Urticaria and Drug Rashes



Urticaria and cutaneous adverse drug reactions are among the most common skin problems seen in the clinic and hospital. They can be associated with urgent medical conditions such as laryngeal edema and toxic epidermal necrolysis. It is important for a clinician to identify the underlying causes for these disorders.




Urticaria (hives) is characterized by the rapid onset of lesions called wheals that consist of a central mid-dermal swelling with or without surrounding erythema, with associated pruritus, lasting anywhere from 1 to 24 hours. Associated angioedema can sometimes be seen, characterized by swelling of the deeper dermis and subcutaneous tissue lasting up to 72 hours.1 The lifetime prevalence of urticaria is estimated to be approximately 20% and it can present in patients ranging in age from infants to the elderly. Urticaria can be divided into acute and chronic forms and urticaria elicited by physical factors. Acute urticaria is defined as urticaria of less than 6 weeks duration, whereas chronic urticaria lasts more than 6 weeks. Only 5% of patients with urticaria will be symptomatic for more than 4 weeks.


The underlying event leading to urticaria is mast cell degranulation, with release of histamine and other pro-inflammatory molecules. There are numerous stimuli that can lead to mast cell activation through various pathways. The most common cause of acute urticaria is viral infections, particularly of the upper respiratory tract.2 Other common causes of acute urticaria are listed in Table 14-1. Food-induced type I hypersensitivity reactions are a rare cause of acute urticaria in adults, but are a more common cause in children.3

Table 14-1.

Causes of acute urticaria.

Chronic urticaria can be associated with rheumatologic disorders, chronic infections including Hepatitis B and C, sinus infections and Helicobacter pylori, as well as parasitic infections (more common in developing countries).1 In the majority of patients with chronic urticaria, an underlying disease will not be found. Approximately 35% to 40% of cases of chronic urticaria area caused by autoantibodies directed against the IgE receptor of mast cells.4

Angioedema occurs with wheals in approximately 40% of cases of urticaria in adults and possibly more frequently in food-induced urticaria.3 Angioedema without urticaria is often related to drug therapy with angiotensin-converting enzyme (ACE) inhibitors, but may be due to hereditary or acquired complement deficiencies.

The physical urticarias are caused by a physical stimulus leading to mast cell degranulation (Table 14-2).

Table 14-2.

The physical urticarias.

Clinical Presentation


Patients with urticaria usually present with a chief complaint of a sudden onset of itchy spots that they may describe as hives, welts, or welps. A thorough history is important in establishing the diagnosis of urticaria, because the lesions may have disappeared by the time of the office visit. A detailed history is the most effective way to determine an underlying cause of urticaria.5 It is important to inquire about the location, associated pruritus, and especially the duration of the lesions. Any lesions that last for longer than 24 hours should raise suspicion of an alternative diagnosis, such as urticarial vasculitis.

To determine the underlying cause of urticaria, one should inquire about associated symptoms, including those of upper respiratory infection, sinus infection, autoimmune disease, and H. pylori infection. Any symptoms that point to an anaphylaxis-type reaction or to swelling of the throat are important as these are rare, but life-threatening complications. A thorough review of recent medications and foods should be done as these can be triggers for urticaria that usually appears 1 to 2 hours after ingestion. Finally, it is important to ask about any physical stimuli that may be causing the urticaria (Table 14-2).

Physical Examination

Urticaria presents with

  • Wheals, which are white to pink, pruritic, edematous papules or plaques that may be round (Figure 14-1), annular (Figure 14-2), or arcuate. The surface of the lesion is smooth because the pathology is in the dermis, not in the epidermis.

  • The lesions are usually symmetrically distributed and may be on any location of the body.

  • Individual wheals have a rapid onset and last less than 24 hours, but the entire episode of urticaria may last much longer.

  • The skin returns to its normal appearance after the wheals have resolved.

Figure 14-1.

Urticaria on hand. Uniform pink wheals with smooth surface.

Figure 14-2.

Urticaria on back. Multiple annular wheals with central clearing.

Angioedema presents with

  • A sudden onset of diffuse swelling of the lower dermis and subcutaneous tissues, typically involving the lips, periorbital area (Figure 14-3), the hands, and the feet.

  • The tongue, larynx, and the respiratory and gastrointestinal tracts may also be affected.

  • The swelling may persist for up to 3 days. The involved skin returns to its normal appearance after the swelling has resolved.

Figure 14-3.

Angioedema. Swelling of lips and periorbital area (Reproduced with permission from Usatine RP, Smith MA, Chumley H, Mayeaux, Jr. E, Tysinger J, eds. The Color Atlas of Family Medicine. New York: McGraw-Hill; 2009. Figure 143-4).

Angioedema without wheals often has differing underlying causes; therefore, it is important to determine if the primary lesions are wheals, angioedema, or both.

Hoarseness can be a sign of laryngeal edema that can be a life-threatening complication due to airway compromise. Dyspnea, wheezing, abdominal pain, dizziness, and hypotension are clues to an anaphylaxis-like reaction.

All patients with suspected urticaria should be evaluated for dermatographism (Figure 14-4) by scratching the skin with a shearing force (the wooden end of a cotton-tip applicator works well) for approximately 10 seconds and examining for the presence of a wheal in 3 to 5 minutes. Tests for other types of physical urticarias listed in Table 14-2 are best left to specialists.

Figure 14-4.

Dermatographism. Linear wheals appearing 5 minutes after skin was stroked with wooden end of a cotton applicator.

Laboratory Finding

Unless indicated by history, laboratory examination for acute urticaria is usually not helpful in determining the cause of the outbreak. There is an association between Hashimoto’s thyroiditis and chronic urticaria, so it is prudent to check thyroid function studies and thyroid antibodies in such patients. When indicated by history, tests for autoimmune disease and chronic infections should be performed in patients with chronic urticaria. Several tests to check for autoantibodies against mast cell IgE receptor are available; however, the results can be difficult to interpret. A complement (C4) level can screen for acquired or hereditary complement deficiency in patients with angioedema without wheals who are not on angiotensin-converting enzyme (ACE) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs).


The key diagnostic findings of urticaria are sudden onset of pruritic wheals with individual lesions lasting less than 24 hours.

The key diagnostic findings of angioedema are sudden onset of swelling of the mucous membranes or the hands and/or feet. The swelling lasts less than 72 hours.

Differential Diagnosis

  • Urticarial vasculitis: Presents with wheal-like lesions that last for more than 24 hours and may be accompanied by fever, malaise, and arthritis. These findings should prompt a skin biopsy or specialty referral.

  • Viral exanthems: May present with urticarial lesions, which can fade quickly, but these lesions typically last for more than 24 hours.

  • Insect bites: The papular urticarial lesions of insect bites usually have a blanched center and may have a central crust or puncta at the site of the bite (Figure 14-5). The lesions usually last longer than 24 hours.

  • Still’s disease: Associated with juvenile rheumatoid arthritis; may present transient urticarial lesions that last less than 24 hours. Symptoms of arthritis as well as an exceptionally high ferritin level can help distinguish this rare disease.

  • Other: Drug reactions such as fixed drug eruption, Stevens–Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS).

Figure 14-5.

Mosquito bites presenting as papular urticaria. Group of 3 bites with central blanched center.

Only gold members can continue reading. Log In or Register to continue

Jan 15, 2019 | Posted by in Dermatology | Comments Off on Urticaria and Drug Rashes
Premium Wordpress Themes by UFO Themes