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Living and Dying with Primary Sjögren's Syndrome Studies on Aetiology, Treatment, Lymphoma, Survival and Predictors

Theander, Elke LU (2005) In Lund University Faculty of Medicine Doctoral Dissertation Series 2005:59.
Abstract
This work was aimed at improving our understanding of the course of primary Sjögren's syndrome (SS). The Malmö SS patient register and the 2002 American-European Consensus Criteria formed the basis of all studies.



Helicobacter pylori (H. pylori) was not more prevalent in SS patients or associated with severe glandular or immunological dysfunction. Consequently, our results do not support screening for or eradication of latent H. pylori infection.



Fatigue and reduced health-related quality of life contribute to sick leave, early retirement and mental distress. After 5 years quality of life was preserved at the same level, in contrast to the expected age-dependent decline in the normal... (More)
This work was aimed at improving our understanding of the course of primary Sjögren's syndrome (SS). The Malmö SS patient register and the 2002 American-European Consensus Criteria formed the basis of all studies.



Helicobacter pylori (H. pylori) was not more prevalent in SS patients or associated with severe glandular or immunological dysfunction. Consequently, our results do not support screening for or eradication of latent H. pylori infection.



Fatigue and reduced health-related quality of life contribute to sick leave, early retirement and mental distress. After 5 years quality of life was preserved at the same level, in contrast to the expected age-dependent decline in the normal population.



Our double-blind randomized controlled trial with gammalinolenic acid (GLA), an essential omega-6 fatty acid, failed to alleviate fatigue, precluding a general recommendation of this complementary treatment.



Longitudinal follow-up of glandular dysfunction revealed slight deterioration of objective measures after 5 years, predicted by low complement levels at baseline. However, the available measures of assessment suffer from considerable floor/ceiling effects.



Linking our register to the Swedish Cause-of-Death and Cancer Registers, we calculated standardized mortality ratios (SMRs) and incidence ratios (SIRs) for solid and lymphoproliferative malignancies. SIR (95% confidence interval (CI)) for non-Hodgkin lymphoma: 15.57 (CI 7.77-27.85), cause-specific SMR for death from haematological neoplasms: 7.89 (CI 2.89-17.18). Aggressive diffuse large B-cell lymphomas predominated. Risk factor for both death and lymphoma was low complement at diagnosis. Novel strong predictors of lymphoma development were CD4+ T-lymphocytopenia (hazard ratio (HR): 8.14, CI 2.10-31.53) and a low CD4+/CD8+ T-cell ratio ?0.8 (HR 10.92, CI 2.80-41.83). All-cause mortality, cardiovascular mortality and the incidence of non-haematological malignancies were not increased. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Denna avhandling hade som målsättning att belysa långtidsförloppet vid primärt Sjögrens syndrom (SS). Studierna är baserade på registret över SS-patienter vid Universitetssjukhuset MAS och de Amerikansk-Europeiska konsensuskriterierna för SS från 2002.



Helicobacter pylori (H. pylori) är inte mer prevalent bland SS-patienter än bland kontrollpersoner. Bakteriens förekomst är inte associerat med allvarlig körteldysfunktion eller immunologisk rubbning. Således behövs inte screening av H. pylori om inte symtom föreligger.



Trötthet och nedsatt livskvalitet bidrar till sjukskrivning, sjukpension och mental ohälsa. Vid en 5 års uppföljning upptäcktes ingen... (More)
Popular Abstract in Swedish

Denna avhandling hade som målsättning att belysa långtidsförloppet vid primärt Sjögrens syndrom (SS). Studierna är baserade på registret över SS-patienter vid Universitetssjukhuset MAS och de Amerikansk-Europeiska konsensuskriterierna för SS från 2002.



Helicobacter pylori (H. pylori) är inte mer prevalent bland SS-patienter än bland kontrollpersoner. Bakteriens förekomst är inte associerat med allvarlig körteldysfunktion eller immunologisk rubbning. Således behövs inte screening av H. pylori om inte symtom föreligger.



Trötthet och nedsatt livskvalitet bidrar till sjukskrivning, sjukpension och mental ohälsa. Vid en 5 års uppföljning upptäcktes ingen progredierande försämring av livskvaliteten i motsats till en förväntad åldersrelaterad reduktion i normalbefolkningen.



Vår dubbel-blinda randomiserade kontrollerade studie med gammalinolensyra (GLA), en essentiell Omega-6 fettsyra, visade ingen överlägsenhet över placebo vad gäller förbättring av trötthet vid primärt SS. En generell rekommendation att använda denna hälsokostmedicinen vid SS kan således inte utfärdas.



En longitudinell uppföljning av körteldysfunktionen resulterade i fyndet att objektiva mätresultat tyder på en lätt försämring efter 5 år, vilket predikterades av lågt komplement vid baselineundersökningen. Tolkningen försvårades av påtagliga golv- och takeffekter vid användning av de tillgängliga mätmetoderna.



Efter samkörning av vårt patientmaterial med svenska dödsorsaks- och cancerregistret kunde vi beräkna standardiserade dödsrisker och cancerincidensrisker (SMRs och SIRs). SIR för non-Hodgkin's lymfom: 15,57 [95% konfidens intervall (CI) 7,77-27,85]. Osaksspecifik SMR för död till följd av hematologisk malignitet: 7,89 [CI 2,89-17,18]. Aggressiva diffusa stora B-cells-lymfom predominerade. Riskfaktorer för både död och lymfom var lågt komplement vid tiden för diagnosen. Nya starka prediktorer för lymfomutveckling var CD4+ T-lymfocytopeni, hazard ratio (HR) 8,14 [CI 2,10-31,53] och låg CD4+/CD8+ T-cells kvot, HR 10,92 [CI 2,8-41,83]. Totalmortalitet, kardiovaskulär mortalitet och incidens av icke-hematologisk malignitet var inte ökade. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Isenberg, David, Centre for Rheumatology, Department of Medicine, The Middlesex Hospital and University College, Lond
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Skeleton, transplantation, muskelsystem, Skelett, rheumatology locomotion, long-term outcome, Sjögren's Syndrome, Helicobacter pylori infection, prospective cohort studies, SMR, SIR for lymphoproliferative disease, fatigue, health-related quality of life, complement function, oncology, Cytologi, Immunology, cancer, serologi, Immunologi, serology, cancerology, onkologi, reumatologi, muscle system, CD4+ T-lymphocytopenia, Cytology
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2005:59
pages
144 pages
publisher
Department of Rheumatology, Lund University
defense location
Medicinklinikens Aula, Universitetssjukhuset MAS, Ingång 35
defense date
2005-08-26 13:00:00
ISSN
1652-8220
ISBN
91-85439-63-0
language
English
LU publication?
yes
additional info
. 2001. Seroprevalence of Helicobacter pylori Helicobacter pylori in primary Sjögren's syndrome Clinical and Experimental Rheumatology, vol 19 pp 633-8.
. 2002. Gammalinolenic acid treatment of fatigue associated with primary Sjögren's syndrome Scandinavian Journal of Rheumatology, vol 31 pp 72-9.
. 2005. Proposed core set of outcome measures in patients with primary Sjögren's syndrome. A 5 year followup The Journal of Rheumatology, vol 32 pp 1495-502.
. . Lymphoma and other malignancies in primary Sjögren's syndrome. A cohort study on cancer incidence and lymphoma predictors (submitted)
. 2004. Mortality and causes of death in primary Sjögren's syndrome Arthritis & Rheumatism, vol 50 pp 1262-9.
id
455e29a3-2a78-45b5-b312-d4f3bd182e37 (old id 545178)
date added to LUP
2016-04-01 16:11:52
date last changed
2019-05-21 20:56:23
@phdthesis{455e29a3-2a78-45b5-b312-d4f3bd182e37,
  abstract     = {{This work was aimed at improving our understanding of the course of primary Sjögren's syndrome (SS). The Malmö SS patient register and the 2002 American-European Consensus Criteria formed the basis of all studies.<br/><br>
<br/><br>
Helicobacter pylori (H. pylori) was not more prevalent in SS patients or associated with severe glandular or immunological dysfunction. Consequently, our results do not support screening for or eradication of latent H. pylori infection.<br/><br>
<br/><br>
Fatigue and reduced health-related quality of life contribute to sick leave, early retirement and mental distress. After 5 years quality of life was preserved at the same level, in contrast to the expected age-dependent decline in the normal population.<br/><br>
<br/><br>
Our double-blind randomized controlled trial with gammalinolenic acid (GLA), an essential omega-6 fatty acid, failed to alleviate fatigue, precluding a general recommendation of this complementary treatment.<br/><br>
<br/><br>
Longitudinal follow-up of glandular dysfunction revealed slight deterioration of objective measures after 5 years, predicted by low complement levels at baseline. However, the available measures of assessment suffer from considerable floor/ceiling effects.<br/><br>
<br/><br>
Linking our register to the Swedish Cause-of-Death and Cancer Registers, we calculated standardized mortality ratios (SMRs) and incidence ratios (SIRs) for solid and lymphoproliferative malignancies. SIR (95% confidence interval (CI)) for non-Hodgkin lymphoma: 15.57 (CI 7.77-27.85), cause-specific SMR for death from haematological neoplasms: 7.89 (CI 2.89-17.18). Aggressive diffuse large B-cell lymphomas predominated. Risk factor for both death and lymphoma was low complement at diagnosis. Novel strong predictors of lymphoma development were CD4+ T-lymphocytopenia (hazard ratio (HR): 8.14, CI 2.10-31.53) and a low CD4+/CD8+ T-cell ratio ?0.8 (HR 10.92, CI 2.80-41.83). All-cause mortality, cardiovascular mortality and the incidence of non-haematological malignancies were not increased.}},
  author       = {{Theander, Elke}},
  isbn         = {{91-85439-63-0}},
  issn         = {{1652-8220}},
  keywords     = {{Skeleton; transplantation; muskelsystem; Skelett; rheumatology locomotion; long-term outcome; Sjögren's Syndrome; Helicobacter pylori infection; prospective cohort studies; SMR; SIR for lymphoproliferative disease; fatigue; health-related quality of life; complement function; oncology; Cytologi; Immunology; cancer; serologi; Immunologi; serology; cancerology; onkologi; reumatologi; muscle system; CD4+ T-lymphocytopenia; Cytology}},
  language     = {{eng}},
  publisher    = {{Department of Rheumatology, Lund University}},
  school       = {{Lund University}},
  series       = {{Lund University Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Living and Dying with Primary Sjögren's Syndrome Studies on Aetiology, Treatment, Lymphoma, Survival and Predictors}},
  volume       = {{2005:59}},
  year         = {{2005}},
}