Epidemiology

• It has an annual incidence of approximately 3.5 per million.
• The peak age of onset is 40 to 50, but it can strike at any age.
• Males and females appear to be equally affected, whereas in most autoimmune diseases there is a female preponderance.
• The disease has mainly been reported in Caucasians, although it can occur in all races.

Presentation

It is a multisystem disorder and so can present in many ways:

• Weight loss.
• External ear pain (present in almost all cases).
• Dizziness and ataxia of vestibular origin.
• Hearing impairment (46% in later stages).
• Arthralgia (50-85%, may affect any synovial joint).
• Nasal pain and chondritis.
• Hoarseness and difficulty talking.
• Glottic, subglottic and laryngeal inflammation and oedema.
• Cough, dyspnoea, wheezing and choking.
• Costochondritis (may lead to joint dissolution and flail chest).
• Recurrent scleritis and episcleritis.
• Cardiovascular involvement including valve problems, pericarditis, myocarditis, myocardial infarction, aneurysms.
• Renal involvement, glomerulonephritis, glomerulosclerosis (associated with poorer prognosis - 30% survival at 10 years).
• Nervous system involvement (rare), cranial nerve lesions, aneurysms.

Diagnostic criteria

As it is a rare multisystem disorder with no specific diagnostic test and numerous possible symptoms, a number of diagnostic criteria have been devised. The most widely used are the McAdam's criteria.^[1] The following features are sought:

• Recurrent chondritis of both auricles.
• Chondritis of nasal cartilages.
• Chondritis of the respiratory tract, involving laryngeal or tracheal cartilage.
• Non-erosive inflammatory polyarthritis.
• Inflammation of ocular structures.
• Cochlear or vestibular damage.

In addition, cartilage biopsy may be taken to confirm a compatible histological picture. Biopsy of cartilage is not to be undertaken lightly. It does not have its own blood supply and it heals poorly, if at all.

There are 3 grounds to make the diagnosis:^[4]

• At least 3 criteria: no histological confirmation is required.
• One or more of these features, including histological confirmation.
• Chondritis in 2 or more separate anatomical locations with response to steroids and/or dapsone.

Alternative criteria have been proposed with 2 possible routes to diagnosis:^[3]

• Proven inflammation in 2 of 3 of the auricular, nasal, or laryngotracheal cartilages.
• Proven inflammation in 1 of 3 of the auricular, nasal, or laryngotracheal cartilages plus 2 other signs, including ocular inflammation, vestibular dysfunction, seronegative inflammatory arthritis, and hearing loss.

Differential diagnosis

A number of conditions can resemble relapsing polychondritis (RP) and may even occur in association with it. Wegener's granulomatosis and systemic lupus erythematosus often have to be excluded before a diagnosis of RP is entertained.

Other conditions may mimic the clinical presentation, including trauma, infections, allergic reactions and tumour.

Investigations

There are no discrete investigations for the disease, and the diagnosis is made using the agreed diagnostic criteria referred to above.

• During acute flares, various surrogate markers of inflammation may be raised, such as ESR and CRP.
• There may be an anaemia and leukocytosis. If there is anaemia at presentation, it implies a worse prognosis.
• Antinuclear factor (ANF) and rheumatoid factor are generally negative.
• Serum antibodies to type II collagen may be positive (20%).
• Cartilage biopsy may show evidence of inflammation.
• Pulmonary function testing and flow volume loop.
• Bronchoscopy if there is respiratory involvement.
• Echocardiography to assess heart valve function.
• Cardiac catheterisation and angiography if there is cardiovascular involvement.
• CT scanning, especially spiral CT, may help to identify problems with the airways.
• MRI imaging may be useful to demonstrate inflammation in cartilage.

Associated diseases

Relapsing polychondritis (RP) is commonly associated with a diverse collection of other diseases including:

• Wegener's granulomatosis
• Systemic lupus erythematosus
• Myeloma
• Hashimoto's thyroiditis
• Primary biliary cirrhosis
• Myasthenia gravis

It is commonly found (35%) in association with a large number of other diseases as outlined above, the diagnosis of the associated disease usually preceding the diagnosis of RP.

Management

Many systems can be involved and it is important to adopt a team approach with good communication between the specialists involved.

Nondrug

Because of involvement of auricular and nasal cartilage, counselling, support and specialist cosmetic advice may be required due to the change in facial appearance.

Drugs

The rarity of the disorder has meant that few clinical trials have been performed.

• Corticosteroids remain the most commonly used therapeutic measure but, despite bringing relief from symptoms and reducing the severity and duration of relapses, they do not appear to alter the disease progression.^[5]
• Other agents have been used such as dapsone, methotrexate, colchicines, cyclophosphamide and azathioprine with apparent success, although the numbers involved are small and no controlled trials have been performed.
• In recent years, anti-TNF-alpha drugs have been tried and there are a number of case reports in the literature:
  • Infliximab and etanercept are effective in some subtypes of juvenile idiopathic arthritis and have been tried in children with relapsing polychondritis (RP).^[6] Although frequent, adverse events could be controlled most of the time.
  • Infliximab has been tried for respiratory complications.^[7]
  • It has been tried in RP refractory to other treatments, with apparent success.^[8]

Surgery

• Collapse of upper airways may require tracheostomy.
• Males are more susceptible to heart valve disease, possibly requiring aortic valve replacement.^[9]

Complications

Complications due to collapse of cartilage can include facial disfigurement and obstruction of airways. Structures in the ear and eye can collapse with devastating results. Vasculitis and unrelated malignancy is also common.

Prognosis

The disease follows a relapsing and remitting course with steady progression of the disease. The prognosis for any individual will vary considerably depending on which systems are involved and their response to therapy. With earlier recognition of the disease and optimal treatment, the prognosis has improved, and in one study a 94% survival rate was reported with an average 8-year follow-up.^[10] Up to 50% of deaths will be due to pneumonia following involvement of cartilage in the respiratory system, with cardiovascular involvement being the next most common cause of death. Another group found that respiratory disease caused only 10% of deaths.^[3] The most frequent causes of death were infection, systemic vasculitis, and malignancy.