Wegener's granulomatosis: clinical and laboratory results of a university hospital study of 20 patients from Turkey.

The aim of this study was to evaluate the clinical and laboratory features, the treatment approaches, and the long-term outcome of patients with Wegener's granulomatosis (WG) who were followed up in our hospital. The hospital files of the patients with the diagnosis of WG who were followed up between the years 1985 and 2003 in Hacettepe University Hospital were retrospectively evaluated. Male/female ratio was 12:8. The mean age was 39 years (range 20-65 years). Constitutional symptoms and upper and lower airway involvement were seen in 95% of all patients. Renal and musculoskeletal symptoms were seen in 90 and 80% of the patients, respectively. Five patients were treated with oral monotherapy (three with methylprednisolone and two with cyclophosphamide). Three patients were given a combination of orally administered cyclophosphamide and methylprednisolone. Ten patients were treated with pulse cyclophosphamide and methylprednisolone combination together with oral alternate-day methylprednisolone therapy. The remaining two resistant patients were treated with pulse cyclophosphamide, methylprednisolone, and intravenous immunoglobulin combination together with oral alternate-day methylprednisolone. Four patients died because of the disease activity. Intravenous pulse therapies with oral, alternate-day methylprednisolone were well tolerated. Sixteen patients experienced long-term remission after immunosuppressive treatment. Eleven patients have been asymptomatic for more than 12 months. In five patients, residual symptoms persisted: constitutional symptoms and renal and respiratory tract symptoms in varying combinations. The demographic and laboratory findings in this trial were similar with those of the previous results. Alternate-day glucocorticoids plus cyctotoxic drugs may be beneficial in patients with WG.

Intensified, intermittent, low-dose intravenous cyclophosphamide together with oral alternate-day steroid therapy in lupus nephritis (long-term outcome).

The objective of this study is to evaluate the efficacy, toxicity, and long-term outcome of low-dose IV cyclophosphamid therapy with repeated frequent intervals in combination with oral and IV methylprednisolone in patients with SLE nephritis. In this study, 113 patients diagnosed as having SLE and glomerulonephritis were assessed in between 1993 and 2002, with a median follow-up of 44.1+/-41.2 months. The patients were treated with 500 mg IV cyclophosphamide and 1 g IV methylprednisolone together with 60 mg/alternate-day oral methylprednisolone in a given schedule. The clinical and laboratory data were evaluated. There were significant improvements in the clinical and the laboratory parameters. Six patients died shortly after being hospitalized due to the disease activity itself. Eight patients were excluded from the study because of low compliance. The renal functions of the patients remained stable throughout the therapy; only 16/99 patients needed one or two additional pulses. Temporary leukopenia developed in 18/99 patients and diminished with the suspension or prolongation of the IV cyclophosphamide administration. Gastrointestinal side effects, which needed extra medication, developed in 20 patients. Hematuria was observed in 6/99 patients. Menstrual abnormalities were seen in 7/99 patients. No serious infections due to immunosuppression were observed with the given regimen. Hypertension was observed in 13 patients (minimum of 140/90 mmHg, maximum of 190/110 mmHg) and controlled with angiotensine-converting enzyme inhibitors. Mild central obesity was observed in 15 of the patients. Leimyosarcoma was observed in one patient who died during the follow-up period. Therapy starting with the weekly low-dose IV cyclophosphamide to induce remission together with IV and oral steroids, followed by prolonged intervals with the same doses for 2 years, appears to be useful in preserving renal function without major side effects in patients with lupus nephritis, in comparison to other studies.

Plasma thrombopoietin in patients with cavernous transformation of the portal vein.

Thrombopoietin (TPO), the primary regulator of thrombopoiesis, is produced mainly in the liver. Previous studies investigating blood TPO in chronic liver diseases revealed conflicting results. It has been suggested that hepatic TPO production is regulated by the portal blood supply to the liver. However, the role of TPO in the pathobiological basis of idiopathic portal vein thrombosis (PVT) and cavernous transformation of the portal vein (CTPV) has not been elucidated. The objective of this study is to assess plasma TPO concentrations in patients with CTPV. Eleven patients (4 men and 7 women, aged 38+/-12 years) with CTPV were studied. Sixteen healthy adults served as the control group (8 men and 8 women, aged 34+/-12 years). Median plasma TPO concentration was 326 pg/mL (range, 15-1402 pg/mL) in the patients with CTPV and 62.65 pg/mL (range, 38.5-102 pg/mL) in the control group (P = .003). In this study, we found significantly higher TPO concentrations in the plasma of patients with CTPV. The higher concentrations could be a result of the altered portal hemodynamics due to thrombosis. Moreover, TPO release by activated platelets might lead to the subsequent propagation of thrombosis in PVT.

Successful treatment of rheumatoid arthritis is associated with a reduction in serum sE-selectin and thrombomodulin level.

The aim of this study was to investigate the changes in serum levels of endothelial cell injury markers, soluble (s) E-selectin and thrombomodulin (TM), in patients with rheumatoid arthritis (RA) before and after antirheumatic drug treatment and to assess the relationship between these changes and clinical responses to the drug treatment. Eleven patients with RA having active arthritis and 12 healthy volunteers were enrolled in the study. They were monitored by clinical and laboratory parameters while receiving a combination of methotrexate, hydroxychloroquine and sulphasalazine. Pre- and post-treatment clinical and laboratory parameters, including sE-selectin and sTM levels, were measured. The ages of the patients were comparable with those of the control groups. Significant improvements were detected in erythrocyte sedimentation rate, C-reactive protein, hemoglobin, morning stiffness, patients' global assessment, physicians' global assessment, number of tender joints and number of swollen joints improved at the end of the therapy (for each parameter p < 0.05). Significant improvements were detected in clinical and laboratory parameters. In the patient group there were significant decreases in the levels of sTM and sE-selectin after treatment (p < 0.05). The patient group had significantly higher sTM and sE-selectin levels than the control group at the beginning of the study (p < 0.01), but the difference returned to normal after the treatment (p > 0.05). The sE-selectin and sTM levels significantly correlated with each other, and also with clinical and laboratory findings. Combination treatment successfully treated RA patients. sE-selectin and sTM levels probably reflect disease activity and can be helpful in monitoring disease status and response to therapy.

The efficacy of interferon-alpha in a patient with resistant familial Mediterranean fever complicated by polyarteritis nodosa.

Familial Mediterranean fever (FMF) is a recurrent self-limiting polyserositis. Polyarteritis nodosa (PAN) complicating FMF is very rare. Here, we present a 17-year-old male patient with FMF who subsequently developed PAN 2 weeks after hepatitis A infection. This case was also complicated with perirenal haematoma, and right nephrectomy was performed. The clinical condition of the patient was improved after therapy with intravenous and oral corticosteroid and intravenous cyclophosphamide. However, the FMF attacks and vasculitic skin lesions again occurred while he was using colchicine plus immunosuppressive agents a few months later. Interferon-alpha therapy was administered and the attacks were resolved within 3 months. He has not experienced any other symptom during the follow-up period of 28 months.

Is visual loss due to giant cell arteritis reversible?

Giant cell arteritis (GCA) is a common systemic vasculitis with an unknown etiology. It mainly affects people older than 50 years of age and often presents with symptoms such as headache, jaw claudication, visual loss, polymyalgia rheumatica and increased erythrocyte sedimentation rate (ESR). Established blindness is irreversible if the steroid treatment is not administered within a few days. Here, we report a case of GCA in a patient with a normal ESR whose left eye perceived just light at the initiation of treatment. Immediately prior to the combined treatment with high dose oral steroids and cyclophosphamide, the ESR level had increased to 80 mm/h and the vision improved after the combined treatment four months later.

Combination therapies in spondyloarthropathies.

OBJECTIVES: To compare the efficacy and tolerability of single-agent sulfasalazine (SSZ) with combination therapies composed of SSZ and methotrexate (MTX) and SSZ, MTX and hydroxychloroquine (HCQ) in active spondyloarthropathy (SpA) patients with peripheral arthritis. METHODS: One hundred and fifty SpA patients with peripheral arthritis (male/ female: 92/58) who were treated in our clinic between 1994 and 1998 were enrolled in this trial. Patients treated with SSZ alone (1-3 gr/day) were included in Group I, patients treated with combination of SSZ (1-3 gr/day) and MTX (7.5-15 mg/week) in Group II, and patients treated with combination of SSZ (1-3 gr/day), MTX (7.5-15 mg/week) and HCQ (200 mg/day) in Group III. Forty-eight patients in Group I, 45 patients in Group II and III were eligible for statistical analysis at the end of study. RESULTS: The combination of MTX, SSZ, and HCQ, and the combination of MTX and SSZ were more effective regarding the clinical and laboratory parameters than SSZ alone (p<0.05). Moreover, the combination of MTX, SSZ, and HCQ was more effective than the combination of MTX and SSZ (p<0.05). CONCLUSION: Combination therapies seem to be more effective and no more toxic than monotherapy in SpA patients with peripheral arthritis.

Neutrophil CD64 expression in Behçet's disease.

OBJECTIVE: Hyperfunction of neutrophils is a characteristic finding in Behçet's disease (BD). Microbial agents have been proposed as causative agents in the disease flares. Fc gamma receptor 1 (CD64) is not normally expressed by neutrophils of healthy individuals, but is upregulated by these cells in response to microbial wall components and proinflammatory cytokines. The degree of polymorphonuclear leukocyte (PMN) CD64 expression is different in autoimmune diseases and systemic infectious diseases. We investigated PMN CD64 expression in patients with BD. METHODS: Thirty-seven patients with active BD (M/F: 18/19, mean age: 34.4 +/- 9.7 yrs), 35 patients with inactive BD (M/F: 11/24, mean age: 35.9 +/- 11.6 yrs), 27 patients with culture proven infections (M/F: 19/8, mean age: 54.4 +/- 15.2 yrs), 31 healthy controls (M/F: 14/17, mean age: 37.7 +/- 8.7 yrs), and 42 patients with active inflammatory disease (M/F: 13/29, mean age: 39.3 +/- 14.9 yrs) were enrolled in this study. Flow cytometry was used to assess the prevalence of CD64-bearing PMN in whole blood samples. RESULTS: The prevalence of CD64-bearing PMN was significantly higher in patients with infectious disease (77.1 +/- 18.4), inflammatory disease (37.1 +/- 27.5), and active BD (48.9 +/- 22.5) than in healthy controls (9.5 +/- 7.8) or patients with inactive BD (12.9 +/- 9.5). CD64 expression was similar in controls and patients with inactive BD. In the infectious disease group, expression of CD64 was significantly higher than in the active BD and active inflammatory disease groups, while there was no significant difference between the groups of patients with active BD and inflammatory disorders. CONCLUSION: Neutrophil CD64 expression increases during exacerbation of BD. This increase appears to be a non-specific inflammatory response and does not reflect PMN activation triggered by a living microorganism.

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

Cancer-associated venous thromboembolism is a severe form of paraneoplastic syndrome. It rarely leads 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.

Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis.

OBJECTIVE: The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes. METHODS: Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2-2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti-double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls. RESULTS: In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2-135.5) and 33.4 ng/ml (range 23-62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8-120.5) and 74.6 ng/ml (range 23.3-91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period. CONCLUSION: Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.