Relapsing polychondritis is a systemic disease characterized by repeated episodes of inflammation and in some cases deterioration of cartilage. The disease can be life-threatening if the respiratory tract, heart valves, or blood vessels are affected. The exact mechanism is poorly understood.
The diagnosis is based on the symptoms and supported by investigations such as blood tests and sometimes other investigations. Treatment may involve symptomatic treatment with painkillers or anti-inflammatory medications, and more severe cases may require suppression of the immune system.
Signs and symptoms Though any cartilage in the body may be affected in people with relapsing polychondritis, in many cases, the disease affects several areas while sparing others. The disease may exhibit variable signs and symptoms, resulting in a challenging diagnosis that can lead to delayed recognition for several months, years, or even decades.
Associated diseases Several other overlapping diseases associated with RP should also be considered. Approximately one-third of people with RP might be associated with other autoimmune diseases, vasculitides, and hematologic disorders. Systemic vasculitis is the most common association with RP, followed by rheumatoid arthritis and systemic lupus erythematosus. The following table displays the main diseases associated with RP. Class of disease Specific type of disease Vasculitides Granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, polyarteritis nodosa, Behçet's disease, Takayasu's arteritis, leukocytoclastic vasculitis, temporal arteritis and systemic vasculitis. Autoimmune diseases Systemic lupus erythematosus, systemic scleroderma, mixed connective tissue disease, autoimmune thyroiditis, Sjögren's syndrome, dermatomyositis, antiphospholipid syndrome, autoimmune hemolytic anemia, Hashimoto's thyroiditis. Other Rheumatologic diseases Rheumatoid arthritis, spondyloarthropathy, reactive arthritis, polymyalgia rheumatica. Hematologic disorders Myelodysplasia, myeloproliferative neoplasm. Dermatologic diseases Psoriasis, atopic dermatitis, lichen ruber planus, vitiligo. Autoinflammatory diseases Familial Mediterranean fever. Others Primary biliary cirrhosis, ulcerative colitis, Crohn's disease, diabetes mellitus, pulmonary fibrosis.
Cartilage inflammation Cartilage inflammation (technically known as chondritis) that is relapsing is very characteristic of the disease. These recurrent episodes of inflammation over the course of the disease may result in breakdown and loss of cartilage. The signs and symptoms of cartilage inflammation in various parts of the body will be described first.
Ear
Inflammation of the cartilage of the ear is a specific symptom of the disease and affects most people. It is present in about 20% of persons with RP at presentation and in 90% at some point. Both ears are often affected, but the inflammation may alternate between either ear during a relapse. It is characteristic for the entire outer part of the ear except the earlobe to be swollen, red, or less often purplish, warm, and painful to light touch.
The inflammation of the ear usually lasts a few days or more, rarely a few weeks, and then resolves spontaneously and recurs at various intervals. Because of the loss of cartilage, after several flares cauliflower ear deformity may result. The outer part of the ear may be either floppy or hardened by calcifications of the scar tissue that replaces the cartilage. These cauliflower ear deformities occur in about 10% of persons with RP.
Nose The inflammation of the cartilage of the nose involves the bridge of the nose and is often less marked than the ears. Statistics show that this clinical manifestation is present in 15% of persons with RP and occurs at some point in 65% of persons with RP. Nasal obstruction is not a common feature. Atrophy may eventually develop secondarily during the disease; this appears gradually and may go unnoticed. This can result in collapse of the nasal septum with saddle-nose deformity, which is painless but irreversible.
Respiratory tract Inflammation occurs in the laryngeal, tracheal, and bronchial cartilages. Both of these sites are involved in 10% of persons with RP at presentation and 50% over the course of this autoimmune disease, and are more common among females. The involvement of the laryngotracheobronchial cartilages may be severe and life-threatening; it causes one-third of all deaths among persons with RP. Laryngeal chondritis is manifested as pain above the thyroid gland and, more importantly, as dysphonia with a hoarse voice or transient aphonia. Because this disease is relapsing, recurrent laryngeal inflammation may result in laryngomalacia or permanent laryngeal stenosis with inspiratory dyspnea that may require emergency tracheotomy as a temporary or permanent measure.
Tracheobronchial involvement may or may not be accompanied by laryngeal chondritis and is potentially the most severe manifestation of RP.
The symptoms include shortness of breathing (dyspnea), wheezing, and a nonproductive cough. Obstructive respiratory failure may develop as the result of either permanent tracheal or bronchial narrowing or chondromalacia with expiratory collapse of the tracheobronchial tree. Endoscopy, intubation, or tracheotomy has been shown to hasten death.
Ribs Involvement of the rib cartilages results in costochondritis. Symptoms include chest wall pain or, less often, swelling of the involved cartilage. The involvement of the ribs is seen in 35% of persons with RP but is rarely the first symptom.
Other manifestations Relapsing polychondritis can affect various organ systems of the body. At first, some people with the disease may have only nonspecific signs and symptoms such as fever, weight loss, and malaise.
Joint The second most common clinical finding of this disease is joint pain with or without arthritis, after chondritis. All synovial joints may be affected.
At presentation, around 33% of people have joint symptoms that involve polyarthralgia and/or polyarthritis or oligoarthritis that affects various parts of the body and often appears to be episodic, asymmetric, migratory, and non-deforming. The most common sites of involvement are the metacarpophalangeal joints, proximal interphalangeal joints, and knees. Other affected joints include the ankles, wrists, metatarsophalangeal joints, and the elbows. Involvement of the axial skeleton is very rare. Tests for rheumatoid factor are negative in affected persons with RP, unless there is a co-morbidity with RA.
Less often, it has been reported that persons may experience arthralgia, monoarthritis, or chronic polyarthritis that mimics rheumatoid arthritis, leading to a difficult diagnosis for this disease. The appearance of erosions and destruction, however, is exceedingly rare, and this may point instead to rheumatoid arthritis as a cause.
Diseases and inflammation of tendons have been reported in small numbers of people with RP. During the course of the disease, around 80% of people develop joint symptoms.
Eye Involvement of the eye is rarely the initial symptom but develops in 60% of persons with RP. The most common forms of ocular involvement are usually mild and often consist of unilateral or bilateral episcleritis and/or scleritis, that is often anterior and could be lingering or relapsing. Scleritis that is necrotizing is found to be exceedingly rare. Less often, conjunctivitis occurs. Other ocular manifestations occur in persons with RP, these include keratoconjunctivitis sicca, peripheral keratitis (rarely with ulcerations), anterior uveitis, retinal vasculitis, proptosis, lid edema, keratoconus, retinopathy, iridocyclitis and ischemic optic neuritis that can lead to blindness. Cataract also is reported in relation to either the disease or to glucocorticoid exposure.
Neurological The involvement of the peripheral or central nervous system is relatively rare and only occurs in 3% of persons affected with RP, and is sometimes seen in relation to concomitant vasculitis. The most common neurological manifestations are palsies of the cranial nerves V and VII. Also hemiplegia, ataxia, myelitis and polyneuropathy have been reported in scientific literature. Very rare neurological manifestations include aseptic meningitis, meningoencephalitis, stroke, focal or generalized seizures and intracranial aneurysm. Magnetic Resonance Imaging of the brain shows multifocal areas of enhancement consistent with cerebral vasculitis in some cases.
Kidney The involvement of the kidney can be caused by primary renal parenchymal lesions, an underlying vasculitis, or another associated autoimmune disease. Actual kidney involvement is quite rare, elevated creatinine levels are reported in approximately 10% of people with RP, and abnormalities in urinalysis are reported in 26%. Involvement of the kidney often indicates a worse prognosis, with a 10-year survival rate of 30%. The most common histopathologic finding is mild mesangial proliferation, which is followed by focal and segmental necrotizing glomerulonephritis with crescents. Other abnormalities that are found include glomerulosclerosis, IgA nephropathy and interstitial nephritis. Immunofluorescence studies most often reveal faint deposits of C3, IgG or IgM in the primarily mesangium.
Constitutional symptoms These symptoms could consist of asthenia, fever, anorexia, and weight loss. They mostly occur during a severe disease flare.
Others Skin and mucous membranes: 20 to 30% of people with relapsing polychondritis have skin involvement, including aphthous ulcers, genital ulcers, and several non-specific skin rashes, including erythema nodosum, livedo reticularis, hives, and erythema multiforme. Cardiovascular system: Relapsing polychrondritis may cause inflammation of the aorta. It can also cause leaky heart valves (aortic valve regurgitation in 4 to 10%, mitral valve regurgitation in 2%).
Causes Relapsing polychondritis is an autoimmune disease in which the body's immune system begins to attack and destroy the cartilage tissues in the body. It has been postulated that both cell-mediated immunity and humoral immunity are responsible.
The reasons for disease onset are unknown.
Diagnosis There is no specific test for relapsing polychondritis. Some people may exhibit abnormal lab results, while others may have completely normal labs even during active flares. Patients with ear and nose chondritis with hematological (blood) abnormalities, including macrocytic anemia and thrombocytopenia, should be tested for a newly-recognized disease called VEXAS syndrome.
Diagnostic criteria Several clinical criteria are used to diagnose this disease. McAdam et al. introduced the clinical criteria for RP in 1976. These clinical criteria have later been expanded by Damiani et al. in 1979 and finally Michet et al. modified them in 1986. See the following table for these diagnostic clinical criteria and the number of conditions required for an official diagnosis.
Authors Criteria Conditions required McAdam et al. Bilateral auricular chondritis Nasal chondritis Respiratory tract chondritis Non-erosive seronegative polyarthritis Ocular inflammation Audiovestibular damage 3 out of 6 criteria Damiani et al. Bilateral auricular chondritis (A) Nasal cartilage inflammation (A) Respiratory tract chondritis (A) Non-erosive sero-negative polyarthritis (A) Ocular inflammation (A) Audiovestibular involvement (A) Histologic confirmation (B) Positive response to corticosteroids or dapsone (C) 3 (A) criteria or 1 (A) and (B) or 2 (A) criteria and (C) Michet et al. Auricular cartilage inflammation (A) Nasal cartilage inflammation (A) Laryngotracheal cartilage inflammation (A) Ocular inflammation (B) Hearing loss (B) Vestibular dysfunction (B) Sero-negative arthritis (B) 2 out of 3 (A) criteria or 1 out of 3 (A) criteria and 2 (B) criteria