IMMUNOLOGICAL CONTACT URTICARIA AND PROTEIN CONTACT DERMATITIS

An Goossens, Cristina Amaro*

Department of Dermatology, University Hospital, K.U. Leuven, B-3000 Leuven, Belgium

*Department of Dermatology, Hospital de Curry Cabral, Rua da Beneficência, n° 8, P-1069-166 Lisbon, Portugal

Macromolecules can penetrate the skin and cause immunological urticarial or eczematous clinical pictures, i.e. contact urticaria (ICU) and protein contact dermatitis (PCD), which seem to share a common pathogenic mechanism of a type I immediate reaction (2). Such adverse effects may be associated with pre-existing dermatitis, i.e. atopic dermatitis, for which associations have been noted in about 50 % of the cases, as well as irritant contact dermatitis, physical damage (burns, wounds), chemical damage (detergents and other penetration enhancers), increased hydration (excessive hand washing), and occluded skin (e.g. wearing gloves). Reduced stratum corneum barrier integrity indeed facilitates high molecular weight proteins to penetrate into the skin.

The exact patho-physiological mechanism in PCD is still unclear. Several authors have reported a combination of type I and IV allergic skin reactions, the latter supported by positive delayed patch tests, while this association has been difficult to prove in most cases. Negative patch testing on intact skin does not necessarily mean that a type IV reaction is not involved though: false-negative results might be due to insufficient penetration of the proteins. Since the demonstration of IgE receptors on the epidermal Langerhans cells, it has been speculated that these cells could be responsible for a delayed IgE-mediated reaction, a similar process to that of atopic dermatitis.

The clinical manifestations of ICU reflect the dose and route of exposure to the allergen: itching erythema or a wheal and flare reaction following external contact with a substance usually appearing within 30 minutes and clearing within hours can be strictly limited to the contact areas, but may also affect other contact sites, as for example the face, or even present as generalized urticaria. Also internal organs, i.e. the respiratory or gastrointestinal tracts may be involved, depending upon the allergen or pre-existing conditions such as atopic eczema. The severity of this possible multi-systemic disease has been reported as the “contact urticaria syndrome”.

The most frequent clinical presentation of PCD is a chronic or recurrent eczema. It may be manifested just as a fingertip dermatitis or extend to wrists and arms. An urticarial or vesicular exacerbation can be noted a few minutes after contact with the causal protein on previously affected skin. Some cases of chronic paronychia were considered a variety of PCD, with redness and swelling of the proximal nail fold, for example, after handling food and natural rubber latex.

Classically the protein sources are divided into four main groups. Group 1: fruits, vegetables, spices, plants and woods; group 2: animal proteins; group 3: grains and group 4: enzymes. Taking into account the nature of the causal proteins, a wide variety of jobs can be affected (1, 2).

Food handlers, cooks, housewives, caterers are at risk from fruits, vegetables and spices Typical localizations can be observed as with garlic and onion, affecting only the first, third and fourth fingers of the non-dominant hand.

Plants and woods are known to cause immediate skin and mucosal symptoms among gardeners, greenhouse workers, florists, plant caretakers, mushroom growers, and researchers. Numerous families of plants have been implicated, making the prevalence of ICU fairly high in this occupational group.

Proteins of animal origin constitute the largest group: they can cause problems in slaughterhouse workers and butchers, but also veterinarians are at great risk of CU or PCD from amniotic or seminal fluid, blood and saliva having their origin in obstetric procedures or daily contact with the animals. Geographic differences, reflecting countries’ costumes, have become evident. In statistical data from Finland, cow dander persists as a major cause of occupational disease among farmers, their exposure to cow dander being extremely high, as cows are kept inside for most of the year.

Animal keepers can be affected in multiple contexts, such as in zookeepers and laboratory workers professional entomologists or breeders, who may suffer from skin and respiratory symptoms following contact with insects or cockroaches, or locusts.

Numerous fish or seafood species, as well as fishing bait maggots (Nereis diversicolor, Calliphora vomitoria, Chironomus thummi thummi and Lumbrinereis impatientis) have been described in relation to fisherman and fishing for leisure time.

Different grains and enzymes are known to cause CU and PCD, sometimes accompanied by respiratory problems in bakers. Also protein hydrolysates obtained from wheat, oat, etc. may cause problems due to their presence in hair- and skincare products (e.g. Crotein Q ®, trimonium hydrolysed collagen).

With regard to the diagnosis, tests for immediate IgE-mediated allergy are of paramount importance when CU or PCD are investigated and reactions appear within 20 minutes. Skin prick tests with fresh material or commercial reagents are the gold standard.

Open testing (quite similar to the Skin Application Food Test or SAFT, which has only been mentioned in the diagnosis of food allergy in atopic children, can be helpful, but is generally negative unless the substance is applied on damaged or eczematous skin (where it even may cause a vesicular reaction). Sometimes a rubbing test (gentle rubbing with the material) on intact or lesional skin might be indicated, if an open test is negative. Scratch and scratch-patch testing carry a higher risk of false-positive reactions and the latter lacks sensitivity compared to prick-testing. Patch tests in PCD are usually negative. If there is a suspicion of any kind of serious extra-cutaneous symptoms, tests should be done with the necessary precautions and resuscitation facilities should be adequately available.

Measurement of specify IgE in serum (e.g. radioallergosorbent-RAST) is useful for some of the known proteins. Indeed, many of the protein allergens have not been identified yet.

The basophil activation test is a relatively new procedure: it is based on the demonstration of a membrane protein marker that appears following exposure to allergens and can be particularly interesting when assessing reactions to rare allergens, for which routine diagnostic tests, such as measurement of specific IgE antibodies, are not available.

Regarding the differential diagnosis, ICU from low-molecular chemicals also exists, such as, for example, with persulfates in hairdressers. Moreover, a variety of low molecular weight substances frequently encountered in our environment, such as preservatives, fragrances and foodstuffs can induce a distinct form of non-immunological contact urticaria (NICU). These agents may produce a reaction without any previous sensitization in most, if not all, exposed persons.

Concerning PCD, an allergic contact dermatitis to low molecular weight allergens, should be ruled out as the major cause of the eczematous clinical picture. Both conditions can occur simultaneously, however: for example, PCD from proteins in onion and garlic and allergic contact dermatitis from diallyldisulfide present in them.

Last but not least, atopic and irritant contact dermatitis have to be considered in the differential diagnosis.

References

1. Amaro C, Goossens A. Immunological occupational contact urticaria and contact dermatitis from proteins: a review. Contact Dermatitis; 2008, 58: 67-75.

2. Morren M, Janssens V, Dooms-Goossens A, Hoeyveld E, Cornelis A, De Wolf-Peeters C, Heremans A. α –Amylase, a flour additive: An important cause of protein contact dermatitis in bakers. J Am Acad Dermatol, 1993; 29: 723-728.