- Some patients with chronic idiopathic urticaria (CIU) are resistant to conventional doses of antihistamines (AHs). This study was designed to check whether the skin wheal and flare reaction produced by the intradermal injection of autologous serum (AS) and by histamine differs in AH-resistant and AH responder CIU patients. CIU patients with treatment failure under fexofenadine at 180 mg q.d. increased their daily dose of AH to 4 tablets daily. Those with significant improvement of urticaria activity score under fexofenadine at 180 mg were included in the CIU group. Subjects with treatment failure despite a full 8-week fourfold fexofenadine treatment were included in the resistant CIU (R-CIU group). The control group consisted of sex- and age-matched patents with allergic rhinitis. The AS skin test and intradermal histamine-induced wheal and flare reaction were performed at baseline (without AH), after 8 and 16 weeks (under AH treatment). Forty-six subjects were included in the CIU group, 21 were in the R-CIU group, and 44 were in the control group. Under AH therapy, the skin reaction to intradermal histamine injection was significantly diminished in all study groups. In the R-CIU group, fexofenadine at 180 mg did not suppress AS-induced wheal reaction (5.96 ± 2.25 mm; p = 0.85), and with a fourfold AH dose some reduction of AS-induced wheal (3.79 ± 1.74 mm; p = 0.008) was observed but remained larger than in the CIU (2.31 ± 1.12; p = 0.006) and control groups (2.52 ± 1.36; p = 0.037). AHs do not inhibit the wheal induced by the intradermal injection of AS in R-CIU.