Published Online: February 15, 2015
Chronic urticaria (CU) refers to hives that occur continuously or intermittently for at least 6 weeks. Between 0.5-5% of the world’s population, and up to 1% of the US population is affected. Chronic urticaria has a significant impact on patient quality of life, and is associated with increased poor health and economic costs—with an estimated $244 million related to medications alone. These costs are even more significant when one considers that treatment of CU may be required for many years. Treatment of hives remains a challenge to doctors because there have been no well-defined treatment recommendations based on the presence or absence of specific patient characteristics. The most recent Joint Task Force Practice Parameter (JTFPP) for hives recommends a four step approach for the treatment of CU but it doesn’t link the step care approach to objective patient characteristics. In this issue of The Journal of Allergy and Clinical Immunology: In Practice, Dr. Amin and co-investigators studied patient characteristics including sex, age, duration of hives, prior medication use and blood or tissue markers of hive patients associated with their response to treatment. Of note, this study was conducted prior to the FDA approval of Xolair for hives.
The authors of this study performed a chart review of patients with chronic hives older than 18 seen by a large allergy practice between January 1, 1991 and January 1, 2011. Patients with at least four or more clinic visits for chronic hives with a complete medical record that would allow for assessment of their hives before and after treatment were included in this study. A total of 221 patients were included. Information was collected about patient demographics, medication use and treatment response at each clinic visit, blood testing, skin biopsy results, and family history. Complete control of chronic hives was defined as no hives for at least 30 days on medications and at least one of the following criteria: the first visit when no new medications were added (i.e., a step up in therapy was not required) or the first visit where a step down in medications was made. Partial control of CU was defined as a decrease in the frequency and/or severity of the urticaria episodes after starting or changing a medication(s) and remission was defined as no hives for 3 months off all medications. Statistical methods were used to identify significant associations.
Amin et al. found that the majority of patients achieved complete control (n=140/221). In the controlled group, combined therapy with a 2nd generation antihistamine and a leukotriene receptor blocking agent was associated with the highest rate of control compared to all other medication combination options. Although chronic hives with physical urticaria was generally more difficult to control, use of a 1st or 2nd generation antihistamine or leukotriene receptor blocking medication was associated with significantly better hive control in patients with dermatographia. The presence of thyroid antibodies were found in 28% of patients similar to other reports and these patients had almost a 3.5 times higher likelihood of obtaining control of their hives with H1-antihistamines. In patients not controlled on antihistamines and leukotriene blocking agents, addition of either anti-inflammatory or immunosuppressive agents were associated with even better rates of control. 33% of these hive patients obtained control with Cyclosporine. Between 15-25% of hive patients were also controlled on Sulfasalazine, Dapsone and Hydroxychloroquine. Caucasian patients were significantly more likely to have better hive control when treated with Colchicine. This medication was associated with a 32 times better likelihood of hive control in patients with all forms of physical urticaria except dermatographia compared to other anti-inflammatory medications. The presence of dermatographia, other physical urticarias and a neutrophil cell infiltrate on skin biopsy were all associated with more difficult to control CU. However, those patients who had neutrophilic cells in their skin biopsy responded to Dapsone 5 times more effectively than other anti-inflammatory medications.
Specific clinical characteristics were identified based on medication-specific control of disease for some subpopulations of CU patients. The best overall control of CU using Step 1-3 therapies is more likely to be achieved with the use of a 2nd generation H1-antagonist plus a LTRA, and with Cyclosporine when the addition of a Step 4 therapy is required. Although, CU associated with physical urticaria was in general more difficult to control, 1st or 2nd generation H1-antagonist were associated with the highest odds of complete CU control in patients with dermatographia, while the addition of colchicine to Steps 1-3 therapy (Table 4) was associated with the best control for all other types of physical urticarias.
Although the majority of the patients in this cohort achieved control and in some cases complete remission, a substantial number of patients remained symptomatic despite aggressive management with Step 4 therapies available at the time of this analysis—emphasizing a role for additional novel therapeutic agents such as omalizumab in the management of CU.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.