih ciljanih sintetskih molekula u algoritam liječenja odraslih bolesnika sa SpA. Prijedlog preporuka usklađen je s preporukama uglednih europskih i drugih međunarodnih organizacija iz ovog područja. Nadamo se da će standardizirani, sveobuhvatni i aktualni pristup u ispunjavanju kriterija, odabiru lijekova, praćenju i evaluaciji ishoda koji smo primijenili u cijelom spektru bolesnika sa SpA pomoći kliničarima i drugim zainteresiranima u postizanju optimalnih rezultata liječenja ovih bolesnika

Tofacitinib (CP-690, 550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis. In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily ; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20) ; the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability) ; and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity). At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P

Ako se avaskularna nekroza glave bedrene kosti ne tretira, subhondralni kolaps kosti razvije se više od 85% simptomatskih pacijenata. za prevenciju nastanka subhondralne frakture te smanjenje boli kod ANV-a od modaliteta fizikalne medicine upotrebljava se udarni val a od lijekova bifosfonati, antikoagulanti i vazodilatatori no bez dokaza u znanstvenoj literaturi. hiperbarična oksigenoteraija nameće se kao metoda izbora kod ranih studija AVN-a glave bedrene kosti jer može uzrokovati regresiju promjena te pospješuje cijeljenje kosti.

This work showed the incidence and prevalence of systemic sclerosis in Split-Dalmatia county, Croatia, as well as 5-year survival of the disease.

Avascular necrosis of the femoral head is a progressive disease characterized by bone ischemia which evolves to subchondral collapse in more than 85% of patients. We describe a case of an early stage idiopathic avascular necrosis of the femoral head in a female patient that was characterized by bone marrow edema involving the whole femoral head and the majority of the femoral neck with a small subchondral fracture and slight applanation of the femoral head. This condition was suspected by physiatrist after the detection of substantial effusion in the hip joint during ultrasound examination and confirmed after magnetic resonance imaging. The patient was treated with hyperbaric oxygen therapy with complete regression of both the clinical symptoms and the MRI findings. Clinical Rehabilitation Impact: Ultrasound examination during physiatrist evaluation can help in establishing the early diagnosis and in reducing the number of hip arthroplasties caused by avascular necrosis.

Anti TNF inhibitori su okosnica u liječenju reumatskih autoimunih bolesti. Ipak kod jedne trećine bolesnika je zabilježena je primarna ili sekundarna neučinkovitost. Pokazano je da prisutnost protutijela na anti TNF inhibitore je u korelaciji je sa nižom razinom lijeka i sa slabijim odgovorom na terapiju. Iako u posljednjih desetak godina, veliki broj reumatskih bolesnika širokog geografskog područja koje gravitira prema KBC Split je liječeno antiTNF terapijom do sad a nije bilo prilike određivanja koncentracija lijeka kao ni prisutnost protutijela na antiTNF

Biološki lijekovi donijeli su značajan napredak u liječenju upalnih reumatskih bolesti. Broj bolesnika na skupoj biološkoj terapiji neprestano raste, pa visoki troškovi liječenja značajno opterećuje zdravstveni sustav i ograničavaju dostupnost bioloških lijekova. Već više od jedne godine u Hrvatskoj se primjenjuje prvi biosličan infliksimab u liječenju bolesnika u upalnim reumatskim bolestima i upalnim bolestima crijeva. Infliksimab je monoklonsko protutijelo složene heterogene strukture s jedinstvenom tercijarnom i kvartarnom strukturom, koju je teško reproducirati. S obzirom da i male razlike u proizvodnom procesu mogu utjecati na biološku aktivnost, imunogeničnost i sigurnost biološkog lijeka, za kliničare je važno razumijevanje kvalitete i terapijske ekvivalencije biosličnog lijeka. Poznavanje koncepta biosličnosti i robusnog regulatornog procesa ocjene biosličnih lijekova od strane Europske agencije za lijekove (EMA) ključno je za njihovo prihvaćanje. Rezultati provedenih studija upućuju na barem jednaku učinkovitost biosličnog infliksimaba u odnosu na izvorni lijek, a bez novih sigurnosnih signala. Hrvatska je među prvim državama u Europi započela s rutinskom primjenom biosličnog infliksimaba u liječenju bolesnika s upalnim reumatskim bolestima i upalnim bolestima crijeva. U Hrvatskoj se više od stotinu pacijenata liječi biosličnim infliksimabom Inflectra®. Prva iskustva pokazala su da je biosličan infliksimab jednako siguran i učinkovit kao i izvorni infliksimab. Biosličan infliksimab je terapijska alternativa izvornom inf liksimabu. S obzirom da je cjenovno povoljniji od izvornog lijeka, biosličan infliksimab omogućuju bolju dostupnost biološke terapije i uštedu, uz jednaku kvalitetu liječenja.

Objectives: Despite advances in systemic lupus erythematosus (SLE) treatment, many patients suffer from the disease and side effects. Atacicept is a fusion protein that blocks B-lymphocyte stimulator and a proliferation-inducing ligand, which are increased in patients with SLE. Methods: In this double-blind, placebo-controlled study, patients with moderate-to-severe SLE were randomised to atacicept 75 mg or atacicept 150 mg administered subcutaneously, or placebo twice-weekly for 4 weeks, then weekly for 48 weeks. Primary and secondary efficacy measures were the proportion of patients experiencing at least one flare of British Isles Lupus Assessment Group A or B, and time to first flare, respectively.

Sirs, We have recently published a paper entitled “Extremely rare coincidence of non- radio graphic axial spondyloarthropathy HLA- B27 positive and stiff person syndrome rheumatologist point of view“ in which we were the first to describe such a coincidence (1). In the three months following the publication of our case report, we have received e-mails from two patients in the United States of America (USA) that had been treated as non- radiographic HLA B27 positive spondyloarthritis for 10 years until they have been diagnosed with anti-GAD positive stiff person syndrome (SPS). Their story is similar to our patient’s and we believe that HLA B27 positive in truncal form of stiff person syndrome may not be as rare as we thought. It seems that there is an entire subgroup of patients with non radiolographic axial spondyloarthritis (axSpA) that are B27 positive and have SPS. Non- radiographic spondyloarthritis that does not involve radiographic changes of the sacroiliac joints was acknowledged as a variant of axial spondyloarthritis (axSpA) in 2009. by Assessment of Spondyloarthritis International Society (ASAS). Besides the non-radiografic spondyloarthritis, these criteria include ankylosing spondylitis (that fulfils the modified New York criteria) in axSpA group (2). A paper was published on national prevalence of axSpA in the USA following ASAS criteria to 0.70% (701 per 100, 000 individuals). The prevalence estimates of ankylosing spondylitis and non radiographic axial SpA are 0.35%, respectively (3). Although there are clinical similarities between patients with axSpA, a growing number of papers testify to the heterogeneity of non-radiographic axial spondyloarthritis. Furthermore, these papers emphasise the need for further observation of non-radio graphic axSpA in order to define the disease, the treatment and the prognosis more precisely (4-6). SPS is a rare autoimmune neurological disorder. It is characterised by progressive stiffness and rigidity and the prominence of truncal muscles accompanied with co-contraction of agonist and antagonist muscles. Its prevalence is less than 1 in a million individuals. Auto-antibodies against glutamic acid decarboxylase (GAD) are present in 80% of all patients (7), while amphiphysine antibody is present in fewer patients and is connected to cervical stiffness (8). Since we are now aware of three cases of HLA B27 positive of non radiographic axSpA and SPS, we think that in the group of patients with the diagnosis of non-radiographic axSpA HLA-B27 +, an additional anti-GAD, amphiphysine antibodies together with EMG of paravertebral muscles should be done to exclude SPS. We presume that HLA typisation of truncal form of SPS might show high HLA-B27 incidence. However, there is a possibility that non-radiographic axSpA is misdiagnosed in some patients with truncal rigidity and that those patients have unrecognised SPS. Related to that, attention should be focused on patients that do not react well to disease modifying anti-rheumatic drugs (especially anti-TNF drugs) and in whom the stiffness of paravertebral muscles persists. Our dilemma is best summed up in the question: is it really a coincidence of two diseases or were the patients with Stiff-Person syndrome misdiagnosed from the start? In order to answer our question, we have started a multicenter research trial in which all the patients with non-radiographic axSpA and SPS will be included and we will try to compare their clinical, radiological and laboratory findings. Our plan is to collect more data about these conditions that will help physicians in the early detection and differential diagnosis of these two autoimmune diseases. Moreover, we are willing to cooperate with other medical centres, which are also considering that the real nature of this new axSpA group is still not familiar enough. Since there is a significant heterogeneity of clinical and radiological presentation of axSpA, long-term studies are needed to better understand this disease and to achieve greater homogeneity (6).

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. Caspases are a family of endoproteases that provide critical links in cell regulatory networks controlling inflammation and cell death. Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled. Objectives This pilot study aimed to explore the expression of caspase-3 in stomach tissue in SSc patients and possible correlation with disease activity and severity. Methods A total of thirteen stomach tissue biopsies (11 SSc and 2 controls) were collected. The same investigator, blind to clinical features, performed upper gastrointestinal endoscopy. The sections of stomach tissue were separately incubated for 45 min with rabbit anti-human/mouse active caspase-3 primary antibody. The intensity of apoptosis according to the caspase 3 activity was semiquantitatively selected into four categories: mild, moderate and abundant. We evaluated the disease activity and severity using clinical and laboratory parameters according to a modified Medsger severity scale and activity score. The disease activity was assessed according to Valentini's Scleroderma Disease Activity Index. In all the patients skin involvement was assessed by the modified Rodnan skin score (mRSS). The study was approved by the University Hospital Split Ethics Committee. Results Eleven SSc female patients [mean age 54.3 (13.6) years, median disease duration 13 years with minimum–maximum range 1–35 years] were enrolled in this study after they gave written informed consent. All patients fulfilled the ACR criteria for the diagnosis of SSc. Five SSc patients had moderate/abundant and six had mild apoptosis on the basis of the caspase 3 activity. In SSc patients, the number of apoptotic cells is high, and their distribution is observed in several layers of the stomach wall, including blood vessels (Figure 1). The skin involvement and disease duration were highly different between SSc patients regarding to the apoptosis level (P

Golimumab je humano monoklonsko protutijelo koje inhibira čimbenik nekroze tumora-alfa (TNF-α), a indiciran je u liječenju upalnih reumatskih bolesti (reumatoidni artritis, psorijatični artritis, ankilozantni spondilitis) nakon što se konvencionalnom farmakološkom i nefarmakološkom terapijom ta stanja ne uspiju dovesti u remisiju ili nisku aktivnost bolesti. U ovom retrospektivnom istraživanju uključeni su bolesnici oboljeli od reumatoidnog artritisa, psorijatičnog artritisa i ankilozantnog spondilitisa u Hrvatskoj, liječeni golimumabom u dvogodišnjem razdoblju (od lipnja 2011. do lipnja 2013.). Promatrane su standardne varijable aktivnosti bolesti i funkcionalne sposobnosti. Rezultati su pokazali znatnu učinkovitost golimumaba u smanjenju aktivnosti bolesti i poboljšanju funkcionalne sposobnosti bolesnika s navedenim upalnim reumatskim bolestima. Zaključno, golimumab se u ovom retrospektivnom istraživanju liječenja kroz dvije godine pokazao učinkovitim u smanjenju aktivnosti bolesti i poboljšanju funkcionalne sposobnosti bolesnika s reumatoidnim artritisom, psorijatičnim artritisom i ankilozantnim spondilitisom.

A 56-year-old woman, treated with tocilizumab (TCZ) for 8 months for severe rheumatoid arthritis (RA), was admitted to the hospital due to the swelling and tenderness of parotid glands. The patient was diagnosed with seropositive erosive RA in 1988, and treated with different disease modifying antirheumatic drugs (DMARDs) that were used together with a low dosage of glucocorticoides, followed by biologic therapy with infliximab and adalimumab which also proved to be inefficient. The patient had an excellent initial response on TCZ therapy. After 8 months, she was presented with an extreme enlargement of parotid glands. Bacterial, viral, and granulomatous diseases were excluded. A spectrum of autoantibodies including anti-Ro and anti-La showed normal values, expect for slightly elevated anti- cyclic citrullinated peptide (anti-CCP) and extreme elevation of the rheumatoid factor (RF) to 10, 100 IU/ml. The biopsy of salivary glands was done and histological specimen showed limphoplasmocytic syaloadenitis. Tocilizumab therapy was stopped and the dosage of glucocorticoids and methotrexate (MTX) was raised. After 6 weeks, the patient was in better condition with slightly lower levels of RF (9, 010 IU/ml). We hypothesise that in this patient, TCZ stimulated RF hyper production which can induce a paradoxical secondary syaloadenitis in RA.

Hypoxia is a characteristic feature of systemic sclerosis (SSc).Transforming growth factor alpha (TGF-α) has an important role in excessive inflammation under hypoxic conditions. Since oesophageal dysmotility is one of the most common signs of SSc, the aim of this study was to explore the relation between TGF-α and oesophageal dysmotility in SSc. METHODS: The study included 35 patients with SSc and 32 healthy controls matched for sex and age. Serum concentrations of TGF-α were measured using ELISA. Oesophageal motility was assessed by oesophageal scintigraphy. A multiple-swallow test was performed in the study population with 99mTc-DTPA. A region of interest over the entire oesophagus was defined and the retention index (RI) was calculated. RESULTS: Statistically significant differences in serum concentration of TGF-α as well as of RI of 99mTc- DTPA were found between patients with SSc and healthy controls. A statistically significant correlation was found between serum concentrations of TGF-α and RIs of 99mTc-DTPA. This correlation was inverse, i.e. when serum concentrations of TGF-α increased, the RI of 99mTc-DTPA decreased (Spearman rho =-0361, p=0.033). CONCLUSIONS: These results point to a possible relation between TGF-α and oesophageal dysmotility in SSc. Although the results do not explain the exact role of this cytokine in the pathogenesis of esophageal changes, the finding of inverse correlation between TGF-α and oesophageal dysmotility is intriguing and requires further investigation.

Personalizirani pristup bolesniku s reumatoidnim artritisom-nova saznanja i nove mogućnosti

Reumatoidni artritis (RA) kronična je, progresivna upalna reumatska bolest koja dovodi do oštećenja zglobova, funkcionalnog ograničenja i smanjenja kvalitete života. Bolest je potrebno što prije prepoznati, u fazi ranog artritisa, dok postoji “prozor mogućnosti” u kojem se primjenom adekvatnog liječenja mogu prevenirati strukturna oštećenja. Kako klinička prezentacija nije uvijek tipična, rano prepoznavanje zahtijeva umješnost, kliničko iskustvo te suradnju reumatologa, liječnika obiteljske medicine i samog bolesnika. Liječenje treba započeti odmah, a odluku o načinu liječenja donosi reumatolog individualnim pristupom i u suradnji s bolesnikom. Potrebno je prepoznati bolesnike s rizikom težeg tijeka bolesti, naročito one s visokim titrom protutijela na cikličke citrulinirane peptide (anti-CCP) te ranom pojavom erozija jer ti bolesnici zahtijevaju agresivniji pristup u liječenju. Cilj liječenja je postizanje remisije ili barem niske aktivnosti bolesti U liječenju se koriste lijekovi koji mijenjaju tijek bolesti (DMARD) sintetski i biološki, nesteroidni protuupalni lijekovi, glukokortikoidi i analgetici te iznimno citostatici. RA ima fluktuirajući tijek s izmjenama faza pogoršanja i remisije bolesti, a vrlo je važno pravodobno prepoznati pogoršanje radi intenziviranja liječenja ili promijene terapijske sheme. Poseban problem predstavlja glukokortikoidima inducirana osteoporoza (GIO) koju treba prevenirati preparatima kalcija i vitamina D, a liječiti antiresorptivnim i osteoanabolnim lijekovima. U skrbi bolesnika s RA važno je uz liječenje osnovne bolesti sagledati i zbrinjavati komorbiditete, neželjene učinke liječenja, komplikacije bolesti te psihosocijalne aspekte kronične bolesti., Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional impairment and reduced quality of life. The disease should be recognized early when there is a “window of opportunity” to apply adequate treatment which may prevent structural damage. As clinical presentation of RA is not always typical, great knowledge and clinical experience, including collaboration of rheumatologist, general practitioner and patient, are required. The treatment should be started immediately upon the diagnosis, while the choice of modality of treatment depends on the rheumatologist in accordance with the patient. The RA patients with the higher risk of aggressive disease need to be recognized because they require more aggressive treatment from the start. The goal of the treatment is remission or at least low disease activity. Current treatment of RA includes disease modifying antirheumatic drugs (DMARDs) synthetics and biologics, nonsteroidal antirheumatic drugs (NSAIDs), glucocorticoids, analgesics, and rarely cytostatics. The course of disease is usually fluctuating with the exchange of relapses and remissions. Recognition of the relapsing patient on time enables treatment intensification or modifications in treatment scheme. Special issue in RA represents glucocorticoid-induced osteoporosis (GIO) which should be prevented by usage of calcium and vitamin D supplements and treated by antiresorptive or osteoanabolic agents. Besides the treatment of the primary disease, the care of RA patients should consider comorbidities, side effects of treatment, complications of disease, and psychosocial aspects of chronic disease.

OBJECTIVES: Hypoxia is a characteristic feature of systemic sclerosis (SSc).Transforming growth factor alpha (TGF-α) has an important role in excessive inflammation under hypoxic conditions. Since oesophageal dysmotility is one of the most common signs of SSc, the aim of this study was to explore the relation between TGF-α and oesophageal dysmotility in SSc. METHODS: The study included 35 patients with SSc and 32 healthy controls matched for sex and age. Serum concentrations of TGF-α were measured using ELISA. Oesophageal motility was assessed by oesophageal scintigraphy. A multiple-swallow test was performed in the study population with 99mTc-DTPA. A region of interest over the entire oesophagus was defined and the retention index (RI) was calculated. RESULTS: Statistically significant differences in serum concentration of TGF-α as well as of RI of 99mTc-DTPA were found between patients with SSc and healthy controls. A statistically significant correlation was found between serum concentrations of TGF-α and RIs of 99mTc-DTPA. This correlation was inverse, i.e. when serum concentrations of TGF-α increased, the RI of 99mTc-DTPA decreased (Spearman rho =-0361, p=0.033). CONCLUSIONS: These results point to a possible relation between TGF-α and oesophageal dysmotility in SSc. Although the results do not explain the exact role of this cytokine in the pathogenesis of esophageal changes, the finding of inverse correlation between TGF-α and oesophageal dysmotility is intriguing and requires further investigation.

Our results provide a little evidence that hyper estrogenic levels in premenopausal SLE women are associated with an increased risk of APS and cardiovascular manifestation. An increased risk of hyper estrogenic levels was expected based on the results of other research, particularly the extensive experimental studies of estrogen and androgen exposure in relation to disease progression in mice. Gonadoctomized or intact male and female nonautoimmune C57BL/6 mice treated with exogenous estrogen express aCL. These antibodies persisted for months after estrogen has been terminated, but there was no proof that these antibodies have had a pathologic role. Some antibodies in humans may persist for years without evidence off autoimmune tissue accident and it is the question what can force aCL to become pathologic. It is already proven that estrogens enhance thrombotic events in SLE patients, so we calculate that the estrogens especially stimulate the pathological sort of aCL. This observation, if confirmed by other studies, raises interesting questions about the interrelation between estrogens and autoimmunity, with a potential impact on the risk of thrombosis and cardiovascular disease.

Reumatoidni artritis (RA) kronična je, progresivna upalna reumatska bolest koja dovodi do oštećenja zglobova, funkcionalnog ograničenja i smanjenja kvalitete života. Bolest je potrebno što prije prepoznati, u fazi ranog artritisa, dok postoji "prozor mogućnosti" u kojem se primjenom adekvatnog liječenja mogu prevenirati strukturna oštećenja. Kako klinička prezentacija nije uvijek tipična, rano prepoznavanje zahtijeva umješnost, kliničko iskustvo te suradnju reumatologa, liječnika obiteljske medicine i samog bolesnika.Potrebno je prepoznati bolesnike s rizikom težeg tijeka bolesti, naročito one s visokim titrom protutijela na citrulirane peptide (anti-CCP) te ranom pojavom erozije jer ti bolesnici zahtijevaju agresivniji pristup liječenju. U liječenju se koriste lijekovi koji mijenjaju tijek bolesti (DMARD) sintetski i biološki, nesteroidni protuupalni lijekovi, glukokortikoidi i analgetici te iznimno citostatici. U skrbi bolesnika s RA važno je uz liječenje osnovne bolesti sagledati i zbrinjavati komorbiditete, neželjene učinke liječenja, komplikacije bolesti te psihosocijalne aspekte kronične bolesti.

Hipertrofična osteoartropatija je klinički sindrom obilježen pojavom zadebljanih (batićastih) prstiju, povećanjem ekstremiteta, bolovima i oticanjem stopala te simetričnim periostitisom koji zahvaća duge kosti gornjih i donjih udova. Rijetko se javlja kao paraneoplastički sindrom u sklopu primarnog ili metastatskog karcinoma pluća. Prikazujemo 39-godišnju bolesnicu s artritisom i paraneoplastičnom hipertrofičnom osteoartropatijom u sklopu adenokarcinoma pluća.

Cilj rada je bio istražiti epidemiološka obilježja bolesnika s reumatoidnim artritisom (RA) na području srednje Dalmacije uz moguće izdvajanje zemljopisnih klastera. Anketari osposobljeni za provođenje telefonskog upitnika ispitali su podrijetlo 197 osoba oboljelih od RA koji su kontroliraju pri Odjelu za reumatologiju i kliničku imunologiju KBC-a Split. Za statističku analizu pojavnosti klastera primjenjen je Poisson-ov izračun vjerojatnosti. Potvrđena su četiri klastera, od kojih je najveći zabilježen na području Sinjske krajine. Omjer žena naspram muškaraca bio je 5, 79:1. Najveći broj oboljelih od RA pripadao je dobnoj skupini od 50 do 59 godina starosti (30, 45 %). Rezultati ukazuju na varijacije unutar regije s istaknutim klasterima RA u sjevernom dijelu srednje Dalmacije, što upućuje na postojanje posebnih genetskih ili okolišnih čimbenika. Učestalost bolesti u žena naspram muškaraca bila je veća u odnosu na dosadašnja izvješća, dok je zahvaćenost dobnih skupina 50-59 bila sukladna podacima iz novije literature.