What Causes Relapsing Polychondritis, and Is It Hereditary?

Relapsing polychondritis (RP) is an uncommon, immune-mediated inflammatory disease. It primarily affects cartilage and related structures, most commonly the external ears, nose, and the airways (larynx, trachea, and bronchi) ^[1]. It can also cause inflammatory arthritis in the joints and affect non-cartilage tissues, leading to eye inflammation, inner-ear problems, skin rashes, and cardiovascular issues ^[1].

The exact cause of relapsing polychondritis is currently unknown ^[1]. If you are wondering whether you did something to cause your illness, the answer is no. RP is not a result of a personal failure, it is not contagious, and it is not caused by your diet or typical lifestyle choices ^[1].

Important Safety Note: Because RP can affect the airways, sudden vision, or hearing, you should seek urgent medical assessment if you experience new or worsening trouble breathing, noisy breathing (stridor), a rapidly progressive hoarseness, inability to swallow, or sudden changes in your vision or hearing.

What is Known and What is Not Known

• Known: RP is a rare, immune-mediated disease ^[1]. It is not your fault, and it is not contagious ^[1].
• Unknown: The exact reason the immune system begins attacking the body is still a subject of ongoing research. Proposed environmental triggers and specific immune mechanisms are still being studied and are not fully proven ^[1].

The Immune System’s Role

Current evidence suggests that RP involves abnormal responses from both the general (innate) and specialized (adaptive) parts of the immune system ^[2]. In a healthy body, the immune system fights off infections, but in RP, it is proposed that the immune system mistakenly targets the body’s own tissues ^[1].

Research has shown that some people with RP develop autoantibodies—immune proteins that target normal body structures. In research settings, antibodies targeting specific structural proteins in cartilage (like type II, IX, and XI collagens, or matrilin-1) have been found in some patients ^{[1] [3]}.

• Not a diagnostic test: It is important to know that these antibodies are highly variable, are not present in everyone with RP, and are not specific to this disease ^[3]. There is no single validated blood test that proves you have RP. The diagnosis is based on your clinical symptoms, physical examination, and other targeted investigations ^[3].
• Scientists are still researching whether these antibodies directly cause tissue injury or if they are simply a byproduct of the inflammation ^[3].

Is Relapsing Polychondritis Hereditary?

Many patients worry that their children will inherit the condition. Fortunately, familial cases have been reported, but no consistent inheritance pattern has been established, and most cases are sporadic ^[4].

There is a concept called genetic susceptibility, meaning certain genetic variations might make a person slightly more likely to develop an autoimmune disease ^[5].

• Researchers have found that certain immune system genes (called HLA genes) are sometimes associated with RP ^[5].
• These associations are inconsistent and vary greatly depending on a person’s population or ancestry ^[6].
• Because possessing these genes does not predict who will develop RP, routine genetic screening for asymptomatic family members is not recommended ^[4].

Did Something Trigger It?

Because the root cause is unknown, patients often wonder if a specific event triggered their RP. Researchers have investigated several possibilities, but these remain limited associations or case reports, not proven causes ^[1]:

• Infections: RP has been reported after certain infections, such as COVID-19, leading to a theory that fighting a virus might cross-activate the immune system ^{[7] [8]}.
• Medications: Some cases of RP-like inflammation have been reported after patients started immune-stimulating medications, particularly certain cancer immunotherapies called immune checkpoint inhibitors ^{[9] [10]}. Never stop a prescribed cancer treatment or other medication without first discussing the risks and benefits with your treating clinician.
• Physical Trauma: There are theories that physical injury to the ear or nose cartilage might provoke inflammation, but this is not an established cause ^{[11] [1]}.

The Role of VEXAS Syndrome

Recently, researchers identified a distinct, acquired autoinflammatory condition called VEXAS syndrome, which can overlap with or mimic RP ^[12]. VEXAS is not present in most people with RP. It is typically considered in a specific group of patients—most often older men with unexplained widespread inflammation, specific skin or lung findings, or blood abnormalities like macrocytic anemia (enlarged red blood cells) ^[13].

VEXAS syndrome is caused by a mutation in a gene called UBA1 ^[14].

• It is not inherited: The UBA1 mutation is somatic, meaning it is acquired during a person’s lifetime in their blood-forming cells ^[15]. It cannot be passed down to children.
• If your clinical picture suggests VEXAS, your doctor may recommend a specialized sequencing test of your blood to look for this acquired mutation ^[13].