Our study provides epidemiological evidence on drugs for urticaria. This finding was based on functional mechanism of health care system in China, which was completely different from Western countries. In this study, almost all patients sought help from dermatologists in the first place, because of lack of general practitioners and family doctors. Even acute urticaria patients were treated by dermatologists, rather than emergency departments. Globally, antihistamine therapy is the most commonly applied in clinical practice at present. In our survey, with popularization and wide utilization of the sgAHs, the fgAHs displayed obvious signs of decline. A similar drug administration pattern was reported by Rimoldi M et al. who found that the second-generation H1-antihistamines at the registered dose were the most common treatment in Italy.10 By contrast, in Poland, more than one-third of physicians chose the first-generation sedative H1-antihistamines and systemic steroids either alone or in combination as the initial therapy.11 Approximately 20% of German specialists (mainly dermatologists and allergists) applied the first-generation H1-antihistamines or steroids as the first-line treatment for CU.12 Treatment choice was closely associated with the specialist’s knowledge of current guidelines. Both EAACI/GA2LEN/EDF/WAO and Chinese guidelines suggested the 2nd-generation H1-antihistamines over the 1st-generation H1-antihistamines for chronic urticaria (evidence-based and consensus-based).8, 13 However, these guidelines differ with regards to the second-line treatment, where the international guideline recommended escalated dosing sgAHs up to 4-fold after a maximum for 2 weeks, whereas the Chinese guideline recommended to change the current type of sgAH, multi-sgAH combination, along with the first-generation H1-antihistamine, or mono-sgAH up dosing regimens with informed consent.13 Except for ebastine, no other sgAHs definitely doubled the dose in medicine instruction, which explained why it had been extensively applied.
Taking into account different types of urticaria, we noticed that tripterygium glycoside, hydroxychloroquine as well as systemic steroids were prescribed more often in angioneurotic edema than in others, which might reflect physician’s conviction that this variant of urticaria was more difficult to control by standard regimen. Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause.14 Differentiating histamine-mediated versus bradykinin mediated angioedema is essential, as therapy or response to therapy is quite different.15 In Chinese guidelines for urticaria, tripterygium glycoside, system application glucocorticoids, and/or omalizumab were added as the third-line treatment. Tripterygium wilfordii Hook F (TwHF) is a vital Chinese herb belonging to Celastraceae family, with anti-inflammation, anti-anaphylaxis, and immunosuppression effects.16 It has been reported by Liu et al. 17 and Yao et al. 18 that tripterine, a primary component in TwHF, inhibited degranulation of mast cells and histamine release. Active ingredients in TwHF are toxic components that may be harmful to liver, kidneys, reproductive tissues, and immune system. Because of side effects, TwHF is often used clinically for treating complicated autoimmune and inflammatory diseases in China, such as rheumatoid arthritis,19 diabetic nephropathy,20 purpura nephritis, 21 and urticaria.22, 23 Except for omalizumab and ciclosporin A, which both have restrictions due to high cost, alternative protocols, such as combinations of sgAHs with tripterygium glycoside, are based on clinical trials lack of supporting evidence. In this study, efficacy index of tripterygium glycoside (36.3% in 1 week) was lower than other drugs (Table 3), indicating that tripterygium glycoside was not outstanding and dominant. A large sample-size, multi-center, high-quality clinical study is required to verify efficacy and safety of tripterygium glycoside in angioneurotic edema and urticaria.
Interestingly, this study provides preliminary evidence that compound glycyrrhizin holds potential as a versatile collaborator, which has been widely used in combination with a variety of drugs. The oral compound glycyrrhizin is a preparation composed of glycyrrhizin, cysteine hydro- chloride, and glycine. Primary active component is glycyrrhizic acid, an active substance found in licorice.24 Glycyrrhiza glabra (Fabaceae) commonly known as liquorice is considered to possess carminative, antimicrobial, hypolipidemic, anti-atherosclerotic, antiviral, antiulcerogenic, hepatoprotective, cardio- protective, immunomodulatory, antimutagenic, anti-pyretic, and anti-inflammatory activities.25 Broad anti-inflammatory activity of glycyrrhizin is mediated by interaction with lipid bilayer, thereby attenuating receptor-mediated signaling. In China, although not recommended in guidelines, compound glycyrrhizin has been widely used to treat urticaria with high clinical efficacy as an anti-allergic and anti-inflammatory agent. compound glycyrrhizin has minor adverse effects, including hypertension, hypokalemia, and pseudo-aldosteronism. In particular, glycyrrhizin in conjunction with conventional therapy has been used in clinical practice, especially for severe clinical symptoms, however, supporting evidence for such practice has not been evaluated systematically. In our survey, combination has achieved better therapeutic effect (efficacy index of 54.2% in 1 week, whereas 90.7% in 4 weeks). To our knowledge, few high-quality studies have been published on efficacy evaluation of compound glycyrrhizin in urticaria. Further research is required to determine acceptable long-term efficacy and safety of compound glycyrrhizin in urticaria patients.
In general, urticaria patients obtained good clinical outcome in response to single or in combination regimen. After 4-week followed up, 71.8% of patients recovered from urticaria, 11% was highly effective, and 14.2% was effective. Patients with more severe symptoms were often treated with a combination regimen, such as an antihistamine drug in combination with compound glycyrrhizin or traditional Chinese medicine. In the current study, patients on olopatadine, who had the highest starting USA7 scores (33.7), showed a high first-week efficacy indicator (55.2%) with an efficacy index of > 90% at the end of follow-up. Previous studies on olopatadine and levocetirizine have shown that urticaria activity score (UAS) and urticaria total severity score (TSS) values declined significantly over the treatment period, however, the reduction was greater with olopatadine.26 Mild to moderate urticaria could be controlled by standard application, while severe urticaria could be managed by a standard application of olopatadine, however, levocetirizine might need an additional dose to control severe urticaria.27 The booklets of medicine instruction indicate that olopatadine is more suitable for poor first-line treatment, attributed to the highest starting USA7 scores. Compared with other sgAHs, olopatadine has fast-acting and curative effect, especially during the first week.