Relapsing polychondritis is an uncommon disorder of unknown cause characterized by inflammation of cartilage predominantly affecting the ears, nose, and laryngotracheobronchial tree. Other manifestations include scleritis, neurosensory hearing loss, polyarthritis, cardiac abnormalities, skin lesions, and glomerulonephritis. Relapsing polychondritis has been estimated to have an incidence of 3.5 per million population per year. The peak age of onset is between the ages of 40 and 50 years, but relapsing polychondritis may affect children and the elderly. It is found in all races, and both sexes are equally affected. No familial tendency is apparent. A significantly higher frequency of HLA-DR4 has been found in patients with relapsing polychondritis than in healthy individuals. A predominant subtype allele(s) of HLA-DR4 was not found. Approximately 30% of patients with relapsing polychondritis will have another rheumatologic disorder, the most frequent being systemic vasculitis, followed by rheumatoid arthritis, and systemic lupus erythematosus (SLE). Nonrheumatic disorders have also been associated with relapsing polychondritis (Table 359-1). In most cases, these disorders antedate the appearance of relapsing polychondritis, usually by months or years; however, in other instances, the onset of relapsing polychondritis can accompany disease presentation.
Table Graphic Jump Location TABLE 359-1Disorders Associated with Relapsing Polychondritisa ||Download (.pdf) TABLE 359-1 Disorders Associated with Relapsing Polychondritisa
|Systemic vasculitis |
|Rheumatoid arthritis |
|Systemic lupus erythematosus |
|Overlapping connective tissue disease |
|Behçet’s disease |
|Polymyalgia rheumatica |
|Primary biliary cirrhosis |
|Pulmonary fibrosis |
|Hashimoto’s thyroiditis |
|Grave’s disease |
|Crohn’s disease |
|Ulcerative colitis |
|Myelodysplastic syndrome |
PATHOLOGY AND PATHOPHYSIOLOGY
The earliest abnormality of hyaline and elastic cartilage noted histologically is a focal or diffuse loss of basophilic staining indicating depletion of proteoglycan from the cartilage matrix. Inflammatory infiltrates are found adjacent to involved cartilage and consist predominantly of mononuclear cells and occasional plasma cells. In acute disease, polymorphonuclear white cells may also be present. Destruction of cartilage begins at the outer edges and advances centrally. There is lacunar breakdown and loss of chondrocytes. Degenerating cartilage is replaced by granulation tissue and later by fibrosis and focal areas of calcification. Small loci of cartilage regeneration may be present. Immunofluorescence studies have shown immunoglobulins and complement at sites of involvement. Extracellular granular material observed in the degenerating cartilage matrix by electron microscopy has been interpreted to be enzymes, immunoglobulins, or proteoglycans.
The accumulating data strongly suggest that both humoral and cell-mediated immunity play an important role in the pathogenesis of relapsing polychondritis. Immunoglobulin and complement deposits are found at sites of inflammation. In addition, antibodies to type II collagen and to matrilin-1 and immune complexes are detected in the sera of some patients. The possibility that an immune response to type II collagen may be important in the pathogenesis is supported experimentally by the ...