Consequences of disease and treatment in ANCA-associated vasculitis

Janneke Tuin

    Research output: ThesisThesis fully internal (DIV)

    1025 Downloads (Pure)

    Abstract

    ANCA-associated vasculitis is a group of auto-immune diseases characterized by inflammation of the small to medium-sized blood vessels. Potentially, every small and medium-sized blood vessel can be involved in these diseases, giving rise to a multiplicity of potential clinical signs, symptoms and disease phenotypes. Standard induction treatment consists of cyclophosphamide and high-dose glucocorticoids in a tapering regime. Despite high survival rates, both drugs are associated with severe short-term and long-term side-effects. Optimizing treatment to reduce short and long-term damage associated with both disease and treatment is essential.
    The work in this thesis is focused on two issues regarding ANCA-associated vasculitis. In the first part, the impact of AAV on reproduction and gonadal function are investigated. In general pregnancy in vasculitis patients is considered high risk and associated with complications. We reported good outcome of pregnancy for both the mother and the child in the largest studied population up to know. Disease remission appears to be an important condition for such good outcome. Treatment with cyclophosphamide affects fertility. We have shown that with the current treatment protocols toxicity is still present, but substantially lower compared to previous protocols. Cyclophosphamide is therefore discouraged, but should not be withheld in the case of life-threatening disease. We have shown that androgen deficiency might play a role in fatigue and impaired quality of life in men with AAV.
    In order to prevent damage, several treatment options to individualize and thereby optimize treatment are studied in the second part of this thesis. Trimethoprim/sulfamethoxazole and mycophenolate mofetil were studied as induction treatment for two different subgroups of AAV patients. Both treatment showed good efficacy in combination with low toxicity or side-effects. We hypothesize that glucocorticoid treatment based on individual sensitivity for glucocorticoids would improve outcome and reduces short- and long-term complications. Overall, this thesis gives insight in several consequences of disease and treatment and provides treatment options for further improvement and prevention of damage.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Stegeman, Coen, Supervisor
    • Sanders, Jan Stephan, Co-supervisor
    • van Beek, Andre, Co-supervisor
    • Luqmani, R., Assessment committee, External person
    • ter Wee, P.M., Assessment committee, External person
    • Wolffenbuttel, Bruce, Assessment committee
    Award date24-May-2017
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-028-0577-2
    Electronic ISBNs978-94-028-0584-0
    Publication statusPublished - 2017

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