Chronic hives affects up to 1.0% of the U.S. population. It is also known as chronic idiopathic urticaria or chronic spontaneous urticaria or chronic autoimmune urticaria. It can often last up to 5 years (80%) or more (20%). Its highest incidence is between 20 and 40 years of age and woman outnumber men (2:1).
Chronic hives is associated with poor sleep and reduced quality of life. Many of the medications used to treat hives (first generation antihistamines, i.e. benadryl, hydroxyzine) cause severe sedation. Others such as Doxepin work very well to control hives, but common side effects are lethargy, dry mouth and constipation.
Recent stepwise guidelines were published by the Annals of Asthma, Allergy and Immunology regarding the treatment of Chronic Urticaria (chronic hives). Most of the treatment discussed below will apply to patients who have chronic idiopathic urticaria. These are people who get hives for greater than 6 weeks duration with no cause found. Another term for chronic idiopathic urticaria (CIU) that is being used is, chronic spontaneous urticaria (CSU).
We spoke about hives in a previous post.
The literature was reviewed and current recommendations are listed below.
All patients: Avoidance of triggers
Step 1– Nonsedating second or third generation antihistamines taken up to 4 times a day. (i.e. Claritin, Zyrtec, Allegra, Xyzal, Clarinex) Decrease the dose as tolerated.
Step 1B-Montelukast (Singulair) and ranitidine (Zantac) (now off market, Pepcid is an alternative) are not first line, placebo controlled studies are not conclusive for using them Although some patients have benefitted from adding these meds to anti-histamines. Anecdotally, some patients have seen benefit from using them.
Patient response to step 1 is approximately 45%
Step 1C- Depending on which guidelines are followed, a potent antihistamine (i.e. doxepin or hydroxyzine) can be added. Of note, these medications can cause sedation and should be dosed initially at nighttime.
Step 2– Omalizumab 300 mg monthly (Xolair). If no response after 3 injections, (some studies say up to 6 injections) proceed to step 3.
Patient response to step 1 and 2 is 80%.
There is some value of updosing the Xolair for non responders to even up to 600mg every 2 weeks, here we discuss it more in the next blog post.
Step 3– Cyclosporine, 200-300mg a day. For this step, patients need to have their blood urea nitrogen, creatine, urinanalysis and blood pressure checked at the onset, which is repeated in 4-6 week intervals. Cyclosporine is contraindicated in hypertension and patients with compromised renal function. Effect is typically seen within 1 week, it can usually be tapered after a few quiescent months. However, more than 60% of patients experience adverse effects to cyclosporine, which limits its use.
Patient response after step 3 is 93%.
Step 4-Options to consider are dapsone, methotrexate, colchicine, sulfasalazine, hydroxychloroquine, IVIG and plasmapheresis. Studies are mixed for all these other alternatives. To learn more about alternative options, click here Alternative Agents for Refractory Chronic Urticaria Patients
Step 5- If all options fail, low dose, long term corticosteroids may be considered for chronic hives.
Chronic hives can be a difficult disease to treat. Studies have shown that many case have no known cause (idiopathic). At that point the chronic hives are treated with medications to reduce the occurrence. It can be very frustrating for both the physician and the patient as to what is causing the hives to break out daily. Fortunately if the medication guidelines are followed as described above, many times the chronic hives can be well controlled and in many patients spontaneous resolution may occur.
The diagnostic evaluation of chronic hives can consist of a CBC, ESR/CRP, Thyroid panel, thyroid antibodies, ANA, IgG antibody to the alpha subunit of the IgE receptor. There is some controversy whether or not to test liver or renal function for chronic hives. Skin biopsy is performed if the lesions are not clearly hives (possibly cutaneous vasculitis), the lesions last longer than 24 hours, presence of petechiae or purpura or if there is arthralgia, arthritis, fever or any involvement of other organ systems.
Research is still ongoing as to the possible causes of chronic hives, but still to this day a definitive cause for them has not been found in many patients. Chronic idiopathic urticaria is very hard to manage for most patients, it is best to speak with your allergist or allergy doctor what the best course of treatment is for you.
For more information on hives, please see the articles below.
In a recent study titled “Autoimmune Chronic Spontaneous Urticaria Detection with IgG Anti-TPO and Total IgE”, researchers findings were that elevated aTPO (IgG anti-thyroid peroxidase), low total IgE levels, is a useful diagnostic maker for Autoimmune chronic spontaneous urticaria in everyday clinical practice. This is also associated with resistance to antihistamine treatment.
There even seems to be 2 types of autoimmune mechanisms. Type 1 autoimmune (autoallergic) is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type 2b autoimmune CSU is mediated by autoantibodies that activate mast cells, for example, via IgE and Fc epsilon R1, and is present in less than 10% with CSU. Patients can have either type or both. As endotypes, type 1 and type 2b autoimmune chronic spontaneous urticaria may differ in disease course, clinical features and response to treatment.