Down regulation of the high-affinity IgE receptor associated with successful treatment of chronic idiopathic urticaria with omalizumab
© Saavedra and Sur; licensee BioMed Central Ltd. 2011
Received: 5 August 2010
Accepted: 19 January 2011
Published: 19 January 2011
Chronic idiopathic urticaria is a condition that is often controllable with antihistamine therapy. However, some patients have disease burden that is difficult to manage, non-responsive to antihistamines and often requires immunosuppressive medications such as corticosteroids or cyclosporine. We present here a study that demonstrates the effectiveness of omalizumab in treating this condition and the temporal relationship between improvement and down regulation of the high affinity IgE receptor (FcεRI). For this, blood samples were obtained from a symptomatic patient before each treatment and processed for flow cytometric analysis of FcεRI levels on the surface of blood basophils. Down regulation of FcεRI was observed in association with significant clinical improvement and discontinuation of immunosuppressive medications.
While approximately 20% of the population will experience an episode of acute urticaria at some point in their lifetime, only 0.1% will experience the scourge of chronic urticaria . This disease is characterized by at least 6 weeks of almost daily episodes of intensely pruritic cutaneous wheals that typically last less than 24 hours and are not associated with residual pigmentation. Half of patients with chronic urticaria are thought to have this disease as a result of autoimmune phenomenon, while the remaining patients are designated as having "idiopathic" disease. It has been estimated that approximately 35-45% of patients possess autoimmune IgG antibodies that target the alpha subunit of FcεRI or, to a lesser extent, target directly the IgE antibody . A link between thyroid autoimmunity and chronic urticaria has also been observed in a subset of patients . Consequently, the evaluation of patients with chronic urticaria may include investigating for thyroid dysfunction and for the presence of microsomal antibodies and/or anti-thyroperoxidase antibodies.
Treatment of patients with chronic urticaria, autoimmune or idiopathic, involves targeting the H1 receptor with sufficient doses of antihistamines that will control the patient's symptoms. When symptoms can not be controlled with maximal doses of antihistamines, immunosuppressive medications such as corticosteroids or cyclosporine are often employed. However, the potential short and long term side effects from these medications make their use less than desirable for both the clinician and patient. Omalizumab is a recombinant monoclonal antibody that selectively binds to IgE and inhibits its binding to FcεRI on the surface of mast cells and basophils. The beneficial effects of this therapy in the treatment of moderate to severe persistent asthma have been well documented . However, the off-label use of omalizumab for treatment of chronic urticaria has shown promise and represents an immunosuppressive sparing treatment option for patients with disease burden that is difficult to manage . Omalizumab has also been shown in a previous study to significantly reduce symptoms in patients with documented chronic autoimmune urticaria . Thus, omalizumab is increasingly becoming an accepted new treatment modality for use in patients with recalcitrant chronic urticaria.
Laboratory values prior to treatment
Thyroid Stimulating Hormone
< 20 mm/hr
Helicobacter Pylori IgG Ab
When compared with the control subject, our patient displayed a five fold greater expression of FcεRI prior to treatment with omalizumab. After the first 14 days of treatment, there was an approximate 80% decrease in the expression of the high affinity IgE receptor that was maintained throughout the duration of treatment. This level of decrease is similar to previous published reports . While mast cells represent the effector cell implicated in chronic urticaria, these experiments utilized antibodies for two surface markers found on the surface of basophils. It has been previously shown that treatment with omalizumab results in a reduction in free IgE and a decrease in FcεRI on blood basophils . Previous studies have also reported that after treatment with omalizumab skin mast cells demonstrate a phenotypic shift and a reduction of surface FcεRI, albeit at a slower rate than is seen with blood basophils . The patient in this study experienced significant improvement after the first treatment, though it was 14 weeks until she was able to completely withdraw from cyclosporine use altogether. This may be due to a slower response for achieving a decrease in mast cell numbers, mast cell function and/or mediator release. Indeed, regulation of mast cell survival is thought to be mediated in part by IgE-FcεRI dependent pathways . While further studies are needed to fully understand the mechanism of efficacy with this new treatment modality, our study points to the importance of decreased FcεRI expression in this process.
Treatment with omalizumab and the resultant down regulation of FcεRI expression is temporally associated with improvement of chronic idiopathic urticaria.
Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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