Relapsing Polychondritis

Original Editor - Pacifique Dusabeyezu
Top Contributors - Pacifique Dusabeyezu, Kim Jackson and Carina Therese Magtibay

Introduction

Relapsing polychondritis (RP) is a rare multisystem autoimmune condition with an unknown cause. It is characterized by recurring episodes of inflammation that lead to the gradual destruction of various cartilaginous tissues in the body. This includes elastic cartilage found in the ears and nose, hyaline cartilage in peripheral joints, fibrocartilage in the spine, and cartilage in the tracheobronchial system. RP can affect structures rich in proteoglycans, such as those in the eye, heart, blood vessels, and inner ear.

Etiology

The etiology of Relapsing polychondritis remains unknown so far, and the pathogenesis appears to be mediated by an autoimmune reaction to type II collagen, which is abundant in cartilage and the sclera. Relapsing polychondritis is suggested to occur in a genetically predisposed individuals who are exposed to the 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.

Epidemiology

It is a rare disease, more common in Caucasians; the prevalence is 4.5 cases per million. Relapse polychondritis (RP) affects 1 in 1.4 million people per year in the UK, with a standardized mortality ratio of 2.16. Onset may be sudden, although in mild cases it can be insidious. In the United States, RP has an estimated annual incidence of 3.5 cases per one million people in the population, and among Department of Defense beneficiaries, the prevalence is approximately 4.5 cases per ten million individuals

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.

Clinical Presentation

The clinical presentation of people with RP varies from person to person and may include different organ systems. The most common clinical features and symptoms of relapsing polychondritis are as follows:

• Auricular Chondritis: is the most common feature of RP, affecting up to 90% of patients and is a symptom of first-line diagnosis in 20% of cases. In individuals with RP, the ear's cartilage matrix is severely inflamed and replaced by fibrous connective tissue, leading to a loss of normal morphology. This often presents as painful, red, swollen ears that may be misshapen due to cartilage damage. Hearing loss, either conductive or sensorineural, is observed in 46% of patients with RP, while vestibular dysfunction is documented in 6%.
• Nasal Chondritis: This condition also affects 24% of patients, develops in 53% of cases. It causes acute redness, tenderness, and pain, often accompanied by epistaxis. The condition lead to a collapsed nose bridge, saddle-nose deformity, and nasal congestion.
• Arthropathy: is the second most common symptom in RP, appearing in 50-85% of patients. It's a pattern of joint involvement affecting metacarpophalangeal, proximal, and knee joints. Joint destruction is rare, and tendinopathy and tenosynovitis are rare.
• Ocular manifestations: in Relapse polychondritis are usually mild and include episcleritis, scleritis, and conjunctivitis. Less frequently, RP can cause other conditions like iritis, retinopathy, muscle paresis, anterior uveitis, optic neuritis, occlusion of retinal arteries, and cataract.
• Respiratory symptoms are very common in individuals with RP and can be lethal, with 25% of patients presenting symptoms at the onset and increasing to 50% during the disease. Inflammation in the larynx, trachea, and broncial cartilage, hoarseness, dry cough, shortness of breath, wheezing, and stridor are common.

Diagnostic Procedures

There’s no specific test to diagnose or confirm relapsing polychondritis (RP). Diagnosis of relapsing polychondritis is primarily based on a combination of clinical features, radiographic findings, and biopsy of an inflamed tissue. It is guided by a set of clinical criteria suggested by McAdams et al. 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.

Biopsy of the auricular cartilage is performed to confirm the diagnosis of polychondritis. Biopsies are helpful in ruling out other causes of symptoms such as tuberculosis, syphilis, leprosy and infectious diseases and sometimes they are not conclusive.

Imaging studies, including a computed tomography (CT) scan of the lungs and other tests, especially pulmonary function test, may be performed to help determine the extent of disease. 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.

Management / Interventions

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

• For individuals presenting with auricular, nasal or articular involvement without systemic involvement, the recommended treatment options include the use of anti-inflammatory medications, colchicine, or dapsone. In many cases, low-dose glucocorticoid therapy may also be necessary.
• In cases where patients present with more severe symptoms, such as significant airway issues like laryngeal or tracheobronchial chondritis, abrupt onset of sensorineural hearing loss or eye-related problems, the recommended treatment option involves initiating glucocorticoid therapy. This typically entails administering 1 gram of IV methylprednisolone for three days, followed by oral prednisone at a dose of 1 mg per kilogram of body weight.
• Surgical interventions such as stenting, airway dilation, tracheostomy, and laryngotracheal reconstruction are needed in cases of airway collapse.

Differential Diagnosis

The diagnosis of relapse polychondritis (RP) is difficult because of its rarity and variable presentation. Therefore, it is important for healthcare providers to consider a comprehensive differential diagnosis in order to rule out other possible causes of the patient's symptoms. Some conditions that can be taken into account in differential diagnosis of RP are as follows.

• Wegener's granulomatosis
• Rheumatoid arthritis
• Ankylosing Spondylitis
• Hansen's disease and syphilis
• Periarteritis nodosa (PAN)
• Behcet Disease

Prognosis

Most individuals with RP typically experience a variable disease course marked by intermittent episodes of inflammation. During each flare-up, the specific sites affected, and the severity of involvement tend to change and are not consistent. Many patients also deal with persistent symptoms in between these acute episodes.

In recent years, the outcome of patients with relapsing polychondritis (RP) has improved. The survival rate has risen significantly, going from 70% at five years to 91% at ten years. The typical clinical presentation tends to be less severe, characterized by a relatively mild course of the disease. However, it's worth noting that respiratory failure resulting from airway collapse, cardiac issues like valvular disease and advanced systemic vasculitis, remains the leading cause of mortality.