Introduction
Background
Relapsing polychondritis (RP) is a severe, episodic, and progressive inflammatory condition involving cartilaginous structures, predominantly those of the ears, nose, and laryngotracheobronchial tree. Other affected structures may include the eyes, cardiovascular system, peripheral joints, skin, middle and inner ear, and CNS. In 1923, Jaksch-Wartenhorst described a patient who experienced an 18-month course of progressive degeneration of the peripheral joints, external ears, nasal septum, external auditory canals, inner ear, and epiglottis. He termed this condition polychondropathia.1
In 1960, Pearson, Kline, and Newcomer reviewed 12 cases and expanded the clinical spectrum of relapsing polychondritis to include nonconcurring inflammation of the auricles, nasal septum, peripheral joints, and larynx, with occasional involvement of the middle and inner ears, the eyes, costal cartilages, spine, trachea, bronchi, and epiglottis. They noted that, after a few episodes of inflammation, the cartilage was replaced by fibrous connective tissue. The term relapsing polychondritis was introduced in that review.2
Pathophysiology
The etiology of this rare disease is unknown; however, the pathogenesis is autoimmune. The evidence for an autoimmune etiology includes pathological findings of infiltrating T cells, the presence of antigen-antibody complexes in affected cartilage, cellular and humoral responses against collagen type II and other collagen antigens, and the observation that immunosuppressive regimens most often suppress the disease.
Humoral response
The specificity of autoimmune injury to cartilaginous tissues has led investigators to test the hypothesis that a cartilage-specific autoantibody is central to the pathogenesis of relapsing polychondritis. Various studies find circulating antibodies to cartilage-specific collagen types II, IX, and XI to be present in 30%-70% of patients with relapsing polychondritis. Researchers have found that antibodies to type II collagen are present during acute relapsing polychondritis episodes and that the levels correlate with the severity of the episode.3
Treatment with prednisone is associated with a decrease in antibody titers. Antibodies to collagen types I, II, and III are believed to result from cartilage destruction; it has been proposed that antibodies are formed as a primary event in relapsing polychondritis.3 However, anticollagen type II antibodies are not specific to relapsing polychondritis; they have been identified in other arthritides such as rheumatoid arthritis (RA). The epitope specificity of the antibodies in relapsing polychondritis differs from those in RA, suggesting different mechanisms for formation and pathophysiologic roles.
Autoantibodies to minor cartilage-specific collagens (ie, types IX and XI) have been described. They are more likely to be found in association with antibodies to type II collagen in patients with relapsing polychondritis. Furthermore, levels of antibodies to matrilin 1, an extracellular matrix protein predominantly expressed in tracheal cartilage, were significantly higher in patients with relapsing polychondritis, especially in those with respiratory symptoms, than in patients with Wegener granulomatosis, systemic lupus erythematosus, or RA and in healthy controls.4
Most patients with relapsing polychondritis had high titers of antifetal cartilage antibodies during the early acute phase. The antifetal cartilage antibodies were found in 6 of 9 patients and only 4 (1.5%) of 260 patients with RA, exclusively in long-standing disease.5 A report of relapsing polychondritis in the newborn of a mother with relapsing polychondritis suggests that antibodies crossing the placenta are necessary and sufficient to elicit the entire clinical syndrome.
Using proteomic surveillance to identify ubiquitous cellular proteins in patients with relapsing polychondritis, researchers identified 5 proteins that may be autoantigens. These include (1) tubulin-alpha ubiquitous/6, which, as a family, are main components in microtubules; (2) vimentin, an intermediate filament protein; (3) alpha-enolase; (4) calreticulin, a Ca2+ –binding chaperon indispensable for cardiac development; and (5) colligin-1/2. All but tubulin-alpha have been described as autoantigens in other autoimmune diseases (eg, RA, mixed connective-tissue disease, Behçet disease). Although autoantibodies to tubulin-alpha have been reported in other autoimmune conditions, immunoglobulin G (IgG) antibodies to tubulin-alpha chains are rarely reported and may have diagnostic value in persons with relapsing polychondritis.6
Cellular response
Although an inflammatory infiltrate of lymphocytes and neutrophils is the dominant histopathologic feature of relapsing polychondritis, little attention has been paid to the possible role of cellular immune responses in this condition. The association of relapsing polychondritis with HLA-DR4 also suggests an autoimmune pathogenesis. Individuals with HLA-DR4 were found to have a relative risk of 2 for developing relapsing polychondritis. The studies suggest the role of genetic factors in determining risk for developing relapsing polychondritis.
An elegant double-transgenic mouse model provides further evidence that HLA associations are important in the development of relapsing polychondritis. The model demonstrated that more than one HLA class II molecule might be required for expression of susceptibility. The model suggests an important role for cell-mediated immune responses and provides a means for acquiring a detailed understanding of its pathogenesis.
Natural killer T (NKT) cells, lymphocytes discrete from other T, B, and natural killer cells, come in two varieties: CD4+ and CD4-/CD8-. Antigen-presenting cells present antigen to the NKT cells via the major histocompatibility complex–like molecule CD1d. NKT cells are decreased in number and function in several other autoimmune diseases, including multiple sclerosis, RA, systemic lupus erythematosus, systemic sclerosis, and type 1 diabetes mellitus.
Researchers have quantified CD4-/CD8- and CD4+ V-alpha+ V-beta11+ NKT cells and found them decreased in patients with active or quiescent relapsing polychondritis compared with healthy controls. Analysis of the secreted cytokine profile and of binding of alpha-galactosylceramide–loaded CD1d to NKT cells suggests that CD4+ NKT cells play an important role in T1-helper responsiveness in patients with relapsing polychondritis.7
Serum levels of 17 cytokines from 22 patients with relapsing polychondritis experiencing a clinical flare were compared with those in age-matched controls. Three of the cytokines, interleukin 8, macrophage inflammatory protein 1-alpha, and monocyte chemoattractant protein-1, were found to be significantly elevated in patients with relapsing polychondritis. All 3 chemokines are proinflammatory and result in accumulation and activation of neutrophils, eosinophils, and monocytes/macrophages.8
Additionally, a group of researchers found T cells directed against collagen type II in one patient. A T-cell clone was identified and was found to be specific for a certain region of the collagen type II peptide. This research indicates that a T-cell response to collagen type II may play a role.9
Animal models
Mouse and rat models have been helpful in elucidating the autoimmune origin of relapsing polychondritis. Immunization of rats with native bovine type II collagen resulted in bilateral auricular chondritis, with histologic findings similar to the findings of human relapsing polychondritis in 12 of 88 (14%) rats. In addition, 8 of 12 rats developed arthritis. Severe auricular chondritis was accompanied by immunofluorescence positive for IgG and C3 in affected cartilage and by circulating IgG that was reactive against native bovine type II collagen.
Immunization of a different strain of rats with native chick type II collagen was associated with auricular chondritis, in addition to the intended collagen-induced arthritis. Biopsy studies showed that the few auricular lesions contained IgG and C3. Antibodies to native type II collagen were found in the sera of rats that developed auricular chondritis and in rats with collagen-induced arthritis.10
Although most data implicate cartilage collagens as the immunogens in relapsing polychondritis, immunization of rats with matrilin 1, a noncollagenous cartilage matrix protein, is associated with development of a clinical syndrome resembling relapsing polychondritis. The syndrome differed significantly from the collagen immunization disease model in that the trachea, nasal cartilages, and kidneys primarily were affected, and the joints and auricles were spared. Matrilin 1 is found in highest levels in the tracheal cartilage and in the nasal septum, likely explaining the observed clinical differences. Matrilin 1 is also found in adult auricular cartilage and costochondral cartilage and is absent in articular cartilage. The presence of both humoral and cellular responses to matrilin 1 has been detected in a patient with significant involvement of the auricular, nasal, and tracheobronchial cartilage and with little arthritis.11
The same investigators demonstrated a crucial role for B cells and C5 in the induction of relapsing polychondritis–like symptoms. Additionally, pathogenicity of matrilin 1–specific antibodies in their matrilin 1–induced relapsing polychondritis mouse model was recently recognized. The authors note that further investigation is needed into the role of B cells, complement, and cell-mediated immunity to better understand this complex disease.11
Recently, transgenic mice that expressed HLA-DQ6a8b developed spontaneous polychondritis in middle age. This condition is characterized by auricular and nasal chondritis with polyarthritis. As opposed to mice with collagen type II–induced polychondritis, mice with spontaneous polychondritis do not show the overwhelming collagen type II immune response and may serve as a better animal model of relapsing polychondritis.12
Other autoimmune disorders
The hypothesis of an autoimmune etiology for relapsing polychondritis is also supported by the high prevalence of other autoimmune disorders found in patients with relapsing polychondritis. McAdam et al reported that 25%-35% of patients with relapsing polychondritis had a concurrent autoimmune disease.13
Autoimmune Conditions Reported in Patients With Relapsing Polychondritis
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Table
Disease | Patients With Condition/Total Patients | References |
Systemic vasculitis | 3 (5%) of 62 | Zeuner et al 14 |
11 (10%) of 112 | Michet et al 15 | |
8 (12%) of 66 | Trentham and Le 16 | |
28 (18%) of 159 | McAdam et al 13 | |
50 (13%) of 399 | Total | |
Cutaneous leukocytoclastic vasculitis | 2 (33%) of 6 | Priori et al 17 |
6 (5%) of 112 | Michet et al 15 | |
8 (7%) of 118 | Total | |
Thyroid disease | 8 (5%) of 159 | McAdam et al 13 |
10 (15%) of 66 | Trentham and Le 16 | |
2 (33%) of 6 | Priori et al 17 | |
4 (4%) of 112 | Michet et al 15 | |
2 (3%) of 62 | Zeuner et al 14 | |
26 (6%) of 405 | Total | |
Rheumatoid arthritis* | 8 (5%) of 159 | McAdam et al 13 |
3 (2%) of 180 | Piette et al 18 | |
8 (7%) of 112 | Michet et al 15 | |
7 (11%) of 62 | Zeuner et al 14 | |
26 (5%) of 513 | Total | |
Systemic lupus erythematosus† | 2 (1%) of 159 | McAdam et al 13 |
9 (5%) of 180 | Piette et al 18 | |
1 (17%) of 6 | Priori et al 17 | |
6 (5%) of 112 | Michet et al 15 | |
3 (5%) of 62 | Zeuner et al 14 | |
21 (4%) of 519 | Total | |
Sjögren syndrome (possible) | 5 (3%) of 159 | McAdam et al 13 |
5 (5%) of 111 | Piette et al 18 | |
10 (4%) of 270 | Total | |
3 (2%) of 159 | McAdam et al 13 | |
2 (3%) of 62 | Zeuner et al 14 | |
5 (2%) of 221 | Total | |
2 (1%) of 180 | Piette et al 18 | |
1 (2%) 62 | Zeuner et al 14 | |
1 (100%) of 1 | Haigh et al 19 | |
4 (2%) of 243 | Total | |
Mixed connective-tissue disease | 5 (3%) of 180 | Piette et al 18 |
2 (2%) of 112 | Michet et al 15 | |
7 (2%) of 292 | Total | |
3 (2%) of 180 | Piette et al 18 | |
Mesenteric panniculitis | 3 (2%) of 180 | Piette et al 18 |
Spondyloarthropathy | 2 (1%) of 180 | Piette et al 18 |
3 (3%) of 112 | Michet et al 15 | |
2 (3%) of 62 | Zeuner et al 14 | |
7 (2%) of 354 | Total | |
Diabetes mellitus | 1 (2%) of 62 | Zeuner et al 14 |
3 (2%) of 159 | McAdam et al 13 | |
4 (2%) of 221 | Total | |
2 (1%) of 159 | McAdam et al 13 | |
1 (<1%) of 112 | Michet et al 15 | |
3 (1%) of 271 | Total | |
2 (1%) of 159 | McAdam et al 13 | |
2 (1%) of 159 | McAdam et al 13 | |
Glomerulonephritis | 2 (1%) of 159 | McAdam et al 13 |
Dysgammaglobulinemia | 2 (1%)of 159 | McAdam et al 13 |
1 (1%) of 159 | McAdam et al 13 | |
Behçet disease* | 1 (<1%) of 112 | Michet et al 15 |
Psoriasis | 2 (1%) of 180 | Piette et al 18 |
2 (1%) of 180 | Piette et al 18 | |
1 (<1%) of 112 | Michet et al 15 |
Disease | Patients With Condition/Total Patients | References |
Systemic vasculitis | 3 (5%) of 62 | Zeuner et al 14 |
11 (10%) of 112 | Michet et al 15 | |
8 (12%) of 66 | Trentham and Le 16 | |
28 (18%) of 159 | McAdam et al 13 | |
50 (13%) of 399 | Total | |
Cutaneous leukocytoclastic vasculitis | 2 (33%) of 6 | Priori et al 17 |
6 (5%) of 112 | Michet et al 15 | |
8 (7%) of 118 | Total | |
Thyroid disease | 8 (5%) of 159 | McAdam et al 13 |
10 (15%) of 66 | Trentham and Le 16 | |
2 (33%) of 6 | Priori et al 17 | |
4 (4%) of 112 | Michet et al 15 | |
2 (3%) of 62 | Zeuner et al 14 | |
26 (6%) of 405 | Total | |
Rheumatoid arthritis* | 8 (5%) of 159 | McAdam et al 13 |
3 (2%) of 180 | Piette et al 18 | |
8 (7%) of 112 | Michet et al 15 | |
7 (11%) of 62 | Zeuner et al 14 | |
26 (5%) of 513 | Total | |
Systemic lupus erythematosus† | 2 (1%) of 159 | McAdam et al 13 |
9 (5%) of 180 | Piette et al 18 | |
1 (17%) of 6 | Priori et al 17 | |
6 (5%) of 112 | Michet et al 15 | |
3 (5%) of 62 | Zeuner et al 14 | |
21 (4%) of 519 | Total | |
Sjögren syndrome (possible) | 5 (3%) of 159 | McAdam et al 13 |
5 (5%) of 111 | Piette et al 18 | |
10 (4%) of 270 | Total | |
3 (2%) of 159 | McAdam et al 13 | |
2 (3%) of 62 | Zeuner et al 14 | |
5 (2%) of 221 | Total | |
2 (1%) of 180 | Piette et al 18 | |
1 (2%) 62 | Zeuner et al 14 | |
1 (100%) of 1 | Haigh et al 19 | |
4 (2%) of 243 | Total | |
Mixed connective-tissue disease | 5 (3%) of 180 | Piette et al 18 |
2 (2%) of 112 | Michet et al 15 | |
7 (2%) of 292 | Total | |
3 (2%) of 180 | Piette et al 18 | |
Mesenteric panniculitis | 3 (2%) of 180 | Piette et al 18 |
Spondyloarthropathy | 2 (1%) of 180 | Piette et al 18 |
3 (3%) of 112 | Michet et al 15 | |
2 (3%) of 62 | Zeuner et al 14 | |
7 (2%) of 354 | Total | |
Diabetes mellitus | 1 (2%) of 62 | Zeuner et al 14 |
3 (2%) of 159 | McAdam et al 13 | |
4 (2%) of 221 | Total | |
2 (1%) of 159 | McAdam et al 13 | |
1 (<1%) of 112 | Michet et al 15 | |
3 (1%) of 271 | Total | |
2 (1%) of 159 | McAdam et al 13 | |
2 (1%) of 159 | McAdam et al 13 | |
Glomerulonephritis | 2 (1%) of 159 | McAdam et al 13 |
Dysgammaglobulinemia | 2 (1%)of 159 | McAdam et al 13 |
1 (1%) of 159 | McAdam et al 13 | |
Behçet disease* | 1 (<1%) of 112 | Michet et al 15 |
Psoriasis | 2 (1%) of 180 | Piette et al 18 |
2 (1%) of 180 | Piette et al 18 | |
1 (<1%) of 112 | Michet et al 15 |
*Individual patients may carry more than one autoimmune diagnosis.
†Reported as 13 (20%) of 66 prevalence by Trentham and Le without division by disease
In addition, several reports have linked relapsing polychondritis with internal malignancy. It is thought to be paraneoplastic in these cases. The underlying malignancy is most often hematological in nature, but solid tumors have also been described.20
Frequency
United States
In clinical reports and reviews, relapsing polychondritis is reported to be a rare disease. By 1997, 600 cases had been reported worldwide. The annual incidence in Rochester, Minnesota, was noted to be 3.5 cases per million population.
International
The international incidence of relapsing polychondritis is unknown.
Mortality/Morbidity
In earlier studies, the 5-year survival rate associated with relapsing polychondritis was reported to be 66%-74% (45% if relapsing polychondritis occurs with systemic vasculitis), with a 10-year survival rate of 55%. More recently, a survival rate of 94% at 8 years has been reported.16 However, these data may represent relapsing polychondritis in patients with less severe disease than patients studied in earlier reports.
- The most frequent causes of death associated with relapsing polychondritis include infection secondary to corticosteroid treatment or respiratory compromise (10%-50% of deaths result from airway complications), systemic vasculitis, and malignancy unrelated to relapsing polychondritis.
- Although the life expectancy in all patients with relapsing polychondritis is decreased compared with age- and sex-matched healthy individuals, patients with renal involvement have a significantly lower age-adjusted life expectancy. Of those with renal disease, uremia is the third most frequent cause of death.
- Complications of relapsing polychondritis such as saddle-nose deformity (see Media File 9), systemic vasculitis, laryngotracheobronchial stricture, arthritis, and anemia in patients younger than 51 years portend a poorer prognosis than in age-matched patients with relapsing polychondritis without complications. Among patients older than 51 years, only anemia is associated with a poorer prognosis. Renal involvement is a poor prognostic factor at all ages.
Saddle-nose deformity. Courtesy of the University of Washington, Division of Dermatology.
- Complications of relapsing polychondritis include vertigo, tinnitus, voice hoarseness, joint deformity, epiglottitis, scleritis, conjunctivitis, iritis, need for permanent tracheotomy (severe cases), severe pulmonary infection, blindness, frail chest wall, respiratory failure, aortic regurgitation, mitral regurgitation, aortic dissection, and glomerulonephritis-associated renal failure.
Race
Relapsing polychondritis is most common in whites. Although relapsing polychondritis has been found in persons of all races, little data are available for nonwhite persons.
Sex
Reviews from the 1970s and 1980s found that relapsing polychondritis has no sexual predilection. However, reviews in 1998 and 2002 suggested a slight female predominance.21,16 Saddle-nose deformity and subglottic stricture are more common in females.
Age
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.
Clinical
History
The array of possible presenting symptoms and the episodic nature of relapsing polychondritis (RP) may result in a significant delay in diagnosis. In a review of 66 patients, the elapsed time from patient presentation for medical care for a related symptom to diagnosis was reported to be 2.9 years.16 In fact, one third of patients with diagnosed relapsing polychondritis see 5 or more physicians before the correct diagnosis is made.
The affected systems and symptoms reported in patients with relapsing polychondritis before and after diagnosis include the following:
- General - Intermittent fever, weight loss, and skin rash (see Physical)
- Audiovestibular - Sudden ear pain (unilateral or bilateral), inability to sleep on affected side, floppy ear, suddenly diminished hearing, tinnitus (occasional or persistent), otitis media, ear drainage, vertigo (with or without nausea and vomiting), and unsteadiness
Floppy ear. Courtesy of the University of Washington, Division of Dermatology.
- Musculoskeletal - Polyarthritis or monoarthritis, myalgias, back pain, rib pain, sternal pain, calf pain or claudication, and migratory or generalized arthralgias
- Respiratory - Dyspnea, wheezing, cough, exercise intolerance, hoarseness, and recurrent infection
- Gastrointestinal - Dysphagia
- Nasal - Feeling of fullness across nasal bridge, saddle-shaped nose, mild epistaxis, and painful, red, and swollen nose
- Ocular - Decreased visual acuity, conjunctivitis, episcleritis, scleritis, history of ocular inflammation, diplopia, and eyelid swelling
- Cardiovascular - Chest pain, abdominal pain, history of pericarditis, abnormal heart rate or rhythm, syncope, and history of subacute myocardial infarction (found on ECG)
- Central nervous system - Headache, ataxia, confusion, cranial nerve palsy, confusion, psychiatric signs, focal weakness/sensation changes, dementia, and seizures
Physical
Diagnostic criteria for relapsing polychondritis first were proposed by McAdam et al and have been modified several times. Perform biopsy only if clinical criteria are in question.McAdam et al criteria (3 of 6 clinical features necessary for diagnosis)
- Bilateral auricular chondritis
- Nonerosive seronegative inflammatory polyarthritis
- Nasal chondritis
- Ocular inflammation
- Respiratory tract chondritis
- Audiovestibular damage
Damiani and Levine criteria (1 of 3 conditions necessary for diagnosis)
- Three McAdam et al criteria
- One McAdam et al criterion plus positive histology results
- Two McAdam et al criteria plus therapeutic response to corticosteroid or dapsone therapy
Michet et al criteria (1 of 2 conditions necessary for diagnosis)
- Proven inflammation in 2 of 3 of the auricular, nasal, or laryngotracheal cartilages
- Proven inflammation in 1 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:
- Auricular chondritis
- Of patients with relapsing polychondritis, 85%-95% develop auricular chondritis.
- Unilateral or bilateral auricular pain, swelling, and redness develop suddenly but spare the lobules.
Auricular edema and erythema sparing the lobule. Courtesy of Gregory J. Raugi, MD, PhD.
- The pain and redness usually resolve within 2-4 weeks but may recur.
- The ear cartilage softens and collapses forward. The external auditory canal can collapse after 1 or more episodes.
Forward listing ear. Courtesy of the University of Washington, Division of Dermatology.
Bilateral inflammation and structural collapse of the auricles in a patient found to have aortic dissection. Courtesy of the University of Washington, Division of Dermatology.
- Nodularity of the auricle may develop.
- Calcification occurs in 40% of patients.
- Nonerosive seronegative inflammatory polyarthritis
- A seronegative nonnodular arthritis develops in 52%-85% of patients. The acute onset of an inflamed joint may mimic a crystal arthropathy.
- Most commonly, the arthritis is asymmetric, oligoarticular or polyarticular, nondeforming, and nonerosive. One case of arthritis mutilans has been reported.22
- The ankles, elbow, wrists, proximal interphalangeal joints, metacarpophalangeal joints, and metatarsophalangeal joints are often involved, although any joint may be affected.
- The costochondral, sternoclavicular, and sternomanubrial joints may be involved.
- The forefeet are usually spared.
- Effusions may accompany arthritis and may be noninflammatory or mildly inflammatory.
- Nasal chondritis
- Nasal chondritis occurs in 48%-72% of patients with relapsing polychondritis.
- The nasal chondritis is acute and painful and accompanied by a feeling of fullness over the nasal bridge.
- Mild epistaxis may be present.
- A saddle-nose deformity may develop in longstanding disease (Media File 9).
Saddle-nose deformity. Courtesy of the University of Washington, Division of Dermatology.
- Ocular inflammation
- Collagen types II, IX, and XI are found in the cornea and sclera. Autoantibodies to these collagens, which are found in patients with relapsing polychondritis, may be responsible for direct harm to the eyes.
- Of patients with relapsing polychondritis, 50%-65% develop ocular sequelae related to episodic inflammation of the uveal tract, conjunctivae, sclerae, and/or corneas.
- The most common conditions are episcleritis (39%) and scleritis (14%).
Unilateral episcleritis. Courtesy of Gregory J. Raugi, MD, PhD.
- Eyelid edema, iritis, and retinopathy are found in 9% of patients, and 5% of patients have ocular muscle paresis or optic neuritis.
- Peripheral ulcerative keratitis is found in 4% of patients and has been associated with perforation, endophthalmitis, and bilateral enucleation.
- Papilledema, visual field defects, ptosis, lid retraction, proptosis, and cataracts may also be found on examination.
- Respiratory tract chondritis
- Respiratory tract involvement affects 40%-56% of patients with relapsing polychondritis and may involve any portion of the respiratory tree, including the distal bronchi.
- Tenderness to palpation may occur over the anterior trachea or thyroid cartilage.
- Chondritis weakens the tracheal cartilage rings, resulting in wheezing, dyspnea, cough, and hoarseness.
- The upper airways can eventually become stenosed and are replaced by collapsible fibrotic tissue. Airways superior to the thoracic inlet collapse upon inspiration, and airways below the thoracic inlet collapse upon expiration; therefore, both inspiratory stridor and expiratory wheezing may be noted on auscultation.
- Inflammation and swelling of the glottis, larynx, and subglottic tissues may require tracheostomy.
- Acute inflammation of the distal airways can lead to obstruction and recurrent pneumonia.
- Audiovestibular damage
- Audiovestibular derangements are experienced by 46%-50% of patients, usually those with concomitant auricular chondritis.
- Sudden loss of hearing is usually permanent, while tinnitus, nausea, vomiting, nystagmus, and vertigo may subside. In some patients, hearing loss is attributed to vasculitic damage to the eighth cranial nerve.
- Cardiovascular disease
- Relapsing polychondritis has been reported to affect the cardiovascular system in 24% of patients.
- Aortic and mitral valve regurgitation, aortic aneurysm, aortitis, aortic thrombosis, pericarditis, first- to third-degree heart block, and myocardial infarction, at times mediated through ostial stenosis of a coronary artery or arteries, have been reported.
- Relapsing polychondritis aortitis exhibits inflammation in the media, resulting in loss of glycosaminoglycans and elastic tissue.
- Any region of the aorta and more than one region simultaneously may be affected. In descending order of frequency, they include the ascending aorta, aortic ring, descending thoracic portion, and abdominal aorta, potentially existing silently rupture and death.
- The most common clinical presentations include aortic arch syndrome, abdominal aortic aneurysm, and aortic regurgitation.
- The clinical presentation of aortic regurgitation (resulting from ascending aorta involvement) may include left ventricular failure. Aortic regurgitation may result from damage to the aortic cusps or from annular dilatation due to destruction of supporting tissues.
- Skin disease
- Skin lesions are found in 17%-39% of patients with relapsing polychondritis.
- Specific lesions are limited to erythema and edema overlying the inflamed cartilaginous structures.
Severe auricular edema and inflammation. Courtesy of the University of Washington, Division of Dermatology.
- Various nonspecific skin lesions have been reported.
- Aphthous ulcers are the most common.
- Limb nodules, purpura, papules, sterile pustules, superficial phlebitis, livedo reticularis, limb ulceration, and distal necrosis have been reported.
- Rarer findings include Sweet syndrome, urticarial vasculitis, and Kaposi sarcoma.
- Some findings likely represent the skin manifestations of the many conditions associated with relapsing polychondritis rather than specific manifestations of relapsing polychondritis itself.
- Cutaneous vasculitis: The prevalence of biopsy-proven cutaneous (small vessel) leukocytoclastic vasculitis is approximately 10%, while the prevalence of systemic (including skin) medium-to-large vessel vasculitis ranges from 11%-56%. It may appear as in its typical form of palpable purpura or as hemorrhagic bullae, typically on the lower extremities or other dependent areas.
- Erythema elevatum diutinum: This has been described in 2 patients with relapsing polychondritis.23,24
- Cutaneous polyarteritis nodosa: A patient with relapsing polychondritis presented with relapsing painful red nodules from 1-3 cm in size, occurring on the entire skin and accompanied by arthralgias and myalgias.
- Other cutaneous lesions reported in patients with relapsing polychondritis and vasculitis included the following:
- Palpable purpura
- Acute febrile neutrophilic dermatosis (Sweet syndrome)
- Subcutaneous inflammatory nodules resembling erythema nodosum
- Localized ulcerating neutrophilic conditions resembling pustules, furuncles, abscesses, and ulcerating abscesses
- Panniculitis: This is characterized by 5- to 10-cm tender erythematous nodules showing septal and lobular inflammation.25
- Other skin conditions: Isolated case reports of other cutaneous manifestations of relapsing polychondritis include the following:
- Hyperpigmentation
- Pustular psoriasis
- Macular purpura of the palms, soles, lower limbs, and buttocks
- Erythematous papular plaques of the face, upper and lower extremities, and thorax
- Alopecia universalis
- Actinic granulomas
- Urticaria
- Angioedema
- Livedo reticularis
- Erythema multiforme
- Mouth and genital ulcers with inflamed cartilage (MAGIC syndrome): MAGIC syndrome is characterized by an overlap of relapsing polychondritis with Behçet disease. Firestein et al proposed this condition in 1985 in a report of 5 patients.26 The two types of MAGIC syndrome are as follows:27
- The more common type begins with the oral and genital ulcers of Behçet disease.
- The second, less common, type is the polychondritis type, in which genital ulcers or erythema nodosum follows the initial presentation of oral ulcers and polychondritis.
- Central nervous system
- CNS manifestations of relapsing polychondritis are rare and can vary.
- It is believed that vasculitis of the small and/or medium sized arteries is the underlying etiology.28 Neurologic symptoms may present before other more frequent manifestations of relapsing polychondritis.
- Patients may present with seizures, memory loss, delusions, limb weakness, paresthesias or gait disturbances, or other cerebellar symptoms.
- Cranial nerve damage is common in relapsing polychondritis-associated CNS vasculitis and most often affects the second cranial nerve, followed less commonly by the sixth, seventh, and eighth cranial nerves.
- Limbic encephalitis has been reported associated with relapsing polychondritis.29,30
- Aseptic meningitis has been reported infrequently in relapsing polychondritis.31
- Clinical neurologic assessment is an important aspect of the physical examination of patients with relapsing polychondritis.
- Renal
- From 1943-1980, 129 patients with relapsing polychondritis were seen at the Mayo Clinic, of whom 29 (22%) had evidence of glomerulonephritis based on a diagnostic renal biopsy or the presence of microhematuria and proteinuria.32
- Patients with renal damage are older and more likely to have extrarenal vasculitis and arthritis.
- A proposed mechanism in the pathogenesis of renal involvement in relapsing polychondritis derives from the deposition of immune complexes leading to glomerular damage.32
- Pathological biopsy findings include segmental necrotizing glomerulonephritis with or without crescents, interstitial lymphocytic infiltrates, interstitial fibrosis, active tubulitis, and glomerulosclerosis.
- The response to treatment varies from stabilization of renal function to renal failure.
- Other conditions
- Relapsing polychondritis has been seen in patients with underlying myelodysplastic syndrome and, less often, lymphoma. These cases may be paraneoplastic in nature.
- Acute mastitis may be found in relapsing polychondritis.19
- Thromboembolism has been reported.
Causes
The cause of relapsing polychondritis is not known. Familial clustering has not been observed. Susceptibility for developing relapsing polychondritis is increased slightly by the HLA-DR4 haplotype.
Three intriguing case reports suggest that hormonal influences may be important in relapsing polychondritis. Two men have developed relapsing polychondritis after receiving injections of luteinizing hormone-releasing hormone, and a woman with arthritis mutilans had a sudden exacerbation of her condition and new onset of atrophy of the auricular cartilage, nasal septum, weight loss, and deafness after receiving an injection of chorionic gonadotropin.33
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Further Reading
Keywords
relapsing polychondritis, RP, cartilaginous inflammation, cartilage inflammation, inflamed cartilage, inflamed ear, ear inflammation, inflamed nose, nose inflammation, inflamed laryngotracheobronchial tree, laryngotracheobronchial tree inflammation, airway chondritis, infection secondary to corticosteroid treatment, respiratory compromise, systemic vasculitis, auricular chondritis, seronegative arthritis, non-nodular arthritis, nonnodular arthritis, respiratory tract chondritis, audiovestibular damage, audio-vestibular damage, aortic arch syndrome, abdominal aortic aneurysm, aortic regurgitation, chondrolysis, chondritis, perichondritis
