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Absztrakt: Az onkoreumatológia a daganatképződés és a reumatológiai kórképek kapcsolatát jelenti. Számos összefüggés van a két orvosi szakterület között. Ezek egy része a reumatológiai kórképben szenvedő betegben jelentkező daganatokat, a másik fele pedig a daganatos betegen fellépő mozgásszervi jelenségeket foglalja magában. Az előbbi csoport keretében a reumatológiai betegségekben jelentkező szekunder tumorokat, a tumorasszociált antigének reumatológiai szerepét, a mozgásszervi betegségek kezelésére használt hagyományos és célzott terápiák esetleges onkogenitását és a korábban vagy jelenleg daganatos, mozgásszervi betegek fizioterápiáját tárgyaljuk. A másik nagy csoport magában foglalja a paraneoplasiás szindrómákat, az onkológiai kezelések (kemoterápia és immunterápia) lehetséges autoimmun-reumatológiai mellékhatásait, a hormondeprivatiós kezelés csonthatásait és a mozgásszervrendszer primer és szekunder daganatait. Orv Hetil. 2020; 161(28): 1151–1165.

Key messages #### What is already known about this subject? #### What does this study add? #### How might this impact on clinical practice or further developments?. Please check and provide Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality, as well as metabolic changes.1 2 Targeted therapies may have beneficial effects on CV outcomes1 3 4 and metabolism2 5 in RA. Four Janus kinase (JAK) inhibitors including tofacitinib have been approved for RA.6 JAK inhibition has been associated with lipid elevation7; however, it had no CV consequences.1 7 Vascular inflammation may precede atherosclerosis. Traditionally, ultrasound-based techniques have been applied to assess preclinical vascular pathophysiology in RA.1 8 Early endothelial dysfunction indicated by abnormal brachial artery flow-mediated vasodilation (FMD), overt atherosclerosis shown by the presence of carotid plaques and increased common carotid intima–media thickness (IMT), as well as arterial stiffness indicated by increased arterial pulse-wave velocity (PWV) have been reported in association with RA.1 8–11 These preclinical abnormalities predict the development of subsequent CV events in arthritis.1 8 Biologics may, at least transiently, dampen the progression of abnormal FMD, IMT and PWV in RA (reviewed in Szekanecz et al 3). There has been only one study showing that tofacitinib decreased carotid atherosclerosis.12 18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG-PET/CT) may be able to simultaneously detect tissue inflammation all over the …

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p &lt, 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p &lt, 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p &lt, 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

Abstract: Oncotherapy has been revolutionised by the introduction of immune-checkpoint inhibitors including CTLA4, PD1 and PDL1 inhibitors. Patients with malignant diseases may largely benefit from these therapies, which may result in long-term remission even in the most therapy-resistant tumour types. Differences in the mode of action of the various agents may result in varying side-effect profiles. In addition to organ-specific side-effects, overt autoimmune syndromes may also develop. Our current view of oncotherapy has changed as these mostly immune-mediated side-effects highly differ from those observed previously during the administration of traditional anti-tumour compounds. These side-effects should be carefully characterized and differentiated from infections or the progression of the underlying malignancy. Fortunately, several recent recommendations have become available on the management of immune-mediated adverse events due to checkpoint-inhibitor therapy. Orv Hetil. 2019; 160(23): 887–895.

Abstract Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p Conclusions BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.

Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p

Oncorheumatology: relationship between malignancies and musculoskeletal diseases Oncorheumatology is the meeting point of tumor formation and rheumatic musculoskeletal diseases (RMD). Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. Within the first group, secondary malignancies may be associated with rheumatic diseases. Mostly sustained inflammation is responsible for transition into cancer. Tumor-associated antigens (TAA) with adhesive properties are present on tumor cells. These molecules may also be expressed by inflammatory leukocytes and soluble TAA levels may be elevated in RMDs. There has been continuous debate with respect to the possible carcinogenicity of conventional and targeted antirheumatic drugs. Very recent data from registries suggest that neither biologics, nor JAK inhibitors increase cancer risk in arthritis patients. The issue of physiotherapy in rheumatic patients with recent or current cancer has also been controversial. Some modalities, primarily exercise, may be safely applied to patients with RMD and cancer. The second large topic includes paraneoplastic syndromes. Musculoskeletal paraneoplasias are triggered by tumor-derived mediators. These syndromes are sometimes slightly different from the classical RMDs. Various chemotherapies may also be associated with autoimmune side effects. Recently, these immune-related complications have also been observed in cancer patients treated with immune-checkpoint inhibitors. Sex hormone-deprivation therapies, such as aromatase inhibitors and anti-androgens are widely used for the treatment of breast and prostate cancer, respectively. These compounds may induce bone loss and lead to osteoporosis. Finally, primary and secondary malignancies of the musculoskeletal system may also interest rheumatologists. In this review, the clinical, practical aspects of these eight pillars of oncorheumatology will be discussed.

Oncorheumatology is the meeting point of tumour formation and rheumatic diseases. Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. In the first group, secondary malignancies associated with rheumatic diseases, role of tumour-associated antigens in rheumatology, the possible carcinogenicity of conventional and targeted antirheumatic drugs and physical therapy of rheumatic patients with recent or current cancer will be discussed. The second large topic includes paraneoplastic syndromes, autoimmune-rheumatic side effects of oncotherapies (chemotherapy and immunotherapy), effects of hormone-deprivation therapies on bone and primary and secondary malignancies of the musculoskeletal system. Orv Hetil. 2020; 161(28): 1151-1165.

Oncotherapy has been revolutionised by the introduction of immune-checkpoint inhibitors including CTLA4, PD1 and PDL1 inhibitors. Patients with malignant diseases may largely benefit from these therapies, which may result in long-term remission even in the most therapy-resistant tumour types. Differences in the mode of action of the various agents may result in varying side-effect profiles. In addition to organ-specific side-effects, overt autoimmune syndromes may also develop. Our current view of oncotherapy has changed as these mostly immune-mediated side-effects highly differ from those observed previously during the administration of traditional anti-tumour compounds. These side-effects should be carefully characterized and differentiated from infections or the progression of the underlying malignancy. Fortunately, several recent recommendations have become available on the management of immune-mediated adverse events due to checkpoint-inhibitor therapy. Orv Hetil. 2019; 160(23): 887-895.Absztrakt: A daganatterápiát forradalmasította az immuncheckpointgátlók, elsősorban a CTLA4-, PD1- és PDL1-gátlók bevezetése. Alkalmazásuk igazi nyertesei a malignus daganatos betegek: bizonyos tumorlokalizációk esetén ezek a kezelések a legnehezebben uralható rosszindulatú betegségeket is hosszú remisszióban tudják tartani. A kezelések különböző fajtáinak hatásmechanizmusában megnyilvánuló különbségek eltérő mellékhatásprofilban nyilvánulnak meg. A szervspecifikus mellékhatások mellett manifeszt autoimmun betegségek is jelentkezhetnek. A mellékhatás-management terén szemléletváltás szükséges: a szövődmények elhárítását célzó tevékenységeink során nem szabad megfeledkezni arról, hogy az immuncheckpointgátló kezelések mellékhatásai mennyire eltérnek a klasszikus gyógyszeres onkoterápiáknál megszokottól. Ezen tünetek pontos differenciálása esetleges infekciótól vagy a daganatos betegség progressziójától nélkülözhetetlen, de nem egyszerű differenciáldiagnosztikai feladat. Szerencsére számos ajánlás jelent meg az immuncheckpointgátló kezelés mellékhatásainak elhárításával, kezelésével kapcsolatban. Orv Hetil. 2019; 160(23): 887–895.

Background:Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with osteoporosis. There have been very few data on the use of peripheral quantitative computed tomography (QCT) in anti-TNF-treated patients.Objectives:We wished to assess volumetric bone mineral density (BMD) by forearm QCT in conjunction with dual-energy X-ray absorptiometry (DXA) and bone biomarkers in RA and AS.Methods:Forty RA and AS patients treated with etanercept (ETN) or certolizumab pegol (CZP) were included in a 12-month follow-up study. Peripheral QCT and DXA BMD were determined. Bone biomarkers, such as PTH, osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin, DKK-1 and cathepsin K (CATHK) were assessed by ELISA.Results:There was no further bone loss during anti-TNF treatment. Volumetric and areal BMD showed significant correlations with each other (pConclusion:QCT confirmed that biologics may attenuate bone loss. Disease activity, CATHK, RANKL and VITD may predict the effects of anti-TNF treatment on volumetric BMD changes. There may be differences between RA and AS in this respect.Acknowledgements:This research was supported by Hungarian National Scientific Research Fund (OTKA) grant No. K 105073 (H.P.B. and Z.S.); by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program ’(Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00050 (Z.S.); and by the Pfizer Investigator Initiated Research Grants no. WS1695414 and WS1695450 (Z.S.).Disclosure of Interests:Balázs Juhász: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Anita Pusztai: None declared, Agnes Szentpetery: None declared, Zsófia Pethö: None declared, Nóra Bodnár: None declared, Attila Hamar: None declared, Levente Bodoki: None declared, Harjit Pal Bhattoa: None declared, Éva Szekanecz: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Szilvia Szamosi Speakers bureau: Roche, Csaba Horváth: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, Novartis, Gabriella Szücs Speakers bureau: Roche, Boehringer, Actelion, Sager, Consultant of: Actelion, Boehringer, Hennie Raterman: None declared, WIllem Lems Speakers bureau: Pfizer, Amgen, Lilly, UCB, Galapagos, Consultant of: Pfizer, Amgen, Lilly, UCB, Galapagos, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer, Consultant of: BMS, Celgene, Eli Lilly, Janssen, Pfizer, Grant/research support from: AbbVie, BMS, Eli Lilly, Novartis, Pfizer, Zoltán Szekanecz Speakers bureau: Pfizer, Roche, Abbvie, Novartis, Lilly, Sanofi, Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: Pfizer, UCB.

Background:Rheumatoid arthritis (RA) has bene associated with atherosclerosis and cardiovascular (CV) disease. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is suitable to detect synovial and vascular inflammation. Tofacitinib has been used to effectively treat RA.Objectives:We wished to assess the effects of tofacitinib treatment on synovitis and vascular inflammation simultaneously by 18FDG-PET/CT.Methods:Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib and evaluated at baseline and after 6 and 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) levels. All patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in order to determine vascular and synovial inflammation in five aortic segments and five articular regions, respectively. In the joints, mean (SUVmean) and maximum standard uptake values (SUVmax), while in the aorta, mean (TBRmean) and maximum target-to-background ratios (TBRmax) were determined. Carotid intima-media thickness (IMT), arterial stiffness (PWV) and endothelial dysfunction (FMD) were determined by ultrasound.Results:One-year tofacitinib treatment significantly attenuated vascular and synovial inflammation as visualized by PET/CT. Articular SUVmean (p=0.010), SUVmax (p=0.001), as well as aorta TBRmax (pmax) inversely correlated with HAQ and positively with ESR, ApoA, and PWV. Uni- and multivariable analyses suggested that articular SUV values were independently associated with CRP, ApoB, LpA, IMT and PWV, while aortic TBRmax was determined by HAQ and PWV.Conclusion:18F-PET/CT is suitable to simultaneously assess synovial and vascular inflammation in RA. One-year tofacitinib treatment dampened inflammation. PET/CT changes were associated with markers of systemic inflammation, atherogenic lipids, carotid atherosclerosis and arterial stiffness.References:[1]Gotthardt M, Bleeker-Rovers CP, Boerman OC, Oyen WJ. Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. J Nucl Med. 2010;51(12):1937-49.[2]Bucerius J, Hyafil F, Verberne HJ, Slart RH, Lindner O, Sciagra R, et al. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis. Eur J Nucl Med Mol Imaging. 2016;43(4):780-92.Acknowledgements:This research was supported by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’ (Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00015 (G.P., G.T. and Z.S.) and by the Pfizer Investigator Initiated Research Grant no. WI188341 (Z.S.).Disclosure of Interests:Attila Hamar: None declared, Zsolt Hascsi: None declared, Anita Pusztai: None declared, Monika Czókolyová: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Katalin Gulyás: None declared, Boglárka Soós: None declared, György Kerekes: None declared, Éva Szekanecz: None declared, Katalin Hodosi: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, MSD, Novartis, Gabriella Szücs Speakers bureau: Boehringer, Actelion, Roche, Consultant of: Boehringer, Actelion, Roche, Tamas Seres: None declared, Zoltán Szekanecz Speakers bureau: Abbvie, Pfizer, Roche, Novartis, Lilly, Sager, Janssen, Consultant of: Pfizer, Abbvie, Roche, Novartis, Grant/research support from: Pfizer, Szilvia Szamosi Speakers bureau: Roche

Background:Rheumatoid arthritis (RA) has been associated with increased cardiovascular (CV) risk and metabolic changes.Objectives:We wished to determine how the Janus kinase (JAK) inhibitor tofacitinib influences vascular pathophysiology and metabolites of the arginine and methionine-homocysteine pathways.Methods:Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib and evaluated at baseline and after 6 and 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels.Results:Twenty-six patients completed the study. Tofacitinib treatment maintained FMD and PWV. Ten mg bid tofacitinib significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. Tofacitinib transiently increased L-citrulline and L-NMMA and decreased homocysteine levels after 12 months. Based on L-citrulline, L-ornithine, ADMA and SDMA levels, L-arginine remained highly available for endothelial NO production. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with aCCP. Regarding vascular pathophysiology, only PWV and methionine correlated with each other after 12 months.Conclusion:Tofacitinib suppressed systemic inflammation in RA yielding stabilization of vascular function. It may exert CV protective effects in RA, at least in part, by shifting L-arginine metabolism to high arginine availability and decreasing homocysteine levels.Acknowledgements:This research was supported by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program ’(Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00015 (Z.S.) and by the WI188341 investigator-initiated research (IIR) grant obtained from Pfizer US (Z.S.).Disclosure of Interests:Boglárka Soós: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Monika Czókolyová: None declared, Edit Végh: None declared, Szilvia Szamosi Speakers bureau: Roche, Zsófia Pethö: None declared, Katalin Gulyás: None declared, György Kerekes: None declared, Éva Szekanecz: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, Novartis, Gabriella Szücs Speakers bureau: Actelion, Roche, Sager, Boehringer, Consultant of: Boehringer, Actelion, Sager, Uwe Christians: None declared, Jelena Klawitter: None declared, Tamas Seres: None declared, Zoltán Szekanecz Speakers bureau: Pfizer, Abbvie, Roche, Lilly, Novartis, Boehringer, Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: Pfizer

Rheumatoid arthritis (RA) has been associated with osteoporosis. Quantitative computed tomography (QCT) is capable of assessing bone density and composition. We found lower bone density in RA compared to controls. Age and RA duration influenced bone density. QCT may be useful to assess bone metabolism in RA. RA is associated with generalized and periarticular osteoporosis. In addition to DXA that determines areal bone mineral density (BMD), peripheral QCT also detects volumetric BMD. QCT differentiates between total, trabecular, and cortical BMD. Here, we compared DXA and QCT in RA patients and healthy controls. BMD of 57 female RA patients and 32 age-matched healthy female controls were assessed by DXA. QCT of the forearm ultradistal region was also performed. Densitometry data were correlated with age, disease duration, disease activity, serum CRP, and anti-CCP levels. Total bone density (310.4 ± 79.7 versus 354.0 ± 54.1 mg/cm3; p = 0.007) and attenuation (0.37 ± 0.05 versus 0.40 ± 0.03 1/cm; p = 0.001), trabecular density (157.6 ± 57.0 versus 193.8 ± 48.7 mg/cm3; p = 0.005) and attenuation (0.28 ± 0.03 versus 0.32 ± 0.04 1/cm; p

Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians' decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224-1231.

Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians’ decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224–1231.

As a result of increasing life expectancy of lupus patients, malignant disorders have become major determinants of morbidity and mortality. The objectives of this study were to analyze cancer-associated morbidity and mortality, the type of malignancies in Hungarian lupus patients, and to analyze association with immune-suppressive therapy, disease duration, and age of the patients. Data from 860 systemic lupus erythematosus (SLE) patients were retrospectively analyzed in a study period between 1970 and 2004. Results were compared to data from age- and sex-matched population obtained from the Health for All database, and also to literature data. A total of 37 patients presented with cancer, reflecting 4.3% cancer-associated morbidity. Patients were 47 (20-73) years old at the onset of malignancy, which appeared 13 (1-45) years later than SLE. Cancer prevalence was the highest in the first 5-10 years of lupus. Breast cancer was the most common malignancy (n = 11) followed by gastrointestinal tumors (n = 9), cervix cancer and hematologic malignancies (n = 5 for both), bronchial cancer (n = 4), bladder, skin, and ovarian cancer (n = 1 for each). Standardized incidence ratio was the highest for non-Hodgkin lymphoma (standardized incidence ratio [SIR] 3.5, 95% CI 0.4-12.5) and cervix cancer (SIR 1.7, 95% CI 0.6-4.1). Although 76% of patients with cancer received immune-suppressive therapy besides corticosteroids, no direct correlation could be confirmed between therapy and malignancy. Out of the 164 patients that expired during the study period, 18 were cancer-related. As such the cancer-associated mortality was 11% (18/164). This peaked during the last 4 years of the study period (8/24, 33%). Lupus patients are at high risk for particular types of malignant disorders, highlighting the importance of screening measures and focused patient examination.

Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators like 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. There is some evidence that systemic inflammatory diseases, such as rheumatoid arthritis (RA), lupus, scleroderma or dermatomyositis may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. However, reports are somewhat controversial. Immunosuppressive and cytotoxic drugs used in antirheumatic therapy, such as methotrexate, cyclophosphamide, azathioprine or anti-TNF biologicals may also lead to the development of such tumors. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in RA and other autoimmune diseases.

Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases, are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma or dermatomyositis, may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. Immunosuppressive drugs and biological agents may also be carcinogenic. However, sustained inflammatory activity seems to be the primary risk factor for malignancies in autoimmune diseases. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in rheumatoid arthritis and other autoimmune diseases.

Objective:We report an extremely rare case of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.Method:Case report presenting a 15-year-old girl referred with hoarseness and soft voice.Results:Right-sided recurrent laryngeal nerve paralysis was observed using videolaryngoscopy. Imaging was used to exclude intracranial, cervical and intrathoracic embryological lesions, vascular malformations and tumours. Laboratory and electrophysiological investigations were used to exclude inflammatory and paraneoplastic processes, endocrinopathy and metabolic disorders. Serological testing was positive for Lyme disease. Parenteral ceftriaxone therapy was commenced. The patient's nerve paralysis showed complete recovery on the seventh day of antibiotic treatment; this was confirmed by videolaryngoscopy.Conclusion:Recurrent laryngeal nerve paralysis is an extremely rare complication of neuroborreliosis associated with Lyme disease. In patients with recurrent laryngeal nerve paralysis in whom the clinical history is uncertain and the usual diagnostic methods give negative results, screening with anti-borrelia immunoglobulin M is suggested.

Recent results suggest that B cells may have multiple pathogenic roles in systemic sclerosis (SSc) and there may be increased incidence of B cell lymphomas in SSc. Here, we assessed the prevalence of lymphomas in a large SSc cohort. We analyzed data of 218 Hungarian patients undergoing follow-ups in our institutions between 1995 and 2007. During this follow-up period, there were three SSc patients, who eventually developed B cell lymphoma. The first case is a woman with diffuse cutaneous form of SSc (dcSSc) including pulmonary, cardiac, gastrointestinal, and renal manifestations and anti-topoisomerase I antibody positivity. B cell chronic lymphocytic leukemia (B-CLL) with Zap70 expression (Rai I stage) developed 2 years after the onset of SSc. The second case is a woman with dcSSc presenting with pulmonary, cardiac, and gastroesophageal manifestations. Twenty-one months after disease onset, a chronic small lymphocytic B cell non-Hodgkin's lymphoma was diagnosed from retroperitoneal lymph nodes. Our third case is a woman with dcSSc and no internal organ manifestations. She also developed Zap70-positive B-CLL, stage Rai I 9 months after the onset of SSc. Thus, there were three cases of B cell lymphoma among our 218 SSc patients (1.38%). The association of scleroderma and non-Hodgkin's lymphoma may be a rather uncommon feature; however, the incidence of lymphoma among Hungarian SSc patients may be 1.9-2.5 times higher than that in the general population. In our three patients, B cell lymphoma developed within 2 years after the onset of SSc. Altered B cell function implicated in the pathogenesis of SSc may lead to the development of lymphoid malignancies.

Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis.We assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement.TAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively.There were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p0.05). The mean absolute serum levels of CEA (6.6+/-1.7 vs 1.8+/-1.4 mg/l) and CA15-3 (22.9 +/- 1.8 vs 18.6 +/- 2.2 kU/l) were also significantly higher in SSc compared to controls (p0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls.The concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.

Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected carcinoembryonic antigen (CEA; CD66) in the rheumatoid (RA) synovium. The production of CEA, CA19-9, CA125, and CA15.3, may be increased in patients with RA, scleroderma, lupus, and Sjogren's syndrome (SS). Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis. We assessed levels of TAAs in the sera of RA patients and healthy subjects. Serum TAA levels were correlated with disease markers including serum rheumatoid factor (RF), C-reactive protein (CRP), and anti-CCP antibody levels, DAS28, age disease duration. TAAs including CEA, CA15-3, CA72-4, CA125, and CA19-9, and neuron-specific enolase (NSE) were assessed by immunoassay in the sera of 75 patients with RA and 50 age- and sex-matched healthy controls. Normal upper limits for these TAAs were 3.4 microg/L, 25 kU/L, 6.9 kU/L, 35 kU/L, 34 kU/L, and 16.3 microg/L, respectively. There were significantly more RA patients showing abnormally high levels of CA125 (10.8% versus 7.1%), CA19-9 (8.1% versus 0%), and CA15-3 (17.6% versus 14.3%) in comparison to controls (P < 0.05). The mean absolute serum levels of CA125 (23.9 +/- 1.8 versus 16.8 +/- 2.2 kU/L) and CA19-9 (14.2 +/- 1.2 versus 10.5 +/- 1.6 kU/L) were also significantly higher in RA compared to controls (P < 0.05). Among RA patients, serum CEA showed significant correlation with RF (r = 0.270; P < 0.05). None of the assessed TAAs showed any correlation with CRP, anti-CCP, DAS28, age or disease duration. The concentration of some TAAs may be elevated in the sera of patients with established RA in comparison to healthy subjects. CEA, CA19-9, CA125, and CA15-3 contain carbohydrate motifs and thus they may be involved in synovitis-associated adhesive events. Furthermore, some TAAs, such as CEA, may also correlate with prognostic factors, such as serum RF levels.