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Etiology and pathogenesis of relapsing polychondritis

Clement J Michet, MD
Section Editor
Jane Hoyt Buckner, MD
Deputy Editor
Paul L Romain, MD


Relapsing polychondritis (RPC) is a systemic inflammatory/degenerative disease with varying clinical manifestations that can include compromise of the structural and functional integrity of cartilage; organs of special sense; and the cardiovascular, renal, and nervous systems (table 1). (See "Clinical manifestations of relapsing polychondritis".)

This topic will review our current understanding of the etiology and pathogenesis of RPC. The pathologic changes in this disorder are described elsewhere. (See "Pathology of relapsing polychondritis".)

The approach to diagnosis and treatment of RPC are presented separately. (See "Diagnostic evaluation of relapsing polychondritis" and "Treatment of relapsing polychondritis".)


The etiology of relapsing polychondritis (RPC) is unknown. Although few clues are evident, there appears to be a genetic susceptibility, an overlap with other disorders associated with immunologic abnormalities, and the potential for multiple inciting events including chemical insults. This hypothesis is supported by a series of observations which imply that RPC is not a primary disease but a syndrome associated with multiple precipitating factors that appear in a genetically susceptible subject. The paraneoplastic myelodysplastic relationship suggests a potential pathophysiologic role for clonally expressed lymphoid stem cells in which functional T cell defects induce both autoimmunity and uncontrolled neoplastic hematopoietic clonal proliferation. However, a report of abrupt onset after recreational drug abuse implies that a direct biochemical insult also can induce the disease. (See 'Genetic susceptibility' below and 'Association with other immunologic diseases' below and 'Induction by toxins' below.)

Genetic susceptibility — No association of RPC with human leukocyte antigen (HLA) class I (HLA-A and HLA-B) antigens has been identified [1]. However, an association has been described between RPC and HLA class II, specifically with HLA-DR4 [2]. Genetic analysis of the frequency of HLA class II histocompatibility antigens was performed in 60 central European Caucasian patients with RPC [2]; the frequency of HLA-DR4 was 56 percent compared with 26 percent in a healthy control group. Genotyping showed no preferential association of specific DR4 subtype alleles, in contrast to the clear association of rheumatoid arthritis (RA) with DRB1*0401 and DRB1*0404 [3]. These RA-associated alleles have in common a region of highly similar sequence, designated the shared epitope (see "HLA and other susceptibility genes in rheumatoid arthritis"). Further, a novel DR4 allele (DRB1*0421), has been identified in a single patient with RPC [4]. Thus, although RPC and RA may share clinical and immunologic features and, at times, may coexist, the contribution of HLA-DRB1*04 alleles to disease may differ between these two disorders.

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Literature review current through: Nov 2017. | This topic last updated: Nov 24, 2016.
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