Relapsing Polychondritis¶
Chapter 378 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Relapsing polychondritis (RP) is a rare systemic disease characterized by recurrent inflammation of cartilaginous structures, primarily affecting ears, nose, respiratory tract, and joints.
- Epidemiology shows an estimated incidence of 0.7–3.5 cases per million per year, with no strong sex predilection, though some studies suggest female predominance.
- Diagnosis relies on clinical pattern recognition due to lack of specific biomarkers, using criteria like McAdam’s and Michet’s, which require combinations of clinical features and histologic evidence.
- Treatment includes corticosteroids, immunosuppressants (e.g., mycophenolate mofetil, azathioprine), and biologics (e.g., rituximab), with special consideration for VEXAS syndrome (UBA1 mutations).
- Complications include airway involvement, hearing loss, and cardiovascular manifestations, requiring multidisciplinary management.
1. DEFINITION & OVERVIEW¶
Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized by recurrent inflammation of cartilaginous structures. It primarily affects the ears, nose, respiratory tract, and joints, with potential involvement of other organs such as the eyes, cardiovascular system, and nervous system. The disease is marked by intermittent flares and remissions, often leading to progressive cartilage destruction and structural deformities.
1.1 VEXAS Syndrome¶
VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an acquired hematologic disorder associated with mutations in UBA1. It presents with recurrent chondritis of the ears and nose, systemic inflammation, and progressive bone marrow failure. Prompt diagnosis is critical to prevent life-threatening complications.
2. EPIDEMIOLOGY¶
The epidemiology of RP is poorly characterized, with limited global data. Estimated incidence ranges from 0.7–3.5 cases per million per year, and prevalence estimates range from 4.5–25 cases per million. The disease predominantly affects middle-aged adults, with no strong sex predilection in large population-based studies. However, some cohort studies suggest female predominance. VEXAS syndrome is more common in older males with severe systemic inflammation and bone marrow failure.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
The exact mechanisms driving RP are unclear, but autoimmunity to cartilage components is implicated. Animal models suggest that antibodies against type II collagen, IX collagen, or matrillin-1 may contribute to disease. Proinflammatory cytokines (e.g., TNF- α , IL-1, IL-6) and chemokines from both innate and adaptive immunity are involved. Genetic factors, environmental triggers, and immune dysregulation likely interact to drive pathogenesis.
3.1 VEXAS Syndrome Pathogenesis¶
VEXAS syndrome is caused by somatic mutations in UBA1, leading to defective ubiquitin ligase activity. This results in chronic inflammation, cartilage destruction, and bone marrow failure. The condition is associated with acquired hematologic mutations and requires genetic testing for confirmation.
4. CLINICAL FEATURES¶
RP presents with a wide range of clinical manifestations, including ear and nasal chondritis, respiratory tract involvement, musculoskeletal arthritis, and systemic complications. Key features include: (1) Ear involvement (80–90% of patients) with pain, swelling, or deformity; (2) Nasal chondritis with saddle nose deformity; (3) Airway involvement (e.g., subglottic stenosis, tracheomalacia); (4) Ocular inflammation (episcleritis, scleritis); (5) Neurologic complications (encephalitis, meningitis); and (6) Cardiovascular manifestations (aortic vasculitis).
4.1 Ear and Nasal Involvement¶
Ear chondritis is the most common manifestation, affecting 80–90% of patients. Pain may be localized to the pinnae or involve the entire ear. Nasal chondritis can lead to saddle nose deformity, septal ulcers, or mucosal inflammation. Patients may present with conductive hearing loss due to eustachian tube dysfunction or middle ear inflammation.
4.2 Airway and Respiratory Involvement¶
Subglottic stenosis, tracheomalacia, and tracheal calcification are common. Severe narrowing may cause stridor, requiring urgent intervention. Chronic airway damage can lead to bronchomalacia or tracheal collapse.
4.3 Musculoskeletal and Systemic Features¶
Nonerosive inflammatory arthritis affects small and large joints, with effusions in knees. Costochondritis may cause severe, bilateral chest pain mimicking acute coronary syndrome. Systemic features include fever, fatigue, and generalized inflammation.
5. DIFFERENTIAL DIAGNOSIS¶
RP must be differentiated from conditions such as granulomatosis with polyangiitis (GPA), autoimmune diseases (e.g., systemic lupus erythematosus), and infections. Key differentiators include: (1) Absence of antineutrophil cytoplasmic autoantibodies (ANCA) in RP vs. GPA; (2) Lack of granulomatous inflammation in RP vs. GPA; (3) Presence of VEXAS syndrome mutations in patients with unexplained chondritis; and (4) Specific imaging findings (e.g., tracheal calcification in RP vs. bronchial abnormalities in GPA).
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis relies on clinical criteria due to the absence of specific biomarkers. Key investigations include: (1) Physical examination for ear, nasal, and airway involvement; (2) Audiometry to assess hearing loss; (3) Chest CT for tracheobronchomalacia; (4) Laboratory tests (e.g., inflammatory markers, CBC); and (5) Histopathology of affected cartilage (not specific for RP).
Diagnostic Criteria for Relapsing Polychondritis¶
| Criteria | McAdam’s | Michet’s |
|---|---|---|
| Major Criteria | Inflammation of ear, nose, respiratory tract | Inflammation of ear, nose, or respiratory tract |
| Minor Criteria | Ocular inflammation, hearing loss, vestibular dysfunction, seronegative arthritis | Ocular inflammation, hearing loss, vestibular dysfunction, seronegative arthritis |
| Diagnosis Requirement | Three of six symptoms | Two major criteria or one major + two minor |
6.1 Diagnostic Criteria¶
McAdam’s criteria: Presence of three of six symptoms (bilateral auricular chondritis, nonerosive seronegative arthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, or vestibular dysfunction). Michet’s criteria: Two major criteria (inflammation of ear, nose, or respiratory tract) or one major plus two minor criteria (ocular inflammation, hearing loss, vestibular dysfunction, seronegative arthritis).
7. MANAGEMENT & TREATMENT¶
Treatment is tailored to disease severity and involves corticosteroids, immunosuppressants, and biologics. Key strategies include: (1) Glucocorticoids (e.g., prednisone) for acute flares; (2) Immunosuppressants (e.g., mycophenolate mofetil, azathioprine, cyclophosphamide) for chronic management; (3) Rituximab for refractory cases; (4) Supportive care for airway involvement (e.g., tracheostomy); and (5) Genetic testing for VEXAS syndrome in patients with unexplained chondritis.
Treatment Options for Relapsing Polychondritis¶
| Therapeutic Class | Drugs | Dosing |
|---|---|---|
| Corticosteroids | Prednisone | 1–2 mg/kg/day (tapered gradually) |
| Immunosuppressants | Mycophenolate mofetil | 1–2 g/day |
| Immunosuppressants | Azathioprine | 100–150 mg/day |
| Biologics | Rituximab | 750 mg/m² IV, repeated every 6–18 months |
| Supportive Care | Tracheostomy | For severe airway involvement |
7.1 Treatment Algorithms¶
- Initial management: High-dose corticosteroids (e.g., prednisone 1–2 mg/kg) for acute flares. 2. Maintenance therapy: Mycophenolate mofetil (1–2 g/day) or azathioprine (100–150 mg/day). 3. Refractory cases: Rituximab (750 mg/m² IV, repeated every 6–18 months). 4. Airway complications: Tracheostomy or surgical intervention for severe stenosis. 5. VEXAS syndrome: Genetic testing and bone marrow evaluation.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis varies depending on disease severity and response to treatment. Complications include progressive cartilage destruction, airway obstruction, hearing loss, and cardiovascular involvement. Mortality is low with appropriate management, but severe airway compromise or VEXAS syndrome-related complications can be life-threatening.
8.1 Long-Term Risks¶
Chronic inflammation may lead to irreversible cartilage damage, structural deformities (e.g., saddle nose), and respiratory failure. VEXAS syndrome is associated with progressive bone marrow failure and hematologic malignancies, requiring close monitoring.
9. SPECIAL CONSIDERATIONS¶
Special considerations include: (1) VEXAS syndrome: Genetic testing and bone marrow evaluation in older males with unexplained chondritis; (2) Pregnancy: Avoidance of immunosuppressants in the first trimester; (3) Pediatrics: Rare but possible, with similar clinical features to adults; and (4) Comorbidities: Coexistence with autoimmune diseases (e.g., Sjögren’s syndrome) requiring tailored management.
10. KEY POINTS & CLINICAL PEARLS¶
- RP is a rare autoimmune disease with recurrent chondritis of cartilaginous structures. 2. Diagnosis relies on clinical criteria due to lack of specific biomarkers. 3. VEXAS syndrome (UBA1 mutations) must be considered in patients with unexplained chondritis. 4. Airway involvement is a medical emergency requiring prompt intervention. 5. Treatment includes corticosteroids, immunosuppressants, and biologics, with careful monitoring for complications.