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According to recent data, one in eight people in the world struggle with obesity. Obesity management is increasingly dependent on bariatric surgical interventions, as the combination of lifestyle modifications and pharmacotherapy could have a modest long-term effect. Surgery is recommended only for individuals whose body mass index (BMI) ≥ 40 kg/m 2 and ≥ 35 kg/m 2 in the presence of weight-related comorbidities. The most commonly performed procedures are sleeve gastrectomy and roux-en-Y gastric bypass. Pharmacokinetic and pharmacodynamic alterations occur as a result of the anatomical and physiological changes caused by surgery, which further differ depending on physicochemical drug factors and factors related to the dosage form. The following modifications are distinguished based on the type of bariatric surgery performed. Most bariatric patients have accompanying comorbidities, including dyslipidemia treated with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins. Significant improvements in the lipid profile are observed early in the postoperative period. The data reported in this review on statin pharmacokinetic alterations have demonstrated substantial inter- and intravariability, making it difficult to adopt clear guidelines. Based on the current literature review, reducing the statin dose to the lowest effective with continuous monitoring is considered an optimal approach in clinical practice.

Objective: The genetic background of HLA-B*27 in spondyloarthritis is known, and the search for another gene with similar role is ongoing. We wanted to investigate clinical presentations of HLA-B*44 patients in rheumatology practice. Methods: A cross-sectional retrospective study of 303 HLA-B*44 adult patients from the outpatient rheumatology clinic from 5/2018-5/2024. Clinical phenotype, confirmed or excluded rheumatic diagnosis, therapy used, and data on HLA A, B, and DR alleles inherited with B*44 were analyzed. Results: A female predominance of 2.79:1 was noted. A total of 150 [49.5%] patients were referred due to peripheral joint pain, 77 [25.4%] due to combined spine and peripheral joint pain or spine alone (57 [18.8%]). A total of 19 [6.3%] patients had no symptoms of the musculoskeletal system. Statistically significant peripheral joint affection was proved in females but not in males ( p = 0.04). A total of 121 [40%] patients from B*44 group had established rheumatic disease, with the rest being excluded or under observation. The most common working diagnoses were polyarthritis (32 [10.5%]) and mono-oligoarthritis (14 [4.6%]). A second allele in addition to HLA B*44 showed a similar frequency to the general population. Patients with HLA B*44/44 and B*27/44 genotypes were at the most risk for having definitive rheumatic disease (>60%). Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) were used in 38.6% of patients, non-steroidal anti-inflammatory drugs were used in 31.6% of patients, biologic DMARDs were used in 8.9% of patients, and corticosteroids were used in 7.3% of patients. Conclusions: The most common presentation in HLA-B*44 patients is peripheral joint affection. Most patients with HLA-B*27/44 and B*44/44 genotypes had definitive rheumatic disease. B*44 homozygosity or B*27/44 might be risk factors for arthritis development.

Various connective tissue diseases tend to affect specific organs, lungs being the organ with the most serious repercussions and consequences. The diagnosis of interstitial lung disease makes the treatment more difficult and worsens long-term prognosis and overall survival. Positive results from the registration studies of nintedanib led to approval of the drug for the treatment of idiopathic pulmonary fibrosis and chronic fibrosing interstitial lung diseases in connective tissue diseases. After registration, real-world data on the use of nintedanib are being collected in everyday clinical practise. The objective of the study was to collect and analyse real world experience gathered after the registration of nintedanib for the treatment of CTD-ILD and to show if the positive results collected from a homogeneous and "representative" study population can be applied to everyday clinical practice. We are presenting a retrospective observational case-series study of patients treated with nintedanib from the three largest Croatian centers specialised in the treatment of connective tissue diseases with interstitial lung diseases. Stabilisation or improved of lung function tests was reported in 68% of patients when changes in predicted FVC were observed and in 72% of patients when changes in DLco were analysed. Almost all of the reported patients (98%) were treated with nintedanib as an add-on drug to immunosuppressants. The most common side-effects were gastrointestinal symptoms and abnormal liver function tests in less extent. Our real-world data confirm the tolerability, efficacy and similar side-effects of nintedanib as reported in pivotal trials. Key Points • Interstitial lung disease is a common manifestation of several connective tissue diseases and its progressive fibrosing phenotype contributes to high mortality rate and many unmet needs regarding the treatment remain. • Registration studies of nintedanib obtained sufficient data and positive results to support approval of the drug. • Real-world evidence from our CTD-ILD centres confirm the clinical trial data regarding efficacy, tolerability and safety of nintedanib., (© 2023. International League of Associations for Rheumatology (ILAR).)

Biologic disease-modifying antirheumatic drugs (DMARDs) are very effective in treating rheumatic diseases with a good patient tolerance. However, high cost and individualistic approach requires dedication of the physician. Therefore, the aim of this study was to determine how the COVID-19 pandemic has affected the prescription of biologic DMARDs in rheumatology at the University Hospital of Split. The data collection was conducted through an archive search in the Outpatient Clinic for Rheumatology in the University Hospital of Split, Split, Croatia. The search included the period before and after the start of the COVID-19 pandemic in Croatia (31 March 2020). Collected data included age, sex, ICD-10 code of diagnosis, generic and brand name of the prescribed drug, date of therapy initiation, and medication administration route. In the pre-COVID-19 period, 209 patients were processed, while in the COVID-19 period, 185 patients were processed (11.5% fewer). During pre-COVID-19, 231 biologic medications were prescribed, while during COVID-19, 204. During COVID-19, IL-6 inhibitors were less prescribed (48 (21%) vs. 21 (10%) prescriptions, p = 0.003), while IL-17A inhibitors were more prescribed (39 (17%) vs. 61 (30%) prescriptions, p = 0.001). In ankylosing spondylitis (AS), adalimumab was prescribed more during pre-COVID-19 (25 vs. 15 patients, p = 0.010), while ixekizumab was prescribed less (1 vs. 10 patients, p = 0.009). In rheumatoid arthritis, tocilizumab was prescribed more in the pre-COVID-19 period (34 vs. 10 patients, p = 0.012). Overall, the prescription trends of biologic DMARDs for rheumatologic diseases did not vary significantly in the University Hospital of Split, Croatia. Tocilizumab was prescribed less during COVID-19 due to shortages, while ixekizumab was more prescribed during COVID-19 due to an increase in psoriatic arthritis patients processed and due to being approved for treating AS.

To determine salivary flow rate, oral and periodontal status, oral health-related quality of life (OHRQoL), objective and subjective indexes, and serum antibody reactivity in patients with primary Sjögren's disease (pSD). 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 (DMFT = D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, OHRQoL, objective European League Against Rheumatism (EULAR) SS Disease Activity Index (ESSDAI) and subjective (EULAR SS Patient Reported Index (ESSPRI), 6-items-VAS-SS (Visual Analog Scale), Profile of Fatigue) indexes were analyzed. The patients with pSD had a blood sample taken in the morning between 7 and 10 a.m. for comprehensive laboratory analysis. Patients with pSD had statistically significant lower UWSFR (0.20 vs. 0.90 mL/min) and SWSFR (0.56 vs. 1.64 mL/min) values compared with control subjects ( p < 0.001, Mann-Withney U test). Salivary pH value of pSD patients was significantly lower compared with control subjects (6.00 vs. 7.00; p < 0.001, Mann-Whitney U test). The mean DMFT index of patients with pSD compared to control subjects was not statistically significant (23.74 ± 7.28 vs. 20.77 ± 5.73; p = 0.08, t -test). Interincisal distance was significantly decreased in the pSD group compared with control subjects (43.80 ± 0.38 vs. 47.60 ± 0.50; p = 0.003, t -test). The prevalence of periodontitis was similar in patients with pSD and control subjects (83.9% vs. 77.4%; p = 0.35, λ 2 test). The mean Oral Health Impact Profile (OHIP-49) total score was statistically significantly higher in pSD patients compared with control subjects (32.00 vs. 8.00; p < 0.001, Mann-Whitney U test). Patients with pSD have decreased salivary flow and salivary pH, poor oral health, decreased interincisal distance, high prevalence of periodontitis, and worse OHRQoL. These findings highlight the need for a multidisciplinary approach to the management of patients with pSD that includes physical and psychological aspects of the disease.

Determination of salivary flow rate and oral status in patients with primary Sjögren's Syndrome (pSS) and diffuse cutaneous systemic sclerosis (dcSSc) and comparison with control subjects. Thirty-one pSS patients, 28 dcSSc patients, and 28 control subjects participated in this single-center, cross-sectional study. Unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, and OHRQoL (oral health-related quality of life) were analyzed in all three groups of subjects. Primary SS and dcSSc patients had statistically significant lower values of UWSFR (0.20; 0.38 vs. 0.91 mL/min) and SWSFR (0.56; 0.70 vs. 1.64 mL/min) compared with control subjects ( p < 0.001, Kruskal-Wallis test). Salivary pH values were statistically significantly lower in pSS and dcSSc patients compared with control subjects (6.00; 6.25 vs. 7.00, respectively) ( p < 0.001, Kruskal-Wallis test). The DMFT index of dcSSc patients was higher (28.50) and statistically significant compared to control subjects (20.00) ( p = 0.01). The prevalence of periodontitis was the same in pSS and dcSSc patients and control subjects ( p = 0.384). Primary SS and dcSSc patients had a statistically significant decreased interincisal distance compared to control subjects (43.80; 38.00 vs. 48.00) ( p = 0.003 and p < 0.001, respectively). Primary SS and dcSSc patients show decreased UWSFR and SWSFR, salivary pH values closer to an acidic medium, higher DMFT index, higher prevalence of periodontitis, decreased interincisal distance, and poorer OHRQoL, i.e., poor oral and periodontal health.

Epidermolysis bullosa acquisita (EBA) is a rare chronic autoimmune subepidermal blistering disease of the skin and mucous membranes, usually beginning in adulthood. EBA is induced by autoantibodies to type VII collagen, a major component of anchoring fibrils in the dermal-epidermal junction (DEJ). The binding of autoantibodies to type-VII collagen subsequently leads to the detachment of the epidermis and the formation of mucocutaneous blisters. EBA has two major clinical subtypes: the mechanobullous and inflammatory variants. The classic mechanobullous variant presentation consists of skin fragility, bullae with minimal clinical or histological inflammation, erosions in acral distribution that heal with scarring, and milia formation. The inflammatory variant is challenging to differentiate from other autoimmune bullous diseases, most commonly bullous pemphigoid (BP) but also mucous membrane pemphigoid (MMP), Brunsting-Perry pemphigoid, and linear IgA dermatosis. Due to its recalcitrance conventional treatment of epidermolysis bullosa acquisita is shown to be demanding. Here we discuss novel therapeutic strategies that have emerged and which could potentially improve the quality of life in patients with EBA.

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.

Recently, the number of patients with acute telogen effluvium (ATE), among other forms of hair loss, has increased in comparison with previous years. The COVID-19 pandemic, taking place during this period, may be the cause of this phenomenon. The exact mechanisms by which this virus causes hair loss are not entirely understood; still, the most likely cause is an excessive release of proinflammatory cytokines during SARS-CoV-2 infection. This process can trigger the development of telogen effluvium (TE) by damaging hair matrix cells. Additionally, the psychosocial condition of patients recovering from COVID-19 will have deteriorated, contributing to hair loss. Based on data collected until now, post-COVID TE is expected to improve without any treatment. Although there is no specific treatment for post-COVID TE, eliminating psychophysical stress, managing systemic complications, and explaining the course of the condition to the patient will potentially improve and speed up the hair recovery process.

Objective: The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia County (SDC) in Croatia and to determine their relationship with disease severity., Methods: A total of 74 RA patients and 80 healthy controls from the SR, and 74 RA patients and 80 healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C‑reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index., Results: The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%; P = 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%; P = 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (P = 0.014 and P = 0.004, respectively), higher disease activity (P = 0.043), and worse functional status (P < 0.001), than SE-positive patients from the rest of the SDC., Conclusion: The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Objective : The most prominent feature of systemic sclerosis (SSc), besides vasculopathy and autoimmune disorders, is excessive fibrosis. Serotonin affects hemostasis and can induce vasoconstriction, which is presumed to be one of the pathophysiological patterns in SSc that leads to fibrosis. Our aim was to explore the possible association of serotonin with some of the clinical features of SSc in our cohort of patients. Materials and Methods : We measured serotonin levels in sera of 29 female SSc patients. Patients were 41-79 years old, their average disease duration was 9 years. Serotonin values were analyzed in correlation with clinical and laboratory parameters, such as modified Rodnan skin score (mRSS), digital ulcers (DU), and spirometry parameters-forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and lung diffusion capacity of carbon monoxide (DLCO). Statistical analyses were performed using statistical software Statistica. Results : We found correlation of serotonin level with mRSS (r = 0.388, p = 0.038). The highest values of serotonin were documented in patients with refractory DU, but this was not statistically significant. We also found a negative correlation between serotonin and FVC (r = -0.397), although it did not reach the level of significance ( p = 0.114). Conclusions : Our study suggests that levels of serum serotonin could affect the course of skin fibrosis and partially restrictive pulmonary dysfunction in patients with SSc. We assume that serotonin might have influence on several features of SSc, but more studies are needed to reveal those relations.

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/m 2 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., (© 2020. Springer-Verlag GmbH Austria, part of Springer Nature.)

Primary Sjögren's syndrome (pSS) patients have higher prevalence of endothelial dysfunction and premature atherosclerosis. Recent studies investigated adropin, a secretory protein that can regulate lipid metabolism and insulin resistance and protect endothelial cells' function and that has an anti-inflammatory effect. The aim of this study was to determine adropin levels in pSS patients compared to healthy controls. Additional goals were exploring the correlation between adropin and several metabolic and immunological parameters in pSS, including disease specific antibodies, EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), and Sjögren's Syndrome Disease Damage Index (SSDDI). This research included 52 pSS patients and 52 healthy controls. pSS patients have significantly higher adropin levels compared to the control group (3.76 ± 0.68 vs. 3.14 ± 0.69 ng/mL, p < 0.001). Correlation analysis showed that adropin levels in pSS patients have positive correlation with high-density lipoprotein (HDL) (r = 0.290, p = 0.036) and anti SSA/Ro52 antibodies (r = 0.307, p = 0.026) and negative correlation with SSDDI (r = -0.401, p = 0.003). Multivariant linear regression showed that adropin levels are independently associated with HDL (β ± SE, 0.903 ± 0.283, p = 0.002) and SSDDI (β ± SE, -0.202 ± 0.073, p = 0.008). Our findings imply that adropin could be involved in the pathophysiology of pSS, yet it remains to be elucidated in future studies whether adropin has a protective or detrimental role in this setting.

Patients with systemic lupus erythematosus (SLE) are often interested in which diets to follow. Our aim was to investigate which dietary habits were common among our patients, and which of them were in correlation with laboratory parameters of disease activity, such as complement values and 24-h proteinuria. This study included 76 patients with SLE in clinical remission with a 6-month flare free period. They completed a specialized, self-administered, 23-item food frequency questionnaire about their weekly dietary habits. Basic anthropometric data, levels of C3 and C4, and 24-h proteinuria were recorded and analyzed with respect to their dietary habits. The majority of patients had a normal body mass index of 18.5-25 kg/m 2 , and worked out regularly. The most frequently consumed foods reported by the patients were fruits, milk, vegetables, meat, pasta, rice, and bread. Decreased values of C3 were found in 34 (44.7%) patients, and decreased values of C4 in 28 (36.8%) patients. Decreased values of C3 were found in patients who often consumed meat ( P  = .015), and decreased values of C4 in patients who often consumed fast food ( P  = .043). Patients who often consumed fast food demonstrated a decreasing trend of C3 ( P  = .060), and patients who often consumed fried food had a decreasing trend of C4 ( P  = .051). Significant correlation between daily proteinuria and dietary habits was not found. Dietary habits can influence the disease course of SLE. Our study confirms that decreased levels of complement compounds C3 and C4, which are possible predictors of disease activation, are associated with frequent consumption of low quality proteins and food rich in calories.

Objective: To analyze the correlations of saliva production and pH value with disease activity, disease severity, and oral health-related quality of life in patients with diffuse cutaneous systemic sclerosis (dcSSc) without concomitant Sjögren's syndrome (SS) or SS-related antibodies., Methods: This cross-sectional study included 28 patients with dcSSc and matching healthy controls. Sialometric assessment and caries status were compared between the two groups. Clinical and laboratory parameters were used to evaluate disease severity, in accordance with the Medsger Severity Scale., Results: In patients with dsSSc, reduced saliva production and higher pH value were associated with disease activity and severity; moreover, caries status was correlated with SSc disease characteristics, including disease duration and disease severity. Oral health-related quality of life was negatively correlated with mean salivary flow rate., Conclusions: These findings contradict the existing notion that reduced saliva production in patients with SSc is linked to SS-related antibodies or caused by underlying SS. In addition, patients with dcSSc exhibit elevated risk of cardiovascular disease and invasive dental treatment has been shown to enhance the rates of stroke and heart attack in the general population; therefore, oral health is particularly important in patients with SSc.

Objective: This study was performed to identify a possible association of the clinical parameters of systemic sclerosis (SSc) and the socioeconomic status (SES) with oral health-related quality of life (OHrQoL) as measured by the Oral Health Impact Profile 49 (OHIP 49), taking into account the effect of educational level (as a proxy of SES) on oral health., Methods: Subjects were recruited from the Croatian SSc Center of Excellence cohort. Detailed dental and clinical examinations were performed according to standardized protocols. The associations of OHrQoL with disease characteristics and socioeconomic status were examined., Results: Thirty-one consecutive patients with SSc were enrolled (29 women; mean age, 56.45 ± 13.60 years). OHIP 49 scores were significantly correlated with disease activity and severity. Furthermore, OHrQoL was positively correlated with skin involvement as evaluated by the modified Rodnan skin score. Impaired OHrQoL was positively correlated with the severity of general, skin, gastrointestinal, and joint/tendon involvement. The OHIP 49 score differed between patients who were positive and negative for anti-topoisomerase I antibody. Higher OHIP 49 scores were detected in patients with lower SES (primary school educational level)., Conclusion: Collaboration between rheumatologists and dental professionals is required to improve dental care and oral health outcomes of SSc.

Polymyositis (PM) is an autoimmune disease which affects skeletal muscles. In young age, it usually occurs as an idiopathic disorder associated with specific autoantibodies (anti-Jo), while in older age it is often associated with neoplasms. It can present with symptoms of other autoimmune diseases, such as systemic sclerosis (SSc), a rare progressive 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 confirmed by the characteristic pathohistological finding. The patient had sclerodermal skin lesions on his back, but he did not have other typical SSc symptoms, and the specific autoantibodies were negative. He received glucocorticoid therapy (GC) after we had finished 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 often 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 different onsets. There 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 effects of GC in SSc.

Vasculitis is clinicopathologic process characterized by inflammation and damage of blood vessels, often resulting in complete or partial occlusion of the involved vessels and ischemic damage to the supplied organ or tissue. The vasculitides are a large group of heterogeneous diseases for which it has been assumed that pathogenesis is largely autoimmune. It may be a primary or secondary manifestation of a disease process and may affect single or multiple organs. Inflammation affects vessel's walls partly or completely resulting with the loss of vascular integrity. Vasculitides has been classified by whether inflammation predominantly damage small, medium, or large vessels.

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.

It is a well-documented fact that sex hormones are implicated in the immune response and that androgens and estrogens modulate susceptibility and progression of autoimmune rheumatic diseases. Estrogens are considered to stimulate cell proliferation and humoral immune responses while androgens exert suppressive effects on both humoral and cellular immune responses. Autoimmune diseases are common in females, especially during the generative period, the most representative of estrogen-related autoimmune diseases being systemic lupus erythematosus. Estrogens and androgens are involved in the pathogenesis of the disease; both exogenous and endogenous estrogens are strong stimulators of cytokine production and disease activity. Some physiological conditions, as well as some drugs and chronic stress, can modulate hormone levels. Low levels of gonadal androgens have been detected in body fluids of both male and female rheumatoid arthritis patients, supporting the possibility of the pathogenic role for decreased androgen levels. Views on hormone replacement therapy or hormonal contraception in rheumatic diseases have been modified and in most rheumatic diseases, including rheumatoid arthritis, hormones are not prohibited. There are still controversies regarding systemic lupus; the new standpoint being that hormonal contraception is not contraindicated in women with inactive or stable active SLE, except for those with positive antiphospholipid antibodies.

Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional im- pairment and reduced quality of life. The disease should be recognized early when there is a "window of oppor- tunity" 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 practi- tioner 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.

Hypertrophic osteoarthropathy is a syndrome presenting with dclubbing, limbs enlargement, pain and swelling of foot and long bones osteitis. Hypertrophic osteoarthropathy is a rare paraneoplastic syndrome in the patients with primary or metastatic lung cancer. We report 39-year old female patient who presented with arthritis and paraneoplastic hypertrophic osteoarthropathy revealing lung adenocarcinoma.

The objective was to analyse epidemiological tendencies of rheumatoid arthritis (RA) in Dalmatia County in order to identify possible spatial clusters of RA. Patient-interviewers were trained to administer telephone surveys. 197 RA patients controlled at Rheumatology and immunology department of Clinical hospital of Split were mapped to place of residence by telephone survey. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. Four clusters were identified; the largest one was in the region of Sinj. The female/male ratio was 5.79:1. Majority of RA patients were among age 50 to 59 (30.45 %). The results show inter-regional variations with the marked clusters in the north of Dalmatia suggesting that clusters with higher incidence of RA have specific genetic and environmental background. Prevalence of RA in female was higher than in current literature, while the age of onset 50-59 years is similar with data from recent studies.

Polymyositis and Dermatomyositis are often connected with autoimmune diseases and are closely linked with specific autoantibodies. Clinical manifestations are mild in correlation with clinical picture ofmyositis related to malignancy. Pulmonary complications are main cause of mortality in overlap syndromes with autoimmune diseases. Infection, cardiovascular complications and underlying malignancy provide greater mortality risk.

Treatinent of systemic lupus erythematosus is very difficult because of heterogeneous clinical manifestations. Standard therapy includes non-steroidal anti-inflammatory drugs, glucocorticoids, anitimalarials and cytotoxic agents. A numerous biological agents have been investigated for treatment of the systemic lupus erythematosus. They are directed to B and T cell depletion, blockade of co-stimulatory molecules, inhibition of cytokines and complement modulation. Sirolimus, tacrolimus, autologous hematopoietic stem cell transplantation and allogenic mesenchymal stem cells transplantation have been also investigated for treatment of systemic lupus erythematosus.

Churg-Strauss syndrome is a rare form of eosinophilic vasculitis associated with asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have recently been reported in asthmatic patients being treated with antileukotriene receptor antagonists. However, whether these drugs have a direct pathogenic role remains controversial. We describe two patients who developed Churg-Strauss syndrome after starting treatment with montelukast.

Neuropsychiatric disorders appear in about 70% of the patients diagnosed with systemic lupus erythematosus (SLE). The aim of this study was to evaluate morphological and functional abnormalities of central nervous system (CNS) in SLE patients with neuropsychiatric manifestations (NP) of disease by testing their relationship. We tested 10 patients (9 females, 1 male) with clinical manifestations of neuropsychiatric systemic lupus erythematosus (NP-SLE). That means clinical evaluation of symptoms, standard immunoserological tests, electroencephalogram (EEG), component of audio--evoked potentials P300, MMPI-202 test, Rey Complex Test and magnetic resonance imaging (MRI). MRI abnormalities were seen in all of our patients, while in 9 patients abnormalities in neuropsychological and neurophysiologic tests have been proved. The most common structural brain change, detected by MRI, was cortical atrophy (in 8 out of 10 patients). According to revised classification of the American College of Rheumatology (ACR) NP-SLE, the most frequent disorder was cognitive dysfunction (in 9 out of 10 patients). Cortical atrophic brain changes have been established in 7 out of 9 patients with cognitive dysfunction. Because of already known correlation of cortical atrophy with cognitive dysfunction in SLE patients, without neuropsychiatric manifestation, we can conclude that neuropsychological examination is required in every patient with systemic lupus erythematosus.

Background and Aims: Computed tomography (CT), especially contrast-enhanced CT (CECT), provides important information on the severity and prognosis of acute pancreatitis (AP). Magnetic resonance imaging (MRI) has become a useful tool as an alternative to CT in the assessment of AP. The primary aim of our study was to determine the diagnostic value of nonenhanced MRI (NEMRI) to assess severity and predict outcome in patients with AP from the third to fifth day after admission. We also correlated MRI findings with CT and biochemical parameters., Patients and Methods: The study included 101 patients (49 men, 52 women, median age 62 yr, range 20-82) with a diagnosis of AP admitted to our hospital between January 1, 2004 and June 31, 2005. The inclusion criteria consisted of a combination of clinical features, a typical case history, elevation of serum pancreatic enzymes, and diagnosis confirmed by imaging studies. Contrast-enhanced spiral CT exams were performed in all patients from the third to fifth day after admission, and Balthazar grade and CT severity index were calculated. All patients underwent NEMRI, and MR severity index (MRSI) was calculated. We also performed magnetic resonance cholangiopancreatography (MRCP) in all patients to detect bile duct lithiasis., Results: Significant correlation between CECT and NEMRI was found for Balthazar grade (P<0.001) and the assessment of pancreatic necrosis (P<0.001), as well as between the combined severity indices (rho=0.819, P<0.001). MRSI correlated with Ranson score (rho=0.656, P<0.01), C-reactive protein (CRP) levels 48 h after admission (rho=0.502, P<0.01), appearance of systemic complications (rho=0.576, P<0.01), and length of hospital stay (rho=0.484, P<0.01). Considering the Atlanta criteria as the gold standard and the Ranson score, no difference in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the two methods was observed. Comparing the group of patients with presumed acute pancreatic hemorrhage with the group of patients with severe AP, we found a significantly higher APACHE II score on the first day (P<0.05), that the development of systemic complications was more frequent (P < 0.05), and that the hospital stay and ICU management of patients with MRI signs of pancreatic hemorrhage tended to be longer., Conclusion: NEMRI is comparable to CECT in the early assessment of the severity of AP, and both methods are equally efficient in predicting local and systemic complications of AP. MRI has a potential advantage over CT in detecting bile duct lithiasis and pancreatic hemorrhage.

Background: Nausea and vomiting are well-known gastrointestinal complications in chronic renal failure and are frequent indications for the commencement of dialysis. Although the administration of antiemetic drugs (metoclopramide and, recently, ondansetron) is usually mentioned, there are scanty data on their effects., Methods: A double-blind crossover study was done in 10 uremic patients. All the patients were uremic and suffered from nausea and vomiting. The drugs were randomly administered intravenously (either metoclopramide 10 mg or ondansetron 8 mg) 2 h after blood drawing for laboratory tests either on the 1st or on the 3rd study day at the same time. The outcomes were scored after 24 h of follow-up by (1) one of us (D.P.; 1-3 points: 1 = no effect; 2 = moderate effect - decreased frequency of vomiting, and 3 = good effect - no vomiting), and (2) by the patients (1-5 points)., Results: The results obtained showed that ondansetron was more effective in controlling nausea and vomiting than metoclopramide, either objectively (2.80 +/- 0.422 vs. 1.40 +/- 0.699, p < 0.005) or subjectively (4.10 +/- 0.738 vs. 2.10 +/- 0.994, p < 0.005)., Conclusions: We conclude that at the dosage level studied ondansetron is about twice as effective as metoclopramide in the symptomatic relief of uremia-induced nausea and vomiting., (Copyright 2002 S. Karger AG, Basel)

Aim: To assess the incidence and timing of cardiac rupture following streptokinase (SK) administration in acute myocardial infarction (AMI)., Methods: We analyzed retrospectively the clinical sheets of AMI patients treated at the Coronary Care Unit in University Hospital Split, Croatia, between January 1, 1996, and December 31, 1998. We selected the patients who died after SK administration (1.5 million U in a 30 min iv. infusion), with a discharge diagnosis of "AMI" and "cardiac tamponade - ventricular rupture". AMI was defined by typical chest pain, ECG, and/or enzymatic changes. Echo or autopsy verified diagnosis of cardiac tamponade and/or rupture, as well as pericardial effusion and/or free-wall rupture., Results: Out of 726 AMI patients, 136 (18.7%) were treated with SK, and 6 had cardiac rupture (4 men and 2 women; 4.4%). Autopsy revealed that 1 patient had ischemic and 2 had transmural hemorrhagic AMI. Three out of 6 patients died 2-4, and 3 died 5-7 hours after SK administration. Six patients who died from cardiac rupture (mean age 72.3+/-9.0) were significantly older than AMI survivors treated with SK (121 patients, mean age 60.5+/-12.0 years, p<0.001)., Conclusion: In case of unexplained clinical deterioration in AMI patients over 70 during the first hours after SK administration, cardiac tamponade due to a free-wall rupture should be suspected. SK administration in patients with AMI over 70 years should be a selective and not a routine treatment.

As a primarily intestinal pathogen. Yersinia enterocolitica (Y. e.) may cause generalized infection in patients with malignant and other serious diseases or immunodeficient subjects. In certain conditions, elevated serum and tissue iron concentrations represent an additional risk factor for systemic infection with this opportunistic bacterium. In our patient, Y. e. septicemia developed during liver cirrhosis decompensation. Clinical signs of infection were alleviated by appropriate antibiotic therapy (gentamycin, cefuroxime), but as septicemia had been present for several days prior to therapy, it aggravated the patient's general condition, which entailed the development of hepatorenal syndrome and eventually lethal outcome.

From a sample of occupationally disabled persons who had retired because of a disease of the locomotive system 48 men and 22 women with pronounced arthrotic changes in lower extremities were selected for the study. A comparative group, which was matched to the experimental one by age (53.8 +/- 4.2 years) and sex, consisted of occupationally disabled persons who had rheumatic complaints, but no arthrotic changes in the lower extremities. All the subjects in the study were given a questionnaire to answer and underwent a clinical examination and an X-ray of the locomotive system. Marked symptoms of arthrosis were manifest in those aged 46 +/- 6 years. Besides occupation (coxarthrosis and gonarthrosis occurred more frequently among unskilled (54.2%) and skilled (25%) workers) a major risk factor were injuries (37.1% as against 5.7% in the comparative group). At clinical examination men complained much more often of spontaneous pain in the hip joints (60% as against 22.3% in women), whereas women more often complained of painful movements (63.6% as against 45.8% in men). The objective symptoms of gonarthrosis, crepitations and restricted movements in the first place, were present in men and women alike. The relative body mass (RBM), expressed as percentage of decline from ideal was, particularly among women, a significant risk factor for the occurrence and development of coxarthrosis and gonarthrosis. As much as 50% of the women with arthrosis had RBM higher than 140%, and another 40% had RBM between 120 and 140%. In the comparative group the respective percentage was 27.3% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)