URTICARIA

By Gary M. White, MD

Urticaria


Urticaria, or hives, is a common, pruritic, allergic condition of the skin. It often occurs after an IgE-mediated allergic reaction to an allergen such as a food or drug, but some cases are not IgE-mediated.

Clinical

Transient, pruritic, pink, edematous plaques come and go during a 24-hour period. Several subtypes exist including spontaneous urticaria, inducible urticaria, acute urticaria, chronic urticaria, cold urticaria, heat urticaria, delayed pressure urticaria, solar urticaria, and symptomatic dermatographism. Chronic urticaria may be defined as urticaria lasting 6 weeks or longer. Sometimes a questionnaire is helpful.

Chronic Autoimmune Urticaria

Approximately 30% of patients with chronic spontaneous urticaria have antibodies to IgE which gives them the diagnosis of chronic autoimmune urticaria (CAU). Patients with CAU are more likely to have:

Workup for Acute Urticaria

Physical urticarias, also called inducible urticarias, comprise about 20-30% of all chronic urticaria cases and should be identified. They include:

A sample patient questionnaire is available. See also causes of urticaria. For acute urticaria (present less than 6 weeks), key questions involve any new medications, unusual or new foods, or any new infection. If there is recent travel to a tropical country, stool sample for ova and parasites should be sent. Limited blood work may include vitamin D, CBC, ESR, urinalysis, and SGPT or OT. For a differential of urticarial lesions, see urticarial.

Workup for Chronic Urticaria

There is no uniformly agreed upon approach, but the following may be considered. Screen for liver disease in patients who come from areas of high prevalence of hepatitis. Screen for thyroid autoimmunity (e.g., thyroid microsomal and thyroglobulin antibodies) especially in women or in those patients with a family history of thyroid disease [JAAD 1999;40;229]. Vitamin D levels should be measured (see below). SPEP may be obtained to rule out Schnitzler Syndrome.

Treatment

Line Treatment
First Line Oral antihistamines, single or in combination at standard doses.
Second Line Oral antihistamines up to 4x standard dosing
Third Line Omalizumab, cyclosporin or monetelukast.
For Flares Prednisone
Miscellaneous Vitamin D, methotrexate, thyroid

It is important for all patients with urticaria to avoid high-dose aspirin and non-steroidal antiinflammatory drugs (e.g., ibuprofen, naproxen, etc.) as these can worsen the urticaria. Acetaminophen (Tylenol) is okay. H2 blockers are not recommended

Antihistamines

The usual goal of therapy is the complete elimination of symptoms with daily therapy (not on demand). The lowest effective dosing regimen with this effect should be employed.

Second generation non-sedating antihistamines are recommended as initial therapy. Examples include: cetirizine (10 mg Qday-BID), fexofenadine (180 mg QD-BID) and loratadine (10 mg Qday-BID). Some allergists believe cetirizine is the most potent of the H1 blockers. It may be dosed as high as 20 mg BID. Fexofenadine may be the least likely to cause sedation.

First-generation antihistamines are most helpful at night to help with sleep, e.g., diphenhydramine (Benadryl 25 mg Q 1-3 hours up to 12 per day), chlorpheniramine (4 mg), hydroxyzine 10–25 mg, or doxepin 25–50 mg (doxepin has the potential advantage of H2 as well as H1 blockade). Hydroxyzine has a significantly longer half-life than diphenhydramine and may not be preferred as sedation takes time to wear off. Desloratadine (Clarinex) 5 mg daily is also available and has been shown to have clinical benefit.

Doxepin may be given as monotherapy and begun at a dose of 25 mg QHS. If needed after 4 days, the dose may be pushed to 50 mg QHS and even 75 mg QHS. Caution drowsiness.

Combination Therapy

Combining any of the oral antihistamines is often done, with the most sedating given at night. For example, one may give fexofenadine 180 QAM and doxepin 25-50 QHS etc.

Vitamin D

Chronic urticaria has been associated with low vitamin D levels and supplementation improves response to standard therapy [Rasool R, et al. World Allergy Organ J. 2015].

Omalizumab

If antihistamines alone are not sufficient, omalizumab may be tried. Omalizumab, a humanized anti-IgE monoclonal antibody (Xolair) is highly effective against urticaria resistant to high-dose antihistamines. In one study of 51 patients, omalizumab treatment led to complete remission in 83% of chronic spontaneous urticaria and 70% of chronic inducible urticaria patients [J of Derm Science 2014;73;57–62]. The most effective dose in studies has b een 300 mg subQ once every 2-4 weeks. One may start with 150 mg subQ monthly and increase the dose if needed. Almost all patients relapse once the therapy is stopped [JAMADerm March 2014;150;288].

Cyclosporine

Cyclosporine (4-6 mg/kg/day) can be very effective.

Montelukast

Singulair (montelukast) may be given as well.

Prednisone

Prednisone 40 mg/day for 1-2 weeks and even pushed to 60 mg/day for 3 days initially may be needed. One study of antihistamine-resistant urticaria found benefit in a 10-day course of prednisone, 25 mg/day on days 1-3; 12.5 mg/day on days 4-6; and 6.25 mg/day on days 7-10 [J Investig Allergol Clin Immunol 2010; Vol. 20(5): 386-390]. Approximately 50% of patients were able to be controlled with standard doses of antihistamine after one prednisone taper, and an additional 9% after a second.

Methotrexate

Methotrexate 15-20 mg/week in combination with other orals was very helpful in two patients [BJD 2001;145;340].

Low Histamine Diet

A low-histamine diet for a period of 3–4 weeks in patients with chronic spontaneous urticaria reduced symptoms and antihistamine intake as well as to improve quality of life [JEADV 2017;31;650]. There are a variety of internet sources for this diet, e.g. here. Briefly, such a diet avoids cheese, preserved meats, strawberries, raspberries, citrus fruit, bananas, kiwis, plums, papaya and alcohol. It includes foods such as dairy, vegetables, fresh meats, eggs, bread, pasta, rice and certain varieties of fish.

Miscellaneous

If the patient has antithyroid antibodies, a course of levothyroxine might help. Phototherapy with either UVB or PUVA added benefit to oral antihistamines in recalcitrant CU [BJD 2017;176;62].

Pregnancy

Cetirizine and loratadine are category B.

Urticaria in Children

See urticaria in children.

Additional Pictures

Urticaria 1 hour after taking minocycline.
Urticaria Urticaria

Urticaria in a child and annular urticaria.
Urticaria Urticaria

urticaria urticaria urticaria urticaria urticaria

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