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Background:In the last 20 years, anti-tumor necrosis factor (TNF) alpha agents re-designed the management of rheumatoid arthritis (RA). Despite this, unmet needs in the management of RA brought several drugs targeting different molecules and cytokines. It is still a research question that how did these developments changed daily-practice in RA patients who are intolerant/unresponsive to the first biological disease modifying anti-rheumatic drugs (bDMARD).Objectives:In this study, we aimed to explore the second biologic agent trends of our 20-years of single-center experience.Methods:HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single center biological disease modifying anti-rheumatic drug (DMARD) registry since 2005. Patients who were started biologics before 2005 were registered retrospectively. Until the end of the 2020, 21 different rheumatologists contributed to the development of HUR-BIO. Distribution of the second-line biological agents (switch from first-line biological agent because of either adverse events or unresponsiveness) was calculated according to 5-year periods starting from the 2001. Also, demographic and serologic data of RA patients were reported.Results:A total of 776 (776/2080, 37.3%) RA patients, who was prescribed a second biological agent, was registered in HUR-BIO by the end of 2020. Of these patients, 83.7% was female. Mean age at the starting of bDMARD was 53.1 ± 13.3 years. Rate of rheumatoid factor and anti-cyclic citrullinated peptid positivity was 69.1% and 60.5%, respectively. Distribution of first-line bDMARDs was as follows: adalimumab 194 (24.9%), etanercept 209 (26.9%), infliximab 105 (13.5%), golimumab 39 (5.0%), certolizumab 35 (4.5%), abatacept 78 (10.0%), rituximab 46 (5.9%), tofacitinib 37 (4.7%), tocilizumab 33 (4.2%). 11 (1.4%), 85 (11.0%), 282 (36.3%) and 398 (51.3%) patients were prescribed with their second bDMARD in 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively. There was a trend towards the increasing prescription of non-Anti-TNF bDMARDs as second-line over time.Table 1.Distribution of second biologic DMARDs in RA patients according to 5-years periods2001-20052006-20102011-20152016-2020TotalAdalimumab3 (27.3)15 (17.6)69 (23.9)77 (18.9)164 (20.8)Etanercept8 (72.7)35 (41.2)49 (17.0)41 (10.1)133 (16.8)İnfliximab012 (14.1)13 (4.5)25 (6.2)50 (5.4)Golimumab0019 (6.6)8 (2.0)27 (3.4)Certolizumab002 (0.7)26 (6.4)28 (3.5)Anti-TNF11 (100)62 (72.9)152 (53.9)177 (44.5)402 (51.8)Tofacitinib004 (1.4)73 (17.9)77 (9.7)Tocilizumab0012 (4.2)81(19.9)93 (11.7)Rituximab022 (25.9)53 (18.3)32 (7.8)107 (13.5)Abatacept01 (1.2)61 (21.1)35 (8.6)97 (12.2)Non-Anti-TNF023 (27.1)130 (46.1)221 (55.5)374 (48.2)Total11 (100)85 (100)282 (100)398 (100)776 (100)Approval years of drugs in Turkey; Infliximab: 2003, etanercept:2004, adalimumab: 2005, golimumab: 2013, certolizumab: 2014, abatacept: 2010, tocilizumab: 2013, rituximab:2009, tofacitinib: 2015Conclusion:As the choice of second-line biologic and targeted synthetic DMARD, non-Anti-TNF bDMARDs, especially tofacitinib and tocilizumab becoming more frequent year-by-year. Despite that, anti-TNF agents as a group are still highly-prescribed options as second-line bDMARD.Disclosure of Interests:None declared

Background:Psoriatic arthritis (PsA) is a multi-dimensional chronic disease, which can affect joints, skin and enthesis. Extrapolation of the positive treatment results of anti-tumor necrosis factor (TNF) alpha agents on spondyloarthritis and rheumatoid arthritis to the treatment practice of PsA lead to a new era for the management of PsA. However, unmet needs in the management of PsA lead to development of several drugs targeting different molecules and cytokines. The impact of these developments on PsA patients who are intolerant/unresponsive to the first biological disease-modifying anti-rheumatic drugs (bDMARD) still needs to be defined.Objectives:To explore the second biologic agent trends on PsA patients of our 10-years of single-center experience.Methods:HURBIO-PsA (Hacettepe University Rheumatology Biologic Registry) is a single center biological disease modifying anti-rheumatic drug (DMARD) registry since 2005 on PsA patients. Until the end of the 2020, 19 different rheumatologists contributed to the development of HURBIO-PsA. Anti-TNF drugs were approved as first line bDMARD for PsA patients. Distribution of the second-line biological agents (switch from first-line biological agent because of either adverse events or unresponsiveness) was calculated according to 5-year periods starting from the 2011. Also, demographic and serologic data of RA patients were reported.Results:A total of 225 PsA (225/443, 50.8%) patients, who was prescribed a second biological agent, was registered in HURBIO-PsA by the end of 2020. Of these patients, 74.7% was female. Mean age at the starting of bDMARD was 47.1 ± 11.6 years. 90 (40.0%) and 135 (60.0%) patients were prescribed with their second bDMARD in 2011-2015 and 2016-2020, respectively. There was a trend towards the increasing prescription of non-Anti-TNF bDMARDs as second-line over time, especially for secukinumab.Table 1.Distribution of second biologic DMARDs in PsA patients according to 5-years periods2011-20152016-2020TotalAdalimumab30 (33.3)33 (24.4)66 (29.3)Etanercept33 (36.7)8 (5.9)41 (18.2)Infliximab9 (10)15 (11.1)24 (10.6)Golimumab9 (10)5 (3.7)14 (6.2)Certolizumab5 (5.6)34 (25.2)39 (17.3)Anti-TNF86 (95.6)95 (70.4)181 (80.5)Secukinumab026 (19.3)26 (11.5)Ustekinumab010 (7.4)10 (4.4)Abatacept4 (4.4)2 (1.5)6 (2.6)Tofacitinib02 (1.5)2 (0.9)Non-Anti-TNF4 (4.4)40 (29.6)44 (19.5)Total90 (100)135 (100)225 (100)Approval years of drugs in Turkey; Infliximab: 2003, etanercept:2004, adalimumab: 2005, golimumab: 2013, certolizumab: 2014, secukinumab: 2018, ustekinumab: 2018; abatacept and tofacitinib were given with the permission from the Ministry of Health of Turkey for off-label use authorizationConclusion:Almost half of the PsA patients switched their anti-TNF drugs to others. Non-Anti-TNF bDMARDs, especially secukinumab, becoming more frequently used as a second-line biologic agent in PsA in recent years. These bDMARD prescription trend is appropriate to EULAR PsA recommendations.Disclosure of Interests:None declared.

Background:In the last 20 years, there have been extraordinary improvements and practice-changing developments in the management of rheumatoid arthritis (RA). Exploring the pathogenetic mechanisms first enabled clinicians to use anti-tumor necrosis factor (TNF) alpha agents, then drugs targeting different molecules. Parallel to these developments, treatment guidelines have been changed accordingly. Meanwhile, how these developments have been reflected into the real-word practice is a question of interest.Objectives:In this study, we aimed to explore the first biologic agent trends of our 20-years of single-center experience.Methods:HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single center biological disease modifying anti-rheumatic drug (DMARD) registry since 2005. Patients who were started biologics before 2005 were registered retrospectively. In brief; demographic data, treatment-related data (including adverse events) and disease-related data of RA patients have been recorded in HUR-BIO. Until the end of the 2020, 21 different rheumatologists contributed to the development of HUR-BIO. In this study, distribution of the first-line biologic agents was calculated according to 5-year periods starting from the 2001. Also, demographic and serologic data of RA patients were reported.Results:A total of 2080 RA patients was registered in HUR-BIO by the end of 2020. Of these patients, 79.5% was female. Mean age at the starting of bDMARD was 53.3 ± 17.8 years. Rate of rheumatoid factor and anti-cyclic citrullinated peptide positivity was 67.6% and 61.0%, respectively. 65 (3.2%), 335 (16.1%), 858 (41.2%) and 822 (39.5%) patients were prescribed with their first bDMARD in 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively. There was a trend towards the increasing prescription of non-Anti-TNF bDMARDs over time.Table 1.Distribution of first biologic DMARDs in RA patients according to 5-years periods2001-20052006-20102011-20152016-2020TotalAdalimumab15 (23.1)111 (33.0)187 (21.8)153 (18.6)466 (22.4)Etanercept30 (46.2)154 (45.8)229 (26.7)54 (6.6)467 (22.4)İnfliximab20 (30.8)58 (17.3)64 (7.5)7 (0.9)149 (7.1)Golimumab0037 (4.3)43 (5.2)80 (3.8)Certolizumab0037 (4.3)68 (8.3)105 (5.0)Anti-TNF65 (100)323 (96.4)554 (64.5)325 (39.5)1267 (60.9)Tofacitinib006 (0.7)212 (25.8)218 (10.5)Tocilizumab009 (1.0)102 (12.4)111 (5.3)Rituximab012 (3.6)136 (15.8)84 (10.2)232 (11.1)Abatacept00153 (17.8)99 (12.0)252 (12.1)Non-Anti-TNF012 (3.6)304 (35.5)497 (60.5)813 (39.1)Total65 (100)335 (100)858 (100)822 (100)2080 (100)Approval years of drugs in Turkey; Infliximab: 2003, etanercept:2004, adalimumab: 2005, golimumab: 2013, certolizumab: 2014, abatacept: 2010, tocilizumab: 2013, rituximab:2009, tofacitinib: 2015,Conclusion:Real-life practice in RA seems consistent with treatment guidelines. Use of non-Anti-TNF bDMARDs becoming more frequent year-by-year. Jak kinase inhibitor has rised through the last 5 years. Next decade may be the years of Jak kinases inhibitors.Disclosure of Interests:None declared

Objective: Pulmonary arterial hypertension (PAH) is a devastating complication of inflammatory rheumatic diseases. The aim of this study was to determine the role of screening for the early diagnosis of pulmonary hypertension (PH) in inflammatory rheumatic diseases. Material and Methods: Data of patients with inflammatory rheumatic diseases and PH who had no obvious cause of PH and who were evaluated by Working Group for Pulmonary Hypertension in Hacettepe University were investigated retrospectively. All patients with inflammatory disease were evaluated by right heart catheterization (RHC) to check if they had systolic pulmonary arterial pressure (sPAP) ≥40 mmHg and/or symptoms related to PH unless explained by other causes. Results: RHC was performed in 47 patients with inflammatory rheumatic diseases and PH out of 50 patients who were to be evaluated by RHC based on clinical and Doppler echocardiographic findings. There was a positive correlation between sPAP estimated by Doppler echocardiography and sPAP determined by RHC in patients with inflammatory rheumatic diseases (r=0.66; p

Background Exercise programs have been being provided in Hacettepe University for 12 years. The group exercises were transformed into a book named as “Bilissel Egzersiz Terapi Yaklasimi (BETY) (1)” in 2014 and were registered as a trademark by the Turkish Patent Institute in 2015. This approach includes cognitive processes in pain management, clinical pilates exercises and awareness of mood state via dance therapy (2).When rheumatic patients participating in BETY sessions, they are evaluated with appropriate scales for their diseases and it is stated that these scales do not express enough the healing properties they feel with BETY. Objectives The aim was to develop a new scale assessing the biopsychosocial aspects of healing properties in rheumatic patients. Methods After 12 years of treatment, cognitive beliefs about health perceptions were gathered from the patients who participates in the BETY group for at least 5 years, with the open-ended question “What kind of changes did you make in this group?”. After elimination of similar sentences, 30 cognitive beliefs about different health perceptions were obtained. The newly developed scale was applied to 89 patients aged 18–69 years (42,94±12.85), who had different rheumatic diseases and were not included in the BETY group. Working questions were determined. Results The internal consistency was found to be 0.89. In this process, 5 items that didn9t work and had the same meaning were removed from the scale. After this, “What kind of improvements did you make in Daily life by participating in the BETY group?” question was asked to the patients participated in BETY group to narrow the expressions and 5 new sentences are determined. The scale was sent to 24 rheumatologists and 2 physiatrists for expert opinion. 15 rheumatologists and 1 physiatrist were returned. When the survey items were examined on a question-based basis, the acceptance rate of all questions was 70.83%. According to this result, the scale was finalized. Structural validity of the created draft will be investigated in the subheadings of functional activity, pain, sexual life, fear of movement, mood. Conclusions As a result, an original scale which will assess the biopsychosocial aspects of healing properties in rheumatic patients is developed. Our future purpose is to investigate the validation of this scale in different rheumatic diseases. References E.Unal (Ed.) Romatizmal Hastaliklarda Biyopsikososyal Model: Bilissel Egzersiz Terapi Yaklasimi (BETY), 2014, Pelikan Yayincilik, Ankara. ISBN: 9786056474101. Kisacik,P. Unal,E. Akman,U. Yapali,G. Karabulut,E. Akdogan,A. Investigatition the effects of a multidimensional exercise program on sypmtoms and antiinflammatory status in female patients with ankylosing spondylitis. Complementary Ther. Clin. Pract. 22(2016):38–43. Acknowledgements The authors declare that they have no conflict of interest. Disclosure of Interest None declared

An aseptic abscess (AA) is an auto-inflammatory disorder characterized by necrotic lymph nodes and internal organ abscesses, most frequently located in the spleen. Described herein are two cases of aseptic abscesses; one in a patient with Behçet's disease and the other in a patient with mesenteric panniculitis.

Objective: The six minute walk test (6MWT) is used for the assessment of functional capacity in pulmonary and cardiovascular diseases. Left ventricular diastolic dysfunction (LVDD) is the most common cardiac abnormality in systemic sclerosis (SSc). The aim of this study was to define the effect of LVDD on 6MWT parameters in patients with SSc. Methods: We studied 45 (female : male 40 : 5) SSc patients. Patients with obvious conditions that can affect 6MWT distance (6MWD) were excluded. All subjects were evaluated by 6MWT. Additionally, 6MWD of the participants was calculated as the percentage of normal predicted values. LVDD was assessed by using echocardiographic findings and classified into three categories: impaired relaxation, pseudonormal or restrictive. Results: There were 12 (27%) patients with LVDD. SSc patients with LVDD were older than SSc patients without LVDD (50 ± 12 years vs. 41 ± 10 years; P = 0.017). In all, the mean 6MWD was 487.9 ± 98.3 m. The 6MWD was shorter in SSc patients with LVDD as compared to those without LVDD (438.0 ± 94.7 m vs. 506.0 ± 94.5 m; P = 0.039). There was significant difference between the groups regarding the percentage of the predicted 6MWD (74.1 ± 10.1%vs. 82.8 ± 13.1%; P = 0.041). Conclusion: The presence of LVDD alters 6MWD in SSc patients. Reduction of 6MWD in a patient with SSc should prompt the investigation of LVDD.

Familial Mediterranean fever (FMF) is an autosomal recessive disease which predominantly affects certain ethnic groups mainly Sephardic Jews, Turks, Arabs, and Armenians. Differential diagnosis of an attack of FMF with appendicitis could be difficult in patients presenting with acute abdomen. Circulating levels of resistin and visfatin have been shown to increase in several inflammatory conditions. In this study we aimed to investigate the role of resistin and visfatin in diseases activity by monitoring these adipokines' levels in patients with FMF (attacks and attack-free period) and acute appendicitis. The study involves four groups: group 1-31 FMF patients at attack (M/F, 14/17), group 2-27 FMF patients at attack-free period (M/F, 9/18), group 3-29 acute appendicitis patients (M/F, 16/13), and group 4-20 healthy controls (M/F, 10/10). Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, fibrinogen, resistin, visfatin, interleukin-1β, interleukin-6, interleukin-10, TNF-α, and IFN-γ were evaluated concurrently. Resistin level could be a useful test in diagnosis of FMF patients in attacks period but not in acute appendicitis as differential diagnosis. Measuring visfatin levels would not give additional information neither for attacks and attack-free period nor FMF attack and appendicitis.

Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). High frequency ultrasonography (US) is a sensitive and specific method in diagnosis of CTS. This study is aimed to: firstly assess diameter frequency of CTS in RA with US and compare with a control group; secondly, investigate relationship of CTS with disease activity. One hundred consecutive RA patients (women/men: 78/22) fulfilling ACR 1987 RA criteria and 45 healthy controls (women/control: 34/11) were enrolled into study. Disease activity parameters, RA and CTS patient global assessment and health assessment questionnaire (HAQ-DI) were recorded. Both patient and control group were questioned about secondary causes of CTS, and Katz hand diagram, Boston CTS questionnaire and Phalen ve Tinel tests were applied once for each hand. Wrist joint and carpal tunnel were assessed with US grey scale and power Doppler US, then cross-sectional area of median nerve (CSA) was calculated. Patients with median nerve CSA between 10.0 and 13.0 mm(2) were evaluated with electromyography (EMG). CTS was diagnosed if CSA of median nerve13.0 mm(2) or CTS was shown with NCS. Although there was no difference between RA patients and controls in age, sex, history of DM (+) and goitre, CTS was more frequent in RA group (respectively, 17.0% vs. 4.4%, P = 0.038). In RA group with CTS, age, history of DM, disease duration, HAQ-DI score, CTS patient global score, Boston symptom severity and functional status scores were elevated compared to without CTS [respectively, 57 (36-73) vs. 50 (24-76), P = 0.041; 35.3% vs. 6.0%, P0.001; 108 (12-396) months vs. 72 (6-360) months, P = 0.036; 1.93 (0.75-2.87) vs. 1.125 (0-2.75), P = 0.013; 52 (1-97) vs. 25 (0-91), P = 0.001; 2.81 (1.18-4.17) vs. 2.0 (1.0-4.01), P = 0.01; 3.37 (1.37-5.0) vs. 2.25 (1.0-5.0), P = 0.008]. No difference was found between CTS (+) and (-) RA patients in acute phase reactants, disease activity and US findings (P0.05). Sensitivity of Katz hand diagram was higher than Tinel and Phalen tests (respectively, 100, 60.0, 66.7%). Boston symptom and functional scores of RA patients with CTS diagnosed by EMG were increased than patients CTS (-) by EMG [respectively, 3.05 (1.90-4.27) vs. 1.55 (1.0-2.90), P = 0.002; 3.25 (1.73-3.82) vs. 1.12 (1.0-2.10), P = 0.008]. CTS frequency in RA was found higher than normal population, especially in patients with additional risk factors of CTS. There was no relationship between CTS and disease activity. CTS group had long disease duration and worse functional status. CTS could be a result of the chronic course in RA. In patient with CSA between 10 and 13 mm(2), Boston CTS questionnaire might give additional idea about CTS.

Resume Objectif La maladie de Still de l’adulte (MSA) peut se compliquer d’un syndrome d’activation macrophagique secondaire ou reactionnel (SAMr). L’objectif de ce travail etait de mesurer les taux de vitamine B12 dans la MSA avec et sans SAMr. Methodes Tous les dossiers des patients atteints de MSA issus d’un meme centre ont ete revus retrospectivement. L’hemophagocytose etait definie par la phagocytose de nombreuses cellules hematopoietiques par les macrophages. Les donnees cliniques comprenant fievre, rash, douleur pharyngee, arthrite et lymphadenopathie ont ete colligees. Les examens biologiques effectues ont ete les suivants : numeration formule sanguine complete, ferritinemie, transaminases, triglyceridemie et vitamine B12 serique. Le groupe temoin etait constitue de notre groupe de patients atteints de MSA, sans SAMr. Resultats Sept patients (cinq femmes) avaient une MSA avec SAMr. L’âge median au moment du diagnostic de SAMr etait de 32 ans (extremes, 27–37) et la duree mediane de suivi apres le diagnostic de SAMr etait de 18 mois (extremes, 2–60). Tous les patients avec SAMr presentaient une fievre, une douleur pharyngee, une arthrite, une anemie et une hyperferritinemie. Cinq des sept patients avaient une hepatosplenomegalie et une lymphadenopathie. Quatre des sept patients avaient un taux de leucocytes normal ou bas, trois une hypertriglycecidemie. Les patients avec MSA et SAMr avaient des taux de vitamine B12 (en moyenne ± D.S.) significativement plus eleves que les patients sans SAMr (1903 ± 960 vs 542 ± 328 pg/ml, p = 0,001). La sensibilite (75 %) des taux eleves de vitamine B12 etait elevee et la specificite (100 %) etait excellente. Conclusion Un taux eleve de vitamine B12 semble etre un bon marqueur diagnostique de MSA lorsqu’elle se complique d’un SAMr.

Background Adult-onset Still's disease (AOSD) can be complicated by reactive macrophage activation syndrome (rMAS). The objective of this study was to evaluate vitamin B 12 values in AOSD with and without rMAS. Methods All patients’ files with AOSD in one center were retrospectively reviewed. Hemophagocytosis was defined as phagocytosis of various hematopoietic cells by macrophages. Clinical data including fever, rash, sore throat, arthritis, lymphadenopathy were recorded. Laboratory tests included complete blood count, serum ferritin, transaminases, serum triglyceride and vitamin B 12 level. The control group was selected from our AOSD pool who had AOSD without rMAS. Results Seven patients (5 female) had AOSD with rMAS. Median age at the diagnosis of rMAS was 32 (range, 27–37) and median follow-up duration after rMAS diagnosis was 18 months (range, 2–60). All of the patients with rMAS had fever, sore throat, rash, arthritis, anemia and hyperferritenemia. Five of seven patients had hepatosplenomegaly and lymphadenopathy. Four of seven patients had normal or low leucocyte count, three of seven patients had increased triglyceride level. The patients with AOSD and rMAS mean ± standard deviation (S.D.) vitamin B 12 levels were significantly higher than without rMAS (1903 ± 960 vs 542 ± 328 pg/ml, p = 0.001). The specificity (75%) of increased vitamin B 12 level was high and sensitivity (100%) was excellent. Conclusion Elevated vitamin B 12 levels seems to be a good marker for diagnostic marker in AOSD when complicated with rMAS.

The objective of this study was to assess nurse-guided patient completion of the Bath Ankylosing Spondylitis Activity Index (BASDAI). Between April and June 2008, all consecutive patients diagnosed with ankylosing spondylitis in a university clinic who were over 18 years old were enrolled in this study. Demographic data and socioeconomic status were collected by a questionnaire. First, the BASDAI forms were completed by the patient (self-report). The forms were completed again by the patient, this time with the guidance of an experienced study nurse (nurse-guided). If the absolute value of difference of self-reported and nurse-guided BASDAI was $ 1 cm (the minimum clinically important difference), these patients were defined as discordant. One hundred sixty-two patients (101 male, 62%; 61 female, 38%); mean age 35.6 years (standard deviation [SD] 11.4); and with a mean disease duration of 12.7 years (SD 7.8), were enrolled in the study. Mean BASDAI scores were no different between self-reported (3.07, SD 2.31) and nurse-guided (2.89, SD 2.31) scores. Thirty-eight patients (23.4%) had discordant results. Comparing the discordant to non-discordant patients, the discordant patients had more active disease (53% versus 27%, P = 0.004); were older (39 years, SD 11, versus 34 years, SD 11, P = 0.029); were more frequently female (58% versus 32%, P = 0.003); had # 8 years' education (55% versus 22%, P

We conducted this study to determine familial Mediterranean fever (FMF)-associated central nervous system involvement including demyelinating lesions, stroke, and posterior reversible leukoencephalopathy syndrome (PRES). Patients with MEFV mutations were systematically reviewed through the Medical Biology Unit database. All samples sent for mutation analysis were screened for 10 common MEFV mutations. Patients with FMF and neurologic disorders according to the clinical records were invited for reevaluation. Lumbar puncture, electroencephalography, and evoked potentials were used to determine the type of neurologic involvement in selected cases. Electrocardiography, transthoracic and/or transesophageal echocardiography, and magnetic resonance imaging and/or angiography were performed to clarify the etiology of cerebrovascular disease. Of 8864 patients in the genetic testing database, 18 with neurologic signs were assessed. The mean age of patients was 31.0 +/- 11.8 years, mean age at first FMF symptom was 12.6 +/- 5.6 years, and mean age at neurologic involvement was 25.8 +/- 12.2 years. Fifty-five percent of patients were women. A homozygote MEFV mutation was detected in 16 of 18 patients (88.8%), and a homozygote M694V mutation was found in 72.2% of patients. We found 7 FMF patients with demyelinating lesions, 7 with cerebrovascular disease, and 4 with PRES. The mean interval between first FMF sign and neurologic involvement was 13.7 +/- 8.9 years in the demyelinating group, and 23.4 +/- 10.3 years in the group with cerebrovascular disease. Mean stroke age was 28.5 +/- 16.4 years. All patients in the PRES group had hypertension. Three different neurologic conditions in FMF patients were noticeable. Demyelinating lesions and cerebrovascular disease were the most common clinical presentations. Approximately 70% of patients had the homozygote M694V mutation. Neurologic involvement is rare but serious in FMF.

Severe primary central nervous system (CNS) involvement such as vasculitis and pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence of systemic disease activation. The authors illustrate a female patient with well-controlled RA who presented with headaches, encephalopathy, seizures and relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR) imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography. MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral angiography findings were consistent with vasculitis. Aggressive treatment resulted in significant clinicoradiological resolution. Cerebral vasculitis is a rare but certain manifestation of RA. This complication can be diagnosed in the presence of suggestive angiographic and CSF findings. The condition may be steroid resistant, and needs to be treated more aggressively.

The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations of a number of diseases such as multiple sclerosis (MS) and collageneous tissue disorders. In the present study, particular systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) patients, who were followed up with the initial diagnosis of possible MS with no evidence of collagen tissue disorders for several years, are described. Five patients with the final diagnosis of SLE and five pSS patients are evaluated with their neurologic, systemic and radiologic findings.Over several years, all developed some systemic symptoms like arthritis, arthralgia, headache, dry mouth and eyes unexpected in MS. During the regular and close follow-up laboratory evaluations of vasculitic markers revealed positivity, leading to the final definite diagnosis of SLE or pSS. Patients with atypical neurological presentation of MS, a relapsing remitting clinical profile, or lack of response to the regular MS treatment should be evaluated for the presence of a connective tissue disease. Various laboratory tests, such as cerebrospinal fluid findings, autoantibodies profile, markers, cranial and spinal magnetic resonance imaging, can be helpful for the differential diagnosis. Lack of response to the regular multiple sclerosis treatment, even increasing rate of relapses can force the clinician for the differential diagnosis. In particular cases an accurate diagnosis can only be made after close follow-up.

Resume Objectif L’objectif de cette etude retrospective etait de rechercher des correlations entre le volume plaquettaire moyen (VPM) et les indices qui refletent l’activite de la polyarthrite rhumatoide (PR) et de la spondylarthrite ankylosante (SA). Methodes Nous avons etudie 32 malades souffrant de PR active (25 femmes et sept hommes ; âge moyen, 49 ± 13 ans), pour qui les temoins etaient 26 malades arthrosiques (22 femmes et quatre hommes ; âge moyen, 52 ± 8 ans), et 30 malades souffrant de SA active (15 femmes et 15 hommes ; âge moyen, 36 ± 12 ans), pour qui les temoins etaient 29 individus bien portants apparies pour l’âge (24 femmes et cinq hommes ; âge moyen, 41 ± 7 ans). Resultats Le VPM etait significativement plus bas dans les groupes PR et SA que dans les groupes temoins respectifs (PR versus arthrose, p p p p = 0,019). Dans le groupe SA apres deux mois de traitement, une correlation negative a ete constatee entre le VPM et le score BASDAI ( r = −0,507 et p = 0,004). Conclusion Nos resultats laissent penser que le VPM pourrait apporter des informations supplementaires sur l’intensite de l’inflammation dans la PR et la SA.

The aim of this retrospective study was to investigate the correlation between MPV and the clinical disease activity indices of rheumatoid arthritis and ankylosing spondylitis.The study consisted of 32 active RA patients (males/females: 7/25, mean age: 49+/-13) and 30 active AS patients (males/females: 15/15, mean age: 36+/-12) along with 26 osteoarthritis (OA) patients (males/females: 4/22, mean age: 52+/-8) and 29 age-matched healthy subjects (males/females: 5/24, mean age: 41+/-7) as control groups for RA and AS, respectively.MPV was significantly lower in both AS patients and RA patients with active disease as compared to controls (RA vs OA p0.001, AS vs healthy subjects p0.001). After treatment MPV values significantly increased in AS and RA (p0.001 for all). However, MPV values remained somewhat lower in RA patients than OA patients (p=0.019). There was a negative correlation between MPV values and BASDAI scores in AS patients after two months of treatment (r=-0.507; p=0.004).Our results suggest that assessment of MPV may provide additional information about inflammation in AS and RA.

BACKGROUND Cardiac involvement is one of the major problems in systemic sclerosis (SSc). Subclinical cardiac involvement has a higher frequency than thought previously. In this study we investigated whether subclinical cardiac involvement can be detected by using echocardiographic strain imaging in SSc patients without pulmonary hypertension. METHODS Echocardiographic examinations were performed to 27 SSc patients and 26 healthy controls. Left ventricular strain parameters were obtained from apical views and average strain value was calculated from these measurements. RESULTS There were no significant differences between patients and controls regarding two-dimensional (2D), conventional Doppler and tissue Doppler velocity measurements. Strain was reduced in 6 of 12 segments of the left ventricle (LV) and in 1 of 2 segments of the right ventricle (RV). Strain rate (SR) was reduced in 2 of 12 segments of the LV and 1 of 2 segments of the RV in SSc patients as compared to controls (P < 0.05 for all). These involvements did not match any particular coronary artery distribution. More important differences were detected by average strain and SR values of the LV between patients and controls (19.78 +/- 3.00% vs 23.41 +/- 2.73%, P < 0.001; 2.01 +/- 0.41 vs 2.23 +/- 0.27/sec, P = 0.026, respectively). Furthermore, carbon monoxide diffusion capacity (DLCO) in scleroderma patients significantly correlated with LV average strain (r = 0.59; P = 0.001). CONCLUSION Evaluation of ventricular function by using echocardiographic strain imaging appears to be useful to detect subclinical cardiac involvement in SSc patients with normal standard echocardiographic and tissue Doppler velocity findings.

The aim of this study is to investigate the relationship between chemokines and the inflammation in Familial Mediterranean Fever (FMF). Forty-nine patients with FMF (41 in remission and 8 in acute attack period) and 20 healthy controls were included in the study. Serum levels of macrophage inflammatory protein-1α (MIP-1α) were assessed in the patients and the controls, along with other parameters of disease activity, i.e., fibrinogen, C-reactive protein and erythrocyte sedimentation rate. Serum MIP-1α levels of the patients with FMF in acute attack period were significantly higher than the patients in remission and healthy controls ( p = 0.02 and p = 0.038, respectively). MIP-1α levels were weakly correlated with CRP ( r = 0.32, p = 0.032) levels. MIP-1α may have a role in the pathogenesis of FMF attacks. MIP-1α and other chemokines may constitute a link between the innate immune system and FMF.

Resume Objectifs Evaluer les taux de recepteur soluble de type I du facteur de croissance endothelial vasculaire (sVEGFR-1) chez des patients atteints de maladie periodique. Methodes Les taux plasmatiques de sVEGFR-1 etaient mesures chez 33 patients atteints de maladie periodique en dehors d'une periode de crise (moyenne d'âge 30,8 ans ; hommes/femmes 10/23), chez 15 patients en phase aigue (moyenne d'âge : 32,7 ans ; hommes/femmes : 7/8), et chez 19 sujets sains (moyenne d'âge : 32 ans ; hommes/femmes : 11/8). Les taux de sVEGFR-1 etaient aussi compares chez les patients traites par de la colchicine et chez ceux qui ne l'etaient pas. Resultats Les taux plasmatiques de sVEGFR-1 etaient de 49 ± 1,10 ng/ml, 3,53 ± 1,02 ng/ml, et 0,37 ± 0,28 ng/ml, respectivement, chez les patients en dehors d'une periode de crise, chez les patients en phase aigue de maladie periodique, et chez les sujets sains. Les taux de sVEGFR-1 etaient significativement plus eleves chez les patients en dehors d'une periode de crise ou en phase aigue de maladie periodique, que chez les sujets sains (p 0,05). Les taux plasmatiques de sVEGFR-1 etaient aussi comparables entre les patients traites par la colchicine et ceux qui ne l'etaient pas. Conclusion Nos resultats suggerent un role du sVEGFR-1 dans le processus inflammatoire de la maladie periodique.

To assess the levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in patients with familial Mediterranean fever (FMF).Plasma levels of sVEGFR-1 were investigated in 33 FMF patients in an attack-free period (mean age 30.8 years; males/females 10/23), in 15 patients with acute FMF attack (mean age 32.7 years; males/females 7/8), and 19 healthy controls (mean age 32 years; males/females 11/8). Levels of sVEGFR-1 were also compared among patients who were receiving colchicine and those who were not.Plasma sVEGFR-1 levels were 3.49+/-1.10, 3.53+/-1.02, and 0.37+/-0.28 ng/ml for FMF patients in the attack-free period, FMF patients with acute attack, and healthy controls, respectively. Plasma sVEGFR-1 levels were significantly higher in FMF patients with and without acute attack compared to the control group (p0.05). sVEGFR-1 levels were not statistically significant between patients with acute attack and attack-free FMF patients (p0.05). The plasma levels of sVEGFR-1 were also comparable in colchicine treated and untreated patients.Our data suggest that sVEGFR-1 may have a role in the ongoing inflammatory cascade in FMF.

Objectives There have been some studies on the burden of certain rheumatological disorders on the tendons; however, patients with familial Mediterranean fever (FMF) and Behcet's disease (BD) have not, up to now, been studied in this regard in the literature. Thus, this current study centers on ensuing changes in the tendons of these patients. Methods The study comprised 32 patients with FMF (13 male, 19 female), 31 with BD (18 male, 13 female) and 35 control subjects (17 male, 18 female). Sonographical evaluations were performed from the triceps, quadriceps and Achilles tendons on the non-dominant extremities of the individuals using a linear array probe of 8–16 MHz. Results The mean triceps tendon (TT) thickness value of FMF patients was greater than that of BD patients ( P = 0.03) or the controls' ( P = 0.02). The mean quadriceps tendon (QT) thickness value of BD patients was greater than that of FMF patients ( P = 0.00) or the controls' ( P = 0.01). The mean Achilles tendon (AT) thickness value of BD patients was greater than that of controls' ( P = 0.05) only. There was not any difference between the tendon thickness measurements of either group of patients with and without arthritic involvement. Conclusion Our first and preliminary findings pertaining to increased tendon thicknesses in FMF ( TT ) and BD ( QT and AT ) patients should be complemented with future histological and clinical studies. The functional relevance of tendon thickening, its probable reflection on the rupture risk and the role of each disease related contributing factor remain to be uncovered.

Resume Objectifs Contrairement a d'autres pathologies rhumatologiques, le retentissement de la maladie periodique et de la maladie de Behcet sur les tendons n'a pas ete etudie jusqu'a present dans la litterature. Le but de notre etude a donc ete de rechercher des anomalies des tendons chez les patients atteints de ces maladies. Methodes Notre etude a ete effectuee chez 32 malades (19 femmes et 13 hommes) atteints de maladie periodique, 31 malades (13 femmes et 18 hommes) atteints de maladie de Behcet et 35 sujets temoins sains (18 femmes et 17 hommes). L'evaluation echographique a porte sur les tendons du triceps, du quadriceps et le tendon d'Achille, du cote non dominant, a l'aide d'une sonde lineaire de 8 a 16 MHz de frequence. Resultats L'epaisseur moyenne du tendon du triceps etait plus importante chez les malades atteints de maladie periodique par rapport a ceux atteints de maladie de Behcet (p = 0,03) et par rapport aux temoins (p = 0,02). L'epaisseur moyenne du tendon quadricipital etait plus elevee chez les malades atteints de maladie de Behcet par rapport a ceux atteints de maladie periodique (p = 0,00) et par rapport aux temoins (p = 0,01). L'epaisseur moyenne du tendon d'Achille etait plus importante chez les malades atteints de maladie de Behcet mais uniquement par rapport aux sujets temoins (p = 0,05). Il n'a pas ete observe de difference de l'epaisseur de ces tendons selon qu'il y ait ou non une atteinte articulaire et ce, dans chacun des groupes de malades. Conclusion Ces resultats preliminaires indiquent une augmentation de l'epaisseur du tendon du triceps au cours de la maladie periodique et de celle du quadriceps et du tendon d'Achille au cours de la maladie de Behcet. Ils devraient etre completes a l'avenir par des etudes cliniques et histologiques. La signification fonctionnelle de l'epaississement tendineux, sa relation probable avec le risque de rupture, et le role physiopathologique de chacune de ces maladies dans ces anomalies reste a preciser.

Objectives: Subclinical cardiac involvement may occur in patients with Behcet's disease (BD). The purpose of our study was to assess the noninvasive parameters of biventricular function derived from Doppler tissue imaging (DTI) of the tricuspid and mitral annular motion in BD. Methods: Twenty- one patients with BD and 20 control subjects were enrolled in this study. All subjects were selected to exclude those with cardiovascular risk factors. Standard echocardiography and pulsed DTI were obtained in every patient. Results: Peak systolic (13.71 ± 2.09 vs 20.01 ± 1.57, P < 0.001), peak early diastolic (11.26 ± 2.52 vs 15.35 ± 2.06, P < 0.001) tricuspid annular velocities were significantly lower in patients than controls. Peak systolic (8.68 ± 1.4 vs 12.25 ± 1.7, P < 0.001), peak early diastolic (7.89 ± 1.07 vs 9.94 ± 1.12, P < 0.001), and peak end diastolic (8.30 ± 1.32 vs 9.23 ± 0.91, P = 0.013) lateral mitral annular velocities were significantly lower in patients than controls. Conclusions: We demonstrated that myocardial velocities, were affected in patients with BD. Therefore, we conclude that right and left ventricular function is impaired in patients with BD. (ECHOCARDIOGRAPHY, Volume 23, October 2006)

Objective: Inflammation is known to alter lipid profiles and to induce insulin resistance. This study was planned to test the hypothesis that familial Mediterranean ferver (FMF) patients and their first-degree asymptomatic relatives may have lipid profile changes and/or insulin resistance, similar to other inflammatory diseases. Material and Methods: We studied 72 FMF patients, 30 asymptomatic first-degree relatives, and 75 healthy controls. Fasting and 2-hour postprandial glucose, insulin, apolipoprotein (Apo) A1, Apo B, acute phase reactants, and lipid profiles of all subjects were studied. Insulin resistance was determined by the HOMA (Homeostasis Model Assessment) index. Results: There was no difference between the groups with regard to sex, mean systolic and diastolic blood pressure, body mass index, smoking status, fasting and postprandial 2-hour glucose, insulin, acute phase reactants, and HOMA index levels. High-density lipoprotein cholesterol (HDL-C) levels were similar between FMF patients and FMF relatives (48.9±12.4 mg/dL vs 49.3±13.8 mg/dL; p=NS), and both were lower than controls (48.9±12.4 mg/dL vs 59.6±15.1 mg/dL; p

Calciphylaxis may be considered a small vessel vasculopathy which is generaly associated with end-stage renal disease and hyperparathyroidism. The precise pathogenesis of the disease is not known. It needs sensitizers and challengers to occur. Steroids and immunosuppressive drugs including methotrexate are among those challenger agents. Calciphylaxis in collagen vascular diseases is rare. Only one case in rheumatoid arthritis was recently reported. Here we describe a case of calciphylaxis associated with active rheumatoid arthritis. This patient had active disease despite treatment of steroids and methotrexate for a long time. She died shortly after the diagnosis of calciphylaxis due to sepsis.

Cancer-associated venous thromboembolism is a severe form of paraneoplastic syndrome. It rarely leads to venous gangrene. We report a case who presented with multiple deep venous thrombosis and venous gangrene of the lower extremity. During the follow-up period, the patient developed bilateral cervical and right supraclavicular lymphadenopathies. The fine needle aspiration of the lymph nodes revealed metastatic epidermoid carcinoma of an unknown primary. Thrombotic manifestations may complicate the clinicopathological course of malignancies.

Background: Takayasu's arteritis (TA) is a rare disease which appears to be most common in East Asia. However, the disease has been reported to be worldwide. The clinical features of the disease can show variations in different geographical areas. The aim of this study is to evaluate clinical, laboratory and radiological features and the outcome of patients with TA in our hospital. Methods: The hospital files of patients who were followed with the diagnosis of TA between the years 1973 and 2003 in Hacettepe University Hospital were retrospectively evaluated. Results: Male/female ratio was 5/40, and the mean age was 34 years (18–59). Constitutional symptoms were present in 71% of the patients. Claudication and pallor of the extremity, decreased extremity pulsations, arterial hypertension, and arterial bruits were present in 44%, 56%, 58%, and 27% of the patients, respectively. Aortic valvular insufficiency, abdominal aortic aneurism, and cardiomegaly were present in four, one, and four patients, respectively. The initial complaint of six patients was cerebrovascular events. The distribution of the patients according to the angiographic findings was as follows, 56% Type I, 18% Type II, 22% Type III, and 4% Type IV arteritis. The need for vascular surgical interventions were significantly less common in patients who were treated with immunosuppressives plus alternate dose steroids (6%) compared to patients who were treated only with antiaggregant agents (33%). Conclusions: The demographic and angiographic findings of our patients were similar to previous observations from Japan and Italy, and disclose distinct clinical features in comparison to other Asian countries. Alternate-day glucocorticoids plus cytotoxic drugs may be beneficial and safe in patients with TA.

Pharmacological treatment of diffuse systemic sclerosis (SSc) directed at the tissue fibrosis has generally been ineffective. Many immunosuppressive drugs have been tried as therapy for SSc, regardless of the disease subtype and/or stage. The aim of this study was to show the efficacy and the toxicity of oral cyclophosphamide and prednisolone therapy on the prevention of fibrosis-based tissue damage in the early stages of the diffuse SSc. Twenty-seven patients with early diffuse SSc were treated with oral cyclophosphamide (1-2 mg/kg/day) plus oral prednisolone (40 mg/every other day) between the years 1995 and 1998. The results regarding the efficacy and toxicity of cyclophosphamide were compared with those of 22 early SSc patients who had been treated with oral D-penicillamine between 1992 and 1995. All the patients were evaluated using clinical and laboratory parameters every 6 months for 2 years. There was a significant improvement on the skin score, maximal oral opening, flexion index, predicted forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) in the cyclophosphamide group. The decrease in skin score in the cyclophosphamide group started earlier than in the D-penicillamine group. No life-threatening or irreversible adverse reaction was observed. This open study supports the use of oral cyclophosphamide plus prednisolone therapy to prevent fibrosis and its complications in the early stages of diffuse SSc.

This study aimed to assess the frequency of all palpable lymph nodes during active disease and remission in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Hospital records of 100 SLE patients, 100 RA patients, 100 spondyloarthropathy patients, and 150 osteoarthritis patients, treated in our rheumatology department, were evaluated retrospectively. Overall frequencies of enlarged lymph nodes in patients with active RA and SLE were 82% and 69%, respectively. Enlarged lymph nodes associated with RA were mostly located in the axillary region, and in SLE the nodes were smaller and lymphadenopathy was more generalized compared with RA. Palpable lymph nodes disappeared in the majority of patients during remission. Lymphadenopathy was significantly less frequent in patients treated with steroids before admission. Lymph node enlargement is an important physical finding associated with RA and SLE disease activity. Atypical locations and unusually large lymph nodes should raise clinical suspicion of another underlying disease.

Objective The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes. Methods Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2–2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti–double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls. Results In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2–135.5) and 33.4 ng/ml (range 23–62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8–120.5) and 74.6 ng/ml (range 23.3–91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period. Conclusion Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.

Background: Familial Mediterranean Fever (FMF) is caused by mutations in the gene encoding pyrin and is characterized by self-limited, recurrent attacks of fever and serositis. Vasculitis has been increasingly reported in FMF. A study evaluating the prognosis in FMF and polyarteritis nodosa (PAN) patients has not been reported previously. Objectives: To determine the special characteristics and the prognosis of PAN in FMF patients. Methods: A questionnaire was used for the present survey. The setting was 7 referral centers from Turkey and Israel. Seventeen patients who were diagnosed with FMF and who developed PAN were included. PAN was diagnosed in those who met the Chapel Hill consensus criteria for microscopic polyarteritis or classic PAN. The clinical features of these 17 patients and the outcomes of their vasculitis were analyzed. Results: The age at diagnosis of PAN in these FMF patients ranged from 3.5 to 37 years. All patients had constitutional symptoms, elevated acute phase reactants, and myalgia at the time PAN was diagnosed. The diagnosis of PAN was confirmed by renal angiography in 8 patients, by renal biopsy in 6 patients, and by muscle and/or nodule biopsies in 6 patients. A number of patients had definite features of both classic PAN and microscopic polyarteritis. Conclusions: When compared with other PAN patients, those with FMF tended to have a younger age at PAN onset, more frequent perirenal hematomas, and an overall better prognosis. The cases with overlapping features of microscopic and classic PAN pose a problem for the current classification of vasculitis. We suggest that the clinical representation of PAN in FMF patients has certain characteristics and may be a feature of FMF per se. Semin Arthritis Rheum 30:281-287. Copyright © 2001 by W.B. Saunders Company

Objective.Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder characterized by recurrent attacks of fever and serositis. Although colchicine is the standard therapy for preventing attacks and suppressing inflammation, 5%–10% of compliant patients are colchicine-resistant. We report the effect of anti-tumor necrosis factor therapy (etanercept) and anti-interleukin 1 (IL-1) treatment (anakinra) in 6 cases resistant to colchicine therapy.Methods.Five children and an adult patient (3 female, 3 male) who were experiencing at least 2 attacks per month and had consistently elevated C-reactive protein levels despite regular colchicine therapy were given either etanercept or anakinra.Results.Although etanercept lowered the number of attacks (from 3–4 attacks per month to 2 attacks per month), attacks still recurred and acute-phase reactants remained high in 2 patients; thus etanercept was considered ineffective. All 4 patients were switched to anakinra. In 2 patients anakinra completely resolved clinical and laboratory findings. The other 4 patients have been switched to anakinra recently; to date anakinra has reduced the number of attacks (to < 1 per month) and lowered the levels of acute-phase reactants.Conclusion.In this small series, anakinra was succesful in suppressing inflammation and decreasing the number of attacks in FMF. This may be explained by the role of pyrin in the regulation of IL-1ß activation.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not filly understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragmentl+2 (PF1 +2), thrombin-antithrombin complex (TAT), plasmin--a2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PFl + 2 and sTM were significantly elevated (P < 0.0001, P = 0.0002, P < 0.0001, and P < 0.0001, respectively), while TFPI antigen levels were found to be reduced (P < 0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P < 0.05), PFl + 2 (P < 0.05), and sTM (P < 0.01) concentrations and negatively with plasma TFPI levels (P < 0.05). SLEDAI scores were correlated positively with plasma TAT (P < 0.01), PFl + 2 (< 0.01), and sTM (P < 0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.

To the Editor: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by periodic attacks of fever and serositis caused by mutations in FMF gene (MEFV). Although FMF patients are symptom free between the attacks, subclinical inflammation continues during the attack-free

Background Pulmonary hypertension (PH) is a life-threatening complication of systemic lupus erythematosus (SLE). Pulmonary hypertension in SLE has a variety of causes. Diagnosing early and defining the cause of PH accurately can provide better clinical outcome in SLE. We investigated the causes and characteristics of PH in patients with SLE. Methods One hundred twenty-one patients with SLE who had a visit in a 6-month period were assessed retrospectively. Patients who ever had a systolic pulmonary arterial pressure of 40 mm Hg or greater by Doppler echocardiography were considered to have PH. Results Among 122 patients, 65 had echocardiography for some reason, and 10 (8.2%) were diagnosed as having PH by echocardiographic examination. This number reduced to 9 (7.4%) when we excluded the patient with normal pulmonary artery pressure at right heart catheterization. Causes of PH were as follows: thromboembolic events in 4 patients (44.4%) (2 of them had chronic thromboembolic PH), left-sided heart disease in 2 patients (22.2%), pulmonary arterial hypertension in 1 patient (11.1%), high cardiac output state in 1 patient (11.1%), and transient elevation of systolic pulmonary artery pressure in 1 patient (11.1%) who had a history of venous thromboembolism. Venous thromboembolic disease was significantly higher in patients with SLE with PH in comparison to patients with SLE without PH (7 patients [6.3%] vs 5 patients [50.0%]; P = 0.001). All patients improved clinically during their short-term follow-up. Conclusions Patients with SLE are at increased risk for PH. This study highlights the complexity of the differential diagnosis of PH in patients with SLE once again and emphasizes the importance of pulmonary thromboembolism as a cause of PH. One should investigate patients with SLE with unexplained symptoms and/or signs related to PH for possible treatable causes.

Recent studies point out a probable role of streptococcal antigens in the pathogenesis of Behçet's disease (BD). This has led to the proposal of benzathine penicillin as a therapeutic modality in BD.A prospective study was conducted to compare the efficacy of colchicine and colchicine + benzathine penicillin treatments on mucocutaneous manifestations of BD.60 patients (group I) were given colchicine alone and 94 (group II) were given colchicine + benzathine penicillin. Frequency, number, duration and severity of oral aphthous ulcers, genital ulcers and erythema nodosum were determined before and after treatment.In group I, all parameters of oral ulcers and the frequency and healing time of genital ulcers and erythema nodosum decreased significantly. In group II, all parameters of oral aphthous ulcers, genital ulcers and erythema nodosum were significantly improved. When treatment results in the two groups were compared, the decrements in the frequency and duration of oral ulcers and erythema nodosum and the frequency of genital ulcers were significantly greater in group II than in group I (p0.05).We conclude that prophylactic benzathine penicillin combined with colchicine is more effective in controlling mucocutaneous manifestations of BD than colchicine alone.

Particular interleukins, namely interleukin (IL)-6, IL-4 and IL-1, with pro-inflammatory mediator activities have also been shown to be involved in the regulation of megakaryocytopoiesis. As rheumatoid arthritis (RA) is not uncommonly associated with reactive thrombocytosis, we investigated serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations in RA patients with marked thrombocytosis, and compared them to the levels in RA patients with normal platelet counts and healthy volunteers. IL-1 beta. IL-4 and IL-6 concentrations were found to be correlated with the disease activity in both groups of RA patients, with higher serum levels of each cytokine in the thrombocythaemic group. Significant positive correlations of IL-1 beta and IL-4 with the platelet counts were documented only in patients with thrombocytosis. According to our results. IL-6 and IL-1 beta were found to be good indicators of disease activity in RA, while IL-1 beta and IL-4 seemed to be related more with the process of reactive thrombocytosis secondary to rheumatoid inflammation.

The mainstay of RA treatment is the disease-modifying antirheumatic drugs, and triple DMARD combination is now known to be better than monotherapies. Our aim in this trial was to report our clinical experience with triple DMARD therapy for resistant rheumatoid arthritis. Data of 140 patients with RA resistant to methotrexate and steroid combination were evaluated retrospectively. One hundred and nineteen (85 %) were female, and the median age at diagnosis was 56 (29–82) years. The median time between the diagnosis and beginning of triple therapy was 45.5 (6–564) months. Fifty-two (37.1 %) patients (group 1) on triple therapy protocol achieved remission, but the others (88; 62.9 %) (group 2) did not. The mean DAS28 scores for the study group before triple DMARD therapy and after 12 months under triple DMARD therapy were 4.93 and 3.24, respectively. The DAS28 scores after 12 months for groups 1 and 2 were 2.57 and 3.64. The median follow-up period for patients in group 1 was 60 months (23–118), and the mean DAS28 score at the time of the analysis for group 1 was 2.36. Triple DMARD combination may save one-third of the MTX-resistant RA patients from the serious side effects and the cost of anti-TNF.

Background: Cardiovascular involvement is one of the leading causes of death among patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate cardiac autonomic functions in SLE patients. Methods: We enrolled 36 patients (25 female; mean age 34.2 ± 10.2 years) with SLE and 32 healthy subjects (23 female; mean age 35.0 ± 10.3 years). All participants underwent 24-h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting first, second, and third-minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV), heart rate turbulence (HRT) and QT dispersion analysis. The mean SLE duration was 8.4 ± 4.0 years. Results: According to the baseline demographic characteristics, both groups were similar with regard to age, gender, body mass index and left ventricular ejection fraction. Mean HRR1 (32.6 ± 10.9 vs. 42.5 ± 6.5, p = 0.038), HRR2 (51.0 ± 16.9 vs. 61.0 ± 10.8, p = 0.01) and HRR3 (52.8 ± 17.5 vs. 65.8 ± 9.8, p

Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in colchicine-resistant familial Mediterranean fever (FMF) patients has attracted attention in recent years.We analyzed the effect of anti-TNF agents on clinical findings of colchicine-resistant FMF patients with chronic arthritis and/or sacroiliitis.Data from 10 FMF patients (5 male and 5 female patients: mean age, 30.1 [SD, 8.5] years) with chronic arthritis and/or sacroiliitis who were on anti-TNF agents are reviewed. Frequency of FMF attacks before and after treatment with anti-TNF agents was recorded from hospital files. The effects of the anti-TNF treatment were determined by using the number of tender and/or swollen joints, serum acute phase reactant levels, and Bath Ankylosing Spondylitis Disease Activity Index scores. Change in urine protein loss was also evaluated in patients with amyloidosis. In 6 patients, FMF attacks had been considered to be unresponsive to colchicine, and 4 patients were partial responders before treatment with anti-TNF agents.Mean attack frequency of the patients in the 3 months' period before anti-TNF agent treatment was 3.8 (SD, 3.1). After anti-TNF treatment, in 3 patients, FMF attack frequency decreased, and in the remaining 7 patients, no attack occurred. Serum acute phase reactant levels were decreased significantly at 3 and 6 months after anti-TNF treatment (P0.05 for all). After anti-TNF treatment Bath Ankylosing Spondylitis Disease Activity Index scores were also decreased significantly (6.2 [SD], 1.7 vs. 2.1 [SD], 1.7; P = 0.012). In all 3 patients with amyloidosis, urine protein loss decreased without any increase in serum creatinine levels.Anti-TNF treatment can have beneficial effects for controlling FMF attacks in FMF patients with chronic arthritis and/or sacroiliitis.

Familial Mediterranean fever (FMF) is characterized by sporadic, acute attacks of fever and serositis. Cardiovascular involvement is one of the leading cause of morbidity and mortality among FMF patients. Herein, we aimed to evaluate cardiac autonomic functions in FMF patients without overt cardiac symptoms.We enrolled 38 patients (20 female; mean age 34.4 ± 10.2 years) with FMF and 34 healthy subjects (18 female; mean age 33.2 ± 9.3 years). All participants underwent 24-hour Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting first, second, and third minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV), heart rate turbulance (HRT) and QT dispersion analysis. The mean FMF duration was 9.8 ± 4.2 years.Both groups were similar with regard to baseline characteristics. Mean HRR1 (p=0.001), HRR2 (p=0.003) and HRR3 (p0.001) were significantly lower in FMF group. SDNN (standard deviation of all NN intervals), SDANN (SD of the 5 min mean RR intervals), RMSSD (root square of successive differences in RR interval), and PNN50 (proportion of differences in successive NN intervals50 ms) and high-frequency (HF) components were significantly decreased, but low frequency (LF) and LF/HF were significantly higher in FMF patients. HRT onset and slope were significantly less negative in FMF patients. Also, QTd was significantly higher in FMF patients (p0.001).Patients with FMF showed delayed recovery of heart rate and abnormal HRV and HRT parameters with respect to normal subjects. Cardiac autonomic functions might be involved in FMF patients even in patients without cardiac symptoms.

Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder characterized by recurrent attacks of fever and serositis. Although colchicine is the standard therapy for preventing attacks and suppressing inflammation, 5%-10% of compliant patients are colchicine-resistant. We report the effect of anti-tumor necrosis factor therapy (etanercept) and anti-interleukin 1 (IL-1) treatment (anakinra) in 6 cases resistant to colchicine therapy.Five children and an adult patient (3 female, 3 male) who were experiencing at least 2 attacks per month and had consistently elevated C-reactive protein levels despite regular colchicine therapy were given either etanercept or anakinra.Although etanercept lowered the number of attacks (from 3-4 attacks per month to 2 attacks per month), attacks still recurred and acute-phase reactants remained high in 2 patients; thus etanercept was considered ineffective. All 4 patients were switched to anakinra. In 2 patients anakinra completely resolved clinical and laboratory findings. The other 4 patients have been switched to anakinra recently; to date anakinra has reduced the number of attacks (to1 per month) and lowered the levels of acute-phase reactants.In this small series, anakinra was successful in suppressing inflammation and decreasing the number of attacks in FMF. This may be explained by the role of pyrin in the regulation of IL-1ß activation.

A possible relationship between Takayasu arteritis (TA) and tuberculosis (TB) has been suggested. An increased frequency of tuberculin skin test (TST) was observed in TA patients. Quantiferon-TB Gold test (QFT) is a new in vitro assay measuring interferon-gamma response to M. tuberculosis antigens and helpful in diagnosing latent TB infection. The aim of this study was to investigate latent TB infection among TA patients by the use of both TST and QFT Gold test. Ninety-four (male/female: 7/87) TA patients fulfilling ACR 1990 TA criteria from three different university hospitals in Turkey and 107 control subjects without inflammatory diseases were included in the study. Data about medical history (TA and TB) were collected for both groups. TST and QFT were performed. TST valuesor =5 mm for TA patients andor =15 mm for controls was accepted as TST positivity. Even though TA group was older (40 +/- 12 vs. 32 +/- 8, P0.001), there was no significant difference between TA patients and controls regarding demographic characteristics. Six TA patients and one control had a history of previous TB infection (P = 0.054). Although TST positivity was higher in TA group [55 patients (62.5%) vs. 24 controls (41.4%), P = 0.008], QFT positivity was similar between two groups [21 patients (22.3%) vs. 24 controls (22.4%), P0.05]. QFT was negative in two of six TA patients with previous TB history. Rate of latent TB infection in TA patients measured with QFT is no more than controls. QFT seems to be a good and favorable test compared with TST in detecting LTBI in TA.

Behçet's disease, a multisystemic inflammatory disorder, has been associated with a number of cardiovascular dysfunctions, including ventricular arrhythmias and sudden cardiac death. Heart-rate recovery after exercise can provide both an estimate of impaired parasympathetic tone and a prognosis in regard to all-cause and cardiovascular death. The aim of our study was to evaluate heart-rate recovery in Behçet's disease. From January through July 2008, we examined at our outpatient clinic and prospectively enrolled 30 consecutive patients with Behçet's disease and 50 healthy control participants who were matched for age and sex. Basal electrocardiography, echocardiography, and treadmill exercise testing were performed in all patients and control participants. The heart-rate recovery index was calculated in the usual manner, by subtracting the 1st-minute (Rec1), 2nd-minute (Rec2), and 3rd-minute (Rec3) recovery heart rates from the maximal heart rate after exercise stress testing. Patients with Behçet's disease exhibited significantly lower heart-rate recovery numbers, compared with healthy control participants: Rec1, 24.28 +/- 8.2 vs 34.4 +/- 7.6, P = 0.002; Rec2, 49.28 +/- 11.2 vs 57.5 +/- 7.0, P0.05; and Rec3, 56.2 +/- 12.11 vs 67.4 +/- 8.7, P = 0.014. To our knowledge, this is the 1st study that shows an impaired heart-rate recovery index (indicative of reduced parasympathetic activity) among patients with Behçet's disease. Given the independent prognostic value of the heart-rate recovery index, our results may explain the increased occurrence of arrhythmias and sudden cardiac death in Behçet's patients. Therefore, this index may be clinically useful in the identification of high-risk patients.

Cardiac involvement is one of the major problems in systemic sclerosis (SSc). Subclinical cardiac involvement has a higher frequency than thought previously. In this study we investigated whether subclinical cardiac involvement can be detected by using echocardiographic strain imaging in SSc patients without pulmonary hypertension.Echocardiographic examinations were performed to 27 SSc patients and 26 healthy controls. Left ventricular strain parameters were obtained from apical views and average strain value was calculated from these measurements.There were no significant differences between patients and controls regarding two-dimensional (2D), conventional Doppler and tissue Doppler velocity measurements. Strain was reduced in 6 of 12 segments of the left ventricle (LV) and in 1 of 2 segments of the right ventricle (RV). Strain rate (SR) was reduced in 2 of 12 segments of the LV and 1 of 2 segments of the RV in SSc patients as compared to controls (P0.05 for all). These involvements did not match any particular coronary artery distribution. More important differences were detected by average strain and SR values of the LV between patients and controls (19.78 +/- 3.00% vs 23.41 +/- 2.73%, P0.001; 2.01 +/- 0.41 vs 2.23 +/- 0.27/sec, P = 0.026, respectively). Furthermore, carbon monoxide diffusion capacity (DLCO) in scleroderma patients significantly correlated with LV average strain (r = 0.59; P = 0.001).Evaluation of ventricular function by using echocardiographic strain imaging appears to be useful to detect subclinical cardiac involvement in SSc patients with normal standard echocardiographic and tissue Doppler velocity findings.