8th June 2025

Urticaria

Background

Urticaria (hives) is a common cutaneous disorder characterized by well-demarcated raised, erythematous, pruritic welts on the skin. These welts, or “wheals,” vary in size and shape and can appear anywhere on the body. They result from oedema in the dermis as a result of plasma exudate. These wheals can be accompanied by angioedema which, in contrast, are poorly defined areas of swelling of the deeper layers of the dermis, subcutaneous or submucosal tissues of the skin or the mouth. Angioedema is more common around the eyes and lips and is often asymptomatic but can sometimes be painful rather than itchy.

Urticaria can be broadly classified into acute and chronic. Acute urticaria lasts less than six weeks, while chronic urticaria lasts more than six weeks. The exact cause of urticaria is often difficult to determine, but it is thought to be an immune response to a trigger such as an allergen, infection, or physical stimulus. It can occur spontaneously (with no stimulus) or inducible (physical urticaria). The symptoms of physical urticaria are similar to those of other types of urticaria, but they are typically more localized and are triggered by specific physical stimuli. Dermatographism is the most common type of inducible/physical urticaria. Other common types include cholinergic urticaria, a condition that is triggered by an increase in body temperature due to exercise, hot weather, or emotional stress. And primarily driven by the release of acetylcholine which causes small blood vessels in the skin to dilate.

Common drug triggers include aspirin, penicillins, NSAIDs and opiates. These are often termed pseudo-allergens as the urticaria is triggered without a systemic immune response.

Classification 

Acute Urticaria

Acute urticaria is the most common form of the condition. The lifetime prevalence of acute urticaria is approximately 20%. Possible triggers include: 

• Infections (viral and bacterial), 
• Allergens e.g food allergens 
• Drugs – typically ACE inhibitors (due to neurokinin accumulation) and NSAIDs
• Emotional stress 

 Typically, it resolves in hours to days. It is more common in atopic individuals. Severe, acute allergic urticaria may lead to anaphylactic shock. Acute urticaria does not usually involve the lung tissue or cause wheeze in the milder forms, but in anaphylaxis or severe urticaria, this is part of the clinical picture. 

Acute urticaria coupled with fever can be the first sign of COVID-19 infection although this is an uncommon presentation.

Chronic Urticaria

Chronic urticaria is a more severe form of the condition, and it is characterized by the persistence of symptoms for more than six weeks. The symptoms of chronic urticaria are similar to those of acute urticaria, but they can last for several months or even years. Wheeze and respiratory symptoms are not a feature of chronic urticaria. 20-45% of patients presenting with acute urticaria will subsequently develop chronic urticaria.

Epidemiology

Both forms of urticaria are more common in women. Acute urticaria has a lifetime prevalence between 12-24% in Europe. The total urticaria prevalence in children is around 3.4% to 5.4%.

Aetiology 

The primary cells responsible for the pathogenesis of urticaria are basophils and mast cells, degranulation of which results in preformed vaso-mediators such as histamine to be released. The consequence of this is vasodilatation and increased permeability resulting in the manifestation of dermal oedema. IgE-mediated immediate hypersensitivity reaction is the typical mechanism by which mast cells are known to degranulate, however this is not present in all cases. IgE is probably less implicated in chronic urticaria. This is supported by a lack of correlation between IgE levels and disease severity. Patients with chronic urticaria show activation of the extrinsic pathway of the coagulation and fibrinolysis cascade, and this has been shown to correlate with disease activity. The implications are unclear but it suggests a more complex aetiology than simple mast cell degranulation explaining the disease process.

Urticaria is implicated in a host of larger disease processes. The most common of which are:

Table 1: Causes of urticaria (Adapted from (Antia et al., 2018)

Diagnosis

Acute urticaria is often a clinical diagnosis. However, chronic urticaria can have a broader range of differentials and if there is diagnostic uncertainty skin biopsy may be warranted although the results can often be difficult to interpret. Pathology typically reveals oedema in the dermis and dilated blood vessels as well as inflammatory cells. As such, often a skin biopsy will rule out other important differentials such as urticarial vasculitis. Skin prick tests and radioallergosorbent tests (RAST) or CAP fluoroimmunoassay can be used to try to identify specific allergens if the trigger/s are unclear.

Management

The management of urticaria typically involves identifying and avoiding triggers and using antihistamines to reduce symptoms. In cases of acute urticaria, second-generation oral antihistamines such as cetirizine and fexofenadine are often effective. In patients who are having a severe type 1 reaction, an A to E approach and rapid resuscitation including the use of intramuscular adrenaline is required. Very uncommonly, in severe refractory urticaria, a 4 to 5-day short course of oral prednisolone may be warranted.

In cases of chronic urticaria, however, more potent antihistamines or immunosuppressive agents may be necessary to control symptoms. After a trial of maximum-dose second-generation oral antihistamines taken for at least four weeks, patients should be considered for omalizumab or ciclosporin therapy. Corticosteroids have a weak evidence base in the management of the condition and are generally not recommended.

References

• Antia, C., Baquerizo, K., Korman, A., Bernstein, J. A., & Alikhan, A. (2018). Urticaria: A comprehensive review: Epidemiology, diagnosis, and work-up. Journal of the American Academy of Dermatology, 79(4), 599–614. https://doi.org/10.1016/J.JAAD.2018.01.020
• Asero, R., Tedeschi, A., Coppola, R., Griffini, S., Paparella, P., Riboldi, P., Marzano, A. v., Fanoni, D., & Cugno, M. (2007). Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria. Journal of Allergy and Clinical Immunology, 119(3), 705–710. https://doi.org/10.1016/j.jaci.2006.08.043
• Borriello, F., Granata, F., & Marone, G. (2014). Basophils and Skin Disorders. Journal of Investigative Dermatology, 134(5), 1202–1210. https://doi.org/10.1038/JID.2014.16
• Brodell, L. A., Beck, L. A., & Saini, S. S. (2008). Pathophysiology of chronic urticaria. Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, 100(4), 291–298. https://doi.org/10.1016/S1081-1206(10)60588-1
• Cicardi, M., Aberer, W., Banerji, A., Bas, M., Bernstein, J. A., Bork, K., Caballero, T., Farkas, H., Grumach, A., Kaplan, A. P., Riedl, M. A., Triggiani, M., Zanichelli, A., & Zuraw, B. (2014). Classification, diagnosis, and approach to treatment for angioedema: Consensus report from the Hereditary Angioedema International Working Group. Allergy: European Journal of Allergy and Clinical Immunology, 69(5), 602–616. https://doi.org/10.1111/ALL.12380
• Kjaer, H. F., Eller, E., Høst, A., Andersen, K. E., & Bindslev-Jensen, C. (2008). The prevalence of allergic diseases in an unselected group of 6-year-old children. The DARC birth cohort study. Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology, 19(8), 737–745. https://doi.org/10.1111/J.1399-3038.2008.00733.X
• Sheldon, J. M., Mathews, K. P., & Lovell, R. G. (1954). The vexing urticaria problem: present concepts of etiology and management. The Journal of Allergy, 25(6), 525–560. https://doi.org/10.1016/S0021-8707(54)90034-9
• Zuberbier, T., Aberer, W., Asero, R., Abdul Latiff, A. H., Baker, D., Ballmer-Weber, B., Bernstein, J. A., Bindslev-Jensen, C., Brzoza, Z., Buense Bedrikow, R., Canonica, G. W., Church, M. K., Craig, T., Danilycheva, I. v., Dressler, C., Ensina, L. F., Giménez-Arnau, A., Godse, K., Gonçalo, M., … Maurer, M. (2018). The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy: European Journal of Allergy and Clinical Immunology, 73(7), 1393–1414. https://doi.org/10.1111/ALL.13397
• https://dermnetnz.org/topics/acute-febrile-neutrophilic-dermatosis
• https://dermnetnz.org/topics/mastocytosis
• https://dermnetnz.org/topics/urticarial-vasculitis