Protein Contact Dermatitis

The term protein contact dermatitis (PCD) refers to an allergic skin reaction induced by proteins of either animal or plant origin. ^{[1, 2]} The specific criteria for protein contact dermatitis are (1) a chronic dermatitis caused by contact with proteinaceous material, (2) an acute urticarial or vesicular eruption occurring minutes after contact with the causative protein, (3) immediate prick- or scratch-test results that are usually positive, and (4) patch-test results that are often negative. ^[3]

Four groups of proteins can cause protein contact dermatitis: plant, animal, flour, and proteolytic enzymes (see Etiology). Anecdotally, risk factors for the development of protein contact dermatitis include a history of atopy, chronic irritant dermatitis, and an occupation or hobby involving exposure to one of these protein allergens. 

In treatment, avoidance of the particular allergen is of primary importance. Symptomatic relief may be provided with short-term corticosteroids, immunomodulatory agents, or antihistamines (see Treatment).

Go to Irritant Contact Dermatitis, Allergic Contact Dermatitis, and Pediatric Contact Dermatitis for complete information on these topics.

Several theories have been proposed. The most accepted theory is that protein contact dermatitis is a type I immediate hypersensitivity reaction due to high-molecular-weight proteins penetrating the epidermis with superimposed irritant contact dermatitis or allergic contact dermatitis. In fact, this theory is supported by the observation that there is a history of atopy in approximately 56-68% of patients with protein contact dermatitis and that flares of urticaria often accompany contact with the causative material. ^{[4, 5]}

Others posit that protein contact dermatitis may be a result of combined type I and type IV delayed hypersensitivity reactions. Negative patch-test results may occur because large protein-based molecules cannot penetrate intact, uninvolved skin. Also possible is that the type I histamine response may block the detection of a type IV response. This is supported by experimentation of chronic dermatophytosis, wherein Trichophyton mentagrophytes induces an immediate type I reaction with no subsequent delayed type IV response. However, when the antihistamine chlorpheniramine is injected, blocking the type I reaction, a positive delayed type IV reaction is uncovered. ^[6]

Finally, the pathogenesis of protein contact dermatitis may involve an immunoglobulin E (IgE)–mediated delayed hypersensitivity reaction, similar to that proposed for atopic dermatitis. In atopic dermatitis, IgE-bearing Langerhans cells are proposed to promote systemic expansion of T_H 2 memory T cells, ^[7] inducing influx of interleukin (IL)–5, IL-4, IL-13, and IL-3. This leads to eosinophilia, an increase in IgE, and the development of mast cells.

A mouse model of protein contact dermatitis induced by natural rubber latex revealed an increase in CD4⁺ CD3⁺ T cells and mast cells and a T_H 2-type response with a strong IgE-mediated response. ^[8] Another experimental model of protein contact dermatitis induced the generation of T cells, the infiltration of eosinophils, and the production of IL-4 and IL-5. ^[9]

With many foods, contact with raw food is more likely to induce reactions compared with cooked food, where proteins are partially denatured. There are notable exceptions to this rule, including onions. ^[10]

Four groups of proteins can cause protein contact dermatitis. ^{[11, 12]} The first group consists of fruits, vegetables, spices, and plants and is most common in kitchen workers, caterers, food vendors, food packers, and gardeners. ^{[5, 13, 14]} Protein sources include the following:

• Apple

• Asparagus

• Banana

• Bean

• Carrot

• Chrysanthemum

• Cornstarch

• Flour ^[15]

• Mugwort

• Natural rubber latex

• Paprika

• Peach

• Peanut

• Pear

• Shiitake mushroom

• Soy

The second group consists of animal proteins and is observed in slaughterhouse workers, butchers, commercial anglers, cooks, farmers, and veterinarians. Those in contact with animal intestines are most susceptible. Common triggers include the following:

• Blood

• Bovine amniotic fluid

• Cheese

• Cow dander

• Egg yolk

• Maggots

• Meat

• Milk

• Salmon

• Squid

• Worms

The third group is flour-associated protein contact dermatitis, reported primarily in bakers. A generalized dermatitis may be observed in this group, often involving the face. The most common culprits are wheat and rye.

The fourth group is proteolytic enzyme–associated protein contact dermatitis, most common among soap makers, bakers, pharmaceutical workers, and chemical enzyme factory workers. Respiratory symptoms are most common in this group. Reported enzymes include alpha amylase, glucoamylase, and lactase.

Protein contact dermatitis is most often caused by direct contact with one of the above allergens. However, systemic exposure, including inhalation or ingestion of the allergen, may also induce a protein contact dermatitis. In one study, 3 of 22 patients with protein contact dermatitis exhibited a systemic reaction to protein. In another case report, a housewife with known protein contact dermatitis to cabbage had a flare of her hand dermatitis after eating okonomiyaki, a dish whose primary ingredient is heat-cooked cabbage. ^{[5, 16]}

The prevalence of protein contact dermatitis, in the United States or internationally, is unknown. In Finland, the total number of occupational skin diseases reported in 2002 was 965, 11.2% (108) of which were cases of contact urticaria and protein contact dermatitis. ^[17] A study in Denmark of 144 slaughterhouse workers revealed a cumulative prevalence of 22%, with the highest prevalence amongst those who cleansed the animal gut. ^[18] A retrospective study from 2006-2014 in a French dermatology and allergy center revealed that only 0.41% of patients with contact dermatitis had positive skin tests with proteins. ^[19]

Demographics

No racial or sexual predilection is known for protein contact dermatitis. Persons of all ages can be affected, but protein contact dermatitis is most common in adulthood. A history of atopy has been reported in 56-68% of persons with protein contact dermatitis. ^{[19, 20]} Protein contact dermatitis is most common in food handlers, especially cooks and fish handlers. The allergenicity may increase with the postmortem age of the fish, handling fish bare-handed, and coming into direct contact with the fish liquid. Protein contact dermatitis also occurs with high frequency in those caring for animals. Other risk factors that predispose to protein contact dermatitis include irritant contact dermatitis, skin trauma, wet work, skin abrasions, cuts, burns, and other factors that cause a disruption of the skin barrier. ^{[13, 21]}

Avoidance of the allergen should result in clearing of the dermatitis. No cases of death secondary to protein contact dermatitis have been reported. However, morbidity may be significant, including angioedema, gastrointestinal symptoms, rhinoconjunctivitis, and bronchial asthma. These systemic symptoms are more likely to occur if the allergen is ingested. In one study, food handlers with protein contact dermatitis were more likely to change their job, retire, or require sick leave of greater than 3 weeks duration as compared with those with other types of occupational hand dermatitis. ^[21]