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The following article is used with permission from Dr David E. Trentham.

 

The members of the Relapsing Polychondritis support group
would like to thank Dr Trentham for allowing us to post this review.

 

 Contents
 Introduction
  Methods
 Demographics
 Delay in diagnosis
 Clinical Features
     Features at presentation
 Later Features
 Pathology (Changes occuring from the disease)
 Pathogenesis (Causes)
 Associated Diseases
 Prognosis (Probable course of the disease)
 Medical Therapy
 Conclusions
 Reference

 

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CLINICAL REVIEW

Relapsing Polychondritis

David E. Trentham, MD, and Christine H. Le, MBBS, FRACP

______________________________________________________________________________________

Relapsing polychondritis, an uncommon, chronic, multisystem disorder characterized by recurrent episodes of inflammation of cartilaginous tissues, can be life-threatening, debilitating, and difficult to diagnose. This review is based on the authors' experience with 36 patients with relapsing polychondritis who were followed from 1980 to 1997, 30 patients located elsewhere who completed a detailed questionnaire and interview, and a perusal of English-language textbooks and papers located by a systematic search of the MEDLINE database. Relapsing polychondritis can present in a highly ambiguous fashion; therefore, in the authors' series, the mean delay from the time medical attention was sought because of symptom onset until diagnosis was 2.9 years. Although prednisone was the main form of treatment, methotrexate seemed to be of additional value. Survival was much more favorable than previously thought. Greater awareness of relapsing polychondritis would probably lead to earlier diagnosis and better outcomes.

Ann Intern Med 1998; 129:114-122.

From Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. For current author addresses, see end of text.

Relapsing polychondritis is an uncommon, multisystem disease that can be life-threatening, debilitating, and difficult to diagnose. It is characterized by recurrent, potentially severe, and frightening episodes of inflammation of cartilaginous tissues. All types of cartilage may be involved, including the elastic cartilage of the ears and nose, the hyaline cartilage of peripheral joints, the fibrocartilage at axial sites, and the cartilage in the tracheobronchial tree. Relapsing polychondritis can also inflame other proteoglycan-rich structures, such as the eye, heart, blood vessels, and inner ear. Systemic symptoms (for example, fever, lethargy, and weight loss) are common, and vasculitis affecting skin or internal organs may occur. Patients can present with a wide array of painful symptoms that often pose major diagnostic dilemmas. Because no specific tests for it are available, relapsing polychondritis must be diagnosed on clinical grounds. Pathogenetically, a linkage to HLADR4 and, occasionally, other autoimmune disease suggests that antiself reactions may be operative.

In most patients, relapsing polychondritis assumes a fluctuating but progressive course in which polycyclic bouts of inflammation eventually lead to the permanent destruction of the involved structure.

In a minority of patients, the pattern of disease is more limited. Corticosteroids provide the most effective treatment and can even lead to a dramatic response, but long-term therapy is substantially limited by unwanted side effects. Traditionally, such drugs as dapsone, cyclophosphamide, and azathioprine have provided additional therapy. Recent experience in an uncontrolled trial suggests that methotrexate may be efficacious.

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Methods

The information for this review (Table 1) is based on our experience with 36 patients followed from 1980 to 1997. We also include details on 30 other patients located in part through the National Organization of Rare Diseases. All patients satisfied the criteria for a diagnosis of relapsing polychondritis, as suggested by McAdam and colleagues (1) and Damiani and Levine (3). All patients completed a questionnaire that solicited information on specific personal and medical details, and all were interviewed by telephone or in person. Complete medical records of 46 patients were available for study.

We also did a systematic search of the MEDLINE database for all relevant English-language articles published between January 1980 and September 1997. Textbook chapters, reference lists, and abstracts selected for presentation at the annual meetings of the American College of Rheumatology (formerly the American Rheumatology Association) during these years were also collected. Because the information located in abstracts was too preliminary or lacked detail, only data from our patients and full-length reports are included in the following composite.

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Demographic Characteristics

Although previous studies have reported that relapsing polychondritis has an equal sex distribution (1, 2), the female-to-male ratio in our 66 patients was 3:1 (Table 1) . The peak age of onset is the fifth decade of life; among the 337 patients studied by us or by other investigators (1, 2), the average age was 47 years. Cases have been reported at both extremes of life (2). Relapsing polychondritis predominantly affects white persons; it has been reported rarely in other ethnic groups.

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Delay in Diagnosis


Patients with relapsing polychondritis usually present to primary care physicians, otolaryngologists, rheumatologists, and ophthalmologists. In our series of 66 patients, the mean delay from the time medical attention was sought for symptom onset until diagnosis was 2.9 years; this delay reflects the diagnostic ambiguities that may be encountered. The delay was longer than 1 year for 68% of patients, and one third of patients needed to see five or more physicians before diagnosis. Substantial delay has also been noted in the literature (2).

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Clinical Features

Features at Presentation
Clinical features are key in the diagnosis of relapsing polychondritis. The onset of relapsing polychondritis is generally sudden and often flagrant. External ear pain usually occurs as an isolated presenting symptom (Table 1) . Almost invariably, this is misdiagnosed as infectious perichondriits of the ear. It can be helpful to note that, in contrast to an infectious process, relapsing polychondritis typically spares the lobule, which lacks cartilage (Figure 1). Also included in the differential diagnosis of ear inflammation are trauma, insect bite, and overexposure to sunlight or extreme cold.

Nasal pain, hoarseness, throat pain, and difficulty talking are also common presenting symptoms. Nasal and respiratory symptoms in concert with fever, weight loss, and arthralgias may mimic Wegener granulomatosis. Unlike relapsing polychondritis, Wegener granulormatosis also affects noncartilaginous tissues early in its course and is associated with serum positivity for antineutrophil cytoplasmic antibody and granulomas on biopsy specimens. Nasal or throat symptoms sometimes occur in isolation. This is noteworthy because early throat involvement is often severe and life-threatening (1). Emergency tracheostomy may be needed because of acute airway obstruction from glottic, laryngeal, and subglottic inflammation and edema. In some of our patients, this occurred before the diagnosis was established.

Polyarthritis or oligoarthritis affecting small or large peripheral joints may be the presenting symptom, leading to a mistaken diagnosis of rheumatoid arthritis. Polyarthralgia is also a common presenting symptom. It is often migratory or transient, and patients who have it have been mislabeled as malingerers. Acute monoarthritis affecting a knee or ankle occasionally simulates septic or crystal-induced arthritis.

Ocular symptoms, reflecting recurrent episcleritis or scleritis, may occur early (Figure 2). When it is an isolated symptom, ocular inflammation offers little to specifically suggest the diagnosis of relapsing polychondritis. When eye and joint symptoms coexist, the condition may be misdiagnosed as reactive arthritis or spondyloarthropathy.

Less often, patients present with impaired hearing and symptoms of vestibular dysfunction, such as dizziness, ataxia, nausea, and vomiting. When they are abrupt in onset, these symptoms mimic a posterior-circulation stroke. The acute vestibular symptoms usually improve with time, but the hearing loss is often permanent. When interstitial keratitis occurs with audiovestibular symptoms, the Cogan syndrome is part of the differential diagnosis. In the presence of isolated problems, such as persistent hoarseness, costochondritis, monoarthritis, tracheitis, or fever, relapsing polychondritis can be extremely difficult to diagnose. Auricular chondritis infrequently develops in the setting of other preexisting rheumatic diseases, such as systemic lupus erythematosus, some primary Vasculitides and even lepromatous leprosy (4); this generates considerable diagnostic confusion.

McAdam and colleagues' diagnostic algorithm (1) is generally accepted. The diagnosis of relapsing polychondritis is deemed conclusive if patients have at least three of the six defined features of the disease (bilateral auricular chondritis, nonerosive seronegative inflammatory arthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, and audiovestibular damage) and histologic confirmation. Other researchers have proposed that the following may be sufficient: one or more of McAdam and colleagues' criteria plus chondritis affecting at least two distinct areas, response to steroids or dapsone, or positive findings on biopsy (3)

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Later Features
Constitutional symptoms, such as fatigue and weight loss, are common in relapsing polychondritis, and fever frequently accompanies acute flares. Although initial symptoms vary, most patients eventually have bilateral ear involvement. Typically, the cartilaginous part of the ear (helix, antihelix, tragus, and external auditory canal) becomes extremely painful, tender, and swollen. The external auditory meatus may narrow because of edema, and a clear, serous discharge may exude. With repeated attacks, the ear can become nodular and, in severe cases, floppy and deformed as the cartilaginous support is lost. Microcalcific deposits can occur in the ear. Hearing may be impaired suddenly or gradually; impairment affects up to 46% of patients at some stage. The hearing deficit may be conductive or sensorineural. Conductive hearing loss is due to closure of the eustachian tube from inflammation in the cartilaginous wall, auricular cartilage collapse, or edema of the canal. These obstructive processes can lead to serous otitis media, which further impedes hearing. The basis of sensorineural deafness is thought to be vasculitis in the vestibular or cochlear branch of the internal auditory artery (1). With this problem, vestibular symptoms, such as dizziness or vertigo, are likely to occur.

The second most frequent clinical feature in relapsing polychondritis is joint pain with or without swelling. It was seen in 50% (2) to 80% (1) of previously described patients and up to 85% of patients in our series (Table 1). All synovial joints, including the temporomandibular joint, and the costochondral junctions, pubic symphysis, and sternoclavicular and sternomanubrial joints, may be affected. The most commonly involved joints are metacarpophalangeal joints, proximal interphalangeal joints, and knees, followed by ankles, wrists, metatarsophalangeal joints, and elbows. Peripheral large and small joint polyarthritis or oligoarthritis, lasting weeks to months, is the most frequently encountered, but all patterns have been seen. The arthritis is nondeforming and nonerosive, and affected patients are negative for rheumatoid factor (1, 5). Examination of synovial fluid reveals a noninflammatory transudate.

Transient tenosynovitis is rare but has been reported. Relapsing polychondritis can also develop in patients with preexisting forms of inflammatory arthritis, such as rheumatoid arthritis and systemic lupus erythematosus. Ocular inflammation, one of the most constant features of relapsing polychondritis, can affect almost any part of the eye (Table 2). Acute or chronic eye inflammation may be mild or severe and can reduce vision. It may be more frequent in men (6). Episcleritis, scleritis, iritis, or keratoconjunctivitis sicca occur most often (6, 7). Keratitis, although less common, may lead to perforation (8). Proptosis presumably results from inflammation in the posterior elements of the globe, such as choroiditis, or contiguous cartilage inflammation in the nasal septum. Posterior and subcapsular cataracts frequently form and may be a consequence of chronic inflammation or may reflect cumulative steroid exposure. Nasal chondritis, often of sudden onset, targets the cartilaginous distal half of the septum. Patients experience severe pain, a feeling of fullness in the nose and adjacent tissues, and occasional epistaxis. With repeated episodes of inflammation, the nasal cartilage is destroyed, leading to a saddle nose deformity (Photo) . As this series shows, this tends to occur more often in women and those younger than 50 years of age. Episodes of nasal chondritis may also resolve spontaneously over several days.

Hoarseness, signifying laryngotracheal inflammation, is likely to develop during the course of the disease. It can progress to complete aphonia and may be associated with tenderness and swelling over the thyroid cartilage and anterior trachea. Other symptoms of laryngotracheal involvement include cough, dyspnea, wheezing, and choking. Involvement of the airway may be localized or diffuse. The larynx and upper trachea are affected most frequently (16). In severe cases, inflammatory edema can cause acute airway narrowing. Persistent inflammation can destroy the cartilaginous rings and create luminal collapse. Obstruction may also be induced iatrogenically by bronchoscopy, intubation, or tracheostomy (17). Bronchial cartilage inflammation may lead to diffuse narrowing of the lower airway and can impair mucociliary functions. Both factors predispose to recurrent lower respiratory tract infections. Pulmonary parenchymal involvement is not characteristic of relapsing polychondritis.

Conventional radiography and computed tomography identify laryngotracheal lesions (16), and thinsection computed tomography defines abnormalities in lobar and segmental bronchi (18). Three-dimensional or spiral magnetic resonance imaging may provide better resolution. The nature of airway obstruction, whether fixed or dynamic, and the location, whether intra or extrathoracic, can be assessed by pulmonary function tests, especially flow volume loops (19). Pulmonary function tests are useful tools for monitoring change over time. In addition, computed tomography and pulmonary function tests may detect otherwise asymptomatic lower airway disease (2, 19). Bronchoscopy may also be informative but carries a risk for exacerbating airway inflammation (20). Intubation for any reason may be difficult because of a small glottis caused by edema or cartilage destruction (21). In patients without laryngeal involvement, trauma at the time of endotracheal tube insertion may incite localized disease (22).

Because it leads to inflammation of one or more costosternal cartilages, costochondritis may further impair breathing; rarely, it culminates in partial or complete joint dissolution, leaving an anterior flail chest. Involvement of the cartilaginous structures of the respiratory tract is one of the most serious complications of relapsing polychondritis (23) and accounts for 10% (2) to 50% (24) of deaths related to relapsing polychondritis.

Cardiovascular deterioration, although uncommon, is the second most frequent cause of death in patients with relapsing polychondritis (1, 2). Aortic regurgitation develops in 4% to 6% of cases, and mitral regurgitation occurs in 2% to 4% (1, 2). Other manifestations include thoracic and abdominal aortic aneurysms, myocarditis, pericarditis, silent myocardial infarction, abnormal electrocardiograms, paroxysmal atrial tachycardias, and first-degree or even complete heart block (2, 6, 25). The aortic regurgitation is more often attributable to progressive dilatation of the aortic ring and the ascending aorta than to inflammation of the valve leaflets (26-28). However, cusp rupture with a normal aortic root has been reported (29). Rarely, dilatation of the annulus of both the mitral and tricuspid valves may cause mitral and tricuspid regurgitation (29).
The arterial and venous thromboses reported in relapsing polychondritis (30) may be due to vasculitis or the presence of an antiphospholipid antibody (31). Skin lesions, found in 17% to 39% of cases (2, 6, 9, 10, 32), include macules, papules, nodules, vesicles, and bullae (Table 2). Biopsy specimens often show necrotizing, leukocytoclastic, or even granulomatous vasculitis (28). Neurologic abnormalities not due to infections rarely occur in patients with relapsing polychondritis (Table 2). The most common manifestations are cranial nerve palsies. The underlying mechanism is uncertain, although vasculitis may account for a few cases (29). Cerebral aneurysms have also been reported (15).

Renal involvement can occur in relapsing polychondritis in the absence of an associated disease, such as systemic lupus erythematosus or systemic vasculitis (33-35). Among 129 patients with relapsing polychondritis, 11 (80/v) had biopsy-proven kidney disease (36). Before that article was published, only 11 of the more than 300 cases of relapsing polychondritis reported were accompanied by well documented renal disease. Although rare, renal disease indicates a worse prognosis; a 10-year survival rate of 30% has been reported (33). The most common histopathologic finding is mild mesangial proliferation, followed by focal and segmental necrotizing glomerulonephritis with crescents. Other abnormalities include glomerulosclerosis, IgA nephropathy, and tubulointerstitial nephritis. Immunofluorescence studies most often reveal faint deposition of C3, IgG, or IgM, primarily in the mesangium. During acute flares, patients may have surrogate markers of inflammation, such as elevated erythrocyte sedimentation rate, anemia, leukocytosis, and thrombocytosis. Patients are generally negative for antinuclear antibodies and rheumatoid factor unless they also have a connective tissue disease. Serum antibodies to type 11 collagen have been found in about 20% of patients (37), a frequency too low for the presence of this antibody to be a useful diagnostic marker. They do not predict subsequent disease severity or pattern. Low titers of cytoplasmic antibody or perinuclear-antinuclear cytoplasmic antibody have been reported in 8 of 33 patients, and 3 of the 8 patients positive for perinuclear-antinuclear cytoplasmic antibody had coexisting vasculitis (38).

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Pathology


No biopsy finding is pathognomonic for relapsing polychondritis. Unless true perichondral tissue at marginal sites of involvement is sampled, nonspecific granulation tissue is found on biopsy. Specimens of inflamed cartilage may show distinctive features (39). There is loss of basophilic staining of the cartilage matrix accompanied by perichondral inflammation at the cartilage-soft tissue interface and fibrocytic and capillary endothelial cell proliferation; perivascular mononuclear and polymorphonuclear cell infiltrates are also visible. The chondrocytes become vacuolated and necrotic and are eventually replaced by fibrous tissue. Wegener granulomatosis and fatal midline granuloma can be excluded. Biopsies of the nose and tracheobronchial tree infrequently provide useful information. Finally, when the clinical picture is prototypic of relapsing polychondritis, corroboration by histologic examination is unnecessary. Biopsies may contribute to the anatomic damage at the involved sites and may create additional cosmetic deformity. Thus, a posterior approach should be used to obtain suitable auricular tissue.

Autopsy of the ocular globe in one patient revealed mononuclear inflammatory cells and plasma cells scattered about (lie episcleral vessels (39). When valvular regurgitation develops in patients with protracted relapsing polychondritis, the valves themselves are often normal and the aorta is grossly dilated, with loss of basophilia, degeneration, necrosis, and fibrosis. Less often, the valve cusps may be directly affected by active necrotizing inflammation.

(25). Rarely, fibrosis of the conducting system, pericardial fibrous adhesions, and coronary artery vasculitis occur (25); all of these lesions can be symptomatic. Large vessels, such as the thoracic and abdominal aorta, may become grossly dilated; the predominant change is found in the media and consists of loss of elastic tissue, reduced basophilia, and fibrosis.

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Pathogenesis


Although the cause and pathogenesis of relapsing polychondritis remain unknown, several factors fit an autoimmune paradigm involving both humoral and cell-mediated arms. Cartilage contains large amounts of type 11 collagen. Serum antibodies to type 11 collagen can be found during an acute attack (40, 41), and immunofluorescence studies of affected cartilage have shown granular deposits of IgG, IgA, IgM, and C3, suggesting the presence of immune complexes (42). Some authors have found evidence of cell-mediated immune responses to various cartilage components (43), and experimental immunization of animals with type 11 collagen can induce pronounced auricular chondritis that is histologically similar to the human disease, along with arthritis and positive findings on immunofluorescence (44, 45). More recently, an increase in HLADR4 antigen was detected in patients with relapsing polychondritis, although no subtype predominated (43). An occasional association with other autoimmune disorders and the general effectiveness of high-dose steroid treatment also support the hypothesis that relapsing polychondritis is immunologically mediated.

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Associated Diseases
(Table 3)


Vasculitis, the most commonly reported associated condition (1, 2, 46), may range from isolated cutaneous leukocytoclastic vasculitis to systemic polyarteritis-type vasculitis with serious organ involvement (Table 3). Vessels of all sizes may be affected, and large-vessel vasculitis is a well-recognized and potentially fatal complication. Although vasculitis most often dilates the aortic ring and ascending aorta, the descending thoracic and abdominal aorta may also be affected by aneurysm formation (47). Aortic rupture may occur; in one of our patients, this event led to spinal cord ischemia and lower-limb paraplegia. Microscopic angiitis is the likely explanation for many dermatologic and renal manifestations, neuropathies, audiovestibular abnormalities, and episcleritis (1, 47). Vasculitis occurring in the context of relapsing polychondritis seems to signify worse prognosis (2).
Relapsing polychondritis has infrequently been reported to occur in association with defined vasculitides, such as Wegener granulormatosis and polyarteritis nodosa (46). The MAGIC (mouth and genital ulcers with inflamed cartilage) syndrome was first reported by Firestein and colleagues (48) when they described five patients with features of both relapsing polychondritis and Behcet disease. In about one quarter of patients, relapsing polychondritis is associated with connective tissue and autoimmune diseases (Table 3)(1). Thirteen patients in our series (20%) have coexisting systemic lupus erythematosus, rheumatoid arthritis, Behcet disease, the Sjogren syndrome, or mixed connective tissue disease. As previously reported (1), we have also noted a high incidence of hypothyroidism (15% of patients). Myelodysplastic syndromes, occurring simultaneously with or before relapsing polychondritis, have been documented in at least 18 cases (27, 53-55). These syndromes affect males more than females. Although treatment of relapsing polychondritis may be effective in some cases, it usually does not influence progression of the myelodysplastic syndromes. Patients die of the myelodysplastic syndromes rather than of relapsing polychondritis.

Patients with both rheumatoid arthritis and relapsing polychondritis exhibit typical manifestations of relapsing polychondritis but also have symmetric, erosive, deforming arthropathy (50). When relapsing polychondritis is associated with a spondyloarthropathic-like condition, patients are usually negative for HLA-B27; this dissociation suggests that relapsing polychondritis infrequently leads to carti-lage inflammation at axial skeletal sites.
Relapsing polychondritis has been detected in pregnant women (60, 61). All of these patients delivered normal infants, and pregnancy did not seem to adversely or favorably affect the disease.

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Prognosis


Most patients with relapsing polychondritis experience intermittent or decidedly fluctuant inflammatory manifestations. Within individual patients, the sites of involvement and the severity of inflammation remain constant or, more often, are completely unpredictable. Many patients have persistent symptoms between acute flares. Relapsing polychondritis is a generally progressive disease; most patients develop some degree of disability during the later stages. At worst, this includes bilateral deafness, impaired vision, phonation difficulties, and cardiorespiratory problems (Table 1). The sequelae of long-term corticosteroid use cause additional morbidity.
In one 1986 series (2), overall survival rates were 74% at 5 years and 55% at 10 years. In another series reported in 1976 (1), the 4-year survival rate was 70%. The outcome was far less dismal in our cohort, which had a survival rate of 94% and an average disease duration of 8 years (Table 1.) In previous studies, referral bias may have led to more ominous estimates of prognosis. In addition, improved medical and surgical management of the respiratory and cardiovascular complications of relapsing polychondritis during the past decade could contribute to the better survival rate.
Pneumonia is the most common cause of death related to relapsing polychondritis; these cases are often associated with airway stricture and long-term steroid use (2). Nonetheless, the requirement for steroid therapy itself did not affect outcome (2). Other causes of death include respiratory failure from airway collapse or obstruction and complications of valvular heart disease and vasculitis.
Anemia has been reported to be a poor prognostic sign in relapsing polychondritis (2). Among patients younger than 51 years of age, additional factors predictive of a decreased survival rate included saddle nose deformity, arthritis, tracheolaryngcal strictures, vasculitis, and microhematuria (2). In our series, however, these features did not correlate with outcome.

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Medical Therapy


In a minority of cases, nonsteroidal anti-inflammatory drugs can control mild episodes of inflammation. Our anecdotal experience indicates that low-dose colchicine may also be helpful. In most cases, however, corticosteroids are the main form of treatment. Doses of prednisone initially approaching 0.75 to 1 mg/kg of body weight per day are often needed to suppress active inflammation. Maintenance administration may be required. Corticosteroids reliably lead to resolution of an attack of chondritis and probably decrease the frequency and severity of attacks. Therefore, despite the inherent side effects of long-term steroid use, most patients with relapsing polychondritis require long-term steroid therapy.
Many immunosuppressive drugs have been tried in attempts to allow tapering of the steroid dose or to achieve a lower maintenance dose. Adjunct therapies include azathioprine (1, 19, 62), cyclophosphamide (1, 63), cyclosporine (64), penicillamine (62), and plasma exchange (65). Dapsone has been advocated as effective therapy for relapsing polychondritis (66-68), but 9 of 14 patients in our series did not respond to this drug; most experienced some degree of toxicity, including nausea, headache, rashes, fevers, and anemia. Clearly, the most efficacious nonsteroid drug in our experience has been methotrexate. Twenty-three of 31 patients receiving methotrexate at an average weekly dose of 17.5 mg responded to this treatment; their average prednisone dosage was reduced from 19 mg/d at the start of methotrexate therapy to 5 mg/d. More re-cently, anti-CD4 monoclonal antibody was reported to be effective in two patients with relapsing polychondritis (69, 70). Oral minocycline, as used for treating rheumatoid arthritis, was associated with improvement in a patient who had developed methotrexate toxicity (71).
High-dose oral prednisone is needed for respiratory tract involvement, and intravenous pulse steroids may be useful for acute airway obstruction (72). Tracheostomy may be required for severe localized subglottic involvement, and stenting of the respiratory tree can alleviate more extensive tracheobronchial disease (21). The feasibility of attempted surgical repair of nasal or airway deformity is uncertain. Topical steroid therapy generally does not curtail ocular manifestations in relapsing polychondritis; thus, systemic steroid therapy is necessary. Immunosuppressive agents are reserved for refractory cases (15).
More than one third of patients with valvular regurgitation have needed valve replacement (27). Recurrent perivalvular leaks and dehiscence are frequent complications because of preexisting aortic root and mitral annulus dilatation and adjacent friable tissues from previous or ongoing chronic inflammation (31, 73). Oral cyclophosphamide and azathioprine have been given in such cases, but the outcome has varied (25, 74).

Prednisone is also used to treat renal involvement and is most effective for patients with interstitial nephritis. Patients with segmental necrotizing glomerulonephritis and crescent formation often need additional therapy, such as oral or pulse intravenous cyclophosphamide (33, 63, 75); favorable results have been reported in some cases. Other approaches include combination regimens of azathioprine, steroids, heparin, and dipyridamole (76); dapsone and steroids (34); and plasmapheresis and cyclophosphamide (34); responses have varied.

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Conclusions

 

Relapsing polychondritis is an uncommon, multisystem, presumably autoimmune disease that may present in an enigmatic fashion and is often misdiagnosed. Cardinal features are repeated inflammatory episodes involving auricular, nasal, or laryngotracheal cartilage and, occasionally, joints or ocular tissues. Diagnosis is often based solely on the clinical picture. The disease follows a fluctuating but frequently progressive course. Potential serious complications include laryngotracheal collapse, valvular heart disease, large-vessel aneurysms, bilateral deafness, and impaired vision. Prednisone has been the main form of treatment, and methotrexate may help lessen corticosteroid requirements. The apparent natural history is more favorable than previously thought, and patients and treating physicians, while being cautious, should feel more optimistic. Greater awareness would assist in timely diagnosis and might decrease morbidity.

Grant Support In part by the Relapsing Polychondritis and Rheumatoid Arthritis Research Endowment Fund at Beth Israel Deaconess Medical Center.

Requests for Reprints: David E. Trentham, MD, Division of Rheuumatology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.

Current Author Addresses: Drs. Trentham and Le: Division of Rheumatology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.

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