URTICARIA: DIFFICULT TO DIAGNOSE, HARD TO TREAT
management of urticaria--one of the most common dermatological conditions--can
be a challenge. While acute cases of urticaria often are caused by an allergic
reaction or a viral infection, the etiology of chronic cases may be more difficult
to determine, according to new guidelines developed by a task force of allergists.
"With chronic or recurrent urticaria, the inciting event may have 'come and gone'--eg, a viral prodrome in a child who presents with recurrent bouts of urticaria during the winter, or purported viral antigen exposure stimulating thyroid autoimmunity and subsequent chronic urticaria in an adult at a much later date," explained co-author of the guidelines David L. Goodman, MD. "Even with acute urticarial syndromes, the exposure that triggered urticaria may have been such an ordinary or common exposure that the patient may not readily recall it."
The Diagnosis and Management
of Urticaria: A Practice Parameter, which was designed for both allergy specialists
and primary care physicians, presents separate diagnostic and management algorithms
for acute and chronic urticaria. Physicians should suspect urticaria in patients
who present with wheals that are pruritic, erythematous, and circumscribed.
The condition may or may not be accompanied by angioedema, which is subcutaneous swelling that usually occurs in areas of loose connective tissues (eg, face, eyelids, and mucous membranes in the lips or tongue).
MANAGEMENT OF ACUTE CASES
Acute urticaria is defined
as an episode of urticaria (with or without angioedema) lasting less than six
weeks. The cause of acute cases often is apparent because symptoms occur soon
after exposure to the trigger (eg, drug administration, exposure to cold, food
allergy, or an insect sting). To determine the cause, physicians should ask patients
about the following:
Recent use of medications
(including herbal agents and supplements).
Food exposures, including
ingestion, inhalation, and contact.
Physical triggers (eg, cold,
physical activity, heat, sweating, pressure, and sun [or light] exposure).
Viral infections, including
respiratory viral infections, viral hepatitis, and infectious mononucleosis.
Exposure to allergens or
Recent insect sting or bite.
Patients presenting with acute urticaria should be evaluated for systemic diseases that can manifest as that and/or as angioedema. For example, the presence of an enlarged thyroid suggests an autoimmune disorder and/or hormonal dysregulation; lymphadenopathy or visceromegaly may result from an underlying lymphoreticular neoplasm; and joint, renal, central nervous system, skin, or serous surface abnormalities are suggestive of a connective tissue disorder. If an underlying cause cannot be identified at this point, a limited laboratory diagnostic evaluation may be necessary to identify occult underlying conditions. The evaluation should include a complete blood count with white blood cell (WBC) differential, urinalysis, erythrocyte sedimentation rate, and liver function tests.
Treatment can be initiated during or following patient evaluation. In cases that involve anaphylaxis, treatment should take precedence over diagnostic evaluation; epinephrine should be used in life-threatening situations. Removal of triggers of urticaria/ angioedema (such as alcohol ingestion or use of nonsteroidal anti-inflammatory drugs) also may be beneficial.
Antihistamine therapy is the cornerstone of treatment for acute urticaria, according to the guidelines. Because first-generation H1-antihistamines can cause daytime sedation, use of second-generation H1-antihistamines is preferable. H2-antihistamines can be added if adequate hive control has not been achieved. In addition, tricyclic antidepressants with potent H1- and H2-antihistamine properties, such as doxepin, may be helpful; however, the side effects of these agents may limit their tolerability. Short courses of oral glucocorticosteroids also can be used, if necessary.
MANAGEMENT OF CHRONIC CASES
The longer urticaria persists, the harder it is to pinpoint the exact cause. Cases lasting longer than six weeks are labeled chronic. Referral to an allergist or immunologist may be warranted at this point, especially when the cause cannot be determined.
The differential diagnosis
of chronic urticaria/angioedema should include the factors listed in Table 1.
Diseases that can mimic chronic urticaria include erythema multiforme minor, nonspecific
maculopapular exanthemata, and mast cell releasability syndromes (eg, urticaria
pigmentosa and urticarial vasculitis). The following tests may be useful in detecting
etiology: a complete blood count with WBC differential, erythrocyte sedimentation
rate, urinalysis, and liver function assays.
Factors That Should
Be Included in the Differential Diagnosis of Chronic Urticaria/Angioedema
- Complement-mediated disorders.
- Cutaneous or systemic mastocytosis.
- Mixed connective tissue diseases.
- Cutaneous blistering disorders (eg,
bullous pemphigoid and dermatitis herpetiformis).
| Data extracted from Wanderer
et al. Ann Allergy Asthma Immunol. 2000.
Because up to 28% of patients diagnosed with urticaria/angioedema have thyroid autoantibodies, it may be helpful to obtain a thyroid function panel with thyroid peroxidase antibody assay. Small doses of thyroid hormone or an adjustment of ongoing thyroid hormone supplementation benefit some patients with thyroid autoantibodies.
"The effective longitudinal management of chronic urticaria requires excellent rapport between physician and patient, and constant vigilance to uncover clues to the etiology that may facilitate resolution or control of the hives," said Dr. Goodman, who is Medical Director of the Allergy and Asthma Consultants of the Rockies, in Englewood, Colorado. "With the advent of newer, non-sedating or low-sedating antihistamines, achieving control of chronic urticaria can frequently be achieved without compromising the patient's safety or functional status, which were often considerations with soporific, older antihistamines. These newer agents should be considered by primary care physicians, patients, and insurers to be the cornerstone of therapy and should thus be available for use with the least formulary restrictions feasible," he explained.
If antihistamines are ineffective, oral glucocorticosteroids or other anti-inflammatory agents (eg, antileukotrienes, dapsone, colchicine, and cytotoxic drugs) may be considered. Additional testing may also be worthwhile. "For patients with refractory chronic urticaria, it may be important to perform a skin punch biopsy to elucidate the underlying cellular influx; ie, lymphocytic predominant perivascular cellular infiltrates may indicate the potential for responsiveness to treatment with antihistamines," said Dr. Goodman. "In contrast, polymorphonuclear predominant perivascular cellular infiltrates may indicate the need for oral glucocorticosteroids or other anti-inflammatory agents to achieve control of the process."
CHRONIC CONDITIONS AND PATIENT QUALITY OF LIFE
"Chronic urticaria is an often debilitating illness, with significant effects on quality of life in all arenas of the human experience," Dr. Goodman concluded. "Many patients with chronic hives find that controlling their disease is a significant hurdle, and they also find that getting answers about their condition, or even expressing their concerns, is an equal challenge." He added, "If we can heighten the sensitivity of health care providers who interface with urticaria patients to the level of disease morbidity that accompanies this disorder--and by doing so, engage those providers in empathic, compassionate care for their patients, bolstered by a comprehensive evaluation and management approach--then the years of constructing this practice parameter will have been well worthwhile for the Joint Task Force."
--Kristin Della Volpe
1. Wanderer A, Bernstein IL, Goodman DL, et al, eds. The diagnosis and management
of urticaria: a practice parameter. Ann Allergy Asthma Immunol. 2000;85(part