The effect of TNFalpha blockade in complicated, refractory Kawasaki disease.

In Kawasaki disease (KD), a systemic vasculitis of childhood, serum levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFalpha) are elevated during the acute phase of the disease. Although the majority of children recover completely from a single dose of intravenous immunoglobulin (IVIG), the treatment is not always effective. In refractory cases of KD there are no documented treatment guidelines. A future role of biological agents directed against proinflammatory cytokines has recently been suggested by the American Heart Association (AHA). We describe two infants with severe KD, complicated by coronary as well as extracoronary aneurysms, who responded neither to repeated treatment with IVIG plus aspirin nor to corticosteroids. The children were subsequently treated with infliximab. In both cases, the effect was prompt and long-lasting. Clinical improvement was seen within a few days after the first dose, and regression of the aneurysms occurred within weeks.

Histamine release from gut mast cells from patients with inflammatory bowel diseases.

Inflammatory mediators from intestinal mast cells may serve as initiators of acute and delayed inflammation. Mast cell histamine release was measured in 19 patients with inflammatory bowel diseases using gut mast cells from enzymatically dispersed endoscopic forceps biopsy specimens of macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects. The mast cell count in patients with ulcerative colitis was increased compared with that in control subjects and patients with Crohn's disease, and the mast cell count obtained from inflamed tissue was greater than that of normal tissue. The study also shows the heterogeneity of the responsiveness of the histamine releasing cells to various secretagogues. Thus, mast cells released 0.4 (0.0-2.0) (median (range)) ng histamine per sample at anti-IgE challenge, and basophils were also anti-IgE responsive. In contrast, mast cells did not respond to FMLP but the corresponding basophils did. Gut mast cells released 0.3 (0.0-1.0) (median (range)) ng histamine per sample at anti-IgG4 challenge; however, the corresponding basophils did not respond to anti-IgG4. In addition, the anti-IgG4 mediated histamine release was primarily confined to patients with inflammatory bowel disease. This study substantiates previous histopathological findings that mast cells may play a functional role in the inflammatory process of inflammatory bowel diseases and provides evidence for a possible role of subclass IgG4 as a reaginic antibody.