Multicentric Castleman's disease is a rare lymphoproliferative disorder 
characterised by disseminated lymphadenopathy. Symptoms and outcomes differ 
widely from one patient to another. The median survival time is about 2.5 years. 
There is no consensus on treatment. Siltuximab, a monoclonal antibody that 
antagonises interleukin-6, has been authorised in the European Union for 
patients with multicentric Castleman's disease who are not infected with HIV or 
HHV-8. In a randomised, double-blind trial in 79 patients, most of whom had mild 
or moderate symptoms, the estimated one-year survival rate was 100% in the 
siltuximab group versus 92% in the placebo group after a median follow-up of 60 
weeks. However, half of the patients in the placebo group received siltuximab 
after disease progression. Symptoms disappeared for at least 18 weeks in 
one-quarter of patients in the siltuximab group versus none of those in the 
placebo group; the median symptom-free period in the siltuximab group was about 
16 months. The known adverse effects of siltuximab are related to its 
immunosuppressive effect. They include frequent infections, neutropenia and 
thrombocytopenia. Reactions can occur during the infusion, and mouth sores have 
been reported. Other adverse events that appear to be more frequent with 
siltuximab include cutaneous disorders, oedema, renal and cardiac disorders, and 
peripheral neuropathy. Cases of gastrointestinal perforation have been reported 
in trials in other clinical settings. Siltuximab can mask the signs and symptoms 
of acute inflammation, in particular by suppressing fever and acute-phase 
markers such as C-reactive protein. Interleukin-6 is a cytochrome P450 
inhibitor. Siltuximab activates its isoenzymes and can thus reduce the 
effectiveness of the numerous drugs that are substrates of this enzyme system. 
This risk of interactions is likely to persist up to several weeks after 
siltuximab withdrawal, because of its long plasma elimination half-life (about 
16 days). In practice, the only available trial suggests that siltuximab has a 
marked impact on the symptoms of mild or moderate multicentric Castleman's 
disease in patients who are not infected with HIV or HHV-8. Siltuximab seems to 
be a reasonable option in this setting, despite its numerous adverse effects, 
provided patients are fully informed of the many unknowns and are closely 
monitored.