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Autoimmune disorder that affects cartilage structures and other connective tissues such associated elastic tissues of heart valves and aorta.
RP is a rare, progressive, relapsing/remitting, autoimmune disorder that affects cartilaginous and proteoglycan rich tissues throughout the body.
It results in recurrent episodes of inflammation that can destroy tissue.
Rare disorder with the peak age of onset between 40 and 50 years.
Estimated incidence of 0.7-3.5 cases per million people per year.
All racial groups are involved, and men and women or equally affected.
Typical onset is in middle age.
Women are affected slightly more than men.
Cause is not known.
Not associated with familial clustering, but susceptibility is increased slightly by the HLA-DR4 haplotype.
A severe, episodic, and progressive inflammatory condition involving cartilaginous structures, predominantly those of the ears, nose, and laryngotracheobronchial tree, eyes, cardiovascular system, peripheral joints, skin, middle and inner ear, and CNS.
Approximately 1/3 of patients have another systemic illness such as vasculitis, connective tissue disorder, or myelodysplastic syndrome.
Diagnosis is often delayed due to the frequent spontaneous resolution of flares and variability of presentation.
Manifested by abrupt onset of inflammation of the Cartilaginous ear, nose, joints, laryngotracheobronchial tree or heart valves.
Auricular chondritis affects approximately 90% of patients with relapsing polychondritis.
Recurring episodes can destroy airicular cartilage resulting in a cauliflower appearance of the ear, and hearing loss occurs and approximately 40% of cases.
Nasal chondritis can cause saddle nose deformity.
Ocular involvement can cause blindness and, approximately half of patients present with scleritis episcleritis uveitis, and conjunctivitis.
In 20 to 50% of patients with RP affects the larynx with tracheobronchial tree with laryngeal or tracheal stenosis, tracheal malacia or tracheobronchial obstruction.
Sudden death secondary to tracheal/bronchial airway edema/obstruction has been reported.
Cardiovascular involvement includes aortic regurgitation, mitral regurgitation, and ascending aortic aneurysms.
Costochondritis may cause chest pain and impair breathing.
About a half of patients have asymetric nonerosive arthritis of large and small joints and many patients have systemic symptoms such as fatigue and weight loss.
The process follows in an indolent, relapsing-remitting course but may also present fulminantly and threatening vision and organ function.
Diagnosis is made if three of six clinical findings are present: 1) auricular chondritis, 2) nonerosive inflammatory arthritis, 3) nasal chondritis, and 4) ocular inflammation including conjunctivitis, keratitis, scleritis, episcleritis, or uveitis, 5) laryngotracheal chondritis, and 6) cochlear or vestibular damage presenting as sensorineural hearing loss, tinnitus or vertigo.
No specific laboratory tests exist, however, C reactive proteins and ESR are elevated in approximately 60% of patients.
Biopsy is generally not required.
A diagnosis can be made if a patient has one of the six criteria and has compatible cartilage biopsy histology or meets two of six criteria and improves clinically after receiving corticosteroids or dapsone.
Some patients experience glomerulonephritis, skin lesions including erythema nodosum, urticaria and also constitutional symptoms.
Disease complications include vision or hearing loss, saddle nose or ear deformity, cardiac valve insufficiency, respiratory tract inflammation that can lead to strider, obstructive pneumonia, or tracheomalacia, and large vessel vasculitis.
Average age at diagnosis is 40-50 years.
The annual incidence only 3.5 cases per million population.
Relapsing polychondritis may occur at any age; however, the disease usually has an onset during the fifth decade of life. No relationship exists between age of onset and sex.
Most common in Caucasions, although it is found in persons of all races.
5-year survival rate 66%-74%, and 10-year survival rate of 55% reported in early studies, while contemporary survival rate of 94% at 8 years has been reported and reflects diagnosis at earlier stage of disease.
Circulating antibodies to type II collagen, correlate with disease activity.
Pathological findings include infiltration of T cells, and the presence of antigen-antibody complexes in affected cartilage.
Cellular and humoral responses against collagen type II and other collagen antigens are present.
Immunosuppressive regimens suppress the disease and suggest the presence of cartilage-specific autoantibody is central to the pathogenesis.
Circulating antibodies to cartilage-specific collagen types II, IX, and XI are present in 30%-70% of patients.
Antibodies to type II collagen are present during acute relapsing polychondritis episodes and that the levels correlate with the severity of the process.
Such antibodies are felt to be a result of cartilage destruction.
No specific laboratory findings are crazy are present, but may have mild leukocytosis, normocytic anemia, thrombocytosis, eosinophilia , elevated ESR, elevated C-reactive protein and anti-nuclear antibodies may be positive in low titer, and positive rheumatoid factor.
Up to 1/3 of cases present prior to, during, or after another illness.
The most common associated syndromes include systemic vasculitis, rheumatoid arthritis, and systemic lupus erythematosus.
The association of Behcet disease, Hashimoto’s thyroiditis, inflammatory bowel disease, polymyalgia rheumatica, spondyloarthropathies and myelodysplastic syndrome have been reported.
Corticosteroid therapy is associated with a decrease collagen antibody titers.
Anticollagen type II antibodies are not specific for RP and may be seen in other rheumatological disese states, such as rheumatoid arthritis.
Autoantibodies to minor cartilage-specific collagens may be present.
Antibodies to matrilin 1, an extracellular matrix protein predominantly expressed in tracheal cartilage, is significantly higher in patients with relapsing polychondritis, especially in those with respiratory symptoms.
Most patients have high titers of antifetal cartilage antibodies during the early acute phase of the disease.
Association with a relative risk in individuals with HLA-DR4, suggests an autoimmune pathogenesis.
Cytokines interleukin 8, macrophage inflammatory protein 1-alpha, and monocyte chemoattractant protein are elevated in patients with relapsing polychondritis and result in accumulation and activation of neutrophils, eosinophils, and monocytes/macrophages.
25%-35% of patients with relapsing polychondritis had a concurrent autoimmune disease.
Most frequently associated with systemic vasculitis, rheumatoid arthritis, SLE, and Sjögren syndrome.
May be associated with internal malignancy as a paraneoplastic process.
Wide clinical spectrum of disease manifestations and episodic nature of the disease may result in a significant delay in diagnosis.
Signs and symptoms include: fever, weight loss, ear pain, floppy ear, impaired hearing of sudden onset, tinnitus, otitis media, vertigo, impaired balance, rash, polyarthritis, monoarthritis, myalgias, bone pain, claudication, arthralgias, dyspnea, wheezing, cough, deconditioned status, hoarseness,
dysphagia, saddle-shaped nose, epistaxis, painful, red, and swollen nose, conjunctivits, episcleritis, conjunctivitis, scleritis, diplopia, eyelid swelling,
chest pain, arrhythmias, pericarditis, myocardial ischemia, abdominal pain, syncope, headache, confusion, ataxia, focal weakness, impaired mentation, seizures, and cranial nerve palsies
Auricular involvement is most common, but the eyes, nose, airways, heart, skin, joints, kidneys, nervous system and vascular system may be involved.
Cardiac involvement includes, myocarditis, aortic regurgitation, mitral regurgitation, pericarditis, heart block, large artery aneurysms, atrial tachyarrhythmias, and ischemic changes.
Cardiac involvement in 15-46% of cases.
Cardiovascular involvement is the second leading cause of death following laryngo-tracheal disease.
Aortic regurgitation prevalence ranges from 4-6% and mitral regurgitation 2-3%, respectively.
Aortic regurgitation may develop months to years after the onset of disease.
Severe valvular disease requiring valve replacements is rare and associated with poor prognosis.
Valvular regurgitation is secondary to aortic root and mitral annulus dilation.
The aorta shows cystic degeneration of collagen with elastic fiber destruction and decreased mucopolysaccharides.
Clinical manifesttions include:systemic vasculitis, arthritis, anemia, vertigo, laryngeal-bronchial strictures,epiglottitis, saddle -nose deformity,scleritis, iritis, conjunctivitis, blindness, pulmonary infections, respiratory infection, flail chest, blindness, tinnitus, hoarseness, respiratory failure, aortic regurgitation, mitral regurgitation, aortic dissection, and renal failure.
Most frequent causes of death associated with infection secondary to corticosteroid treatment or respiratory compromise.
Ten-fifty percent of deaths result from airway complications, systemic vasculitis, and malignancy.
Life expectancy decreased compared with healthy individuals, patients with renal involvement have a significantly lower age-adjusted life expectancy.
Renal involvement is a poor prognostic factor at all ages.
In patients with renal disease, uremia is the third most frequent cause of death.
Diagnostic criteria: Bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, audiovestibular damage
Other criteria include a therapeutic response to corticosteroid or dapsone therapy, and proven inflammation in 2 of 3 of the auricular, nasal, or laryngotracheal cartilages plus 2 other signs including ocular inflammation, vestibular dysfunction, seronegative inflammatory arthritis, and hearing loss.
Signs and symptoms of relapsing polychondritis include the following:
85%-95% develop auricular chondritis.
Unilateral or bilateral ear pain, swelling, and redness can begin suddenly, and usualy resolves within 2-4 weeks, but does not involve the ear lobules.
The ear cartilage softens and can collapse.
The ear may develop nodularity and calcification.
46%-50% of patients with concomitant auricular chondritis may develop sudden loss of hearing, tinnitus, nausea, vomiting, nystagmus, and vertigo.
52-85% of patients develop seronegaive arthritis, usually nondeforming, assymetrical, mono or polyarticular in nature.
Any joint may be involved with nonerosive.
Nasal chondritis occurs in 48%-72% of patients manifested by pain and full sensation over the nasal bridge, and may be associated with mild epistaxis.
In the presence of long-standing disease saddle-nose deformity may develop.
Because collagen types II, IX, and XI are found in the cornea and sclera autoantibodies to these collagens associated with RP may be responsible for inflammation to the eyes.
50%-65% develop episodic inflammation of the uveal tract, conjunctivae, sclerae, and/or corneas, with the most common conditions episcleritis occur in 39% and scleritis in 14%, eyelid edema, iritis, and retinopathy are found in 9% of patients, and 5% of patients have ocular muscle paresis or optic neuritis.
Uncommonly, peripheral ulcerative keratitis associated with perforation, endophthalmitis, papilledema, visual field defects, ptosis, lid retraction, proptosis, and cataracts may be present.
Respiratory tract involvement affects 40%-56% of patients, and involve any part of the respiratory tree.
Tenderness to palpation over the anterior trachea or thyroid cartilage may occur anf inflammation of the tracheal cartilage may weaken the tracheal cartilage rings, resulting in wheezing, dyspnea, cough, and hoarseness.
Upper airways can become stenosed and replaced by fibrotic tissue with respiratory symptoms that may result in a tracheostomy.
Affects the cardiovascular system in 24% of patients and manifestations include: aortic and mitral valve regurgitation, aortic aneurysm, aortitis, aortic thrombosis, pericarditis, heart block, and myocardial infarction.
CNS manifestations of relapsing polychondritis are rare and are related to vasculitis of the small and/or medium sized arteries.
CNS disease may precede other manifestations of relapsing polychondritis and include:impaired memory, extremity weakness, seizures, gait abnormalities, paresthesias, delusional ideation, cranial nerve palsies, and meningo/encephalitis symptoms.
Renal involvement with microscopic hematuria and proteinuria may be present as a manifestation of vasculitis of the glomeruli.
May be a paraneoplastic process with underlying myelodysplastic syndrome and lymphoma.
Differential diagnosis includes: Addison Disease,Behcet Disease, hyperthyroidism, polyarteritis nodosa, rheumatoid arthritis, syphilis, and Wegener’s granulomatosis.
Treatment is to decrease symptoms and to preserve the integrity of cartilaginous structures.
The mainstay of treatment is systemic corticosteroid therapy.
Most patients require a low daily dose of prednisone for maintenance therapy, and may need high doses during epidsodic flares.
Multiple other agents are efficacious and include: azathioprine, methotrexate, cyclophosphamide, cyclosporin A, dapsone, and tumor necrosis factor inhibitors.
Nonsteroidal anti-inflammatory drugs are not effective agents.