Contact Urticaria Syndrome

Updated: Dec 09, 2016
  • Author: Saqib Bashir, MB, ChB, MD, FRCP; Chief Editor: Dirk M Elston, MD  more...
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Maibach and Johnson [1] defined contact urticaria syndrome in 1975; since then, numerous reports of contact urticaria syndrome caused by a variety of compounds, such as foods, preservatives, fragrances, plant and animal products, and metals, have been made. Because exposure to causal agents for contact urticaria can be similar to exposure to contact irritants (eg, in healthcare workplaces), vigilance is required to ensure that the patient is properly investigated and diagnosed. (See Etiology, Presentation, and Workup.) See the image below.

Urticaria associated with a drug reaction. Urticaria associated with a drug reaction.

Contact urticaria syndrome can be divided in two broad categories: nonimmunologic contact urticaria and immunologic contact urticaria. The former does not require presensitization of the patient's immune system to an allergen, whereas the latter does. However, some contact urticaria reactions of unknown mechanism are unclassified and associated with generalized histamine-type reactions. (See Etiology.)


The following staging system for contact urticaria syndrome has been described by Amin and Maibach [2] (see Presentation and Workup):

  • Stage 1 - Localized urticaria (redness and swelling); dermatitis (eczema); nonspecific symptoms (eg, itching, tingling, burning sensation)
  • Stage 2 - Generalized urticaria
  • Stage 3 - Bronchial asthma (wheezing); rhinitis, conjunctivitis (eg, runny nose, watery eyes); orolaryngeal symptoms (eg, lip swelling, hoarseness, difficulty in swallowing); GI symptoms (eg, nausea, vomiting, diarrhea, cramps)
  • Stage 4 - Anaphylactoid reactions (shock)

Stages 1 and 2 are characterized only by cutaneous reactions, while stages 3 and 4 demonstrate extracutaneous and systemic reactions.



Immunologic contact urticaria reactions are considered immediate IgE-mediated reactions that may spread beyond the site of contact and progress to generalized urticaria. When more severe, immunologic contact urticaria may lead to anaphylactic shock. This can happen, for example, as a result of contact with natural rubber latex. Typically, latex gloves cause a wheal and flare reaction at the site of contact but can generalize to anaphylaxis. Nonimmunologic contact urticaria is thought to be caused by the direct release of vasoactive substances from cells or potentially other granulocytes. However, the precise mechanisms by which both immunologic and nonimmunologic urticaria are elicited remain poorly defined.



Nonimmunologic contact urticaria  [3]

Nonimmunologic contact urticaria is the most common immediate contact reaction and occurs without prior sensitization in most individuals who are exposed. The symptoms may vary according to the site of exposure, the concentration, the vehicle, the mode of exposure, and the substance itself.

The mechanism of nonimmunologic contact urticaria is incompletely understood. Previously, histamine was assumed to be released from mast cells in response to exposure to an eliciting substance. However, evidence suggests that nonimmunologic contact urticaria may also be mediated by prostaglandins.

Immunologic contact urticaria

Immunologic contact urticaria is less common in clinical practice than is nonimmunologic contact urticaria but is typically more severe and can result in anaphylaxis. Immunologic contact urticaria is a type 1 hypersensitivity reaction mediated by IgE antibodies specific to the eliciting substance or antigen. Therefore, prior immune (IgE) sensitization is presumed to be required for this type of contact urticaria. Sensitization can be at the cutaneous level, but it may also be via other mucosal sites such as in the respiratory or gastrointestinal (GI) tract. The latter 2 routes of sensitization have frequently been reported among patients with immunologic contact urticaria to latex.

Persons with atopic dermatitis are predisposed to immunologic contact urticaria.

Cross-sensitization can also induce immunologic contact urticaria–type reactions. The patient may be sensitized to one protein and cross-react to other proteins that contain the same or similar antigenic components. In the example of latex allergy, patients may experience symptoms from banana, chestnut, and avocado, as well as a number of other fruits, vegetables, and nuts. [4] This phenomenon places patients with immunologic contact urticaria at increased risk for allergy to multiple substances.

Causative agents

Some of the more commonly reported causes of nonimmunologic contact urticaria include the following [5, 6, 7] :

  • Benzoic acid
  • Dimethylsulfoxide (DMSO)
  • Cinnamic aldehyde
  • Sorbic acid
  • Cobalt chloride
  • Trafuril (Ciba)
  • Polyaminopropyl biguanide (in wet wipes) [8]
  • Melon peel [9]
  • Levofloxacin hydrate ophthalmic solution [10]
  • Animal hair (ferrets) [11]

In some patients, nonimmunologic contact urticaria may account for cosmetic intolerance syndrome. [12, 13]

Reported causes of immunologic contact urticaria include the following [5, 14, 6, 15] :

  • Natural rubber latex
  • Raw meat and fish
  • Potatoes
  • Phenylmercuric propionate
  • Hair dye (in a hairdresser) [16]


Food handlers can develop contact urticaria in response to vegetables, raw meats, and fish and shellfish. [6]

Airborne agents

Importantly, causative agents may be airborne (eg, in a manufacturing facility, plant/animal dander exposure).

For example, some caterpillars (eg, Thaumetopoea pityocampa) have fine hairs that can become scattered and airborne, leading to exposure among forestry workers and recreational visitors to endemic areas, including children. [17] Affected personnel in one study included pinecone or resin collectors, woodcutters, farmers, and stockbreeders. [18] The mechanism is an immunologic contact urticaria that can lead to severe reactions; in one cohort of 16 patients, 80% had angioedema and 14% had severe anaphylaxis. Wheals were seen primarily on the neck and forearms. [19]



Occurrence in the United States

Much of the epidemiologic data regarding contact urticaria syndrome is from occupational studies, which may therefore skew the reported etiologies. Little data exist regarding contact urticaria syndrome in the general population. Extrapolation of occupational data is difficult because the demography of the occupations concerned may not reflect that of the general population.

Despite the well-known risks of latex allergy in health care workers, Suneja and Belsito suggest that the incidence of immunologic contact urticaria to latex in healthcare workers remains high in the United States, in comparison to falling rates worldwide. [20] In their study based on patch test clinic attendees, they found that 13% of healthcare workers were sensitized to latex.

Atopic individuals and healthcare workers who have a coexisting type IV allergy (allergic contact dermatitis) may be predisposed to latex type I allergic reactions, although the precise contribution of these risk factors is unclear and may be compounded by the presence of irritant dermatitis, which is widespread in healthcare workers.

In a study of volunteer blood donors in southeastern Michigan, none of whom was a medical or dental professional, Ownby et al found that 6.4% had IgE-mediated hypersensitivity to latex. [21]

International occurrence

An older Polish study of patients attending an urticaria clinic found that contact urticaria constituted an estimated 1.1% of all urticaria cases at the facility.

Occupational contact urticaria

Kanerva et al gathered statistical data on occupational contact urticaria in Finland and found that the incidence more than doubled between 1989 (89 cases reported) and 1994 (194 cases reported). [22] Between 1990 and 1994, 815 cases were reported. The most common causes (in decreasing order of frequency) were cow dander, natural rubber latex, and flour/grains/feed.

These causal agents accounted for 79% of all cases. Reflecting on this data, the most affected occupations (per 100,000 workers), in decreasing order of frequency, were bakers, preparers of processed food, and dental assistants.

A large, retrospective Australian study of patients attending an occupational dermatology clinic found healthcare workers to be particularly at risk for contact urticaria from natural rubber latex, but the study also highlighted chefs and hairdressers as being at risk of nonlatex-related contact urticaria. Although a wide variety of industries can be affected, the top 3 were health care, food service, and hairdressing/beauty salons. [23]

In Germany, powdered natural rubber latex gloves have been banned in the workplace since 1998. By 2002, an 80% decrease had occurred in occupational contact urticaria in German healthcare workers. [24]

A Singaporean study showed no difference in sensitization between operating staff and other healthcare workers (8-9% sensitized). [25] This contrasts with older Finnish data, [26] which reported that operating staff were more likely to be sensitized. The contrast may represent changing patterns of glove use in modern health care. However, Singaporean hospital workers with no occupational exposure to latex had a latex sensitization prevalence of 3%.

Latex sensitivity in surgical patients

Spina bifida patients are at increased risk of latex sensitization because of early exposure to latex and the number of surgical procedures to which they are exposed. An Italian study of 80 children with spina bifida found that 40% were radioallergosorbent test (RAST) ̶ positive for latex, although only approximately one third of those were actually symptomatic. Nevertheless, symptoms could be severe, including urticaria and angioedema. Those who were either sensitized or clinically affected were more likely to have had surgery on the first day of life and more likely to have had multiple surgical procedures. [27]

Adults undergoing surgery are also at risk of latex immunologic contact urticaria, with a high risk of systemic consequences, because of direct exposure of viscera to the latex-gloved hands of the surgeon. An Italian study of anaphylactic reactions in cesarean deliveries found an incidence of 1:310 (4 of 1240 cases). All were a result of latex sensitivity, with rash and facial edema developing within 30 minutes of skin incision. [28] Given the high volume of cesarean deliveries performed, obstetric and anesthetic staff must be vigilant for latex allergy, because early intervention can be lifesaving.

Race-, sex-, and age-related demographics

In a Hawaiian study, Elpern demonstrated no racial predisposition in contact urticaria syndrome. White, Asian Filipino, Asian Japanese, and Hawaiian/part Hawaiian were the major groups studied. [29, 30]

Occupational and nonoccupational studies have demonstrated a slightly increased incidence of contact urticaria syndrome in female patients. However, this may reflect the exposure of females to causative agents in the groups studied. Regarding age, Elpern found that the incidence of contact urticaria was constant from the second to the eighth decade. Patients at the extremes of age constituted a smaller proportion of persons with the condition. [30]

The aforementioned Australian study of occupational contact urticaria found a mean age of 31 years (range 15-79 y). [23] However, children with spina bifida are affected at a much younger age, showing evidence of latex sensitization/allergy at approximately age 12 years. [27]



The prognosis in contact urticaria syndrome is entirely dependent on the ability of the patient to avoid etiologic substances. However, even in cases of severe immunologic contact urticaria to latex, the long-term prognosis can be good if patients take an active role in controlling their environment by educating themselves and others and by taking all proper precautions.

Morbidity and mortality

A delayed (48-72 h) allergic eczematous contact dermatitis can result from some compounds that produce immunologic contact urticaria and, to a lesser extent, from compounds that produce the nonimmunologic form. When this occurs in occupational contact urticaria syndrome, debilitating hand dermatitis may ensue. If immediate contact reactions are not specifically sought, routine patch testing may miss the diagnosis.

Contact urticaria syndrome can also extend extracutaneously. In a study of 70 German patients with contact urticaria, 51% had rhinitis, 44% had conjunctivitis, 31% had dyspnea, 24% had systemic symptoms, and 6% had severe systemic reactions during surgery. Extracutaneous contact urticaria syndrome has led to anaphylaxis in severe cases and is believed to be a cause of death intraoperatively in some cases (due to allergy to latex). In fact, topical antibiotics such as bacitracin have also been associated with anaphylactic reactions. [31]


Patient Education

Patient education is critical to prevention. For ubiquitous allergens, such as latex, multiple consumer educational sites are available on the Internet. Most of these sites can be accessed from the US Department of Labor Occupational Safety and Health Administration.

For patient education information, see the Allergies Center and the Skin Conditions and Beauty Center, as well as Hives and Angioedema.