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

Elke Theander

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

Internmedicin - epidemiologi

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Sammanfattning

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.

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution	Institutionen för kliniska vetenskaper, Malmö
Handledare	Jacobsson, Lennart, handledare
Tilldelningsdatum	2005 aug. 26
Förlag	Department of Rheumatology, Lund University
ISBN (tryckt)	91-85439-63-0
Status	Published - 2005

Bibliografisk information

Defence details

Date: 2005-08-26
Time: 13:00
Place: Medicinklinikens Aula, Universitetssjukhuset MAS, Ingång 35

External reviewer(s)

Name: Isenberg, David
Title: Professor
Affiliation: Centre for Rheumatology, Department of Medicine, The Middlesex Hospital and University College, Lond

---

<div class="article_info">. <span class="article_issue_date">2001</span>. <span class="article_title">Seroprevalence of Helicobacter pylori Helicobacter pylori in primary Sjögren's syndrome</span> <span class="journal_series_title">Clinical and Experimental Rheumatology</span>, <span class="journal_volume">vol 19</span> <span class="journal_pages">pp 633-8</span>.</div>
<div class="article_info">. <span class="article_issue_date">2002</span>. <span class="article_title">Gammalinolenic acid treatment of fatigue associated with primary Sjögren's syndrome</span> <span class="journal_series_title">Scandinavian Journal of Rheumatology</span>, <span class="journal_volume">vol 31</span> <span class="journal_pages">pp 72-9</span>.</div>
<div class="article_info">. <span class="article_issue_date">2005</span>. <span class="article_title">Proposed core set of outcome measures in patients with primary Sjögren's syndrome. A 5 year followup</span> <span class="journal_series_title">The Journal of Rheumatology</span>, <span class="journal_volume">vol 32</span> <span class="journal_pages">pp 1495-502</span>.</div>
<div class="article_info">. <span class="article_issue_date"></span>. <span class="article_title">Lymphoma and other malignancies in primary Sjögren's syndrome. A cohort study on cancer incidence and lymphoma predictors</span> (submitted)</div>
<div class="article_info">. <span class="article_issue_date">2004</span>. <span class="article_title">Mortality and causes of death in primary Sjögren's syndrome</span> <span class="journal_series_title">Arthritis & Rheumatism</span>, <span class="journal_volume">vol 50</span> <span class="journal_pages">pp 1262-9</span>.</div>

Ämnesklassifikation (UKÄ)

Klinisk medicin

Citera det här

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title = "Living and Dying with Primary Sj{\"o}gren's Syndrome Studies on Aetiology, Treatment, Lymphoma, Survival and Predictors",

abstract = "This work was aimed at improving our understanding of the course of primary Sj{\"o}gren's syndrome (SS). The Malm{\"o} 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.",

keywords = "Skeleton, transplantation, muskelsystem, Skelett, rheumatology locomotion, long-term outcome, Sj{\"o}gren'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",

author = "Elke Theander",

note = "Defence details Date: 2005-08-26 Time: 13:00 Place: Medicinklinikens Aula, Universitetssjukhuset MAS, Ing{\aa}ng 35 External reviewer(s) Name: Isenberg, David Title: Professor Affiliation: Centre for Rheumatology, Department of Medicine, The Middlesex Hospital and University College, Lond --- <div class={"}article_info{"}>. <span class={"}article_issue_date{"}>2001</span>. <span class={"}article_title{"}>Seroprevalence of Helicobacter pylori Helicobacter pylori in primary Sj{\"o}gren's syndrome</span> <span class={"}journal_series_title{"}>Clinical and Experimental Rheumatology</span>, <span class={"}journal_volume{"}>vol 19</span> <span class={"}journal_pages{"}>pp 633-8</span>.</div> <div class={"}article_info{"}>. <span class={"}article_issue_date{"}>2002</span>. <span class={"}article_title{"}>Gammalinolenic acid treatment of fatigue associated with primary Sj{\"o}gren's syndrome</span> <span class={"}journal_series_title{"}>Scandinavian Journal of Rheumatology</span>, <span class={"}journal_volume{"}>vol 31</span> <span class={"}journal_pages{"}>pp 72-9</span>.</div> <div class={"}article_info{"}>. <span class={"}article_issue_date{"}>2005</span>. <span class={"}article_title{"}>Proposed core set of outcome measures in patients with primary Sj{\"o}gren's syndrome. A 5 year followup</span> <span class={"}journal_series_title{"}>The Journal of Rheumatology</span>, <span class={"}journal_volume{"}>vol 32</span> <span class={"}journal_pages{"}>pp 1495-502</span>.</div> <div class={"}article_info{"}>. <span class={"}article_issue_date{"}></span>. <span class={"}article_title{"}>Lymphoma and other malignancies in primary Sj{\"o}gren's syndrome. A cohort study on cancer incidence and lymphoma predictors</span> (submitted)</div> <div class={"}article_info{"}>. <span class={"}article_issue_date{"}>2004</span>. <span class={"}article_title{"}>Mortality and causes of death in primary Sj{\"o}gren's syndrome</span> <span class={"}journal_series_title{"}>Arthritis & Rheumatism</span>, <span class={"}journal_volume{"}>vol 50</span> <span class={"}journal_pages{"}>pp 1262-9</span>.</div>",

year = "2005",

language = "English",

isbn = "91-85439-63-0",

series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",

publisher = "Department of Rheumatology, Lund University",

school = "Department of Clinical Sciences, Malm{\"o}",

}

TY - THES

T1 - Living and Dying with Primary Sjögren's Syndrome Studies on Aetiology, Treatment, Lymphoma, Survival and Predictors

AU - Theander, Elke

N1 - Defence details Date: 2005-08-26 Time: 13:00 Place: Medicinklinikens Aula, Universitetssjukhuset MAS, Ingång 35 External reviewer(s) Name: Isenberg, David Title: Professor Affiliation: Centre for Rheumatology, Department of Medicine, The Middlesex Hospital and University College, Lond --- <div class="article_info">. <span class="article_issue_date">2001</span>. <span class="article_title">Seroprevalence of Helicobacter pylori Helicobacter pylori in primary Sjögren's syndrome</span> <span class="journal_series_title">Clinical and Experimental Rheumatology</span>, <span class="journal_volume">vol 19</span> <span class="journal_pages">pp 633-8</span>.</div> <div class="article_info">. <span class="article_issue_date">2002</span>. <span class="article_title">Gammalinolenic acid treatment of fatigue associated with primary Sjögren's syndrome</span> <span class="journal_series_title">Scandinavian Journal of Rheumatology</span>, <span class="journal_volume">vol 31</span> <span class="journal_pages">pp 72-9</span>.</div> <div class="article_info">. <span class="article_issue_date">2005</span>. <span class="article_title">Proposed core set of outcome measures in patients with primary Sjögren's syndrome. A 5 year followup</span> <span class="journal_series_title">The Journal of Rheumatology</span>, <span class="journal_volume">vol 32</span> <span class="journal_pages">pp 1495-502</span>.</div> <div class="article_info">. <span class="article_issue_date"></span>. <span class="article_title">Lymphoma and other malignancies in primary Sjögren's syndrome. A cohort study on cancer incidence and lymphoma predictors</span> (submitted)</div> <div class="article_info">. <span class="article_issue_date">2004</span>. <span class="article_title">Mortality and causes of death in primary Sjögren's syndrome</span> <span class="journal_series_title">Arthritis & Rheumatism</span>, <span class="journal_volume">vol 50</span> <span class="journal_pages">pp 1262-9</span>.</div>

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Skeleton

KW - transplantation

KW - muskelsystem

KW - Skelett

KW - rheumatology locomotion

KW - long-term outcome

KW - Sjögren's Syndrome

KW - Helicobacter pylori infection

KW - prospective cohort studies

KW - SMR

KW - SIR for lymphoproliferative disease

KW - fatigue

KW - health-related quality of life

KW - complement function

KW - oncology

KW - Cytologi

KW - Immunology

KW - cancer

KW - serologi

KW - Immunologi

KW - serology

KW - cancerology

KW - onkologi

KW - reumatologi

KW - muscle system

KW - CD4+ T-lymphocytopenia

KW - Cytology

M3 - Doctoral Thesis (compilation)

SN - 91-85439-63-0

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Rheumatology, Lund University

ER -

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

Sammanfattning

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Ämnesklassifikation (UKÄ)

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