[Relationship between vitamin D status and bone mineral density in Croatian postmenopausal women]. / Povezanost statusa vitamina D s mineralnom gustocom kosti u hrvatskih zena u postmenopauzi.

The aim of the study was to investigate correlation of vitamin D status meassured as 25-hydoxyvitamin D (25(OH)D) concentration with bone mineral density (BMD) in Croatian postmenopausal women. This study was based on the sample of 194 adult, postmenopausal women aged 50 years or over from Croatia. Assessment of 25(OH)D concentration and BMD by dual-energy xray absorptiometry (DXA) was performed to all participants. The average age of the participants in this study was 60.6 years. The average menopause duration was 11.4 years. Among the included participants only 13.9% of women complied with diagnostic criteria for osteoporosis. Mean serum concentration of 25(OH)D was 49.1 nmol/L (+/-17.1 SD). The prevalence of severe vitamin D deficiency was significantly higher in participants with osteoporosis compared with participants with normal BMD (<30 nmol/L; 29.6% vs. 9.8%). Correlation between serum 25(OH)D concentration and BMD was significant and positive at the proximal femur (r=0.18; p=0.026), and at the femoral neck (r=0.15; p<0.001). The results of this study indicate significant and positive correlation between serum 25(OH)D concentration and BMD meassured at the proximal femur and at the femoral neck in Croatian postmenopausal women.

[The proposal of the Croatian Society for Rheumatology for the treatment of adult rheumatoid arthritis patients with biologics, 2013]. / Prijedlog Hrvatskog reumatoloskog drustva HLZ-a za lijecenje reumatoidnog artritisa odraslih bolesnika bioloskim lijekovima, 2013.

Standardized approach to the patients with rheumatoid arthritis (RA) is one of the requirements of good clinical practice. Croatian Society for Rheumatology (HRD) of Croatian Medical Association (HLZ) updated the Proposed treatment of rheumatoid arthritis (RA) with biologic agents in line with recent findings in rheumatology for the last 3 years. By complying with the agreed standards of treatment we can avoid malpractice and irrational consumption, and to the most patients provide a greater chance for a favorable outcome.

[The proposal of Croatian Society for Rheumatology for anti-TNF-alpha therapy in adult patients with spondyloarthritides, 2013]. / Prijedlog hrvatskog reumatoloskog drustva HLZ-a za primjenu inhibitora TNF-alpha u odraslih bolesnika sa spondiloartritisima, 2013.

Croatian Society for Rheumatology of Croatian Medical Association updated the proposal for the application of TNF-alpha inhibitors in adult patients with spondyloartritides (SpA) in accordance with the new classification of SpA and european recommendations for the treatment of SpA with biologic agents. In this way a standardized method of diagnosis, targeted treatment, monitoring and evaluating outcomes are proposed.

Analysis of granulysin-mediated cytotoxicity in peripheral blood of patients with psoriatic arthritis.

The objective of the present study was to investigate possible changes in granulysin (GNLY)-mediated cytotoxicity of peripheral blood lymphocytes in psoriatic arthritis (PsA) patients with respect to different phases of the disease. We prospectively enrolled 25 PsA patients in the active phase, 26 PsA patients in remission and 24 healthy controls. The simultaneous detection of intracellular GNLY and cell surface antigens (CD3 and CD56) was performed with flow cytometry. GNLY apoptotic protein was visualised by immunocytochemistry. Natural killer (NK) cell cytotoxicity was analysed with a cytotoxicity assay against human erythroleukaemia K-562 cells. The percentage of GNLY(+) cells did not differ significantly between PsA patients in the acute phase and those in remission; however, it was always higher than in healthy examinees due to the increased percentage of GNLY(+) cells within T cells, NKT cells, and both, and in the CD56(+dim) and CD56(+bright) NK subsets. The mean fluorescence intensity for GNLY was higher in all lymphocyte subpopulations in the acute phase than in remission and in healthy controls. Accordingly, GNLY-mediated NK cell cytotoxicity against K-562 cells of active phase PsA patients was significantly higher than that in patients in remission or in healthy controls. These findings demonstrated the involvement of GNLY in the worsening of PsA and suggested that GNLY mediated the development of joint lesions.

[Scoring of disease activity using BASDAI and ASDAS method in ankylosing spondylitis]. / Ocjena aktivnosti ankilozantnog spondilitisa primjenom BASDAI i ASDAS instrumenta.

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is the most frequently used ankylosing spondylitis activity assesment by which through 6 questions 5 basic diseases symptoms (fatigue, back pain, joint pain/swelling, enthesitic points, intensity and duration of morning stiffness) are being evaluated. In distinction from mentioned, Ankylosing Spondylitis Disease Activity Score (ASDAS) is the first validated index for the AS activity assessment with the patient's assessments of the disease symptoms (back pain, duration of the morning stiffess, activity of the disease, pains and swelling of the peripheral joints) includes the acute phase reactants (SE or CRP). We compared BASDAI and ASDAS indexes to the group of patients with the AS, in order to evaluate their congruence and to evaluate the inluence of SE, fatigue and back pain at obtained values. The cross-sectional study was performed in a group of 36 patients with the AS whose disease activity levels were evaluated by the BASDAI and ASDAS (SE) index. Statistical data analysis was performed by Student t-test and frequency tables for non-parameter data. As it has been expected the significant correlation between BASDAI and ASDAS indexes has been confirmed (r=0.796; p=0.00). BASDAI/ASDAS average value of all of the patients was 4.2/2.8. From 36 patients with the AS according to the BASDAI index 42% had mild active disease (BASDAI <4), while according to ASDAS index 44% patients had very active disease (ASDAS 2.1-.5.3). Higher activity of the disease according to ASDAS index is the result of the elevated sedimentation which is assessed only in ASDAS index. Patients with higher BASDAI index statistically have more significantly expressed fatigue and spinal pain without statistically significant difference in sedimentation (p=0.120). Examinees with higher ASDAS index have also significantly more expressed fatigue and back pain, but unlike BASDAI they have sedimentation (p=0.001). ASDAS is more recent clinical indicator of the AS activities which could be compared to BASDAI instrument. In this group of patients ASDAS seems to be more sensitive index because it discriminates more patients with the active disease.

[Conventional treatment of gout]. / Konvencionalno lijecenje uricnog artritisa.

Gout is a severely disabling disorder, leading to poor quality of life, functional impairment with repercussion on physical activity, social functioning and emotional health. On the other hand, gout is probably the best understood and most manageable of all common systemic rheumatic diseases. The treatment of gout is appropriately divided into treatment of the acute attack and prevention of further attacks and of joint damage. Standard management of acute attacks of gout consists of rest, application of ice to the affected joint, and prescription of non-steroidal anti-inflammatory drugs, or glucocorticoids which should be started immediately to be most effective. Colchicin and interleukin-1 inhibitors can be used as alternative, when are indicated and available. Urate lowering therapy (usually alopurinol) is indicated to treat recurrent gout attacks, chronic arthropathy, tophi and uric acid renal lithiasis.

[Diagnosis and conservative treatment of low back pain: review and guidelines of the Croatian Vertebrologic Society]. / Dijagnostika i konzervativno lijecenje krizobolje: pregled i smjernice Hrvatskog Vertebroloskog Drustva.

Low back pain (LBP) is a very common condition with high costs of patient care. Medical doctors of various specialties from Croatia have brought an up-to-date review and guidelines for diagnosis and conservative treatment of low back pain, which should result in the application of evidence-based care and eventually better outcomes. As LBP is a multifactorial disease, it is often not possible to identify which factors may be responsible for the onset of LBP and to what extent they aggravate the patient's symptoms. In the diagnostic algorithm, patient's history and clinical examination have the key role. Furthermore, most important is to classify patients into those with nonspecific back pain, LBP associated with radiculopathy (radicular syndrome) and LBP potentially associated with suspected or confirmed severe pathology. Not solely a physical problem, LBP should be considered through psychosocial factors too. In that case, early identification of patients who will develop chronic back pain will be helpful because it determines the choice of treatment. In order to make proper assessment of a patient with LBP (i.e. pain, function), we should use validated questionnaires. Useful approach to a patient with LBP is to apply the principles of content management. Generally, acute and chronic LBP cases are treated differently. Besides providing education, in patients with acute back pain, advice seems to be crucial (especially to remain active), along with the use of drugs (primarily in terms of pain control), while in some patients spinal manipulation (performed by educated professional) or/and short-term use of lumbosacral orthotic devices can also be considered. The main goal of treating patients with chronic LBP is renewal of function, even in case of persistent pain. For chronic LBP, along with education and medical treatment, therapeutic exercise, physical therapy and massage are recommended, while in patients with a high level of disability intensive multidisciplinary biopsychosocial approach has proved to be effective.

Proximal tibial stress fracture associated with mild osteoarthritis of the knee: case report.

Stress fractures are considered as multifactorial overuse injuries occurring in 0.3%-0.8% of patients suffering from rheumatic diseases, with rheumatoid arthritis being the most common underlying condition. Stress fractures can be classified according to the condition of the bone affected as: 1) fatigue stress fractures occurring when normal bone is exposed to repeated abnormal stresses; and 2) insufficiency stress fractures that occur when normal stress is applied to bone weakened by an underlying condition. Stress fractures are rarely associated with severe forms of knee osteoarthritis, accompanied with malalignment and obesity. We present a patient with a proximal tibial stress fracture associated with mild knee osteoarthritis without associated malalignment or obesity. Stress fracture should be considered when a patient with osteoarthritis presents with sudden deterioration, severe localized tenderness to palpation and localized swelling or periosteal thickening at the pain site and elevated local temperature. The diagnosis of stress fractures in patients with rheumatic diseases may often be delayed because plain film radiographs may not reveal a stress fracture soon after the symptom onset; moreover, evidence of a fracture may never appear on plain radiographs. Triple phase nuclear bone scans and magnetic resonance imaging are more sensitive in the early clinical course than plain films for initial diagnosis.

[The connection between HLA microsatellites and HLA-B*27 gene in patients with psoriatic arthritis in Croatian population]. / Povezanost mikrosatelita HLA i gena HLA-B*27 u bolesnika s psorijaticnim artritisom u hrvatskoj populaciji.

The polymorphism at HLA microsatellites (D6S248, D6S2674, D6S2811 and D6S273) among patients with psoriatic arthritis (PsA) (N = 22) and healthy control subjects (K; N = 94), as well as haplotypic associations between tested loci were analysed in this study. All subjects were previously typed for HLA-A and -B by PCR-SSP method and were HLA-B*27 positive. HLA microsatellites were analysed using PCR-STR method and electrophoresis in an ALFexpress sequencer. The results demonstrated statistically significant P value for following alleles: D6S273-3 (PsA-21.1% vs. K-4.9%; P = 0.0013) and D6S273-4 (PsA-15.8% vs. K-32.1%; P = 0.0180). Analysis of haplotypic associations showed the only statistically significant difference for combination HLA-B*27/D6S273-4 (PsA-10.5% vs. K-40.2%; P = 0.0164). The results presented in this study lead to the assumption that some other gene/s involved in ethiology of PsA are located in the proximity of D6S273 microsatellite, but in order to reach a final conclusion, an increase in the number of patients is necessary.

[The pharmacotherapy of spondyloarthritis]. / Farmakoterapija spondiloartritisa.

The objectives of treatment of spondyloarthritis are to improve functional status, diminish pain, prevent structural deterioration and reach drug free remission of disease. Nonsteroidal antiinflammatory drugs are the cornerstone of pharmacological intervention for ankylosing spondylitis, rapidly reducing pain and stiffness, and possibly modifying natural course of disease when given continuously. Conventional disease-modifying antirheumatic drugs which have been shown to be effective in the treatment of rheumatoid arthritis, have no proven such efficacy in spondyloarthritis. TNF-alpha blockade is highly effective in targeting the different disease features (axial disease, peripheral arthritis, enthesitis, and extra-articular features such as psoriasis or uveitis). There is no current evidence for the efficacy of other biological therapies in ankylosing spondylitis and psoriatic arthritis and every effort must be made to use TNF-alpha antagonists optimally.

[Benign joint hypermobility syndrome--a case report: unrecognized or undiagnosed condition?]. / Benigni hipermobilni sindrom--prikaz bolesnice: neprepoznato ili nedijagnosticirano stanje?

Hypermobility denotes an increased range of joint movements and is the result of ligamentous and joint capsule laxity. Benign joint hypermobility syndrome is hypermobility associated with symptoms--arthralgia, myalgia, fatigue, anxiety and fibromyalgia. Clinical manifestations of benign joint hypermobility syndrome include almost all organic systems, and reflect the ubiquity of connective tissue in the body. Beighton score help us to diagnoses hypermobility. Hypermobility syndrome is diagnosed using the 1998 "Brighton criteria". The purpose of this case report was to emphasize the importance of recognition hypermobility syndrome because such individuals represent a significant percentage patients who seek help of different specialist and because of the diversity of the clinical presentation very long stay unrecognized (undiagnosed). Hypermobility can be easily detected if you are looking for, but is easily overlooked if you do not think about it.

[Proposal for biologic drugs therapy in rheumatoid arthritis]. / Prijedlog primjene bioloskih lijekova u reumatoidnom artritisu.

Rheumatoid arthritis is a chronic, inflammatory disease with the prevalence about 1%. Rheumatoid arthritis is characterized with synovitis, often evolve erosions of the joints, pain and functional deficit. Etiology is unknown, but the development of such autoimmune disease is due to genetic and environmental factors. Most of the patients with diagnosis of rheumatoid arthritis use nonbiologic disease modifying antirheumatic drugs. Advances in the undersstanding of the disease process have led to the development of biological agents to treat rheumatoid arthritis. With the use of biologic agents we wish to evolve the goal of therapy from that of symptomatiic relief to clinical remission. Biologic drugs have documented, fast and continuous efficacy with generaly well accepted safety profile. On behalf of Croatian Society for Rheumatology we propose recommendations for the biologic therapy in rheumatoid arthritis.

[Guidelines of the Croatian Society for Rheumatology for the treatment of knee and hip osteoarthritis]. / Smjernice Hrvatskoga reumatoloskog drustva. Za lijecenje osteoartritisa kuka i koljena.

Osteoarthritis of the hip and the knee belongs to one of the most disabiliting conditions. Treatment goals for these patients include a reduction in pain, an improvement in joint mobility and to limit functional impairment. To properly manage osteoarthritis, both nonpharmacologic (non-interventional) and pharmacologic modalities may be employed, while minority of patients will require surgery. According to the available evidence for available therapies and experts' opinion here we present guidelines for the treatment of hip and the knee osteoarthritis in Croatia.

[Non-pharmacologic treatment of rheumatoid arthritis]. / Fizikalna terapija u reumatoidnom artritisu.

Non-pharmacologic interventions are the part of comprehensive therapy of rheumatoid arthritis, proposed by all guidelines and recommendations. Patients with rheumatoid arthritis have pain, limited joint mobility, and impaired quality of life. Physical modalities are prescribed exactly with idea to diminish pain, iprove joint mobility and quality of life. Physical procedures are generally safe and well tolerated.

[Recommendations of the Croatian Society for Rheumatology for prevention, diagnostics and treatment of post-menopausal osteoporosis]. / Preporuke Hrvatskog reumatoloskog drustva za prevenciju, dijagnostiku i lijecenje postmenopauzalne osteoporoze.

Osteoporosis is a disease characterized by loss of bone mass and the structural deterioration of bone tissue leading to increased bone fragility and fractures. Preventive measures for osteoporosis and osteoporotic fractures include adequate calcium and vitamine D intake, adequate physical activity and reduction of the risk factors can be influenced. Currently, measurement of bone mineral density using dual energy x-ray absorptiometry (DXA) is still the gold standard for the diagnosis of osteoporosis. Non-pharmacological therapy is the integral part of the management ofosteoporosis. Nitrogen-containing bisphosphonates in weekly or more prolonged (monthly) dosing intervals are now the firstline osteoporosis therapy. Oral bisphosphonates show, generally, similar efficacy on vertebral fractures risk reduction. There, might be some differences among bisphosphonates, regarding risk reduction of non-vertebral, hip and glucocortiocoid related fratures. On behalf of Croatian Society of Rheumatology of Croatian Medical Association we propose recommendations for the prevention, diagnosis and management ofpostmenopausal osteoporosis.

[Treatment strategy for rheumatoid arthritis in Croatia]. / Kako lijeciti bolesnike s reumatoidnim artritisom u Hrvatskoj?

The main objectives of the current treatment of rheumatoid arthritis are disease control, inhibition of radiographic progression and finally remission. Presumptions to achieving these goals are early diagnosis of rheumatoid arthritis and early administered therapy with disease modifying drugs as monotherapy or combination of drugs. The optimal therapeutic response is influenced by tight control of the patients, evaluation of efficacy and tolerability and change of therapeutic strategy as needed. For the patients refractory to standard disease modifying drugs anti-TNFa drugs can be added. The choice of anti-TNFalpha drug should be done regarding efficacy, tolerability and method of drug administration. In a patient who is failing to respond after 3 months to one anti-TNFalpha we can try other one or rituximab.

Persistence of weekly alendronate: a real-world study in Croatia.

Long-term treatment of osteoporosis is required for optimal efficacy, but adherence to therapy is suboptimal with daily and weekly oral bisphosphonates. The aim of this study was to assess real-world persistence (long-term adherence) with weekly alendronate. Persistence data were collected according to World Health Organization criteria for the prior month and year for 102 consecutive patients with osteoporosis at three outpatient clinics in Croatia. Persistence was assessed using medication possession ratios (MPR). Adequate persistence was defined as sufficient medication supply to ensure antifracture efficacy (MPR >or=80%). Self-reported persistence data were compared with resupply prescription data from primary care physicians (PCPs). The effect of patient age, co-therapy, co-morbidity, and time since osteoporosis was diagnosed were evaluated. A diagnosis of osteoporosis was established 3.21+/-1.83 years prior for the 96 women and six men enrolled (mean age 66.92+/-8.05 years). During the previous year, 86.3% patients reported not missing any tablets. Age correlated with the number of missed tablets, with older patients missing more tablets (p=0.038). Patients with co-therapy (p=0.042) missed more tablets. PCPs reported that 65.7% of the patients were issued prescriptions for 52 tablets. A total of 68.7% had MPR >80%. Patients with rheumatoid arthritis did not impact MPR (p=0.936). Previous fractures or number of fractures were not associated with persistence (p>0.05). In Croatia, persistence was superior with weekly-administered alendronate than has been reported elsewhere, perhaps due to socio-cultural factors. Larger, longitudinal studies are needed to confirm these results.

Coexistence of ochronosis and B 27 positive ankylosing spondylitis.

We describe a 49-year-old man with coexistence of ochronosis and B27 positive ankylosing spondylitis. This is the first report documenting the simultaneous occurrence of ochronosis and B27 positive ankylosing spondylitis, with no positive familiar history for seronegative spondylarthropathies. The relations of these rheumatic diseases are discussed.

[Leukocytoclastic vasculitis in primary Sjögren syndrome: a case report]. / Leukocitoklasticki vaskulitis u primarnome sjögrenovu sindromu: prikaz bolesnika.

We report a case of primary Sjögren's syndrome (SSjö with cutaneous leukocytoclastic vasculitis. The accurate diagnosis of SSjö was established based on objective signs and symptoms of ocular and oral dryness and characteristic appearance of a biopsy sample from a minor salivary gland, and presence of anti-SS-A autoantibody. Another autoimmune disorder was not present, so diagnosis of primary SSjö was established. Histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. The patient was treated with small doses of glucocorticoids and with local symptomatic therapy for ocular and oral dryness. SSjö is one of the most common autoimmune disorders and vasculitis is one of the most characteristic extraglandular manifestations, but wide spectrum of cutaneous involvement in primary SSjö has been little studied.