**1. Introduction**

The term "contact urticaria" 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**).

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

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**Table 1.** Contact allergens causing contact urticaria [5, 6].

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.

#### **2.2. Immunologic contact urticaria**

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

• Preservatives and disenfectants: sodium benzoate, benzoic acid, benzyl alcohol, sorbic acid, formaldehyde, para-

• Animal-animal derivated products (blood, urine, saliva, seminal fluid, hair), meat, milk, cheese, eggs, honey silk,

• Cosmetic components: hair care products (ammonium persulphate, henna, parafenilendiamin), emulsifiers,

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

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.

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, sub-

"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

stance A and eicosanoids are also responsible for this reaction [4, 10].

by Maibach and Johnson [8, 9].

**2. Classification of contact urticaria**

**2.1. Non-immunologic contact urticaria**

the suspect agent.

wool

• Enzymes

• Natural rubber latex

• Plants: weed, wood, ornamental

fragnances, allantoin, aloe gel

48 A Comprehensive Review of Urticaria and Angioedema

• Dyes: an azo, anthraquinone or phthalocyanine derivative

• Foods: furits, vegetables, meat, fish, spice, plants, grains • Food additives:flavoring, fragnansec, taste enhancer

bens, povidone-iodine, chloramine, chlorhexidine

**Table 1.** Contact allergens causing contact urticaria [5, 6].

• Metals: aluminum, chromium cobalt, copper, gold, nickel, zinc

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

#### **Immunological contact urticaria**


**Immunological contact urticaria**

50 A Comprehensive Review of Urticaria and Angioedema

• Di(2-ethylhexyl) phthalate (DOP)

• Methylhexahydrophthalic anhydride

• Diglycidyl ether of bisphenol A (DGEBA) epoxy resin

• Diethyltoluamide I

• Methylmetacrylate • Naphthylacetic acid

• *O*-phenylphenate

• Phenylmercuric acetate

• Polyfunctional aziridine hardener

• Penicillins • Phenoxyethanol

• Platinum salts • Polyethylene

• Etofenamate • Gentamycin • Levomepromazine

• Lindane

• Nickel • Neomycin • Nylon • Oleic acid

• Acetylsalicylic acid • Aminophenazone

• Bacitracin • Benzophenone • Benzoyl peroxide • Benzylic alcohol • Butylhydroxytoluene • Cephalosporins • Chloramine T • Chlorhexidine • Chlorpromazine • Colophony • Copper


#### **Non-immunological contact urticaria**


#### **Immunological/non-immunological contact urticaria**


**Table 2.** Non protein molecules responsible for contact urticaria [10].

#### **Animals and their derivates**


#### **Plant and derviates**


#### **Plant derivates**


#### **Vegetables**

**Animals and their derivates**

52 A Comprehensive Review of Urticaria and Angioedema

• Hair (human, mice, rat)

• Aminiotic fluid

• Blood • Calf • Cow • Caterpillar • Dogs • Guinea pig • Horse

• 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


#### **Fruit**


**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 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].

#### **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**).


**Table 4.** Contact urticaria syndrome staging [9].
