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Adult-onset Still’s disease (AOSD) is a multisystemic inflammatory disease of unknown cause, characterised by daily spiking fever, rash, leucocytosis and arthritis. Cytokines such as interleukin (IL)1, 6 and 18, interferon γ, tumour necrosis factor are thought to have a role in the pathogenesis of the disease.1 2 Treatments such as non-steroidal anti-inflammatory drugs, steroids, methotrexate (MTX), gold, azathioprine, leflunomide, ciclosporin and biological agents (tumour necrosis factor blockers, IL1 receptor antagonist or rituximab) can help in the management of patients, depending on presentation and disease course.3–5
We report on a young woman with refractory AOSD successfully treated with anti-IL6 receptor antibody (tocilizumab), whose efficacy has been shown in systemic onset juvenile idiopathic arthritis.
AOSD started in this patient when she was age 26. She had spiking fever, rash, arthritis, high leucocytes count, lymphadenopathy and splenomegaly, she was rheumatoid factor and antinuclear antibody negative. She was treated with non-steroidal anti-inflammatory drugs and steroids. As the disease persisted (febrile polyarthritis, polycyclic form) she was treated with steroids, gold and MTX, with poor response. Typical carpometacarpal destruction occurred on both hands.
She worsened in 2004 (age 34) with intensification of articular and systemic manifestations despite high doses of steroids (1 mg/kg/day) and subcutaneous MTX (20 mg/week). She was unsuccessfully treated with leflunomide (20 mg/day), thalidomide (200 mg/day), etanercept (50 mg/w), infliximab (5 mg/kg) and anakinra (100 mg/day), with no control of the rheumatic, systemic and biological manifestations. At that time she became unable to work.
Treatment was started with tocilizumab in July 2006 (8 mg/kg) every other week, on a compassionate regimen, with steroids and MTX. After four infusions, laboratory tests normalised (erythrocyte sedimentation rate, C-reactive protein, ferritin, blood count, haemoglobin), systemic manifestations disappeared after five infusions and articular complaints after seven. Seven months later steroids and MTX were discontinued, tocilizumab monotherapy continued and she returned to work. The treatment is well tolerated with normal liver enzymes and cholesterol levels.
An attempt to reduce the dose in June 2007 was followed by articular manifestations, which disappeared when the initial regimen was resumed. In October 2007 she developed a flu-like disease, due to cytomegalovirus infection, complicated with documented macrophage activation syndrome on bone marrow biopsy. Tocilizumab was stopped. She received pulse prednisolone and ciclosporin and recovered promptly. During this episode the acute phase proteins (erythrocyte sedimentation rate, C-reactive protein) remained normal, probably owing to high doses of tocilizumab and continuing IL6 signalling blockade. Articular and systemic manifestations recurred 6 weeks later, tocilizumab was resumed (same dose) with good response. At that time (January 2008), she was doing well after18 months’ tocilizumab treatment.
IL6, a pleiotropic cytokine with important roles in the regulation of immune response and inflammation,6 is raised in the active phase of AOSD. Inhibiting the IL6 receptor has been proved to be therapeutically effective.7 8 The SAMURAI study demonstrated efficacy in patients with rheumatoid arthritis treated with tocilizumab.9 An open-label trial of tocilizumab in children with severe systemic onset juvenile idiopathic arthritis, despite high-dose prednisolone and MTX,10 was effective, supporting the hypothesis that IL6 is a key cytokine in the inflammation process of Still’s disease. This report suggest that the same strategy might be useful in AOSD.
We thank Roche and Chugai for providing us with tocilizumab for treatment of this patient.
Competing interests: None.
Patient consent: Obtained.