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Relapsing Polychondritis

Chapter 378 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders · Part 11 – Rheumatology & Immunology · Chapter 378

Key Clinical Points

  1. Relapsing polychondritis (RP) is a rare systemic disease characterized by recurrent inflammation of cartilaginous structures, primarily the ears, nose, respiratory tract, and joints.
  2. Diagnosis is based on clinical pattern recognition; no specific circulating or tissue-based biomarkers currently exist.
  3. Ear involvement occurs in 80–90% of patients; hallmark finding is auricular chondritis (inflammation of the pinnae) that spares the earlobe.
  4. Nasal involvement may present as acute redness/swelling or chronic 'saddle nose' deformity, which typically lacks a septal perforation (unlike GPA).
  5. VEXAS syndrome (UBA1 mutation) must be suspected in older males with severe systemic inflammation and bone marrow failure (macrocytosis and lymphopenia).
  6. Costochondritis can cause severe pain at the rib-sternum junction, often mimicking an acute coronary event.
  7. Scleritis is a medical emergency requiring immediate ophthalmologic evaluation due to risks of vision loss, scleromalacia, or global rupture.
  8. Airway involvement (subglottic stenosis, tracheomalacia) may cause stridor and requires urgent intervention to prevent mortality.
  9. GPA can be differentiated from RP by the presence of ANCA and glomerulonephritis.
  10. Audiometry and dynamic expiratory phase CT chest are critical for assessing hearing loss and tracheobronchomalacia.

1. DEFINITION & OVERVIEW

• Relapsing Polychondritis (RP): A rare systemic disease characterized by recurrent inflammation in cartilaginous structures. • Hallmark Features: Involvement of the ears, nose, respiratory tract, and joints. • Systemic Involvement: Can affect other organs including eyes, inner ear, nervous system, skin, and cardiovascular system. • Comorbidities: May occur alongside other rheumatologic diseases (e.g., Sjögren's syndrome or systemic lupus erythematosus). • VEXAS Association: Older male patients with severe inflammation and bone marrow failure may have UBA1 mutations (VEXAS syndrome).

2. EPIDEMIOLOGY

• Demographics: Primarily affects middle-aged adults; no strong sex predilection reported. • Pediatric/Familial: Children can be affected (limited to case reports); rare instances of familial aggregation reported. • Incidence: 0.7–3.5 cases per million per year. • Prevalence: 4.5–25 cases per million. • Data Limitations: Data are based on older studies; actual prevalence may be underestimated due to diagnostic challenges.

3. ETIOLOGY & PATHOPHYSIOLOGY

• Mechanism: Exact mechanisms remain unclear despite study of genetic, environmental, and immunologic factors. • Autoimmunity Theory: Animal models suggest autoimmunity to cartilage components (type II collagen, type IX collagen, or matrillin-1) may play a role. • Diagnostic Limitations: Antibodies to type II collagen are not sensitive/specific enough for clinical use. • Immune Response: B-cell–depleting therapies are not particularly effective; acute phase reactants (ESR, CRP) are not reliably elevated. • Cytokines: Proinflammatory cytokines and chemokines related to both innate and adaptive immunity are associated with RP.

3.1 VEXAS Syndrome

• Definition: A condition characterized by recurrent chondritis of the ears and nose in older male patients with severe systemic inflammation and progressive bone marrow failure, associated with acquired mutations in UBA1. • Clinical Trigger: Presence of cytopenia (notably macrocytosis and lymphopenia) in older males should trigger genetic testing and bone marrow assessment.

4. CLINICAL FEATURES

• General: Diagnosis relies on detailed history and physical exam; clinical features may be intermittent, requiring review of past photos.

• Ears, Nose, and Throat: • Ear (80–90%): Involvement of pinnae; inflammation/swelling; 'cauliflower ear' is rare and seen in recurrent episodes. • Nose: Pressure at bridge; redness/swelling of base or tip; saddle nose deformity (common in chronic cases). • Differentiation: Unlike GPA, RP with saddle nose typically lacks septal perforation (most perforations in RP are anterior). • Throat: Pain or globus sensation ('choking sensation'); pain on anterior neck (thyroid cartilage level).

• Musculoskeletal: • Arthritis: Nonerosive inflammatory polyarthritis of small/large joints and axial skeleton. • Costochondritis: Severe, constant pain at rib-sternum junction; often leads to ER visits for suspected coronary events. Pain is bilateral and reproducible with palpation.

• Inner Ear: • Hearing Loss: Conductive or sensorineural (requires audiometry). • Vestibular: Dizziness requires evaluation via finger-to-nose, Romberg, and nystagmus to rule out vestibular involvement.

• Ocular Involvement: • Episcleritis: Most frequent type. • Scleritis: Rare but mandates urgent ophthalmologic evaluation (risk of vision loss, scleromalacia, or global rupture).

• Cardiovascular: • MAGIC Syndrome: Patients with mouth/genital ulcers and inflamed cartilage may show Behçet's-like features. • Vasculitis: Large-vessel vasculitis involving the aorta.

• Neurologic: • Exclusionary Diagnosis: Must rule out infection and malignancy; encephalitis and meningitis can occur.

5. DIFFERENTIAL DIAGNOSIS

• Ear Chondritis Mimics: Infectious/cutaneous diseases, traumatic otohematoma, or red ear syndrome. • Nose Chondritis Mimics: Infectious diseases, angiocentric centrofacial lymphoma. • Airway Chondritis Mimics: Asthma, traumatic airway stenosis, infectious diseases, and congenital disorders. • Systemic Disease Mimics: • GPA: Differentiated by presence of ANCA and glomerulonephritis (not seen in RP). • VEXAS: Identified in older males with cytopenia/macrocytosis/lymphopenia.

5.1 Diagnostic Criteria

• McAdam's criteria: Requires 3 of 6 symptoms (bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, or vestibular/cochlear dysfunction). • Damiani and Levine modified McAdam's: Requires either 3 clinical features OR (1 clinical feature + histologic evidence of chondritis) OR (2 clinical features + response to glucocorticoids, dapsone, or both). • Michet's criteria: Requires 2 major criteria OR (1 major + 2 minor). • Major: Inflammation of ear, nose, or respiratory tract. • Minor: Ocular inflammation, hearing loss, vestibular dysfunction, and seronegative inflammatory arthritis.

6. INVESTIGATIONS & DIAGNOSIS

• Clinical Recognition: Diagnosis is based on clinical patterns as no specific biomarkers exist.

• Diagnostic Criteria: 1. McAdam's criteria: 3 of 6 symptoms (auricular chondritis, nonerosive seronegative polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, or vestibular/cochlear dysfunction). 2. Damiani and Levine modified McAdam's: 3 clinical features OR (1 + histology) OR (2 + response to glucocorticoids/dapsone). 3. Michet's criteria: 2 major (ear, nose, respiratory tract) OR (1 major + 2 minor: ocular, hearing loss, vestibular dysfunction, seronegative inflammatory arthritis).

• Critical Investigations: 1. Audiometry: To assess for conductive and sensorineural hearing loss. 2. Dynamic Expiratory Phase CT Chest: To evaluate for tracheobronchomalacia (tracheal/bronchial cartilage involvement). 3. Urgent Evaluation: Required for any signs of airway compromise or scleritis.

7. MANAGEMENT & TREATMENT

  1. Airway Management: • Subglottic Stenosis: Identify and treat promptly to prevent stridor, cough, voice changes, or breathlessness. • Urgent Intervention: Required for severe narrowing causing stridor to avoid mortality. • Long-term Monitoring: Patients with intermittent wheezing must be evaluated for tracheomalacia, bronchomalacia, or tracheal calcification.
  2. Ocular Management: • Scleritis: Mandates immediate ophthalmologic evaluation to prevent vision loss, scleromalacia, or global rupture.
  3. Systemic Treatment: • Pharmacotherapy: Standard treatment includes glucocorticoids and dapsone (used in Damiani/Levine criteria for diagnosis). • Note: B-cell–depleting therapies are not typically effective.

8. PROGNOSIS & COMPLICATIONS

• Airway Compromise: Subglottic stenosis and tracheomalacia can lead to permanent damage or death. • Ocular Damage: Scleritis can lead to catastrophic outcomes including vision loss or globe rupture. • VEXAS Progression: Associated with progressive bone marrow failure in affected males.

9. SPECIAL CONSIDERATIONS

• Pediatrics: Limited data; primarily reported in case reports. • Genetics: Rare instances of familial aggregation reported. • VEXAS Screening: Older males with cytopenia (macrocytosis/lymphopenia) must be screened for UBA1 mutations.

10. KEY PEARLS & CLINICAL TRAPS

• Ear Pain Triggers: Ask about trauma (lying on side, glasses) or temperature changes. • Nasal Findings: Saddle nose in RP typically lacks septal perforation (unlike GPA). • Ocular Emergency: Scleritis requires immediate ophthalmology referral. • Airway Risk: Subglottic stenosis can cause stridor; early recognition is vital to prevent permanent damage. • VEXAS Trigger: Older males with cytopenia/macrocytosis/lymphopenia must be screened for UBA1 mutations.