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Chronic spontaneous urticaria (CSU) can be frustrating. The red, itchy hives are unpredictable, often popping up and fading away for no clear reason. But it can be even more stressful when your CSU symptoms refuse to respond to basic treatment or lifestyle changes.

“If you have CSU, the very definition of the disease means that it lasts for more than 6 weeks, which is hard,” says Ronald Purcell, MD, an allergist at the Cleveland Clinic in Cleveland, Ohio. “But it also often means putting up with intense itching that prevents you from focusing on work and causes you to have trouble sleeping at night.”

These steps might help you find relief when the hives of CSU don’t seem to be going away.

Do Some Basic Testing

The definition of chronic spontaneous urticaria is hives for more than 6 weeks with no known cause, says Jeffrey Cohen, MD, a dermatologist at the Yale School of Medicine. It’s also unclear why some cases are more severe or last longer than others.

But there’s evidence that up to half of people with this condition have an underlying autoimmune disorder. The most common one is Hashimoto’s thyroiditis, Cohen says. It’s a form of hypothyroidism, when the thyroid gland doesn’t make enough hormones.

CSU has also been linked to rheumatoid arthritis, lupus, type 1 diabetes, and even celiac disease. To check for these things, your doctor will most likely do blood tests on things like your thyroid hormones as well as something called your erythrocyte sedimentation rate (ESR), which measures the degree of inflammation in your body.

“If you do have an underlying autoimmune disorder, then your urticaria will most likely improve with standard treatment for the disease,” Cohen says.

Try Medications

If there’s no clear cause for your urticaria, your doctor will probably recommend over-the counter (OTC) antihistamines, says Lindsey Bordone, MD, a dermatologist at Columbia University Medical Center in New York City.

Usually, these are “second-generation” antihistamines like cetirizine (Zyrtec), fexofenadine (Allegra), or loratadine (Alavert, Claritin). You may take much higher doses than normal, such as two to four times the standard dose. Your doctor will watch for side effects like nausea or dry mouth.

Sometimes, this isn’t enough to control CSU symptoms. In these cases, your doctor may want to add another type of antihistamine called an H2 antihistamine. These are found in OTC heartburn meds like cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac).  

An antidepressant and antihistamine called doxepin (Silenor) can also ease chronic hives. Side effects include tiredness, dry mouth, and constipation.

Some of the same receptors in your stomach are also found in your skin, Purcell says, which is why some people’s CSU symptoms respond to these drugs. But they aren’t ideal for long-term use. “H2 drugs inhibit stomach acid, which can make it harder for your body to absorb certain nutrients such as iron,” Bordone says.

Your doctor may add in another kind of prescription drug: leukotriene receptor antagonists, such as montelukast. This group of medications is usually used to treat allergies and asthma, but it has shown promise with CSU, Purcell says. The antibiotic dapsone has also helped some people with CSU.

If your symptoms are really severe, like if you have hives all over your body or if you’re up all night scratching, your doctor may consider a short course of 3 to 10 days of an oral steroid like prednisone. This can help quell some of the inflammation that’s causing your symptoms.

If your CSU doesn’t respond to antihistamines, your doctor can prescribe omalizumab (Xolair). It’s a monoclonal antibody that is FDA-approved to treat CSU in people 12 and older who haven’t found relief with antihistamines. It prevents hives by keeping certain types of cells called mast cells from releasing histamine. You get it through monthly injections at home or in your doctor’s office.

Research shows that combining omalizumab with antihistamine therapy gets rid of CSU in about 80% of cases. “It’s a great treatment that works very well, but it’s expensive, and insurance often doesn’t cover it unless you try other options like antihistamines first,” says Tiffany Owens, MD, an allergist at Ohio State University Wexner Medical Center in Columbus.

Look for Other Forms of Relief

The combination of omalizumab and antihistamines still isn’t enough for some people with CSU. In these cases, immune-weakening drugs such as cyclosporine (Gengraf, Neoral, Sandimmune), methotrexate (Trexall), mycophenolate mofetil (Myfortic, CellCept), or tacrolimus (Astigraf XL, Protopic) may be the best option.  

“These shut your immune system down hard and carry potentially serious side effects, so they need to be used with caution,” Purcell says. Your doctor will keep close watch on things like your blood pressure and kidneys when you’re on these drugs. They’ll usually prescribe them for only a few months.

One important thing to keep in mind is that in the vast majority of cases, CSU goes away with time.

“In my practice, about 95% my patients respond to at least one of these medications,” Purcell says. “Sometimes, it takes a while to find the right drug and to get it to work, which can be frustrating to patients. But it’s very rare for someone not to eventually respond.”

Show Sources

Photo Credit: BCFC / Getty Images


Ronald Purcell, MD, allergist, the Cleveland Clinic.

Jeffrey Cohen, MD, dermatologist, Yale School of Medicine.

Lindsey Bordone, MD, dermatologist, Columbia University Medical Center.

Tiffany Owens, MD, allergist, Ohio State University Wexner Medical Center.

Frontiers in Immunology: “Autoimmune Theories of Chronic Spontaneous Urticaria.”

American Academy of Family Physicians: “Acute and Chronic Urticaria: Evaluation and Treatment.”

UptoDate: “Chronic spontaneous urticaria: Treatment of refractory symptoms.”

Journal of Allergy and Clinical Immunology: “Efficacy of doxepin in the treatment of chronic idiopathic urticaria.”

Medscape: “What is the role of doxepin in the treatment of urticaria (hives)?”

Journal of the American Academy of Dermatology: “Tacrolimus in the treatment of severe chronic idiopathic urticaria: an open-label prospective study.”

International Journal of Dermatology: “Treatment of severe chronic idiopathic urticaria with oral mycophenolate mofetil in patients not responding to antihistamines and/or corticosteroids.”