Continuing Education Activity

Relapsing polychondritis (RP) is a rare autoimmune condition which presents as recurrent episodes of cartilaginous inflammation of the auricular, nasal and tracheal cartilage. Jaksh-Wartenhorst described the first case in 1923. A 32-year-old patient presented with fever, pain, and swelling of the ears and later developed stenosis of external auditory canal and saddle nose deformity. A biopsy of the nasal cartilage showed the absence of cartilage. The term relapsing polychondritis was coined by Pearson and his coworkers in 1960. This activity reviews the cause, pathophysiology and presentation of relapsing polychondritis and highlights the role of the interprofessional team in its management.

Objectives:

• Identify the etiology of relapsing polychondritis.
• Review the presentation of relapsing polychondritis.
• Outline the treatment and management options available for relapsing polychondritis.
• Describe interprofessional team strategies for improving care coordination and outcomes in patients with relapsing polychondritis.

Introduction

Relapsing polychondritis (RP) is a rare autoimmune condition which presents as recurrent episodes of cartilaginous inflammation of the auricular, nasal and tracheal cartilage. Jaksh-Wartenhorst described the first case in 1923, when a 32-year-old patient presented with fever, pain, and swelling of the ears and later developed stenosis of external auditory canal and saddle nose deformity. A biopsy of the nasal cartilage showed the absence of cartilage. The term relapsing polychondritis was coined by Pearson and his coworkers in 1960. They recognized it as an inflammatory condition of the cartilaginous and noncartilaginous structures.[1][2][3]

Etiology

The etiology of relapsing polychondritis is not known. It is suggested to occur in a genetically predisposed individual on exposure to a triggering factor. The triggering factor may be an infectious agent, chemical, toxic exposure, or direct trauma. Relapsing polychondritis cases have been reported after trauma occurring to the pinna. A possible explanation includes cryptogenic antigenic release after trauma and recognition of the antigen by the immune system. Genetic studies have shown an association between HLA-DR4 antigen and relapsing polychondritis.[4][5]

Epidemiology

It is a rare disease, more common in Caucasians; the prevalence is 4.5 cases per million. The peak age at onset is between 40 years to 50 years of age, though it can occur at any age. It occurs with equal frequency in both sexes and all racial groups. Over 30% of cases are associated with an existing autoimmune or hematologic comorbidity. [6][7]

Pathophysiology

Relapsing polychondritis primarily involves cartilaginous structures, suggesting that immune mechanisms are acting against proteoglycan -- the main constituent of cartilage. Circulating and tissue-specific antibodies against collagen types II, IX and XI are seen in patients with relapsing polychondritis. In addition to humoral immunity, cellular immunity propagates inflammation of the cartilage. CD4+ cells secrete cytokines such as interleukin-8, macrophage inflammatory protein 1β, and monocyte chemoattractant protein-1 which leads to the recruitment of monocytes and macrophages. Macrophages release proteolytic enzymes, metalloproteinase (MMP-3), cathepsin L and K which leads to the destruction of cartilage. In the early stages of disease, there is polymorphic inflammatory cell infiltration; later there is chondrocyte apoptosis, focal calcification, and fibrosis of the cartilage.[8]

History and Physical

The clinical spectrum of relapsing polychondritis varies with the duration and severity of disease. Auricular involvement is present in 90% of cases, and inflammation is restricted to the cartilaginous portion of the ear, with relative sparing of the ear lobes. Patients most frequently present with discoloration and pain of the ear. Articular involvement is the second most common manifestation and is present in 50% to 75% of patients. Wrist, metacarpophalangeal, and proximal interphalangeal joints are commonly involved. Ocular manifestations occur in 20% to 60% of relapsing polychondritis patients and include episcleritis, scleritis, keratitis, and uveitis. Nasal chondritis occurs in about 25% of cases. Inflammation of the cartilaginous rings around the trachea and bronchi results in the collapse of these airways (tracheobronchomalacia). Such patients present with a cough, hoarseness of voice, and wheezing. Respiratory compromise is the most frequent cause of death in these patients.

Evaluation

Diagnosis of relapsing polychondritis is primarily based on a combination of clinical features, radiographic findings, and biopsy of a cartilaginous site. It is guided by a set of clinical criteria suggested by McAdams et al. [9]  [10] Three of out of six criteria are required to make the diagnosis. These include:

1. Recurrent chondritis of both auricles
2. Nonerosive inflammatory arthritis
3. Chondritis of nasal cartilage
4. Inflammation of ocular structures presenting as conjunctivitis, keratitis, scleritis, or uveitis
5. Chondritis of the respiratory tract with laryngeal or tracheal cartilage involvement
6. Cochlear or vestibular damage presenting with neurosensory hearing loss, tinnitus, or vertigo

Any patient suspecting of having relapsing polychondritis should have a dynamic exploratory CT scan to evaluate for airway involvement. CT scans findings include functional airway abnormalities such as air trapping and collapse. Additional findings include thickening of the airway wall and luminal narrowing. Pulmonary function testing is done to further evaluate for airway trapping and to assess lung volumes. PET-CT is a new diagnostic modality that aids in early disease recognition and provides a site for targeted biopsy.

Biopsy of the auricular cartilage is performed to confirm the diagnosis of polychondritis. Positive serologic testing for rheumatoid factor and anti-nuclear antibody may be seen in patients with other associated rheumatologic diseases. Complement levels are usually normal in patients with relapsing polychondritis. Radiographic findings can include a non-erosive juxta-articular osteopenia and uniform, joint space narrowing; these findings are suggestive of arthropathy in relapsing polychondritis. Anti-type II collagen antibody tests are not routinely available, and, when these tests are done, these antibodies are not present in all the cases. There are no lab markers to assess for ongoing cartilage damage.

Treatment / Management

Due to the rarity of the disease, there are no there is no standardized treatment approach, and the treatment is guided by the clinical presentation and the severity of the disease.[2][11]

For patients presenting with auricular, nasal or articular involvement without systemic involvement, treatment includes anti-inflammatory medications, colchicine, or dapsone. Low-dose glucocorticoid therapy is often required.

For patients with more severe presentation such as large airway involvement such as laryngeal or tracheobronchial chondritis, abrupt onset of sensorineural hearing loss, or ocular involvement, glucocorticoid therapy with  IV methylprednisolone 1 gram for three days followed by oral prednisone 1 mg/kg along with immunosuppressive therapy is indicated. The most commonly used immunosuppressive agents include cyclophosphamide, methotrexate, azathioprine, and cyclosporine. Cyclophosphamide is commonly used as the initial medication (1-2 mg/kg); after remission is achieved, cyclophosphamide is switched to other less toxic immunosuppressive agents like azathioprine or methotrexate.

Biologics have been used in the treatment of relapsing polychondritis. The most commonly used biologic is the TNF-alpha inhibitor infliximab. Other biologics which have been tried with variable results include adalimumab, etanercept, abatacept, tocilizumab. Data on rituximab has not shown success, and this agent is not recommended as the first-line biologic agent.

Surgical interventions such as stenting, airway dilation, tracheostomy, and laryngotracheal reconstruction are needed in cases of airway collapse.

Differential Diagnosis

The diagnosis of RP may be challenging. Nasal damage may occur as a result of drug abuse (cocaine), infections from fungi, tuberculosis, or syphilis, and granulomatous conditions such as ANCA-associated vasculitis and lymphomatoid granulomatosis. Eye involvement seen in relapsing polychondritis may also occur with rheumatoid arthritis, ANCA-associated vasculitis, polyarteritis nodosa, Behcet syndrome, or Cogan syndrome.

Prognosis

The outcome of patients with relapsing polychondritis has improved in recent years; survival has increased from 70% at five years to 91% at ten years. The more common clinical presentation is a relatively benign disease, with respiratory failure due to airway collapse being the most common cause of death.

Enhancing Healthcare Team Outcomes

RP is a very rare disorder that typically causes inflammation in cartilage bearing tissues like the ear, nose, larynx and the airways. The inflammatory episodes are recurrent and unpredictable. A concomitant autoimmune disease also occurs in more than 30% of patients. The diagnosis is not always easy because there are no specific tests. Even when diagnosed, the treatment is not standardized. The drug treatment is tailored to each patient and the cornerstone of therapy is the use of glucocorticoids. For patients with severe disease, other immunosuppressive are used including methotrexate and cyclophosphamide.[12][13] (level III)

Because these drugs have potent adverse effects, the role of the pharmacist and nurses are critical. Both these professionals play a role in educating the patient on the signs and symptoms of the adverse effects and also ensuring compliance with the medications. Recently newer biological agents have also been used to manage RP patients with varying results. However, prior to initiating treatment with these novel agents, the patient needs a thorough work up to ensure that he or she is fit to receive the therapy. Any patient with worsening of symptoms should be referred to the specialist. [14] (level III)

Outcomes

Patients with RP have frequent relapses and the quality of life is poor. The mortality rate of RP patients is twice that of the general population. Until randomized controlled studies are available, the treatment of RP will remain empirical and based on personal experience. For healthcare workers who have never treated such a patient, referral to a tertiary care center is recommended.[15] (level III)