Sistemske manifestacije Sjögrenovog sindroma

Sjögren’s syndrome (SS) is a heterogeneous disease which, in the majority of cases, includes a mild clinical course. However, in some patients it takes on a severe form with numerous systemic manifestations and results in an adverse outcome. Systemic manifestations occur in approximately 25% of patients with primary Sjögren’s syndrome (pSS). The clinical presentation of systemic manifestations of SS is very diverse and can involve any organ system. Systemic manifestations can occur due to lymphocytic infiltration of organs or proliferation of B lymphocytes and deposition of immune complexes. Fatigue is the most common systemic manifestation. The most significant cutaneous manifestations of the disease are palpable purpura, ulcerations, urticarial vasculitis and leukocytoclastic vasculitis. Musculoskeletal manifestations can range from arthralgias to erosive arthritis. Pulmonary involvement may include symptoms such as nonspecific interstitial pneumonia with fibrosis and tracheobronchial disease. Renal changes are observed in 10% to 30% of patients with SS. Tubulointerstitial nephritis, type 1 renal tubular acidosis and nephrogenic diabetes insipidus can develop as a consequence of lymphocytic infiltration. Less often, the inflammatory process affects the glomeruli which leads to glomerulonephritis. Liver diseases are found in approximately 20% of patients with SS and their symptoms usually include inflammation of intrahepatic bile ducts resembling primary biliary cirrhosis. The manifestations of peripheral nervous system involvement include sensorimotor axonal polyneuropathy, mononeuritis multiplex, neuropathies and radiculopathies. Optic neuropathy, hemiparesis, movement disorders, cerebellar syndromes, transient ischemic attacks, transverse myelitis (less commonly), and progressive myelopathy have been described as central nervous system changes. Symptoms of vasculitis can range from mononeuritis multiplex to intestinal ischemia and dysfunction of the affected organs. The development of non-Hodgkin’s B-cell lymphoma is a major complication of the disease which occurs in 5%–7% of patients with SS.Sjögrenov sindrom (SS) je heterogena bolest koja se najčešće prezentira blagim kliničkim tijekom. Međutim, u manjeg dijela bolesnika poprima teški oblik bolesti s brojnim sistemskim manifestacijama i mogućim lošim ishodom. Sistemske manifestacije se pojavljuju u približno 25% bolesnika s primarnim Sjögrenovim sindromom (pSS). Klinička prezentacija sistemskih očitovanja SS-a vrlo je raznolika i može zahvatiti bilo koji organski sustav. Mogu nastati uslijed limfocitne infiltracije organa ili proliferacije limfocita B i odlaganja imunih kompleksa. Umor je najčešća sistemska manifestacija. Najznačajnije dermatološke manifestacije bolesti su palpabilna purpura, ulceracije, urtikarijalni i leukocitoklastični vaskulitis. Koštano-mišićne manifestacije u bolesnika s pSS-om pojavljuju se u širokom rasponu od artralgija do erozivnog artritisa. Zahvaćenost pluća može se očitovati kao fična intersticijska pneumonija s fibrozom i traheobronhalna bolest s povećanom reaktivnošću bronha, bronhiektazijama, bronhiolitisom ili ponavljajućim respiratornim infekcijama. Bubrežne promjene se uočavaju u 10–30% bolesnika sa SS-om. Kao posljedica limfocitne infiltracije razvija se tubularni intersticijski nefritis, renalna tubularna acidoza tipa I, nefrogeni dijabetes insipidus i ostali poremećaji tubularne funkcije. Znatno rjeđe upalni proces zahvaća glomerule dovodeći do glomerulonefritisa. Jetreni poremećaji se nalaze u oko 20% bolesnika sa SS-om, a najčešće se očituju upalnim promjenama intrahepatalnih žučnih vodova nalikujući primarnoj bilijarnoj cirozi. Zahvaćenost perifernoga živčanog sustava manifestira se senzomotornom aksonalnom polineuropatijom, senzornom ataksičnom i autonomnom neuropatijom, mononeuritisom multipleks, kranijalnim neuropatijama i radikulopatijama. Od promjena središnjega živčanog sustava opisuju se optička neuropatija, hemipareza, poremećaji pokreta, cerebelarni sindromi, tranzitorne ishemijske atake, rjeđe transverzalni mijelitis i progresivna mijelopatija. Simptomi vaskulitisa mogu varirati od mononeuritisa multipleksa do ishemije crijeva i disfunkcije zahvaćenih organa. Razvoj non-Hodgkinovog limfoma B-stanica predstavlja glavnu komplikaciju bolesti i pojavljuje se u 5–7% bolesnika sa Sjögrenovim sindromom

POLYMYALGIA RHEUMATICA, GIANT CELL ARTERITIS AND MALIGNANCY – IS THERE AN ASSOCIATION?

Reumatska polimialgija (PMR) i temporalni arteritis (TA) česte su upalne reumatske bolesti u osoba starijih od pedeset godina. Usko su povezane i često se pojavljuju u istog bolesnika. Uobičajeni simptomi su bol i nelagoda te zakočenost mišića ramenog obruča, vrata i kukova, a praćeni su povišenim vrijednostima upalnih reaktanata i anemijom kronične bolesti. Uz navedeno u TA se javlja temporalna glavobolja, smetnje vida i sluha te bol čeljusti. Dobar i brz terapijski odgovor na primjenu glukokortikoida ključno je obilježje ovih dvaju poremećaja. Kod nekih upalnih autoimunih reumatskih bolesti zabilježena je veća incidencija malignoma. Premda razlozi te veće pojavnosti nisu jasni, smatra se da je u podlozi poremećena regulacija imunosnog sustava. Više prikaza slučaja, serija slučaja i epidemioloških studija sugerira poveći rizik od malignih bolesti u bolesnika s PMR i TA, ali su rezultati epidemioloških studija kontradiktorni. U svrhu istraživanja ove povezanosti nedavno je provedena nekolicina prospektivnih istraživanja. Povišen rizik malignih oboljenja u bolesnika s PMR/TA nedvojbeno je utvrđen u prvih 6 – 12 mjeseci od dijagnoze, a poslije se taj rizik gubi i izjednačava s rizikom opće populacije. Uočena je veća pojavnost karcinoma urogenitalnog, limfatičkog, hematopoetskog i živčanog sustava. Kako se do dijagnoze PMR i TA dolazi „per exclusionem“, a klinička slika često nije specifična i može nalikovati paraneoplastičkom sindromu, potrebna je vrlo pažljiva klinička evaluacija i pridržavanje klasifikacijskih kriterija. Nužno je razmotriti sve što diferencijalno dijagnostički dolazi u obzir, uključujući malignitet, posebno tijekom prve godine kliničkog praćenja. Unatoč tome u oko 20 % bolesnika s PMR/TA dolazi do naknadne revizije dijagnoze u neku od upalnih reumatskih ili malignih bolesti.Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two common chronic inflammatory rheumatologic disorders in adults aged over 50 years. These disorders are closely related and commonly occur together. Classic symptoms are bilateral pain, aching, and stiffness in the shoulders and pelvic girdle, usually accompanied by elevated inflammatory markers and anemia of chronic disease. The hallmark of these two diseases is a good and quick response to glucocorticoid therapy. An increased incidence of malignancy has been observed in some autoimmune inflammatory disorders. The mechanism of this association is poorly understood, but is believed to be related to a dysregulation of the immune system. Several case reports and case series have suggested that an increased risk of malignancy also exists in patients with GCA and PMR, but no clear association has been proven due to conflicting data coming from epidemiological studies. Recently, a few larger prospective cohort studies were performed to explore this association. An increased risk of a cancer diagnosis was found within the first 6-12 months after a PMR/GCA diagnosis. The data suggested an excess of cancers of the genitourinary, lymphatic, hematologic, and nervous systems. Beyond that period, the risk of malignancy in PMR/GCA was only slightly elevated, or even equal to the control population. As a diagnosis of PMR and GCA is usually achieved “per exclusionem“, and the clinical presentation is non-specific and may resemble paraneoplastic syndrome, making an accurate diagnosis of these disorders in the elderly population is essential. Clinicians need to be aware of the possibility of alternative diagnoses, including cancer. Thus, patients diagnosed with PMR and GCA should be carefully monitored, especially in the first year after the initial diagnosis, to exclude underlying cancer. In up to 20% of cases of PMR/GCA the diagnosis is subsequently revised to other inflammatory rheumatic disease or malignant disease

The prevalence of smoking among Croatian hospitalized coronary heart disease patients [Prevalencija pušenja u hospitaliziranih bolesnika u Hrvatskoj]

The aim of this paper was to investigate the prevalence of smoking using selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia (N = 1,298). A total of 444 subjects (34.6%) were non-smokers, 548 (42.6%) were smokers and 293 (22.8%) were ex-smokers. Men, on average, smoked more cigarettes per day than women (22.62 vs. 19.84 cigarettes, p < 0.001) and they also had bigger index "pack-years" than women (36.96 vs. 33.91, p = 0.024). Men were more often smokers and ex-smokers than women (47.4% vs. 30.8% for smokers and 25.0% vs. 22.8% for ex-smokers, p < 0.001). In this study a high prevalence of smoking was found among CHD patients in Croatia. Unless it is decreased, it can be expected that CHD patients in Croatia will continue to experience adverse effects more often than other CHD patients in the rest of Europe

Spolne razlike u Sjögrenovu sindromu – desetogodišnje iskustvo jednog centra

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

LONG-TERM GLUCOCORTICOID THERAPY AND THE RAPID DEVELOPMENT OF SQUAMOUS CELL CARCINOMA IN SYSTEMIC SCLEROSIS: IS THERE A CONNECTION?

Sistemska skleroza (SSc) autoimunosna je bolest, koju prati rizik od razvoja malignoma, posebice karcinoma pluća, među kojima se prema učestalosti ističu adenokarcinom i planocelularni karcinom. Šezdesettrogodišnja bolesnica sa SSc-om hospitalizirana je zbog nesvjestice, lošeg općeg stanja i gangrenoznih promjena okrajina. Zbog epileptičkih napadaja koji su uslijedili te popratne ljevostrane slabosti učinjena je kompjutorizirana tomografi ja (CT) neurokranija koja je otkrila lezije tipa rasadnica (metastaza). Na CT-u pluća bila je vidljiva novotvorina u desnom hilusu koja je patohistološki evaluirala kao planocelularni karcinom 2. stupnja. Bolesnica je nakon jednomjesečne hospitalizacije uz potpornu terapiju, u klinički poboljšanom stanju, otpuštena na kućnu njegu s preporukom daljnjeg onkološkog liječenja, no nekoliko dana potom je preminula. S obzirom na adenokarcinome, planocelularni karcinomi pluća uobičajeno se razvijaju u znatno dužem razdoblju te držimo da je atipično ubrzan njegov razvoj u ove bolesnice potaknut imunosupresivnim djelovanjem srednje visokih doza glukokortikoida koje je bolesnica samoinicijativno uzimala više godina.Systemic sclerosis (SSC) is an autoimmune disease associated with the risk of malignancies, especially lung cancer, among which adenocarcinoma and squamous cell carcinoma are the most frequent. A 63-year-old female patient with SSC was hospitalized due to blackouts, poor general condition, and changes in her fi ngers. Because of subsequent epileptic seizures resulting in weakness of the left side of her body, computerized tomography (CT) of the neurocranium was performed which showed metastatic lesions. A CT scan of the thoracic organs displayed pulmonary neoplasia in the right hilum, which were histologically evaluated as grade 2 squamous cell carcinoma. Aft er one month of hospitalization with supportive therapy, the patient’s clinical condition improved, and she was discharged into home care with recommendations for further oncological treatment. However, the patient died several days later. In comparison to adenocarcinomas, squamous cell carcinomas of the lungs usually develop through a signifi cantly longer period. We consider that the unusually rapid development of the carcinoma in this patient was stimulated by the immunosuppressive eff ect of high doses of glucocorticoids that she had been taking for several years on her own initiative

Spearheading into the Neolithic: last foragers and first farmers in the Dinaric Alps of Montenegro

This article presents a summary of new evidence for the Mesolithic in the Dinaric Alps of Montenegro. The region is one of the best areas in south-eastern Europe to study Early Holocene foragers and the nature of the transition to Neolithic lifeways at the end of the seventh and the beginning of the sixth millennium cal BC thanks to the existence of biodiverse landscapes and numerous karstic features. We argue that harpoons found at two different sites in this regional context represent a curated technology that has its roots in a local Mesolithic cultural tradition. The continued use of this standardized hunting tool kit in the Neolithic provides an important indication about the character of the Mesolithic–Neolithic transition. We also use this regional case study to address wider questions concerning the visibility and modes of Mesolithic occupation in south-eastern Europe as a whole