Contact Urticaria

Abstract

The term “contact urticaria” was first used by Fisher in 1973 as a pruritic wheal and flare reaction appearing within minutes after the contact of the skin with the substance causing the reaction. The incidence is not clearly known due to misdiagnosis. The causative agents can be plants, food substances, drugs, cosmetic products, chemicals and animal products. Contact urticaria is classified according to the underlying mechanism as non-immunologic (irritant), immunologic (allergic) and mixed (undetermined). It is usually local but can rarely cause systemic symptoms and sometimes result in anaphylaxis. Diagnostic tests include the prick test, open test and RAST test. The main treatment step is avoiding the causative agent.

1. Introduction

The term “contact urticarial” was first described by Fisher in 1973 as a pruritic wheal and flare reaction occurring within minutes after contact with the suspected contact substance [1]. Contact urticaria is accepted as one of the chronic inducible urticaria disorders and is seen in 1–2% of chronic urticaria patients [2, 3]. Although the disorder is thought to be common, its clear incidence is not known due to underreporting and underdiagnosis [4–6]. It is often seen on the face, hands and arms and is characterized by itching, redness and swelling [7]. A wide variety of allergens including animal products, plants, food, chemicals, cosmetics, flavoring, medications, enzymes and metals are responsible for contact urticaria development (Table 1).

Animal-animal derivated products (blood, urine, saliva, seminal fluid, hair), meat, milk, cheese, eggs, honey silk, wool Cosmetic components: hair care products (ammonium persulphate, henna, parafenilendiamin), emulsifiers, fragnances, allantoin, aloe gel Dyes: an azo, anthraquinone or phthalocyanine derivative Enzymes Foods: furits, vegetables, meat, fish, spice, plants, grains Food additives:flavoring, fragnansec, taste enhancer Metals: aluminum, chromium cobalt, copper, gold, nickel, zinc Natural rubber latex Plants: weed, wood, ornamental Preservatives and disenfectants: sodium benzoate, benzoic acid, benzyl alcohol, sorbic acid, formaldehyde, parabens, povidone-iodine, chloramine, chlorhexidine

Table 1.

Contact allergens causing contact urticaria [5, 6].

Contact urticaria is classified according to the underlying mechanism as non-immunologic/irritant, immunologic/allergic urticaria and those with mixed/undetermined pathomechanism [4]. Non-immunologic contact urticaria (NICU) is often characterized by localized reactions regressing within a short time. Immunologic contact urticaria (ICU) occurs as a type 1 hypersensitivity reaction in previously sensitized individuals and there may be involvement in the respiratory and gastrointestinal system in addition to the skin, resulting in anaphylactic reaction [7]. Contact urticarial syndrome (CUS) is characterized by systemic findings occurring within minutes after contact with the contact allergen, and it was first identified in 1975 by Maibach and Johnson [8, 9].

Contact urticaria usually causes a localized and transient reaction and the diagnosis is therefore often missed. However one must consider that it leads to a marked decrease in the patient’s quality of life. It is therefore essential to diagnose the condition and determine the suspect agent.

This chapter reviews the definition of contact urticaria together with the causative agents, diagnostic tests and ways to avoid the disorder together with a survey of the literature.

2. Classification of contact urticaria

2.1. Non-immunologic contact urticaria

Non-immunologic contact urticaria occurs with the first contact of the person to the substance causing reaction. It is the most common type of contact urticaria. NICU is thought to occur with the stimulation of vasogenic mediators without involvement of immunological processes [4]. In addition to nonspecific histamine secretion, leukotriene, prostaglandin, substance A and eicosanoids are also responsible for this reaction [4, 10].

“Stinging nettle (Urtica dioica)” is best known among the agents that lead to NICU. Preservatives, fragrances, foodstuffs, cosmetics, toiletries, topical medications, chemicals and insecticides can also cause NICU (Table 2). The severity and duration of the reaction in NICU vary according to the size of the contact area and the substance. It is characterized by localized redness, swelling, itching and burning. The lesion tends to regress within hours [4]. NICU is mostly seen on the face, antecubital fossa, upper back, upper arm, volar forearm and lower back.

Immunological contact urticaria Acetylsalicylic acid Aminophenazone Bacitracin Benzophenone Benzoyl peroxide Benzylic alcohol Butylhydroxytoluene Cephalosporins Chloramine T Chlorhexidine Chlorpromazine Colophony Copper Di(2-ethylhexyl) phthalate (DOP) Diethyltoluamide I Diglycidyl ether of bisphenol A (DGEBA) epoxy resin Etofenamate Gentamycin Levomepromazine Lindane Methylhexahydrophthalic anhydride Methylmetacrylate Naphthylacetic acid Nickel Neomycin Nylon Oleic acid O-phenylphenate Penicillins Phenoxyethanol Phenylmercuric acetate Platinum salts Polyethylene Polyfunctional aziridine hardener Promethazine Propylene glycol Pyrazolone Rifamycin Wool alcohol Xylene

Non-immunological contact urticaria Acetic acid Amyl alcohol Balsam of Friar Benzaldehyde Benzoic acid Butyl alcohol Butyric acid Capsaicin Chlorocresol Chloroform Cinnamaldehyde Cinnamic acid Cobalt chloride Diethyl fumarate Ethyl alcohol Isopropyl alcohol Nicotinic acid Sodium benzoate Sorbic acid Tar

Immunological/non-immunological contact urticaria Benzocaine Balsam of Peru (Myroxylon pereirae) Formaldehyde Fragrances Iodine Menthol Persulfates

Table 2.

Non protein molecules responsible for contact urticaria.

2.2. Immunologic contact urticaria

Immunologic contact urticaria is a type 1 hypersensitivity reaction after contact of the allergen to the skin and mucosa. It often occurs with IgE sensitization but IgG and IgM can also be responsible for complement activation [10]. The penetration of the allergen to the epidermis results in IgE binding to the mast cells and the secretion of vasoactive substances such as histamine, prostaglandin, leukotriene and quinine [6]. While proteins with a molecular weight over 10,000 lead to sensitization directly, chemicals with a low molecular weight (below 1000) act like a hapten and bind to carrier proteins such as albumin to cause ICU [6, 10].

Atopic individuals are more prone to ICU development [10–12]. The identification and diagnosis of the disorder therefore become difficult especially in individuals with eczema. One of the significant characteristics of the disease is that it is not only related to the skin but can be generalized with respiratory and gastrointestinal system involvement and anaphylactic shock, leading to systemic findings [4]. Protein (animal proteins, plants) and non-protein (chemicals, drugs and metals) materials can cause ICU (Table 3).

Natural rubber latex is the most common allergen held responsible for ICU [4]. Latex is a fluid obtained from the body of the tropical rubber tree (Hevea brasiliensis) and is a natural rubber resource. Latex proteins are allergenic and preserve their antigenic characteristics in the final product. Gloves, catheters, tourniquets, stethoscopes, masks, electrode tips, balloons, condoms, pacifiers, stretch clothes, shoe soles and underwater goggles contain latex [13]. Health workers, cleaning workers and hairdressers are often at risk. However, natural latex rubber is common in daily life and the general population is also at risk in terms of ICU development [13–15]. Cross-reaction with latex has been identified with fruits (avocado, banana, apple and kiwi), vegetables (paprika, carrot, celery, potato and tomato), plants and pollens [4, 16–21]. It must also remember that the raw food protein can show allergenic reaction, but the reaction disappears when these cooked. This applies to raw fish, garlic and herbs in particular [22].

2.2.1. Contact urticaria syndrome

The term “contact urticaria syndrome” was first used in 1975 by Maibach and Johnson to identify the systemic reaction developing after contact with a substance [8]. CUS is more common in ICU, but can also develop in NICU [23]. It is characterized by a heterogeneous clinical picture including systemic findings occurring immediately following a contact urticaria reaction. The systemic involvement consists of four stages identified by von Krogh and Maibach [9] (Table 4). Localized urticaria is seen at stage 1 and generalized urticaria at stage 2. Stage 3 is characterized by bronchial asthma, rhinoconjunctivitis, orolaryngeal syndrome and gastrointestinal dysfunction and stage 4 by anaphylaxis [9]. CUS is characterized by itching, burning and pain associated with an urticarial plaque in the localized form. The disease can result in nasal symptoms, conjunctivitis, bronchospasm, dyspepsia and anaphylactic shock following angioedema. Non-dermatologic symptoms can be seen in 15% of the patients [9].

Animals and their derivates Aminiotic fluid Blood Calf Cow Caterpillar Dogs Guinea pig Horse Hair (human, mice, rat) Jellyfish Mites Pig Plasenta Rat Saliva Serum Silk Urine Worm

Plant and derviates Algae Aloe Birch Camolile Corn powder Elm tree Larch Lime Mulbery Poppy flowers Sunflower seeds Tobacco Tropical woods Tulips

Plant derivates Abietic acid Colophony Cornstrach Latex rubber Turpedine

Vegetables Asparagus Beans Cabbage Celery Fungi Garlic Lettuce Mushroom Mustard Onion Rice Soybean Tomato

Fruit Apple Apricot Banana Kiwi Lemon Lime Mango Orange Peach Peanut Plum Strawbery Watermelon ; Meat: beef, calf, lamb, chicken, Turkey; Fish: cod, crab, frog, seafood, raw fish; Other animal product: cheese, egg, honey, milk

Table 3.

Protein molecules responsible for contact urticaria [6].

Stage 1: Localized urticaria, dermatitis, nonspecific symptoms (itching, tingling, burning, etc.) Stage 2: Generalize urticaria Stage 3: Bronchial asthma, rhinoconjunctivitis, orolaryngeal symptom and gastointestinal dysfunction Stage 4: Anaphylactic and anaphylactoid reaction

Table 4.

Contact urticaria syndrome staging [9].

2.3. Mixed/undetermined pathomechanism

The pathogenesis is not clear for some of the substance, while certain agents result in only immunologic or non-immunologic urticaria. Ammonium persulfate is an example of these substance that can cause contact urticaria with an undetermined pathomechanism [4, 9] (Table 2).

3. Special types of contact urticaria

3.1. Occupational contact urticaria

Skin diseases are the second most common occupational diseases in Europe and occupational contact urticaria (OCU) makes up 1–8% of occupational skin disorders [12]. The most commonly affected professional groups are healthcare employees, food handlers, farmers and hairdressers [24, 25]. Immunologic and non-immunologic contact urticaria types can be seen in OCU. The risk of sensitization against all proteins is high in presence of atopy in OCU [10]. Besides, atopy is also important in OCU associated with NICU [10].

Natural rubber latex is the most commonly identified allergen and this allergy is seen in 1–3% in general population and 5–10% of healthcare workers in Europe [10]. H. brasiliensis proteins are the main responsible agents for natural rubber latex allergy [10]. A reaction against modified proteins (wheat, soy and Croetin Q) that are added to shampoo and especially ammonium persulfate is often observed in hairdressers [26, 27]. Reactions against saliva, amniotic fluid, urine and seminal fluid of animals have been defined in animal handlers, farmers and veterinarians. Dyes cause contact urticaria at significant levels in the cosmetic and industrial sectors [4, 6].

3.2. Oral allergy syndrome (food contact dermatitis)

“Oral allergy syndrome” is used to identify ICU developing in the mucosa [28]. It is characterized by mucosal edema, itching and a burning sensation after contact of the oral mucosa with respiratory allergens [29]. Cross-reactivity between homologous pollen and food allergens is accused in the etiology [29]. The term pollen-food allergy syndrome (PFAS) can therefore also be used [30].

Fruits and vegetables especially apples, carrots, tomatoes, pears, cherries, plums, celery, spices and hazelnuts are the agents that are often blamed for the oral allergy syndrome. The individuals who have oral allergy syndrome frequently suffer from atopy and pollen allergy, therefore a cross allergy against IgE antibodies has been observed [30].

3.3. Physical contact urticaria

Some physical urticaria cases occur following skin contact with hot, cold, light (UV: solar urticaria), water or as dermographism, pressure hives and vibratory angioedema. A physical agent does not cause a reaction alone but leads to the activation of a chemical product in some cases. It is possible to see this mechanism in induced contact urticaria. Benzophenones, chlorpromazine, methenamine hippurate and formaldehyde are included among the agents that can cause such a reaction [31–33].

3.4. Delayed and prolonged contact urticaria

Contact urticaria, protein contact dermatitis and allergic contact dermatitis can sometime coexist. The patients can primarily present with an urticarial lesion and the contact dermatitis and eczematous lesions can develop later [32, 34]. Elm, vaseline and castor oil are agents that often cause delayed and prolonged contact urticaria [10].

4. Diagnosis

The contact urticaria diagnosis is made with a detailed history and dermatologic examination. The detailed history should include the occupation, hobbies, additional systemic disorders and current medication of the patient, and when the lesion started, how long it lasted and the presence of accompanying symptoms (allergic rhinitis, conjunctivitis, gastrointestinal symptoms and angioedema) [7]. An open test, patch test, prick test, scratch test and intradermal test are the test mainly used for diagnosis.

The allergens are properly prepared and applied to the skin of the inner surface of the forearm or back in the open test. The test is conducted both with cooked and uncooked samples of the foods. The evaluation of the contact urticaria response should be performed 45-60 minutes after the contact of allergen with the skin [13]. This duration can be extended to 1 hour if NICU is suspected. A positive response in contact urticaria consists of edema and/or erythema [6].

The test substances for the rubbing test are prepared as in the open test and are applied by rubbing with a finger or cotton swab 15–20 times to increase the absorption. Dermographism should be tested before the rubbing procedure and the test should not be performed with latex gloves. The evaluation is performed 15–20 minutes after the test substances are removed [13].

The short-term patch test can be used to prevent the contact urticarial factors from spreading or drying. In the closed test method, the patch test sites are opened after 20 minutes and the urticarial reaction evaluated [13].

The prick test demonstrates the presence of specific tissue IgE against the allergen. It is used in the diagnosis of immunologic contact urticaria [13]. Commercial antigens in 2–3 ml bottles are used for the test. The test can be conducted on the skin of the inner surface of the forearm or the back. The evaluation is performed 15–20 minutes after the contact of the allergen with the skin. However, the test should be finalized early in case of severe reaction development. The most important point during the test is to use a separate lancet for each allergen and to apply the allergens 2 cm away from each other [13].

After a superficial scratch of 5–10 mm is formed with the lancet, the test substance is applied to the scratch and evaluation is performed 5–20 minutes later [13].

In the closed scratch test, the test substance is applied similarly and then covered. The evaluation of the test is performed 20 minutes later [13].

It is possible to use histamine hydrochloride as a positive control and aqueous sodium hydroxide as a negative control for the prick and scratch tests.

The radioallergosorbent test (RAST) measures specific IgE in the serum. It can be used for the diagnosis of ICU and CUS and also detect cross-allergenicity [16].

If a strong early reaction is suspected, the first step should be specific IgE measurement and it should be followed by non-invasive skin tests (open test-rubbing test and close test) and invasive skin tests (prick test, scratch test and closed scratch test) at the final stage [13]. Besides specific IgE measurement, open test should be used first when a direct puncture test is risky in latex allergy. It should not be forgotten that latex can cause cross-react with fruits, vegetables and seafood, plants and pollen while latex allergy is evaluated [18–21].

It is necessary to discontinue H1 antihistamines for 1 week, H2 antihistamines for 1 day, steroids (if used for longer than 1 week) for 1–3 weeks and phototherapy for a couple of weeks before skin tests [13, 35]. The possibility of an anaphylactic reaction should be considered during skin tests. All skin tests should therefore be conducted in the special clinic where the proper and necessary equipment are available.

5. Prevention and treatment

The first step in the treatment is to avoid and eliminate the allergen. Identification of the allergens is therefore the main step of the treatment [36].

The secretion of histamine and other mediators from mast cells should be prevented to decrease symptoms. The first treatment step consists of 2nd generation H1 antihistamines. The antihistamine dose can be increased if there is no benefit at first. In addition to oral antihistamines, systemic steroid treatment can also be used in severe cases. Conducting the treatment in units where resuscitation can be performed is appropriate for anaphylaxis and anaphylactic shock cases [6].