Is early diagnosis of pulmonary arterial hypertension possible in inflammatory rheumatic diseases? Experience from a single center in Turkey.

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<0.001). The mean pulmonary arterial pressure (mPAP) was found to be <25 mmHg in 27.7% of the patients. New York Heart Association functional capacity (NYHA FC) was class III or IV in 79.0% of the patients with PAH. PAH was more frequent in patients with NYHA FC III-IV compared with patients with NYHA FC I-II [58.7% (15) patients vs. 19.0% (4) patients; p=0.009]. CONCLUSION: In this study, approximately 80% of the patients with inflammatory disease-associated PAH were diagnosed late in NYHA FC III or IV. There are still unresolved issues in the diagnosis and treatment of PH in inflammatory diseases. Collaboration and multidisciplinary approach are the key points to overcome the challenges in this field.

MEFV mutation frequency and effect on disease severity in ankylosing spondylitis.

BACKGROUND/AIM: To define the frequency of familial Mediterranean fever gene (MEFV) mutations in ankylosing spondylitis (AS) and describe different clinical aspects of MEFV mutation carrier and noncarrier AS patients. MATERIALS AND METHODS: In 112 AS patients, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were calculated. The frequencies of 12 different MEFV mutations were studied by multiplex polymerase chain reaction/reverse hybridization method and were compared to those of previously studied healthy controls for 5 common MEFV mutations. RESULTS: MEFV mutations were identified in 46 of 224 (20%) alleles and in 39 (35%) of AS patients. The distribution of mutations was: M694V, 30% (14); E148Q, 30% (14); P369S, 17% (8); V726A, 13% (6); A744S, 8% (4); and K695R, 2% (1). There were no significant differences between MEFV mutation carriers and noncarriers with respect to sex, age of symptom onset, disease duration, peripheral joint involvement, acute phase reactant levels, and BASDAI and BASFI scores (P > 0.05 all). MEFV mutation allelic frequency was not different between AS patients and healthy controls after adjusting for mutations studied (34/224 versus 22/200; P > 0.05). CONCLUSION: Although we did not find significant clinical and laboratory differences between MEFV mutation carrier and noncarrier AS patients, further investigations are needed to define the impact of MEFV mutations on AS disease course.

Serum lipid changes and insulin resistance in familial Mediterranean fever.

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<0.001 and 49.3±13.8 mg/dL vs 59.8±15.1 mg/dL; p=0.001, respectively). Apo A1 levels in FMF patients and asymptomatic first-degree FMF relatives were both lower than in controls, similar to the HDL-C levels (126.1±25.7 mg/dL vs 151.2±31.4 mg/dL; p<0.001 and 129.5±29.0 mg/dL vs 151.2±31.4 mg/dL; p=0.002, respectively). TG levels were significantly higher in FMF relatives as compared to controls (113.4±53.6 mg/dL vs 97.1± 54.9 mg/dL; p=0.025). CONCLUSION: Low HDL-C and low Apo A1 levels are found in FMF patients and their first-degree asymptomatic relatives. Low-grade inflammation caused by MEFV mutations may be responsible for these lipid profile changes.

Pulmonary hypertension in systemic lupus erythematosus: pulmonary thromboembolism is the leading cause.

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.

Successful management of severe acute liver disease related with adult-onset Still's disease in a pregnant patient.

Adult-onset Still's disease is a rare systemic inflammatory disease, which is characterized by varying degrees of liver involvement. Herein we present a rare case of pregnancy onset adult onset Still's disease with severe acute liver disease which worsened after labor. The patient was successfully managed with medical treatment preventing acute liver failure, and is currently in remission from adult onset Still's disease with liver tests that have returned to normal.

Triple DMARD combination for rheumatoid arthritis resistant to methotrexate and steroid combination: a single-center experience.

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.

Tocilizumab for giant cell arteritis: an amazing result.

Giant cell arteritis (GCA), previously Horton's disease, is a systemic vasculitis affecting the middle-sized or large arteries in patients older than 50 years of age. The mainstay of the treatment of GCA is glucocorticoid therapy. Herein, we present a case with giant cell arteritis resistant to oral and intravenous steroid, intravenous cyclophosphamide and mycophenolate mofetil, but successfully treated with tocilizumab.

Sonographic assessment of carpal tunnel syndrome in rheumatoid arthritis: prevalence and correlation with disease activity.

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 nerve >13.0 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%, P < 0.001; 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 (P > 0.05). 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.

Resistin and visfatin: are they valuable enough to be the differential diagnosis in familial Mediterranean fever with acute appendicitis?

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-1ß, 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.

Evaluation of various cardiac autonomic indices in patients with familial Mediterranean fever on colchicine treatment.

BACKGROUND: 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. METHODS: 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. RESULTS: Both groups were similar with regard to baseline characteristics. Mean HRR1 (p=0.001), HRR2 (p=0.003) and HRR3 (p<0.001) 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 intervals >50 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 (p<0.001). CONCLUSION: 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.

Relationship between left ventricular diastolic dysfunction and six minute walk test in patients with systemic sclerosis.

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.

Effects of anti-tumor necrosis factor agents for familial mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment.

BACKGROUND: Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in colchicine-resistant familial Mediterranean fever (FMF) patients has attracted attention in recent years. OBJECTIVE: We analyzed the effect of anti-TNF agents on clinical findings of colchicine-resistant FMF patients with chronic arthritis and/or sacroiliitis. METHODS: 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. RESULTS: 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 (P < 0.05 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. CONCLUSION: Anti-TNF treatment can have beneficial effects for controlling FMF attacks in FMF patients with chronic arthritis and/or sacroiliitis.

Anti-interleukin 1 treatment for patients with familial Mediterranean fever resistant to colchicine.

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 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.

Familial Mediterranean fever and central nervous system involvement: a case series.

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.

Assessment of latent tuberculosis infection in Takayasu arteritis with tuberculin skin test and Quantiferon-TB Gold test.

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 values > or =5 mm for TA patients and > or =15 mm for controls was accepted as TST positivity. Even though TA group was older (40 +/- 12 vs. 32 +/- 8, P < 0.001), 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%), P > 0.05]. 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.

Increased serum vitamin B12 levels are associated with adult-onset Still's disease with reactive macrophage activation syndrome.

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+/-328pg/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.

Heart-rate recovery index is impaired in Behçet's disease.

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, P < 0.05; 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.

An unusual central nervous system involvement in rheumatoid arthritis: combination of pachymeningitis and cerebral vasculitis.

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.

Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders.

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.