The Influence of Rheumatoid Arthritis and Osteoarthritis on the Occurrence of Arterial Hypertension: An 8-Year Prospective Clinical Observational Cohort Study.

Rheumatoid arthritis (RA) increases the risk of cardiovascular mortality and morbidity, including a 50-60% increased risk of cardiovascular disease (CVD). Arterial hypertension (HT) is considered the major contributing risk factor for CVD development in RA patients. In this investigation, we compared the incidence and prevalence of HT between RA and osteoarthritis (OA) and the influence of HT on CVD development in CVD-naive patients in both groups. This was a prospective clinical cohort investigation with an 8-year follow-up period. A total of 201 participants, 124 with RA (investigation group) and 77 with OA (control group), without diagnosed CVD or symptomatic heart failure were included. After selection according to inclusion and exclusion criteria, both groups underwent initial and final visits, and the investigation group underwent annual visits to assess disease activity. Case report forms were completed for each visit. The obtained data were analyzed by a statistician. No difference in the incidence or prevalence of HT was found between the investigation and control groups. No difference in the prevalence of HT was reported between the study groups and age-standardized data from the general population. The investigation group had a higher incidence of CVD than the control group. RA participants with long-term remission had a marginally lower HT prevalence. Although previous studies reported a higher HT prevalence in RA than in OA and the general population, our findings did not support this. The RA group had a higher incidence of CVD, but it is possible that optimal disease control with long-term remission could reduce HT incidence and prevalence while also having beneficial effects on other cardiovascular risk factors (CV) and, consequently, CVD occurrence.

Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study).

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.

Successful treatment with Cinryze® replacement therapy of a pregnant patient with hereditary angioedema: a case report.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized with recurrent swelling of subcutaneous or mucosal tissue that resolves in approximately 3 days. It can be presented with peripheral edema, abdominal and life-threatening laryngeal angioedema. A variety of triggers are known to cause episodes of angioedema including estrogen exposure. There are different reports regarding the effect of pregnancy on HAE attacks, and in some patients, the pregnancy is a recognized triggering factor. CASE PRESENTATION: We present a female Caucasian patient with pre-existing HAE and disease exacerbations during pregnancy, requiring prophylactic use of plasma-derived C1 inhibitor concentrate. She was treated with Cinryze® replacement therapy throughout the pregnancy 1000 IU i.v. 48 times. She gave birth to a healthy male infant, via C-section. After the delivery, the patient was symptom-free for 6 months and required no treatment for HAE. CONCLUSIONS: In the case presented, the angioedema attacks worsened as the pregnancy progressed. The treatment with Cinryze® replacement therapy was effective and safe during pregnancy, with no adverse effects on the infant.

Optic neuritis as a presenting feature of Behçet's disease: case-based review.

Behçet's disease (BD) is vasculitis affecting vessels of variable sizes characterized with recurrent oral and/or genital aphthous ulcers accompanied by cutaneous, ocular, articular, gastrointestinal, and/or central nervous system inflammatory lesions. The disease is characterized by recurrent attacks and remissions of different durations, which is one of the reasons why the diagnosis is, in most cases, made several years after the onset of first symptoms. We present a 24-year old male, with South Eastern European heritage, with relapsing bilateral optic neuritis as a first symptom of the disease, followed by aseptic meningitis 2 years, and vascular manifestation 3 years after onset, which finally led to the diagnosis of Behçet's disease. Vascular symptoms were thromboembolism of the right leg and aneurism of the right popliteal artery that due to the size required surgical treatment. The patient was treated with glucocorticoids, azathioprine and anti-tumor necrosis factor-alpha therapy, that proved to be the best treatment options for all manifestations of the disease. Based on our literature review, optic neuritis is a known and rare clinical feature of BD. To our knowledge, there are only several literature reports in which optic neuritis is the initial symptom of BD. Our case report and literature review emphasize the importance of recognizing optic neuritis without inflammatory eye disease as a possible presenting symptom of BD and accentuate detailed medical history review at each patient's visit.

[CLINICAL ENTITIES AND CHARACTERISTICS OF PAIN IN PATIENTS WITH RHEUMATIC DISEASES].

Musculoskeletal pain is the most common symptom present in almost all rheumatic diseases. Rheumatic diseases include more than 150 clinical entities. There is no uniform classification of rheumatic diseases. In general, we distinguish inflammatory rheumatic diseases, non-inflammatory degenerative articular diseases, systemic connective tissue diseases, metabolic disorders with articular manifestations, and regional and extended pain syndromes. According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensation associated with tissue damage or reported simultaneously with such damage. Pain has a physical, mental, and social component. In rheumatic diseases the pain is mostly chronic and may severely impair the patient's general condition. The defining criteria involve a period of more than 3 or 6 months, and according to some definitions more than 6 weeks. In most cases the pain is nociceptive rather than neuropathic. Musculoskeletal pain, especially chronic pain, is a global public health problem because of its prevalence, as well as the frequently associated muslculoskeletal function impairment and development of chronic pain syndrome, which can be considered as a separate clinical entity and requires a biopsychosocial treatment approach.

Differences in the prevalence and characteristics of metabolic syndrome in rheumatoid arthritis and osteoarthritis: a multicentric study.

The purpose of the study was to examine whether rheumatoid arthritis (RA) patients have higher prevalence of metabolic syndrome (MetS) than osteoarthritis (OA) patients in association with a higher level of chronic systemic inflammation in rheumatoid arthritis. A total of 583 RA and 344 OA outpatients were analyzed in this multicentric study. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. A 1.6-fold higher prevalence of MetS was found in patients with OA compared with the RA patients. Among the parameters of MetS, patients with OA had significantly higher levels of waist circumference, systolic blood pressure, fasting blood glucose and triglycerides, whereas HDL cholesterol and diastolic blood pressure values were similar in both groups of patients. Higher values of inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] in MetS than in non-MetS patients and higher prevalence of MetS in patients with CRP level ≥5 mg/L in both RA and OA patients were found. In multivariate logistic regression analysis, significant predictors of MetS were type of arthritis (OA vs. RA; OR 2.5 [95 % CI 1.82-3.43]), age (OR 1.04 [95 % CI 1.03-1.06]) and ESR (OR 1.01; [95 % CI 1.00-1.01]). The significant association between OA and MetS was maintained in the regression model that controlled for body mass index (OR 1.87 [95 % CI 1.34-2.61]). The present analysis suggests that OA is associated with an increased risk of MetS, which may be due to a common underlying pathogenic mechanism.

[RETROSPECTIVE DATA ANALYSIS OF THE PATIENTS WITH INFLAMMATORY JOINT DISEASES TREATED WITH GOLIMUMAB IN CROATIA]. / RETROSPEKTIVNA ANALIZA PODATAKA BOLESNIKA OBOLJELIH OD UPALNIH REUMATSKIH BOLESTI U HRVATSKOJ LIJECENIH GOLIMUMABOM.

Golimumab is a human monoclonal antibody which inhibits tumor necrosis factor-alpha (TNF-α) and is approved for the treatment of inflammatory arthritides (rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis) when the conventional non-pharmacological and pharmacological therapies fail to cause remission or low disease activity. In this retrospective study there were included patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis who were treated in Croatia with golimumab, from June 2011 to June 2013. included and these retrospective data are compared with similar data from clinical trials and other available databases. Standard variables of disease activity and functional ability were observed. Results demonstrated significant efficacy of golimumab regarding lowring the disease activity and imrpving functional ability in pateints with these inflammatory rherumatic disease. In conclusion, in this retrospective study during two years treatment golimumab showed efficacy in decreasing disease activity and imrpove functional ability in patiemts with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

[CRYOGLOBULINEMICVASCULITIS AS A MANIFESTATION OF PARANEOPLASTIC SYNDROME--A CASE REPORT]. / KRIOGLOBULINEMICNI VASKULITIS KAO MANIFESTACIJA PARANEOPLASTICKOG SINDROMA--PRIKAZ BOLESNIKA.

Cryoglobulinemia refers to the presence of circulating cryoglobulins in the serum which may lead to organ damage and systemic response characterized by fatigue, arthralgias, purpura, glomerulonephritis and neuropathy. The disease mainly affects small and medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Mixed cryoglobulinemia (type I and II) are most often associated with infections, especially hepatitis C virus (HCV), but may occur as part of lymphoproliferative and autoimmune diseases. We present a 75-year-old male patient with acrocyanosis and digital necrosis of the left hand and purpura of the lower extremities. Since 2001 the patient was treated for Non-Hodgkin's lymphoma of the stomach (MALT) and since 2002 for Sjogren's syndrome. Extensive diagnostic procedures revealed cryoglobulinemia type II, but without evidence of HCV infection or relapse of lymphoproliferative disorder. Furthermore, poorly differentiated prostate adenocarcinoma was diagnosed and antiandrogen treatment was initiated. One year after the onset of symptoms acrocyanosis and digital necrosis, gastric adenocarcinoma was diagnosed, without metastatic disease, and surgical treatment was performed. However, postoperatively recurrence of new digital necrosis of the hands occurred along with clinical deterioration and multiple organ failure leading to lethal outcome. Association of cryoglobulinemia and solid tumors is rarely described in the literature, so it is very important to perform comprehensive diagnostic evaluation and detect potential underlying disease as soon as possible.

[Pathophysiology of osteoporosis]. / Patofiziologija osteoporoze.

The balance of degradation and bone formation is important for the normal process of remodeling and maintenance of bone mass. Genetic, hormonal, immunological and other factors affect bone remodeling throughout life. Disorder of bone turnover plays key role in the pathophysiology of osteoporosis and presents a complex process which involves bone cells, cytokines and their receptors. Nowadays, important role of RANK/RANKL/OPG system in the pathophysiology of osteoporosis is well known, but it is still important to investigate the intracellular signaling pathways in the development of osteoporosis and other metabolic bone diseases.

[Antisynthetase syndrome - a case report]. / Antisintetaza sindrom - prikaz bolesnice.

Twenty-eight year-old woman with predominant signs of polymyositis, pulmonary interstitium involvement and with positive anti-Jo1 antibodies was suspected for antisynthetase syndrome. Over the next three months sores and ulcerations have appeared at the fingertips. In the later course of the disease clinical picture of mixed connective tissue disease associated with interstitial lung disease, with a dominant picture of systemic sclerosis have emerged. She was treated with glucocorticoides and immunosuppressive therapy. Patient condition was mostly stable, without significant progression of lung lesions. Early diagnosis and treatment antisynthetase syndrome significantly contributes to more favorable course and outcome of disease. A prerequisite for that are well-defined diagnostic criteria and an appropriate choice of treatment.

Is the prevalence of arterial hypertension in rheumatoid arthritis and osteoarthritis associated with disease?

In this study, we compare the prevalence of arterial hypertension (HT) in rheumatoid arthritis (RA) and osteoarthritis (OA) patients, exposed to high- and low-grade chronic inflammation, respectively, to assess the possible association between chronic inflammation and HT. A total of consecutive 627 RA and 352 OA patients were enrolled in this multicentric study. HT was defined as a systolic blood pressure (BP) ≥ 140 and/or diastolic BP ≥ 90 mmHg or current use of any antihypertensive drug. Overweight/obesity was defined as body mass index (BMI) ≥ 25, and patients ≥65 years were considered elderly. The prevalence of HT was higher in the OA group than in the RA group [73.3 % (95 % CI, 68.4, 77.7) and 59.5 % (95 % CI, 55.6, 68.4) P < 0.001, respectively]. When the results were adjusted for age and BMI, the HT prevalence was similar in both groups [RA 59 % (95 % CI, 55.1, 63.8) OA 60 % (95 % CI, 58.4, 65.0)]. In both groups, the prevalence of HT was higher in the elderly and those who were overweight than in the younger patients and those with a BMI < 25. Overweight (BMI ≥ 25) and age ≥65 were independent predictors of HT in multivariate logistic regression model, which showed no association between HT and the disease (RA or OA). The results indicate a robust association of age and BMI with HT prevalence in both RA and OA. The difference in HT prevalence between RA and OA is due rather to age and BMI than to the features of the disease, putting into question specific association of HT with RA.

[Laboratory diagnostics of polymyositis/dermatomyositis]. / Laboratorijska dijagnostika polimiozitisa/dermatomiozitisa.

Polymyositis/dermatomyositis is chronic systemic inflammatory disease that usually affects the skin and muscle tissue. The diagnosis of polymyositis/dermatomyositis isn't simple, and represents challenge for clinicians, it is based on the integration of results: medical history and clinical presentation, laboratory findings enzymes more or less specific to muscle tissue, myositis-specific autoantibodies and autoantibodies associated with myositis which can be found at other inflammatory connective tissue diseases without myositis, electromyography findings, and biopsy of muscle and skin. Laboratory tests contribute and assist in the diagnosis of polymyositis/dermatomyositis but they should always be evaluated in context with clinical picture and other tests and decisions about diagnosis and/or treatment are based on the integration of the results.

[Pathophysiology of gout]. / Patofiziologija uricnog artritisa.

Hyperuricemia is rather often metabolic disorder in general population. It is multifactorial disorder influenced by purine rich diet, alcohol consumption, diuretics use and renal deterioration. In the presence of local urate superasturation and lower solubility, monosodium crystals are deposited in joints, kidneys and soft tissue leading to clinical manifestations, such as gout, tophaceus deposits, nephrolithiasis and uric nephropathy. Major advances in understanding the pathogenesis of hyperuricemia and gout have been made recently, including genetic studies of urate transporters in kidneys as well as innate immune inflammatory responses and cytokine production which will be discussed thoroughly in this paper.

[Digital ulcers in systemic sclerosis]. / Digitalne ulceracije u sistemskoj sklerozi.

Digital ulcers occur in up to 50% of patients with limited or diffuse systemic sclerosis. The lesions are extremely painful leading to substantial functional disability, local infection susceptibility and can escalate to gangrene and amputation. Underlying vasculopathy and angiopathy cause obliteration of digital arteries and ischemic tissue changes. Management of digital ulcers includes non-pharmacological and pharmacological modalities. Early diagnosis in preclinical phase would enable preventive treatment prior to irreversible changes.

Human leptospirosis in eastern Croatia, 1969-2003: epidemiological, clinical, and serological features.

This survey presents epidemiological, serological and clinical features of 270 patients (85% males, 18% children) treated for leptospirosis from 1969 to 2003 at the Clinic for Infective Diseases, University Hospital Osijek, Osijek, eastern Croatia. 75% of the admissions were between July and October. The route of transmission was mostly by indirect contact with domestic animals, less frequently by direct contact with urine or tissue of infected animals. Clinical presentation included signs and symptoms with expected and common frequency, with the exception of jaundice (62%) and aseptic meningitis (60%), which occurred with higher incidence than previously reported. Acute renal failure ensued in 53% of patients, 7% of whom required haemodialysis. No deaths were observed. Therapy consisted of antimicrobials (penicillin and doxycycline) and symptomatic measures. Diagnosis was confirmed by microscopic agglutination test (MAT). There were in total 18 serological types of Leptospira detected, and types L. sejroe, L.pomona, L. australis and L. icterohaemorrhagiae prevailed. During the last 10 y some new types were observed. Leptospirosis was not rare in the region of eastern Croatia, and its course could be life-threatening if not recognized and adequately treated.

[Ragweed hypersensitivity in Osijek-Baranja region]. / Preosjetljivost na pelud ambrozije na podrucju Osjecko-baranjske zupanije.

Hypersensitivity of the respiratory system to pollens depends on the dominant kind of pollen grains in the air. It manifests as seasonal allergic rhinoconjunctivitis and asthma. The appearance and the severity linearly correlate with the pollen concentration in the air. In the last few years an increase in the number of people hypersensitive to pollen has been observed in the Osijek-Baranja region. It correlates with the expansion of ragweed and the increase of its air pollen concentrations. Since 2001, pollen and spores are being monitored in Osijek. This project has been initiated by the Association for the Prevention of Allergic Diseases and has been carried out in cooperation with the Regional Office of Public Health. Measurements are done using the Burkard volumetric apparatus according to the predetermined standard and are presented in pollen/m3 of air. Ragweed pollen is found in the air from the beginning of August until the end of September, with the maximum contentrations from the end of August until the middle of September.