| Relapsing polychondritis = التهاب الغضروف العديد الناكس |
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Relapsing Polychondritis
EPIDEMIOLOGY The incidence of relapsing polychondritis (RP) has been estimated to be 3.5 per 1 million in Rochester, Minnesota.1 The peak age for disease onset is the fifth decade; however, development of the disease may occur in young children and in the elderly.2 Although most cases have been reported in Caucasians, there is no evidence supporting a role for ethnic or geographic factors. ETIOLOGY AND PATHOGENESIS Several lines of evidence have been accumulated that suggested the role of autoimmunity in RP. More than 30 percent of patients have an associated disease, mainly of autoimmune origin. The role of the humoral immune response was based on the presence of antibodies to collagen type II in the acute phase of RP. Antibody titers seemed to correlate with the severity of symptoms. Other antibodies were also detected in patients with RP: antibodies to type IX and type XI collagen, minor collagens which represent 5 percent to 10 percent of cartilage collagens, antibodies to matrilin-1, an extracellular matrix protein, predominantly expressed in upper respiratory tract cartilage; and antibodies to cartilage oligomeric matrix protein, another cartilage protein. Several animal models have been described in which immunization with these various cartilage proteins induced a variety of chondritis manifestations that mimic those seen in patients. A role for immune complexes and subsequent activation of the complement system is suggested by examination of tissue lesions, which usually shows the presence of granular deposits of immunoglobulins and the C3 component of complement associated with CD4+ lymphocytes and plasma cells. A role for T cells in RP pathogenesis, although less well studied, has also been demonstrated in patients and in animal models with specificity against the same cartilage proteins. T-cell clones isolated from a RP patient were found to be specific for a peptide corresponding to residues 261 to 273 of the type II collagen and were restricted to either the DRBI*0101 or the DRBI*0401 allele.5 A significant near twofold increase in DR4 antigen frequency was found in RP patients as compared to that in healthy controls, but the genotyping of DR-4 positive patients and controls did not show predominance of any DR4 sub-type. Genetic susceptibility was also confirmed by animal models.
▪ CLINICAL FINDINGS Disease onset is usually sudden with characteristic chondritis, with arthritis or ocular inflammation occurring less frequently. Non-specific initial symptoms, such as fever or weight loss, are rare. Attacks of chondritis usually occur in a relapsing and remitting pattern. Inflammatory episodes generally last a few days or weeks and may subside spontaneously or with treatment; recurrences after weeks or months occur and subsequently result in cartilage destruction. Auricular chondritis is the most frequent sign, occurring in 85 percent of patients, causing pain, redness, and swelling of the cartilaginous portion of the pinna, sparing the non-cartilaginous lobe . Biopsy of the auricular cartilage is not needed to make a correct diagnosis. After several attacks, the pinna may become soft and floppy, looking like a cauliflower ; sometimes it is stiff due to calcifications. Nasal chondritis (65 percent) is less inflammatory, presenting with nasal pain, stuffiness, rhinorrhea, and, sometimes, epistaxis. The characteristic saddle-nose deformity may appear with or without previous clinical inflammatory episodes. OTHER ORGAN INVOLVEMENT Respiratory tract chondritis, though uncommon at presentation, occurs in up to 50 percent of patients, and may be lethal. The respiratory involvement results in complaints of hoarseness, nonproductive persistent cough, dyspnea, and wheezing. Complications include
Joint pain is a common presenting feature in RP (30 percent). Large and small joints of the peripheral or axial skeleton may be affected (> 70 percent). Arthritis is intermittent, migratory, asymmetric, seronegative, and usually nonerosive. Nearly 60 percent of patients develop ocular inflammation. Episcleritis and scleritis are the most common manifestations, followed by keratoconjunctivitis sicca, iritis, retinopathy, keratitis. Rarely corneal perforation, retinal vasculitis, and optic neuritis lead to blindness. Conductive hearing loss is secondary to stenosis of the external auditory canal, eustachian tube chondritis, or serous otitis media, while perception hearing loss may occur as a consequence of sensorineural involvement. Symptoms of vestibular dysfunction, such as dizziness, ataxia, nausea, and vomiting, are usually acute and improve with time. The spectrum of cardiovascular manifestations is wide, including different cardiac tissues (aortic and/or mitral regurgitation, impairment of the conduction system, pericarditis) and all types of vessels (thoracic and abdominal aortitis leading to aneurysms, Takayasu-like aortic arch syndrome, medium and large vessels vasculitis, leukocytoclastic vasculitis, thrombophlebitis). Lesions are inflammatory and/or thrombotic. Some, but not all, thrombotic manifestations have been linked to anti-phospholipid syndrome. Large vessel vasculitis tends to occur after several years of smoldering and often, occult disease, despite immunosuppressive therapy. Dermatologic manifestations are sometimes the presenting feature of RP (12 percent), and ultimately become apparent in more than one-third of patients.6 They are non-specific including nodules on the limbs , purpura , oral or complex aphthosis , papules, sterile pustules , superficial phlebitis, livedo reticularis, ulcerations on the limbs, and distal necrosis . They appear concomitantly or in the absence of attacks of chondritis. Pathologic features include inflammatory or thrombotic vascular lesions, neutrophil infiltrates as in neutrophilic dermatoses, and inflammation of the dermis or subcutis. Patients with and without dermatologic manifestations have similar clinical manifestations of RP. However, the frequency of dermatologic manifestations (> 90 percent), age of onset of chondritis, and male-female ratio seems higher when RP is associated with myelodysplasia. LABORATORY FINDINGS Histopathology Histopathology of affected cartilage shows perichondrial inflammation and the loss of the normal cartilaginous basophilia. Other Laboratory Tests Laboratory findings in RP are non-specific, consistent with acute or chronic inflammation. Urinalysis may be abnormal in the presence of renal involvement (mesangial expansion, immunoglobulin A nephropathy, tubulointerstitial nephritis, or necrotizing glomerulonephritis). Pulmonary function tests, including inspiratory and expiratory flow volume curves, should be performed systematically to detect occult pulmonary involvement, which may be confirmed by computed tomography of the respiratory tract. Three-dimensional or spiral magnetic resonance imaging may provide better resolution. Although not routinely available, autoantibodies to type II, IX, and XI collagen and to matrilin I can be found in patients with RP. Urinary type II collagen neoepitope measurement may be a useful tool to follow the evolution of disease.7 Box 160-1 Empirical Diagnostic Criteriaa
▪ PROGNOSIS AND CLINICAL COURSE The clinical course of RP is progressive with intermittent flares. The number of different organs involved, the severity of involvement, and the response to treatment are unpredictable. Common causes of death are respiratory or cardiovascular complications and secondary infections. Patients have an increased risk of developing lethal myelodysplastic malignancies. TREATMENT
Because of the highly variable course of RP, individualized therapy is the key to optimum management. General therapeutic guidelines are based on retrospective analyses of series of patients or isolated case reports. Nonsteroidal anti-inflammatory drugs, colchicine, or dapsone may be useful for patients with mild auricular or nasal chondritis, arthralgia, or mild arthritis. More serious manifestations
Differential Diagnosis of Relapsing Polychondritis
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