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  • 51.
    Mercer, Louise
    et al.
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England..
    Mariette, Xavier
    Univ Paris 11, Dept Rheumatol, Paris, France..
    Dixon, Will
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hellgren, Karin
    Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Dreyer, Lene
    Gentofte Univ Hosp, Dept Rheumatol, Hellerup, Denmark..
    Hetland, Merete
    Univ Copenhagen, Copenhagen Ctr Arthrit Res, DANBIO, DK-1168 Copenhagen, Denmark..
    Mellemkjaer, Lene
    Danish Canc Soc, Danish Canc Soc Res Ctr, Copenhagen, Denmark..
    Hyrich, Kimme
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England..
    Strangfeld, Anja
    German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany..
    Zink, Angela
    German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany..
    Canhao, Helena
    Univ Lisbon, Rheumatol Res Unit, P-1699 Lisbon, Portugal..
    Martins, Fernando
    Univ Lisbon, Rheumatol Res Unit, P-1699 Lisbon, Portugal..
    Hernandez, Victoria
    BIOBADASER Registry, Madrid, Spain..
    Tubach, Florence
    Univ Paris Diderot, Dept Epidemiol & Rech Clin, Paris, France..
    Gottenberg, Jacques-Eric
    CHU, Dept Rheumatol, Strasbourg, France..
    Morel, Jacques
    Univ Montpellier, F-34059 Montpellier, France..
    Zavada, Jakub
    Charles Univ Prague, Inst Rheumatol, Prague, Czech Republic..
    van Riel, Piet
    Radboud Univ Nijmegen, Dept Rheumat Dis, NL-6525 ED Nijmegen, Netherlands. Univ Geneva, Geneva, Switzerland..
    Finckh, Axel
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England.;Univ Copenhagen, Copenhagen Ctr Arthrit Res, DANBIO, DK-1168 Copenhagen, Denmark..
    Iannone, Florenzo
    Univ Bari, Bari, Italy..
    Askling, Johan
    Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Listing, Joachim
    German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany..
    First Results Of A European Registries Collaborative Project To Describe The Spectrum Of Lymphomas Across Different Drug Treatment Groups In Rheumatoid Arthritis2015Inngår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, s. 25-25Artikkel i tidsskrift (Annet vitenskapelig)
  • 52. Mercer, Louise
    et al.
    Mariette, Xavier
    Dixon, William
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hellgren, Karin
    Dreyer, Lene
    Hetland, Merete Lund
    Mellemkjaer, Lene
    Hyrich, Kimme
    Strangfeld, Anja
    Zink, Angela
    Canhao, Helena
    Martins, Fernando
    Hernandez, Victoria
    Tubach, Florence
    Gottenberg, Jacques-Eric
    Morel, Jacques
    Zavada, Jakub
    van Riel, Piet
    Finckh, Axel
    Iannone, Florenzo
    Askling, Johan
    Listing, Joachim
    First Results of a European Registries Collaborative Project to Compare the Spectrum of Lymphomas Between Different Exposure Groups in Rheumatoid Arthritis2014Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, Vol. 66, nr S10, s. S806-S807, artikkel-id 1837Artikkel i tidsskrift (Annet vitenskapelig)
  • 53.
    Mörth, Charlott
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Valachis, Antonios
    Örebro Univ, Dept Oncol, Fac Med & Hlth, Örebro, Sweden.
    Sabaa, Amal Abu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Marshall, Katharina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hedström, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Flogegård, Max
    Falun Gen Hosp, Dept Internal Med, Falun, Sweden.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Autoimmune disease in patients with diffuse large B-cell lymphoma: occurrence and impact on outcome2019Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, nr 8, s. 1170-1177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well as the impact of AID on outcome has not been extensively studied. The main purpose of this study was to establish the occurrence of AIDs in a population-based cohort of DLBCL patients and to compare outcomes in patients with or without AID treated with rituximab(R)-CHOP/CHOP-like treatment. We also aimed to analyse gender differences and the potential role of different AIDs on outcome and the frequency of treatment-associated neutropenic fever.

    Patients and methods: All adult patients treated 2000–2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n = 612). Lymphoma characteristics, outcome and the presence of AID were obtained through medical records.

    Results: The number of patients with AID was 106 (17.3%). Thyroid disease dominated (n = 33, 31.1%) followed by rheumatoid arthritis (RA) (n = 24, 22.6%). The proportion of AID was significantly higher in females (59/254, 23.2%) vs. in males (47/358, 13.1%) (p = .001). In the whole cohort there was no difference in event free survival (EFS) or overall survival (OS) between patients with or without AID. However, patients with an AID primarily mediated by B-cell responses (thyroid disorders excluded) had a worse OS (p = .037), which seemed to affect only women. The AID group more often had neutropenic fever after first treatment (16.0% vs 8.7%, p = .034) and those with neutropenic fever had a worse OS (p = .026) in Kaplan-Meier analyses.

    Conclusion: There is a high prevalence of AID among patients with DLBCL. AIDs categorized as primarily B-cell mediated (in this study mainly RA, systemic lupus erythematosus and Sjögren’s syndrome) may be associated with inferior OS. AID patients may be more prone to neutropenic fever compared to patients without concomitant AID.

  • 54.
    Nordmark, Gunnel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kristjansdottir, Gudlaug
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Theander, E.
    Appel, S.
    Eriksson, P.
    Vasaitis, Lilian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Kvarnström, M.
    Delaleu, N.
    Lundmark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Lundmark, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Sjöwall, C.
    Brun, J. G.
    Jonsson, M. V.
    Harboe, E.
    Gøransson, L. G.
    Johnsen, S. J.
    Söderkvist, P.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Alm, G.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Wahren-Herlenius, M.
    Omdal, R.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jonsson, R.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome2011Inngår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 12, nr 2, s. 100-109Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.

  • 55. Raaschou, Pauline
    et al.
    Frisell, Thomas
    Askling, Johan
    TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis: a nationwide cohort study.2015Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 74, nr 12, s. 2137-2143Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the risk of breast cancer recurrence in rheumatoid arthritis (RA)-patients with tumour necrosis factor inhibitor (TNFi) treatment and a history of breast cancer, taking several breast cancer, comorbidity and RA-related prognostic factors into account.

    METHODS: 143 female TNFi-treated patients (1999-2010) with RA and a history of breast cancer before start of TNFi were identified through register linkages, and matched 1:1 from a cohort of 1598 comparable biologics-naive individuals. 120 TNFi-treated and 120 matched biologics-naive individuals with a history of equally recent/distant breast cancer met the eligibility criteria and comprised the final study population. The primary outcome was first recurrence of breast cancer. Through register-linkages and chart review, individuals were followed until 2011. HRs for recurrence were calculated using Cox regression.

    RESULTS: The median time from breast cancer diagnosis until TNFi-treatment/start of follow-up was 9.4 years. Modest differences in breast cancer characteristics and/or treatment among TNFi-treated and biologics-naive individuals were noted at time of breast cancer diagnosis. Median follow-up from TNFi start was 4.9 years (4.6 years among biologics-naive). Among the TNFi-treated, 9 developed a breast cancer recurrence (crude incidence rate 15/1000 person-years) during follow-up, compared with 9 among the matched biologics-naive (16/1000 person-years). The adjusted corresponding HR was 1.1 (95% CI 0.4 to 2.8).

    CONCLUSIONS: Among patients with RA and a history of breast cancer, those who started TNFi-treatment did not experience more breast cancer recurrences than patients with RA treated otherwise. The generalisability of our findings to women with a very recent or a poor prognosis of breast cancer remains unknown.

  • 56.
    Sepulveda, Jorge I. Ramirez
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Expt Rheumatol, SE-17176 Stockholm, Sweden..
    Kvarnstrom, Marika
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Expt Rheumatol, SE-17176 Stockholm, Sweden..
    Eriksson, Per
    Linkoping Univ, Div Rheumatol, Dept Clin Expt Med, Linkoping, Sweden..
    Mandl, Thomas
    Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden..
    Norheim, Katrine Braekke
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Johnsen, Svein Joar
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Hammenfors, Daniel
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway..
    Jonsson, Malin V.
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Univ Bergen, Sect Oral & Maxillofacial Radiol, Dept Clin Dent, Bergen, Norway..
    Skarstein, Kathrine
    Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway.;Haukeland Hosp, Dept Pathol, Bergen, Norway..
    Brun, Johan G.
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Forsblad-d'Elia, Helena
    Umea Univ, Dept Publ Hlth & Clin Med, Rheumatol, Umea, Sweden..
    Bucher, Sara Magnusson
    Orebro Univ, Fac Med & Hlth, Dept Rheumatol, Orebro, Sweden..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Theander, Elke
    Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden..
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Jonsson, Roland
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wahren-Herlenius, Marie
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Expt Rheumatol, SE-17176 Stockholm, Sweden..
    Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients2017Inngår i: Biology of Sex Differences, ISSN 2042-6410, Vol. 8, artikkel-id 25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjogren's syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS. Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 +/- 7.6 for women and 8.5 +/- 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women. Results: Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0. 02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0. 008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009). Conclusions: We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.

  • 57. Simard, J. F.
    et al.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Kinch, Amelie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Brattström, C.
    Ingvar, Å.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Adami, J.
    Fernberg, P.
    Wilczek, H.
    Ekbom, A.
    Smedby, K. E.
    Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden2011Inngår i: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 11, nr 1, s. 146-151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged < 18 in Sweden between 1970-2007 (n = 536) in the National Patient Register and linked to the Cancer Register. Nationwide rates were used to calculate standardized incidence rate ratios and 95% CI estimating the association between transplant and cancer during maximum 36 years of follow-up. Nearly 7% of pediatric solid organ transplant recipients developed a premalignant or malignant tumor during follow-up. Transplantation was associated with an increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0-18.6): non-Hodgkin lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68-217), renal cell (n = 3, SIR = 105, 95% CI: 22-307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137-1934) and nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8-233.8). NHL typically appeared during childhood, while other tumors were diagnosed during adulthood. Apart from short-term attention toward the potential occurrence of NHL, our results suggest cancer surveillance into adulthood with special attention to skin, kidneys and the female genitalia.

  • 58. Simard, Julia F.
    et al.
    Arkema, Elizabeth V.
    Sundström, Anders
    Geborek, Pierre
    Saxne, Tore
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Coster, Lars
    Dackhammar, Christina
    Jacobsson, Lennart
    Feltelius, Nils
    Lindblad, Staffan
    Rantapää-Dahlqvist, Solbritt
    Klareskog, Lars
    van Vollenhoven, Ronald F.
    Neovius, Martin
    Askling, Johan
    Ten years with biologics: to whom do data on effectiveness and safety apply?2011Inngår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 50, nr 1, s. 204-213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Methods. We identified all adult patients with RA (n = 9612), PsA (n = 1417) and other SpA (n = 1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Results. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite < 50% drug retention at 5 years, most patients remained exposed to some biologic. Conclusions. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.

  • 59. Simard, Julia F
    et al.
    Baecklund, Fredrik
    Chang, Ellen T
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hjalgrim, Henrik
    Adami, Hans-Olov
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Smedby, Karin E
    Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes2013Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, nr 11, s. 2659-2666Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lifestyle factors and medical history are known to influence risk of non-Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all-cause and lymphoma-related mortality was assessed in a population-based cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma Etiology study in 1999-2002. Participants contributed time from NHL diagnosis until death or October 1, 2010, with virtually complete follow-up through linkage to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using stratified and multivariable-adjusted Cox regression models. During a median follow-up of 8.8 years, 670 patients (44%) died, with the majority of deaths attributed to lymphoma (86%). Current versus never smoking at diagnosis was associated with increased rate of all-cause death for all NHL (HR = 1.5, 1.2-1.8) and diffuse large B-cell lymphoma (HR = 1.8, 1.2-2.7). Low educational level (HR = 1.3, 1.1-1.7, <9 vs. >12 years) and NHL risk-associated autoimmune disease (HR = 1.4, 1.0-1.8) were associated with death for all NHL combined. However, evidence of an association with lymphoma-related death was limited. Body mass index, recent sunbathing and family history of hematopoietic malignancy were not consistently associated with death after NHL or its specific subtypes. These results add to the evidence that cigarette smoking, socioeconomic status and certain autoimmune diseases affect survival after NHL. Further investigations are needed to determine how these factors should be incorporated into clinical prognostic assessment.

  • 60. Smedby, K. E.
    et al.
    Askling, J.
    Mariette, X.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Autoimmune and inflammatory disorders and risk of malignant lymphomas: an update2008Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 264, nr 6, s. 514-527Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    As specific autoimmune disorders now constitute established risk factors for malignant lymphomas, we describe this association.

    We review reported risk levels, risk determinants, lymphoma subtypes and biological mechanisms in autoimmunity/inflammation, emphasizing on recent findings.

    Whilst numerous reports describe average lymphoma risks in large patient groups, there's a recent shift of focus to risk determinants and the role of inflammatory activity. Studies highlight associations with diffuse large B-cell lymphoma, apart from lymphoma development in target organs of inflammation.

    Future studies of high-risk patient subsets using detailed assessments of autoimmunity/inflammation and lymphoma may give important clues to lymphomagenesis.

  • 61. Smedby, Karin Ekström
    et al.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Askling, Johan
    Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics2006Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, nr 11, s. 2069-2077Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Certain autoimmune and chronic inflammatory conditions, such as Sjögren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general. Likewise, it is debated whether the increased risk identified in association with some disorders pertains equally to all individuals or whether it varies among groups of patients with different phenotypic or treatment-related characteristics. It is similarly unclear to what extent the increased lymphoma occurrence is mediated through specific lymphoma subtypes. This update reviews the many findings on risks, risk levels, and lymphoma characteristics that have been presented recently in relation to a broad range of chronic inflammatory, including autoimmune, conditions. Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sjögren's syndrome. Thus, the average risk of lymphoma in RA may be composed of a markedly increased risk in those with most severe disease and little or no increase in those with mild or moderate disease. The roles of immunosuppressive therapy and EBV infection seem to be limited. Furthermore, RA, Sjögren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sjögren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma. However, there is also obvious heterogeneity in risk and risk mediators among different inflammatory diseases.

  • 62. Sokka, T.
    et al.
    Kautiainen, H.
    Pincus, T.
    Toloza, S.
    Castelar Pinheiro, G. da Rocha
    Lazovskis, J.
    Hetland, M. L.
    Peets, T.
    Immonen, K.
    Maillefert, J. F.
    Drosos, A. A.
    Alten, R.
    Pohl, C.
    Rojkovich, B.
    Bresnihan, B.
    Minnock, P.
    Cazzato, M.
    Bombardieri, S.
    Rexhepi, S.
    Rexhepi, M.
    Andersone, D.
    Stropuviene, S.
    Huisman, M.
    Sierakowski, S.
    Karateev, D.
    Skakic, V.
    Naranjo, A.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Henrohn, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi.
    Gogus, F.
    Badsha, H.
    Mofti, A.
    Taylor, P.
    McClinton, C.
    Yazici, Y.
    Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database2009Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, nr 11, s. 1666-1672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis ( RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP'' countries with GDP per capita greater than US$ 24 000 and 11 "low GDP'' countries with GDP per capita less than US$ 11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP'' and "low GDP'' countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP'' than in "high GDP'' countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

  • 63. Sokka, Tuulikki
    et al.
    Kautiainen, Hannu
    Pincus, Theodore
    Verstappen, Suzanne M.
    Aggarwal, Amita
    Alten, Rieke
    Andersone, Daina
    Badsha, Humeira
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Belmonte, Miguel
    Craig-Müller, Jürgen
    da Mota, Licia Maria Henrique
    Dimic, Alexander
    Fathi, Nihal A.
    Ferraccioli, Gianfranco
    Fukuda, Wataru
    Géher, Pál
    Gogus, Feride
    Hajjaj-Hassouni, Najia
    Hamoud, Hisham
    Haugeberg, Glenn
    Henrohn, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Horslev-Petersen, Kim
    Ionescu, Ruxandra
    Karateew, Dmitry
    Kuuse, Reet
    Laurindo, Ieda Maria Magalhaes
    Lazovskis, Juris
    Luukkainen, Reijo
    Mofti, Ayman
    Murphy, Eithne
    Nakajima, Ayako
    Oyoo, Omondi
    Pandya, Sapan C.
    Pohl, Christof
    Predeteanu, Denisa
    Rexhepi, Mjellma
    Rexhepi, Sylejman
    Sharma, Banwari
    Shono, Eisuke
    Sibilia, Jean
    Sierakowski, Stanislaw
    Skopouli, Fotini N.
    Stropuviene, Sigita
    Toloza, Sergio
    Valter, Ivo
    Woolf, Anthony
    Yamanaka, Hisashi
    Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study2010Inngår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 12, nr 2, s. R42-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION:

    Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries.

    METHODS:

    The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses.

    RESULTS:

    At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score.

    CONCLUSIONS:

    Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

  • 64. Sokka, Tuulikki
    et al.
    Kautiainen, Hannu
    Toloza, Sergio
    Mäkinen, Heidi
    Verstappen, Suzan M.
    Lund Hetland, Merete
    Naranjo, Antonio
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Herborn, Gertraud
    Rau, Rolf
    Cazzato, Massimiliano
    Gossec, Laure
    Skakic, Vlado
    Gogus, Feride
    Sierakowski, Stanislaw
    Bresnihan, Barry
    Taylor, Peter
    McClinton, Catherine
    Pincus, Theodore
    QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries2007Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, nr 11, s. 1491-1496Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA.

    METHODS:

    The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries.

    RESULTS:

    Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 50% of patients had high disease activity of DAS28 >5.1.

    CONCLUSIONS:

    This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.

  • 65.
    Sundbaum, J. K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Berglund, V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Back, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Lehto, N.
    Vikman, I.
    Rollman, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Methotrexate in rheumatoid arthritis and psoriasis/psoriatic arthritis: a comparative study of hepatotoxicity2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr S127, s. 29-29Artikkel i tidsskrift (Annet vitenskapelig)
  • 66.
    Sundbaum, J. K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Ericsson, N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hallberg, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lehto, N.
    Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: a long-term follow-up of occurrence, predictors, surveillance, and outcome in clinical practice2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 977-977Artikkel i tidsskrift (Annet vitenskapelig)
  • 67. Tessier-Cloutier, Basile
    et al.
    Bernatsky, Sasha
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gascoyne, Randy
    Johnson, Nathalie
    Kamen, Diane L.
    Clarke, Ann E.
    Ramsey-Goldman, Rosalind
    Lee, Jennifer L. F.
    Farinha, Pedro
    Cell of Origin (COO) of Diffuse Large B-Cell Lymphoma (DLBCL) in Patients with Systemic Lupus Erythematosus (SLE)2017Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 30, nr Suppl. 2, s. 381A-381A, artikkel-id 1526Artikkel i tidsskrift (Annet vitenskapelig)
  • 68. Tessier-Cloutier, Basile
    et al.
    Bernatsky, Sasha
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gascoyne, Randy
    Johnson, Nathalie
    Kamen, Diane L.
    Clarke, Ann E.
    Ramsey-Goldman, Rosalind
    Lee, Jennifer L. F.
    Farinha, Pedro
    Cell of Origin (COO) of Diffuse Large B-Cell Lymphoma (DLBCL) in Patients with Systemic Lupus Erythematosus (SLE)2017Inngår i: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 97, s. 381A-381AArtikkel i tidsskrift (Fagfellevurdert)
  • 69.
    Tessier-Cloutier, Basile
    et al.
    Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada.
    Twa, David
    Univ British Columbia, Dept Med, Vancouver, BC, Canada.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gascoyne, Randy
    British Columbia Canc Agcy, Dept Pathol, Vancouver, BC, Canada.
    Johnson, Nathalie A.
    McGill Univ, Dept Oncol, Montreal, PQ, Canada.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Kamen, Diane L.
    Med Univ South Carolina, Med Rheumatol & Immunol, Charleston, SC 29425 USA.
    Clarke, Ann E.
    Univ Calgary, Cumming Sch Med, Dept Med, Calgary, AB, Canada.
    Ramsey-Goldman, Rosalind
    Northwestern Univ, FSM, Chicago, IL 60611 USA.
    Lee, Jennifer L. F.
    McGill Univ, Ctr Hlth, Res Inst, Med, Montreal, PQ, Canada.
    Farinha, Pedro
    British Columbia Canc Agcy, Dept Pathol, Vancouver, BC, Canada.
    Bernatsky, Sasha
    McGill Univ, Ctr Hlth, Res Inst, Div Rheumatol, Montreal, PQ, Canada;McGill Univ, Ctr Hlth, Res Inst, Div Clin Epidemiol, Montreal, PQ, Canada.
    An Analysis of Cell-of-Origin in Diffuse Large B-Cell Lymphoma in Systemic Lupus Erythematosus, Including Molecular and Clinical Factors Associated with Survival2018Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikkel i tidsskrift (Annet vitenskapelig)
  • 70.
    Tessier-Cloutier, Basile
    et al.
    Univ British Columbia, Anat Pathol & Lab Med, Vancouver, BC, Canada.
    Twa, David D. W.
    Univ British Columbia, Fac Med, Vancouver, BC, Canada.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gascoyne, Randy
    Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada;British Columbia Canc Agcy, Pathol Dept, Vancouver, BC, Canada;British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada.
    Johnson, Nathalie A.
    Sir Mortimer B Davis Jewish Hosp, Dept Med, Montreal, PQ, Canada.
    Backlin, Carin
    Med Univ South Carolina, Dept Rheumatol & Immunol, Charleston, SC 29425 USA.
    Kamen, Diane L.
    Med Univ South Carolina, Med, Charleston, SC 29425 USA.
    Clarke, Ann E.
    Univ Calgary, Calgary, AB, Canada.
    Ramsey-Goldman, Rosalind
    Northwestern Univ, Med Rheumatol, Chicago, IL 60611 USA.
    Lee, Jennifer L. F.
    McGill Univ, Hlth Ctr, Div Clin Epidemiol, Montreal, PQ, Canada.
    Farinha, Pedro
    Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada;British Columbia Canc Agcy, Pathol Dept, Vancouver, BC, Canada;British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada.
    Bernatsky, Sasha
    McGill Univ, Hlth Ctr, Div Clin Epidemiol, Montreal, PQ, Canada;McGill Univ, Dept Med, Montreal, PQ, Canada.
    Cell of origin in diffuse large B-cell lymphoma in systemic lupus erythematosus: molecular and clinical factors associated with survival2019Inngår i: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 6, nr 1, artikkel-id e000324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background SLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and indicating better prognosis in the general population. We studied COO subtyping in patients with SLE diagnosed with DLBCL and their survival. Patients and methods We evaluated 20 cases of SLE with DLBCL. Immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1) in tissue microarrays. We examined associations between molecular and clinical features, including overall survival. Results Of the 20 DLBCL SLE cases, 12/20 cases (60%) were classified as non-GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20 (40%) SLE cases, respectively, with 2/20 (10%) co-expressing both markers. Seven (7/20) had only extranodal involvement at DLBCL diagnosis. As expected, non-GCB cases had worse survival. Cases presenting exclusively with extranodal disease were associated with shorter SLE duration and better survival despite higher BCL2 protein expression. Conclusions We present novel data characterising DLBCL in SLE. Sixty per cent of the DLBCL in patients with SLE were non-GCB. The nodal and extranodal distribution in SLE was similar to what is known in the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer overall survival. More research on cancer in SLE is the key to further understanding the complex interplay between cancer and the immune system.

  • 71. Theander, Elke
    et al.
    Vasaitis, Lilian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Warfvinge, Gunnar
    Liedholm, Rolf
    Brokstad, Karl
    Jonsson, Roland
    Jonsson, Malin V.
    Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjogren's syndrome2011Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, nr 8, s. 1363-1368Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker.

    METHODS:

    Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ(2) or Fisher's exact tests.

    RESULTS:

    At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001).

    CONCLUSIONS:

    The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.

  • 72.
    Thorlacius, Gudny Ella
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Hultin-Rosenberg, Lina
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sandling, Johanna K.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Imgenberg-Kreuz, Juliana
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theander, Elke
    Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden.
    Kvarnstrom, Marika
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Forsblad-d'Elia, Helena
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Bucher, Sara Magnusson
    Orebro Univ, Fac Med & Hlth, Dept Rheumatol, Orebro, Sweden.
    Norheim, Katrine Braekke
    Stavanger Univ Hosp, Dept Internal Med, Stavanger, Norway.
    Johnsen, Svein Joar
    Stavanger Univ Hosp, Dept Internal Med, Stavanger, Norway.
    Hammenfors, Daniel
    Haukeland Hosp, Dept Rheumatol, Bergen, Norway.
    Skarstein, Kathrine
    Haukeland Hosp, Dept Pathol, Bergen, Norway.
    Jonsson, Malin V.
    Univ Bergen, Dept Clin Dent, Bergen, Norway.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mandl, Thomas
    Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden.
    Eriksson, Per
    Linkoping Univ, Dept Clin Expt Med, Linkoping, Sweden.
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Stavanger, Norway.
    Jonsson, Roland
    Univ Bergen, Broegelmann Res Lab, Bergen, Norway.
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA USA.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wahren-Herlenius, Marie
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Genetic basis and clinical evidence for two variants of primary Sjögren's syndrome with distinct outcomes2018Inngår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 3, s. S246-S247Artikkel i tidsskrift (Annet vitenskapelig)
  • 73.
    Vasaitis, Lilian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Askling, J.
    Ekstrom-Smedby, K.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Theander, E.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Comparison of lymphomas in primary and secondary Sjogren's syndrome2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr suppl. 127, s. 83-83Artikkel i tidsskrift (Annet vitenskapelig)
  • 74.
    Vasaitis, Lilian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theander, E
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Smedby, K E
    Askling, J
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Comparison of patients with and without pre-existing lymphoma at diagnosis of primary Sjögren's syndrome2019Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 48, nr 3, s. 207-212Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: In the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome (pSS), pre-existing lymphoma is not an exclusion criterion for pSS diagnosis, as in earlier criteria. We aimed to explore whether there are differences between pSS patients with and without pre-existing lymphoma at pSS diagnosis.

    METHOD: Patients with ICD-7-10 codes for Sjögren's syndrome (SS) and a diagnosis of malignant lymphoma before or after SS diagnosis were identified by linking the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007 (n = 224). Clinical data were collected from medical records. Lymphoma diagnoses were evaluated by tissue review. Characteristics of pSS patients with and without pre-existing lymphoma were compared.

    RESULTS: We identified 107 patients with pSS as the reason for an SS diagnosis code and a verified lymphoma. Of these, 18 (17%) had a pre-existing lymphoma at pSS diagnosis, defined as lymphoma diagnosed before or within 6 months of pSS diagnosis. Male gender (39% vs 10%, p = 0.006), enlarged lymph nodes during the pSS disease (61% vs 27%, p = 0.01), mucosa-associated lymphoid tissue (MALT) lymphoma (50% vs 22%, p = 0.02), and salivary gland lymphoma (61% vs 26%, p = 0.006) were more common in patients with a pre-existing lymphoma at pSS diagnosis. Other pSS characteristics were similar.

    CONCLUSION: In a substantial proportion of patients, particularly in men, pSS remains undiagnosed until after lymphoma diagnosis. The study highlights the importance of pSS investigation in patients with lymphoma, especially MALT lymphoma, in the salivary glands.

  • 75.
    Vasaitis, Lilian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theander, E.
    Lund Univ, Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden..
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Smedby, K. E.
    Karolinska Inst, Dept Med Sci, Clin Epidemiol Unit, Stockholm, Sweden..
    Askling, J.
    Karolinska Inst, Dept Med Sci, Clin Epidemiol Unit, Stockholm, Sweden..
    Sundstrom, C.
    Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Primary Sjögren's Syndrome and Lymphoma – A Population-Based Study Focused on Lymphoma as Exclusion Criterion for Primary Sjögren's Syndrome Diagnosis2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 779-780Artikkel i tidsskrift (Annet vitenskapelig)
  • 76.
    Vasaitis, Lilian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sporadic Occurrence of Non-Diagnosed IgG4-Related Disease in Lymphoma Patients with a Previous Sjogren's Syndrome Diagnosis2015Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, nr 5, s. 407-407Artikkel i tidsskrift (Annet vitenskapelig)
  • 77.
    Vasaitis, Lilian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a previous Sjögren's syndrome diagnosis.2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 9-10, s. 1139-1144Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4-RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma.

    METHODS: Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964-2007 and the Cancer Register 1990-2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD.

    RESULTS: Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B-cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies.

    CONCLUSION: Histopathological findings of IgG4-RD may co-exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD.

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