CE/CME Chronic Urticaria It’s More Than Just Antihistamines! Randy D. Danielsen, PhD, PA, DFAAPA, PA-C Emeritus, Gabriel Ortiz, MPAS, PA-C, DFAAPA, Susan Symington, MPAS, PA-C, DFAAPA The discomfort caused by an urticarial rash, along with its unpredictable course, can interfere with a patient’s sleep and work/school. Adding to the frustration of patients and providers alike, an underlying cause is seldom identified. But a stepwise treatment approach can bring relief to all. Randy D. Danielsen is Professor and Dean CE/CME INFORMATION rticaria, often referred to as hives, is a of the Arizona School Earn credit by reading this article and common cutaneous disorder with a life- 1 of Health Sciences, successfully completing the posttest time incidence between 15% and 25%. and Director of the U Center for the Future at www.mdedge.com/clinicianreviews/ Urticaria is characterized by recurring pruritic of the Health ce/cme/latest. Successful completion wheals that arise due to allergic and nonallergic Professions at A.T. is defined as a cumulative score of at reactions to internal and external agents. The Still University in least 70% correct. Mesa, Arizona. name urticaria comes from the Latin word for Gabriel Ortiz This program has been reviewed and “nettle,” urtica, derived from the Latin word uro, practices at Breathe is approved for a maximum of 1.0 hour meaning “to burn.”2 America El Paso in of American Academy of Physician Urticaria can be debilitating for patients, who Texas and is a former Assistants (AAPA) Category 1 CME AAPA liaison to the may complain of a burning sensation. It can last American Academy credit by the Physician Assistant for years in some and reduces quality of life for of Allergy, Asthma & Review Panel. [NPs: Both ANCC many. Recently, more successful treatments for Immunology (AAAAI) and the AANP Certification Program and National Institutes recognize AAPA as an approved urticaria have emerged that can provide tremen- of Health/National dous relief. Asthma Education provider of Category 1 credit.] Approval and Prevention is valid until December 31, 2018. It is important to understand some of the Program—Coordinat- ways to diagnose and treat patients in a primary ing Committee. care setting and also to know when referral is ap- Susan Symington LEARNING OBJECTIVES has practiced in • Differentiate between acute and propriate. This article will discuss the diagnosis, allergy, asthma, chronic urticaria. treatment, and referral process for patients with and immunology for • List common history questions chronic urticaria. more than 10 years. required for the diagnosis of chronic She is the current AAPA liaison to the urticaria. PATHOPHYSIOLOGY AAAAI and is • Explain a stepwise plan for treatment Hives most commonly arise from an immuno- President-Elect of of chronic urticaria. logic reaction in the superficial skin layers that the AAPA-Allergy, • Describe serologic testing that results in the release of histamine, which causes Asthma, and should be ordered for chronic Immunology swelling, itching, and erythema. The mast cell is subspecialty urticaria. organization. • Demonstrate knowledge the major effector cell in the pathophysiology of 3 of when to refer patients urticaria. In immunologic urticaria, the antigen The authors have no financial relationships to a specialist for binds to immunoglobulin (Ig) E on the mast cell to disclose. alternative treatment options. surface, causing degranulation and release of histamine, which accounts for the wheals and itching associated with the condition. Histamine binds to H1 and H2 receptors in the skin to cause arteriolar dilation, venous constriction, and in- 36 Clinician Reviews • JANUARY 2018 clinicianreviews.com TABLE 1 Etiology of Urticaria Type Examples Infectious disease Viral infection*; hepatitis; infectious mononucleosis; bacterial, parasitic, or fungal infection Medications Penicillin and other antibiotics, aspirin, insulin, vaccines, allergy injections, morphine, meperidine, codeine, NSAIDs, ACE inhibitors Environmental allergens Grass, animal dander or saliva, insect stings Foods Eggs, milk, wheat, soy, peanuts, tree nuts, fish, shellfish Autoimmune or Autoimmune hives†, collagen vascular disease, malignancy, thyroid disease, hormonal noninfectious causes changes Physical agents Cold, heat, sunlight, pressure, vibration, exercise Psychologic factors Stress, anxiety * Most common cause of acute urticaria. † Most common cause of chronic urticaria. Sources: Arizona Asthma & Allergy Institute5; Wanderer. Hives: The Road to Diagnosis and Treatment of Urticaria. 2004.7 creased capillary permeability, accounting group but is most often seen in children.1 for the accompanying swelling.3 Not all ur- Acute urticaria and angioedema frequently ticaria is mediated by IgE; it can result from resolve within a few days, without an iden- systemic disease processes in the body that tified cause. An inciting cause can be iden- are immune related but not related to IgE. tified in only about 15% to 20% of cases; An example would be autoimmune urti- the most common cause is viral infection, caria. followed by foods, drugs, insect stings, Urticaria commonly occurs with angio- transfusion reactions, and, rarely, contac- edema, which is marked by a greater de- tants and inhalants (see Table 1).1,5 Acute gree of swelling and results from mast cell urticaria that is not associated with angio- activation in the deeper dermis and subcu- edema or respiratory distress is usually self- taneous tissue. Either condition can occur limited. The condition typically resolves be- independently, however. Angioedema typi- fore extensive evaluation, including testing cally affects the lips, tongue, face, pharynx, for possible allergic triggers, can be done. and bilateral extremities; rarely, it affects The associated skin lesions are often self- the gastrointestinal tract. Angioedema may limited or can be controlled symptomati- be hereditary, but its nonhereditary causes cally with antihistamines and avoidance of can be similar to those of urticaria.3 For ex- known possible triggers.1 ample, a patient could be severely allergic Chronic urticaria, sometimes called to cat dander and, when exposed to this al- chronic idiopathic urticaria, is more com- lergic trigger, develop swelling of the lips, mon in adults, occurs on most days of the facial edema, and flushing. week, and, as noted, persists for more than six weeks with no identifiable triggers.6 It FORMS OF URTICARIA affects about 0.5% to 1% of the population Urticaria can be broadly divided based on (lifetime prevalence).3 Approximately 45% the duration of illness: less than six weeks of patients with chronic urticaria have ac- is termed acute urticaria, and continuous or companying episodes of angioedema, and intermittent presence for six weeks or more, 30% to 50% have an autoimmune process chronic urticaria.4 involving autoantibodies against the thy- Acute urticaria may occur in any age roid, IgE, or the high-affinity IgE receptor clinicianreviews.com JANUARY 2018 • Clinician Reviews 37 CE/CME FIGURE 1 there are special evaluations that can con- Dermatographism firm the diagnosis. CLINICAL FEATURES The main feature of urticaria is raised skin lesions that appear pale to pink to erythem- atous and most commonly are intensely pruritic (see Figure 2). These lesions range from a few millimeters to several centime- ters in size and may coalesce. Characteristically, evanescent old le- sions resolve, and new ones develop over 24 hours, usually without scarring. Scratching generally worsens dermatographism, with new urticaria produced over the scratched area. Any area of the body may be involved. From the Latin for “write on skin,” dermatographism is another The lesions of early urticaria may vary name for pressure urticaria, in which pressure applied to skin causes in size and blanch when pressure is ap- increased release of histamine and subsequent development of plied. An individual hive may last min- wheals and itching. utes or up to 24 hours and may reoccur Source: Dr P. Marazzi/Science Source. intermittently on various sites on the body for an unspecified period of time.1,6 (FcR1).3 The diagnosis is based primarily on DIFFERENTIAL DIAGNOSIS clinical history and presentation; this will Other dermatologic conditions may be mis- guide the determination of what types of di- taken for chronic urticaria. Common rash- agnostic testing are necessary. es that may mimic it include anaphylaxis, Chronic urticaria requires an extensive, atopic dermatitis, medication allergy or but not indiscriminate, evaluation with his- fixed drug eruption, ACE inhibitor–related tory, physical examination, allergy testing, angioedema, mastocytosis, contact derma- and laboratory testing for immune system, titis, autoimmune thyroid disease, bullous liver, kidney, thyroid, and collagen vascu- pemphigoid, and dermatitis herpetiformis. lar diseases.3 Unfortunately, an identifiable Patients should be encouraged to bring cause of chronic urticaria is found in only pictures of the rash to the office visit, since 10% to 20% of patients; most cases are id- the rash may have waned at the time of the iopathic.3,7 visit and diagnosis based on the patient’s Several forms of chronic urticaria can description alone can be challenging. Most be precipitated by physical stimuli, such rashes in the differential can be identified as exercise, generalized heat, or sweat- or eliminated through a careful history and ing (cholinergic urticaria); localized heat complete physical exam. When necessary,