Thalidomide dramatically improves the symptoms of early-onset Sarcoidosis/Blau syndrome: Its possible action and mechanism.

OBJECTIVE: Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, is associated with granulomatous lesions and a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 that causes constitutive NF-kappaB activation. The symptoms of EOS can be uncontrollable, progressive, and associated with profound complications. However, appropriate therapy is still under investigation. The aim of this study was to assess the efficacy of thalidomide in patients with severe EOS, based on etiology supporting an initial role of NF-kappaB in activation of this disease. METHODS: Thalidomide was given to 2 patients with EOS (a 16-year-old girl and an 8-year-old boy) at an initial dosage of 2 mg/kg/day, and the dosage was increased if necessary. To elucidate the mechanism of the drug, peripheral blood monocytes were isolated from the patients and stimulated with cytokines (macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-4), and their ability to form multinucleated giant cells (MGCs) and osteoclasts was measured. RESULTS: Both patients showed dramatic improvement of their clinical symptoms (alleviation of fever and optic nerve papillitis, achievement of a response according to the American College of Rheumatology Pediatric 50 and Pediatric 70 criteria) and laboratory findings. Monocytes from patients with EOS had a greater ability to survive and induce MGCs and osteoclasts than those from healthy control subjects. The formation of MGCs and osteoclasts was inhibited by the presence of thalidomide. CONCLUSION: The ability of thalidomide to improve clinical symptoms and laboratory findings in patients with EOS indicates a central role for NF-kappaB activity in this disorder. Inhibition of IKK might be a pharmacologic action by which thalidomide down-regulates NF-kappaB signaling. Thalidomide may be an effective medication in patients with severe complications of EOS, including ocular involvement. [ABSTRACT FROM AUTHOR]