Endgames Picture Quiz

Painful ears and a cough

BMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b4150 (Published 29 October 2009) Cite this as: BMJ 2009;339:b4150
  1. Leena Patel, specialist registrar in rheumatology,
  2. Sonya Abraham, consultant rheumatologist
  1. 1Department of Rheumatology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London W6 8RF
  1. Correspondence to: leenapatel410{at}hotmail.com

    A 76 year old man was seen in the rheumatology clinic with a rash (fig 1), monoarthritis of the right wrist, and fatigue. He also had bilateral painful ears (fig 2), an intermittent hoarse voice, and hearing loss. He had a history of gout and was a non-smoker.

    Six months before presentation, the patient had an episode of anterior uveitis. One year before presentation, he had a prolonged episode of central pleuritic chest pain and an associated dry cough. At this time he was diagnosed with severe atypical pneumonia or possible early interstitial lung disease. He did not respond to three courses of antibiotics, but his symptoms spontaneously improved within six months.

    At presentation his erythrocyte sedimentation rate was 110 mm (normal range 0-10 mm) in the first hour, C reactive protein was 154 mg/l (0-10 mg/l), haemoglobin was 86 g/l (125-170 g/l), and albumin was 23 g/l (33-34 g/l). Audiometry showed right sided sensorineural hearing loss. Atypical pneumonia, viral serology, and autoimmune serology were negative. High resolution computed tomography of the chest showed mild non-specific fissural nodularity, with minor basal reticulation. Transbronchial biopsy had shown a mild chronic inflammatory interstitial infiltrate and mild fibrosis, but no granulomas or vasculitis. Pulmonary function tests were normal.

    Questions

    • 1 What is the diagnosis?

    • 2 What do the pictures show?

    • 3 How is the diagnosis made?

    • 4 What are the treatment options?

    Answers

    Short answers

    • 1 This patient has relapsing polychondritis.

    • 2 The images show purpuric vasculitic rash (fig 3) and auricular chondritis (fig 4).

    Figure3

    Fig 3 Purpuric vasculitic rash on the legs (arrow)

    Figure4

    Fig 4 Auricular chondritis (arrow)

    • 3 The diagnosis is made on clinical grounds and is suggested by the presence of characteristic clinical features including auricular, nasal, or laryngotracheal chondritis; ocular inflammation; audiovestibular damage; and an inflammatory arthritis.

    • 4 Mild disease in which no organs are affected can be managed with non-steroidal anti-inflammatory drugs or colchicine. However, most patients require corticosteroids with the addition of a steroid sparing agent such as methotrexate or azathioprine. Cyclophosphamide is used in cases of life threatening or organ threatening disease.

    Long answers

    1 Diagnosis

    Relapsing polychondritis is a rare chronic multisystem autoimmune disorder characterised by recurrent episodes of cartilage inflammation that can eventually cause progressive and permanent destruction of the affected tissue. It typically affects cartilaginous tissue of the ear, nose, laryngotracheobronchial tree, and the joints, in addition to proteoglycan rich tissues of the eyes, heart, blood vessels, and skin.

    Diagnosis is often considerably delayed,1 because presenting symptoms are non-specific and can be misdiagnosed as infection or confused with the symptoms of coexisting conditions—these are usually autoimmune, rheumatic, or haematological in origin and occur in up to 35% of patients.2

    2 What the pictures show

    A purpuric rash (fig 3) that shows leucocytoclastic vasculitis on skin biopsy, limb nodules resembling erythema nodosum, and aphthous ulcers are the most common dermatological manifestations in relapsing polychondritis.3 Skin involvement is more common in patients with associated myelodysplastic syndromes (91%).

    Auricular chondritis (fig 4) is the most common presenting feature of relapsing polychondritis and the most distinctive. Attacks are usually bilateral, affecting the pinna but sparing the non-cartilaginous earlobe. Pain develops subacutely with erythema, swelling, and tenderness that lasts a few days to weeks and can resolve spontaneously. Recurrent inflammation can eventually disrupt cartilage architecture giving rise to a disfiguring “cauliflower” appearance or a soft pinna that flops forward with movement.

    3 Making the diagnosis

    The diagnosis is made on clinical grounds and is based on characteristic features, blood abnormalities, and the exclusion of differential diagnoses. The box details the diagnostic criteria and provides their relative frequencies.4

    Diagnostic criteria

    • Auricular chondritis (relative frequency 89%).

    • Seronegative inflammatory arthritis (72%), which is intermittent, migratory, asymmetric, and non-erosive. It affects large and small joints, especially of the wrist, knees, and hands.5

    • Nasal chondritis (61%). Repeated attacks may lead to a collapsed nasal bridge and saddle nose deformity.

    • Laryngotracheobronchial chondritis (50%). This can manifest as anterior throat pain, hoarse voice, persistent non-productive cough, breathlessness, and wheeze.4 6 Glottic, laryngeal, or subglottic oedema can lead to stridor and potentially life threatening acute airway obstruction. Persistent airway inflammation can cause collapse or stenosis of cartilage rings, which lead to dynamic or fixed airway obstruction, respectively. Pulmonary infections are common7 and are a cause of death from respiratory disease. 1 8 All patients need to be screened for occult respiratory disease with pulmonary function tests including flow loops.9 In symptomatic patients, computed tomography or magnetic resonance imaging of the major airways will delineate the extent of disease. Pulmonary infiltrates are not characteristic,1 10 but their presence in our patient contributed to the delay in diagnosis.

    • Audiovestibular damage (40%). Manifestations include permanent sensorineural deafness or vestibular dysfunction secondary to internal auditory artery vasculitis,4 or temporal conductive deafness secondary to oedema, chondritis, or collapse of the external auditory canal or eustachian tube.11 This may be complicated by serous otitis media.1

    • Ocular inflammation (60%). Episcleritis, scleritis (rarely necrotising), conjunctivitis, and uveitis are the most common manifestations.10

    Three of the six criteria need to be positive to make the diagnosis; alternatively, two criteria and a suggestive cartilage biopsy from affected tissue will suffice. Our patient was positive for all criteria except for nasal chondritis.

    Cardiovascular involvement is common, occurs late,12 can be clinically silent, and can progress in spite of treatment.13 14 Aortic regurgitation is most common, either as a result of valvular ring inflammation or as part of an ascending aortitis.12 Large vessel vasculitis and aneurysm formation are also well described.15 Neurological and renal involvement are rare.

    Blood abnormalities during flares include a raised erythrocyte sedimentation rate, anaemia, leucocytosis, thrombocytosis, and polyclonal hypergammaglobulinaemia. Autoimmune rheumatic serology is negative unless these antibodies are present because of an associated condition. Anti-collagen type 2 antibodies have been detected in a third of patients during the acute phase of illness,16 but they are also present in 15% of patients with rheumatoid arthritis, so this is an unsuitable diagnostic test.17

    The differential diagnosis18 includes conditions that cause:

    • Auricular chondritis—namely, trauma and infection. However, both ears are usually affected, and the earlobe is not spared.

    • Inflammatory lesions of the larynx and subglottic region—namely, Wegener’s granulomatosis, sarcoidosis, amyloidosis, and tuberculosis.

    • Nasal chondritis—namely, Wegener’s granulomatosis, congenital syphilis, and leprosy.

    4 Treatment

    No standardised treatment strategy exists because of the lack of randomised controlled trials and heterogeneous expression of the disease. Mild auricular and nasal chondritis or synovitis can be managed with a non-steroidal anti-inflammatory drug, low dose colchicine (500 μg twice a day),1 19 20 or dapsone.21 22

    Organ involvement or repeated attacks require corticosteroids (0.5-1 mg/kg/day) to reduce the frequency, severity, and duration of attacks, although overall disease progression may not halt.4 Most patients require long term steroids, with the addition of steroid sparing agents such as methotrexate,1 ciclosporin,23 azathioprine,1 4 24 or penicillamine.25 Life threatening airway obstruction requires immediate pulsed intravenous methylprednisolone26 and possible tracheostomy.

    Indications for cyclophosphamide include refractory respiratory tract disease, cardiac and renal involvement,27 necrotising scleritis,24 and systemic vasculitis. Refractory cases have reportedly been treated with plasmapheresis,28 anti-CD4 monoclonal antibodies,29 and autologous stem cell transplantation.30 Stenotic respiratory tract lesions may require tracheostomy or stenting, and more than a third of patients with aortic regurgitation need valve replacement.31

    More recently, isolated cases with refractory disease have been treated successfully with anti-tumour necrosis factor agents including infliximab,32 33 etanercept,34 and adalimumab.35 Tocilizumab (anti-interleukin 6 receptor antibody)36 and anakinra (anti-interleukin 1 receptor antagonist)37 have also induced remission in patients who have failed treatment with anti-tumour necrosis factor agents. Rituximab has not been shown to improve outcome significantly.38

    Our patient was treated with prednisolone 60 mg daily, which rapidly improved his systemic symptoms. Within six weeks his C reactive protein was 5 mg/l and erythrocyte sedimentation rate was 37 mm in the first hour. Methotrexate was introduced at two months, when inflammatory markers started to rise again, to allow the steroid dose to be reduced. At four months, his disease was in remission and this has been maintained at one year with methotrexate (20 mg weekly) and low dose prednisolone (5 mg daily).

    Notes

    Cite this as: BMJ 2009;339:b4150

    Footnotes

    • Competing interests: None declared.

    • Provenance and peer review: Not commissioned; externally peer reviewed.

    • Patient consent obtained.

    References