BACKGROUND Spontaneous urticaria (SU) persisting for ≤6 weeks is classified as acute SU (ASU) and tends to remit shortly, whereas SU persisting for >6 weeks is classified as chronic SU (CSU) and is likely to last longer. However, 6 weeks to separate them is based on the traditional clinical practice, and the time of pathological conversion from ASU to CSU remains unclear. METHODS We aimed to retrospectively analyze the time course of 1029 patients with SU in whom treatment was initiated within 7 days of onset. Time to complete control (no symptoms with medication) and time to remission (no symptoms without medication) were analyzed, in association with age, preceding acute infection, and treatment initiation day. RESULTS Of the 1029 patients, 902 were analyzed for time to complete control and 877 for time to remission. The survival rate of patients without remission rapidly decreased during the first 16 days and slowly declined thereafter. No sex-related differences were observed between the groups. Preceding acute infection, age <30 years, and earlier treatment initiation were associated with better prognosis in terms of both time to complete control and time to remission. Among patients with ASU who initiated treatment within 7 days of onset, those who started treatment by day 4 were more likely to achieve remission within 6 weeks than those who started on days 5-7. CONCLUSIONS ASU pathogenicity may change at around 16 days, rather than at 6 weeks. Early treatment initiation for ASU may be beneficial in preventing CSU progression.
Sublingual immunotherapy (SLIT) is a safe and convenient treatment for allergic diseases, but it usually requires several years to achieve sufficient clinical benefit. Therefore, effective adjuvants are needed to enhance its efficacy and shorten the time required to achieve a therapeutic response. In this review, we summarize the rationale for using Toll-like receptor 4 (TLR4) agonists as adjuvants for SLIT and describe our recent preclinical findings with synthetic TLR4 agonist derivatives. We established a mouse model of sublingual administration using a small administration volume and a defined retention period after administration. Several TLR4 agonist derivatives enhanced allergen-specific serum IgG responses when administered with allergen. The adjuvant activity of one derivative was abolished in TLR4-knockout mice, indicating that its activity was dependent on TLR4 signaling. A selected derivative was further evaluated in combination with Japanese cedar pollen (JCP) extract. Co-administration of the derivative with JCP extract increased Cry j 1-specific IgG and IgA levels in serum and IgA levels in nasal lavage fluid. It also enhanced allergen-induced IL-10 production without substantially increasing IFN-γ or IL-4 production. Moreover, IgG from mice treated with the derivative and JCP extract more effectively inhibited allergen-induced mast cell degranulation than IgG from mice treated with JCP extract alone. These findings suggest that synthetic TLR4 agonists may enhance SLIT by promoting functional allergen-specific antibody responses. Further studies are needed to confirm their safety and clinical efficacy in humans.
