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Background Recent researches demonstrated presence of local RAS in myocardium, ovary and brain. Angiotensin converting enzyme (ACE) was shown to be produced by synovial membrane macrophages. Angiotensin II is a potent vasoconstrictor, and also can stimulate angiogenesis, fibroblast proliferation and growth factor expression. Hypertrophy and hyperplasia of synovium and angiogenesis are well documented in persistant rheumatoid synovitis. Objectives In this cross-sectional study we aimed to detect ACE and renin levels in serum and synovial fluid (SF) of patients with RA and osteoarthritis OA. Methods Sixteen patients with RA (13F, 3M), 13 patients with OA (8F, 5M) and 11 healthy controls (HC) (5F, 6M) were enrolled in the study. The commercially available Angiotensin-Converting Enzyme kit and ACE calibrator were used. Renin assay was carried out with a two-site immunoreactive assay. Results Median serum ACE levels were 48 U/l, 45 U/l, and 33 U/l in RA patients, OA patients, and HC, respectively. Median serum renin levels were 12.9 pg/ml, 11.8 pg/ml, and 17.9 pg/ml in RA patients and OA patients, respectively. Neither of these results were statistically significant (p > 0.05). SF levels of ACE and renin were found to be increased in RA patients (44 U/l and 3.5 pg/ml) compared to OA patients (24 U/l and 1.2 pg/ml) (Table 1). Synovial fluid renin levels in patients with RA was negatively correlated with disease duration. Conclusion In this study we demonstrated that ACE and renin levels were elevated in SF of RA patients while serum ACE and renin levels were comparable to those in OA patients and healthy controls. These observations suggest presence of local RAS in RA synovium. Since angiotensin have stimulatory roles in angiogenesis and fibroblast proliferation, local RAS may participate in pannus formation and joint destruction in patients with RA. Negative correlation of synovial renin with disease duration may be compatible with previous observations that joint erosion is most prominent during the first months of the disease. Further studies, including mRNA of ACE and angiotensin II are needed to clarify exact roles of RAS in the pathogenesis of RA.

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. 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.

Background Objectives This study is planned as a prospective investigation of the accuracy of magnetic resonance imaging for the demonstration of early-stage rheumatoid arthritis findings of both hands, with the goal of differentiating magnetic resonance imaging and plain film findings of the patients having early -stage rheumatoid arthritis. Methods Ten patients who met American Rheumatism Association criteria for rheumatoid arthritis and symptoms of less than one year duration were accepted for the study. After full clinical assessment, laboratory tests and radiographs of the hands were undertaken, magnetic resonance imaging was performed on a 1.5 tesla imager using an extremity coil using SE T1, TSE T2, fat suppressed T2, flash 2d 3DGRE and postcontrast fat suppressed T1 weighted sequences. Results 6 of 10 patients had periarticular osteoporosis on plain radiography. All of the 10 patients had subcondral erosions, 8 patients had effusion in proximal interphalangeal joints, 8 had synovial hypertrophy, 7 had tendonitis, 5 had tendon erosions and tears and 2 had ulnar collateral ligament ruptures. Conclusion Magnetic resonance imaging not only allows direct visualisation of the inflammatory soft tissue, but also its effect on the bone, cartilage, tendons and ligaments. Magnetic resonance imaging, due to its superior soft-tissue contrast and tomographic changes is more sensitive to than plain radiography in demonstrating the changes due to rheumatoid arthritis. This may contribute to more accurate diagnosis in early-stage rheumatoid arthritis patients and allow an earlier decision to start proper medication and defining progression or remission of the disease.

Background Amyloidosis is the drastic complication of familial Mediterranean Fever (FMF). Amyloidosis may be characterised by a tendency for keratinocytes to undergo filamentous degeneration and apoptosis. However, a possible association of FMF and apoptosis has not been previously evaluated. Binding of Fas ligand (FasL) to the Fas antigen trigger the cytoplasmic apoptotic signal. Induced cell death can be inhibited by soluble Fas protein (sFas) which binds to and functions as competitive antagonist of FasL. Objectives The aim of this study was to investigate sFas in patients with FMF complicated with amyloidosis compared to FMF patients without amyloidosis and controls. Methods Ten FMF patients with amyloidosis (mean age: 41.8, min-max: 33–51), 12 patients with FMF without amyloidosis (mean age: 24.8, min-max: 17–38) and 16 controls (mean age: 48.7, min-max: 38–63) were enrolled in the study. All FMF patients were in attack-free period during blood sampling. sFas levels were measured using a commercially available ELISA kit (Quantikine sFas Immunoassay). Results Conclusion Decreased serum sFas levels may lead to unbalanced binding of FasL to its receptor, inducing apoptosis. In vitro experiments demonstrated that long-term enhancement of Fas expression in Fas-normal mice resulted in an increased acute-phase response and renal amyloidosis in aged transgenic mice. Increased Fas expression in T cells of aged CD2-Fas transgenic CD-1 mice resulted in an increased immune response and T cell apoptosis. Therefore, enhanced Fas-mediated apoptosis can be associated with amyloidosis in FMF patients, and this association may be related to the dysregulated immune system activation. On the other hand, elevated levels of sFas protein in patients with FMF may also be related to the imbalanced inflammatory activity. Induced cell death of autoreactive T cells could be inhibited by sFas. sFas levels were shown to be elevated in patients with active SLE. However this observation could not be confirmed by some other authors. Since the changes in autoimmune inflammatory disorders are dynamic and complex, it is difficult to establish a relationship between sFas and their pathogenesis. It also remains to be detected which cells release the elevated amounts of sFas. Future studies are needed to elucidate exact state of sFas protein in the etiopathogenesis of FMF.

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.

Background Acromegalic arthropathy is a noninflammatory condition in which cartilage hypertrophy and hyperplasia lead to the disruption of joint geometry and chondrocyte metabolism, and ultimately to degenerative changes. It is reversible in cases of early and prompt diagnosis. Rheumatoid arthritis is an inflammatory disease with joint destruction. Erosion in rheumatoid arthritis is caused by invasion of articular cartilage by the synovial pannus. Erosion in rheumatoid arthritis may be regressed with early and aggressive treatment. In this report we present a case of acromegaly who developed rheumatoid arthritis. Objectives Methods Case report:A 64-year-old male was admitted in April 2000 for evaluation of a 2-year history of polyarthritis. He was followed in 1985 with symptoms and signs of acromegaly, which was confirmed by radiology and a basal GH level of 30 mU/l. His acromegalic features improved after he had been operated. In 1995, therapy with sandostadin was started. In 1997, he was given external radiation. In 1998, he started to complain symmetric polyarthritis in proximal interphalangial and metacarpophalangial, wrist, and knee joints. In laboratory evaluation, erythrocyte sedimentation rate (ESR) was 93 mm/hour and rheumatoid factor was 685 IU/l. No improvement was observed with the treatment protocol consisting of non-steroid anti-inflammatory drug and exercise which was given in another hospital. Two years later, he was evaluated in our rheumatology clinic. At that time, he had arthritis in PIF, MCF, and wrist joints and three-hour morning stiffness. Bilateral ulnar deviation at MCF joint and interosseous muscle atrophy were observed. In laboratory examination, ESR, CRP, Hb, RF, platelet count were 89 mm/hour, 6.7 mg/dL, 12.6 gr/dL, 789 IU/L, 540000/ml respectively. In radiological evaluation, osteoporosis in lumbar vertebrae and in hand graph were observed. Widening and tufting of distal phalanx and subchondral erosive and cystic changes in PIF and MCF joints were seen. In MRI, synovitis and erosive changes were marked. The patient was diagnosed as rheumatoid arthritis and treated with methotrexate, sulfasalazine, and hydroxychloroquine. After three months of treatment, the patient improved regarding in clinical and laboratory values. He is still being followed by our clinic in good health. Results Conclusion The incidence of significant joint complains in large series of acromegalic patients have been reported to be 15%-64%. The changes seen in acromegaly are similar to those seen in degenerative joint disease. The occurrence of rheumatoid arthritis and acromegaly in the same patient are not reported, except one case. The slow progression of the erosive changes in this case proposed that GH might modify the catabolic effect of rheumatoid arthritis. Evaluation of laboratory parameters such as ESR, CRP, RF, thrombocytosis and anaemia help us to make a differential diagnosis of rheumatoid arthritis and acromegaly arthropathy.

Background Objectives Methods Case Report: A 17-year old Turkish boy was admitted to our clinic with complaints of weight loss, fatigue and abdominal pain. He had been on colchicine therapy for 6 years with the diagnosis of FMF. On January 2000, he was diagnosed as having acute hepatitis A infection in another centre. Two weeks later he was hospitalised due to severe abdominal pain and abrupt decrease in his haemoglobin values. A right renal subcapsular hematoma was demonstrated by computerised tomography (CT). During follow-up haemoglobin values progressively declined and the hematoma showed enlargement in control CT. Therefore right nephrectomy was performed. After the patient was stabilised he was discharged. However he was again hospitalised with similar complaints 4 days later. This time subcapsular hematoma was demonstrated in the left kidney and he was referred to our hospital in March 2000. In physical examination, blood pressure was 160/125 mmHg. Laboratory evaluation demonstrated anaemia and elevated erythrocyte sedimentation rate and C-reactive protein. Serological tests for anti-hepatitis B surface antigen, anti-hepatitis A IgG and IgM were positive. Nephrectomy slides were re-evaluated in our pathology department. Patchy and segmental areas of renal infarct were demonstrated. No amyloid deposits could be noted in the histopathology specimens. Renal angiography demonstrated 2 microaneurisms on intertubular arteries. Together with these findings the diagnosis of PAN was made and the patients was treated with intravenous corticosteroids, intravenous cyclophosphomide and oral corticosteroids together with antihypertensive therapy. He is still being followed-up by our clinic in good health. Results Conclusion Perirenal hematoma, which is a rare complication of isolated PAN, have been reported in approximately half of the patients with FMF who developed PAN. The exact pathogenetic relationship of FMF and PAN also is not clear. Immune-related mechanisms have been demonstrated in FMF. It has been proposed previously that infection-related antigenic stimuli could trigger the development of vasculitides. In the present case an usual response to hepatitis A infection and/or previous hepatitis B infection might have been among the triggers of vasculitic process. Additional reports demonstrating direct causal relationship between infectious agents and vasculitic syndromes in patients with FMF will help us to clarify the relationship between the two disorders.

Background Behcet’s disease (BD) is a multisystem disorder originally described by the Turkish dermatologist Hulusi Behcet. Although its aetiology is unknown, vasculitis is widely accepted as the underlying pathological process. Viral infections, especially hepatitis B and C viruses, have been proposed to be triggering factors via soluble immune complexes in vasculitic syndromes. Viral aetiology has also been postulated in the etiopathogenesis of BD. A possible association of Hepatitis C virus have been investigated previously, but no definite relationship has been found. More recently, serological evidences of previous Hepatitis A, Hepatitis C and Hepatitis E virus infections were found to be similar between Behcet’s patients and control group. Objectives In this cross-sectional study we aimed to investigate the prevalence of Hepatitis E virus (HEV), which is the major cause of non-parenteral non-A non-B hepatitis, in our group of patients with BD. Methods Sixty-four patients (22 female, 42 male, mean age: 39, min-max: 16–68) were enrolled in this study. Clinical and demographical characteristics of our study group were given in table. Hepatitis E antigen was studied in serum of patients using commercial kits (International Immuno-Diagnostics, USA). Results Seropositivity for HEV was detected in 3 patients (4.69%). This result is comparable to previous report of seroprevelance of HEV in Turkish population (5.9%). Conclusion We concluded that HEV does not seem to have a place in the etiopathogenesis of BD, at least in our population.

Background Here in this case report we present a patient complaining of soft-tissue swelling on his hand, who had excision of giant cell tumour of the tendon sheath 1 year ago which has recurrence rates range from 9%–44%. He also met American Rheumatism Association criteria for rheumatoid arthritis. We described plain radiography and magnetic resonance findings of this soft tissue mass, which firstly presumed to be recurrence of giant cell tumour of the tendon sheath and later on diagnosed to be pannus pathologically and have characteristic radiological findings of pannus. Objectives Methods Radiographs of the hands were undertaken, magnetic resonance imaging was performed on a 1.5 tesla imager using an extremity coil. Magnetic resonance imaging of the hand was performed using SE T1, T2, PD, FL2D 3O sequences and followed by T1 weighted postcontrast examination immediately after Gd-DTPA(0.1 mmol/kg body weight) was injected intravenously as a bolus. Results Plain films demonstrated cortex erosion on the second metacarpophalangeal joint. Magnetic resonance imaging demonstrated soft-tissue mass which is isointense with muscles on T1 weighted precontrast images and T2 weighted images showed relatively high signal intensity with heterogeneous enhancement of T1 weighted post-contrast images. Increased synovial fluid was interpreted as tenosynovitis was also demonstrated as well as the cortex erosions. Conclusion It is established that giant cell tumour of the tendon sheath can be evident in a joint or a tendon sheath of a patient with rheumatoid arthritis. Although this combination of diseases may represent no more than a coincidence, it is possible that rheumatoid arthritis predisposes a person to develop giant cell tumour of the tendon sheath. While evaluating a patient complaining soft tissue mass on his hand with a history of giant cell tumour of the tendon sheath excision, pannus due to rheumatoid arthritis should be considered as well as recurrence of giant cell tumour of the tendon sheath.