Treatment of respiratory complications in recalcitrant relapsing polychondritis with infliximab

S. Mpofu, C. Estrach, J. Curtis1 and R. J. Moots

Academic Rheumatology Unit and
1 Department of Radiology, University Hospital Aintree, Liverpool, UK

SIR, the outcome of relapsing polychondritis (RP) depends on remission of the underlying inflammatory process. Most patients experience a fluctuant inflammatory course, but the disease is generally progressive. Ten per cent of deaths in RP are due to respiratory complications. The optimal therapeutic approach to patients with RP is poorly understood. Corticosteroids are able to suppress disease activity but do not stop disease progression and are associated with side-effects. Various disease-modifying anti-rheumatic drugs have been used in an attempt to achieve a lower dose of steroid or for refractory cases. Infliximab is a monoclonal antibody that binds and inactivates tumour necrosis factor {alpha} (TNF-{alpha}) and has been successfully used in the management of TNF-{alpha}-mediated diseases, such as Crohn's disease and RA. Infliximab is not licensed for the treatment of RP, but because TNF-{alpha} has a potential pathological role in this condition, it may be of therapeutic benefit, especially after failure of conventional therapeutic approaches. We report here a patient with RP who developed recalcitrant and life-threatening respiratory tract complications, in whom treatment with infliximab led to resolution of disease activity.

A 51-yr-old female presented at the age of 49 yr with a 1-yr history of sudden intermittent bilateral redness, pain and swelling of the ears. She later developed nasal stuffiness, dysphonia and throat pain. On examination, both cartilaginous parts of the ears showed a dusky erythema and were swollen and tender. The rest of the examination was normal. Renal function, liver function, echocardiogram and all serological investigations [anticardiolipin, antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), Borrelia burgdorferi] were all normal. Computed tomography (CT) scanning showed circumferential deformity and oedema of the proximal tracheal rings and sclerosis of the left arytenoid cartilage, with normal signal in the cricoid cartilage and vocal cords. A diagnosis of RP was made using the diagnostic criteria of McAdam et al. [1]. She was treated with intravenous methyl prednisolone pulses followed by oral prednisolone 30 mg daily in a reducing course, which cleared her symptoms. However, when steroid was reduced she relapsed. She developed methaemoglobinaemia 3 days after a trial of dapsone and continued on prednisolone 7.5 mg daily with azathioprine 200 mg daily added.

During the following year she experienced several relapses of ear involvement and associated hoarse voice, which improved with high doses of steroid and substitution of methotrexate 25 mg once a week for azathioprine. Five months later, she developed a hoarse voice and throat pain. On examination she was tender over the anterior cervical trachea and larynx. Her spirometry showed non-reversible obstructive ventilatory impairment with reductions in expiratory flow rates and maximal voluntary ventilation. Her diffusion capacity was normal. Bronchoscopy showed inflammation of the laryngeal cartilages. CT scan showed pronounced soft-tissue thickening affecting almost the entire cervical trachea with sclerosis of the cricoid and arytenoid cartilages (Fig. 1Go). Following counselling on the benefit and possible risks of infliximab therapy, she consented to commence on infliximab 5 mg/kg 0, 2, 4, 8 weekly. She tolerated this well and no immediate adverse effects were noted. She is now symptom-free and in remission. Repeat CT scanning showed essentially a marked improvement in the tracheal thickening (Fig. 2Go).



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FIG. 1. Before infliximab. CT with intravenous contrast medium below the level of the vocal cords. Note the circumferential tracheal wall thickening (black line) with mild anterior displacement of the posterior membranous part of the trachea (arrow).

 


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FIG. 2. CT at the same level as that shown in Fig. 1Go. Circumferential thickening remains, but to a markedly reduced degree (black line).

 
In 1923, Jaksch-Wartenhorst [2] gave the first clinical description of RP. Relapsing polychondritis is an inflammatory disease characterized by episodes of inflammation and fibrosis that destroy all types of cartilage with high concentrations of glycosaminoglycans [3]. In addition, it can affect proteoglycan-rich tissues, such as the eyes, aorta, heart and skin [4]. Pathogenetically, linkage to the human leucocyte antigen DR4 gene and other autoimmune diseases suggests anti-self pathophysiology. Auricular chondritis and inflammation are the most common presenting complaints of relapsing polychondritis [1, 2, 5]. Laryngotracheal involvement may occur in up to 50% of patients and can be manifested as dysphonia, dysphagia, throat pain, dyspnoea and stridor [6]. Airway involvement results in the high mortality seen with relapsing polychondritis [7]. Biopsy of the tracheal and thyroid cartilage was not done in this case on bronchoscopy, as this is usually complicated by perforation. Our patient had the characteristic pulmonary function test result of non-reversible obstructive ventilatory impairment and normal diffusion capacity. As demonstrated in previous studies, CT appears to be a reliable method of identifying tracheal involvement and can be repeated safely during the course of the disease [8, 9]. A standardized therapeutic protocol for RP has not been established. Non-steroidal anti-inflammatory drugs, dapsone and/or colchicine may control disease activity in some patients. In other patients, immunosuppressive drugs and prednisone have been effective. RP bears many of the hallmarks of a TNF-{alpha}-mediated disease. T-cell clones reactive to type II collagen have been identified in RP, suggesting a Th1-type autoimmune response, producing TNF-{alpha}. TNF-{alpha} has also been demonstrated in vitro to induce the synthesis and release of matrix-degrading proteinases from chondrocytes, of the type that causes damage in RP [10]. We thus considered infliximab to be a potential therapeutic agent.

Infliximab treatment resulted in a rapid and complete clinical response in potentially life-threatening RP that had not responded to conventional immunosuppression. RP is so rare that controlled therapeutic trials have not been carried out. Multicentre studies are required, with careful examination of treatment benefits. This may result in unique insights into the mechanism of action of infliximab in RP and increase our knowledge of the pathophysiology of RP. This case highlights the usefulness of anti TNF-{alpha} therapy in patients with refractory RP.

Notes

Correspondence to: S. Mpofu, Academic Rheumatology Unit, University Hospital Aintree, Lower Lane, Liverpool L9 7AL, UK. E-mail: smpofu{at}liv.ac.uk Back

References

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Accepted 16 January 2003