Protein Contact Dermatitis

Updated: Oct 11, 2021
Author: Cheryl Levin, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

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.

Pathophysiology

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 TH 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 TH 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]

Etiology of Protein Contact Dermatitis

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]

Epidemiology

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]

Prognosis

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]

 

Presentation

History

A detailed history should be performed for any individual suspected of having protein contact dermatitis (PCD). While not confirmed with formal studies, anecdotal 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 protein allergens. Persons at particular occupational risk include kitchen workers, food vendors, gardeners, slaughterhouse workers, butchers, commercial anglers, farmers, and veterinarians.

Many agents are capable of causing protein contact dermatitis, as is elucidated in Etiology. Identification of the agent may be aided by the rapid onset of the reaction upon exposure: an acute, urticarial, or vesicular eruption may occur within minutes after contact with the causative protein. A chronic recurrent dermatitis also ensues at the site of allergen application. 

Patients may report itching, burning, stinging, or pain in the affected area. Upon ingestion of the allergen, patients may rarely experience angioedema, rhinoconjunctivitis, gastrointestinal symptoms, and/or bronchial asthma.  

The International Contact Dermatitis Research Group proposed a classification for contact allergies based on clinical presentation.[22]

Physical Examination

Protein contact dermatitis is characterized by pruritic, erythematous papules and vesicles with overlying fine scale. Lichenification may occur, especially with long-term exposure. The dermatitis usually affects the hands and forearms, which are typically diffusely involved. Sometimes, only the fingertips are affected. Paronychia and periungual edema and erythema may be observed.[23] Urticarial papules and plaques may occur within minutes following contact with the causative allergen, although, in one large series, this was rarely observed.[24] Paronychia with periungual erythematous edema is suggestive of a diagnosis of protein contact dermatitis.[13, 19] In one report, a fixed pigmented erythema with central bullae was observed.[19]

 

DDx

Diagnostic Considerations

A history of burning, stinging, or itching immediately upon contact with the allergen may help differentiate other types of hand dermatitis.[25] Patients may have more than one concomitant condition, and preexisting irritant or atopic dermatitis may commonly occur.

Differential Diagnoses

 

Workup

Approach Considerations

The most sensitive methods for detecting protein contact dermatitis (PCD) include prick and scratch tests, although open application testing may also be performed. Patch-test results are usually negative. If the prick testing is negative, some authors suggest performing a rub test by applying the allergen to the area affected by protein contact dermatitis.[24] If available, specific recombinant IgE testing to the allergens revealed by prick testing may be performed. This allows for specification of epitopes and evaluation of potential cross-reactants.[5]

Systemic symptoms, including anaphylaxis, have been reported with prick and scratch tests. Therefore, these tests should be performed only in settings where appropriate resuscitation equipment is available.

For prick testing, a commercial extract should be used for the testing when available. If none is available, a prick-by-prick method may be used, whereby the allergen is pricked and immediately afterward, the forearm is pricked.[19]

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

Fungal Testing

Testing should be performed to exclude a tinea infection. This may consist of potassium hydroxide (KOH) testing, fungal culture, or periodic acid-Schiff staining

Open Application Testing

Open application testing involves placing or rubbing the allergen on intact skin and/or damaged, eczematous skin.

Prick Testing

Prick testing involves placing one drop of diluted test allergen, vehicle (negative control), and histamine (positive control) onto the volar forearm of the patient. The test sites are pierced with lancets to introduce the allergen into the dermis. The results are read at 15-minute intervals over 1 hour. A positive reaction is a wheal of at least 3 mm in diameter that is also at least half the size of the histamine control in the absence of a reaction in the vehicle control.

Scratch Testing

Scratch testing involves placing one drop of diluted test allergen, vehicle, and histamine onto the volar forearm and scratching the skin lightly with a needle. The test sites are read at 15-minute intervals over 1 hour. A positive reaction is a wheal that is at least half the diameter of the histamine control in the absence of a reaction in the vehicle control.

Radioallergosorbent Testing

A radioallergosorbent test (RAST) with a particular allergen may be performed to measure allergen-specific IgE in the patient's serum, although a negative test result does not rule out protein contact dermatitis. RAST testing measures only circulating antibodies and does not assess tissue-bound antibodies.

Imaging Studies

If the patient is experiencing extracutaneous symptoms, appropriate imaging studies may be performed. No specific imaging study is required in the evaluation of protein contact dermatitis.

Histologic Findings

Histology findings are relatively nonspecific. Biopsy may reveal perivascular lymphocytic infiltrate with eosinophils or spongiosis with lymphocytic exocytosis. One report of protein contact dermatitis describes a clinical presentation of a fixed pigmented eruption, and the biopsy revealed a dense polynuclear neutrophilic infiltrate.[19]

 

Treatment

Approach Considerations

In protein contact dermatitis (PCD), avoidance of the particular allergen is of primary importance. Gloves and other protective clothing are necessary if avoidance is not possible. Symptomatic relief may be provided with short-term corticosteroids, immunomodulatory agents, or antihistamines.[26] Inpatient care may be necessary for protein contact dermatitis patients if the pruritus is so severe that patients cannot care of themselves or if they experience angioedema or severe gastrointestinal distress.

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

Consultations

If chronic hand dermatitis does not resolve, consultation with a dermatologist should be arranged. The dermatologist may conduct patch testing and prick or scratch testing.

Diet

Patients with protein contact dermatitis may need to eliminate the implicated allergen from their diet. Ingested allergens may cause exacerbation of the chronic dermatitis or may cause extracutaneous symptoms.

 

Medication

Medication Summary

Short-term treatment may include high-potency topical corticosteroids, such as clobetasol propionate, to decrease inflammation. Topical tacrolimus 1% ointment may be a good long-term choice. Oral antihistamines may be administered if severe pruritus ensues.[27]

Corticosteroids, Topical

Class Summary

Corticosteroids are immunosuppressives with anti-inflammatory properties that modify the body's immune response to diverse stimuli. Other actions include vasoconstriction and antiproliferation. These agents have limited use in the treatment of protein contact dermatitis.

Clobetasol propionate (Temovate, Clobex, Cormax)

A class I superpotent topical steroid, clobetasol suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. This agent decreases inflammation by stabilizing lysosomal membranes, inhibiting polymorphonuclear leukocyte and mast cell degranulation.

Immunomodulators, Topical

Class Summary

These agents modify immune processes that promote inflammation.

Tacrolimus (Protopic, Prograf)

The mechanism of action of tacrolimus in atopic dermatitis not known. Reduces itching and inflammation by suppressing release of cytokines from T cells. It also inhibits transcription for genes that encode interleukin (IL)–3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor–alpha, all of which are involved in early stages of T-cell activation.

Additionally, tacrolimus may inhibit release of preformed mediators from skin mast cells and basophils and may down-regulate expression of high-affinity IgE receptor (FCeRI) on Langerhans cells.

Tacrolimus can be used in patients as young as 2 years. It is more expensive than topical corticosteroids. This agent is available as an ointment in concentrations of 0.03% and 0.1%. It is indicated only after other treatment options have failed.

Antihistamines

Class Summary

Antihistamines act by competitive inhibition of histamine at the H1 receptor. They may control itching by blocking effects of endogenously released histamine.

Hydroxyzine hydrochloride (Vistaril)

This agent antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical region of the central nervous system.

 

Questions & Answers

Overview

What are the diagnostic criteria for protein contact dermatitis (PCD)?

What is protein contact dermatitis (PCD)?

What is the pathophysiology of protein contact dermatitis (PCD)?

Which plant proteins cause protein contact dermatitis (PCD)?

Which animal proteins cause protein contact dermatitis (PCD)?

What is a primary cause of protein contact dermatitis (PCD) in bakers?

Which enzyme-associated proteins cause protein contact dermatitis (PCD)?

What is the prevalence of protein contact dermatitis (PCD)?

Which patient groups have the highest prevalence of protein contact dermatitis (PCD)?

What is the prognosis of protein contact dermatitis (PCD)?

Presentation

Which clinical history findings are characteristic of protein contact dermatitis (PCD)?

Which physical findings are characteristic of protein contact dermatitis (PCD)?

DDX

Which conditions are included in the differential diagnoses of protein contact dermatitis (PCD)?

What are the differential diagnoses for Protein Contact Dermatitis?

Workup

How is protein contact dermatitis (PCD) diagnosed?

What is the role of fungal testing in the workup of protein contact dermatitis (PCD)?

What is open application testing in the workup of protein contact dermatitis (PCD)?

What is the role of prick testing in the workup of protein contact dermatitis (PCD)?

What is the role of scratch testing in the workup of protein contact dermatitis (PCD)?

What is the role of the RAST test in the workup of protein contact dermatitis (PCD)?

What is the role of imaging studies in the workup of protein contact dermatitis (PCD)?

Which histologic findings are characteristic of protein contact dermatitis (PCD)?

Treatment

How is protein contact dermatitis (PCD) treated?

Which specialist consultations are beneficial to patients with protein contact dermatitis (PCD)?

Which dietary modifications are used in the treatment of protein contact dermatitis (PCD)?

Medications

What is the role of medications in the treatment of protein contact dermatitis (PCD)?

Which medications in the drug class Antihistamines are used in the treatment of Protein Contact Dermatitis?

Which medications in the drug class Immunomodulators, Topical are used in the treatment of Protein Contact Dermatitis?

Which medications in the drug class Corticosteroids, Topical are used in the treatment of Protein Contact Dermatitis?