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Sir,

Relapsing polychondritis is an uncommon, chronic, multisystem inflammatory disorder of cartilaginous structures. The specific cause is unknown, but it is believed that an immunologic reaction to type II collagen plays a key role. Type II collagen is present in cartilage and sclera of the eye. Patients with relapsing polychondritis have demonstrated both circulating antibodies and cellular immune reactions to type II collagen.1, 2 Relapsing polychondritis is characterized by an episodic and progressive course affecting predominantly the ear, nose and laryngotracheobronchial tree. It often presents in an enigmatic fashion and is easily misdiagnosed. The disease can be debilitating and even life threatening. Ocular manifestations may appear in approximately 51% of cases,3 episcleritis and scleritis being the most common. Misdiagnosis of reactive arthritis or spondyloarthropathy is often made when eye and joint symptoms coexist.4

Case report

A 45-year-old lady has been attending the outpatient department for the past 20 years. She has a history of recurrent episodes of episcleritis, scleritis, and anterior uveitis which was controlled by topical steroids, mydriatics, and oral nonsteroidal anti-inflammatory drugs. A full systemic evaluation was carried out during the early stage revealed erosive changes of the sacroiliac joint compatible with ankylosing spondylitis in addition to being positive for HLA-B27.

She presented 3 years ago to the accident and emergency department with a painful, red swollen left outer ear and was admitted to the ENT ward. She was treated with intravenous antibiotics for possible infective perichondritis but did not respond. In addition, her right eye was red and painful, and she also complained of experiencing intermittent joint pains with swelling of the left ankle. Of importance in her medical history was a 12-year history of sudden hearing loss in her right ear of unknown cause, and she has also recently been diagnosed with hypertension.

Examination of her eyes confirmed a diffuse anterior scleritis of the right eye. After consulting with the rheumatologist and otolaryngologist, a diagnosis of relapsing polychondritis was established according to Mc Adam's criteria.5

Treatment with prednisolone (40 mg/day) was started and colchicine (500 μg bd) was added later to help with her joint symptoms. As her clinical condition improved, the prednisolone dose was lowered, but after 4 months she developed another episode of a diffuse scleritis with other systemic manifestations of relapsing polychondritis. Addition of methotrexate up to 10 mg once weekly failed to control her disease, which relapsed on two occasions with inflammatory polyarthritis and respiratory chondritis. In each instance it was associated with a diffuse anterior scleritis (see Figure 1), which has resulted in signs of early scleromalacia of the left eye. At this stage, she was also developing a cushingoid appearance with impaired glucose tolerance and high blood pressure because of the high steroid dose. Owing to these harmful side effects and frequent relapses she was weaned off the prednisolone and methotrexate was stopped. Cyclosporin A was considered, but as she was complaining of fatigue and her high blood pressure we decided against it.

Figure 1
figure 1

Right eye showing diffuse anterior scleritis.

Full size image

Screening tests for active infection and latent tuberculosis were carried out followed by an induction scheme with intravenous infliximab 3 mg/kg at baseline, week 2 and 6 was then started followed by a maintenance dose every 8 weeks. After 2 weeks of treatment, her appetite had increased and her general health had improved. The scleritis resolved completely after 3 weeks and has not recurred over the past 6 months. In addition, her joint problems and laryngotracheal symptoms which she experienced before the infliximab infusion were no longer present. Up until her last clinic appointment (which was 6 months from the induction scheme), she remained in remission and sustained the improvement from the infliximab treatment. No adverse effect from the TNFα-blocking agent was observed.

Comment

This is the first report, to our knowledge, of the successful treatment of relapsing polychondritis associated with active scleritis with infliximab therapy. In chronic inflammatory disease much of the pathology is mediated by proinflammatory molecules that are linked in a network controlled by cytokines such as TNFα. TNFα is produced predominantly by activated macrophages. It enhances activation of T helper cells, which results in promotion of both cellular and humoral immune responses. Anti-inflammatory therapy with TNFα inhibitors has emerged as a major advancement in the treatment of various immune mediated diseases. Infliximab is a chimeric human/murine monoclonal antibody to TNFα. It neutralizes the effects of TNFα by binding to the soluble and transmembrane forms, and thus inhibits binding of TNFα with its receptors. In a randomized double-blind study by Van Den Bosch et al,6 they found that patients with active spondyloarthropathy showed significant clinical and laboratory improvements with infliximab infusions as compared to placebo. Hoang-Xuan et al7 reported on the outcome of 11 patients with relapsing polychondritis associated with active scleritis. They indicated that immunosuppressive chemotherapy is usually required to successfully treat the ocular manifestations of relapsing polychondritis, especially nodular and necrotizing scleritis.

TNFα inhibitors hold promise for patients with refractory disease. Infliximab had a profound effect on the ocular and systemic manifestations of relapsing polychondritis in our patient. It not only improves the symptoms but may also limit disease progression, and is well tolerated. The safety profile of specific TNFα inhibitors deserves consideration as recent updates have reported cases of reactivation of tuberculosis,8 and severe infections associated with infliximab treatment.9 Careful patient selection and thorough evaluation is therefore important before starting treatment with TNFα inhibitors.