Relapsing Polychondritis (RP) is a rare, systemic, chronic inflammatory disease that primarily targets the body’s cartilage and connective tissue. It is characterized by recurrent, episodic inflammation affecting the ears, nose, trachea, joints, and heart valves. Repeated inflammation leads to the progressive destruction of cartilage, resulting in structural changes like a saddle nose deformity or life-threatening airway collapse. While the resulting damage is clear, the precise cause of RP remains unknown, leading researchers to focus on contributing triggers and underlying biological mechanisms.
The Autoimmune Basis of Relapsing Polychondritis
Relapsing Polychondritis is classified as an autoimmune disorder, where the immune system mistakenly attacks the body’s healthy cartilage. The mechanism involves a pathological immune response directed against components of the cartilage matrix, driven by both humoral (antibody) and cellular (T-cell) arms of the immune system.
The attack is mediated by specific autoantibodies in the bloodstream. Between 30 and 70 percent of patients with RP have circulating antibodies directed against Type II collagen, the primary protein in hyaline cartilage. Antibodies against minor collagens, like Type IX and Type XI, are also detected. Antibodies targeting matrilin-1, an extracellular matrix protein in the trachea, are often elevated in patients experiencing respiratory symptoms.
The cellular immune system also propagates the inflammatory cycle. T-lymphocytes infiltrate the affected tissue and release pro-inflammatory signaling molecules called cytokines. These cytokines, such as interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-alpha), drive inflammation and recruit more immune cells. This coordinated attack by autoantibodies and inflammatory cells causes the characteristic breakdown and replacement of cartilage with fibrous tissue.
Genetic Predisposition and Associated Conditions
Underlying genetic factors establish a susceptibility to developing Relapsing Polychondritis, though there is no clear inheritance pattern. Research has identified associations with certain human leukocyte antigen (HLA) markers, which regulate the immune system. Specific types, such as HLA-DR4, occur more frequently in people with RP than in the general population.
VEXAS Syndrome
A recently identified genetic mechanism involves VEXAS syndrome, an X-linked autoinflammatory disorder caused by somatic mutations in the UBA1 gene. This syndrome predominantly affects older men and presents as a severe form of RP often refractory to standard treatments. The mutation acts as a foundational trigger for the RP phenotype, frequently co-occurring with hematologic conditions like Myelodysplastic Syndrome (MDS).
Autoimmune Overlap
RP often overlaps with other systemic autoimmune diseases, affecting 25 to 35 percent of patients. This co-existence suggests shared mechanisms or genetic predispositions. Conditions frequently seen alongside RP include systemic vasculitis, rheumatoid arthritis, and systemic lupus erythematosus. The presence of an established systemic disease can be considered a chronic trigger that sets the stage for RP onset.
Acute Events That Trigger Relapse
For patients living with Relapsing Polychondritis, acute events can trigger a sudden flare-up or relapse. Infections are commonly suspected triggers, as they activate the immune system and can push the dysregulated system into an inflammatory episode. Viral or bacterial illnesses, particularly those affecting the upper respiratory tract, often precede the onset of a relapse.
Physical trauma or localized injury to cartilaginous structures can also initiate a flare. Documented cases show that localized cartilage damage, such as pressure on the ears from an accident or contact sport, precedes a painful inflammatory episode. This suggests that physical damage to the target tissue exposes cartilage antigens, leading to a renewed immune response.
General physical and emotional stressors are frequently observed preceding a relapse, though they are not scientifically confirmed as direct causes. This may be due to the systemic release of stress hormones, which modulate immune function and contribute to a lowered inflammatory threshold. The episodic nature of RP suggests that a combination of internal immune dysfunction and external stressors contributes to the overall disease course.