eMedicine Specialties > Dermatology > Allergy & Immunology

Urticaria, Contact Syndrome

Author: Saqib Bashir, MB, ChB, MD, MRCP, Consultant Dermatologist and Dermatological Surgeon, King's College Hospital, NHS Foundation Trust, UK; Research Fellow, Department of Dermatology, University of California, San Francisco, School of Medicine
Coauthor(s): Howard I Maibach, MD, Professor and Vice Chairperson, Department of Dermatology, University of California School of Medicine at San Francisco; Consulting Staff, University of California Hospitals
Contributor Information and Disclosures

Updated: Feb 11, 2009

Introduction

Background

Maibach and Johnson¹ 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.

Pathophysiology

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

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

Clinical

History

• Many agents are capable of causing contact urticaria syndrome; therefore, a detailed history is essential in establishing the etiology.
  • Contact urticaria reactions appear within minutes to approximately 1 hour after exposure of the urticariant to the skin.
  • The patient may report a local burning sensation, tingling, or itching. Swelling and redness may be seen (wheal and flare).
  • The patient may be able to associate the symptoms to exposure to a specific substance. In some cases, this exposure may include the application of cosmetic products, especially to the face (cosmetic intolerance syndrome).
  • Details of the patient's employment provide insight into possible causes in the workplace, especially if the symptoms are temporally related to work.
  • The patient may be able to identify what he or she was doing at the onset of symptoms, again allowing the physician to narrow down the possible causes.
  • The extent of extracutaneous involvement (eg, asthma, rhinitis, conjunctivitis, gastrointestinal upset) should be ascertained.
  • A history of previous anaphylaxis should be sought, as should a personal or family history of atopy.
• A staging system of contact urticaria syndrome has been described by Amin and Maibach.¹⁶
  • Cutaneous reaction only (stages 1 and 2)
    • Stage 1 - Localized urticaria (redness and swelling); dermatitis (eczema); nonspecific symptoms (eg, itching, tingling, burning sensation)
    • Stage 2 - Generalized urticaria
  • Extracutaneous reactions (stages 3 and 4)
    • Stage 3 - Bronchial asthma (wheezing); rhinitis, conjunctivitis (eg, runny nose, watery eyes); orolaryngeal symptoms (eg, lip swelling, hoarseness, difficulty in swallowing); gastrointestinal symptoms (eg, nausea, vomiting, diarrhea, cramps)
    • Stage 4 - Anaphylactoid reactions (shock)

Physical

Signs upon physical examination may be variable depending on when the patient presents to the clinic. At one extreme, the patient may be asymptomatic, while at the other extreme, the patient may have a generalized urticaria with extracutaneous symptoms.

• Skin findings
  • Localized or generalized wheals may be present, especially on the hands, or eczematous skin may be observed if contact urticaria syndrome has progressed to or developed in association with an eczematous dermatitis.
  • By definition, contact urticaria syndrome lesions disappear within 24 hours of onset. Therefore, the skin may appear healthy, depending on when the patient presents to the physician.
  • An ordinal scale to score erythema is as follows¹⁷ :
    • Slight erythema, either spotty or diffuse - 1+
    • Moderate uniform erythema - 2+
    • Intense redness - 3+
    • Fiery redness with edema - 4+
  • An ordinal scale to score edema is as follows¹⁸ :
    • Slight edema, barely visible or palpable - 1
    • Unmistakable wheal, easily palpable - 2
    • Solid, tense wheal - 3
    • Tense wheal, extending beyond the test area - 4
• Respiratory findings
  • The patient may be in varying degrees of respiratory distress if a respiratory component to the contact urticaria syndrome is involved.
  • Rhinitis may be present, and wheezing may be heard upon auscultation.
  • Results of the examination, however, may be normal if the disease is quiescent or if no extracutaneous expression is present.
• Ocular findings: Conjunctivitis may be seen in active extracutaneous disease.

Causes

• Some of the more commonly reported causes of nonimmunologic contact urticaria include balsam of Peru, benzoic acid, cinnamic alcohol, cinnamic aldehyde, sorbic acid, and dimethylsulfoxide.¹⁹ In some patients, nonimmunologic contact urticaria may account for cosmetic intolerance syndrome.
• Reported causes of immunologic contact urticaria include natural rubber latex, raw meat and fish, semen, many antibiotics, some metals (eg, platinum, nickel), acrylic monomers, short-chain alcohols, benzoic and salicylic acids, parabens, polyethylene glycol, polysorbate, and other miscellaneous chemicals.¹⁹
• Food handlers, exposed to a variety of proteins, may develop immunologic contact urticaria or an eczematous reaction known as protein contact dermatitis on the hands and forearms. The 2 phenomena may overlap and may be different clinical appearances of the same IgE-mediated process. Also of note, the development of eczematous skin in food handlers is also likely to have an irritant component, which should be in the clinical differential. The list of triggers is long, but, conveniently, it has been categorized into the following 4 groups²⁰ :
  • Group 1 - Fruits, vegetables, spices, plants, and woods
  • Group 2 - Animal proteins
  • Group 3 - Grains
  • Group 4 - Enzymes
• Processionary pine caterpillars (Thaumetopoea pityocampa) have fine hairs that can become scattered and airborne, leading to exposure amongst forestry workers and recreational visitors to endemic areas, including children.²¹ Affected personnel in one study included pinecone or resin collectors, woodcutters, farmers, and stockbreeders.²² The mechanism is an immunologic contact urticaria, which 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.²³
• Importantly, remember that the causative agent may be airborne, in the correct context (eg, in a manufacturing facility, plant/animal dander exposure).

• Search for CME/CE on This Topic »

• Urticaria, Cholinergic (Dermatology)
• Urticaria (Emergency Medicine)
• Urticaria, Acute (Dermatology)
• Urticaria (Pediatrics: General Medicine)

• Hives and Angioedema Overview
• Hives and Angioedema Treatment
• Hives and Angioedema Causes
• Skin, Hair, and Nails Center
• Hives and Angioedema Symptoms
• Allergy Center

• Omalizumab Safe in Young Kids With Allergic Asthma
• Diclofenac Liquid-Filled Capsules Approved for Pain Relief
• FDA Approves Bepotastine Ophthalmic Solution for Treating "Allergy Eyes"

• Urticaria - A Review
• Mastocytosis With Urticaria Pigmentosa and Osteoporosis
• Selective Immediate Hypersensitivity Reactions to NSAIDs

• Allergy Resource Center