Relapsing Polychondritis and Its Rheumatologic Implications

Introduction

Relapsing polychondritis (RP) is a systemic immune-mediated disease characterized by recurring inflammatory episodes affecting cartilaginous and proteoglycan-rich tissues. These episodes impact various areas, including the elastic cartilage of the ear and nose, hyaline cartilage in peripheral joints, fibrocartilage at axial sites, and tracheobronchial tree cartilage. These inflammatory events lead to progressive anatomical deformities and functional impairments in the affected structures. The majority of RP cases, around 80 %, manifest through auricular chondritis and polyarthritis, but other organs can also potentially be affected. The onset is often gradual, marked by acute, painful inflammatory crises. It can reoccur and create challenges for diagnosis. Delayed diagnosis may result in therapeutic delays and an increased risk of permanent or life-threatening consequences. About 30 % of adult RP patients also exhibit associations with other autoimmune disorders, with rheumatoid arthritis (RA) being the most common. This article explains the clinical presentation, laboratory and instrumental investigations, diagnostic criteria, and therapeutic options.

What Is Relapsing Polychondritis?

Relapsing polychondritis is an autoimmune disease affecting cartilaginous tissue. Joint pain, inflammation, and tenderness contribute to rheumatological aspects of RP. The symptoms of RP include inflammation of the eye, ear, large joints, and nose. Sometimes, in severe cases, hearing loss is also seen.

What Causes Relapsing Polychondritis?

The cause of relapsing polychondritis remains unidentified. It is proposed to develop in individuals with a genetic predisposition when exposed to a triggering factor, which could be an infectious agent, chemical substance, toxic exposure, or direct trauma. Some studies show that it can occur due to trauma to the ear. One plausible explanation involves the release of cryptogenic antigens after trauma, leading to the immune system recognizing and responding to the antigen. Genetic investigations have indicated a connection between the HLA-DR4 antigen and relapsing polychondritis. Basically, it is caused due to alterations in the genetic structure.

What Are the Symptoms of Relapsing Polychondritis?

Chondritis and polyarthritis stand out as the primary clinical features of RP. However, since inflammation of cartilaginous tissue has the potential to occur in numerous anatomical regions, the disease often presents with diverse combinations of seemingly unrelated signs and symptoms. RP can also affect other structures rich in proteoglycans, such as the eye, heart valve, and blood vessels. This complexity complicates the diagnostic process, especially when auricular and nasal involvement is not yet evident or when constitutional symptoms, including fever, weight loss, night sweats, fatigue, and lympho-adenomegaly, precede the appearance of characteristic manifestations.

The following are the symptoms of RP:

• Inflammation of the ear.

• Bone pain.

• Nasal tissue inflammation.

• Inflammation of the eye (conjunctivitis).

• Hearing loss in severe cases.

• Vertigo.

How To Diagnose Relapsing Polychondritis?

The diagnosis of relapsing polychondritis relies primarily on a combination of clinical features, radiographic findings, and biopsy of a cartilaginous site, following clinical criteria proposed by McAdams et al. Three out of six criteria are necessary for diagnosis, which include:

• Recurrent chondritis of both auricles

• Non-erosive inflammatory arthritis

• Chondritis of nasal cartilage

• Inflammation of ocular structures (conjunctivitis, keratitis, scleritis, or uveitis)

• Chondritis of the respiratory tract with laryngeal or tracheal cartilage involvement

• Cochlear or vestibular damage resulting in neurosensory hearing loss, tinnitus, or vertigo.

The following are the methods to diagnose RP:

1. Examination - Patients suspected of having relapsing polychondritis are advised to undergo a dynamic exploratory CT scan (computed tomography) to assess airway involvement. CT scan findings may reveal functional airway abnormalities like air trapping and collapse, along with thickening of the airway wall and luminal narrowing. Pulmonary function testing is conducted to evaluate airway trapping and assess lung volumes. PET-CT, a novel diagnostic modality, aids in early disease recognition and provides a targeted biopsy site.

2. Biopsy - A biopsy of auricular cartilage confirms the diagnosis of polychondritis. Positive serologic testing for rheumatoid factor and antinuclear antibody may be observed in patients with associated rheumatologic diseases. Complement levels are typically normal in relapsing polychondritis.

3. Radiographs- Radiographic findings may include non-erosive juxta-articular osteopenia and uniform joint space narrowing, suggestive of arthropathy. Anti-type II collagen antibody tests are not routinely available, and when conducted, these antibodies are not universally present. No laboratory markers exist to assess ongoing cartilage damage.

What Are Rheumatological Implications of Relapsing Polychondritis?

The following are the rheumatological implications of RP:

• Cartilage Inflammation - RP is characterized by the inflammation of the cartilage of ears, nose, trachea, and joints. This leads to inflammation, pain, and tenderness of the cartilage.

• Involvement of the Joints- The rheumatological symptoms include inflammation of joints (arthritis) and stiffness in the large joints such as knees and ankles.

• Involvement of the Skin- The dermatological symptoms include rashes and ulcers of the skin.

• Involvement of the Eye - The rheumatological aspects include inflammation of the eye, redness of the eye, pain, and sensitivity to light.

What Is the Treatment of Relapsing Polychondritis?

The therapeutic objective is to manage the inflammatory crises and achieve long-term suppression of immune-mediated pathogenic mechanisms. Ideally, treatment should provide swift symptom relief and prevent multi-organ impact on cartilaginous structures, with minimal side effects, considering the requirement for chronic administration.

The following are the ways by which RP can be treated:

Medication

• For non-severe forms of RP, characterized by involvement of the nose, external ear, or joints only, non-steroidal anti-inflammatory drugs (NSAIDs) may be employed for pain control and inflammation. Mild manifestations can also be addressed with Dapsone (50 to 100 mg, once daily; maximum dose of 200 mg, once daily) or Colchicine (0.6 mg 2 to 4 times daily).

• In cases of NSAID resistance or severe forms, including ocular, laryngotracheal, or cardiac involvement, systemic vasculitis, and severe polychondritis, systemic corticosteroids are the preferred treatment.

• Oral Prednisone typically initiates at a dose ranging from 0.25 to 1 mg/kg daily, with a reduction in dose, if feasible, throughout the course of the disease.

• In situations requiring a rapid effect, intravenous Pulse Methylprednisolone (500 to 1000 mg/day) can be beneficial.

Conclusion

RP is a rare and potentially life-threatening autoimmune disease with an unknown origin, primarily impacting cartilaginous and proteoglycan-rich structures. Patients exhibit a diverse range of clinical manifestations. In the absence of standardized treatment guidelines, therapy for RP remains empirical, determined by disease activity and organ involvement severity. Mild cases are managed with NSAIDs, Colchicine, Dapsone, and low-dose corticosteroids. Severe or life-threatening complications necessitate high-dose corticosteroids and immunosuppressants. The rheumatological implications of RP were discussed above in this article. Moreover, there should be more research on the treatment of RP.