Relapsing Polychondritis Clinical Presentation

The wide 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. ^[19] In fact, one third of patients with diagnosed relapsing polychondritis see five 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 (See the image below.)
• Floppy ear. Courtesy of the University of Washington, Division of Dermatology.

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•  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 ^[32]
• 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

On the basis of a retrospective study of 142 patients with RP, Dion et al proposed that the following three distinct clinical phenotypes of the disease exist ^[31] :

• Patients with concomitant myelodysplastic syndrome (MDS) or other hematologic malignancy (< 10% of patients); most are older men; poor prognosis 
• Patients with tracheobronchial involvement (about 25% of patients)
• Patients with neither hematologic nor tracheobronchial involvement (about 65% of patients); good prognosis

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

Three of the six following clinical features are necessary for diagnosis:

• Bilateral auricular chondritis
• Nonerosive seronegative inflammatory polyarthritis
• Nasal chondritis
• Ocular inflammation
• Respiratory tract chondritis
• Audiovestibular damage

Damiani and Levine criteria

One of the following three sets are 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)

One of the following two conditions is 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

Signs and symptoms of relapsing polychondritis include the following:

• Auricular chondritis
• Nonerosive seronegative inflammatory polyarthritis
• Nasal chondritis
• Ocular inflammation
• Respiratory tract chondritis
• Audiovestibular damage
• Cardiovascular disease
• Skin disease
• Central nervous system (CNS) manifestations
• Renal manifestations
• A variety of other conditions

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. ^[33]  See the image below.

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 one or more episodes. See the images below.

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. ^[34]  Effusions may accompany arthritis and may be noninflammatory or mildly inflammatory.

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.

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. ^[33]  See the image below.

Ocular inflammation

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%). Less common manifestations include keratitis, retinopathy, optic neuropathy, and muscle palsy. ^[35]

See the image below. 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.

Other ocular findings may include the following:

• 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. Findings may include the folllowing:

• 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, leading to loss of glycosaminoglycans and elastic tissue. ^[36]  Any region of the aorta and more than one region simultaneously may be affected. In descending order of frequency, they include the following:

• Ascending aorta
• Aortic ring
• Descending thoracic portion
• Abdominal aorta

The most common clinical presentations include aortic arch syndrome, abdominal aortic aneurysm, and aortic regurgitation. Silent rupture and death may occur.

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. See the image below.

Various nonspecific skin lesions have been reported, as follows:

• 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 two patients with relapsing polychondritis. ^{[37, 38]}
• 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) ^{[39, 40]}
• 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. ^[41]

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. ^[42]

Two types of MAGIC syndrome exist.  ^[43]  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. ^[44]  Neurologic symptoms may present before other more frequent manifestations of relapsing polychondritis. Manifestations may include the following:

• 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. ^{[45, 46]}
• Aseptic meningitis has been reported infrequently in relapsing polychondritis. ^[47]
• 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. ^[48]  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. ^[48]

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. ^[22]  Thromboembolism has been reported.