Relapsing polychondritis (RPC) is a rare systemic inflammatory disease affecting the cartilaginous structures, and diagnosis of RPC is based on criteria suggested by Michet, et al [1, 3, 12]. The criteria require confirmed inflammation in two of three auricular, nasal or laryngotracheal cartilage, or proven inflammation in one of the above types of cartilage and two other minor criteria including hearing loss, ocular inflammation, vestibular dysfunction, and seronegative arthritis. Among the affected organs, auricular chondritis is a hallmark of RPC because it develops in more than 90% of such patients . Tracheobronchial involvement appears in nearly half of RPC patients and most of the RPC patients have more than one organ symptom besides that of the airway . Localized tracheobronchial RPC is much rarer and the diagnosis is generally difficult because of the absence of typical auricular or nasal symptoms at the onset [14,15,16]. A prolonged undiagnosed period can sometimes result in life-threatening tracheomalacia, which cannot be cured once it is established . Therefore, early diagnosis of this disease is crucial. Until now, endoscopic EBUS and positron-emission tomography have been reported to be useful to evaluate the airway involvement of RPC patients [9, 16, 17]. However, as a differential diagnosis for localized tracheobronchial RPC, there remain other diseases, such as granulomatosis with polyangiitis, sarcoidosis and amyloidosis [15, 18]. In the present case, there was no sign of cartilaginous inflammation except for airway symptoms. Although endoscopic and EBUS findings and increased levels of serum anti-type II collagen antibody suggested RPC in this patient, we finally confirmed the diagnosis with histological examination of surgical tracheal biopsies.
Occasionally, RPC has been known to coexist with other autoimmune diseases [2, 19]. Antinuclear antibodies or anti-neutrophil cytoplasmic antibodies have been also reported to be present in RPC patients. In the present case, the patient suffered from systemic sclerosis for a long time before the onset of RPC. This background suggested the presence of an autoimmunity contribution to the onset.
At present, some types of cartilage antigens are presumed to be involved in the RPC pathogenesis. One of the candidates is type II collagen, which consists of 95% of the total collagen in cartilage, and anti-type II collagen antibody is detected in one third of RPC patients, the same as in rheumatoid arthritis [10, 20]. In the present case, anti-type II collagen antibody was in fact elevated. However, type II collagen seems not to explain the pathogenesis of localized tracheobronchial RPC because this collagen is expressed in other types of cartilage such as articular cartilage. On the other hand, a non-collagenous cartilage matrix protein, matrilin-1, is known to be abundantly expressed in tracheal cartilage, but less so in articular cartilage in bovine and mice . In human, the serum level of matrilin-1 has been shown to be higher during the active phase in RPC patients  and an increased level of anti-matrilin-1 antibodies has been also detected in 13.4% of RPC patients . In the present case, we did not measure the serum level of matrilin-1 and anti-matrilin-1 antibodies because there was no serum sample left and no means of measuring the level commercially. In an animal model, immunization with matrilin-1 has been demonstrated to cause severe respiratory dysfunction in mice and rats [5, 6]. Therefore, autoimmunity against the matrilin-1 has been assumed to be involved in the pathogenesis of RPC with respiratory symptoms. However, until now, there has been no study that verified the expression of matrilin-1 in the cartilage of localized tracheobronchial RPC patients, as far as we know. In RPC animal models, the expression of matrilin-1 has been demonstrated on the surface of tracheal cartilage [6, 8]. As is the case with RPC animal models, this patient showed the expression of matrilin-1 in the boundary region of cartilage and some chondrocytes in the trachea, but not in the auricular cartilage. Consistent with these findings, cartilage destruction in this patient was only seen in the trachea, not in auricular cartilage. This finding suggests that expression level of matrilin-1 and autoimmunity to this protein could be involved in the pathogenesis of localized tracheobronchial RPC in human. However, immunochemical staining of matrilin-1 in the tracheal tissue would not be useful for the diagnosis of RPC at present, because there has been no reported comparison of the expression levels between RPC patients and normal subjects. Further studies are needed to clarify this point.
In conclusion, we first demonstrated the expression of matrilin-1 in tracheal but not auricular cartilage in a patient with localized tracheobronchial RPC. This result supports the possibility that matrilin-1 could be involved in the pathogenesis of localized tracheobronchial RPC. However, this is only one case report and further observations will be needed to confirm this result.