Sule Apras

Effects of interferon α treatment on the clinical course of refractory Behçet’s disease: an open study

Interferon α (IFNα) has recently been introduced in the treatment of uveitis, mucocutaneous lesions, and arthritis of Behcet’s disease (BD).1–6 To our knowledge, there is currently no clinical trial which has evaluated the efficacy of IFNα treatment in the vascular or neurological involvement in BD. In this open study we evaluated the efficacy, toxicity, and tolerability of IFNα in the management of BD with ocular, articular, vascular, or neurological manifestations which had previously been unsuccessfully treated conventionally. A total of 29 patients (17 men, 12 women; mean age 33.2 months, range 16–51) who were resistant to conventional treatments were treated with systemic IFNα. Previous conventional treatments had been colchicine, aspirin, and penicillin plus sulfasalazine for patients with arthritis; or colchicine, aspirin, and penicillin plus steroids and/or immunosuppressive agents, azathioprine, cyclosporin A, or cyclophosphamide for ocular, vascular, and/or neurological involvement. The mean duration of the disease was 8.86 years (range 1–30). Four patients were excluded from the statistical analysis because of the short duration of treatment (<4 months). Seventeen patients had ocular inflammation. Eleven patients had arthritis. Ten patients had vascular disease (aneurisms in the internal cerebral and ophthalmic arteries; thrombosis of popliteal veins and left anterior descending coronary artery causing myocardial infarction; organised thrombus in superior and inferior caval, …

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

Abstract: 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.

AB0652 Thrombin Activated Fibrinolysis Inhibitors (TAFI) Levels in Active Diffuse Systemic Sclerosis Patients

Background Thrombin-activated fibrinolysis inhibitors (TAFI) is activated by the endothelial surface thrombin and has an important role on the relation of coagulation, fibrinolysis and inflammatory systems. Basically, activation of TAFI down-regulates fibrinolysis and also, leads the neutrophil activation triggered by C5 and kinin related inflammatory systems. Objectives We aimed to show the relation between the serum TAFI levels and disease activity of diffuse systemic sclerosis patients (SSc). Methods 13 active SSc female patients with interstitial lung disease and 10 healthy women were involved in to the study. From the serum samples of both groups, TAFI levels were measured by ELISA method using pefakit TAFI (Penthafarm, Basel). Results Serum TAFI levels of SSc patients was 63.1±19.1 mg/dL SD (min-max: 30-90 mg/dL) and control groups TAFI level was 41.0±11.1mg/dL SD (min-max: 9-59 mg/dL). All data was analysed by Mann-Whitney U test. P<0.05 was accepted as significant. Comparison between the scleroderma and control groups TAFI levels revealed that TAFI levels in patient group was significantly higher (p=0.009). Conclusions Fibrinolytic activity is linked to inflammation. Increased amount of TAFI in serum may explain why fibrin formation is so prominent in SSc. And also TAFI may play important roles in the mechanism of intraalveolar hypofibrinolysis associated with interstitial lung disease. References MJ Peters. Ann Rheum Dis 2009; 68(7):1232-3. Ringwald J. Throm Res 2002; 119(1):129-31. Sak S. J Throm Haemost 2003; Dec;1(12): 2510-5. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4853

Massive deep venous thrombosis and venous gangrene in a 29-year-old case: metastatic epidermoid carcinoma with an unknown primary.

Abstract Cancer-associated venous thromboembolism is a severe form of paraneoplastic syndrome. It rarelyleads 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.

AB0079 Cyclophosphamide exposure during pregnancy: two cases

Background Lupus nephritis is a severe clinical entity that should be treated with cytotoxic drugs. Cyclophospamide is an effective cytotoxic agent against lupus nephritis. Cyclophosphamide is probably a potent teratogen. Severe birth defects reported in several cases after cyclophosphamide given as little as 200 mg during pregnancy. Some authorities, however, recommend the use of cyclophosphamide in life-threatening lupus during pregnancy. Objectives In this report, we present two cases that used cyclophosphamide during unpredicted pregnancy. Methods Results Case-I: A 20-year-old female was diagnosed as SLE with arthritis, photosensitivity, haemolytic anaemia, leukopenia, proteinuria and positive antinuclear and anti-ds-DNA antibodies. Anti-phospholipid antibodies were negative. The disease remained under control with corticosteroids, hydroxychloroquine and cyclophosphamide. In June 1999, it was noticed that she had been pregnant for 24 weeks and she had received five cycles of intravenous pulse cyclophosphamide (500 mg for each cycle, 2500 mg total dose). Until the end of pregnancy, the treatment was continued with corticosteroids. The baby is now 16 months-old and in good health. Case-II: A 21-year-old female patient presented with arthritis, carditis, and proteinuria. She had positive antinuclear, anti-ds-DNA, and negative anti-phospholipid antibodies, and the diagnosis of SLE was made. She was treated with oral corticosteroids and intravenous cyclophosphamide. In September 1999, while she was in remission, it was noticed that she had been pregnant for 12 weeks. Since that time, she had been given intravenous 500 mg pulse cyclophosphamide twice (1000 mg totally). During pregnancy, only corticosteroids and salicylic acid were given. In March 2000, she delivered a healthy male baby. The baby is now 9 month old and healthy. Conclusion Although fertility is decreased in SLE due to lupus nephritis and cyclophosphamide treatment, some pregnancies may occur. The pregnancies of SLE patients with anti-phospholipid syndrome have poorer prognosis. The absence of anticardiolipin antibodies in these two patients might have protected from poor outcome. Some authors believe that cyclophosphamide should not be used due to its teratogenic effect. Reported abnormalities due to cyclophosphamide during pregnancy include absent thumbs, absence of the great toes or all toes, palatal abnormalities, and a single coronary artery. However there are also reports of normal infants born from cyclophosphamide-treated mothers, and cyclophosphamide was proposed in life-threatening lupus. Experiences of cases like the present two may help the physician to make decisions on cyclophosphamide therapy during pregnancy in life-threating cases.

THU0231 Rheumatic disease as the cause of fever of unknown origin: an update of classical data

Background Fever of unknown origin (FUO) remains one of the major diagnostic challenges for the clinician. Although infection, malignancy and collagen vascular disease are accepted the 3 most important causes of FUO, the relative importance of these major categories might have changed because of improvements in serodiagnosis, culture techniques and radiologic imaging modalities. Rheumatic diseases not uncommonly present with fever. Objectives Our objective was to make an uptake of our knowledge regarding causes of FUO in our hospital together with more detailed analysis of collagen vascular and granulomatous disorders presenting with FUO. Methods In this clinical investigation, we retrospectively evaluated hospital records of patients who were hospitalised in our Infectious Diseases Service from January 1990 through September 2000 to investigate the cause of prolonged fever. One hundred forty-five patients (63 female, 82 male, mean age: 38.5, min-max: 16–80) meeting the classical criteria of FUO were included in the present study. Results Infections, rheumatic diseases and malign disorders were found in 93 (64.1%), 24 (16.6%) and 8 patients (5.5%), respectively. Infectious causes are the most common cause in all age groups, and rheumatic disease are the second. Malign diseases were diagnosed in 2.7% of patients under age 50, and percentage of these disorders increased to 15.6% among patients over 50. Miscellaneous conditions were found in 2 patients (1.4%), and despite detailed evaluation 18 patients (12.4%) remained undiagnosed. List of rheumatic diseases diagnosed as causes of FUO in the present study are given in Table 1.Abstract THU0231 Table 1 List of rheumatic diseases diagnosed as causes of FUO Frequency Percent FMF 2 8.3 Unclassified collagen tissue disease 4 16.6 Sarcoidosis 2 8.3 Seronegative arthritis 2 8.3 SLE 3 12.5 Temporal arteritis 2 8.3 PAN-like vasculitis 4 16.6 Others (Behçet’s D, PM, Still’s, RA, WG) 5 20.8 Conclusion In conclusion, despite widespread use of antibiotics and increasingly useful diagnostic technologies, infectious disease still remain the leading cause of FUO among our group of patients, and collagen vascular diseases together with granulomatous disorders are the second most common group. The percentage of tumours was higher in our elderly patients than in the younger ones but still clearly lower than other causes of FUO in adults. Infectious Diseases Department of Hacettepe University is one of the reference centres in Turkey, and many undiagnosed cases are being referred to our hospital. Therefore we believe that, although we performed the present study only from our hospital reports, the results may reflect the general population of central Anatolia.