Relapsing Polychondritis (RP) is a rare, chronic, systemic inflammatory disorder that causes recurrent episodes of destructive inflammation primarily targeting cartilage throughout the body. This condition frequently affects the flexible cartilage of the ears and nose, the structural cartilage of the joints, and the rings of the trachea and bronchi. The recurring inflammation leads to progressive structural damage, such as the collapse of the nasal bridge or the narrowing of the airways.
The Autoimmune Foundation
The underlying mechanism of Relapsing Polychondritis involves a breakdown of the body’s self-tolerance, establishing it as an autoimmune disease. The immune system mistakenly identifies healthy tissues as foreign invaders and mounts an attack against them. The targets of this misdirected response are the structural components of cartilage.
The immune attack is driven by both cellular and antibody-mediated responses. Circulating autoantibodies have been detected in the blood of many patients, specifically targeting Type II collagen, which is the most abundant structural protein in hyaline cartilage. These immune proteins may also target Type IX and Type XI collagen, along with other cartilage-specific proteins.
This humoral response is complemented by an aberrant cellular immune response involving T-cells. These T-cells become activated and infiltrate the cartilage, releasing inflammatory signaling molecules that promote the destruction of the surrounding matrix. The presence of elevated levels of autoantibodies against Type II collagen often correlates with the severity of acute flare-ups.
Identifying Acute Environmental Causes
While the autoimmune mechanism sets the stage for the disease, external factors are suspected of acting as triggers for the initial onset or subsequent relapses. These acute environmental causes generally fall into categories of infectious agents, intense physical stressors, or direct tissue injury. The theory is that in a genetically susceptible individual, an external event ignites the dormant autoimmune potential.
Infections, both viral and bacterial, are frequently proposed as initiating events for RP. The hypothesis of molecular mimicry suggests that a component of an invading microbe shares a similar molecular structure with a protein found in human cartilage, such as Type II collagen. When the immune system responds to the microbe, this structural similarity causes immune cells to mistakenly cross-react and attack the body’s own cartilage components.
Physical trauma and major surgical procedures have also been documented as preceding events in numerous case reports of RP onset or flare-ups. Trauma to a cartilaginous site, such as the ear, may cause antigenic release, exposing previously hidden cartilage proteins to the immune system.
The systemic inflammatory response and immune dysregulation that follow significant surgery can similarly disrupt the existing immune balance, potentially precipitating the autoimmune attack. For instance, the rapid progression of RP has been observed following surgeries for lung cancer, suggesting that the intense stress of medical intervention can sometimes serve as a direct trigger.
Inherited Susceptibility and Demographic Risk
Beyond external triggers, an individual’s inherent biological makeup plays a significant part in determining susceptibility to Relapsing Polychondritis. The influence of genetics is highlighted by the association between RP and certain types of Human Leukocyte Antigens (HLA), proteins that regulate the immune response by presenting antigens to T-cells. Studies have identified an increased frequency of the HLA-DR4 type in patients, particularly those of Caucasian descent.
More detailed genetic analyses have also linked specific alleles, such as HLA-DRB116:02 and HLA-DQB105:02, with an elevated risk of developing RP. These HLA associations indicate that the ability of an individual’s immune system to present cartilage antigens is a key factor in the disease process. The typical age of onset for RP is between 40 and 60 years old.
While some studies have suggested a slight male or female predominance, the general consensus suggests that the disease occurs with roughly equal frequency across both sexes. This lack of a strong gender preference distinguishes it from many other systemic autoimmune conditions, which tend to affect women more frequently. The disease is also found across all racial groups, although the prevalence is extremely low.
Connection to Other Systemic Autoimmune Diseases
Relapsing Polychondritis rarely occurs in isolation, frequently presenting alongside other systemic conditions, a phenomenon sometimes referred to as RP-plus syndrome. This co-occurrence suggests a shared underlying pathway of immune dysregulation with other autoimmune or hematological disorders. Approximately 25 to 35 percent of all RP patients have a concomitant diagnosis of another systemic disease.
The most common co-morbidities involve other rheumatologic conditions, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and various forms of vasculitis. RP can overlap with large vessel vasculitis, leading to inflammation and damage of the aorta and other major arteries. The presence of these associated diseases points toward a common genetic or environmental vulnerability.
RP also shows a notable association with hematological malignancies, most commonly myelodysplastic syndromes (MDS). The simultaneous presentation of RP with MDS suggests a paraneoplastic mechanism, where the cancer itself or the body’s immune response to it triggers the inflammation of the cartilage. This frequent overlap with other serious systemic disorders underscores the complex, multi-systemic nature of Relapsing Polychondritis.