Contact Urticaria Syndrome 

Maibach and Johnson^[1] defined contact urticaria syndrome (CUS) 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, continue to be reported. Because the exposure to contact urticariants can be similar to contact irritants (eg, health care workplaces), vigilance is required to ensure that the patient is properly investigated and diagnosed because contact urticaria in the setting of hand eczema may be overlooked.

Contact urticaria syndrome can be described in 2 broad categories: nonimmunologic contact urticaria (NICU) and immunologic contact urticaria (ICU). 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, such as that for ammonium persulfate.

Nonimmunologic contact urticaria is the most frequent 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 be mediated by prostaglandins.

Immunologic contact urticaria is less common in clinical practice than nonimmunologic contact urticaria. Immunologic contact urticaria is a type 1 hypersensitivity reaction mediated by immunoglobulin E (IgE) antibodies specific to the eliciting substance. Therefore, prior immune (IgE) sensitization is required for this type of contact urticaria. Sensitization can be at the cutaneous level, but it may also be via the mucous membranes, such as in the respiratory or gastrointestinal 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. In addition, it has been shown for immunologic contact urticaria to latex that exposure through mucosa or dermatitic skin enhances the risk of developing immediate hypersensitivity.

Immunologic contact urticaria reactions may spread beyond the site of contact and progress to generalized urticaria. When more severe, immunologic contact urticaria may lead to anaphylactic shock. One such example is immunologic contact urticaria from natural rubber latex. Typically, latex gloves cause a wheal and flare reaction at the site of contact. This reaction can affect either the person wearing the gloves or the person being touched by the person wearing the gloves. In addition to direct skin contact, allergy may be caused by airborne natural rubber latex. Thus, sensitized, yet undiagnosed, individuals are at risk when in contact with airborne immunologic contact urticaria allergens.

Cross-allergy can also induce immunologic contact urticaria reactions. The patient may be sensitized to one protein and react to other proteins that contain the same or similar allergenic molecules. 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.^[2] This phenomenon places patients with immunologic contact urticaria at further risk.

Both immunologic contact urticaria and nonimmunologic contact urticaria can display site specificity; for example, the neck and perioral areas are more sensitive than the forearm.^[3] This finding can be important in diagnostic testing.

Frequency

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 requires care because the demography of the occupations concerned may not reflect that of the general population.

In a Hawaiian study, Elpern studied the relationship of contact urticaria syndrome in regard to race, sex, and age; the results of the study are described in the relevant sections below.^{[4, 5]} He demonstrated that 46% of patients with contact urticaria syndrome had a personal history of atopy, whereas 44% had a family history of atopy. Only 21% of patients without contact urticaria syndrome had a personal history of atopy.

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 as determined by the AlaSTAT (Diagnostic Products; Los Angeles, Calif) assay and confirmed by the CAP assay (Pharmacia Diagnostics; Dublin, Ohio).^[6]

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 health care workers remains high in the United States in comparison to falling rates worldwide.^[7] In their study based on patch test clinic attendees, they found that 13% of health care workers were sensitized to latex. Atopic persons and health care workers who have a coexisting type IV allergy (allergic contact dermatitis) may be predisposed to latex type I sensitization, although the precise contribution of these risk factors is unclear and may be compounded by the presence of irritant dermatitis, which is widespread in health care workers.

International

Kanerva et al gathered statistical data on occupational contact urticaria in Finland.^{[8, 9]} The incidence more than doubled from 89 reported cases in 1989 to 194 cases in 1994. 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 3 groups comprised 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.

In Germany, powdered natural rubber latex gloves have been banned in the workplace since 1998, with an 80% decrease in occupational contact urticaria in health care workers by 2002.^[10] A Singaporean study has shown no difference in sensitization between operating staff and other health care workers (8-9% sensitized).^[11] This contrasts with older Finnish data,^[12] 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%.

An older Polish study of patients attending an urticaria clinic describes that contact urticaria constituted an estimated 1.1% of all urticaria cases seen at the clinic. In contrast to the Hawaiian study, in this study, only 1 of 5 patients had a personal or family history of atopy.

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, these 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.^[13]

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.^[14] Given the high volume of cesarean deliveries performed, obstetric and anesthetic staff must be vigilant for latex allergy because early intervention can be life saving.

A large Australian retrospective study of patients attending an occupational dermatology clinic also found health care workers to be particularly at risk, but it 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.^[15]

Mortality/Morbidity

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 nonimmunologic contact urticaria. 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).

Race

Elpern's studies^{[4, 5]} demonstrated no difference in racial predisposition. White, Asian Filipino, Asian Japanese, and Hawaiian/part Hawaiian were the major groups studied.

Sex

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 urticariants in the groups studied.

Age

In the Hawaiian demographic study of contact urticaria syndrome, the incidence was constant from the second to the eighth decade. Patients at the extremes of age constituted a smaller proportion of persons with the condition.^[5] The Australian study of occupational contact urticaria found a mean age of 31 years (range 15-79 y).^[15] However, children with spina bifida are affected much younger, showing evidence of latex sensitization/allergy at approximately 12 years.^[13]