Contact Urticaria Syndrome

Contact urticaria syndrome is a transient wheal and flare reaction (or urticaria) occurring 10-60 minutes at sites of contact of the skin or mucosa to a suspected allergen. It is a form of acute urticaria lasting less than 6 weeks. Although it is typically a local reaction, it may have distant affects such as anaphylaxis. ^[1] Contact urticaria was first cited in the literature by Alexander Fischer in 1973. ^[2] Thereafter, Maibach and Johnson ^[3] defined contact urticaria syndrome in 1975.

Contact urticaria syndrome can be caused by a variety of compounds, such as foods, preservatives, fragrances, plant and animal products, and metals. Because exposure to causal agents for contact urticaria can be similar to exposure to contact irritants, vigilance is required to ensure that the patient's workplace and household exposures are investigated. (See Etiology, Presentation, and Workup.)

Contact urticaria syndrome can be divided in two 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. The remainder of contact urticaria types are due to unknown mechanisms. ^[2]

The image below demonstrates a visual example of skin lesions described as urticaria. These lesions demonstrate erythema with a ring of surrounding pallor.

The general mechanisms of immunologic contact urticaria (ICU) and nonimmunologic contact urticaria (NICU) are understood. However, the precise molecular mediators and pathways by which both immunologic and nonimmunologic urticaria are elicited remain poorly defined.

Immunologic contact urticaria

Immunologic contact urticaria occurs secondary to allergen interaction with IgE antibody reactions. Owing to its immunologic mechanism, it may spread beyond the site of contact and progress to generalized urticaria. When severe, it 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 into anaphylaxis. Immunologic contact urticaria is less common in clinical practice than is nonimmunologic contact urticaria.

Immunologic contact urticaria is a type 1 hypersensitivity reaction mediated by IgE antibodies specific to the eliciting substance or antigen. Once the IgE antibody binds to the antigen, vasoactive substances such as leukotrienes, prostaglandins, and histamine are released by mastocytes and basophils. ^[4] 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 two 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 because of impaired skin barrier function secondary to filaggrin mutations. Other risk factors include hay fever and asthma. ^[2]

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. ^[5] This phenomenon places patients with immunologic contact urticaria at increased risk for allergy to multiple substances.

Nonimmunologic contact urticaria

Nonimmunologic contact urticaria is thought to be caused by the direct release of vasoactive substances (urticariants) from cells or potentially other granulocytes. These substances cause vasodilation of blood vessels. This reaction does not require prior sensitization to an allergen. ^[6] 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, because patients with nonimmunologic contact urticaria do not respond to antihistamines, this is no longer thought to be the case. Evidence suggests that nonimmunologic contact urticaria may be mediated by prostaglandin D2, owing to its immediate response to treatment with NSAIDs.

Unlike immunologic contact urticaria, nonimmunologic contact urticaria does not lead to systemic manifestations such as anaphylaxis.

Immunologic contact urticaria

The etiologic agents for immunologic contact urticaria can be divided into the following four categories ^[2] :

• Plant-derived proteins (eg, fruits, vegetables, spices)
• Animal-derived proteins (eg, raw meat, raw fish)
• Grains (eg, wheat, barley, rye)
• Enzymes (eg, alpha-amylase)

Reported causes of immunologic contact urticaria include the following ^{[7, 8, 9, 10]} :

• Natural rubber latex (eg, found in urinary catheters)
• Raw meat and fish
• Potatoes
• Phenylmercuric propionate
• Hair dye (eg, at a hairdresser) ^[11]
• Grass
• Animals

Nonimmunologic contact urticaria

The etiologic agents for nonimmunologic contact urticaria can be divided into the following seven categories:

• Animals (eg, arthropods, caterpillars, corals)
• Foods (eg, pepper, mustard, thyme)
• Fragrances and flavorings (eg, balsam of Peru, cinnamic acid, cinnamic aldehyde)
• Medications (eg, benzocaine, camphor, witch hazel)
• Metals (eg, cobalt)
• Plants (eg, nettles, seaweed)
• Preservatives and disinfectants (eg, benzoic acid, formaldehyde)

Some commonly reported causes of nonimmunologic contact urticaria include the following as mentioned above ^{[1, 7, 9, 12]} :

• Benzoic acid (eyedrops)
• Sorbic acid (eyedrops)
• Dimethylsulfoxide (DMSO)
• Cinnamic aldehyde (cosmetics) 
• Cobalt chloride
• Tetrahydrofurfuryl nicotinate (Trafuril, Ciba Laboratories)
• Polyaminopropyl biguanide (eg, in wet wipes) ^[13]
• Melon peel ^[14]
• Levofloxacin hydrate ophthalmic solution ^[15]
• Animal hair (eg, ferrets) ^[16]

In some patients, nonimmunologic contact urticaria may account for cosmetic intolerance syndrome. ^{[17, 18]}

Specific occupational exposures

Food handlers can develop contact urticaria in response to vegetables, raw meats, and fish and shellfish. ^[9] Important to note is that 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. ^[19] Affected personnel in one study included pinecone or resin collectors, woodcutters, farmers, and stockbreeders. ^[20] 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. ^[21]

Occurrence in the United States

Little data exist regarding contact urticaria syndrome in the general population, and the incidence in this population is unknown. Much of the epidemiologic data regarding contact urticaria syndrome are from occupational studies, which may therefore skew the reported etiologies. Extrapolation of occupational data is difficult because the demographics of the occupations concerned may not reflect that of the general population. Those who work in healthcare, food handling, hair salons, and maintenance have higher rates of contact urticaria.

Despite the well-known risks of latex allergy in healthcare 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. ^[22] 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. ^[23]

International occurrence

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). ^[24] 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. The reaction to cow dander is likely related to high exposure, as cattle care kept indoors from September to May/June. ^[1]

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 three were health care, food service, and hairdressing/beauty salons. ^[25]

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. ^[26]

A Singaporean study showed no difference in sensitization between operating staff and other healthcare workers (8-9% sensitized). ^[27] This contrasts with older Finnish data, ^[28] 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. ^[29]

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. ^[30] 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. ^{[31, 32]}

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. ^[32]

The aforementioned Australian study of occupational contact urticaria found a mean age of 31 years (range 15-79 y). ^[25] However, children with spina bifida are affected at a much younger age, showing evidence of latex sensitization/allergy at approximately age 12 years. ^[29]

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 proper precautions.

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.

Immunologic contact urticaria 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. ^[33]

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. Another resource includes the Australasian society of clinical immunology and allergy

Many patient resources do not specifically discuss contact urticaria and only discuss acute urticaria and hives. It is important to discuss with patients the specific nature of contact urticaria.