The Biology of RP, Mimics, and the VEXAS Connection

To understand relapsing polychondritis (RP), it helps to look at the “instruction manual” of your immune system. In a healthy body, the immune system acts like a security team that ignores your own tissues. In RP, that security team mistakenly identifies cartilage—the flexible structural tissue in your ears, nose, and airways—as a threat and begins to attack it ^[1].

The Biology of Cartilage Attack

The exact mechanism of the immune system’s attack on cartilage is incompletely understood. Researchers propose that in some people with RP, the body produces autoantibodies (proteins that attack the self) against specific components of the cartilage, most notably type II collagen ^[2].

When these antibodies bind to the cartilage, they may trigger an inflammatory response. Specialized white blood cells rush to the area and release chemicals (cytokines) that further damage the cartilage matrix ^[1][3]. Over time, this repeated inflammation can cause the cartilage to lose its structure, leading to the “softening” or collapse of tissues in the nose or windpipe ^[4]. However, not every patient has these antibodies, and there is no single diagnostic blood test based on them; the immune pathways are complex.

Sorting Through the ‘Mimics’

Because RP is so rare and lacks a definitive biomarker, doctors must carefully rule out other conditions that can look very similar. This process is called a differential diagnosis.

• Granulomatosis with Polyangiitis (GPA): Formerly called Wegener’s, this is a type of vasculitis (inflammation of blood vessels). Like RP, it can cause a “saddle-nose” deformity and ear pain ^[5]. However, GPA is more likely to affect the sinuses, lungs, and kidneys. Doctors often use an ANCA test (a blood test for specific antibodies), urine tests, and imaging to tell them apart, though ANCA can be negative and the two conditions can sometimes overlap ^[6][7].
• Leprosy: While rare in many parts of the world, this infection can cause ear inflammation. A key difference is that leprosy can affect the earlobe, whereas RP often spares the lobe because it lacks cartilage ^[8].
• Infections: Bacterial infections of the ear (perichondritis) can look exactly like an RP flare. Never assume a red, painful ear is just an RP flare. If the ear is draining, rapidly worsening, or accompanied by a fever, it requires prompt clinical assessment. Do not increase your immunosuppressive medications until infection has been ruled out ^[9].

The VEXAS Connection

In recent years, scientists discovered that some people with RP symptoms actually have an overlapping condition called VEXAS syndrome. Understanding this distinction is crucial because VEXAS often requires different management ^[10].

VEXAS is caused by an acquired mutation in a gene called UBA1. “Acquired” (or somatic) means you were not born with this mutation and cannot pass it on to your children; instead, the mutation developed spontaneously in your blood-forming cells later in life ^[11].

Who is evaluated for VEXAS?

VEXAS testing is specialist-directed and not a routine test for everyone with RP. Doctors may recommend genetic testing for the UBA1 mutation based on clinical clues ^[12][13]:

• Demographics: It is most strongly associated with older men (usually over 50), though women or atypical patients can also be affected.
• Blood Clues: A common sign is macrocytic anemia (where red blood cells are unusually large, measured as “MCV” on a blood test) or a low platelet count ^[12].
• Systemic Signs: Persistent fevers, skin lesions (like painful bumps or rashes), and a history of blood clots (thrombosis) are common ^[14].
• Refractory Disease: Inflammation that is unusually resistant to standard steroid treatments ^[15].

Why the Distinction Matters

VEXAS-associated RP tends to be more refractory, meaning it is harder to treat with standard medications. Because VEXAS involves the blood-forming cells in the bone marrow, patients with this condition need a care team that includes both a rheumatologist and a hematologist (blood specialist) to monitor for related conditions like myelodysplastic syndrome (MDS) ^[16].

While identifying VEXAS opens discussions for other therapies, such as JAK inhibitors or, in highly selected cases, bone marrow transplantation, these remain specialist, evolving, and often off-label options with important risks (like infection and clotting) rather than routine pathways ^[17].