Hydroxychloroquine in the treatment of anti-histamine refractory chronic spontaneous urticaria, randomized single-blinded placebo-controlled trial and an open label comparison study.

SUMMARY: Background. The management of anti-histamine refractory chronic spontaneous urticaria (CSU) has poorly defined therapeutic options. Some patients with CSU respond poorly to a fourfold increase in dosage of H1-anti-histamines treatment. Aim. The objective of this study was to determine the effect of an adjunct treatment of hydroxychloroquine (HCQ) on remission rate and reduction of urticarial symptoms. Methods. Sixty subjects with anti-histamine refractory CSU were randomly assigned to 400 mg of HCQ daily or placebo for 12 weeks in a single blind placebo controlled trial. In a second follow up trial, non-remission subjects were offered open-label HCQ in the placebo group or a leukotriene receptor antagonist (LTRA) in the HCQ group for 12 weeks. All subjects took 4 H1-anti-histamines tablets throughout the study. The endpoints measured were the urticarial symptom score (USS) and dermatology life quality index (DLQI). Results. Forty-eight patients (24 HCQ, 24 placebos) completed the randomized trial medication. Five of 24 on HCQ treatment but none on placebo had a remission at 12 weeks (P = 0.01). There was a low proportion of therapeutic failures occurred with 12-week HCQ treatment (n = 5) compared with placebo (n = 14, P = 0.001). After 12 weeks, USS and DLQI significantly improved in HCQ group over the placebo group. Forty non-remission subjects completed an open-label HCQ (n = 22) or LTRA (n = 18) comparison study. The remission rates on HCQ and LTRA were 22.72% and 5.55% at 12 weeks. However, no significant difference between the two groups in the therapeutic responses was observed. The mean USS on HCQ significantly decreased compared to the LTRA group, but there was no significant difference in DLQI. The adverse events reported were minimal and there were no subjects who discontinued the trial. Conclusions. This study suggests that HCQ is clinically effective as an adjunct treatment for CSU.

High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers.

BACKGROUND: The involvement of B cells in allergen tolerance induction remains largely unexplored. This study investigates the role of B cells in this process, by comparing B-cell responses in allergic patients before and during allergen immunotherapy (AIT) and naturally exposed healthy beekeepers before and during the beekeeping season. METHODS: Circulating B cells were characterized by flow cytometry. Phospholipase A2 (PLA)-specific B cells were identified using dual-color staining with fluorescently labeled PLA. Expression of regulatory B-cell-associated surface markers, interleukin-10, chemokine receptors, and immunoglobulin heavy-chain isotypes, was measured. Specific and total IgG1, IgG4, IgA, and IgE from plasma as well as culture supernatants of PLA-specific cells were measured by ELISA. RESULTS: Strikingly, similar responses were observed in allergic patients and beekeepers after venom exposure. Both groups showed increased frequencies of plasmablasts, PLA-specific memory B cells, and IL-10-secreting CD73- CD25+ CD71+ BR 1 cells. Phospholipase A2-specific IgG4-switched memory B cells expanded after bee venom exposure. Interestingly, PLA-specific B cells showed increased CCR5 expression after high-dose allergen exposure while CXCR4, CXCR5, CCR6, and CCR7 expression remained unaffected. CONCLUSIONS: This study provides the first detailed characterization of allergen-specific B cells before and after bee venom tolerance induction. The observed B-cell responses in both venom immunotherapy-treated patients and naturally exposed beekeepers suggest a similar functional immunoregulatory role for B cells in allergen tolerance in both groups. These findings can be investigated in other AIT models to determine their potential as biomarkers of early and successful AIT responses.