If you’ve ever had hives, you know that these red, itchy welts can be very uncomfortable. Most of the time, hives — also known as urticaria — go away on their own. But sometimes, they last weeks or months and doctors can’t figure out a cause. When this happens, it’s known as chronic spontaneous urticaria (CSU).

“It can be very frustrating for patients because unlike other types of hives, we can’t just tell them to avoid a certain allergen or specific triggers like cold or sun exposure,” says Jeffrey Cohen, MD, a dermatologist at the Yale School of Medicine. “CSU can last for months or even years — although most of the time, it does eventually clear up on its own.”

Hives themselves are common. An estimated 20% of all Americans will get them at some point. CSU is much rarer. Less than half of 1% of all people in the United States have ever had it. It happens most often in adults between the ages of 20 and 40, and women are twice as likely to have CSU than men.

What Does CSU Look Like?

CSU looks like any other hives: batches of red or skin-colored welts (wheals) that can appear anywhere on the body, says Michael Cameron, MD, an assistant professor of dermatology at the Mount Sinai Health System in New York. They usually itch and can vary in size and shape. They typically disappear within 24 hours. But unlike acute hives, they come back frequently, with entire episodes lasting more than 6 weeks. There’s also no known trigger.

“Sometimes, when providers take a careful history, the patients may realize that their hives are due to sun exposure or water or due to the pressure from a heavy bag or seatbelt for several hours,” Cameron says. “But for patients with CSU, the source of their hives is a mystery.”

Many people with CSU also get a condition called angioedema, which is puffiness and swelling in places like your lips, cheeks, eyelids, hands, or feet.

What Causes CSU?

The hives of CSU have no clear cause. “Chronic spontaneous urticaria used to be known as chronic idiopathic urticaria, which means we don’t know exactly what causes it,” Cohen says.

Most of the time, if your hives last more than 6 weeks — even if they come and go — your doctor will refer you to a specialist like an allergist or a dermatologist for more specific testing, says Tiffany Owens, MD, an allergist at Ohio State University Wexner Medical Center in Columbus. This will include a physical exam in their office as well as blood tests such as:

• Thyroid hormones. About 30% of the time, people with CSU also have Hashimoto’s disease, an autoimmune disorder that causes your thyroid gland to not make enough hormones. “When you treat the Hashimoto’s, usually the hives themselves completely disappear or at least improve,” Owens says.
• Erythrocyte sedimentation rate (ESR). This looks at the degree of inflammation in your body. If your ESR is high, you may have an autoimmune disorder that’s causing hives. “One theory is that CSU is an autoimmune disease where your immune system is attacking your own allergy cells,” Owens explains.
• Hepatitis. Sometimes, hepatitis B or C can trigger CSU, Owens says.

Is CSU Treatment Different?

If your doctor thinks you have CSU, they will still often start you with the same medications they’d recommend for acute hives — over-the-counter (OTC) antihistamines — but at a different dosage.

“If you have acute urticaria, your doctor may recommend that you take an OTC antihistamine like cetirizine (Zyrtec) or loratadine (Claritin) as needed to treat itching,” Cohen says.  

But with CSU, the focus is to take high levels daily to keep the urticaria from even emerging. Your doctor may have you take three to four times the recommended amount, every day, while watching you closely for side effects such as dry mouth and nausea.

If that doesn’t work, your doctor may try other medications like:

• H2 blockers. Like other antihistamines, these keep the substances that cause itching and hives from attaching to receptors in certain kinds of cells. They’re in heartburn medications like cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac).
• Corticosteroids. Drugs like prednisone may ease swelling and itching. But you won’t take them for long because they can have serious side effects over time.
• Leukotriene modifiers. Medicines like montelukast are often used to treat asthma and allergies but may also help with CSU.
• Doxepin (Silenor). This antidepressant also keeps histamines from attaching to receptors. Side effects include drowsiness, dry mouth, and constipation.
• Dapsone (Aczone). This is an antibiotic that also fights inflammation, Cohen says. Small studies show that it can help people whose hives haven’t responded to traditional antihistamines.
• Immunosuppressants. These medications reduce the strength of your body’s immune system, explains Cohen. They include cyclosporine (Gengraf, Neoral, Sandimmune), methotrexate (Rheumatrex, Trexall), mycophenolate mofetil (CellCept, Myfortic), and tacrolimus (Astagraft XL, Prograf, Protopic).
• Omalizumab (Xolair). This is an injected anti-inflammatory that keeps your cells from releasing chemicals like histamine that are thought to trigger hives, Owens says. It’s not approved to treat any type of hives other than CSU.

The good news is that CSU is usually not permanent. Almost half of people are hive-free within a year.  

“Most of the time, with a little bit of trial and error, we can get CSU under control so that even if they don’t disappear completely, patients can continue to live their lives without too much redness and itching,” Cohen says.