Infliximab, a TNF-α antagonist treatment in patients with ankylosing spondylitis: the impact on depression, anxiety and quality of life level.

The objective of this study was to assess the effect of infliximab on depression, anxiety and quality of life in patients with active ankylosing spondylitis (AS). In this 6-week longitudinal study, 16 patients with AS were assessed. Active disease as defined by BASDAI ≥4.0 was sought for inclusion. Infliximab was administered 5 mg/kg at 0, 2 weeks and 6 weeks. Collected data included age, sex and date of onset of rheumatologic disease. Activity of disease was measured using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Biological activity was evaluated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). ESR and CRP were assessed at baseline and day 42. The Hospital Anxiety and Depression scale (HADS), Beck Depression Inventory (BDI) and 36-item Short Form Health Survey (SF-36) were used to evaluate anxiety, depression and quality of life. BASDAI, SF-36, HADS and BDE were assessed prior to the initial infliximab dose and at 2nd, 14th and 42nd day. Seven (43.8%) AS patients had depression scores above the cut off value for both the HADS depression (HADS-D) and BDI and 4 (25 %) had high HADS anxiety scores at baseline. Significant time effect for BDI and HADS-D scores were observed. Although significantly lower BDI scores were found after first, second and third infusions of infliximab, compared to initial score, the significant decrease in HADS-D appeared after second and third infusions. A significant time effect for HADS-anxiety scores were found as well. All of the subscales of SF-36 improved significantly during the course, with an exception of role emotional, for which the difference approached to the significance. The change in BASDAI scores and CRP and ESR, in the treatment process, were not correlated with the change in depression and anxiety scores. Infliximab which is an anti-TNF-α drug, may be effective in the treatment of depression accompanying AS. Possible implications for the treatment of major depressive disorder were discussed, as well.

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.

The efficacy of continuous interferon alpha administration as an adjunctive agent to colchicine-resistant familial Mediterranean fever patients.

OBJECTIVE: About 10-20% of familial Mediterranean fever (FMF) patients are resistant to regular colchicine treatment and have painful recurrent attacks due to polyserositis. In clinical practice there is no alternative drug for such patients. In a previous pilot study on a small number of colchicine-resistant patients, interferon-alpha (IFN-alpha) was administered when painful attacks were about to occur. METHODS: In this study we gave IFN-alpha continuously to 8 colchicine-resistant FMF patients in a schedule while the colchicine therapy had been continued. All those patients were complicated with vasculitis or arthritis or together during the FMF course. Those complications were treated with the other immunosuppressive drugs. While they were under intense immunosuppressive therapy, the abdominal and the other serosal attacks remained to continue. RESULTS: After the administration of IFN-alpha therapy only one out of eight patients had abdominal painful attacks in twice, and one patient had arthritis in knees and ankles, the others responded well. Observed side effects were generally mild and acceptable. CONCLUSION: Continuous IFN administration in addition to the regular colchicine treatment may be useful for the colchicine-resistant attacks in FMF patients.

Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis.

OBJECTIVE: The response to single disease modifying antirheumatic drug (DMARD) is often suboptimal in patients with rheumatoid arthritis (RA). Thus, despite the limited data on the therapeutic efficacy of combination therapies, many patients are currently treated with a combination of DMARDs. METHODS: We studied prospectively the efficacy of combination therapy with DMARDs. The study was designed as a randomized trial and a single DMARD or two or three DMARD combinations were administered to 180 consecutive, age- and sex-matched patients with active RA, each of whom was followed up for a period of 2 years under treatment. Patients were divided into 3 groups which did not differ with regard to demographic, clinical and laboratory parameters. Patients in group I were treated with a single DMARD [methotrexate (MTX) 7.5-15 mg/week or sulfasalazine (SSZ) 1-2 g/day or hydroxychloroquine (HCQ) 200 mg/day], group II with MTX + SSZ or MTX + HCQ, and group III with a combination of all three drugs. Patients were re-evaluated at regular intervals by means of clinical and biochemical tests designed to detect specific rheumatic activity. Radiological assessments were also performed and scored according to Larsen by the same radiologist who was blinded to the treatment groups. RESULTS: At the end of the trial there were significant improvements in the clinical and laboratory parameters in all 3 groups. However, improvements were greater and much more significant in the patients who were given combination therapies. The combination of MTX + SSZ + HCQ was more effective than both monotherapy and the two-drug combinations. CONCLUSION: In conclusion, we suggest that patients with RA should be treated with combinations of DMARDs.

The efficacy of oral cyclophosphamide plus prednisolone in early diffuse systemic sclerosis.

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.

No evidence of cardiac autonomic involvement in ankylosing spondylitis, as assessed by heart rate variability.

The aim of this study was to investigate the involvement of autonomic nervous system (ANS) function by using power spectral analysis of heart rate variability (HRV) method in patients with ankylosing spondylitis (AS). The study included 94 AS patients all fulfilling the New York criteria for AS, and 49 healthy volunteers. Recordings for HRV were obtained with a PC-based high-resolution electrocardiographic system and analysed using power spectral analysis. The peak around 0.04-0.15 Hz was defined as low-frequency peak (LF) and the other, around 0. 15-0.40 Hz, was defined as high-frequency peak (HF), representing mostly the sympathetic and the parasympathetic components of the ANS, respectively. The following variables were calculated and compared between groups: the LF in absolute and normalised units (LF nU); the HF in absolute and normalised units (HF nU); and LF/HF ratio. The AS group included 47 male and 47 female subjects with a mean age of 33 +/- 11 years (range 16-64). In the control group there were 23 male and 26 female healthy subjects (mean age 33 +/- 8; range 19-60). None of the patients or control subjects had any cardiac or neurological symptoms. Both groups were similar with respect to age and sex characteristics (p > 0.05). The HRV analysis indicated that the peaks of LF, LF nU, HF, HF nU and LF/HF ratio were similar in both groups. Groups also did not differ with respect to heart rate at the time of examination. Our data demonstrated no evidence of ANS involvement as assessed by HRV analysis in AS patients.

Evaluation of vascular injury with proinflammatory cytokines, thrombomodulin and fibronectin in patients with primary fibromyalgia.

OBJECTIVE: Cold intolerance, cold induced peripheral vasospasm, Raynaud's phenomenon, livedo reticularis and immunoglobulin deposition in the skin are often encountered clinical and laboratory findings in patients with primary fibromyalgia (FM). These findings are suggestive of vascular injury. METHODS: Eighty patients (4 male, 76 female) with fulfilling primary FM criteria (FM (+) patient group), 60 patients (3 male, 57 female) with chronic musculoskeletal complaints but without FM (FM (-) patient control group) and 40 healthy volunteers (1 male, 39 female) without musculoskeletal complaints (healthy control group) were enrolled in this cross-sectional study. The study was carried out in two steps. In the first step, the clinical findings, routine laboratory tests, autoantibodies and radiological findings were investigated. The second step were consisted of the laboratory investigations of thrombomodulin and fibronectin as the mediators indicating vascular injury and proinflammatory cytokines in FM patients with Raynaud's phenomenon and/or livedo reticularis and in control groups. RESULTS: There were no differences between study and control groups with regard to laboratory, radiological and immunological (ANA, AntidsDNA, ENA, anticardiolipin IgG and IgM) results. No statistically significant differences were found in the levels of proinflammatory cytokines between FM (+) patient group and control groups (p > 0.05). Thrombomodulin was also shown statistically insignificant difference between FM (+) patient group and control groups (p > 0.05). However, fibronectin, another mediator of vascular injury, was higher in FM (+) patient group and the differences between FM (+) patients and each control groups were statistically significant (p < 0.0001). CONCLUSION: Our results were suggestive of the presence of a non-immunological vascular injury in FM patients with Raynaud's phenomenon and/or livedo reticularis.

Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state.

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 fully 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 fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-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, PF1+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), PF1+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), PF1+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.