Schnitzler syndrome:
Schnitzler syndrome is a rare disabling autoinflammatory syndrome characterized by a chronic
urticarial rash and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or
arthritis or bone pain. Diagnostic criteria have been established. The disease never remits
spontaneously. Although there is no standard of care, there have been promising developments
in therapeutic options, especially anti-interleukin-1 therapy. Anakinra, a synthetic analogue
of the endogenous interleukin-1 receptor antagonist, has caused rapid clinical remission in
24 patients with Schnitzler syndrome. However, to sustain remission, continuous daily
administration (100 mg sc) is required. The level of monoclonal protein does not decrease.
Side effects of anakinra include painful injection site reactions and neutropenia.
Interleukin-1 and the autoinflammatory diseases:
As a key proinflammatory cytokine mediating local and systemic responses to infection and
tissue injury, interleukin-1 can induce a range of responses, including fever, pain
sensitization, bone and cartilage destruction, and the acute-phase inflammatory response. The
so-called autoinflammatory diseases are mediated entirely by interleukin-1; reducing
interleukin-1 activity brings about a rapid and sustained remission. Autoinflammatory
diseases include relatively uncommon disorders such as familial Mediterranean fever, adult
and juvenile Still's disease, the hyper-IG D syndrome, Behçet's syndrome, the
cryoporin-associated periodic syndrome (CAPS), deficiency of the interleukin-1 receptor
antagonist (DIRA) and Schnitzler's syndrome. Some common conditions such as gout and type 2
diabetes, are also likely to be autoinflammatory diseases.
Canakinumab:
Canakinumab (Ilaris, Novartis Pharma) is a fully human anti-interleukin-1-bèta monoclonal
antibody. Treatment with subcutaneous canakinumab (150 mg) once every 8 weeks was associated
with a rapid remission of symptoms in the great majority of children and adults with CAPS.
Serum inflammatory markers quickly returned to normal. In general, the side effects seen in
this small study (35 patients) were not serious, though suspected infections ware
significantly more prevalent in patients receiving canakinumab than in those receiving
placebo. The prolonged duration of action of canakinumab and low incidence of injection-site
reactions may confer certain advantages over other interleukin-1 inhibitors (anakinra and
rilonacept), since both are frequently associated with injection-site reactions, and both
require more frequent administration (daily for anakinra and weekly for rilonacept).
Canakinumab was approved for the treatment of CAPS by the US Food and Drug Administration in
June 2009 and by the European Medicines Agency in October 2009.
Canakinumab is currently being evaluated for its potential in the treatment of systemic-onset
juvenile idiopathic arthritis, diabetes mellitus, and difficult-to-treat gouty arthritis.