Urticaria Crónica Espontánea

Chronic spontaneous urticaria (CSU) symptoms include the recurrent spontaneous appearance of wheals and intense itch that may last from hours to days and occur for several years. Some patients develop localized and self-limiting angioedema. These manifestations result from a temporary increase in vascular permeability. Almost 13% of patients with CSU experience angioedema and do not develop wheals.

There are 2 main autoimmune mechanisms for CSU: type I autoimmune (autoallergic) CSU, which is associated with with IgE antibodies against autoantigens; and type IIb autoimmune CSU, which is mediated by autoantibodies that activate mast cells via IgE and FceRI. Type IIb autoimmune CSU is present in almost 10% of patients and is characterized by higher disease severity, concomitant autoimmune diseases, low levels of total IgE, elevated levels of IgG-anti–thyroid peroxidase, basopenia, eosinopenia, poor response to antihistamines and to omalizumab, and a good response to cyclosporine. Some new targeted therapies are under development, such as the anti-IgE, ligelizumab, and the Bruton’s tyrosine kinase inhibitors, fenebrutinib and remibrutinib, and an anti-IL-4Ra, dupilumab.

There are missing some studies on the overlap between autoallergic and type IIb autoimmune CSU and on the optimal management of both types of autoimmune CSU, with easy-to-perform, noninvasive and inexpensive markers to assess the treatment response.

Chronic spontaneous urticaria is characterized by wheals, angioedema, or both for at least 6 weeks and can last for a long time, up to 5 years. The effects of chronic spontaneous urticaria on quality of life are comparable to psoriasis, atopic dermatitis, or even ischemic heart disease.

Antihistamines continue to be the first choice for treatment of urticaria, however rates of response are low (ranging from 38.6% in standard doses to 63.2% in higher doses), some patients don’t experience a complete of symptoms. The use of omalizumab has shown a major advance in treating patients with chronic spontaneous urticaria, however, there is a subgroup of patients who have a partial or even lack of response to omalizumab.

Some of the upcoming targeted therapies for chronic spontaneous urticaria include:

1. anti-IgE antibodies, such as ligelizumab, a monoclonal antibody directed against the Cε3 domain of IgE and which has shown a six- to ninefold greater potency in vivo compared to omalizumab; UB-221, another monoclonal antibody against IgE with up to eightfold greater affinity for free IgE, compared to omalizumab; quilizumab, a humanized monoclonal antibody directed against membrane-bound IgE.
2. Anti-Siglec-8. Siglecs are a transmembrane family with regulatory effects on intercellular and intracellular signaling, with Siglec-8 having expression on eosinophils and mast cells.
3. Bruton’s Tyrosine Kinase (BTK) inhibitors. BTK is a tyrosine kinase expressed in hematopoietic cells, including macrophages, mast cells and basophils. BTK inhibitors are used to treat different malignancies of B-cell origin. Ibrutinib, dasatinib, AVL-292 and CNX-774 effectively suppressed IgE-induced activation and histamine release from basophils and mast cells.
4. Chemoattractant receptor-homologous molecule expresses on Th2 (CRTH2) inhibitors; Spleen Tyrosine Kinase (SYK) inhibitors; Anti-CD20; Anti-IL-1; Anti-IL-4/13; and Anti-IL-5.

The future treatment of chronic urticaria will probably change once potential new treatments are completely developed.