New inflammatory markers in early rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder and is associated with progressive destruction of synovial joints and physical disability. Therapies with known benefits include disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, as well as more recent biologic agents, such as tumor necrosis factor inhibitors (anti-TNF therapy). METHOD: This was a retrospective study, which included 205 RA and 112 early RA (ERA) patients from the Rheumatology Clinic at Gaziantep University School of Medicine Research Center as well as 104 healthy controls. RESULTS: The mean neutrophil to lymphocyte ratio (NLR) was found to be 3.15 ± 2.64 in the patient group and 2.03 ± 0.94 in the control group. The mean platelet to lymphocyte ratio (PLR) was 162.39 ± 107.76 in the patient group and 131.23 ± 48.09 in the control group. There was a significant difference in both the NLR and PLR between the patient and control groups (both p < 0.01). There was a significant difference in both the NLR and PLR between patients with active disease and remission (both p < 0.001) in RA, including anti-TNF therapy and DMARDs groups. There was a significant difference in NLR (p = 0.001) but not in PLR (p = 0.051) between active disease and remission in ERA. CONCLUSION: The results of the present study suggest that the NLR may be considered a useful marker of disease activity in RA and one that can aid the diagnosis of ERA. The PLR can be used in the assessment of disease activity in RA patients undergoing anti-TNF therapy but is not suitable for diagnosing ERA.

Risk factors for malignancy in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.

Systemic vasculitis in a patient with rhupus syndrome.

Rhupus is a rare syndrome characterized by overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Previous reports mentioned that rhupus patients have prominent RA associated clinical manifestations and only mild organic damage related to SLE. Progressive or life-threatening manifestations are rare in rhupus patients. Our patient diagnosed as rhupus was a young women, presented with multi-organ involvement of systemic vasculitis. Rheumatologists should be aware of possibility that rhupus may be accompanied by progressive or life-threatening conditions such as vasculitis.

Validity and reliability of the Lupus QoL index in Turkish systemic lupus erythematosus patients.

BACKGROUND: Systemic lupus erythematosus (SLE) patients have seriously impaired quality of life (QoL). In addition to activity and damage indices used in the past, tools to evaluate QoL in SLE have been developed in recent years. In this study, we test the validity of the Turkish version of the Lupus-QoL (LupusQoL-TR) score, and investigate its association with clinical findings and activity indices. METHODS: A total of 132 patients diagnosed with SLE according to ACR 1997 criteria were included. The clinical and demographic features, and biochemical data were retrieved from hospital records. SLE Disease Activity Index (SLEDAI) and damage score (SLICC-ACR) were determined at the time of administration of Lupus-QoL questionnaire. The Lupus-QoL includes 34 questions divided into eight domains. We reevaluated the LupusQoL-TR and pretested its understandability. SLE patients were concomitantly administered the LupusQoL-TR and generic SF-36. Internal consistency, test-retest reliability, convergent and discriminant validity were calculated. RESULTS: The mean age of our SLE patients was 37.9 ± 12.8 years. Internal consistency reliability ranged from 0.88 to 0.93, and test-retest reliability from 0.84 to 0.94. LupusQoL-related domains in SF-36 were correlated (from 0.66 to 0.74). Most LupusQoL-TR domains, except planning, were able to discriminate between active and inactive SLE groups. Scores in all domains of the LupusQoL-TR were found to be discriminative for patients with and without damage according to SLICC-ACR score. CONCLUSION: The LupusQoL-TR was found to be a valid patient-reported outcome measure method when evaluating QoL in Turkish SLE patients.

Effects of periodontal therapy on disease activity and systemic inflammation in rheumatoid arthritis patients.

OBJECTIVE: This observational prospective cohort study aimed to evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements and systemic inflammatory mediator levels in low or moderate to highly active rheumatoid arthritis (RA) patients with chronic periodontitis. SUBJECTS AND METHODS: Rheumatoid arthritis activity was assessed with disease activity score test (DAS28). Thirty patients with RA with moderate to high disease activity (DAS28 ≥ 3.2) and chronic periodontitis (MHDA group) and thirty patients with RA with low disease activity (DAS28 < 3.2) and chronic periodontitis (LDA group) were enrolled in the study. The patients were monitored at the beginning and 3 months after undergoing periodontal therapy. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α) levels in serum, DAS28 and periodontal parameters were evaluated. RESULTS: Erythrocyte sedimentation rate, CRP, TNF-α levels in serum, DAS28 and periodontal parameters exhibited similar and significant reduction 3 months after the non-surgical periodontal treatment. CONCLUSION: Non-surgical periodontal treatment may prove beneficial in reducing RA severity as measured by ESR, CRP, TNF-α levels in serum and DAS28 in low or moderate to highly active RA patients with chronic periodontitis.

Serum cytokine levels and periodontal parameters in ankylosing spondylitis.

BACKGROUND AND OBJECTIVE: Multiple studies support the role of periodontal disease in contributing to the chronic systemic inflammatory burden in a variety of diseases, including ankylosing spondylitis (AS), in the progression which the inflammatory process plays an important role. We assume that patients with AS are more likely to have periodontal disease than healthy individuals. The aim of this study was to determine the possible relationship between inflammatory periodontal diseases and AS by evaluating clinical periodontal parameters and serum cytokine levels. MATERIAL AND METHODS: Forty-eight adults with AS (35 women and 13 men; age range 18-56 years; mean age 34.27 years) and 48 age- and sex-matched systemically healthy control subjects participated in the study. The clinical periodontal parameters, venous blood and Bath Ankylosing Spondylitis Disease Activity Score were obtained, and serum C-reactive protein, tumour necrosis factor-α and interleukin-6 (IL-6) levels were evaluated. RESULTS: There was statistically no significant difference in the frequency of periodontitis between AS patients and the control group. Furthermore, there was no significant difference in probing depth, clinical attachment level and plaque index, and the only significant clinical difference between groups was in levels of bleeding on probing (p < 0.001). Serum concentrations of IL-6, tumour necrosis factor-α and C-reactive protein in the AS group were significantly higher than those in the control group (p < 0.001). In the AS group, there was a correlation between serum IL-6 levels and clinical attachment level (p < 0.001). CONCLUSION: The results of present study suggest that bleeding on probing was the only different periodontal parameter between the AS and the control group, and the periodontal status of patients with AS may be affected by IL-6 levels.

Are clinical features in Löfgren's syndrome-related erythema nodosum different from idiopathic erythema nodosum?

BACKGROUND AND OBJECTIVES: We retrospectively evaluated acute sarcoidosis (Löfgren's syndrome) patients diagnosed at 2 centers and compared the clinical features of Löfgren's syndrome (LS) related erythema nodosum (EN) to patients with idiopathic IEN who were diagnosed within the same time frame. METHODS: Thirty patients (10 males, 20 females) who were diagnosed with LS and were being followed up for the last 8 years at 2 centers were included. Thirty patients (4 males, 26 females) who were admitted to the rheumatology outpatient clinics for IEN during that time period were taken as controls. The clinical and laboratory features at the initial admission, treatment modalities and response were recorded. RESULTS: Twentyfour (80%) patients with LS related EN had arthritis and/or arthralgia. Fifteen of them had only findings of periarticular ankle inflammation and 4 had polyarthritis. When LS related EN patients were compared to IEN patients, the former group had more arthritis and/or arthralgia (p < 0.001), leucocytosis (p = 0.02), lymphopenia (p = 0.005) and thrombocytosis (p = 0.05), and higher ESR (p = 0.02). Twentyfive (83.3%) patients with LS related EN were administered oral corticosteroids. In 21 patients, hilar lymphadenopathy disappeared on control chest x-ray and CT; in 3 patients, minimal residual lymph node enlargement was persistent. During a median follow-up of 54 months (range: 10-84 months), none of the LS related EN patients had clinical relapse. CONCLUSIONS: Apart from BHL, arthritis and/or arthralgia especially periarticular ankle inflammation is the feature which could be used to differentiate LS related EN from IEN. There is more need for steroids in LS patients and the symptoms quickly resolve with steroids.

Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far-East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey.

PTPN22 gene polymorphism in Takayasu's arteritis.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, rare granulomatous panarteritis of unknown aetiology involving mainly the aorta and its major branches. In this study, genetic susceptibility to TA has been investigated by screening the functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the lymphoid-specific protein tyrosine phosphatase. METHODS: Totally, 181 patients with TA and 177 healthy controls are genotyped by PCR-RFLP method for the SNP rs2476601 (A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. RESULTS: Detected frequencies of heterozygous genotype (AG) were 5.1% (9/177) in control group and 3.8% (7/181) in TA group (P = 0.61, odds ratio: 0.75, 95% CI: 0.3, 2.0). No association with angiographic type, vascular involvement or prognosis of TA was observed either. CONCLUSION: The distribution of PTPN22 polymorphism did not reveal any association with TA in Turkey.

Autoimmune polyendocrine syndrome with atrial septal defect.

Atrial septal defect is frequently reported with genetic syndromes. But, to the best of our knowledge, it has not been reported with autoimmune polyendocrine syndrome. Here, the case of a 44-year-old-woman with concomitant involvement of the salivary gland, thyroid, intestines, and, possibly endocrine pancreas, diagnosed with autoimmune polyendocrine syndrome type II, is reported with accompanying atrial septal defect. Celiac disease, Hashimoto thyroiditis, and Sjögren syndrome were symptomatic and laboratory confirmed diagnosis; anti-glutamic acid decarboxylase antibody was positive but asymptomatic for type-1 diabetes. She was known to have sinus venosus type atrial septal defect diagnosed at 38 years old, when she had tiredness and chest pain.

Plasma and platelet serotonin levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common auto-inflammatory syndrome with exaggerated acute phase and inflammatory response. After revealing the MEFV gene mutation with the finally disturbed end product pyrin, some of the mechanisms were explained. However it is still unknown what triggers or ends these periodical attacks. Moreover, the treatment of up to 30% of the patients, that are resistant to colchicine is still a problem. In this study we investigated the role of serotonin in colchicine-resistant FMF patients. METHODS: Twenty-four FMF patients (male/female: 15/9) and 32 age- and sex-matched healthy controls (male/female: 17/15) were included into the study. Patients were subdivided into two groups. Thirteen had FMF attacks despite regular colchicine (colchicine-resistant group), other 11 had disease under control with colchicine for at least 6-months. Sampling was done both during the attack and ten days after its cessation. Plasma and platelet serotonin levels and acute phase reactants were studied in patients and controls. RESULTS: Colchicine-resistant patients had plasma serotonin (5-HT) levels of 7.85 +/- 1.0 nmol/l during acute attacks which significantly reduced to the levels of 6.3 +/- 0.6 nmol/l (p < 0.001), after 10 days of acute attacks and these levels were significantly lower than those of attack-free patients' and controls' (10.7 +/- 0.2 nmol/l and 10.1 +/- 0.3 nmol/l, respectively). Platelet 5-HT level was 6.4 +/- 0.3 nmol/10(9) platelets during acute attack, and this level was increased to 9.8 +/- 0.5 nmol/10(9) platelets on the 2(nd) sampling, 10 days after the cessation of the acute attack (p < 0.001). They were both significantly higher than those of attack-free FMF patients (5.9 +/- 0.1 nmol/10(9) platelets) and healthy controls (5.7 +/- 0.3 nmol/10(9) platelets). There was a negative correlation between plasma and platelet 5-HT levels (r=-0.77, p < 0.001). CONCLUSION: Changes in plasma and platelet 5-HT levels may be related to the disturbances in 5-HT transport mechanisms or may also be attributed to the potential role of serotonin in the inflammatory cascade. Last but not least, serotonin may have a role in the pathogenesis of FMF.

Circulating thrombomodulin levels in familial Mediterranean fever.

Increments in circulating thrombomodulin levels reflect endothelial cell injury. Thrombomodulin can also be synthesized by several inflammatory cells including monocytes, neutrophils, and thrombomodulin itself can modulate the inflammatory response. In this study, we assessed circulating thrombomodulin concentrations in patients with familial Mediterranean fever (FMF). Twenty-five patients with FMF (F/M: 14/11) (mean age: 31.1 +/- 9.7 years) and 25 healthy controls (F/M: 13/12) (mean age: 34.6 +/- 7.0 years) were involved in the study. Thrombomodulin levels were measured by commercially available enzyme-linked immunosorbant assay (ELISA) (Immunoassay of thrombomodulin Diagnostica Stago, Asnieres-Sur-Seine, France). Twenty of the patients were in attack-free period and the remaining five had been during acute FMF attacks. Thrombomodulin levels were higher in the study group (20.9 +/- 12.1 ng/ml) than healthy controls (14.1 +/- 8.4 ng/ml) (p < 0.05). Circulating thrombomodulin levels were also higher in attack-free FMF patients (22.4 +/- 12.9 ng/ml) than controls. This study disclosed for the first time significantly higher increments in the circulating levels of thrombomodulin in FMF. This observation could be a consequence of injured endothelium and/or activated inflammatory cells.

Extra-articular manifestations of rheumatoid arthritis: results of a university hospital of 526 patients in Turkey.

OBJECTIVE: Presence of extra-articular manifestations (EAM) in rheumatoid arthritis (RA) is associated with more severe disease and increased mortality. Prevalence of EAM may vary in different geographic areas and in different ethnic populations. In this study we investigated the frequency of EAM in 526 RA patients from a single university hospital in Turkey. METHODS: The hospital records of patients who had been diagnosed as RA in Hacettepe University Department of Rheumatology between the years 1988 and 2003 were retrospectively evaluated. There were 73 males and 453 females, and mean age of the patients was 48.0 +/- 12.3 years. The mean follow-up period was 4.8 +/- 4.1 years. Three hundred and fifty-nine patients were rheumatoid factor (RF) positive (68.3%). RESULTS: The overall frequency of EAM was 38.4% (202 patients). The most common EAM was rheumatoid nodules (18.1%). Sicca symptoms, pulmonary findings, Raynaud's phenomenon, livedo reticularis, carpal tunnel syndrome, vasculitis, amyloidosis, and Felty syndrome were present in 11.4%, 4.8%, 3%, 4.8%, 2.8%, 1.3%, 1.1%, and 0.3% of the patients, respectively. Overall EAM and rheumatoid nodules were significantly more common in RF positive patients than RF negative patients. The frequency of rheumatoid nodules was significantly higher in males than in females. CONCLUSION: The prevalence of EAM in Turkey is higher than East Asia and Africa, and lower than UK and North America. Excluding secondary Sjögren's syndrome, our results are similar to other Mediterranean populations like Italy.

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) mimicking systemic lupus erythematosus: a review of two cases.

Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a benign and self-limited lymphadenitis commonly found in young women. It often shares clinical features with systemic lupus erythematosus (SLE), such as arthralgias, fever and leukopenia. The etiology of KFD remains unknown and controversial. Clinical course is favorable, with spontaneous remission in less than four months in almost all cases. Herein, we present two cases. The former is a 53-year old woman presenting with cervical lymphadenopathy, arthralgia, pancytopenia and positive antinuclear antibody (ANA). Lymph node biopsy revealed histopathological features compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The latter patient was a 20-year old woman presenting with left cervical lympadenopathy, a butterfly rash that was reminiscent of SLE, and a positive antinuclear antibody. Based upon clinical, histological and laboratory findings, the diagnosis of SLE was excluded. Careful attention should be paid to differentiating between KFD and SLE, because of their similar presentations, yet different clinical courses and therapeutic requirements.

Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) attacks are characterized by serosal inflammation rich in PMNL leukocytes and activation of a definite cytokine network. Moreover, there is sustained inflammation in attack-free FMF patients. Interleukin (IL)-17 and IL-18 are recently described proinflammatory cytokines, which can modulate certain neutrophil functions. In this study we measured serum levels of IL-17 and IL-18 in FMF patients. METHODS: The study groups comprised of 18 FMF patients in attack-free period (mean age: 30.2 +/- 9.5 years; male/female: 10/8), and 18 patients with an acute FMF attack (mean age: 25.4 +/- 4.9 years; male/female: 10/8). Twenty age-matched healthy subjects were included as a control group (male/female: 10/10). Levels of IL-17 and IL-18 were determined by commercial ELISA kits (Biosource International, USA). RESULTS: Serum IL-17 levels were 42.8 +/- 3.7, 42.7 +/- 3.2, and 39.9 +/- 2.3 pg/mL for FMF patients in attack-free period, FMF patients with acute attack, and healthy controls, respectively. Serum IL-18 levels were 878.8 +/- 315.0, 854.2 +/- 261.4, and 314.6 +/- 80.8 pg/mL for FMF patients in an attack-free period, FMF patients with acute attack, and healthy controls, respectively. Levels of both IL-17 and IL-18 were significantly higher in FMF patients with and without acute attack compared to control group (p < 0.05). Concentrations of those cytokines were comparable in FMF patients with acute attack and in attack-free period (p > 0.05). CONCLUSION: Our data suggest that IL-17 and IL-18 contribute to the cytokine network in the inflammatory cascade of FMF. However, their roles for the initiation of FMF attacks remain to be established.