Relapsing polychondritis

What is relapsing polychondritis?¹

Relapsing polychondritis is a rare and potentially fatal multisystemic autoimmune disease of unknown aetiology, affecting primarily cartilaginous and proteoglycan-rich structures.

It is an immune-mediated systemic disease characterised by recurrent episodes of inflammation of cartilaginous tissues, resulting in progressive anatomical deformation and functional impairment of the involved structures. Auricular and nasal chondritis and/or polyarthritis represent the most common clinical features, but potentially all types of cartilage may be involved.

Relapsing polychondritis may also affect connective tissues rich in proteoglycans, such as in the heart, eye, blood vessels and inner ear.

How common is relapsing polychondritis? (Epidemiology)¹

• The incidence of RP is less than previously estimated, at around 0.71 per million population per year.²

• The peak age of onset is 40 to 50, but it can strike at any age.³

• 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.

Relapsing polychondritis symptoms¹

The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis, to occasional organ or even life-threatening manifestations like airway collapse.⁴

The presence of auricular inflammation is characteristic of relapsing polychondritis and is an important diagnostic feature.

The inflammation typically spares the auricular lobe as it is devoid of cartilage and this sign can aid in its differentiation from other causes of auricular inflammation.⁵

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

• Weight loss.

• External ear pain (present in almost all cases).⁵

• Dizziness and ataxia of vestibular origin.

• Hearing impairment.

• Arthralgia (this may affect any synovial joint. However, metacarpophalangeal, proximal interphalangeal and knee joints are the most commonly affected).

• Nasal pain and chondritis. Involvement of nasal cartilage can be seen in around half of cases and saddle nose deformity occurs in around 10% of cases.

• Hoarseness and difficulty talking.

• Glottic, subglottic and laryngeal inflammation and oedema.

• Airway involvement in around 505 of cases. Cough, dyspnoea, wheezing and choking.⁶

• 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 in around 25% of cases; glomerulonephritis, glomerulosclerosis (associated with poorer prognosis).⁴

• Nervous system involvement (rare), cranial nerve lesions, aneurysms.

Diagnostic criteria⁷

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. 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 occasionally 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.

Differential diagnosis

A number of conditions can resemble RP and may even occur in association with it. Granulomatosis with polyangiitis (GPA) 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 leucocytosis. 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.

• 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

RP is commonly associated with a diverse collection of other diseases including:

• GPA.

• 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.

Relapsing polychondritis treatment and management^{1 8}

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

Non-drug

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. The choice of therapy is dependent on the severity of symptoms and the extent of disease.

• Non-steroidal anti-inflammatory drugs, dapsone or colchicine may be used for mild manifestations.

• 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.

• Methotrexate is often effective.⁹

• Immunomodulatory agents, such as adalimumab, abatacept and tocilizumab, have shown promising but mixed results.^{10 11 12}

Surgery

• Collapse of upper airways may require tracheostomy.

• Those with heart valve disease may occasionally requiring aortic valve replacement.

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 are also common.

Complications include destruction of the thyroid cartilage, acute upper airway collapse and obstruction necessitating emergency tracheostomy.³

Severe inflammatory changes affecting ocular tissues can lead to permanent damage and loss of vision. Any part of the eye can be affected. Scleritis can be particularly challenging to manage and may lead to globe perforation. Keratitis may also occur, leading to corneal perforation.

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 this disease and optimal treatment, the prognosis has improved over recent years.

A laryngotracheobronchial involvement appears in nearly half of patients and is complicated by local obstructions, which may be life-threatening.¹³

Cardiovascular involvement is seen in 24-52% of the cases and is the second most frequent cause of death in patients with RP.⁴

Mortality in relapsing polychondritis is more than twice that of the general population.²

The most common causes of death in these patients include infection secondary to corticosteroid treatment or respiratory compromise, systemic vasculitis and malignancy unrelated to relapsing polychondritis.