Relapsing polychondritis

Relapsing polychondritis is a rare inflammatory disease with an autoimmune component characterized by chondritis (e.g., auricular, nasal, and/or laryngotracheobronchial) with or without systemic involvement (e.g., arthropathy, episcleritis, and/or valvular heart disease). Laryngotracheobronchial chondritis is the most common cause of mortality in relapsing polychondritis and may necessitate emergency interventions (e.g., tracheostomy). Relapsing polychondritis is sometimes associated with other conditions (e.g., systemic lupus erythematosus, ANCA-associated vasculitis, and solid organ cancers). Diagnosis is clinical and often delayed due to variable manifestations and insidious onset. A comprehensive diagnostic evaluation is used to rule out alternative diagnoses (e.g., autoimmune diseases) and assess for systemic involvement (e.g., laryngotracheobronchitis, valvular heart disease). Treatment aims to control acute inflammation and prevent long-term damage. Mild disease is managed with NSAIDs or dapsone. Severe disease (e.g., severe polychondritis and/or laryngotracheobronchial involvement) is treated with systemic glucocorticoids. Conventional DMARDs and biologic DMARDs may be used in refractory disease. Long-term complications of chondritis include audiovestibular symptoms, ear deformity, and saddle nose deformity.

• Sex: slightly higher prevalence in women
• Incidence: 3.5 cases per million per year ^[1]
• Median age at onset: 40–50 years ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Inflammation occurs in multiple areas of the body and is likely multifactorial with an autoimmune component. ^[1][2]

• Chondritis ^[1]
  • Auricular (unilateral or bilateral): e.g., painful erythema and/or edema in the external ear
  • Nasal: e.g., acute erythema, tenderness, and/or pain (may cause epistaxis and/or lead to saddle nose deformity)
  • Laryngotracheobronchial: e.g., airway obstruction, pain, hoarseness, dry cough, dyspnea, and/or wheezing
  • Costal: e.g., chest wall pain
• Systemic involvement ^[1]
  • Arthropathy: e.g., acute, asymmetric, intermittent, nonerosive polyarthritis or oligoarthritis
  • Audiovestibular damage: e.g., sensorineural hearing loss, tinnitus, and/or vertigo
  • Ocular (usually mild): e.g., unilateral or bilateral episcleritis, scleritis, and/or conjunctivitis
  • Dermatological: e.g., aphthous ulcers, limb nodules, purpura, papules ^[1]
  • Cardiovascular: e.g., valvular heart disease, aortic aneurysm, aortic dissection, myocarditis, pericarditis, atrioventricular block, coronary artery vasculitis ^[2]
  • Renal (e.g., IgA nephropathy, tubulointerstitial nephritis): manifestations include microhematuria and/or proteinuria
  • Neurological: e.g., headache, meningitis, limbic encephalitis, ischemic stroke, dementia, mononeuritis multiplex ^[2]
• Associated disorders ^[1]
  • Autoimmune connective tissue diseases: e.g., systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, ANCA-associated vasculitis
  • Malignancies: e.g., myelodysplastic syndromes, solid organ cancers
  • Other disorders: e.g., selective IgA deficiency, antiphospholipid syndrome ^[2]
• Triggering events: e.g., trauma, piercing, pregnancy, and infections ^[2]

Laryngotracheobronchial chondritis is the most common cause of morbidity and mortality in patients with relapsing polychondritis. Airway obstruction may necessitate emergency tracheostomy. ^[1]

Approach ^[1]

Relapsing polychondritis is a clinical diagnosis based on typical features (e.g., auricular chondritis) with or without systemic connective tissue involvement.

• Refer to a specialist early (e.g., rheumatology).
• Perform a comprehensive diagnostic evaluation to:
  • Rule out alternative diagnoses
  • Assess for connective tissue and organ involvement
• Biopsy is not usually required to confirm the diagnosis.

Diagnosing relapsing polychondritis is often challenging due to variable manifestations and insidious onset.

Laboratory studies ^[1]

• ↑ Inflammatory markers (CRP and ESR): typically elevated during an inflammatory crisis
• CBC: may show anemia, leukocytosis, thrombocytosis (markers of chronic inflammation)
• BMP: ↑ creatinine in patients with renal involvement
• Autoimmune disease workup, e.g.:
  • ANA, rheumatoid factor, and complement : typically normal
  • ANCA may be elevated in patients with ANCA-associated vasculitis.
  • Antiphospholipid antibodies may be present. ^[2]

Imaging ^[1]

Imaging studies and findings in the affected area include:

• X-ray: cartilage calcification
• MRI: inflammation in joints and/or cartilage ^[1]
• CT chest (inspiratory and expiratory)
  • Airway findings (e.g., wall thickening, stenosis, calcification)
  • Lobar findings (e.g., air trapping)

Advanced studies ^[1]

Studies obtained by specialists (e.g., rheumatology, pulmonology) may include:

• PET-CT scan: for more effective disease detection and localization ^[1]
• Echocardiogram
  • For suspected cardiac involvement
  • May show valvular heart disease or aortic root dilatation
• Pulmonary function testing ^[2]
  • For suspected laryngotracheobronchial involvement
  • May show obstructive and/or restrictive patterns (see “PFT findings in obstructive vs. restrictive lung diseases”)
• Bronchoscopy (high risk and thus rarely performed)
  • Considered if there is diagnostic uncertainty ^[2]
  • May reveal dynamic airway collapse during expiration and/or airway narrowing
• Biopsy of cartilage (not routinely needed to establish a diagnosis)
  • Considered if there is diagnostic uncertainty
  • May show inflammatory infiltration ^[1]

Invasive tracheobronchial procedures (e.g., bronchoscopy) may trigger fatal airway inflammation or respiratory failure and are only used for selected patients. ^[1]

Biopsy is not usually required to confirm relapsing polychondritis.

General principles ^[1]

• Refer to a specialist early (e.g., rheumatology).
• Treatment is guided by disease location, severity and patient preferences.
• There are no standardized guidelines due to limited evidence. ^[2][3]
• Consult a surgical specialist as needed for specific manifestations (e.g., tracheostomy for airway obstruction, cardiac valve repair) ^[2]

Pharmacotherapy

The following treatments are used to control acute inflammation and prevent long-term damage. ^[2]

• Mild disease (involvement of nose, external ear, and/or joints only) ^[1]
  • NSAIDs, dapsone (off-label), or colchicine (off-label) to control pain and inflammation
  • Consider oral prednisone in refractory cases.
• Severe disease: e.g., severe polychondritis, laryngotracheobronchial, ocular, and/or cardiac involvement ^[1]
  • First-line: systemic glucocorticoids
    • Oral prednisone
    • IV methylprednisolone ^[2]
  • For patients with refractory disease, consider the following:
    • Conventional DMARDs: e.g., cyclophosphamide, methotrexate, azathioprine
    • Biologic DMARDs: e.g., TNF inhibitors (i.e., infliximab, etanercept, adalimumab), abatacept, tocilizumab