Hungarian Immunology

[Malignancies in systemic autoimmune diseases and due to immunosuppressive therapy]

SZEKANECZ Éva, ANDRÁS Csilla, KISS Emese, TAMÁSI László, SZÁNTÓ János, SZEKANECZ Zoltán

JUNE 20, 2006

Hungarian Immunology - 2006;5(03)

[There is an increased risk for secondary tumor development in some, mostly systemic, rheumatic diseases. Among immunosuppressive agents used in antirheumatic therapy, there is enough data available to support that cyclophosphamide and azathioprine are oncogenic. However, the role of methotrexate, cyclosporine A and anti-TNF agents in tumorigenesis is rather controversial. Authors describe those systemic diseases and immunosuppressive drugs, which may increase the development of malignancies.]

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Hungarian Immunology

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Hungarian Immunology

[Detection of rare phospholipid/co-factor antibodies in lupus patients]

TARR Tünde, KISS Emese, BÓTYIK Balázs, TUMPEK Judit, SOLTÉSZ Pál, ZEHER Margit, SZEGEDI Gyula, LAKOS Gabriella

[OBJECTIVE - Was to detect the rare phospholipid/ co-factor autoantibodies in lupus patients. PATIENTS AND METHODS - In the present study, besides anti-cardiolipin and anti-β2-glycoprotein I, antibodies directed against phosphatidil-serine, protrombin and annexinV were measured by commercial ELISA kits in 85 randomly selected lupus patients, 14 of whom met the criteria of antiphospholipid syndrome. Corralations were determined between the presence and concentration of rare antiphospholipids and those included in the diagnostic criteria of antiphospholid syndrome, as well as with clinical thrombotic manifestations. RESULTS - Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in eight, anti-β2GPI IgG in four and IgM in five patients. Lupus anticoagulant was detected in nine cases. Seven patients were positive for anti-phosphatidilserine IgG, nine for aPS IgM, anti-protrombin IgG was positive in nine cases. Antiprotrombin IgM and anti-annexinV were negative in all patients. Correlation was found between antiphosphatidilserine and anti-cardiolipin antibodies. The frequency and the concentration of rare antiphospholipid/ co-factor antibodies were higher in patients with secondray antiphospholipid syndrome. The presence of such rare antiphospholipid antibodies cumulated in patients with antiphospholipid syndrome. Their presence increased the frequency of thrombotic events in the entire study population, furthermore in those positive for lupus anticoagulant or anti-cardiolipin. CONCLUSIONS - The rare anti-phospholipid/cofactor antibodies were found in 12% of an unselected cohort of lupus patients. Their presence was more frequent in patients with secondary antiphospholipid syndrome, and further increased the risk of thrombotic complications.]

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Hypertension and nephrology

[Hungarian Vasculitis Registry – results of the first five years]

HARIS Ágnes, TISLÉR András, ONDRIK Zoltán, FILE Ibolya, MÁTYUS János, ZSARGÓ Eszter, DEÁK György, AMBRUS Csaba

[Launching the Hungarian Vasculitis Registry aimed to collect information about prevalence and outcome of our patients with ANCA-associated vasculitis, and treatment protocols of the disease. The on-line data collection has been developing dynamically since its initiation five years ago, presently 278 patients’ files are available. Patients’ mean age is 58.2±14.5 years, 62% are women; their disease is associated with c-ANCA positivity in 51% and p-ANCA in 49%. At diagnosis GFR was 24.6±21.6 ml/min/1,73 m2, that time 29%, during the total follow up 39% of the registered subjects needed dialysis. Renal replacement therapy could be discontinued in 23% of them. In cases with focal histological changes, also with upper respiratory tract and skin involvement dialysis was significantly less frequently necessary, which underlines the importance of early diagnosis. In induction therapy steroid was administered for 94% of the patients, 85% of them got cyclophosphamide, 59% was treated by plasmapheresis, 11% got rituximab. Maintenance treat ment contained steroid in 80%, per os cyclophosphamide in 23%, parenteral cyclophosphamide in 22%, furthermore 40% of the patients got azathioprin, 8 subjects got mycophenolate and 6 got methotrexate. Median follow up was 30 months (IQR 6-78), during which period 20% of the patients died, 5% got kidney transplantation, and 5% were lost to follow up. Median survival was 14.8 years, five years survival was 85%, and ten years survival was 70%. Long term survival in patients with c-ANCA vasculitis seemed better comparing to p-ANCA vasculitis, but when correcting by age this difference disappeared. Predictors of death were age and dialysis dependent renal failure. Relapses developed in 27% of patients, 28% of them presented in the first year, 21% suffered it after five years of care. Collected data by the Hungarian Vasculitis Registry shows our society’s successful professional activity. Our results are comparable to the published data in the literature, yet there are several areas in our care where further improvements are warranted in order to increase our patient’s survival and quality of life.]

Lege Artis Medicinae

[SECONDARY MALIGNANCIES IN RHEUMATOID ARTHRITIS]

SZEKANECZ Éva, SZŰCS Gabriella, KISS Emese, SZABÓ Zoltán, SZÁNTÓ Sándor, TARR Tünde, SZÁNTÓ János, SZEKANECZ Zoltán

[INTRODUCTION - Survival data for rheumatoid arthritis (RA) have improved during the past years. Due to longer life expectancy, more attention has to be paid to prevention and treatment of long-term sequelae, including secondary malignancies. Incidence of malignant lymphoproliferative diseases and bronchial cancer is higher in a number of rheumatic diseases including RA. Some drugs nowadays very rarely used in RA - primarily cyclophosphamide and azathioprine - may further increase cancer risk. According to several large meta-analyses, biological therapy may also increase the risk of lymphomas, however, as these agents are used for the treatment of active, refractory arthritis, benefit may override such risks. PATIENTS AND METHODS - Altogether 516 RA patients managed at our department were assessed for the incidence and type of secondary malignancies. Although the absolute number of RA patients with a tumor was relatively small, we compared our cohort to the Health for All database and calculated standard incidence ratios (SIR). RESULTS - We identified 13 cases of malignancy (11 females and 2 males) in 516 RA patients (2.5%). In two patients, cancer developed before the onset of RA. RA patients with malignancy had an even higher female predominance (5.5 to 1) than usual. Mean age at onset of RA was 51.4 years, while age at the diagnosis of malignancy was 61.8 years. Mean duration of RA at the time of cancer diagnosis was 11.2 years. Five patients died, 4 due to the underlying malignancy. In the fifth patient, the tumor was considered cured but the patient died of amyloidosis. Among the 8 surviving patients, mean survival is 7.3 years until now, while overall survival of all 13 cancer patients is 4.7 years. Regarding types of malignancies, there were 6 cases of bronchial cancer, 2 cases of follicular thyroid cancer, and one cutaneous B cell lymphoma, one breast cancer, one gall bladder cancer, one colorectal cancer, and one pancreatic cancer. In comparison to the Health for All database, the overall SIR of all malignancies in RA was 1.12 (CI 0,91-1,33), varying between 2.2 and 70.7 among different tumor types. Only one cancer patient received cyclophosphamide therapy and some received methotrexate or anti-TNF agents. CONCLUSION - We identified 13 cases of malignancy among our RA patients. In RA, secondary tumors including bronchial cancer and lymphomas are more common than in the general population. Adequate treatment and monitoring of these patients may help us to lower the risk of malignancies secondary to RA]

Lege Artis Medicinae

[AUTOIMMUNE DISEASES TREATED BY AUTOLOGOUS HAEMOPOIETIC STEM CELLS]

ZEHER Margit, SZEGEDI Gyula

[Autoimmune diseases are of multifactorial origin. Due to the disturbed immune tolerance, autoreactive T and B cells target self antigens, which lead to permanent organ damages. Despite of the recently introduced therapeutic protocols, the disease has a chronic course, in many cases with lethal outcome. The efficacy of stem cell therapy has been observed in animal models of autoimmune diseases and in autoimmune diseases associated with haematological disorders. Although this approach has been applied for more than 30 years, its widespread use has been delayed by the serious side effects caused by the conditioning treatments based on oncological protocols. The evaluation of the data of patients who had undergone autologous stem cell therapy revealed that the use of protocols for conditioning treatments that mostly cause lymphoablation, and also, if the procedures are carried out in specialized centres significantly reduce mortality, while the therapeutic efficacy remains optimal. Indications for autologous CD34+ stem cell therapy in patients with autoimmune diseases are internationally established and accepted. New, multicentric investigations have been launched in order to compare the efficacy of various protocols.]

Hypertension and nephrology

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Lege Artis Medicinae

[Substitution of drugs with narrow therapeutic window in transplant immunology]

LANGER Róbert, TÖRÖK Szilárd

[Because of the economic crisis affecting the health care system, the Hungarian government have envisaged a number of measures. In Hungary, the system of reference support or fixing is an excellent cost-saving tool in the financing of drugs that have a similar mechanism of effect or contain the same molecule. However, in case of certain patient groups and of “critical drugs”, it is to be feared that an inadequate agent might actually bring loss rather than benefit. In this paper, we would like to draw attention to the fact that switching the original microemulsion cyclosporin to generic, no-microemulsion preparations might pose a direct risk for the safety of the transplanted organ and the transplanted patient.]