Before giving up on antihistamines, I always make sure that my patients are maximizing their dosages. It’s safe to take up to four times the daily recommended dose of non-sedating antihistamines. Examples include loratadine, cetirizine, fexofenadine, or levocetirizine.

When high-dose, non-sedating antihistamines fail, the next steps include sedating antihistamines like hydroxyzine and doxepin. Or, we’ll try H2 blockers, such as famotidine, and leukotriene inhibitors like zileuton.

For difficult-to-treat hives, I usually turn to an injectable medicine called omalizumab. It has the benefit of being nonsteroidal and is highly effective in most patients.

Chronic idiopathic urticaria (CIU) is an immunologically mediated disorder. So, in extreme cases, I may use systemic immunosuppressants such as cyclosporine.

The itch from CIU is due to an internal histamine release. Topical agents — including topical antihistamines — are mostly ineffective at managing symptoms.

Take frequent lukewarm showers and apply soothing and cooling lotions when hives erupt and are most itchy. A topical steroid may also be helpful. However, oral antihistamines and omalizumab or other immune-system modifiers will provide far more relief.

Yes, almost all cases of chronic idiopathic urticaria eventually resolve. However, it’s impossible to predict when this will happen.

The severity of CIU also fluctuates with time, and you may need different levels of therapy at different times. There is also always a risk of CIU coming back once it goes into remission.

There are several theories among researchers about what causes CIU. The most prevalent theory is that CIU is an autoimmune-like condition.

In people with CIU, we commonly see autoantibodies directed at cells that release histamine (mast cells and basophils). Additionally, these individuals often have other autoimmune disorders such as thyroid disease.

Another theory is that there are specific mediators in the serum or plasma of people with CIU. These mediators activate mast cells or basophils, either directly or indirectly.

Lastly, there is the “cellular defects theory.” This theory says that people with CIU have defects in mast cell or basophil trafficking, signaling, or functioning. This leads to excess histamine release.

We don’t routinely recommend dietary changes to manage CIU as studies haven’t proven any benefit. Dietary modifications are also not supported by most consensus guidelines.

Adherence to diets, such as a low-histamine diet, is also extremely hard to follow. It’s also important to note that CIU is not a result of a true food allergy, so food-allergy testing is rarely fruitful.

There are several known triggers that can aggravate your hives. Heat, alcohol, pressure, friction, and emotional stress are well-reported to worsen symptoms.

Additionally, you should consider avoiding aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). They can aggravate CIU in many cases. You may continue to take low-dose, baby aspirin when used to prevent blood clots.

OTC non-sedating antihistamines, or H1 blockers, are able to control hives for the majority of people with CIU. These products include loratadine, cetirizine, levocetirizine, and fexofenadine. You can take up to four times the recommended daily dose without developing side effects.

You can also try sedating antihistamines as needed, such as diphenhydramine. H2-blocking antihistamines, such as famotidine, may provide extra relief.

Sometimes, antihistamines (both H1 and H2 blockers) are unable to manage the hives and swelling associated with CIU. When this happens, it’s best to work with a board-certified allergist or immunologist. They can prescribe medications that provide better control.

Your doctor may try stronger sedating, prescription antihistamines first like hydroxyzine or doxepin. They may later try omalizumab if these drugs do not work in treating your symptoms.

We usually don’t recommend oral corticosteroids for people with CIU. This is due to their potential for significant side effects. Other immunosuppressants are occasionally used in severe, unmanageable cases.


Marc Meth, MD, received his medical degree from the David Geffen School of Medicine at UCLA. He completed his residency in Internal Medicine at Mount Sinai Hospital in New York City. He subsequently completed a fellowship in Allergy & Immunology at Long Island Jewish-North Shore Medical Center. Dr. Meth is currently on the Clinical Faculty at the David Geffen School of Medicine at UCLA and has privileges at Cedars Sinai Medical Center. He is both a Diplomate of the American Board of Internal Medicine and the American Board of Allergy & Immunology. Dr. Meth is in private practice in Century City, Los Angeles.