Description of the condition
Urticaria is a common skin disease triggered by a variety of underlying and potential causes, characterised by the development of wheals (hives), angioedema (swelling of deeper layers of the skin), or both (Zuberbier 2013). The skin lesions, which have a well-defined raised edge, may be round, annular, or serpiginous (having a wavy edge). They are erythematous (reddish) plaques with a central pallor that are variable in size. Urticarial lesions are extremely itchy.
In chronic urticaria, the symptoms persist for at least six weeks by definition and last for three to five years on average. It is quite common for the course of chronic urticaria to last for more than 20 years (Wedi 2008). The first step in the diagnosis of chronic urticaria is based on a thorough history. A physical examination including a provocation test is needed for the second step in diagnosis (Zuberbier 2013). The risk factors cannot be identified in 75% of those with chronic urticaria, as there may be a variety of triggers, such as physical causes; infections; drugs; foods; or vasculitic diseases (Kulthanan 2007; Vonakis 2008), and because of the uncertainty of its cause, it is referred to as chronic idiopathic urticaria.
It is estimated that the prevalence of chronic idiopathic urticaria is approximately 1% of the general population in the United States at any given time, and that figure is considered to be similar in other countries (Gaig 2004; Greaves 2000).
Chronic idiopathic urticaria is a disabling disease having a negative impact on the quality of life as a result of the intense itch (pruritus), which is often worse at night, therefore, causing sleep disturbance and secondary psychosocial problems, such as anxiety and consequent disruption to school and work (Wedi 2008).
Description of the intervention
Spontaneous remission tends to occur at any time and is not associated with urticarial severity. An effective treatment is needed for chronic idiopathic urticaria because of its profound impact on the quality of life. The first-line treatment recommended for urticaria is non-sedating H1 antihistamine (Zuberbier 2009). However, some people with this chronic form of urticaria do not respond to antihistamines. Alternative treatments need to be considered (Zuberbier 2006), and several forms of treatments have been used for chronic idiopathic urticaria, including corticosteroids, ciclosporin, and antileukotrienes (Grattan 2007; Zuberbier 2009). These are outlined below.
Corticosteroids are frequently used in acute urticaria and acute exacerbations of the chronic form of the disease (Grattan 2007; Zuberbier 2009). Corticosteroids may reduce disease duration (Zuberbier 1996) and improve urticarial vasculitis (Grattan 2007), but they should not be used as a long-term medication for urticaria (Grattan 2007).
Ciclosporin is used for people with severe chronic idiopathic urticaria refractory to any dose of antihistamine (Grattan 2007; Zuberbier 2009). Ciclosporin plays a role in the treatment of urticaria through the direct effect on mast cell mediator release (Stellato 1992) and inhibiting basophil histamine release (Zuberbier 2009).
Antileukotrienes are commonly used for people whose urticaria is not well controlled by antihistamines (Grattan 2007; Zuberbier 2009). It might be more effective for chronic urticaria originating from aspirin or food additive hypersensitivity (Di Lorenzo 2006).
Omalizumab, a humanised anti-IgE (immunoglobulin E) monoclonal antibody, has been used in the treatment of severe persistent allergic disease (Maurer 2011). The mechanism by which omalizumab has been used for chronic idiopathic urticaria involves the reduction of the level of IgE autoantibodies and down-regulation of IgE receptor density on cutaneous mast cells (Maurer 2011; Zuberbier 2009).
Phototherapy is beneficial to treatment-resistant patients with chronic idiopathic urticaria by reducing the numbers of mast cells in the upper dermis (Engin 2008; Zuberbier 2009). It has been used as a combination treatment with antihistamines for chronic idiopathic urticaria and symptomatic dermographism (Borzova 2008; Engin 2008).
Dapsone is effective for a small percentage of people with urticarial vasculitis (Kaplan 2012). No high-level evidence has suggested that dapsone is considerably effective for chronic idiopathic urticaria (Kaplan 2012; Zuberbier 2009).
Alternative treatments need to be considered as an add-on to high-dose antihistamine therapy, but it needs clearly stating that corticosteroids should only be used as a short-term intervention.
Why it is important to do this review
Chronic idiopathic urticaria is a complex disease that significantly affects a person's quality of life, although it is not life-threatening. The standard treatment used for its management are H1 antihistamines. Higher doses of H1 antihistamines or H1 antihistamines in combination with H2 antihistamines may be applied in some cases. A Cochrane systematic review (Fedorowicz 2012) has been completed on histamine H2-receptor antagonists for urticaria, and a Cochrane review on H1 antihistamines for chronic urticaria is in preparation (Stanway 2006). Besides antihistamines, there is no standardised evidence base for alternative treatments, although guidelines have been published on the interventions for chronic idiopathic urticaria excluding antihistamines (Zuberbier 2013). Therefore, reviews of randomised controlled trials aiming to evaluate the use of interventions for chronic idiopathic urticaria excluding antihistamines are necessary.
This review will determine the current state of evidence of the non-antihistamine therapies for chronic idiopathic urticaria and will aim to add to the current evidence base to guide clinical decisions on the rational use of such therapies.