By Abby S. Van Voorhees, MD, February 01, 2013
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Nicholas Soter, MD, about his recent Journal of the American Academy of Dermatology article, “The use of mycophenolate mofetil for the treatment of autoimmune and chronic idiopathic urticaria: experience in 19 patients.”
Dr. Van Voorhees: Can you remind us about the differences between autoimmune urticaria and chronic idiopathic urticaria? What are their distinguishing features? Are there laboratory studies that should be utilized to help distinguish between these two types of chronic urticaria?
Dr. Soter: Autoimmune urticaria is a clinical subset of patients with chronic urticaria in whom there is greater pruritus (itching), a greater number of wheals, and a wider distribution of those wheals. They also appear to have more flushing and gastrointestinal features, such as nausea, vomiting, and abdominal pain. There is also an increased prevalence of autoimmune diseases in other family members such as Hashimoto’s thyroiditis, vitiligo, type 1 diabetes, rheumatoid arthritis, and so on. [pagebreak]
These patients can also be distinguished by the fact that they have autoantibodies in their serum that, when incubated with mast cells or basophils, release histamine. This is called the chronic urticaria test. These autoantibodies are directed, for the most part, against a receptor on the mast cell called the high-affinity IgE receptor or against IgE itself. In all patients with chronic urticaria, one ought to order the chronic urticaria test. There’s now also an ELISA test available for the autoantibody against IgE.
Dr. Van Voorhees: Are the treatments for autoimmune urticaria and idiopathic urticaria the same initially? Can you walk us through your first-line treatments for both of these conditions?
Dr. Soter: In both autoimmune urticaria and chronic idiopathic urticaria, one should always begin with the administration of oral H1 antihistamines. Many of my patients end up on three to five different oral antihistamines, often at doses up to four times the normal dose. H1 antihistamines are very safe, and there are European guidelines stating that four times the normal dose of second-generation H1 antihistamines is perfectly acceptable. Second, I would use leukotriene inhibitors. They’re particularly valuable for individuals with salicylate hypersensitivity, but they are also of value in patients with chronic idiopathic urticaria and autoimmune urticaria. We have two of them. The first, montelukast, is active against the receptor. The other agent, zileuton, blocks the enzyme 5-lipoxygenase. In my experience zileuton appeared to work better than does montelukast. Then I move on to the second-line agents, such as other anti-inflammatory agents, particularly colchicine and dapsone. Finally we get to the immunosuppressive agents, such as methotrexate, cyclosporine, mycophenolate mofetil, intravenous immunoglobulin, and omalizumab. [pagebreak]
Dr. Van Voorhees: Your study looked at the role of mycophenolate mofetil as a second-line agent. Tell us what you have found was it useful? Was there a difference between the two types of urticaria? Did patients completely clear? What dose did you use and how quickly did patients respond?
Dr. Soter: Mycophenolate mofetil was used in 19 patients, and both autoimmune and chronic idiopathic urticaria patients were included. Autoimmune patients responded, by which I mean improved, in 91 percent of instances, as did 88 percent of patients with chronic idiopathic urticaria. However, those with autoimmune urticaria seemed to come under complete control more readily. Seventy percent of the patients with autoimmune urticaria achieved complete control, whereas only 30 percent of chronic idiopathic urticaria patients achieved complete control. One presumably can attribute this to suppression of the autoantibodies. Improvement was achieved in three of the other patients with autoimmune urticaria and four of the other patients with chronic idiopathic urticaria. There’s another paper from Israel in which mycophenolate mofetil was used, and significant improvement in urticaria was achieved. [pagebreak]
My starting dose of mycophenolate mofetil is 500 mg twice a day, and I increase the dose by 500 mg twice a day every two to four weeks. It’s a much slower onset-of-action drug than are some of the others. The median time to initial improvement in the patients in the study was four weeks, with a range of one to nine. Complete control was achieved by 12 weeks, with a range of one to 31 weeks. The dose that achieved initial improvement was 1000 mg twice a day with a range of 1000 to 4000 mg a day. The dose to achieve complete control was 2000 mg twice a day, with a range of 1000 to 6000 mg a day. So the doses were rather high.
Dr. Van Voorhees: Of those who responded to treatment with mycophenolate mofetil, were you able to stop therapy or is it necessary to continue treatment without interruptions?
Dr. Soter: We were able to discontinue mycophenolate mofetil in six of the patients who were in complete remission. After discontinuing the drug, complete remission lasted for two to 16 weeks, which was the end of our chart review. However, it tended to recur in all of the patients over time. [pagebreak]
Dr. Van Voorhees: Was this medication regimen well tolerated? What were the side effects that you frequently encountered? Can they be managed?
Dr. Soter: The side effects were few. The most frequent was involvement of the gastrointestinal tract, especially diarrhea. We could often control this, however, with use of H2 antihistamines. Very few patients required discontinuing mycophenolate mofetil because of the diarrhea. There was not an increased risk of infection. We only had one case of viral gastroenteritis, and very importantly when we monitored the patients with laboratory tests there were no changes in complete blood counts, renal function, or liver function tests. This appears to be a very safe drug; in fact, I would say it’s safer than either prednisone or cyclosporine.
Dr. Van Voorhees: Do you think this medication will bump dapsone and colchicine, some of the first-line therapies you’ve listed?
Dr. Soter: No, I think we should still use drugs like leukotriene inhibitors, dapsone, and colchicines before we attempt immunosuppressive agents.