Chronic urticaria guidelines updated

The recommended use of antihistamines for chronic urticaria have been updated in the most recent installment of treatment guidelines written by a European and American work group.

Published in the journal Allergy in January 2018, this marks the fourth update by the group since 2006. The updated European guidelines were written in collaboration with the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO). The American Academy of Dermatology, American Academy of Allergy Asthma and Immunology (AAAAI) and the American College of Allergy Asthma and Immunology (ACAAI) also participated in the review and update. Previously in 2014, the American group, along with the Joint Council of Allergy Asthma and Immunology, published guidelines (call “Practice Parameters”) in the Journal of Allergy and Clinical Immunology.

Based on the strength of the evidence available, the 2017 guidelines makes strong or weak recommendations in favor of certain approaches, strong or weak recommendations against other management options, or makes no recommendation if only insufficient data or conflicting outcome data is available.

Speaking at the American Academy of Dermatology (AAD) annual meeting in February, Diane R. Baker, M.D., a dermatologist in Oregon, addressed antihistamine use for chronic urticaria in her presentation.

DISEASE DEFINITION

Both the updated global guidelines and the 2014 guidelines recommend the classification of urticaria based on its duration as acute (≤ 6 weeks) or chronic length (> 6 weeks) and as inducible (specific eliciting factor such as cold, heat or sunlight involved) or spontaneous (no specific eliciting factor involved). Spontaneous urticaria (also referred to as idiopathic urticaria) and inducible urticaria (also referred to as physical urticarial) often co-exist in patients.

RECOMMENDATION: GOAL

With more than 90% consensus, the 2017 guideline committee members agreed that complete symptom control should be the aim in treating urticaria, taking into consideration as much as possible the safety of treatment and the quality of life of each individual patient.

RECOMMENDATION: ANTIHISTAMINES

As in the 2014 guidelines, the 2017 guidelines continues to recommend a stepwise approach to treatment of chronic urticaria beginning with avoidance of triggers and treatment with a H1-antihistamine. Second-generation H1-antihistamines are recommended over first-generation H1-antihistamines because of their better safety prof le. While effective, first-generation H1-antihistamines are associated with risks of sedation and anticholinergic effects.

“Second generation agents are efficacious and are better tolerated in most patients,” Dr. Baker said.

About 40-50% of patients with CSU will not respond to standard doses of H1-antihistamines. The next step would be to increase the dose of the second-generation H1-antihistamine. The guideline states that the majority of patients with urticaria not responding to standard doses will benefit from up-dosing of antihistamines and highlights studies that have documented the benefit of using up to fourfold higher than licensed doses of cetirizine, desloratadine, fexofenadine, levocetirizine, bilastine, ebastine, and rupatadine. Of these, only cetirizine, desloratadine, fexofenadine and levocetirizine are licensed
for use in the United States.

In contrast to the 2014 guidelines, and because of insufficient evidence in the literature, the 2017 revision does not recommend adding another second-generation H1-antihistamine, a H2-antagonist, a leukotriene receptor antagonist or a first-generation H1-antihistamine at bedtime as next steps in treatment of antihistamine resistant cases of chronic urticaria.

Dr. Baker stated that although many patients respond to up-dosing with second-generation H1-antihistamines, around half of chronic urticaria patients will not achieve satisfactory control with antihistamine treatment - even at four time the standard dose. For such patients, the 2017
guideline recommends adding omalizumab to the second-generation H1-antihistamine.

RECOMMENDATION: ADDING OMALIZUMAB

Omalizumab (300 mg every four weeks) has been shown in randomized double-blind placebo controlled clinical trials, to be effective and safe in the treatment of CSU. It has also been reported to be effective in some but not all cases of chronic inducible urticaria.

The literature includes case reports of its effectiveness in the treatment of cholinergic urticaria, cold urticaria, solar urticaria, heat urticaria, symptomatic dermographism, and delayed pressure urticaria but it is not FDA approved for treatment of any inducible urticaria in the United States. In CSU, omalizumab has been shown to prevent angioedema development, improve quality of life, be suitable for long-term treatment and effectively treat relapse after discontinuation. Dosing of omalizumab in CU is independent of total serum IgE.

The recommended dose in CSU is 300 mg every four weeks. The licensed doses and treatment duration vary between different countries.

RECOMMENDATION: CYCLOSPORIN A

If response to omalizumab is not satisfactory cyclosporin A is recommended as an add-on treatment
to second-generation antihistamines if it is not contraindicated. Cyclosporin A is an effective
treatment for many cases of chronic urticaria but because of the adverse events associated with its use, the 2017 guideline update recommends a trial of omalizumab before cyclosporin A.

The use of systemic corticosteroids in the treatment of chronic urticaria is generally to be avoided. Long term use of systemic steroids is definitely not recommended because of the myriad of associated side effects, but the 2017 guideline suggests that a short course of oral corticosteroids - up to 10 days - may be helpful in reducing disease duration/activity in acute urticaria or exacerbations of CSU.

REFERENCES
1. Zuberbier T, W. Aberer W, Asero R et al. “The EAACI/GA²LEN/EDF/WAO Guideline for the Defi nition, Classifi cation, Diagnosis and Management of Urticaria. The 2017 Revision and Update,” Allergy, Jan. 15, 2018. DOI:10.1111/all.13397

2. Bernstein J, Lang D, Khan D. “The Diagnosis and Management of Acute and Chronic Urticaria: 2014 Update,” the Journal of Allergy and Clinical Immunology, 2014;133:1270-77e.1-66