Urticaria: Varied Presentations and Clinical Trajectories

During his presentation at the American Academy of Allergy, Asthma and Immunology’s 2015 annual conference in Houston, TX, Stephen C. Dreskin, MD, PhD, director of the University of Colorado Allergy, Immunology and Rheumatology Practices, discussed the varied clinical presentations, clinical outcomes, and therapies associated with chronic urticaria (CU).

He said CU is characterized by the presence of hives for six weeks or longer, along with lesions that usually last up to 24-48 hours. In 80% of the cases, CU is spontaneous (CSU), whereas 20% of the cases are related to physical contact.

CSU affects predominantly women (in a 3:1 ratio), and 50% of the cases are characterized by the presence of urticaria only, 40% by the presence of urticaria and angioedema, and 10% by the presence of urticaria/angioedema without urticaria. The differential diagnosis of the clinical subtypes is sometimes difficult.

There is evidence that patients with CSU have autoimmunity, reduced basophil number and function, and precedent or concurrent infections. Based on the literature, Dreskin told the audience that 30% to 50% of patients go into remission in 2 to 5 years.

The presence of immunity in CSU is an important component of the disease. In 1990, it was demonstrated for the first time that some CSU patients were positive for autoantibodies. More recently, in 2000, Confino et al. demonstrated, based on a large cohort study, that 85% of patients with CU developed autoimmunity.

Not surprisingly, CSU patients had higher risk of developing hyperthyroidism and rheumatoid arthritis than healthy populations. These data suggest that defects in the autoimmune system may be present in CSU. Indeed, it has been known for many years that alterations in the number and function of basophils are associated with CSU. In 1998, it was demonstrated that CSU patients have decreased histamine release.

Dreskin emphasized that, regardless of the immunity and changes in basophil function and number, the histology, the severity and prognosis of the diseases are similar. More importantly, the response to CSU therapies is similar. He has also suggested that patients with CSU may develop anti-thyroid antibodies and antibodies against the IgE-FCεR1 receptor.

Next, Dreskin addressed the pharmacological management of CSU. According to the guidelines, there are three steps to follow: first, the use of non-sedating antihistamines; second, the use of sedating antihistamines; and third, the use of anti-inflammatory or immunomodulatory drugs. Unfortunately, not all patients respond equally to these therapies, reflecting that each patient has different severity and pathophysiology. He cited a double-blinded, multi-centered study conducted in 2005 in which researchers showed that patients with CSU presented improvement or worsening of their diseases after treatment with fluticasone and montelukast. Similar results were observed in a study with omalizumab, conducted by Kaplan and collaborators in 2008. He also mentioned a study performed in 2010 by Kessel and collaborators, in which 120 patients were treated with cyclosporine. Of those 120 patients, 20 did not tolerate the use of the drug. Among those who tolerated the drug, 30 had resolution of the disease and 32 were able to return to antihistamine treatment. According to Dreskin, physicians should manage their expectations when treating CSU patients.

To sum up, Dreskin noted that CSU is a very complex disease, resulting in patients with varied presentations and clinical trajectories, distinct resolution time, and varied response to therapy. At present, there are significant unmet needs in the management of CSU.