Occupational contact urticaria and protein contact dermatitis

ARTICLE

Auteur(s) : Marie-Sylvie Doutre

Service de dermatologie Hôpital Haut-Lévêque, Centre Hospitalier de Bordeaux, 33600 Pessac France

accepté le 12 Juillet 2005

Occupational contact urticaria

The whealing reactions can be strictly confined to the area of contact but they can also appear as generalized urticaria, sometimes associated with extra cutaneous symptoms (bronchospasms, rhinoconjunctivitis, swellings of the upper airways, gastro-intestinal manifestations) and anaphylactic reactions. The severity of clinical reactions can be classified according to the system of Von Krogh and Maibach [2]. Stage 1 of CU syndrome indicates localized urticaria ; stage 2 denotes generalized urticaria with or without angioedema; stage 3 includes urticaria with asthma, rhinoconjunctivitis, orolaryngal and gastro-intestinal symptoms and stage 4 is severe anaphylactic shock.

When urticaria has been induced by airborne contact, the parts of the body most often affected are the uncovered areas.

Although aquagenic urticaria and perhaps even physical urticaria could be considered as subgroups of CU, they are conventionally classified separately and are not discussed in this paper.

Physiopathology

• – Allergic (or immunologic) contact urticaria depends on the presence of specific IgE. The symptoms appear after repeated contact, implying a preceding phase of sensitization. Even very small amounts of allergens can induce a reaction and only selected individuals among the exposed persons are affected. Sometimes, immunologic CU spreads beyond the site of contact, producing generalized U, other systemic symptoms and even anaphylaxis.This type of CU develops preferentially in persons with an atopic predisposition or atopic diseases.The list of substances with proven or probable antigen-specific, IgE mediated CU is long. However, this has few epidemiological consequences since many of the allergens have only been published in case reports. Next to latex, foods are the most frequent eliciting agents. Plants, animal products, drugs, cosmetics, industrial agents are also elicitors of immunologic CU.
• – In the non-immunologic (non-allergic) type, the most frequent type of CU, no previous sensitization has occurred and the agents will produce CU in most individuals if contact time and concentration are sufficient. With few exceptions, the skin lesions are restricted to sites of contact and they rarely cause systemic manifestations. Many of the eliciting agents in this category may induce urticarial skin reactions via several mechanisms: direct release of histamine and other mediators from mast cells, direct effect on dermal vessels, without causing mast cell release, by vasoactive amines, acetylcholine, leukotrienes, prostaglandins and others.Non immunological contact urticants are common: plants, animals, cosmetics, topical medications, food preservatives and food flavouring. The most potent and best studied agents are benzoic acid, sorbic acid, nicotinic acid esters and cinnamic aldehyde. Many industrial and laboratory chemicals can also cause non immunological CU.

There are also substances that cause these types of reactions whose mechanism may not be known.

Some agents can induce CU by immunologic and non-immunologic mechanisms. So, pine processionary caterpillars (thaumetopoea pityocampa) are included among the agents that elicit CU by a non-immunologic mechanism, due to urticant hairs that are capable of penetrating the human epidermis and mucous membranes [4]. However, recently published studies have demonstrated that an IgE-mediated reaction is involved in most CU produced by thaumetopoea pityocampa [5]. A major caterpillar allergen has recently been isolated and characterized: it corresponds with Tha p1 and shows no homologies to other insect allergens already described [6]. It is the same for ammonium persulfate, a chemical used by hairdressers as a booster for peroxide bleaches. The mechanism is uncertain with features of both immunologic and non immunologic CU. However, specific binding of IgE to ammonium persulfate was found in some patients [7].

Diagnosis

• – The sites of the lesions, which must be linked to contact with the product, even if in some cases, the area of the lesions is much larger than the area of contact.
• – The list of products handled at work. Some substances are known to trigger CU, such as natural rubber latex, products of animal or vegetal origin, drugs…
• – The relationship between the development of the skin lesions and the work schedule and a recurrence of the disease on re-exposure to the same agents.

Some groups of workers are particularly prone to develop CU: cooks, bakers, butchers, veterinarians, gardeners, florists, health care personals, hairdressers, workers in chemical plants, forestry workers, workers in the leather industry and in the rubber industry… However, this list is not exhaustive.

Skin tests with suspected agents are thus of paramount importance. If the patient has suffered from serious symptoms (stages 2, 3, 4 in the classification of Von Krogh and Maibach), tests should be done with the necessary precautions: very low concentrations of allergens should be used; resuscitation facilities should be immediately available.

Testing should be done in several steps [8, 9]:

• – Open application on non affected skin.
• – Open application on slightly or previously affected skin.
• – Occlusive application on non affected skin.
• – Occlusive application on slightly or previously affected skin.
• – Prick or scratch tests.

The test substances are applied for 15-30 minutes to the skin and readings are taken immediately after their removal as well as 30 and 60 minutes after.

If positive reactions are obtained, further evaluation is discontinued.

On epicutaneous testing, high molecular weight substances like food or latex proteins will at times give positive reactions only on previously involved or possibly even inflamed skin because of better penetration. Suspected foods often give positive skin reactions only with the native substance since commercial extracts are often unreliable. The choice of vehicle is also important: agents suspended in alcoholic solutions or suspensions cause more rapid and fleeting reactions whereas reactions to agents in vaseline last longer. Equivocal tests results should be repeated, simulating the exposure of the patient with the suspected agent.

However, in practice, it is difficult to carry out all the tests. Many authors favour the prick tests ( (figure 1) ). Saline is used as negative control and 1% histamine as a positive control. Dermographism is the chief reason for false positive reactions. To minimize false negative reactions, patients must stop antihistamines and steroids for at least 3 days [10, 11].

Determination of specific IgE is helpful when an allergic CU is suspected. Others tests such as basophil activation tests could be used for biological diagnosis [12].

Etiology

Natural rubber latex allergy

Immediate type reactions are caused by proteins of NRL derived from hevea brasiliensis (allergic contact dermatitis is caused by rubber chemicals, mostly accelerators, particularly thiurams). NRL contains several hundred proteins of which 13, Hev (hevein) b1 to Hev b13 have been recognized by the International Union of Immunological Societies as latex allergens [24].

Cornstarch powder, which has traditionally been added during glove manufacture to facilitate donning, appears to increase exposure to latex allergens both through direct skin contact and via the respiratory tract [25, 26]. It is rarely an allergenic agent [27]. As an alternative to cornstarch, cotton fluff has been introduced into glove manufacture. However, cotton fluff can also serve as a vector for latex allergens [28]. Surgical and examination gloves are involved in about 80% of cases of latex intolerance. However, gloves are not the sole source of contact with NRL in sensitized health care personnel. NRL is found in numerous medical devices (catheters, tourniquets, syringes…).

The diagnosis of an NRL allergy is based on clinical history, skin prick tests, estimation of specific IgE antibodies and use tests. Skin prick tests must be performed with a standardized latex allergen extract. If in doubt, skin tests can be carried out with glove eluates prepared by a short extraction in isotonic sodium chloride solution. When there is some discrepancy between clinical history and skin test reactions, use tests with latex gloves can be performed very carefully. The quantitative measurement of serum specific IgE antibodies to NRL can be helpful for diagnosis [29].

For fifteen years, cross reactions between proteins in NRL and several foods have been demonstrated, particularly tropical fruits, banana, kiwi, avocado [30]… In addition, there are many publications containing reports of associations between concomitant sensitivity to NRL and various fruits, vegetables and plants. It is useful to ask for a history of food hypersensitivity in patients with NRL allergy. In the absence of a positive on suggestive history, routine skin prick tests with food extracts are not useful. However, the patient must be aware of the possibility of future reactions to the most commonly implicated foods, i.e. banana, avocado, kiwi and chestnuts. If the latex-allergic patient’s history is positive or strongly suspicious for a food allergy, skin prick testing should be done with the suspected food allergens, fresh foods when possible [31].

Other occupational contact urticarias

• – In health care personnel, the most frequent cause of CU is NRL. However, some drugs can also induce CU, particularly antibiotics (penicillin, amoxicillin…) [32-34].
• – Laboratory workers can develop sensitivity to furred animals, particularly mice and rats. Urine is a major source of allergen production. Hair, dander and, to a lesser extent saliva, are also important rodent sources. Skin reactions are typically the next most prevalent symptoms, occurring in about 40% of symptomatic individuals [35].
• – Veterinarians are at risk with animal blood, amniotic fluid, placenta, seminal fluid [36].
• – Food handlers, chefs, bakers, butchers… are in constant contact with meats, fruits and vegetables [37, 38].
• – In hairdressers, some products as shampoo, shampoo in hair colour, hair-conditioner containing Crotein q, can induce CU [39, 40].
• – In pine-cone or resin collectors, woodcutters, farmers, stockbreeders and other forestry personnel, processionary caterpillars can induce immunologic and/or non immunologic CU. The parts of the body most often affected were the uncovered areas ( (figure 2) ), although very often covered parts were also affected. The wheals join up around the neck and on the flexor surface of the wrists and forearm, and involve several cutaneous areas. Angioedema, especially of the eyelids, rhinoconjunctivitis and, in rare cases, respiratory symptoms and anaphylactic reactions have also been observed [5].
• – In florists, gardeners, horticulturists, different decorative house-plants (ficus benjamina, yucca…) [18-41] and flowers (gerbera, tulips, lilies, christmas cactus…) can induce CU.

Sporadic cases of occupational CU also arise with metal salts, isocyanates, organic solvents, epoxy resins, anhydrides due to airborne contact… [42-45].

In fact, the agents that are responsible for occupational CU vary in different countries. Thus, in Finland, in Kanerva’s study, cow dander was the most common cause of CU in farmers [46].

So, the diagnosis of occupational CU should be suspected in any worker. The diagnosis must be confirmed or invalidated by a detailed history and skin tests with suspected substances.

Treatment

Protein contact dermatitis

Among patients with hand dermatitis ( (figure 3) ), acute flares of pruritus, urticaria, edema or vesicular lesions are noted a few minutes after the contact with the causative substance. The hands are the most commonly affected site and are generally diffusely involved. Sometimes, lesions may affect only the tips of the first, second and third fingers. Others sites may also be affected, wrists, forearms, face… Extracutaneous reactions such as angioedema, gastro-intestinal symptoms, rhinoconjunctivitis and bronchial asthma may accompany the skin reactions. Data from the literature suggests that an association between atopy and PCD occurred in approximately 50% of the patients.

In food handlers, chronic paronychia can be considered a clinical variety of PCD ( (figure 4) ). Patients have an immediate erythemato-oedematous or vesicular reaction on the proximal nailfold to one or more of the foods that they handled. This reaction is associated with moderate itching. Clinically, the proximal nail fold showed redness and severe swelling [52]. NRL can also induce chronic paronychia [53].

These manifestations are induced by contact with products of animal or vegetal origin. The causative proteins have been classified into four groups [54]:

• – group 1: fruits, vegetables, spices, plants [55];
• – group 2: animal proteins: meat (beef, pork, horse, lamb, chicken…), fish and crustaceans (cod, herring, salmon, lobster, shrimps…) milk, cheese and also saliva, blood, amniotic fluid of animals;
• – group 3: grains, particularly rye and wheat, also barley, oats, corn [56];
• – group 4: enzymes (alpha-amylase…) [57].

The list of these allergens explains the affected professions: food-handlers in general (butchers, bakers…) food vendors, abattoir workers, veterinarians, laboratory animal workers, gardeners…

However, others jobs can be affected, such as industrial workers.

Diagnosis requires skin tests (preferably performed with fresh material), particularly open tests, prick tests or scratch tests. Positive reactions are observed after a few minutes. In some cases, specific IgE to the substance could be detected. However, RAST are not as sensitive as skin tests and are not available for every suspected allergen. Although PCD presents clinically as chronic eczema, patch-tests are usually negative.

The reactions are species- and organ-specific: calf’s liver may provoke an reaction whereas chicken liver may not; chicken meat may provoke an reaction whereas chicken liver may not. Reports of multiple sensitizations are rare [58].

PCD is a type I allergic reaction to high molecular weight proteins. The penetration of these proteins through the epidermis is facilitated by irritant or eczematous dermatitis, particularly in atopic patients. Indeed, atopic subjects have a less effective skin barrier, through which the high molecular weight proteins can penetrate more readily [59, 60].

Conclusion

However, the list of eliciting substances grows from year to year and occupational CU is thus rather frequent. The incidence and severity of these reactions can be decreased by preventive measures including the correct diagnosis based on detailed history and skin tests and adequate information.

References

2 Von Krogh C, Maibach HI. The contact urticaria syndrome. An update review. J Am Acad Dermatol 1982; 5: 328-42.

3 Wakelin SH. Contact urticaria. Clin Exp Dermatol 2001; 26: 132-6.

4 Ducombs G, Lamy M, Bergaud JJ, Tamisier JM, Gervais C, Texier L. La chenille processionnaire (thaumetopoea pityocampa schiff. lepidopteres) et l’homme. Etude morphologique de l’appareil urticant. Enquête épidémiologique. Ann Dermatol Venereol 1979; 106: 769-78.

5 Vega J, Vega JM, Moneo I, Armentia, A, Caballero ML, Miranda A. Occupational immunologic contact urticaria from pine processionnary caterpillar (thaumetopoea pityocampa): experience in 30 cases. Contact Dermatitis 2004; 50: 60-4.

6 Moneo I, Vega JM, Caballero M. Isolation and characterisation of Tha p 1, a major allergen from the pine processionary caterpillar. Allergy 2003; 58: 34-7.

7 Aalto-Korte K, Makinen-Kiljunen S. Specific immunoglobulin E in patients with immediate persulfate hypersensitivity. Contact Dermatitis 2003; 49: 22-5.

8 Amin S, Tangertsampan C, Maibach H. Contact urticaria syndrome. Am J Contact Derm 1997; 8: 15-9.

9 Kim E, Maibach H. Changing paradigms in Dermatology: Science and Art of diagnostic patch and contact urticaria testing. Clin Derm 2003; 21: 346-52.

10 See Ket N. Contact urticaria. A review. Ann Ac Med 1998; 17: 563-8.

11 Tennstedt D. Les urticaires chroniques de contact. Ann Dermatol Venereol 2003; 130: S28-S30.

12 Hemery ML, Arnoux B, Dhivert-Donnadieu H, Rongier M, Barbotte E, Verdier R, Demoly P. Confirmation of the diagnosis of natural rubber latex allergy by the basotest method. Int Arch Allergy Immunol 2005; 136: 53-7.

13 Conso F. Occupational health aspects of latex allergy. Rev Fr Allergol 1997; 37: 1211-4.

14 Smedley J. Occupational latex allergy: the magnitude of the problem and its prevention. Clin Exp Allergy 2000; 30: 458-60.

15 Turjanmaa K, Alenius H, Makinen-Viljunen S, Reunala T, Paluoso T. Natural ruber latex allergy. Allergy 1996; 51: 593-602.

16 Yassin MS, Lierl MB, Fischerr TJ, O’Brien K, Cross J, Steinmetz C. Latex allergy in hospital employees. Ann Allergy 1994; 245: 9.

17 Testas F. Allergie au latex: risque pour le personnel hospitalier. Rev Fr Allergol 1999; 39: 141-7.

18 Paulsen E, Sogaard J, Andersen KE. Occupational dermatitis in Danish gardeners and greenhouse workers. Contact Dermatitis 1998; 38: 140-6.

19 Valks R, Conde-Salazar L, Cuevas M. Allergic contact urticaria from natural rubber latex in healthcare and non healtcare workers. Contact Dermatitis 2004; 50: 222-4.

20 Conde-Salazar L, Gatica ME, Barcol-Iglesias C, Cuevas M, Valks R. Latex allergy among construction workers. Contact Dermatitis 2002; 47: 154-6.

21 De Groot H, DeJong NW, Duijster H. Prevalence of natural rubber latex allergy (type I and type IV) in laboratory workers in the Netherlands. Contact Dermatitis 1998; 38: 159-63.

22 Linn Holness D, Mace SR. Results of evaluating health care workers with prick and patch testing. Am J Contact Derm 2001; 12: 88-92.

23 Turjanmaa K. Natural rubber latex allergy: clinical manifestations (including contact dermatitis) and diagnosis. Rev Fr Allergol 1997; 37: 1177-9.

24 Wagner S, Breitneder H. Hevea brasiliensis latex allergens: current panel and clinical relevance. Int Arch Allergy Immunol 2005; 136: 90-7.

25 Tomazic UJ, Shampaine EL, Lamanna A, Withrow TJ, Adkinson NF, Hamilton RG. Cornstarch powder on latex products is an allergen carrier. J Allergy Clin Immunol 1994; 93: 751-8.

26 Brehler R, Kolling R, Webb M, Wastell C. Glove powder – a risk factor for the development of latex allergy. Eur J Surg 1997; 579: 23-5.

27 Assalve D, Cicioni C, Perno P, Lisi P. Contact urticaria and anaphylactoid reaction from cornstarch surgical glove powder. Contact Dermatitis 1988; 19: 61.

28 Baur X. Cotton fluffs as latex allergen carriers in a glove factory. J Allergy Clin Immunol 2003; 111: 117-9.

29 Brehler R, Kutting B. Natural rubber latex allergy. Arch Intern Med 2001; 161: 1057-64.

30 Blanco C. Latex fruit syndrome. Curr Allergy Asthma Resp 2003; 3: 47-53.

31 Levy DA, Leynadier F. Latex and food allergy. Rev Fr Allergol 1997; 37: 1188-94.

32 Shimizu S, Chen KR, Miyakawa S. Cefotiam-induced contact urticaria syndrome: an occupational condition in Japanese nurses. Dermatology 1996; 192: 174-6.

33 Miyake H, Morishima Y, Kishimoto S. Occupational contact urticaria syndrome from cefotiam dihydrochloride in a latex-allergic nurse. Contact Dermatitis 2000; 43: 230-1.

34 Conde-Salazar L, Guimarens D, Gonzalez MA, Mancebo E. Occupational allergic contact urticaria from amoxicillin. Contact Dermatitis 2001; 45: 109.

35 Bush RK, Wood RA, Eggleston PA. Laboratory animal allergy. J Allergy Clin Immunol 1998; 102: 99-102.

36 Tausher AE, Belsito DV. Frequency and etiology of hand and forearm dermatoses among veterinarians. Am J Contact Derm 2002; 13: 116-24.

37 Bahna SL. Adverse food reactions by skin contact. Allergy 2004; 59(suppl 78): 66-70.

38 Brancaccio RB, Alvarez MS. Contact allergy to food. Derm Ther 2004; 17: 302-13.

39 Niimimaki A, Niiminaki M, Makinen-Kiljunen S, HannukselaM. Contact urticaria from protein hydrolysates in hair conditioners. Allergy 1998; 53: 1078-82.

40 Leino T, Estlander T, Kanerva L. Occupational allergic dermatoses in hairdressers. Contact Dermatitis 1998; 38: 166-7.

41 Kanerva L, Estlander T, Petman L, Makinen-Kiljunen S. Occupational allergic contact urticaria to yucca (yucca aloifolia), weeping fig (ficus benjamina) and spathe flower (spathiphyllum wallisiu). Allergy 2001; 56: 1008-11.

42 Sasseville D. Contact urticaria from epoxy resin and reactive diluents. Contact Dermatitis 1998; 38: 57-8.

43 Yokota K, Hohyama Y, Miyave H, Matsumoto N, Yamaguchi K. Occupational contact urticaria caused by airborne methylhexahydrophtalic anhydride. Ind Health 2001; 39: 347-52.

44 Valks R, Conde-Salazar L, Lopes-Barrantes O. Occupational allergic contact urticaria and asthma from diphenylmethane-4-4’-diisocyanate. Contact Dermatitis 2003; 49: 166-7.

45 Cristaudo A, Jera F, Severino V, De Rocco M, Dilella E, Picardo M. Occupational hypersensitivity to metal salts, including platinum, in the secondary industry. Allergy 2005; 60: 159-64.

46 Kanerva L, Toikkanen J, Jolank R, Estlander T. Statistical data on occupational contact urticaria. Contact Dermatitis 1996; 35: 229-33.

47 Rueff F, Schopf P, Putz K, Przybilla B. Effect of reduced exposure on natural rubber latex sensitization in health care workers. Am Allergy Asthma Immunol 2004; 92: 530-7.

48 Allmers H, Schmengler J, John S. Decreasing incidence of occupational contact urticaria caused by natural rubber latex allergy in German health care workers. J Allergy Clin Immunol 2004; 114: 347-51.

49 Leynadier F, Herman D, Vervloet D, Andre C. Specific immunotherapy with a standardized latex extract versus placebo in allergic health care workers. J Allergy Clin Immunol 2000; 106: 585-90.

50 Sastre J, Fernandez-Nieto M, Rico P, Matrin S, Barber D, Cuesta J. Specific immunotherapy with a standardized latex extract in allergic workers: a double-blind, placebo-controlled study. J Allergy Clin Immunol 2003; 111: 985-94.

51 Hjorth N, Roed-Petersen J. Occupational protein contact dermatitis in food handlers. Contact Dermatitis 1976; 2: 28-42.

52 Tosti A, Guerra L, Morelli R, Bardazzi F, Fanti R. Role of foods in the pathogenesis of chronic paronychia. J Am Acad Dermatol 1992; 27: 706-10.

53 Kanerva L. Occupational protein contact dermatitis and paronychia from natural rubber latex. J Eur Acad Dermatol Venereol 2000; 14: 504-6.

54 Janssens V, Morren M, Dooms-Goossens A, Degreef H. Protein contact dermatitis: myth or reality? Br J Dermatol 1995; 132: 1-6.

55 Meding B. Skin symptoms among workers in a spice factory. Contact Dermatitis 1993; 29: 202-5.

56 Guin JD, Westfall C, Ruddell D, Carlinger K. Occupational protein contact dermatitis to cornstarch in a paper adhesive. Am J Contact Derm 1999; 10: 83-8.

57 Morren MA, Janssens V, Dooms-Goossens A, Van-Hoeyveld EV, 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: 723-8.

58 Iliev D, Wüthrich B. Occupational protein contact dermatitis with type I allergy to different kinds of meat and vegetables. Int Arch Occup Environ Health 1998; 71: 289-92.

59 Smith-Pease CK, White IR, Basketter DA. Skin as a route of exposure to protein allergens. Exp Dermatol 2002; 27: 296-300.

60 Berard F, Marty JP, Nicolas JF. Allergen penetration through the skin. Eur J Dermatol 2003; 13: 324-30.