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Unlabelled: Systemic lupus erythematosus is a chronic autoimmune disorder which affects women with child bearing potential., Aim: The aim of this study was to investigate the successful pregnancies in patients with lupus in the past 10 years. Women were followed up at the 3rd Department of Internal Medicine, University of Debrecen., Results: During this investigated period, 26 patients became pregnant. Seven patients had a positive history for lupus before the pregnancy. A total of 29 children were born. The mean gestational age was 35 weeks. The average birth weight was 2415 grams. Toxemic pregnancy was the most common complication found in 9 patients. Lupus nephritis activity occurred in 2 patients, and 1 of them had it for the first time during the course of her disease., Conclusions: In the past years, the number of pregnancies in patients with lupus has been increasing. Due to proper patient care and education, the outcome is more favourable.

Evolution of immunopathological diseases is usually slow and progressive. Non-differentiated collagen disease (NDC) or the term "undifferentiated connective tissue disease" (UCTD) represents a stage of disease where clinical symptoms and serological abnormalities suggest autoimmune disease, but they are not sufficient to fulfill the diagnostic criteria of any well-established connective tissue disease (CTD) such as systemic lupus erythematosus (SLE), Sjögren's syndrome, mixed connective tissue disease (MCTD), systemic sclerosis (SSc), polymyositis/ dermatomyositis (PM/DM) or rheumatoid arthritis (RA). 30-40 percent of patients presenting undifferentiated profile develops and reaches the stage of a well defined systemic autoimmune disease during five years follow up, while 60 percent remains in an undifferentiated stage.In the stage of NDC, immunoregulatory abnormalities and endothelial dysfunction are present. In conclusion, NDC represents a dynamic state, and it is important to recognize the possibility of a progression to a definite systemic autoimmune disease.

Unlabelled: High dose chemotherapy followed by autologous stem cell support is a promising therapeutical approach in the treatment of severe refractory multisystem autoimmune diseases. The aim of this study was to perform the authors' first experiences in this field., Results: Between August 2006 and November 2007 autologous stem cell transplantation was performed for seven patients: two of them had systemic lupus erythematosus, four of them had rheumatoid arthritis and one of them had systemic sclerosis. Cyclophosphamide plus colony stimulating factor were administered to mobilize stem cells. The conditioning protocol included high dose cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (9 mg/kg). The re-infused stem cells were successfully engrafted by all patients. One of the lupus patients died on the 46th day due to a lethal cytomegalovirus infection, but the rest of them had no severe complications. Complete remission of their diseases and significant improvement in their quality of life were observed during a mean follow-up period of 10 months., Conclusions: Autologous stem cell therapy can be effectively administered in special cases of severe autoimmune disorders.

Several disease susceptibility genes and environmental factors are implicated in the development of autoimmune diseases. Recent investigations help us to gain more and more deep insight into the pathomechanism of diseases with autoimmune pathomechanism. Rare monogenic diseases, caused by mutations of certain key susceptibility genes, animal models of autoimmune diseases as well as SNP- and microarray investigations contribute to our better understanding of autoimmune diseases. There are still numerous problematic questions related to autoimmunity. Current research in genomics might possibly provide us a basis for preventive medicine in the case of autoimmune diseases.

In autoimmune diseases the immune system attacks self antigen(s). There are more then 80 autoimmune diseases occurring in 5-6% of the population. Autoimmune diseases can be classified as systemic or organ-specific, although the basic problem with this categorization is not based on causative pathogenic factors. The diseases are diagnosed based on safe international consensus criteria. Yet, by using these criteria we miss early forms of the diseases. We follow-up the course of the disease by histological and laboratory parameters, but we miss those biomarkers, which reflect the "disease of the immune system" itself. The number of autoimmune diseases is raising, more and more diseases turn out to have autoimmune pathogenesis in the background. The better understanding of the pathogenetic background helps to divide clinical and immunological phenotypes of the disease entities, which have important diagnostic and therapeutical consequences.

Background: Systemic lupus erythematosus is a chronic autoimmune disease with multiple organ involvements. Dup to earlier diagnosis and more effective therapeutic possibilities the survival in lupus has improved significantly in recent decades, however, critical situations may develop., Objectives: In the present work the authors aimed to summarise critical complications of lupus requiring urgent therapeutic modification, hospitalisation, sometimes at intensive care units., Results: As a systemic autoimmune disorder lupus may involve all vital organs of the human body and as such, it may result in heart failure, respiratory and renal insufficiency, and severe, life-threatening central nervous system complications. These can develop within a short period due to an acute flare, but also as the consequence of chronic progression. Infections, pregnancy, withdrawal of therapy, physical and psychological stress may provoke the worsening of the disease. However, critical situations can be the consequence not only directly of lupus, but due to side-effects of therapy, associating disorders and co-incidence with other severe diseases., Conclusions: Lupus may cause several critical situations that require urgent intervention and/or hospitalisation. The recognition and the solution of these severe lupus crises is a complex, multidisciplinary challenge that should be organised by competent, well-prepared immunologic centres.

Introduction: Chronic organ damages and complications have become one of the major problems concerning morbidity and mortality in systemic lupus erythematosus., Aims: Present study was to examine the frequencies and types of malignancies in a lupus population followed regularly in our department, and to find correlation between cancer-associated mortality and the use of immune suppressants., Methods and Results: Authors analysed data 860 lupus patients from 1965 till the end of 2004. During study period 164 patients died, 18 of whom from cancer. The frequency of cancer-associated mortality was 11% that was 2% of the total lupus population. Mortality has increased within 10-year periods reaching the maximum between 2001-2004 (8/24, 33%). Age of the 37 patients affected by malignancy was 47.7 (20-73) years. Cancers appeared 13.4 (1-45) years after the diagnosis of lupus. Breast cancer occurred most frequently (n=11) followed by gastro-intestinal malignancies (n=9), then cervix cancer and different hematologic malignancies (5-5 cases), bronchial cancer (n=4) and skin, ovarian and vesical cancers (1-1-1 cases). Relative risk of non-Hodgkin lymphoma and cervix cancer increased significantly as compared to those of the Hungarian general female population. Before the cancer developed 62.2% of patients received azathioprine and/or cyclophosphamide., Conclusion: Present results describe and analyse for the first time the association between lupus and malignant disorders in a Hungarian population calling the attention for the increased risk for the development of cancers and the importance of regular screening and extended examinations in SLE patients.

Introduction: Systemic lupus erythematosus and Sjögren's syndrome are multisystemic autoimmune diseases which can be associated to each other., Objective: To investigate if there are any distinct clinical, laboratory or serologic features due to the association of the two diseases that can influence the follow up of these patients., Patients and Methods: The authors proved the association of these two autoimmune diseases in 56 patients, and these patients' clinical, laboratory and immunoserologic alterations. 50 patients with Sjögren's syndrome and 50 patients with systemic lupus erythematosus were used as control groups., Results: Compared with Sjögren's syndrome alone, in the cases of the association of the diseases, rheumatoid factor was present less frequently, Ro/SS-A, La/SS-B and DNA antibodies were present more frequently, such as antiphospholipid autoantibodies and antiphospholipid syndrome. Anaemia, leukopenia and lymphopenia were detected more often and the patients were younger than in Sjögren's syndrome. Also, affection of the lung, kidney, skin, central nervous system and serous membranes are more common. The group with systemic lupus erythematosus differs in being older, having thyroiditis, Ro/SS-A, La/SS-B and DNA more frequently., Conclusion: Definitive clinical, laboratory and serological features make the difference between the association of the two diseases and the diseases observed alone.

Introduction: Cyclosporin A is a peptide composed of 11 amino acids. Its immune suppressive effect is attributed to the suppression of proliferation of T lymphocytes. Recently, besides immune suppression after organ transplantation it is used in the treatment of autoimmune disorders, such as systemic lupus erythematosus., Aims: In the present work authors examined the frequency, effectiveness and safety of cyclosporin A in patients with systemic lupus erythematosus, regularly followed at the above mentioned department., Results: Of the 450 lupus patients one male and 21 females received cyclosporin A for 12.4 months (3-96). Before cyclosporin A administration 16 patients received combined immune suppressive therapy; 68.2% azathioprine, 27.3% chloroquine, 18.2% methotrexate, while 3 patients were treated with steroid alone. High autoantibody titres clinical activity and the need for reduction of steroid dose were the mean indications. Furthermore, cyclosporin A was started because of leukopenia in 45.5%, polyarthritis in 36.4% or both in 27.3% of patients. Four patients started cyclosporin A to control skin eruptions. Thrombocytopenia, autoimmune hemolysis, Evans' syndrome and pancytopenia indicated this therapy in one patient for each. Clinical effectiveness was indicated by the reduction of mean daily methylprednisolone dose from 25.1 mg to 8.36 mg and also by the reduction of the disease activity index (SLE-DAI) from 9.47 to 2.47 within the first half year of the treatment. Therapy was well-tolerated. Only 3 patients observed hypertrichosis. Cyclosporin A was stopped in 3 cases due to infection and in 1 patient due to bad compliance., Conclusion: Present results suggest that cyclosporin A is an effective and safe treatment also in a certain group of lupus patients, especially with joint, skin and hematologic complications. Further long-term follow-up is required to evaluate late side-effects.

Introduction: The authors analyzed the incidence of interstitial lung disease in mixed connective tissue disease. They were seeking an answer to the following problems: the nature of the pathological course of mixed connective tissue disease complicated by and the therapy to be used in interstitial lung disease., Patients and Methods: 179 patients were followed up during a period of 15.9 +/- 6.1 years. Interstitial lung disease was diagnosed using high resolution computed tomography. The diagnosis of interstitial lung disease was not obvious in 5 patients thus open lung biopsy was performed, which confirmed common interstitial pneumonitis. The patients were followed-up, and the data of computed tomography and respiratory function tests were detected 6 months, and then 4 years after the acute lung disease complicated by mixed connective tissue disease., Results: Out of the 179 mixed connective tissue disease patients 96 (53.6%) had interstitial lung disease. The onset of interstitial lung disease was the most frequent in the 2-4 years of the disease. Four years after the first appearance of interstitial lung disease severe fibrosis was diagnosed in 24 patients (25%). A honey comb formation in the lung developed only in one patient. For the treatment of interstitial lung disease, corticosteroid treatment had to be combined with cyclophosphamide in 51 cases. In 4 patients (24%), pulmonary arterial hypertension evolved 2-4 years following interstitial lung disease. The high pulmonary arterial pressure decreased using pulsed corticosteroid treatment, cyclophosphamide, prostacyclin analogue, anticoagulants therapy and the 4 patients stay alive. The pulmonary arterial hypertension was caused by obliterative vasculopathy., Conclusion: Pulmonary involvement is found in more than half of the patients with mixed connective tissue disease. Early diagnosis of interstitial lung disease is possible by computed tomography. Interstitial lung disease can be treated by the combination of corticosteroids and cyclophosphamide. The authors were the first to detect the coexistence of interstitial lung disease and pulmonary arterial hypertension in mixed connective tissue disease. Subsequent respiratory alterations in these patient necessitate regular patient follow up.

Introduction: Immune-inflammatory processes play important role in the pathogenesis of atherosclerosis. Therefore, increasing attention is focused on rheumatic diseases with chronic inflammation, such as systemic lupus erythematosus. Besides direct influences, inflammation may modify the development of atherosclerosis by other mechanisms., Aims: To examine paraaoxonase activity and lipid profile in lupus patients., Methods: Authors entered 37 definitive lupus patients and 30 age- and sex-matched normal controls into the present study. Patients' age was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, disease activity index 2.8 +/- 3.4. Lipid parameters (total cholesterol, LDL-C, HDL-C, Apo-AI and ApoB) were determined by an autoanalyser, paraoxonase and arylesterase activities were measured spectrophotometrically. Phenotypic distribution of the enzyme was determined by dual substrate method. Anti-oxLDL was measured by ELISA method, CRP by automatised immunoassay. Statistical analysis was performed by SPSS program., Results: Despite of long disease duration and low inflammatory activity authors found significantly (p < 0.001) decreased paraoxonase activity (121.9 +/- 65.9 U/mL) (p < 0.001) in lupus as compared to control (188.1 +/- 78.9 U/mL), which correlated with the presence of atherothrombotic complications (p = 0.009). High activity BB phenotype did not occur in lupus. Lipid parameters and arylesterase activity were within normal range in both groups. No significant correlation was found between paraoxonase activity and disease activity index, dose of corticosteroid therapy, CRP and anti-oxLDL level. Arylesterase activity did not differ in lupus and control groups., Conclusions: Present results suggest that other mechanisms, e.g. antibodies, genetic factors, alteration in the distribution of HDL-subfractions or ensyme abnormalities in HDL remodelling may stand at the background of reduced paraoxonase activity in lupus.

Aim: Various case presentations in the literature discussed that frequent watery diarrheas introduce the clinical picture of microscopic colitis and intermittent or continuous diarrhea can remain. On the other hand, numerous cases never suffered from episodes of diarrhea but suffered from chronic constipation definitely. The authors present their first observations in Hungary., Methods: A cohort of patients with independently confirmed typical histopathological changes was investigated. 53 patients with histologically proved MC (46 with CC, 7 with LC) were included. The existence of diarrhea or constipation and the co-existence of autoimmune diseases also investigated and all data were retrospectively analyzed., Results: In contrast of the literature, about half of the patients had chronic constipation and cca. 50% of MC patients had autoimmune disease and the diagnosis of autoimmune disease was always prior to MC., Conclusions: Causes of inducing and amplifying the processes of "remodelling" the gut wall are thought to be unknown, but the results are: altered structure (and function?). All useful observations of this study may enrich the practice and can help these patients.

Introduction: The most common systemic autoimmune diseases, as the rheumatoid arthritis (RA) and the systemic lupus erythematosus (SLE) are associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. The authors' aim was to determine the endothelial dysfunction and the accelerated atherosclerosis in patients with undifferentiated connective tissue disease (UCTD), in a preliminary phase of defined connective tissue diseases., Patients and Methods: Twenty-two UCTD patients and twenty age and sex-matched controls were included. Using high-resolution B-mode ultrasound, the authors' measured the intima-media thickness (IMT) of the common carotid artery (CCA), and the diameter of brachial artery at rest, during reactive hyperemia, and after sublingual glyceryl trinitrate administration. The clinical, the demographical status and the serological profile of UCTD patients were also assessed., Results: There was no significant difference between the groups considered to the traditional risk factors. The endothelium dependent vasodilatation was significantly impaired in UCTD patients as compared to the controls (5.3 +/- 3.03% vs. 8.85 +/- 4.02%, P < 0.002). The authors' have not found significant difference between the two groups either at the endothelium independent vasodilatation or at the CCA-IMT. CCA-IMT correlated significantly with the age (R = 0.819, p < 0.001) and with the anti-DNA antibody levels (R = 0.563, P < 0.008)., Conclusions: The endothelium-dependent vasodilatation of patients with UCTD is reduced before development of a defined connective tissue disease and the potential anti-atherogenic treatment. The endothelium dependent vasodilatation is a more sensitive method to determine an early atherosclerotic process. The authors' found moderate correlation between the CCA-IMT and the anti-DNA antibody levels.

The number of patients suffering from autoimmune diseases is increasing and the prognosis of the patients is improving. The article gives an overview of the present status of immunomodulatory therapies. The author deals with the non-specific and the selective forms of immunosuppression. He gives a short summary about biological treatments, the induction of tolerability and about anti-cytokine therapies, In this review the modern treatment strategies of rheumatoid arthritis are also discussed, among them the early, the combined, the antigen-specific and the stem cell treatment modalities are detailed. It is emphasised that the individual differences are important to take into consideration in the treatment of autoimmune diseases.

Introduction: Antiphospholipid syndrome is a multi-organ autoimmune disorder, characterized by arterial and venous thrombotic events, and a well-defined group of recurrent foetal wasteage due to pathologic antibodies against phospholipids and protein co-factors. Antiphospholipid antibodies can be formed in primary antiphospholipid syndrome, but also in other conditions, most often in systemic lupus erythematosus. This may modify the outcome of lupus increasing the risk for thrombotic complications. Less is known about the outcome in primary antiphospholipid syndrome, whether it may precede the development of systemic lupus., Aims: Authors hereby describe the case of four patients with primary antiphospholipid syndrome in whom the disease progressed to systemic lupus erythematosus., Results: Lupus followed the primary antiphospholipid syndrome within around a three-year period. It was indicated by the appearance of different antinuclear autoantibodies and clinical complications, such as polyarthritis, nephritis and hematologic disturbances. All of the patients presented cerebrovascular accident as the thrombotic manifestation. All but one, were around forty years old, and had a milder form of lupus. Symptoms of the antiphospholipid syndrome determined the outcome. On the other hand, a typical lupus developed in the youngest patient., Conclusions: According to present cases antiphospholipid syndrome may be considered as the initiative phase of SLE, but APS being a separate entity also may associate to lupus. Present observations indicate the importance of follow-up the patients with APS by immunologic respect. Future prospective, multi-centre studies with larger number of cases are needed to provide further evidence on the fact that patients with APS may acquire other autoimmune disorder.

Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.

Reactive macrophage activation syndrome or haemophagocytic lymphohistiocytosis is a life-threatening immunoregulatory disorder characterized by the activation of the mononuclear phagocytic system with prominent haemophagocytosis particularly involving the bone marrow, reticuloendothelial system and central nervous system. It frequently occurs in children as a familial autosomal recessive disorder and it has been reportedly associated with infections, underlying hematopoetic malignancies or autoimmune disorders. It has been suggested that central to the pathogenesis of this disorder is uncontrolled T-cell activation which results in the excessive secretion of cytokines. The clinical and laboratory findings are dramatic, at presentation with persistent fever, hepatosplenomegaly, profound depression of three blood cell lines, elevated serum liver enzyme values, coagulopathy and abundant haemophagocytosis can be visualized in bone marrow. Most of the described clinical findings could be explained by the oversecretion of proinflammatory cytokines and the presence of histiocytic infiltrates. In general, immunosuppressive therapy, cytotoxic chemotherapy with immunomodulatory agents will induce remissions in a substantial percentage of patients, whereas others require allogenic bone marrow transplantation.

Authors report the case of a pregnant woman with antiphospholipid syndrome associated with HELLP syndrome. Pregnancy was terminated because of severe preeclampsia. However the patient's condition worsened. New symptoms of antiphospholipid syndrome developed (deep vein thrombosis, ischaemic optic lesion) and ARDS, therefore respiratory therapy was introduced. Plasmaphereses were performed concomitantly with high-dose intravenous immunoglobulin, glucocorticoid, cyclophosphamide and anticoagulant therapy. She responded to the therapy well, and eventually recovered completely. There are only a few case reports about pregnancies complicated with the association of antiphospholipid syndrome and HELLP syndrome. To authors' best knowledge, this is the first Hungarian report about this rare and curious association and it's successful treatment.

Unlabelled: The authors examined the presence of antiphospholipid antibodies in acute coronary syndrome. As their results show the frequency of antibodies against B2-glycoprotein I is significantly higher (14.4%) than the presence of these antibodies in a healthy control group (2%). Occurrence of antibodies against B2-glycoprotein I is much more higher than the occurrence of IgG- or IgM type antibodies against cardiolipin or lupus anticoagulant., Conclusions: The authors emphasize the possible role of anti-B2-glycoprotein I antibodies in thrombotic process of acute coronary syndrome. The previous ischaemic stroke was significantly more frequent in those patients medical history in whose serums antibodies against B2-glycoprotein I were present, so the presence of this thrombophil factor in acute coronary syndrome points out the importance of secunder antithrombotic prevention.

Introduction: 179 patients with mixed connective tissue disease (MCTD) were follow-up, and the cause of death was analyzed in 12 died patients., Patients and Methods: The survival of 179 patients with MCTD was evaluated by using Kaplan-Meier's method. Clinically and immunological data of the patients were analyzed between 1 and 25 years follow-up period (mean: 13.1 +/- 5.5 years)., Results: The five-year survival rate was 96.4%, 10-year survival rate was 93.9%, and the 15-year survival rate was 89.6%. The cause of death was pulmonary hypertension in 5 patients, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in 3 cases, infection in 3 cases (hepatitis C virus induced hepatic coma in 2 patients, Staphylococcus sepsis in one patient), and on one patient myocarditis. The pulmonary hypertension was the most serious prognostic factor., Conclusion: In patients with MCTD the pulmonary hypertension with endothelial cells proliferation and microangiopathy developed very quickly, and there was progressive and therapy resistant statement. The secondary virus and bacterial infections may develop in the patients who were followed-up the long term period. Their survival rate was better than the data in the literature. This fact may cause genetic-demographic factors, and the sequential follow-up of the patients.

Introduction: Evolution of immunopathological diseases is usually slow and progressive. The term the undifferentiated connective tissue disease (UCTD) is used to describe the phase preceding a defined connective tissue diseases (CTD)., Aims: The objective of this work was evaluate the clinical and serological profile of patients with UCTD, who had been followed between 1994-1999. They have investigated the frequency and the type the developed autoimmune diseases from UCTD., Patients: A total of 578 UCTD patients were evaluated., Results: In 143/578 patients (24.7%) with the UCTD differentiated to systemic connective tissue diseases (28 systemic lupus erythematosus, 26 mixed connective tissue disease, 19 progressive systemic sclerosis, 3 polymyositis/dermatomyositis, 45 Sjögren syndrome, and 22 systemic vasculitis). 86.7 percent (124/143) of the systemic connective disease developed in first two years of UCTD. The condition of 435/578 (75.2%) remained UCTD after 5 years, among them in 82 patients with UCTD was regression of the symptoms. The presence of the fever and anti-DNS antibodies correlated with SLE (P = 0.0104, Fisher exact test), arthritis/arthralgia and anti-RNP antibodies with MCTD (P = 0.0302), Raynaud phenomenon and ANA positivity with PSS (P = 0.0144), xerostomia/xerophtalmia and anti-SSA/SSB antibodies with Sjögren syndromes (P = 0.0144)., Conclusions: The UCTD in our patients seem to represents an dynamic phase, one part of the patients show progression to definite connective tissue diseases, one part show regression, and on part of the patients stay in UCTD phase.

Aims of the Study: In the 214 polymyositis / dermatomyositis patients in our department we studied the association of polymyositis / dermatomyositis with malignant tumors, the clinical specificities and therapeutic response changes in these cases., Methods: Retrospective analysis of the data available since 1985 of the patients treated at the DEOEC 3(rd) Department of Internal Medicine., Results: From 60 patients with dermatomyositis 9 were diagnosed with neoplasia. In 5 patients simultaneously with the dermatomyositis diagnosis, in the other 4 patients 2-2-3-7 years after the onset of dermatomyositis. In the 154 patients with polymyositis we did not observe development of tumors., Conclusions: Neoplasm was observed in 15% of patients with dermatomyositis. The patients presented with serious skin involvement which did not respond well to the dermatomyositis treatment. The patients in whom tumors developed simultaneously with the dermatomyositis required more aggressive treatment. After the therapy of the tumor (surgery, radiotherapy), the skin and muscle symptoms responded better to the immunosuppressive therapy.

Inflammatory Bowel Diseases are a group of diseases with chronic inflammation of the gastrointestinal tract, but without proven etiology. Immunologic, environmental, infective and genetic factors equally can play role in their development. Antibodies to an oligomannose epitope of the Saccharomyces cerevisiae demonstrated in 60-70% of the patients with Crohn's disease. The origin and the clinicopathological role are not clarified. It is important that there are no surveys with patients suffering in gluten sensitive enteropathy in the literature. As there are no ASCA survey in Hungary, the aim of this study was to determine the prevalence of the ASCA. The authors examined at their patients the ASCA's occurrence and compared with the clinical picture of the Crohn's disease. The results supported the theory that ASCA positivity correlates with small intestines' Crohn's disease and in these cases both the IgG and IgA type antibodies proved. The antibodies in the sera at the analyzed ASCA positive cases prove a systemic immune response against Saccharomyces cerevisiae and the authors suggest the end of the oral tolerance against the yeast's antigens. The diet restriction (elemental diet, total parenteral nutrition, and fecal diversion) may ameliorate the status of the patients with Crohn's disease. It is speculated that the yeast-free diet as a part of the therapy for the ASCA positive patients can be reasonable: moreover the permanent "forbidding" of the yeast can be an acceptable alternative in case of getting well.

Systemic lupus erythematosus is characterised by the presence of antinuclear autoantibodies (ANA). Native DNA, histone proteins and small nuclear ribonucleoproteins (snRNP) are the main targets of these ANA-s, but some of them may derive against the entire chromatin, which is composed of the listed elements, and also against its fundamental unit, that is nucleosome. Authors investigated at the first time the frequency and the concentration of anti-nucleosome antibodies in a group of 107 consecutively selected Hungarian lupus patients. They calculated correlation between these parameters and the activity as well as organ--mainly kidney--manifestations of the disease. The frequencies of positive anti-nucleosome, anti-dsDNA and anti-histone antibodies were 39.2, 28.0 and 47.6%, respectively. All the three autoantibodies were present more frequently in cases with lupus nephritis, and this correlation was significant by statistical respect. Also a positive correlation was found between the concentration of these autoantibodies and activity of the diseases (SLE-DAI). Results suggest that long disease duration (mean 8.5 year) and consequently low disease activity (mean DAI: 3.28) may stand at the background of the relatively low occurrence of the measured ANA-s. Besides anti-dsDNA, the determination of anti-nucleosome and anti-histone antibodies can be useful in the diagnosis and monitoring of SLE. Authors discuss the possible role of anti-nucleosome autoantibodies in the pathogenesis of lupus nephritis.

PURPOSE: Study of thyroid function in Hodgkin's disease patients in complete remission. PATIENTS AND METHODS: We examined the thyroid function of 160 Hodgkin's disease patients in complete remission for at least one year, and determined the values of supersensitive thyroid stimulating hormone (sTSH), free T4 (fT4), free T3 (fT3) hormones. RESULTS: Normal values were observed in 117 patients, subclinical change (only elevated sTSH) in 28 patients, clinical hypothyroidism in 14 patients (also low fT4 and/or fT3), hyperthyroidism (Basedow's disease) in one patient. Hypothyroidism was one and a half times more frequent in females than in males. The normal and low thyroid function group did not differ from each other in mean age, histological subtypes, disease stage, general symptoms, and whether lymphangiography was performed. Hypothyroidism was more frequent in patients who had undergone mantle or neck radiotherapy. The onset of thyroid gland underfunction was more pronounced from six years after neck radiotherapy. The thyroid disease could be controlled using a daily dose of 25-225 mg levothyroxin. CONCLUSIONS: During the care of Hodgkin's disease patients routine examination of the thyroid function is important for the early recognition and prevention of treatment related late complications. On the other hand in treatment planning phase more attention should be paid to thyroid gland protection when neck radiotherapy is used.

The authors detected lupus anticoagulant and/or anticardiolipin antibodies in 1519 patients' blood samples between 1986-1999 in 3rd Department of Internal Medicine of Medical School of Debrecen. Examining only the proved thrombotic events and fetal losses as symptoms of antiphospholipid syndrome 218 patients had suffered from this syndrome. Secunder antiphospholipid syndrome was the diagnosis in case of 420 patients, the most common in Systemic Lupus Erythematosus (288 patients). In 704 antiphospholipid antibody positivity cases the diagnosis of antiphospholipid syndrome was not fulfilled. Analysing the antibodies profile of primary and secondary antiphospholipid syndrome in SLE, IgG type anticardiolipin antibody positivity was significantly higher in blood samples of SLE patients (82 patients, p < 0.01). Among thrombotic manifestations of antiphospholipid syndrome cerebrovascular thrombosis were significantly higher in patients suffering from SLE (128 patients, p < 0.04), while the occurrence of venous thrombosis, thrombosis of coronary, carotic, aorta and peripheral arteries and recurrent abortions was not significantly different in case of primary and secondary antiphospholipid syndrome. Lupus anticoagulant positivity means higher risk for venous thrombosis (94 patients, p < 0.0001), but anticardiolipin antibody positivity associated with a higher risk for thrombosis of coronary, carotic, aorta and peripheral arteries (59 patients, p < 0.00006). Comparing IgG- and IgM-type anticardiolipin antibody positivity the authors found significantly higher cerebrovascular thrombosis events in IgG-anticardiolipin group (p < 0.004). Sneddon syndrome were detected in 17 patients in the primary antiphospholipid syndrome group and in 16 cases in secundary, SLE-associated antiphospholipid syndrome group. One of the patients had died because of the Catastrophic Antiphospholipid Syndrome.

In this work, the effect of eradication of Helicobacter pylori on complaints and symptoms of infected, primary Raynaud's syndrome patients was studied. Altogether 92 Helicobacter pylori positive patients with gastric complaints and with primary Raynaud's syndrome received eradication therapy. In this prospective study, before and after the eradication the severity and frequency of the complaints and symptoms of the patients were recorded. The eradication was performable in 89 patients; in 75 cases the eradication was successful. In the eradicated patients frequency and duration of Raynaud attacks were improved related to those of the not eradicated group. These results might suggest a potential etiopathogenetical role of Helicobacter pylori infection in the pathogenesis of the primary Raynaud's syndrome.

The minimal residual disease is important in several malignant diseases, such as in hematopoietic malignancies (e.g. in follicular lymphoma) or in solid tumors, due to the presence of a tumor burden following a treatment of these diseases. In case of t(14;18) chromosome translocation, which characterizes most of the follicular lymphomas, the bcl-2 gene translocates to the joining region of the immunoglobulin heavy chain of chromosome 14. The expression of bcl-2 gene alters due to the translocation, and this change results in the inhibition of cellular apoptotic processes, and in turn these series of events may finally lead to the development of lymphoma. It is inevitable to learn the results of radio- and/or chemotherapy, i.e. whether the translocation-bearing cells disappeared from the lymphocytes of peripheral blood as well as from that of bone marrow, or we have to take into account the minimal residual disease. Using nested-PCR one can detect the translocation in 1 out of 10(5) cells, this way the results of the treatments can be controlled: one can establish the emergence of remissions; and the relapses could also be detected earlier than by using conventional diagnostic methods. Our experience, yielded by the follow up studies of follicular lymphoma patients, shows that the results of PCR detection correlate excellently with the conclusions of other diagnostic techniques. Nevertheless, the t(14;18) translocation-bearing cells can also be detected in peripheral lymphocytes of healthy donors as well as in that of different diseases of other types than lymphoma, but not in bone marrow. Therefore we emphasize the importance of the translocation-detection in the bone marrow of the patients of follicular lymphoma. More and more advanced techniques have made it possible to detect the minimal residual disease, this way it will be easier to diagnose and to predict the outcome of different malignant diseases.

Stem cell transplantation is a new possibility to treat autoimmune diseases. Animal data and early clinical trials highlight that rebuilding the completely destroyed immune system leads to the remission of several immune-mediated diseases. The aim of this review was to summarize experimental and clinical results as well as recommendations for the protocol of stem cell transplantation and its complications.

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe a case of a female patients with catastrophic antiphospholipid syndrome associated with gastric cancer. This may be the first case of such association in the literature. Authors also discuss the possible pathomechanism of this disorder, as well as the available therapeutic approaches.

The adult onset Still disease is a systemic disease of an unknown etiology. As a separate entity, it was described firstly in 1971. The diagnosis is problematic and based upon special criteria. In this study, we present the cases of two patients with adult onset Still's disease, causing several serious differential-diagnostic problems. In the beginning of the disease a high, remittent-intermittent fever was present which reacted well to salycilates. Almost simultaneously, a characteristic, confluent, no itching rash appeared on the trunk and limbs. Pain of little joints of the hands was an early symptom of the disease in both of the cases. Before the final diagnosis, the possibility of any infectious diseases, haematologic malignancies or other autoimmune disease had to be excluded. The aim of this work was to show an overall, up-to-date picture of the disease based on two typical cases.

Otosclerosis is a multifactorial disease. A number of theories on the pathogenesis of this disease have been established in the last decades. It is important to review recent data on the pathogenesis of otosclerosis as it is a severe inner ear disease leading to deafness in the majority of cases. Surgical therapy is not always successful or feasible. In this review, authors describe the most relevant genetic, infective, immunological, inflammatory factors, as well as the impaired bone metabolism underlying the pathogenesis of otosclerosis. It is likely that genetic predisposition associated with morbilli infection may lead to bone resorption in the stapes and cochlea followed by spongiosis, fibrosis and sclerosis. It has been suggested that immunological mechanisms play a central role in the development of the disease. Some authors consider otosclerosis as autoimmune disorder based on the presence of several autoantibodies. Apart from classical diagnostic methods, such as audiometry and X-ray, novel radiological techniques including CT, MRI or radionuclide scan are helpful in the localization of otosclerosis. As surgery is sometimes contraindicated or unsuccessful, drug therapy including the use of anti-osteoporotic on non-steroidal antiinflammatory drugs may be administered, especially in the early phase of the disease.

The authors have in their care 286 Raynoud syndrome patients. They present their experience in the study of the microcirculation and the treatment of these patients. In 81% (232 patients, 196 women and 36 men) of the cases they did not find any underlying diseases. In the group of the patients with secondary Raynaud's syndrome (35 women and 19 men) underlying diseases, possibly leading to microcirculatory disturbances, could be identified. In the primary Raynaud's syndrome group the main capillary diameter measured by capillary microscopy was 15 +/- 4 micron. In patients with progressive systemic sclerosis the mean diameter was 43 +/- 9 micron. In the group of women with primary Raynaud's syndrome the authors performed laser Doppler measurements of the nailfold microcirculation. During the reactive hyperaemia test basal values (18.2 +/- 6.2 Perfusin Units, P. U.) and reactive hyperaemia values (a mean of 180% growth compared to the basal values) were similar to that perfusion values referred in the literature. In the progressive systemic sclerosis group the basal flow (9.3 +/- 3.3 P. U.) and the reactive hyperaemia (a mean of 20% increase compared to basal values) were significantly lower. Concerning the fact that the progression of Raynaud's syndrome into systemic autoimmune disease--mainly to progressive systemic sclerosis may be predicted, it is important to follow up carefully all patients with Raynaud's syndrome.

The authors have determined the prevalence of antibodies of cofactor dependent anticardiolipin and beta 2-glycoprotein I and lupus anticoagulant and the frequency of false positive VDRL test in systemic lupus erythematosus. The aim of this retrospective study was to assess the presence of these antibodies and symptoms of antiphospholipid syndrome. The serum samples were examined by modified ELISA method for detecting of cofactor dependent anticardiolipin. The antibodies to beta 2-glycoprotein I were examined by ELISA. The lupus anticoagulant and VDRL test were performed by routine laboratory method. The authors have found that 19 of 58 patients with systemic lupus erythematosus had cofactor dependent anticardiolipin, 10 patients had antibodies to beta 2-glycoprotein I and 4 patients had positive VDRL test. 5 of 34 plasma samples were lupus anticoagulant positive. 19 patients with systemic lupus erythematosus had 14 neuropsychiatric disorders, 9 cardiovascular diseases, 7 thrombocytopenia, 6 histories of recurrent abortion and fetal loss, 5 livedo reticularis and 3 thromboembolic events in all of them had detected antibodies to cofactor dependent anticardiolipin, while these complications were diagnosed in 39 anticardiolipin negative patients much more rarely. The results of this retrospective study suggest that significant association exists between the presence of cofactor dependent anticardiolipin and symptoms of antiphospholipid syndrome in systemic lupus erythematosus.

The ingress of inflammatory leukocytes into the synovium is important for the pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia associated with this disease. In this review authors discuss the role of a number of inflammatory mediators, such as cytokines, chemokines and growth factors in these processes. The outcome of arthritis is highly dependent on the imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokine-related research also has important clinical relevance. Many of these proteins are detectable in the serum of rheumatoid patients and may eventually serve as useful laboratory markers of disease activity. Antirheumatic therapy currently used for the treatment of rheumatoid arthritis is often limited. Therefore, we need to consider alternative therapeutic regimens, such as the inhibition of cytokines and other soluble mediators, in order to prevent severe joint destruction. While there are many complex interactions involving cytokine networks and cascades in the arthritic joint, there are promising attempts to eliminate a single cytokine in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully, the study of cytokines and their networks will lead to specific immunomodulatory therapies that will benefit rheumatoid patients by preventing joint destruction.

The authors survey the literature of Whipple's disease and present two of their patients. They assure that Whipple's disease in either associated with or is a result of an immunopathological clinical picture, but it is else possible that assumed pathogen, the Tropheryma whippleii itself alters the immune system. In the case of their female patient with active disease they showed the rearrangement of the bcl-2 gene [t(14; 18)] in her peripheral blood lymphocytes, while in their male patient in remission this could not be proved. During the observation, in their female patient insulin dependent diabetes mellitus (IDDM) developed. In connection with these cases, the authors draw the attention to the varied symptoms which are characteristic of autoimmune disease, and to the immunoserological laboratory differences in particular the rearrangement of the bcl-2 gene.

Angiogenesis, the production of new blood vessels, plays an important role in a number of physiological and pathological processes, such as development, tissue repair, atherosclerosis, ischemic heart diseases, inflammation and tumor progression. A number of mediators including cytokines, heparin-dependent and -independent growth factors, proteolytic enzymes, extracellular matrix components, cellular adhesion molecules and others, have been implicated in angiogenesis. Certain angiostatic cytokines, growth factor antagonists, steroids, protease inhibitors, antibiotics, antirheumatic drugs, tissue-derived inhibitors and others inhibit neovascularization. Angiogenesis research has important clinical relevance, as targeting angiogenic and angiostatic processes by using angiogenesis inhibitors, receptor antagonists, antibodies, enzyme inhibitors, tumor suppressor genes and other forms of gene therapy, may be a potential therapeutic tool in "angiogenic diseases".

Chromosome translocation of t(14;18) can be detected in most cases of centroblastic/centrocytic follicular lymphomas. They are causative factors of lymphomas but the translocation is present in different other types of diseases although the translocation does not belong to the features of these illnesses. Our present work shows the appearance of t(14;18) translocation in lymphocytes of two patients of Sjögren's syndrome, one that of Whipple disease as well as one of healthy donors' lymphocytes using polymerase chain reaction technique presented in one of our previous publication. The translocation occurred in the mbr of bcl-2 gene in all cases showed and the bcl-2 gene was coupled with the immunoglobulin heavy chain gene. These results are definitively positive concerning the fact of translocation as it has been proved by sequencing of the amplification products showed in our earlier and present paper. Because relatively high percentages of Sjögren's syndrome patients develop later on lymphoma, the early detection of the translocation could result in a more successful diagnosis as well as treatment of the disease. The question arises, however, what role the translocation plays in illnesses such as the Whipple disease or what kind of consequences can be drawn from the appearance of the t(14;18) translocation in lymphocytes of healthy donors.

The cerebral glucose metabolism in eight patients with systemic lupus erythematosus (SLE) and in five healthy controls were examined by positron emission tomography (PET) using 18-F-labeled deoxy-glucose (FDG) as tracer. One of the eight patients had no abnormality by magnetic resonance imaging (MRI), three of them had cerebral atrophy and four patients had multiple white matter hyperintensities and vascular infarcts in the striatum as assessed by MRI. With FDG-PET, inhomogeneous multifocal cerebral glucose hypometabolism was detected, more frequently in the temporal lobe of right hemisphere. The PET findings did not correlate always with the neurological symptoms. Abnormalities in brain metabolism can be detected more frequently by PET, than morphological changes by MRI, indicating the involvement of the central nervous system.

In most cases of centroblastic/centrocytic follicular lymphomas the bcl-2 proto-oncogene (18q21) is translocated to the immunoglobulin JH region of chromosome 14 (14q32). About three quarters of the translocations are concentrated on the 3' nontranslated, a few hundred basepare-long region of bcl-2, the so called major breakpoint region (mbr), the remaining 20-25% is located about 30 kilobases downstream of bcl-2 coding sequences in the minor cluster region (mcr). The majority of the immunoglobulin breakpoints can be found in JH6-4 genes. The polymerase chain reaction method can detect the translocation already in a very few number of cells (> 10(3)). This very sensitive technique makes it possible to detect the translocation in lymphoid/lymphoma of peripheral blood and bone marrow that are missed by other diagnostic methods. This way one can perform a quick, early diagnosis, examine the result of treatments as well as detect the remissions and the possible relapses right at the beginning. All the advantages of this method contribute to a more successful treatment of follicular lymphoma. This present work describes a polymerase chain reaction technique which is capable of a detection of the t(14;18) translocation in a patient of centroblastic/centrocytic lymphoma, moreover shows how this translocation disappears after 4 week of radiotherapy of the patient.

Multiplex lymphomatous polyposis is an uncommon disease characterized by polypoid accumulations of malignant lymphoid cells within the submucosa of long segments of the gastrointestinal tract. Primary gastrointestinal form of disease is referred as an extranodal variant of the entity knows as mantle zone lymphoma. Rarely, this typical lesion may appear as a secondary involvement of the alimentary tract in patients with primary nodal lymphomas. In present article, the clinical, histological features of our two cases of primary nodal lymphoma presenting with gastrointestinal symptoms and secondary involvement of the bowels are discussed. The nodal lymphomas of these patients were classified as a mantle zone and a follicle center cell origin lymphoma. The development of gastrointestinal symptoms occurred 29 and 41 months after the diagnosis. Our cases suggest that lymphomatous polyposis can manifest itself secondarily in patients with nodal lymphomas of not only the mantle cell type. The polypoid lesion might be mediated by lymphocyte homing receptors and the pattern of proliferation can be produced by more than one phenotypically different lymphoma.

The authors report a case of bilateral primary malignant lymphoma of the breast presenting during pregnancy in a 24-year-old woman. After delivery of a healthy premature infant by Caesarean section, polychemotherapy was employed. The efficacy of the treatment could not be evaluated since the patient died within a very short period of time. Autopsy and histological examination revealed infiltration of Burkitt-type lymphoma in the breast, ovary, brain, liver, kidney, adrenal gland, pancreas, stomach, bone marrow and myocardium.

The authors treated 21 advanced, pretreated Hodgkin's disease patients with CEP (CCNU, etoposide, prednimustine) polychemotherapy between March 1988 and February 1993. Complete remission was achieved in 4 patients, partial remission in 8 patients, while 9 patients were unresponsive to treatment. None of the complete responders relapsed during the follow-up period, and the median duration of remission was 24 months. The median survival for the unresponsive and partially responsive patients was less than half a year. Side-effects included gastrointestinal symptoms, myelosuppression and alopecia, but treatment-related deaths did not occur. The present data confirm the favourable impact of CEP polychemotherapy on pretreated, advanced Hodgkin's disease patients.

The authors describe the case of a female patient with a history of simultaneous abortion and deep vein thrombosis as well as moderate bleeding disturbances. Investigations revealed the presence of lupus anticoagulant while a thrombocyte "storage pool" disease was confirmed. This case demonstrates the association of these two haemostatic disturbances, and points to a possible relationship between them. Since detailed analyses failed to demonstrate the presence of antiplatelet antibodies, the authors suggest a possible damaging effect of lupus anticoagulant to the endothelium leading to thrombocyte activation.

Decreased blood cell--e.g. lymphocyte--motility is seen in a number of vascular and autoimmune diseases. Pentoxifylline (Pf) shows a well-known therapeutic effect in several vascular alterations by causing the redistribution of blood cell cytoskeleton and increased microcirculation. As most literary data on Pf concern red blood cells and granulocytes authors here investigated the effect of Pf on previously decreased lymphocyte migration and chemotaxis. Results of in vitro studies suggest that Pf enhances impaired lymphocyte motility in obliterative arteriosclerosis and systemic lupus erythematosus and thus may also be introduced in the treatment of polysystemic autoimmune diseases.