Chronic Urticaria: A novel approach in Treatment

Rationale
To investigate the prevalence of pollen sensitization in patients with chronic spontaneous urticaria (CSU) and to observe the clinical efficacy of specific immunotherapy in patients when pollen sensitization was the only identifiable cause.

Methods
Patients who were diagnosed with CSU between 2005 and 2012 were included in a prospective study. Only patients who had urticaria at least 5/7 days of the week were included. Patients were evaluated by history, duration, severity and frequency of symptoms, drugs used, total and specific IgE for local pollens. Those who were pollen sensitive were observed for 2 weeks before starting specific immunotherapy (SCIT) and monthly follow up at least for one year. The end point was asymptomatic at least for 6 months compared to controls who did not receive SCIT.

Results
Thirty three patients, 23 females and 10 males were included and 15 patients controls. Seven patients had urticaria alone and 26 patients had urticaria with AR or BA or both. Four patients were lost to follow up. Seven patients (24%) became symptom-free compared to 15 controls (p<0.0001), 22/29 (76%) their urticaria became far spaced or went into remission with p<0.001, Visual analogue for 7/24 was 100% and 22/29 visual analogue was between 50% and 95%. In 4 patients there was no improvement. The overall improvement in SCIT patients for one year or more was 80% (25/29).

Conclusion
Patient with CSU, were pollen sensitization is the only identifiable cause may benefit from SCIT. This study is the first to show the benefit of IT in CSU.

Treatment of chronic urticaria is essentially symptomatic. Many drugs have been used but none is curative. This includes antihistamine blockers, anti-leukotrienes, corticosteroids, cyclosporin, hydroxychloroquine, dapsone, sulfasalazine, methotrexate, IV gamma globulin and omalizumab [1,2]. Other biological agents such as Rituximab has been claimed to be successful in treating chronic autoimmune refractory urticaria [3]. Recently, Kocaturk E, et al., showed that investigational substance P antagonists, C5^a/C5^a receptors inhibitors, Anti IL4, Anti IL5 and Anti IL13 and others may targeturticaria treatment [4]. Most recently, more biologic agents have been proposed to treat urticaria, such as Ligelizumab, and molecules targeting intracellular signaling pathways such as spleen tyrosinase kinase inhibitors and others [5]. Other alternative treatment for chronic urticaria that has been tried includes Adalimumab, vitamin D, probiotics, histaglobin, injection of autologous whole blood or serum [6] and phototherapy [7].

None of these modes of treatments gave long lasting remission of chronic urticaria. We asked ourselves what to do with patients with chronic urticaria, where the only identified cause is sensitivity to pollens, especially when urticaria is associated with other symptoms of allergy such as allergic rhinitis, or allergic asthma or both. The most common sensitizing allergens in our patients were Mugwort, Russian Thistle, Amaranthus and Atriplex. Some patients were sensitized to weeds, grasses and Mesquite trees. Because sunshines 12 months a year in our region, plants pollinate all year around. Therefore, we decided to treat those patients with local allergens vaccine starting with the low concentration the patient can tolerate without reactions. We are aware some allergist use higher concentrations of vaccine for maintenance, our patient were unable to tolerate concentration more than 1:500 w/v without reaction. This may be due to the fact that pollen is in the air all the time, in addition to the finding that pollens are crushed by sand particles which make them more potent. All patients were informed that this is a new approach before we got their consent. In one year after starting SCIT the majority of our patient had remarkable improvement and most stopped symptomatic treatment. Xing DR, et al., [8] treated 2885 patients who had chronic urticaria and dust mite allergy, with immunotherapy with good to excellent results; with efficacy of 91.1% (226/248) with 66.1% of excellent or good results. Collins found more mugwort and birch sensitization in patients with chronic urticaria compared to allergicrhinitis but no allergy vaccine was given [9]. Similar studies by other authors showed the same [10,11]. There is one case report by Kasperska-Zajak where a patient with respiratory allergy and CU his Urticaria flared up during Immunotherapy with dust mite suggesting that Immunotherapy is beneficial in sensitized chronic urticaria [12]. Mahesha, et al., found high sensitivity among patients with urticaria to dust mite suggesting that allergy may play a role in the cause of chronic urticaria [13].Our patients had overall efficacy of immunotherapy of 86% with 14% (4/29) patients showed 100% remission of their urticaria compared to patient who stayed on symptomatic treatment. Although some cases of chronic urticaria go into remission even without treatment, our patients were symptomatic all the time and they did not benefit from other forms of treatment. Furthermore, we observed the continuity of their urticaria two weeks before SCIT. Their remission after SCIT cannot be attributed to natural course of remission and relapse. We believe our study proves that chronic urticaria is amenable to treatment with allergy vaccine when pollens are the main or the only underlying cause.This novel approach has no previous similar study in the English literature. Therefore, more studies are needed to confirm our findings. Although some authors mentioned that chronic urticaria is not allergic [14].