What is relapsing polychondritis?

Relapsing Polychondritis: An Uncommon Autoimmune Disorder

Relapsing polychondritis is an uncommon autoimmune disorder characterized by recurrent inflammation and widespread destruction of cartilage and other connective tissues throughout the body, which can lead to significant morbidity and mortality, particularly when respiratory involvement occurs. 1

Definition and Pathophysiology

• Relapsing polychondritis involves perichondral inflammation with cartilaginous fragmentation and destruction that is eventually replaced by fibrosis 1
• It is a rare systemic autoimmune disease that targets cartilaginous structures and can affect any location where cartilage is present 2
• The disease demonstrates an equal male/female ratio with a mean age at diagnosis of 51 years 1

Clinical Presentation

Common Manifestations

• The most frequent symptoms include swelling and erythema of the ears (88%) and arthralgias (81%) 1
• A relapsing course is seen in 86% of patients, while continuous symptoms occur in 14% 1
• Diagnostic delays are common, with a mean delay of 55 weeks reported in one study 2

Respiratory Involvement

• Airway involvement represents one of the most serious manifestations and is responsible for many pulmonary complications 1
• The respiratory system is affected in >50% of patients, with pulmonary symptoms being the presenting features in up to 25% of cases 1
• Respiratory cartilage involvement can include the external nares, nasal septal turbinates, eustachian tubes, epiglottis, larynx, thyroid, cricoid, arytenoid, trachea, and bronchi 1
• Persistent or chronic cough is often one of the first and important symptoms signifying respiratory involvement 1
• Other pulmonary symptoms include wheezing, stridor, dyspnea, hoarseness or aphonia, and tenderness over the laryngotracheal cartilage 1

Ocular Manifestations

• Ocular involvement occurs in up to 65% of cases and includes a wide range of manifestations such as proptosis, eyelid edema, extraocular muscle palsy, episcleritis, scleritis, and other inflammatory conditions 3

Diagnosis

Diagnostic Approach

• Diagnosis is primarily clinical, as no specific laboratory test exists for relapsing polychondritis 4
• Patients with suspected relapsing polychondritis should undergo pulmonary function tests, including inspiratory and expiratory flow-volume curves to identify clinically subtle airway involvement 1
• Chest radiographs are usually unhelpful in diagnosis 1
• CT scanning may reveal:
  • Thickening and stenosis of the tracheobronchial wall
  • Collapse and calcification of cartilage
  • Bronchiectasis (in late stages of disease) 1
• Bronchoscopy is not always required but may show inflammation, collapse, and stenosis of the larynx, trachea, and/or bronchi 1

Disease Patterns

• Recent research has identified three distinct patient clusters with different clinical manifestations and prognostic outcomes 5
• The formal diagnosis cannot be established with certainty before the onset of chondritis, which can sometimes occur several years after the first signs 4

Treatment

Therapeutic Options

• Therapy for relapsing polychondritis typically includes:
  • Salicylates and nonsteroidal anti-inflammatory drugs for milder cases 1
  • Corticosteroids remain the mainstay of treatment 3
  • Cytotoxic agents and immunosuppressants for more severe disease 1
• Patients with acute cases generally exhibit a good response to therapy 1
• Respiratory involvement usually requires long-term use of systemic corticosteroids and other immunosuppressants 1
• For more severe cases, disease-modifying anti-rheumatic drugs (DMARDs) and biologics should be considered early in the disease course to minimize adverse effects of long-term corticosteroid therapy and organ damage 2

Treatment Strategy

• Treatment is often based on the lowest possible dosage of corticosteroids combined with background treatment using conventional immunosuppressants (e.g., methotrexate, azathioprine, mycophenolate mofetil, rarely cyclophosphamide) or targeted therapies 4
• Anti-TNF-α agents may be beneficial in patients with pulmonary involvement 6
• Some minor forms can be treated with non-steroidal anti-inflammatory drugs or a short course of corticosteroids with possibly a background treatment of colchicine 4

Prognosis and Complications

• Forms limited to the cartilage of the nose or ears generally have a good prognosis 4
• Mortality is frequently related to respiratory complications 1
• Involvement of the cartilage of the respiratory tract, cardiovascular involvement, and association with myelodysplasia/VEXAS syndrome are detrimental to the prognosis 4
• In one study, 18% of patients died due to relapsing polychondritis, with 9 having respiratory complications 2
• Other complications included myelodysplasia and lung carcinoma 2

Important Considerations and Pitfalls

• The rarity of relapsing polychondritis often leads to considerable delay in establishing a diagnosis 6
• Differential diagnosis has expanded with the discovery of new somatic and monogenic autoinflammatory diseases, notably VEXAS syndrome, autoinflammatory diseases, and immune checkpoint inhibitor-related adverse events 5
• Specific strategies are required if relapsing polychondritis is associated with myelodysplasia/VEXAS syndrome, which is more frequent in men over 50 years of age 4
• Prognostic variables identified in multivariate regression analysis include ethnicity, nasal chondritis, laryngotracheal stricture, and elevated serum creatinine 2