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This is a review of published literature on current and new treatments for chronic spontaneous urticaria.

Chronic spontaneous urticaria is defined as the spontaneous appearance of wheals, angioedema or both for at least 6 weeks due to unknown causes. The management of chronic urticaria frequently overlap with chronic spontaneous urticaria, with the primary aim of the treatment being to eliminate symptoms. Current guidelines recommend H1-antihistamines (up to 4 times the upper limit of normal dosing) with the possible use of an LTRA, H2-antihistamines or alternative ones prior to omalizumab.

A PubMed search was performed to include relevant articles, including studies if they provided information related to the current understanding of the pathophysiology and management of chronic spontaneous urticaria, as well as potential novel therapeutics.

Current treatments include antihistamines, leukotriene receptor antagonists, omalizumab and immunosuppressants. New therapeutics under investigation include new IgG1 and anti-IgE monoclonal antibody with higher affinity for IgE than omalizumab (ligelizumab), targets of receptors regulating inflammatory cell chemotaxis, such as CRTH2/DP2 antagonists (AZD1981), Btk inhibitors (fenebrutinib), anti-siglec-8 monoclonal antibody (AK002) are thought to lead to apoptosis of eosinophils and anti-mediator effects on mast cells, topical syk inhibitors (GSK2646264) and designed ankyrin repeat proteins (DARPins).

Chronic urticaria may affect the quality of life, namely in respect to an increase of psychiatric disorders.

This study aimed at evaluating the published evidence of psychiatric disorders that may coexist with chronic urticaria and the effect of psychiatric treatments on people with urticaria.

A systematic literature search for studies that investigated the existence of psychiatric comorbidity in patients with chronic urticaria was conducted, and twenty-five studies that met all the criteria were identified. Studies to be included in the study had to possess the following features: distinction between chronic urticaria and allergic conditions, direct collection of diagnostic psychiatric data by using clinical interview and standardized questionnaires, International Classification of Disorders criteria or the Diagnostic and Statistical Manual of Mental Disorders criteria for the diagnosis of mental disorders and manuscripts written or publish in English.

Analysis of the included studies showed that almost one out of three patients with chronic urticaria have at least one underlying psychiatric disorder. However, no studies clarified if the psychiatric disorder pre-existed at chronic urticaria onset and no association between chronic urticaria severity and duration and psychological functioning. Only a case report and two case series referred to the psychiatric disorder treatment as improving of urticaria.

This study shows the importance of a multidisciplinary approach involving recognition and management of any psychiatric disorder in addition to urticaria treatment.

Current international guideline classifies chronic urticaria as inducible or spontaneous, whether there is a defined trigger sign or not. However chronic urticaria is unpredictable in its course and duration and persists for several years in many patients.

Antihistamines and omalizumab are the most common treatments for chronic urticaria.

This study reviewed the off and beyond label use of licensed drugs, novel treatments under development and promising new targets.

A search was performed and some of the key messages include that omalizumab should be explored in chronic inducible urticaria, in children with chronic spontaneous urticaria and at higher doses. Off label treatments, such as dupilumab, reslizumab, mepolizumab and benralizumab are showing effectiveness in chronic urticaria. Ongoing clinical trials include more monoclonal antibodies, ligelizumab and UB-221. Other promising treatments under development for chronic urticaria include a CRTh2 antagonist, a monoclonal antibody to Siglec-8, bruton’s tyrosine kinase inhibitors, a Syk inhibitor and dupilumab.

New pathogenically important targets for chronic urticaria include Mas-related G-protein coupled receptor X2, the H4 receptor, C5a and its receptor, and other inhibitory mast cell receptors.

The ultimate goal remains the development of treatments that can prevent chronic urticaria, alter its course and cure it.