Non-nonsense cosmethic – Enciclopedia della Cosmesi – The Cosmesis Encyclopædia

HAZARD : Allergie cosmetiche

 Quello che è cibo per un uomo è veleno per un altro. 

dal De rerum natura di Lucrezio Caro.

Questo articolo ha richiesto una lunga revisione dopo che era stata segnalata dai lettori la eccessiva complessità della materia. Ho voluto mantenere link e copia-incolla di alcuni paper scientifici evitando traduzioni sommarie che potevano generare errori.

Molto complesso il problema delle allergie.
Gli studi epidemologici forniscono dati controversi, diversi da paese e paese, con una scandalosa, poco scientifica, mancanza di accuratezza.
Nonostante da alcuni anni i laboratori di ricerca siano in grado di identificare esattamente gli allergeni, apteni, proapteni ecc.. la maggioranza degli allergologi continuano a ragionare per classi generiche ( allergico alle graminacee !!! ) o addirittura per nomi commerciali ( allergico al kathon !!! ).
In questo caos di nonsense e cattiva informazione, chiunque debba mettere un cosmetico sul mercato, ma anche chiunque abbia un figlio in età scolare, deve considerare che le allergie sono sempre più frequenti e che alcune di queste possono avere conseguenze gravi, quando non letali.
Al solito la normativa cosmetica europea si dimostra estremamente avanzata nella tutela della salute pubblica. Il tema degli allergeni cosmetici è complesso e ha avuto con alcuni aggiornamenti della direttiva europea e dopo il 40° emendamento dell’IFRA un approccio precauzionario impensabile pochi anni fa. mentre l’IFRA ha adottato una procedura che permette di definire degli standard quantitativi di sicurezza, il comitato scientifico europeo Sccs si è focalizzato sul rischio allergico definendo una soglia di sicurezza per i 26 potenziali allergeni profumanti più comuni.
Nel 2012 il comitato scientifico europeo ha già anticipato che altri allergeni cosmetici ( almeno altri 30) stanno per aggiungersi alla lista delle sostanze cosmetiche con un più alto potenziale allergenico .
La valutazione del rischio allergico è complessa . Infatti per definizione gli allergeni sono assolutamente innocui per la maggioranza della popolazione e l’unica tutela che si può adottare è quella di limitare l’utilizzo delle sostanze che statisticamente hanno più risposte allergiche e di preavvertire il consumatore della loro presenza.
I meccanismi di azione causali ( la “spiegazione cellulare” della sensibilizzazione e della memoria allergica) non sono del tutto compresi e le esatte reazioni chimiche ( la “spiegazione molecolare” ) che attivano la risposta allergica non sono ancora state individuate. Solo recentemente è stato scoperto il presunto recettore che spiegherebbe la aptenizzazione da nickel.
Sulle cause poi dell’aumento di queste risposte allergiche non abbiamo nessuna indicazione scientifica.
I modelli che attribuivano all’allattamento artificiale o alla troppa igiene in età infantile una possibile causa del proliferare delle allergie, possono essere ragionevoli, ma non hanno alcun riscontro e dimostrazione scientifica.

Cosa è una allergia ?

 Nell’allergia, dal greco “reazione anomala”, il sistema immunitario reagisce in modo “esasperato” di fronte ad un “qualcosa” con il quale si è venuti a contatto .Il fatto sconcertante è che questo “qualcosa”, chiamato allergene, è assolutamente innocuo per i più ma, inspiegabilmente, risulta essere dannoso per l’allergico. Ciò che è importante chiarire è che l’allergia, qualunque sia l’allergene, ovunque sia il suo sito d’ingresso nell’organismo (bocca, naso, cute…) e qualunque sia l’organo o il tessuto sul quale la reazione esasperata si manifesta, non è mai una problematica localizzata ma è sempre una problematica sistemica, coinvolgente perciò l’intero organismo. Diversi studi hanno infatti dimostrato che, sebbene si evidenzi con sintomi localizzati (congiuntivite allergica, dermatite atopica, rinite, asma, ecc.) apparentemente scollegati tra loro, l’allergia ha sempre e comunque un’origine sistemica, che sta alla base di tutte le sue manifestazioni. Questa è la chiave per comprendere il perché, ad esempio, un bambino con dermatite atopica nella primissima infanzia (a comparsa entro il primo anno di vita nel 60-70% dei casi) può in seguito, solitamente intorno ai 4-5 anni, iniziare a manifestare sintomi d’asma, proprio nel momento in cui l’iper-reattività cutanea sembra essere ormai risolta. Inoltre, comprendere la base sistemica dell’allergia è fondamentale per capire che, come una forma eritematosa cutanea può essere innescata sia dal contatto con un allergene ambientale sia con un alimento, allo stesso modo anche i sintomi dell’asma, della rinite e della congiuntivite possono essere legati non solo alla sensibilizzazione verso allergeni inalanti ma anche verso allergeni che vengono a contatto con l’organismo in sedi che nulla hanno a che fare con la mucosa respiratoria.

Perchè scatta l'allergia ? Spiegazione cellulare

Alla base di tutto ci sarebbe un disequilibrio della “bilancia” immunitaria. Gli allergeni inducono il sistema immunitario a produrre una particolare classe di anticorpi: le immunoglobuline di tipo E (IgE). L’ipersensibilità IgE-mediata è infatti una caratteristica di tutte le problematiche allergiche. Alla base di questo comportamento immunitario vi è un disequilibrio nella differenziazione delle cellule che funzionano come i “registri” della risposta difensiva, i linfociti T helper. I T helper (Th) sono suddivisi in due sottogruppi con funzioni specifiche, i Th1 e i Th2, tra loro antagonisti. Il cardine dell’efficienza immunitaria, e quindi della salute, dell’individuo ha le sue basi nell’equilibrio tra Th1 e Th2. Per svariati fattori (mancato o scarso allattamento al seno, vaccinazioni, uso di farmaci, soprattutto antibiotici, alimentazione ricca di zuccheri e proteine animali, ecc.), questo equilibrio può venire a mancare, privilegiando un orientamento immunitario, oppure l’altro. Lo sbilanciamento immunitario verso Th2 è una caratteristica che predispone l’individuo all’allergia. I Th2 sono infatti legati all’attivazione e alla differenziazione dei linfociti B, produttori di IgE, gli anticorpi dell’allergia.

Dermatite allergica da contatto

Dermatite allergica da contatto

Allergic contact dermatitis is a delayed hypersensitivity
reaction due to the activation in the skin of hapten-specific
T cells. Two stages are necessary to its development: a
clinically silent stage, sensitization, and the effector stage.
Sensitization: the hapten, having crossed the horny layer,
interacts with the proteins in the cutaneous cells. In particular
it meets the network of epidermal dendritic cells (DC),
the Langerhans cells.

The interaction of the hapten/Langerhans cell induces:

i) activation and maturation of DC which migrate from the epidermis to the dermis and then rejoin the lymph nodes draining the hapten penetration site;

ii) processing of haptenized proteins and exposure at the membrane of the haptenized peptides in the peptide binding groove of MHC class II and class I molecules of DC.

In the lymph nodes the DC present haptenized peptides to naive T cells and activate those which express specific receptors. Thus the T cell clones CD4 + and CD8 + are generated and join the blood circulation and then the cutaneous tissue. It is interesting to note that CD8 + T cells are effectors in the allergic contact dermatitis reaction in murine models while CD4 + T cells are doted with regulatory properties .

The effector stage: this occurs when the same hapten is
applied on the skin. The hapten is diffused through the
corneal layer and interacts with proteins of the epidermal
cells. The hapten is metabolized by the cutaneous cells and
is found in the cellular membrane in the form of haptenized
peptides onMHCclass I and class II molecules. TheDCare
thus capable of presenting the hapten to CD4 + and CD8 +
T cells present in the dermis. The role of keratinocytes and
other cutaneous cells only expressing MHC class I molecules
appears to be essential for the activation of CD8 +
effector T cells and has long been underestimated .

Perchè alcune sostanze sono potenzialmente allergeniche più di altre? Spiegazione molecolare

L’allergene è un antigene ( sostanza estranea ) che scatena una risposta incontrollata. Una sostanza si dice elettrofila quando tende a creare un legame chimico attratta da una coppia di elettroni. Gli allergeni a basso peso molecolare sono comunemente indicati come apteni. Gli Apteni devono legarsi con le proteine ​​per essere riconosciuti dal sistema immunitario. La maggioranza degli apteni sono reattivi elettrofili o producono metaboliti che formano legami covalenti con centri nucleofili delle proteine​​. Sono possibili anche legami non elettrofili con le proteine attraverso lo scambio disolfuro o legami coordinati su ioni metallici. Recenti studi di chimico cinetica suggeriscono che velocità e facilità con cui si forma il legame proteico sono un fattore importante per determinante la capacità allergenica, tuttavia, la forza elettrofila non sembra far prevedere la capacità di un aptene di influenzare la risposta Th1 e Th2.

Perchè una molecola è allergenica

I più comuni allergeni cosmetici

Alcune ricerche su un campione abbastanza ampio hanno identificato gli allergeni dermici più comuni. In queste ricerche normalmente non viene chiaramente individuato l’allergene o l’aptene che a volte potrebbe essere un prodotto di reazione, un metabolita , una impurezza dovuta a fenomeni di perossidazione ecc. ecc.

Allergic Contact Dermatitis to Preservatives and Fragrances in Cosmetics

Tatyana Hamilton, MD, PhD and Gillian C. de Gannes, MD, FRCPC Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

ABSTRACT

Cosmetics are an important cause of allergic contact dermatitis (ACD). Fragrances and preservatives are the two most clinically relevant allergens found in cosmetic products. Patch testing remains the gold standard for identification of causative allergens. Common cosmetic allergens are reviewed. Practical methods of allergen avoidance are also discussed. 

Key Words: allergic contact dermatitis, fragrance, preservative, skin care

Introduction

The term “cosmetic” is used synonymously with “make-up” in the general population. However, it has a much broader definition and includes personal care products, hair care, nail products, and sunscreens.

There is an impressive array of cosmetic products available on the market today, with an even greater number of individual ingredients. The number of new products continues to increase and the rates of adverse cutaneous reactions are expected to rise. Therefore, given the widespread use of cosmetics, it is important to monitor their side-effects. It is estimated that the average woman uses 12 personal care products daily, which comprise 168 unique ingredients. The average man uses six personal care products each day with 85 unique ingredients.1 Skin care products have been found to account for the majority of cases of allergic contact dermatitis (ACD) to cosmetics, followed by hair care and nail cosmetics.2-5 The most common responsible cosmetic allergens are fragrances and preservatives.6

Epidemiology

The prevalence of cosmetic allergy is estimated at less than 1% in the general population.7-9 However, since most people do not seek medical consultation for mild adverse reactions, the actual rates are likely much higher. Pooled data of seven different studies involving 30,207 patients patch tested for suspected contact dermatitis revealed that 9.8% of positive reactions were due to cosmetic allergens.10 A recent Danish study showed that the prevalence of ACD to cosmetic allergens has doubled between 1990 and 1998.11 The majority of patients affected with ACD to cosmetic products are women between the ages of 20 and 55.2,7-9

In addition, a study of 794 patients showed that 34% of patients would have been missed if they were only tested with NACDG (North American Contact Dermatitis Group) screening series of 65 allergens.12 A European analysis of 5911 cosmetic-allergic patients found that one-third reacted only to a personal product and no other allergen.13 Thus, while the optimal number of allergens for patch testing to cosmetics is not firmly established, testing for additional allergens using a specialized cosmetic series and the patient’s own personal products would capture about 30% of additional patients that otherwise would have been missed.

Clinical Features of ACD

ACD may have acute and chronic forms. Acutely, it presents with pruritic papules, vesicles, and bullae. Chronic forms are more common and present with pruritic, scaly papules and plaques distributed in areas of most contact with the offending allergen. The distribution provides very useful clinical clues about the possible causative agent. Occasionally, ACD may produce autoeczematization resulting in a widespread or generalized cutaneous eruption. Allergens may also be transferred from other persons or even pets, resulting in “connubial” or “consort” dermatitis.14-16

The main differential diagnostic possibilities for ACD are exacerbation of atopic dermatitis or irritant contact dermatitis, both of which are far more common than allergic contact reactions.

Classes of Allergens Responsible for ACD

Cosmetic ingredients can be classified into several categories: fragrances, preservatives, antioxidants, vehicles, ultraviolet absorbers, humectants, emollients, emulsifiers, acrylates, hair dyes, nail polish components, and others.

Preservatives and fragrances are the most frequently detected culprits; therefore, this review will primarily deal with these two classes of allergens.

Preservatives

Preservatives were identified as the most common cosmetic contact allergens in several recent studies.6,17,18 They can be classified into three broad categories: antimicrobials, antioxidants, and ultraviolet light absorbers. The antimicrobial agents can be further divided into formaldehyde preservatives, formaldehyde-releasers, and non-formaldehyde-releasing preservatives. Formaldehyde-releasing preservatives (FRP) include quaternium-15, diazolidinyl urea, imidazolidinyl urea, 2-bromo-2-nitropropane-1,3-diol, and DMDM hydantoin. Non-formaldehyde-releasing preservatives include parabens, methylchloroisothiazolinone-methylisothiazolinone (MCI-MI), methyldibromoglutaronitrile-phenoxyethanol (MDBGN-PE), and iodopropynyl butylcarbamate. Individuals allergic to formaldehyde may also be allergic to any of the FRPs.

Formaldehyde-sensitized individuals may experience a flare of ACD with a number of foods, including cod fish, caviar, coffee, shiitake mushrooms, smoked ham, maple syrup, and aspartame.19 Table 1 lists the top 20 NACDG screening allergens associated with cosmetic source in females.17

For comparison, Tables 2a and 2b list the top 10 allergens from the North American Contact Dermatitis Group (NACDG) and the Mayo Clinic Contact Dermatitis Group (MCCDG) identified in all patients presenting for patch testing. It is evident that many of the top allergens are from cosmetic sources.

Fragrances

There are over 3000 different fragrances used in cosmetics today.20 Not surprisingly, fragrances represent the second most common group of cosmetic allergens. Available tools to assess for fragrance allergy are fragrance mix I (FMI), fragrance mix II (FMII), and balsam of Peru. The components of these screening allergens are listed below:

1 Quaternium-15 2% 323 20.4 11.1
2/3 Myroxylon pereirae (balsam of Peru) 25% 302 19.1 10.3
2/3 Fragrance mix 8% 302 19.1 10.3
4 p-Phenylenediamine 1% 247 15.6 8.5
5 Methyldibromoglutaronitrile/phenoxyethanol 2% 131 8.3 4.5
6 Formaldehyde 1% 108 6.8 3.7
7 Tosylamide formaldehyde resin 10% 97 6.1 3.3
8 Cocamidopropyl betaine 1% 84 5.3 2.9
9 Glyceryl thioglycolate 1% 83 5.3 2.8
10/11 Diazolidinyl urea 1% 79 5.0 2.7
10/11 Diazolidinyl urea 1% 79 5.0 2.7
12 DMDM hydantoin 1% 77 4.9 2.6
13 Lanolin alcohol 30% 71 4.5 2.4
14/15 Imidazolidinyl urea 2% 70 4.4 2.4
14/15 Methylchloroisothiazolinone/methylisothiazolinone 100 ppm* 70 4.4 2.4
16 Methyl methacrylate 2% 65 4.1 2.2
17 Amidoamine 0.1% 63 4.0 2.2
18 Propylene glycol 30% 61 3.9 2.1
19 DMDM hydantoin 1% 58 3.7 2.0
19 Imidazolidinyl urea 2% 51 3.2 1.8
Table 1: Top 20 NACDG screening allergens associated with cosmetics in females * Not in petrolatum; all others are

Fragrance Mix I (8.0% in petrolatum)

  • Amyl cinnamic alcohol 1.0%
  • Cinnamic alcohol 1.0%
  • Eugenol 1.0%
  • Cinnamic aldehyde 1.0%
  • Hydroxycitronellal 1.0%
  • Geraniol 1.0%
  • Isoeugenol 1.0%
  • Oak moss absolute 1.0%
  • Sorbitan sesquioleate (emulsifier) 5.0%

Fragrance Mix II (14.0% in petrolatum)

  • Hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.5%)
  • Citral 1.0%
  • Farnesol 2.5%
  • Coumarin 2.5%
  • Citronellol 0.5%
  • Hexyl cinnamal 5.0%

Many of the specific fragrance ingredients are protected by the Fair Packaging and Labeling Act as they are considered trade secrets.19It is important to keep in mind that many products labeled as ‘unscented’, ‘hypoallergenic’, or even ‘fragrance-free’ do, in fact, contain masking fragrances.

10 Most Common Allergens NACDG
Nickel sulfate
Neomycin
Balsam of Peru
Fragrance mix
Thimerosal
Gold sodium thiosulfate
Quaternium-15
Formaldehyde
Bacitracin
Cobalt chloride
Table 2a: Top 10 list of common contact allergens from NACDG
10 Most Common Allergens MCCDG
Nickel sulfate
Balsam of Peru
Gold sodium thiosulfate
Neomycin
Fragrance mix
Thimerosal
Cobalt chloride
Formaldehyde
Benzalkonium chloride
Bacitracin
Table 2b: Top 10 list of common contact allergens from MCCDG
Cross Reacting Agents
Balsam of Tolu
Benzoin
Benzyl acetate
Benzyl alcohol
Cinnamic alcohol/cinnamic aldehyde
Cinnamon oil
Clove oil
Essential oils of orange peel
Eugenol
Propolis
Table 3: Cross-reactants with balsam of Peru

Balsam of Peru

Balsam of Peru (BOP) (myroxylon pereirae resin) is an aromatic fluid that comes from the bark of the tree Myroxylon balsamum, a tree native to El Salvador.19 It is a complex mixture of many ingredients, all of which have not yet been completely identified. Key ingredients including benzoyl cinnamate, benzoyl benzoate, benzoic acid, vanillin, and nerodilol can be found in the following three groups of products: fragrance in perfumes and toiletries, flavorings in foods and drinks, and medicaments. In the past, FMI and BOP were able to detect approximately 90% of fragrance allergies. However, with the increasing number of fragrances and botanicals in use today, their screening ability is now estimated to be around 60%.19 Thus, FMII and a number of botanical extracts are now part of the 2010 NACDG screening series that comprise 70 allergens. Often, additional cosmetic and botanical series are required to diagnose fragrance allergy. Patients with contact allergy to BOP may also react to a number of substances that are well known cross-reactants with BOP (Table 3). Thus, patients should be appropriately counseled to avoid these agents.

Practical Considerations and Clinical Pearls

  • Choose allergens carefully: based on history, occupation, hobbies, and distribution of dermatitis. Patch testing may need to be expanded beyond the NACDG screening series to include, for example, a cosmetic/botanical supplemental series. This series may be indicated in patients using a variety of make-up products or for those who use ‘all natural’ botanical products. Testing to personal care products may lead to identification of additional relevant allergens, as well as facilitate discovery of new and emerging allergens, as new compounds are being introduced at an escalating pace.
  • Have a good working knowledge of common allergens and their sources: this is critical for choosing the correct allergens to test as well as for counseling patients on allergen avoidance.
  • Have access to available resources: an excellent review of the main concepts of ACD is found in Contact Allergy: Alternatives for the 2007 NACDG Standard Screening Tray.19 Allergen information sheets are available to the members of the American Contact Dermatitis Society (ACDS) and can be found at www.contactderm.org. Identification of allergen-free products can be accomplished by generating a customized product list with the use of the Contact Allergen Management Program (CAMP) available to the members of the ACDS. Multiple allergens can be entered to generate a ‘shopping list’ of products that are safe to use in a patient with allergic contact dermatitis to their cosmetics.

Conclusion

Allergic contact dermatitis to cosmetics is an important cause of ACD overall. The main causes of cosmetic allergy are fragrances and preservatives. It is rewarding for both the patient and the physician if the responsible agent can be identified and subsequently removed from the patent’s environment. Patient satisfaction and compliance will also improve if meaningful counseling is provided, including detailed information on safe to use personal care products.

References

  1. Environmental Working Group’s Skin Deep Cosmetic Safety Database. Available at: http://www.cosmeticsdatabase.com/research. Last accessed: March 1, 2011.
  2. Eiermann HJ, Larsen W, Maibach HI, et al. Prospective study of cosmetic reactions: 1977-1980. North American Contact Dermatitis Group. J Am Acad Dermatol 6(5):909-17 (1982 May).
  3. Adams RM, Maibach HI. A five-year study of cosmetic reactions. J Am Acad Dermatol 13(6):1062-9 (1985 Dec).
  4. de Groot AC. Contact allergy to cosmetics: causative ingredients. Contact Dermatitis 17(1):26-34 (1987 Jul).
  5. de Groot AC, Bruynzeel DP, Bos JD, et al. The allergens in cosmetics. Arch Dermatol 124(10):1525-9 (1988 Oct).
  6. Wetter DA, Yiannias JA, Prakash AV, et al. Results of patch testing to personal care product allergens in a standard series and a supplemental cosmetic series: an analysis of 945 patients from the Mayo Clinic Contact Dermatitis Group, 2000-2007. J Am Acad Dermatol 63(5):789-98 (2010 Nov).
  7. Romaguera C, Camarasa JM, Alomar A, et al. Patch tests with allergens related to cosmetics. Contact Dermatitis 9(2):167-8 (1983 Mar).
  8. Adams RM, Maibach HI. A five-year study of cosmetic reactions. J Am Acad Dermatol 13(6):1062-9 (1985 Dec).
  9. Kohl L, Blondeel A, Song M. Allergic contact dermatitis from cosmetics. Retrospective analysis of 819 patch-tested patients. Dermatology 204(4):334-7 (2002).
  10. Biebl KA, Warshaw EM. Allergic contact dermatitis to cosmetics. Dermatol Clin 24(2):215-32 (2006 Apr).
  11. Nielsen NH, Linneberg A, Menne T, et al. Allergic contact sensitization in an adult Danish population: two cross-sectional surveys eight years apart (the Copenhagen Allergy Study). Acta Derm Venereol 81(1):31-4 (2001 Jan-Feb).
  12. Cohen DE, Rao S, Brancaccio RR. Use of the North American Contact Dermatitis Group Standard 65-allergen series alone in the evaluation of allergic contact dermatitis: a series of 794 patients. Dermatitis 19(3):137-41 (2008 May-Jun).
  13. Uter W, Balzer C, Geier J, et al. Patch testing with patients’ own cosmetics and toiletries–results of the IVDK*, 1998-2002. Contact Dermatitis 53(4):226-33 (2005 Oct).
  14. Wilkinson DS. Connubial photodermatitis. Contact Dermatitis 1:58 (1975).
  15. Fisher AA. Consort contact dermatitis. Cutis 24(6):595-6, 668 (1979 Dec).
  16. Morren MA, Rodrigues R, Dooms-Goossens A, et al. Connubial contact dermatitis: a review. Eur J Dermatol 2:219-23 (1992).
  17. Warshaw EM, Buchholz HJ, Belsito DV, et al. Allergic patch test reactions associated with cosmetics: retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2004. J Am Acad Dermatol 60(1):23-38 (2009 Jan).
  18. Laguna C, de la Cuadra J, Martin-Gonzalez B, et al. [Allergic contact dermatitis to cosmetics]. Actas Dermosifiliogr 100(1):53-60 (2009 Jan-Feb).
  19. Scheman A, Jacob S, Zirwas M, et al. Contact Allergy: alternatives for the 2007 North American contact dermatitis group (NACDG) Standard Screening Tray. Dis Mon 54(1-2):7-156 (2008 Jan-Feb).
  20. Devos SA, Constandt L, Tupker RA, et al. Relevance of positive patch-test reactions to fragrance mix. Dermatitis 19(1):43-7 (2008 Jan-Feb).

In this issue:

  1. Allergic Contact Dermatitis to Preservatives and Fragrances in Cosmetics
  2. Alcohol and Skin Disorders: With a Focus on Psoriasis
  3. Update on Drugs and Drug News – April 2011

Ma in letteratura vengono segnalati molti altri allergeni cosmetici

Review Article

Contact-Allergic Reactions to Cosmetics

Department of Dermatology, Contact Allergy Unit, K. U. Leuven, 3000 Leuven, Belgium

Received 30 November 2010; Accepted 11 January 2011

Academic Editor: Fabienne Rancé

Copyright © 2011 An Goossens. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Contact-allergic reactions to cosmetics may be delayed-type reactions such as allergic and photo-allergic contact dermatitis, and more exceptionally also immediate-type reactions, that is, contact urticaria. Fragrances and preservative agents are the most important contact allergens, but reactions also occur to category-specific products such as hair dyes and other hair-care products, nail cosmetics, sunscreens, as well as to antioxidants, vehicles, emulsifiers, and, in fact, any possible cosmetic ingredient. Patch and prick testing to detect the respective culprits remains the golden standard for diagnosis, although additional tests might be useful as well. Once the specific allergens are identified, the patients should be informed of which products can be safely used in the future.

1. Introduction

Nowadays almost everyone is using cosmetics products, which includes cleansing products such as soaps, bath and shower products, shampoos and toothpaste, as well as, for example, deodorants and make-up products. Indeed, they are used to clean, perfume, change the appearance, protect from body odours, and protect and keep the skin, teeth, and mucosal membranes in good condition. They differ from drugs because they lack diagnostic and therapeutic properties.

Allergic reactions to cosmetic products are increasingly observed. The cosmetic allergens involved can reach the skin in several different ways: by direct application, by occasional contact with an allergen-contaminated surface, by airborne contact (e.g., vapours or droplets), by transfer by the hands to more sensitive areas (e.g., the eyelids), by a product used by the partner (or any other person), or be photo-induced, resulting from contact with a photo-allergen and exposure to sunlight, particularly UV-A light. An allergic contact dermatitis may sometimes spread (symmetrically) to other areas of the body not in direct contact with the allergen (id-like spread reaction); this is comparable to a reaction by systemic exposure (in which the allergen may reach the skin through the circulatory system and produce a systemic contact-type dermatitis), the latter being extremely rarely observed with cosmetics. Besides contact dermatitis, being a delayed allergic response, also immediate type reactions, that is, contact urticaria (syndrome), may exceptionally occur.

2. Allergic and Photoallergic Contact Dermatitis

2.1. Diagnosis

Physical examination and history taking frequently suggest the etiological factor(s), but patch (or epicutaneous) testing is used for diagnosing, with at least two readings of the test results, that is, at day 2 and 4/5 following their application. Allergen identification for a patient with a possible contact allergy to cosmetics is performed by means of patch testing with the baseline (standard) series, specific cosmetic-test series, the products used, along with their ingredients. With regard to the diagnosis of photoallergic contact dermatitis, photo-patch tests need to be performed: the allergens are tested in duplicate on the back and irradiated with U.V. light (most often UV-A 5 J/cm−2). Readings should be recorded immediately and 2 days, as well as at 3 or 4 days postirradiation.

Sometimes open or semiopen (or semiocclusive) tests [12] and use tests [23] or repeated open application tests (ROAT’s) [4] are additional testing procedures. The former methods are useful modifications for cosmetics that have a slight irritation potential, such as, for example, cleansing products. With an open test, the substance is applied uncovered on the upper arm or upper back twice a day during at least 2 days (without washing the test site). A semiocclusive test consists of one application, with a cotton swab on about 1 cm2 of the upper back, of a minute amount of a test material, which is left to dry completely, and covered with acrylate paper tape. The readings are performed after 2, 3, and/or 4 days. Also diluted products (e.g., 1%-2% aqueous) can be tested this way. When contact allergy is suspected and patch testing with the product as such remains negative, use tests on the previously affected site or better, a repeated open application test (ROAT) can be performed.

With ROAT, a very small amount or about 0.1 mL of test material is applied twice daily to the flexor aspect of the forearm near the cubital fossa, to an area approximately 5  ×  5 cm. The results are read after 1 week, but sometimes ROAT need to be performed up to 21 days, especially with low-concentrated allergens, to reveal an allergic reaction.

Once an allergen has been identified, it is the dermatologist’s task to provide specific advice about the products that can be safely used, since subjects sensitive to specific ingredients must avoid products containing them. Although cosmetic labelling exists, providing the allergic patient with a limited list of cosmetics that can be used is, in our experience, most practical and effective [5].

2.2. The Allergens

In cosmetics, fragrances and preservative agents are the most important culprits, but reactions also occur to category-specific products such as hair dyes and other hair-care products, nail cosmetics, sunscreens, as well as to antioxidants, vehicles, emulsifiers, and, in fact, any possible cosmetic ingredient [6].

2.2.1. Fragrance Components

They are frequent culprits in cosmetic allergies. Sensitization is most often induced by highly perfumed products, such as toilet waters, after-shave lotions, and deodorants, but fragrance-containing skin-care products may also cause reactions [6]. The main skin sites affected are the face, neck, axillae, and hands.

The literature confirms that the fragrance mix, which contains 8 perfume components (amyl cinnamal, cinnamal, cinnamyl alcohol, hydroxycitronellal, eugenol, isoeugenol, geraniol, and Evernia prunastri (oakmoss) extract, all diluted 1% in petrolatum and emulsified with sorbitan sesquioleate) and which is tested routinely in the baseline series, remains the best screening agent for contact allergy to perfumes because it can detect some 70% to 80% of all perfume allergies [7]. However, the literature also insists on the need to test with additional perfume allergens. Indeed, testing with additional markers such as, for example, other individual components, as well as with complex natural mixtures [8] increases the sensitivity of the testing. A new fragrance mix (II) consisting of hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral), farnesol, citral, citronellol, coumarin, and alfa-hexyl cinnamaldehyde, as well as hydroxyisohexyl 3-cyclohexene carboxaldehyde [9] itself has been added to the baseline series as well [10]. Because of the increasing importance of fragrance allergy and to ensure that sensitized consumers are adequately informed, 26 fragrance components are (since March 2005) to be labeled as cosmetic ingredients on the packaging (Annex 3 of the Cosmetic Directive 2003/15/EC).

Multiple positive patch-test reactions are frequently associated with fragrance allergy and often indicate the presence of common or cross-reacting ingredients in natural products (e.g., also to plants of the Compositae or Asteraceae family) [11], the occurrence of cross-reactions between simple fragrance chemicals, or a concomitant sensitivity.

Fragrance components may be allergenic by themselves, but may also contain sensitizing oxidation products, as is the case with, for example, limonene [12] and linalool [13], and even certain contaminants. For example, resin acids and their oxidation products are the main allergens in colophony and are in Evernia furfuracea (tree moss) (a widely used perfume ingredient), as well as in oak moss, both in the qualities used by the industry, and in patch-test materials. Besides, in oak moss, atranol and chloratranol have been identified as the most potent allergens ever described [14].

2.2.2. Preservatives

They are very imporant cosmetic allergens in water-based products such as cleansers, skin-care products and make-up [6]. However, within this class important shifts have occurred over the years [15].

Particularly methyldibromoglutaronitrile—that was used in a mixture with phenoxy-ethanol, better known as Euxyl K400—became such an important cosmetic allergen [615] that the EU did not longer permit its further use in cosmetic products (March 2007). The methyl- and methylchloro-isothiazolinone mixture was commonly used in the 1980s and became a frequent cause of contact allergies, and is actually rising again. The mixture had been recommended (up to 15 ppm) to be used only in rinse-off products; however, it is still found in several leave-on products on the market such as moisturizers, and also in (baby) toilet tissue paper (wipes), which produces allergic contact dermatitis [16], most often in those who take care of the babies! Currently, the mixture is now being replaced by methylisothiazolinone alone, which is less allergenic but also less efficient as a preservative, hence larger use concentrations (up to 100 ppm) are required. Patients sensitized by the mixture often react to the nonhalogenated derivative as well though [17], and methylisothiazolinone is a primary sensitizer of itself. We recently observed several cases, most of which caused by the use of wipes (moist toilet paper) for intimate hygiene (and baby wipes); however, also other cosmetic products may be the sensitization source [18]. Since these preservative agents are widely used in household and industrial products, subsequent reactions frequently occur by contact (also airborne) with detergents, paints, glues, and so forth.

The incidence of positive reactions to formaldehyde and its releasers is slightly increasing again (data from the European Environmental Contact Dermatitis Research Group 2008, not published). Meanwhile, parabens are rare causes of cosmetic dermatitis and when allergy does occur, the sensitization source is most often a topical pharmaceutical product. This is often the case also for, for example, mefenesin, a rubefacient in topical pharmaceutical products, which cross-reacts with chlorphenesin, used as a preservative agent in cosmetics (data on file) and thus a potential sensitizing agent [19]. A further recently introduced preservative is iodopropynyl butylcarbamate, also present in baby and make-up cleansing wipes [20], first reported as a cosmetic allergen by Pazzaglia and Tosti in 1999 [21]. Its presence in cosmetics is being discussed, not because of its potentially allergenic properties, but because of its iodine content.

2.2.3. Antioxidants

They are only a minor group of cosmetic allergens. Examples are propyl gallate, octyl gallate [22], which may cross-react with other gallates and are also used as food additives, and t-butyl hydroquinone, a well-known allergen in the United Kingdom but not in continental Europe. Some antioxidants are used more specifically in sunscreen products and also in moisturizing products to prevent ageing, but are rare causes of allergic contact dermatitis in such preparations, for example, tocoferol (vitamine E) acetate and retinol palmitate [23], and ascorbic acid (vitamin C) [24], and more recently also idebenone or hydroxydecyl ubiquinone (a synthetic analog of Coenzyme Q10 (CoQ10) [25]. Also sulfite-allergy may explain reactions to certain cosmetic creams, cleansing products, as well as hair dyes.

With regard to category-specific ingredients, the number of reactions to oxidative type hair dyes (PPD and related compounds) increases in some centers and do decrease in others [26]. Active sensitization to PPD and related compounds from temporary tattoos has become an epidemic, for example, [27]. Moreover, also immediate-type reactions or the contact-urticaria syndrome may occur [28] (see also below). Hair dyes are important causes of dermatitis both in clients, in whom they often cause severe reactions [29] and hairdressers. Other allergens in hairdressing products [26] are bleaches (persulfates, also causes of immediate-type allergic reactions), permanent-wave solutions (primarily glyceryl mono-thioglycolate which may provoke cross-sensitivity to ammonium-thioglycolate), and sometimes shampoo ingredients, for example, cocamidopropyl betaine and preservative agents.

In nail cosmetics, tosylamide/formaldehyde (= toluenesulfonamide formal-dehyde) resin is the classical allergen and is the cause of “ectopic” dermatitis due to nail lacquer, which also may contain epoxy and (meth) acrylate compounds, as well as certain allergenic copolymers; it often gives rise to confusing clinical pictures, even mimicking occupational dermatitis. (Meth) acrylates are important causes of reactions to artificial nails preparations, more recently to gel formulations being the newest development in this regard, both in clients but particularly in manicurists [30].

Because of media attention being given to the carcinogenic and accelerated skin-aging effects of sunlight, sunscreens are increasingly used, not only in sunscreen products but also in other cosmetic products, including moisturizers. They may be responsible for allergic and photoallergic reactions [31] and, for example benzophenones sometimes also for contact urticaria (see below). In the past, dibenzoylmethane derivatives have been recognized as being important allergens [6,32] and isopropyl dibenzoylmethane was withdrawn from use in cosmetics for this reason. On the other hand, methylbenzylidene camphor, cinnamates, and phenylbenzimidazole sulfonic acid are only occasional, sometimes even rare, causes of cosmetic reactions. Octyl triazone [33] rarely causes problems, but octocrylene [34] is increasingly reported as a contact allergen, often in children, and also frequently causes photo-contactallergic reactions [35], and, as with benzophenones, particularly in relation to photocontact sensitization by ketoprofen, a nonsteroidal anti-inflammatory drug used to treat muscle pain. This is most probably based on cross-reactivity.

The contribution of sunscreens to cosmetic allergy has been considered to be relatively small despite the increase in their use; however, the low rate of allergic reactions observed may well be because a contact allergy or a photo-allergy to sunscreen products is often not recognized, since a differential diagnosis with a primary sun intolerance is not always obvious. Furthermore, the patch-test concentrations generally used might be too low, in part because of the risk of irritancy. Last but not least, photo-patchtesting is not at all routinely performed in a dermatologic practice!

2.2.4. Excipients, Emulsifiers, Surfactants, and Humectants

They are common ingredients to topical pharmaceutical and cosmetic products. The classical contact-allergens reported were rare cosmetic allergens, such as wool alcohols, fatty alcohols (e.g., cetyl alcohol), and propylene glycol [6], but more recently introduced ingredients are also described: for example, dicaprylyl maleate [36], isononyl isononanoate and trioley phosphate [37], and the humectants butylene glycol [38] and pentylene glycol [39], being aliphatic alcohols with similar uses (solvent, humectant, and antibacterial) to propylene glycol that is considered to be more irritant and allergenic. Surfactants, in particular, have long been regarded as irritants, but their sensitization capacities should not be overlooked. It is imperative, of course, that patch testing be properly performed to avoid irritancy and that the relevance of the positive reactions be determined. Some of these substances are also, because of their low irritancy potential and “skin-mildness”, often incorporated in skin-care products “recommended by dermatologists”, “for use on intolerant” or “for sensitive skin” that have become very popular in recent years. A low irritant potential, however, does not preclude the occurrence of, albeit rarely, allergic contact dermatitis from such cosmetics. Examples are cocamidopropylbetaine that is considered to be more irritant than allergenic though, and alkyl glucosides, that is, condensation products of fatty alcohols with glucose such as coco-and lauryl glucosides [40], which are often used as mild surfactants and cleansing agents, as well as emulsifiers, particularly cetearyl- and decyl glucoside, the latter exceptionally being a hidden allergen in sunscreens [41].

Other possible allergens include ethylhexylglycerin (syn.: octoxyglycerin), a skin conditioning agent [42], and methoxy PEG-17 and PEG-22/dodecyl glycol copolymers (alkoxylated alcohols and synthetic polymers used as emulsion stabilizers and suspending and viscosity-increasing agents, and also as skin-conditioning agents) [4344]. Moreover, also other copolymers present in nail lacquers, and skin-care and sunscreen products have been reported as skin sensitizers [45]. The exact sensitizing component in them, however, remains unknown.

2.2.5. Natural Ingredients

Plant extracts and herbal remedies have become very popular in recent years and may give rise to (sometimes severe) contact dermatitis problems [4647]. Patients allergic to perfume components should be advised to avoid cosmetics containing plant extracts (separately labelled on the packaging with their Latin INCI-name), some of which being fragrance ingredients such as essential oils [48] and which are not recognized as such by the consumers, or that are used because of other properties, for example, antibacterial or antifungal, such as, for example, Melaleuca alternifoliaor tea tree oil [49].

Protein-derived ingredients, in particular, are often used in skin-care products, especially in those for treating dry skin in atopic subjects (often children). Allergic contact dermatitis (sometimes located mainly on the eyelids) from, for example, oat meal (Avena) [50], hydrolysed wheat [51], or soyabean extracts [52] may develop occasionally, but such products more frequently induce immediate-type reactions (see below).

3. Contact Urticaria (Syndrome)

Contact urticaria appears immediately (mostly within 5 to 20 minutes, exceptionally later) upon contact with the causal agent. The skin reaction is clinically characterized by redness and oedema (sometimes urticarial papules), and may, when immunologically mediated, be accompanied by extracutaneous symptoms such as conjunctivitis, respiratory problems, dizziness, and even anaphylaxis. This is referred to as the “contact urticaria syndrome” in which 4 stadia can be recognized.

Cutaneous symptoms:Stadium 1: localised urticaria,Stadium 2: generalised urticaria, extracutaneous symptoms,Stadium 3: bronchial asthma, rhinoconjunctivitis, otolaryngeal, gastrointestinal symptoms,Stadium 4: anaphylaxis.

3.1. Diagnosis

The diagnosis of contact urticaria consists of a careful history, inspection of the clinical symptoms, and the performance of immediate tests: the suspected materials are tested as such (open), but mostly with prick testing. Readings are performed immediately and up to 1 hour. Also a provocation or usage test can be performed. However, if the anamnesis or the clinical symptoms observed point to a severe extracutaneous reaction, attention is to be paid not to elicit a severe reaction on testing, which should be performed in a hospital environment only. In case of an immunologic-mediated urticaria, specific IgE-antibodies can be searched for. Indeed, there also exists nonimmunologic contact urticaria (NICU), for example, caused by chemicals, such as cinnamal (a fragrance component), and sorbic and benzoic acids (preservatives).

3.2. The Allergens

Cosmetic examples of substances to which also severe reactions have been reported are permanent hair dyes containing PPD [282953], the sunscreen agents benzophenones [5456], and hair bleaches, that is, persulfates, which are often responsible for respiratory symptoms in hairdressers [57]. However, not only low-molecular chemicals but also proteins and protein-derived, that is, hydrolysed products used in skin- and hair-care products are increasingly reported in this regard: for example, oat or Avena extract [5859]—of which the allergenic proteins may be removed though [60]—hydrolyzed wheat protein [61]. Immediate-type reactions to protein-derived products may sometimes give rise to severe symptoms [6162]. Although such reactions seem to be rare and may sometimes be irritant in nature, especially in atopic subjects, their use has given rise to controversies since subjects may perhaps get sensitized through topical preparations and develop food allergies afterwards, or vice-versa, and also in children [5860].

4. Conclusions

Fragrance components and preservatives are the most frequent cosmetic contact allergens; however, all ingredients must be considered as potential culprits and patchtested. Besides allergic contact dermatitis, also immediate-type reactions may occur, for which prick tests are the golden standard for diagnosis. Once the specific allergens are identified, the patient should be informed on which products can be safely used in the future. Indeed, the so-called “hypoallergenic” products are not necessarily less sensitizing [63].

Acknowledgment

This work received support from several companies to the Dermatology Department to set up databases with information to patients and dermatologists.

References

  1. J. J. Leyden, “Risk assessment of products used on skin,” American Journal of Contact Dermatitis, vol. 4, no. 3, pp. 158–162, 1993.

Un’altro elenco di sostanze riportate in letteratura come a rischio di dermatite allergica da contatto.

Amyl cinnamal 122-40-7
Benzyl alcohol 100-51-6
Cinnamyl alcohol 104-54-1
Citral 5392-40-5
Eugenol 97-53-0
Hydroxy-citronellal 107-75-5
Isoeugenol 97-54-1
Amylcinnamyl alcohol 101-85-9
Benzyl salicylate 118-58-1
Cinnamal 104-55-2
Coumarin 91-64-5
Geraniol 106-24-1
Hydroxymethylpentylcyclohexenecarboxaldehyde 31906-04-4
Anisyl alcohol 105-13-5
Benzyl cinnamate 103-41-3
Farnesol 4602-84-0
2-(4-tert-Butylbenzyl)propionaldehyde 80-54-6
Linalool 78-70-6
Benzyl benzoate 120-51-4
Citronellol 106-22-9
Hexyl cinnamaldehyde 101-86-0
d-Limonene 5989-27-5
Methylheptin carbonate 111-12-6
Cetone Alpha 127-51-5
Tree Moss N/A
Alanroot (Inula helenium) 97676-35-2
Allylisothiocyanate 57-06-7
Benzyl cyanide 140-29-4
p-tert-Butylphenol 98-54-4 (Wormseed oil)
Diethyl maleate 141-05-9
Dihydrocoumarin 119-84-6
(6,7-Dihydrogeraniol)
Dimethyl citraconate 617-54-9
6,10-Dimethyl-3,5,9-undecatrien-2-one 141-10-6
(Pseudoionone)
Diphenylamine 122-39-4
Ethyl acrylate 140-88-5
trans-2-Heptenal 18829-55-5
trans-2-Hexenal diethyl acetal 67746-30-9
trans-2-Hexenal dimethyl acetal 18318-83-7
Hydroabietyl alcohol 13393-93-6
Hydroquinone monoethyl ether 622-62-8
(4-Ethoxyphenol)
7-Methoxycoumarin 531-59-9
4-(p-Methoxyphenyl)-3-butene-2-one 943-88-4
1-(p-Methoxyphenyl)-1-penten-3-one 104-27-8
Methyl trans-2-butenoate 623-43-8
7-Methylcoumarin 2445-83-2
5-Methyl-2,3-hexanedione 13706-86-0
(Acetyl isovaleryl)
Musk Ambrette 83-66-9
4-Phenyl-3-buten-2-one 122-57-6
Verbena oil (Lippia citriodora Kunth) 8024-12-2
Methyleugenol 95-15-2



References:

 

 

 

Rodolfo Baraldini

Pubblicato il : 26 settembre 2012
Reviewed : 5 febbraio 2013

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