Relapsing polychondritis (RP) is a rare autoimmune disease characterized by episodic chondritis and inflammation of connective tissue resulting in cartilage destruction. However the immune damage can spread to involve non-cartilagenous tissues like eyes, kidney, skin and the cardiovascular system. This presentation will focus on respiratory manifestations which are the most common and responsible for half of the deaths in relapsing polychondritis (R.P).

I) INTRODUCTION
            Since the first description by Jaksch-Wartebhorst (1) in 1923, a number of reports have been published concerning the different manifestations of RP. More recently several studies allow to better understand pathogenesis of the disease and have also developed new insights in terms of therapeutic possibilities. Men and women are equally affected. The average age at presentation is 47 years. The diagnosis is established when any three of the 6 following clinical features are present (1).

• bilateral auricular chondritis
• nonerosive seronegative inflammatory arthritis
• nasal chondritis
• ocular inflammation
• respiratory tract chondritis
• audiovestibular damage

No specific pathological finding is considered as pathognomonic of R.P. ; in a typical case, biopsy appears as unnecessary. Similarly it does not exist biological proofs of RP, even if certain autoantibodies against cartilage components have been recently identified (autoantibodies against collagen II or matrilisin-1).

II) RESPIRATORY MANIFESTATIONS OF RELAPSING POLYCHONDRITIS
            Respiratory tract involvement, through uncommon at presentation, occurs up to 50 % of patients with R.P. Moreover airway involvement is a poor prognostic signal responsible of the majority of deaths related to R.P. In a series of nine patients referred to our hospital between 1988 et 1998, 4 were male and 5 female were included with a mean age of 59.3 ± 3.8 (range 39-73 yr) at time of examination. All these 9 patients had respiratory symptoms, which was the reason why they were adressed to chest physicians (3).

• Clinical manifestations (Table 1)

All patients exhibited cough, dyspnea and wheezing. In 1 patient, dyspnea occurred 2 years before the appearance of ear chondritis ; in 2 other cases pulmonary symptoms appeared 1 and 7 years after ear and nose-chondritis. Other findings were hoarseness, aphonia and severe choking. No patient exhibited concomitant COPD or atopy.

The extra-respiratory symptoms were usually ear-chondritis (5/9 cases), nose chondritis 9/9. Other manifestations were ocular symptoms, peripheral arthritis, purpura...

Table 1 – Clinical symptoms in 9 patients with R.P.

            Cough                                                       9/9

            Dyspnea                                                   9/9

            Wheezing                                                 9/9

            Choking                                                   4/9

            Hoarseness                                             6/9

            Aphonia                                                   5/9

            Laryngeal involvement                           6/9

Extra-Respiratory Symptoms

            Ear chondritis                                           5/9

            Nose chondritis                                        9/9

            Ocular symptoms                                     2/9

            Arthritis                                                    4/9

            Purpura                                                     2/9

            Neurologic symptoms                              3/9

                       Venous thrombosis                                   2/9

• Pulmonary function tests (PFT)

PFT demonstrated an obstructive pattern in 8/9 cases which did not improve with Beta-2 agonists. Flow-volume loops showed a marked decrease of the maximal expiratory flow rate at 75 % and 25 % of vital capacity in 8 patients. The most typical abnormalities were in 5 cases flow plateaus on both inspiratory and expiratory  phases of the flow-volume curve.

• Endoscopy

All patients demonstrated abnormal aspects of the tracheobronchial tree : inflammation (8/9 cases), associated with tracheal stenosis (6/9) or tracheal collapse which corresponded to an abnormal decrease of the tracheal diameter (> 50 %) during quiet inspiration.

Results of CT examination are reported in Table 2. One patient had a normal CT at 1 year and 4 years later despite an obstructive ventilatory pattern. Six of the 9 patients presented diffuse tracheal and bronchial stenosis, with thickening and calcifications of airway walls.

Table 2.  CT findings in 9 patients with RP

Localized tracheal stenosis (1/2 sup)*                               1/9

Tracheal thickening                                                            7/9

Tracheal calcifications                                                        6/9

Bronchial stenosis                                                              6/9

Bronchial thickening                                                          7/9

Bronchial calcifications                                                      6/9

Bronchiectasis                                                                    2/9

Mucoïd impaction                                                               1/9

* Stenosis localized to the upper ½ of trachea

            There was a frequent discrepancy between clinical features, endoscopic and radiologic findings :in our study fiberoptic bronchoscopy failed to identify tracheal stenosis in 2 cases because the stenosis was homogeneously spread throughout the trachea. Moreover endoscopy did not detect the thickening of tracheal and bronchial walls which is present at an early stage of the disease. So in our opinion CT examination appears as a non-invasive method that identifies tracheal and bronchial abnormalities (thickening and stenosis) more precisely and more frequently than endoscopy. In the future, CT associated with inspiratory and expiratory views to identify the degree of collapse, will certainly provide additional informations (3D reconstruction) for a more precise  and early diagnosis of respiratory involvement in RP (3, 4).

III) EXTRA-RESPIRATORY MANIFESTATIONS IN RP

Respiratory manifestations are present at initial presentation only in 14 % of patients but occur in 56 % of patients during the course of the disease. Indeed the first clinical symptoms are represented by EXTRARESPIRATORY LOCALIZATIONS. The most frequent are recurrent inflammation and destruction of the ear lobes and of the nose. Other manifestations are arthritis (non-erosive seronegative peripheral arthritis), ocular symptoms (conjunctivitis, iritis, episcleritis and cataracts) cardiovascular manifestations (aortitis, vasculitis, pericarditis and atrioventricular conduction disturbances) (5). Other systemic symptoms are also described but more rarely : purpura, dermatologic (6) or neurologic symptoms, myelodysplastic syndromes….

IV) PATHOGENESIS OF RELAPSING POLYCHONDRITIS

            RP IS A MULTISYSTEM AUTOIMMUNE DISEASE INVOLVING CARTILAGE DESTRUCTION. But exact mechanisms are still discussed. Antibodies to several cartilage proteins are detectable in sera from RP patients : antibodies to type II, IX and XI collagen. Recently the role of matrilin 1, a cartilage-specific protein mainly detected in the tracheal cartilage was emphasized. When sera from RP patients containing matrilin 1 specific antibodies are injected into neonatal mice, such antibodies are able to bind selectively to cartilage of the respiratory tract. Moreover when adult mice deficient of B cells were injected with the same antimatrilin-1 antibodies, they developed erosive chondritis in the respiratory tract (7, 8). So antibodies to matrilin-1 are able to bind tracheolaryngeal cartilage in vivo and are correlated with an inflammatory attack at this site.

            Another way has been explored. In human beings HLA-DQ8, (MHC class II) has been associated with various autoimmune diseases. Interestingly transgenic mice expressing DQ8 in NOD mice that are lacking endogenous class II molecules developed after immunization with type II collagen a severe experimental polychondritis, similar to RP in humans suggesting that presentation of an "cartilage epitope² to CD4 T cells might be important for pathogenesis (9).

IV) TREATMENT OF RESPIRATORY MANIFESTATIONS OF R.P.
            Involvement of the respiratory tract in RP is a signal of severe prognosis. Treatment usually associates corticoteroids at the initial dose of 0,5 to 1 mg/kg/per day. Dapsone is presently discarded because of serious adverse effects like methaemoglobinemia. In this systemic connective tissue disease, it is often necessary to add immunosuppressive drugs like cyclophosphamide, azathioprine or more frequently methotrexate whose toxicity is less marked. In case of RP unresponsive to conventional drugs, some authors report interesting results with Infliximab,  an anti TNFa monoclonal antibody  already used in rheumatoid polyarthritis and Crohn-disease (10).

            In severe respiratory manifestations it is possible to test a mechanical treatment of the tracheal and/or bronchial collapse either by a continuous positive pressure (similarly to the device proposed in SAS) or an artificial ventilation with ²bilevel positive airway pressure" administered via a nasal mask.

création: décembre 2006