SARS-CoV-2 infection and its prevention in pediatric autoimmune diseases / SARS-CoV-2-fertozés és annak megelozése gyermekkori krónikus szisztémás autoimmun betegségekben.

Összefoglaló. A krónikus autoimmun betegségben szenvedokben a súlyos COVID-19 kialakulásának kockázata magasabb, a SARS-CoV-2-fertozés pedig a krónikus alapbetegség progressziójához, fellángolásához vezethet. A COVID-19 elkerülésének legbiztonságosabb, legköltséghatékonyabb módszere a vakcináció, illetve az emellett alkalmazott higiénés szabályok betartása, a megfelelo maszk viselése. A hiedelemmel ellentétben önmagában az autoimmun megbetegedés nem jelent oltási ellenjavallatot, sot a rizikóállapot miatt ezek a betegek az elsok között oltandók. A COVID-19 elleni vakcina alkalmazásának egyetlen egyértelmu kontraindikációja az anamnézisben szereplo súlyos allergiás reakció (anafilaxia) a vakcina valamelyik alkotórészével szemben. A betegek olthatóságát többek között befolyásolja az aktuális betegségaktivitás és az alkalmazott kezelés. Az immunizáció idejét a legbiztonságosabban a gondozó orvos tervezheti meg. Az autoimmun betegek immunizációja során észlelheto oltási reakciók és szövodmények incidenciája megegyezik az egészséges populációban is tapasztalt elofordulási gyakorisággal. Orv Hetil. 2022; 163(11): 414-423. Summary. The risk of developing severe COVID-19 is higher in patients with autoimmune diseases, and SARS-CoV-2 infection can lead to progression and exacerbation of the underlying chronic disease. The safest and most cost-effective way to avoid COVID-19 is to be vaccinated, to follow the hygiene rules and to wear an appropriate mask. Contrary to belief, autoimmune disease alone is not a contraindication to vaccination and, in fact, patients should be among the first to be vaccinated because of the risk. The only clear contraindication to the use of COVID-19 vaccine is a history of severe allergic reaction (anaphylaxis) to any of the components of the vaccine. Indication of vaccination migh be influenced by, among other things, the current disease activity and the treatment applied. The timing of immunization can be the most safely planned by the attending physician. The incidence of vaccination reactions and complications during immunization in autoimmune patients is similar to that seen in the healthy population. Orv Hetil. 2022; 163(11): 414-423.

Diagnosis and treatment of paediatric multisystem inflammatory syndrome / A gyermekkori koronavírus-fertozést követo sokszervi gyulladás diagnosztikája és kezelése.

Összefoglaló. A SARS-CoV-2-fertozés ritka gyermekkori szövodménye a sokszervi gyulladás, angol terminológiával paediatric inflammatory multisystem syndrome (PIMS). Két vagy több szerv érintettségével járó, súlyos tünetekkel induló betegségrol van szó, amelynek tünetei átfedést mutatnak a Kawasaki-betegséggel, a toxikus sokk szindrómával és a makrofágaktivációs szindrómával. A PIMS-betegek intenzív terápiás osztályon vagy intenzív terápiás háttérrel rendelkezo intézményben kezelendok, ahol biztosítottak a kardiológiai ellátás feltételei is. A szükséges immunterápia a klinikai prezentációtól függ. A jelen közleményben a szerzok a releváns nemzetközi irodalom áttekintését követoen ajánlást tesznek a PIMS diagnosztikai és terápiás algoritmusára. Orv Hetil. 2021; 162(17): 652-667. Summary. Pediatric inflammatory multisystem syndrome (PIMS) is a rare complication of SARS-CoV-2 infection in children. PIMS is a severe condition, involving two or more organ systems. The symptoms overlap with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. PIMS patients should be treated in an intensive care unit or in an institution with an intensive care background, where cardiological care is also provided. The required specific immunotherapy depends on the clinical presentation. In this paper, after reviewing the relevant international literature, the authors make a recommendation for the diagnostic and therapeutic algorithm for PIMS. Orv Hetil. 2021; 162(17): 652-667.

The Hungarian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Hungarian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 206 JIA patients (3.9% systemic, 41.3% oligoarticular, 28.2% RF-negative polyarthritis, 26.6% other categories) and 90 healthy children, were enrolled in two centres. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Hungarian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative.

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. OBJECTIVES: To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). RESULTS: In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe.

[Management of Fabry disease]. / Fabry-betegség - terápiás útmutató

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group.

Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand.

OBJECTIVE: Serum cytokines play an important role in the pathogenesis of myositis by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of the present study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with idiopathic inflammatory myopathies (IIMs) and healthy individuals. METHODS: A protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 24 circulating cytokines, including B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) of patients with IIMs and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional interrelationships among these pathological cytokines. RESULTS: Univariate analysis demonstrated that a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with IIMs relative to unaffected controls including IL-10, IL-13, IFN-α, epidermal growth factor (EGF), VEGF, fibroblast growth factor (FGF), CCL3 [macrophage inflammatory protein (MIP-1α)], CCL4 (MIP-1ß) and CCL11 (eotaxin), whereas G-CSF was significantly reduced in IIM patients. Correlational clustering was able to discriminate between, and hence sub-classify patients with IIMs. DFA identified EGF, IFN-α, VEGF, CCL3 (MIP-1α) and IL-12p40, as analytes with the strongest discriminatory power among various myositis patients and controls. CONCLUSIONS: Our findings suggest that these factors modulate myositis pathology and help to identify differences between subsets of the disease.

Myositis-specific and myositis-associated antibodies in overlap myositis in comparison to primary dermatopolymyositis: Relevance for clinical classification: retrospective study of 169 patients.

OBJECTIVE: The current study was performed in order to determine the prevalence of different myositis-specific and myositis-associated antibodies, as well as their association with clinical characteristics, disease course and response to therapy in 169 Hungarian patients with idiopathic inflammatory myopathy. METHODS: Sera of 130 primary and 39 overlap myositis including systemic sclerosis (13), rheumatoid arthritis (12), systemic lupus erythematosus (5) and Sjögren's syndrome (9) cases were analyzed. Antinuclear antibody, scleroderma-associated antibodies (anti-centromere, anti-topoisomerase I), anti-Jo-1, anti-PL-7, anti-PL-12, anti-Mi-2, anti-SRP and anti-PM-Scl, anti-Ku, anti-SS-A, anti-SS-B, anti-U1snRNP were tested. Autoantibody results were compared with clinical characteristics, disease course of overlap versus primary myositis patients, as well as with response to therapy. RESULTS: Associated connective tissue disease occurred in 23.1% of the patients. Myositis-associated antibodies were found in 8.5% of primary myositis patients, indicating that 11 additional primary myositis patients (23% vs. 29.6%) can be classified as overlap in all cohort according to the newly proposed diagnostic criteria. Polymyositis was found to be the most common myositis form in overlap myositis (87.2%), while scleroderma was the most common disease associated (33.3%). ANA was positive in 25.4% of primary and in 61.5% of overlap myositis cases. Altogether 39.6% of myositis patients (n=67) had autoantibodies, most commonly anti Jo-1 (18.3%) correlating with a polycyclic disease course. CONCLUSION: Inclusion of myositis-specific and associated antibodies into the newly proposed diagnostic criteria for inflammatory myopathies is of great importance in order to determine subclasses and to introduce adequate therapy in time.

[Fabry disease--diagnostic guideline]. / Fabry-betegség. Diagnosztikai útmutató.

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group.

Paraneoplastic myopathy.

PURPOSE OF REVIEW: It has been recognized for some time now, that compared with the normal population, patients with idiopathic inflammatory myopathies (IIM) live with an increased risk of developing malignancy. In the majority of these patients, cancer-associated myositis appears to have some paraneoplastic features. The aim of the present review is to describe new data that explain the connection between myositis and malignant diseases, as well as to highlight its value in the current management of these patients. RECENT FINDINGS: Antigen expressions and patterns shared by regenerating muscle and cancers raise questions about whether myositis cases without clinically observable cancer may represent a fully successful antitumor immune response with bystander damage to regenerating muscle. The discovery of anti-155/140 autoantibody may aid in the better diagnosis of adult IIM patients with a higher risk of malignancy. It also may help the better understanding of paraneoplastic myositis. SUMMARY: Cancer-associated myositis differs from primary myositis in many aspects. Prognosis and life-expectancy are determined by the underlying malignancy. Therefore, patient-specific examinations for detection of an underlying cancer are important in the management of patients. Recent clinical findings and new possibilities in immunoserological testing may result in the elaboration of an evidence-based recommendation for cancer screening programs in patients with IIM in the future.

Prevalence of antiphospholipid and antinuclear antibodies in children with epilepsy.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent venous thrombosis or arterial occlusive events and fetal losses associated with elevated levels of antiphospholipid antibodies (aPLs). MATERIAL/METHODS: The presence of antinuclear, anti-beta2-glycoprotein I, and anticardiolipin antibodies were investigated in 60 consecutive children with epilepsy who were followed up in a single Hungarian center. RESULTS: Almost 50% (28/60) of the patients were ANA positive. Twelve (20%) patients had moderate titer (1:160) of ANA. Anti-C1q antibody was positive in 4 cases, all of them symptom free considering renal manifestation of lupus. Interestingly, only 1 child had aCL antibody, while 6/43 patients were LAC positive. Five were also ANA positive among the LAC positive patients (4 children with moderate titer). Anti-beta2GPI antibody positivity was not detected in this cohort of patients. CONCLUSIONS: The clinical relevance of aPL tests in childhood are difficult to explain. In the present study, obviously lower total prevalence of aPLs (aCL and anti-beta2GPI) was observed in children with epilepsy than in previously reported investigations (20-30%). The higher amount of LAC-positive patients indicates that coagulation studies (LAC) should be included in the neuroimmunological assessment of suspected APS patients with epileptic disorders. The difference between the results of serological and LAC studies could be explained by the possible positivity of other, uninvestigated antibodies. The wide spectrum of detected immunological alterations highlight the importance of the participation of pediatric rheumatologists in the management of patients with idiopathic epilepsy or with secondary induced autoimmune disease due to antiepileptic medications.

Improper supplementation habits of folic acid intake by Hungarian pregnant women: improper recommendations.

BACKGROUND: Neural tube defects (NTDs) are some of the most common congenital anomalies. Proper folic acid supplementation is a dominant risk factor, which has been shown to decrease the incidence of NTDs. In Canada, the incidence of neuroblastoma has presented a considerable decrease of 60% as a result of enrichment cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of folic acid intake by pregnant women on the incidence of NTDs and neuroblastoma. METHODS: Regular folic acid intake has been recommended to pregnant women in Hungary since the eighties of the last century by health visitors eventually raking effect as an official protocol which had been released in 1997. During 2001, 2002 and 2003, folic acid intake habits of pregnant women were evaluated by health visitors, proving to be successful in collecting data from 95.06% of the pregnant women. The incidence of NTDs has been registered by the Hungarian National Centre of Epidemiology, Department of Human Genetics and Teratology. The Pediatric Cancer Registry provided the incidence of neuroblastoma in children. RESULTS: Consistent findings revealed a regular intake of supplementary folic acid products by 68.71% of the pregnant women. Out of these, 93.13% of pregnant women who were taking folic acid, started the supplementation after their 7 weeks of pregnancies, a time designated as the completion period of the development of the neural tube. The dose of folic acid supplementation was evaluated as less than 5 mg/day in 84.75% of the pregnant women. In Hungary, the incidence of NTDs has remained constant, while the incidence of neuroblastoma has shown constant slight increase in spite of the introduction of folic acid supplementation in 1997. CONCLUSIONS: Based on our experience, folic acid supplementation was initiated after the recognition of pregnancy and its application in a dose of lower than 5 mg/day neither decreased the incidence of NTDs nor did it have an effect on the neuroblastoma incidence. It is implicated that proper folic acid supplementation, which is started from the conception, can be achieved only with the enrichment of cereal grain flours.

Novel sequence variants of the alpha-galactosidase A gene in patients with Fabry disease.

We carried out molecular studies of 15 unrelated Hungarian families diagnosed with Fabry disease (FD). Genetic analysis of the alpha-galactosidase A gene was performed in 22 hemizygous males and 34 females. One of the female patients with severe disease phenotype showed homozygosity for the recurrent c.644A>G mutation due to parental consanguinity. The c.644A>G mutation that has previously been found mostly in patients with the cardiac variant of FD, was associated with renal but not cardiac involvement in this female and in two other family members. In nine families, eight novel sequence variants such as small deletions (c.363delT, c.477delT, c.746delAC) and single nucleotide changes (c.107T>C, c.493G>C, c.796G>T, c.866T>G, c.871G>A) were found in addition to six previously described private mutations. This report contributes to the identification of novel disease-causing mutations in FD, and increases our knowledge on demographics and molecular characteristics of this rare lysosomal storage disorder. This is the first comprehensive overview of molecular genetic features of Hungarian patients with FD.

Late immune recovery in children treated for malignant diseases.

In this study we analyzed the recovery of the immune system in children after completion of the therapy. We analysed 88 children (51 boys, 37 girls, mean age at diagnosis: 7.8 years) receiving chemotherapy for malignant diseases (43 acute lymphoblastic leukemia, 15 lymphoma, 20 bone tumor, ten other solid tumors). Serum immunoglobulin levels (Ig), natural killer activity (NK), antibody-dependent cellular cytotoxicity (ADCC) and T and B cell proliferation were determined 1 year after cessation of therapy. The mean levels of Ig were in the normal range at a mean of 13 months after chemotherapy (IgG: 11.2 +/- 3.3, IgA: 1.6 +/- 0.9, IgM: 1.0 +/- 0.5 g/l), however in the leukemic patients serum IgG was below the lower limit of the normal range in 3/43 (7.0%) cases, serum IgA was low in 5/43 (11.6%) and serum IgM was decreased in 4/43 (9.3%) cases. In the solid tumor patients IgG values were within the normal range and only 2-2/45 children had lower values for IgA and IgM (4.4%). NK activity decreased in 7/43 (16.3%) leukemic patients, and in 3/45 (6.7%) solid tumor patients, ADCC decreased in 8/43 (18.6%) and 3/45 (6.7%), respectively (p < 0.001). B-cell blastic transformation was decreased in 3/43 (7%) leukemic patients and in 4/45 (8.9%) solid tumor patients. At the same time T-cell blastic transformation was altered in 5/43 (11.6%) and in 4/45 (8.9%) cases, respectively. Leukemic patients had significantly more infections during the first year after chemotherapy than solid tumor patients (1.60 +/- 1.18 vs 0.96 +/- 1.14; p = 0.011). No significant correlations could be found between the investigated immune parameters and the number and severity of infections. It is concluded, that cytotoxic therapy can lead to long-term depression of the immune system, first of all in leukemic patients.

Dermatomyositis and polymyositis associated with malignancy: a 21-year retrospective study.

OBJECTIVE: To analyze clinical and laboratory data of patients diagnosed with dermato- or polymyositis between 1985 and 2006, retrospectively, with particular emphasis on association with malignant diseases. METHODS: A thorough clinical assessment was performed on the immunological features and therapeutic responses, as well as survival data. In the case of 155 myositis patients, HLA haplotypes were also investigated. RESULTS: Out of 309 patients with myositis in our database, malignant disease was found in 37 cases. Thirty patients had dermatomyositis (28.8%), and 7 had polymyositis. In 64.8% of the cases, the malignancy and myositis appeared within 1 year. The highest probability for tumor recognition was before 2 years and after 3 years of the diagnosis of myositis (28 cancer-associated myositis): most frequent was breast tumor, and adenocarcinoma was the predominant histological type. The skin lesions and diaphragmatic involvement were more severe; distal muscle weakness was conventional, along with proximal muscle weakness and frequent immobility. Creatine kinase and lactate dehydrogenase elevations were lower than in primary myositis, and when controlled 1 month after surgical treatment of the malignant disease, these values showed significant reduction. Tumor markers did not predict the occult tumors. We found no correlation between the presence of tumor and DRB1-0301 and -01 alleles. CONCLUSION: In patients with tumor-associated myositis, it was more frequently necessary to administer other immunosuppressive drugs along with glucocorticoids. The successful treatment of the underlying malignant disease improved the clinical course of myositis. The overall survival rate was considerably worse when compared to other forms of myositis.

Treatment of pediatric non-Hodgkin lymphoma in Hungary: 15 years experience with NHL-BFM 90 and 95 protocols.

Retrospective analysis was performed to assess the survival-rates of children with non-Hodgkin lymphoma (NHL), treated according to the NHL-BFM (Berlin-Frankfurt-Münster)-90 and -95 protocols between 1990 and 2004 in Hungary, and to compare our data with the international results. Ninety-one patients had non-B-NHL, 108 B-NHL, and 31 ALCL. Complete remission rate was 89%, while 12% relapsed later. The 5-year-overall-survival was 78% and the event-free survival was 75%. These results are lower than those reported by the BFM study group, but comparable from other European centers. In the last 5 years, the results showed 10% improvement and death during induction was reduced from 10 to 3%.

[Disease course, frequency of relapses and survival of patients with juvenile or adult dermatomyositis]. / Juvenilis és felnott kori dermatomyositisben szenvedo betegek kórlefolyásának jellegzetességei, illetve a kezelés és a késobbi kórlefolyás kapcsolatának vizsgálata.

INTRODUCTION: The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic muscle inflammation resulting progressive weakness and frequent involvement of internal organs, mainly the pulmonary, gastrointestinal and cardiac systems. OBJECTIVE: To present clinical characteristics, disease course, frequency of relapses and survival of 79 patients with juvenile or adult dermatomyositis. METHODS: A national registry of patients with juvenile dermatomyositis was elaborated by the authors in Hungary. The authors summarize data of the register such as signs and symptoms, disease course, frequency of relapses and survival of patients with juvenile dermatomyositis. Analysis was performed using data of 44 patients diagnosed between 1976 and 2004 according to Bohan and Peter's criteria. Survival probability was calculated by Kaplan-Meier method. Data of patients with juvenile dermatomyositis were compared with data of 35 patients with adult dermatomyositis. RESULTS: In view of the disease course, the authors found that more than the half of patients have monophasic disease, while one third of them suffered from polycyclic disease. The risk of the relapse was found to be higher during the first year after the remission. None of the juvenile patients died. Among adult patients, 4 disease-specific deaths occurred. DISCUSSION: There was no correlation between relapse free survival and initial therapeutic regimen. Many of the patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed up for at least 2 years. Despite favourable survival probability, further investigations are needed to assess functional outcome.

[Hungarian experience with non-Hodgkin's lymphoma in childhood]. / Gyermekkori non-Hodgkin-lymphoma kezelésével szerzett magyarországi tapasztalatok.

Between 1990 and 2004, 230 children with non-Hodgkin's lymphoma (NHL) were treated according to the Berlin-Frankfurt-Münster (BFM) protocols (NHL-BFM-90 and -95) in Hungary. The aim of the present study was to summarize our experience with these protocols, to assess the survival rates and to compare the Hungarian data with the international results. The male-to-female ratio was 2.59:1, the mean age at the time of diagnosis was 10 years and 1 month. Ninety-one children had lymphoblastic/T-NHL (LB/T-NHL), 108 B-NHL and 31 anaplastic large cell lymphoma (ALCL). Twenty-eight patients had relapse after a mean time of 13 months from the time of the initial diagnosis. In the above mentioned period, 16 children underwent autologous stem-cell transplantation. Nine patients with B-NHL got anti-CD20 immunotherapy. The five-year overall survival (OS) of our patients is 77.8%+/-3%, the event-free survival (EFS) is 75.1%+/-3%. The 5-year OS and EFS rates were not statistically different in the three histology groups (OS: 71.6%+/-5%, 82.7%+/-4% and 80.3%+/-7%; EFS: 68.7%+/-5%, 81.1%+/-4% and 73.9%+/-8% in LB/T-NHL, B-NHL and ALCL, respectively). We can conclude that non-Hodgkin's lymphoma has a quite good prognosis among the malignant pediatric diseases. The cure rate is over 75%. The Hungarian results are comparable with other international data. In the last five years the mortality during induction was reduced from 10% to 2% and the OS is about 10% better than it was before. In case of relapse or residual disease, therapeutic results can be improved with stem-cell transplantation with or without immunotherapy.

Paraneoplastic rheumatic syndromes.

Paraneoplastic symptoms caused by a malignancy but not directly related to tumour invasion are the result of a wide variety of tumour-derived biologic mediators, such as hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplastic syndromes is important, as it may lead to an early diagnosis of cancer. On the other hand, the clinical severity of the symptoms can be used as a guide to the extent of response to underlying tumour therapy. The quality of life of the patient is affected, therefore the palliative treatment of paraneoplasia is very important.

Prostate cancer underlying acute, definitive dermatomyositis: successful treatment with radical perineal prostatectomy.

The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic inflammation leading to progressive weakness of the proximal muscles. In 7-66% of cases of adult dermatomyositis different malignant tumours can promote the difficult cascade mechanisms at the cell level, leading to rapid weakness of skeletal muscles [1]. We report on a patient with all characteristic signs of acute, severe dermatomyositis associated with a low-grade, low-stage prostate cancer cured by radical perineal prostatectomy.