Relapsing polychondritis is a rare inflammatory disease characterized by recurrent inflammation of cartilage and other structures rich in proteoglycans, and involves damage to eye, ear, nose and cardiovascular system.
Typically, relapsing polychondritis presents with sudden pain and common signs of inflammation at the affected site of inflammation at the onset of the disease . Common symptoms include pain, swelling, erythema, and tenderness of the pinna of one or both ears, nose, throat, joints, and eyes; the ear lobe is typically spared. Fever and weight loss may also occur.
Recurrent inflammation of the cartilages in the ears and nose results in damage to the cartilage of the pinna and the nasal septum causing the deformities called saddle nose and floppy ears . Inner ear involvement may cause vertigo, hearing loss, and nausea. Tracheal involvement may cause throat pain, hoarseness, and difficulty in breathing, which may become life threatening.
An urticarial annular cutaneous eruption is a characteristic early skin manifestation of relapsing polychondritis. Renal involvement is very rare in this disease. MAGIC syndrome is a syndrome in which relapsing polychondritis occurs with Behçet disease.
Other tissues which may be involved in relapsing polychondritis include the aorta, aortic valves, myocardium, pericardium, skin, and neurons. Therefore, possible complications of relapsing polychondritis include aortic aneurysm, aortic valve incompetence, pericarditis, myocarditis, vasculitis and cranial nerve palsies .
No laboratory finding is necessary to confirm a diagnosis of relapsing polychondritis, but it may assist in identifying associated complications. Common baseline blood investigations which might be helpful include complete blood count, blood urea nitrogen, erythrocyte sedimentation rate (ESR), acute phase protein levels. If there is anemia, peripheral blood film typically reveals a normochromic normocytic finding. ESR and C-reactive proteins are usually elevated. Serology is also indicated and includes antinuclear antibody (ANA) test and antineutrophil cytoplasmic antibody (ANCA) titers.
Urinalysis and liver function tests may also be necessary, especially as a workup for vasculitis. Purified protein derivative test is necessary to exclude tuberculosis as an infective cause of polychondritis. Screening tests for syphilis are also indicated.
Cultures are necessary and should be determined by the presentation of the disease. Sputum cultures and acid fast bacilli should be considered in patients with respiratory symptoms and disease signs. Cartilage biopsies from the airway should also be sent for bacterial, fungal, and acid-fast bacilli cultures. If fever is present, blood cultures may be necessary; cultures of the cerebrospinal fluid is necessary to exclude meningitis or CNS vasculitis.
Imaging studies are necessary for detailed evaluation of the pathology and exclusion of systemic complications. Chest X-rays, spiral CT scan (without contrast) PET scans, and MRI are also indicated  .
Mild cases of relapsing polychondritis may respond well to nonsteroidal anti-inflammatory drugs (NSAIDs). However, oral corticosteroids are the mainstay of treatment and are reserved for moderate to severe cases of the disease. Initial treatment is administered at 0.5 to 1.0 mg/kg. Immunosuppressants including azathioprine, dapsone and cyclosporine are reserved for recalcitrant cases which are unresponsive to corticosteroids .
The disease relapses and remits in an episodic pattern with each episode being more severe than the previous. Each episode usually lasts several weeks, with periods of remission lasting several years.
The prognosis of the disease is determined by the degree of systemic involvement and treatment responsiveness of the patient. Involvement of the larynx, trachea, and bronchi may cause a life-threatening acute respiratory obstruction.
Airway involvement occurs in about 50% of all cases, while cardiovascular involvement occurs in 24-52% of cases. Cardiovascular complications are the second most common cause of mortality in patients with relapsing polychondritis . The commonest cause of death in relapsing polychondritis is infection, which is secondary to steroid therapy or airway compromise, systemic vasculitis, and unrelated coexisting malignancy.
Generally, early diagnosis and prompt treatment are associated with a good outcome in patients.
The cause of relapsing polychondritis is largely unknown. A possible role of genetic factors has been suggested. This is based on the findings of familial clusters with the disease and its increased incidence in individuals with HLA-DR4 haplotype.
Some studies have also indicated hormonal factors as etiologic agents in relapsing polychondritis. In one particular study, two men were found to develop relapsing polychondritis after being administered with luteinizing hormone-releasing hormone LHRH). In another report, a woman with a known diagnosis of arthritis mutilans developed an acute exacerbation of the disease with a new onset of auricular damage, hearing loss, weight loss, and nasal septal damage after being injected with human chorionic gonadotropin .
Relapsing polychondritis has an incidence rate of approximately 0.71 per 1 million population annually . Peak onset of the disease occurs at the age of 40-50; however, it affects persons of any age group .
Relapsing polychondritis shows no sexual predilection and affect persons of all races, but has been found to be more common among Caucasians.
Researchers have studied the possibility of autoimmunity as the main pathophysiologic mechanism of the disease. Some studies have identified the presence of circulating autoantibodies against cartilage-specific collagens of types II, IX, and XI in 30%-70% of cases. Studies also revealed that autoantibodies to collagen type II are present in the acute phases of the disease and that the levels of the antibodies are directly proportional to the severity of the episode . These anticollagen types I, II, and III antibodies are thought to appear as a result of carriage destruction. Furthermore, antibodies to collagen type II are not specific to relapsing polychondritis, they also occur in rheumatoid arthritis.
Anticollagen IX and XI antibodies have also been identified and are shown to be associated with anticollagen II antibodies. Other studies have identified an increased titer of antibodies to an extracellular matrix protein called matrillin 1 in patients with relapsing polychondritis. This protein is predominantly found in the trachea. This study showed that this antibody titer was higher than in patients with systemic lupus erythematosus, Wegener's granulomatosis, rheumatoid arthritis, and healthy individuals .
Furthermore, researchers have identified five proteins which may be autoantigens linked to the pathophysiology of relapsing polychondritis. These include alpha enolase, vimentin, colligin-1/2, calreticulin, and tubulin-alpha ubiquitous-6. The tubulin-alpha ubiquitous-6 is a family of proteins which are the main constituents of microtubules. Calreticulin is a calcium binding chaperon which is involved in cardiac function.
The predominant histological feature of relapsing polychondritis is tissue lymphocytic and neutrophilic infiltration. However, there have been few studies done to determine the association of cellular immunity with the pathogenesis of relapsing polychondritis. HLA-DR4 has been linked to an increased risk of relapsing polychondritis. This was also proven by a double-transgenic mouse model which demonstrated that several molecules of HLA class II are required to express predisposition to the disease.
Natural killer T (NKT) cells occur in two forms: CD4+ and CD4-/CD48-. The antigen presenting cells present antigens to these natural killer T cells via CD1d, the major histocompatibility complex (MHC)-like molecule. The number and function of these NKT cells are significantly reduced in autoimmune processes including those involved in type 1 diabetes mellitus, systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis open link.
Studies have also observed reduced levels of CD4-/CD-8, CD4+, V- alpha+, and V-beta11 cells in patients with active relapsing polychondritis as compared to their levels in health individuals. It has also been shown that CD4+ NKT cells play significant role in the responsiveness of T1-helper in patients with relapsing polychondritis .
In individuals with acute exacerbation of relapsing polychondritis, interleukin 8, monocyte chemoattractant protein-1, and macrophage inflammatory protein 1-alpha were observed to be significantly increased. These chemokines are all pro-inflammatory agents and cause activation of neutrophils, eosinophils and monocytes.
Furthermore, a study confirmed the role of T-cell response to collagen type II in the pathogenesis of relapsing polychondritis. The study identified T cells directed against and specific for a certain region of collagen type II .
Preventive measures against relapsing polychondritis are not well established as the cause of the disease is unknown. However, prevention of the complications of the disease is necessary as a tertiary method of prevention. A tracheal stent may be inserted in cases with tracheal involvement to prevent airway collapse or obstruction.
Relapsing polychondritis is a rare inflammatory disease characterized by recurrent episodes of inflammation of the cartilage and cartilaginous tissues. The disease usually involves the ear, nose, cardiovascular system, and the eye.
The etiology of relapsing polychondritis is largely unknown, however autoimmunity, genetic factors, and hormonal involvement have all been shown to contribute to its etiogenesis.
Relapsing polychondritis can occur at any age; however, it has its peak onset in the 5th decade of life. It occurs without sexual or racial preferences.
Presentation of the disease varies from mild inflammatory features to severe life-threatening sequalae . Common features of the disease include unilateral or bilateral ear inflammation presenting as pain, erythema, swelling, and warmth of the pinna, with no involvement of the ear lobule. Ear findings are seen in 90-95% of cases. Involvement of the inner ear and vestibular apparatus may lead to vertigo, tinnitus, nausea, and ataxia. Conductive or sensorineural hearing loss can also occur as a complication of relapsing polychondritis.
Nasal chondritis occurs in 50% of cases and manifests as pain and tenderness of the nasal septum and over the nasal skin. Recurrent damage of the nasal cartilage results in the saddle nose deformity. Airway involvement may cause hoarseness, aphonia, wheezing and stridor, dyspnea, and in severe cases, severe airway obstruction .
Ophthalmic features of relapsing polychondritis include proptosis, conjunctivitis, periorbital edema, peripheral uveitis, and episcleritis. Skin manifestation include presence of purpura, papules, and aphthosis.
Diagnosis of relapsing polychondritis is mainly clinical, however, laboratory investigations and imaging studies may help to corroborate the diagnosis and exclude possible complications.
Mainstay of treatment of relapsing polychondritis is corticosteroid, however mild cases may resolve with Nonsteroidal anti-inflammatory drugs (NSAIDs).
Relapsing polychondritis is a rare disease characterized by episodes of painful inflammation of the cartilage in the joints and other structures in which cartilages are present such as the nose and the ear. It is characterized by severe pain, redness and swelling of the tissues involved.
The cause of this disease is largely unknown, however, researchers have suggested autoimmunity as the basis for this disease. Autoimmunity is a phenomenon whereby the antibodies, which help fight off harmful substances in the body, confuse normal tissues for foreign bodies. This confusion leads to destruction of the normal tissue by the antibodies.
Because autoimmunity is largely genetic, relapsing polychondritis is therefore said to be possibly inherited. Some other scientific reports have observed that hormones may be involved in the development of this disease. This disease can occur to persons of any age and race, but it occurs most commonly in individuals between 40 to 50 years of age.
Relapsing polychondritis presents in episodic manner with asymptomatic intervals. It usually presents with swelling, redness, and severe pain in one or both ears. Severe cases may present with deafness and loss of balance. Basically, the disease affects any part of the body with cartilage. The nose is also commonly affected and it becomes swollen, red, and weak.
The disease may affect the eye causing blindness, the airway involvement may manifest as cough, shortness of breath, and hoarseness of voice. In severe cases, it may cause obstruction of the airway, such that it becomes difficult taking air into the lungs, this may cause death of the patient. Occasionally, it may affect the heart, causing abnormal heart sounds called murmurs and heart failure.
With recurrent inflammation, cartilage damage may occur causing weakness of the tissues involved. This results in floppy ears and saddle nose. Sometimes, the damage done to the cartilages that connect the ribs to the breastbone makes the chest appear like a hollow space. This condition is called pectus excavatum.
Early diagnosis and treatment of this disease promotes survival of the patient. However, some complications may lead to death of the patient, commonest of these is infection. Other common causes of death in these patients include heart damage and airway compromise.
This condition can be diagnosed without any laboratory investigations. If there are at least three of the following symptoms, a diagnosis of relapsing polychondritis is made:
Taking a sample from the affected tissue (commonly the ear) with a needle (biopsy) may reveal characteristic features of the disease when the sample is examined under a microscope. However, blood and urine tests may be necessary to exclude complications of the disease. Computed tomography scans and X-rays of the chest may be recommended if there are signs of airway compromise.
Mild cases of relapsing polychondritis can be treated with nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen. In more severe cases, corticosteroids are prescribed in doses which are gradually reduced as the patient begins to improve. In patients who do not respond to treatment with steroids by resolution of the symptoms, other drugs which suppress the activities of the antibodies are prescribed. These drugs are called immunosuppressants, examples of which include azathioprine, cyclosporine, and cyclophosphamide.
Generally, all these medications do not cure the disease, but alleviate the symptoms. Additionally, surgery may be recommended for some of these complications such as airway obstruction and heart valve damage.