A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis

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1 A 20-year analysis of previous an emerging allergens that elicit photoallergic contact ermatitis FrankC.Victor,MD,DaviE.Cohen,MD,MPH,anNicholasA.Soter,MD New York, New York Backgroun: Retrospective chart reviews are perioically neee to upate allergen series to etect changes in photoallergic contact ermatitis (PACD) over time. Objective: We sought to evaluate photopatch test results uring a 13-year perio an exten the observations to 20 years. Methos: A retrospective chart review was conucte in patients who were photopatch teste. Results: In all, 76 patients were evaluate. A total of 69 positive photopatch an 45 positive patch test reactions were etecte in 30 an 23 patients, respectively. The frequencies of the positive photopatch test reactions were sunscreens 23.2%, antimicrobial agents 23.2%, meications 20.3%, fragrances 13%, plants an plant erivatives 11.6%, an pesticies 8.7%. Of the positive photopatch reactions to antimicrobial agents, 60% were cause by Fentichlor. Limitations: This stuy was a retrospective chart analysis, an the number of patients was small. Conclusions: Sunscreens an antimicrobial agents were the most frequent allergens eliciting PACD, an there was a ecrease in PACD cause by fragrances. The number of reactions to meications increase. This stuy also emonstrate that pesticies can be a cause of PACD. The etection of reactions to Fentichlor was unexpecte an, although they have been attribute in some stuies to cross-reactions to sulfanilamies an bithionol, such a robust association was not observe in this stuy. This stuy extens our experience of the changes in the allergens that elicit PACD to 20 years. ( J Am Aca Dermatol 2010;62: ) Key wors: antimicrobial agents; Fentichlor; pesticies; photoallergic contact ermatitis; sunscreens. Photoallergic contact ermatitis (PACD) is an uncommon ermatosis that can only be iagnose with the use of photopatch tests. The eruption presents as an eczematous eruption that occurs in a photoistribution. PACD is a T celle meiate or elaye-type hypersensitivity reaction From the Photomeicine Section an the Occupational an Environmental Dermatology Section, Charles C. Harris Skin an Cancer Pavilion, Ronal O. Perelman Department of Dermatology, New York University School of Meicine. Funing sources: None. Conflicts of interest: None eclare. Accepte for publication June 30, Reprint requests: Nicholas A. Soter, MD, Ronal O. Perelman Department of Dermatology, New York University School of Meicine, 550 First Ave, New York, NY Nicholas. Soter@me.nyu.eu. Publishe online February 17, /$36.00 ª 2009 by the American Acaemy of Dermatology, Inc. oi: /j.jaa of the skin that occurs in response to a photoallergen or photoantigen in an iniviual who previously has been sensitize to the same chemical or one that cross-reacts with it. 1 The pathogenesis of PACD is similar to that of allergic contact ermatitis, with the aitional requirement of ultraviolet (UV) light. 2 The action spectrum that most commonly elicits a photoallergic response is UVA, which inclues wavelengths from 320 to 400 nm. The allergens that cause PACD change base on prouct use by a population. The ecline in the use of some proucts an the introuction of new ones have an impact on the prevalence of specific photoallergens that inuce PACD. Retrospective chart reviews are one metho to assess the prevalence of PACD an the responsible specific photoallergens. With this information, photoallergen series can be altere, an changes in trens over time may be etecte. As an extension of our previous 7-year stuy, 3 we sought to evaluate photopatch test results 605

2 606 Victor, Cohen, an Soter JAM ACAD DERMATOL APRIL 2010 uring an aitional 13-year perio to etermine changes in the allergens that elicite PACD in the teste population an to seek potential alterations in the prevalence of PACD uring a 20-year perio. METHODS After approval from our institutional review boar, a retrospective chart review of patients presenting to our institution with a iagnosis of photosensitivity from October 1993 to December 2006 was performe. The age an sex of all patients, the ate of the photopatch tests, an positive photopatch an patch test reactions were recore. Light sources A bank of 47 HO-UVA bulbs (National Biologic Corp, Twinsburg, OH) serve as the UVA light source. The output of the UVA light source was monitore monthly with an IL 1700 research raiometer (International Light Inc, Newburyport, MA). CAPSULE SUMMARY Definite relevant causes of photoallergic contact ermatitis were etecte in 11.2% of iniviuals with a photosensitivity isorer. Sunscreens an antimicrobial agents were the most frequent allergens eliciting photoallergic contact ermatitis. During the past 20 years, the number of reactions to meications increase an the reactions to fragrances ecrease. Pesticies were recognize to be a cause of photoallergic contact ermatitis. Reactions to Fentichlor were unexpecte an it remains unknown whether they are a primary response or a crossreaction to other compouns. as both photoallergic an allergic contact ermatitis. The photoallergens use were the Charles C. Harris Skin an Cancer Pavilion photoallergen series (Table I). For the purposes of ata analysis, the photoallergens use were groupe into 7 categories: sunscreens, antimicrobial agents, meications, fragrances, plants an plant erivatives, pesticies, an other substances. Patients with reactions that coul be temporally linke to a specific exposure in their work or home that also was congruent, base on the appearance an location of the eruption, were consiere currently clinically efinite or probable relevant reactions base on the weight of evience. Only those with currently clinical relevant reactions were inclue in this group. When both metrics of exposure an appearance were not met, an clinical suspicion remaine, a esignation of possible relevance was assigne. Phototests an photopatch tests These tests have been escribe previously. 3 On ay 1, uplicate sets of photoallergens were applie. The etermination of the minimal erythema ose to UVA was performe. A series of cm 2 areas of the covere, uninvolve skin of the buttocks was expose to incremental increases of UVA (8-45 J/cm 2 ). On ay 2, the minimal erythema ose-a was quantitate, an one set of photoallergens was expose to UVA (either 10 J/cm 2 or 50% of the minimal erythema ose-a, whichever was lower). On ays 3 an 5 or 7, the irraiate an nonirraiate photopatch test sites were evaluate. The response was grae using a scoring system recommene by the International Contact Dermatitis Group: 11, erythema an papules; 21, eema or vesicles; 31, bullae an/or erosions; 5, irritant reaction; an 6, negative reaction. A positive response at the irraiate sites, in the absence of a response at the nonirraiate site, was interprete as PACD. A positive response of equal intensity at both irraiate an nonirraiate sites was interprete as an allergic contact ermatitis. A response at both sites, in which the reaction was more pronounce at the irraiate site, was interprete RESULTS Photopatch tests were performe in 76 patients. In all, 35 patients were female an 41 were male. The mean age of the patients was 49.2 years, with a range of 11 to 81 years. Of the patients who were teste, 39.5% ha at least one positive photopatch test reaction. In all, 69 positive photopatch test reactions an 45 positive patch test reactions were etecte in 30 an 23 patients, respectively. Of the positive photopatch test reactions, 23.2% were cause by sunscreens, 23.2% by antimicrobial agents, 20.3% by meications, 13% by fragrances, 11.6% by plants an plant erivatives, an 8.7% by pesticies (Tables II an III). Relevance was assesse for each positive photopatch test reaction by class. Of the photopatch test reactions to sunscreens, 56.3% were of probable relevance an 43.7% of possible relevance; to antimicrobial agents, 6.3% were of efinite relevance an 93.7% of unknown relevance; to meications, 21.4% were of possible relevance an 78.6% of unknown relevance; to fragrances, 22.2% were of efinite relevance, 44.4% of probable relevance, 11.2% of possible relevance, an 22.2% of unknown relevance; to plants an plant erivatives, 50% were of efinite relevance, 25% of probable relevance,

3 JAM ACAD DERMATOL VOLUME 62, NUMBER 4 Victor, Cohen, an Soter 607 Table I. Charles C. Harris Skin an Cancer Pavilion photoallergen series Allergen Sunscreens PABA Cinoxate 2-Hyroxy-4-methoxybenzophenone-5-sulfonic aci (sulisobenzone, BZP-4) 4-Isopropyl-ibenzoylmethane (Eusolex 8020) Menthyl anthranilate 4-Methylbenzyliene camphor (Eusolex 6300) Octylimethyl PABA Octyl methoxycinnamate Oxybenzone (BZP-3) Photoplex (Herbert Laboratories, Irvine, CA) Ti-screen 15 (TI Pharmaceuticals Inc, Irvine, CA) 4-tert-Butyl-4 -methoxyibenzoylmethane (Parsol 1789) Antimicrobial agents Bithionol (2, 2 -thiobis [4, 6-ichlorophenol]) Chlorhexiine iacetate Dichlorophen Fentichlor (2, 2 -thiobis [4-chlorophenol]) Hexachlorophene Sulfanilamie Tribromosalicylanilie Trichlorocarbanilie Triclosan Meications Chlorpromazine hyrochlorie Diphenhyramine hyrochlorie Promethazine Fragrances 6-Methylcoumarin Musk ambrette Musk ambrette Sanalwoo oil Plants an plant erivatives Achillea millefolium Alantolactone Arnica montana Chamomilla romana Chrysanthemum cinerariaefolium Diallylisulfie Lichen aci mix a-methylene-g-butyrolactone Propolis Pyrethrum Sesquiterpene lactone mix Tanacetum vulgare Taraxacum officinal Pesticies Benomyl Captan Captafol Folpet Maneb Zineb Ziram Other chemicals Thiourea (thiocarbamie) Pet control Concentration, iluent 5% Alcohol 5% Pet 5% Alcohol 7.5% Pet 3% Pet (Surrogate for Parsol 1789) as is (Surrogate for Parsol 1789) as is 0.5% Water 0. 1% Alcohol Pet 0.3% Pet % Pet % Pet BZP, Benzophenone; PABA, p-aminobenzoic aci; pet, petrolatum.

4 608 Victor, Cohen, an Soter JAM ACAD DERMATOL APRIL 2010 Table II. Positive photopatch test reactions n (%) Patients with at least one positive 30 (39.5) photopatch test reaction Positive photopatch test reactions an relevance Sunscreens 16 (23.2) Probable relevance 9 (56.3) Possible relevance 7 (43.7) Antimicrobial agents 16 (23.2) Definite relevance 1 (6.3) Unknown relevance 15 (93.7) Meications 14 (20.3) Possible relevance 3 (21.4) Unknown relevance 11 (78.6) Fragrances 9 (13) Definite relevance 2 (22.2) Probable relevance 4 (44.4) Possible relevance 1 (11.2) Unknown relevance 2 (22.2) Plants an plant erivatives 8 (11.6) Definite relevance 4 (50) Probable relevance 2 (25) Possible relevance 1 (12.5) Unknown relevance 1 (12.5) Pesticies 6 (8.7) Possible relevance 2 (33.3) Unknown relevance 4 (66.7) 12.5% of possible relevance, an 12.5% of unknown relevance; an to pesticies, 33.3% were of possible relevance an 66.7% of unknown relevance. Of the total number of reactions, 11.2% were of efinite relevance, 25.4% of probable relevance, 16.9% of possible relevance, an 45.5% of unknown relevance. Of the positive patch test reactions, 53.3% were cause by sunscreens, 28.9% by plants an plant erivatives, 11.1% by pesticies, 2.2% by antimicrobial agents, 2.2% by fragrances, an 2.2% by meications. DISCUSSION Definite relevant causes of PACD were etecte in 11.2% of iniviuals with a photosensitivity isorer. This fining is consistent with a previous stuy 3 at our institution, which showe a prevalence of 12%, an with another stuy, 4 which also was conucte in New York, that showe a prevalence of 11%. The prevalence of PACD an of the specific allergens that inuce PACD can vary wiely, change over time, an epen on the population teste. In the 1960s an 1970s, antimicrobial agents, such as salicylanilies, were causes; in the 1970s an 1980s, fragrances, such as musk ambrette an 6-methylcoumarin, were causes; an in the 1980s an 1990s, sunscreens an topical nonsteroial anti-inflammatory rugs became prominent causes. The topical use of nonsteroial anti-inflammatory agents in Europe has been associate with an increase in PACD to these agents (Table IV). 16 In this stuy, sunscreens continue to be the most common allergens that elicite photopatch test reactions. As some of the teste sunscreens containe multiple agents (ie, Photoplex, Herbert Laboratories, Irvine, CA), internal controls were use to etermine the specific allergen that was responsible for the positive photopatch test reactions. p-aminobenzoic aci an its relate esters an benzophenones were the most common sunscreen allergens. The prevalence of positive photopatch test reactions to sunscreens reflects their wiesprea use. Antimicrobial agents also have increase as a cause of PACD. Although their relevance is unclear, there was an increase in the number of reactions to meications. These observations are in contrast to the results obtaine with fragrances, such as musk ambrette an sanalwoo oil, which ecrease in prevalence in the stuy. Plants an plant erivatives an pesticies were the next most common allergens to elicit positive photopatch test reactions. The majority of positive photopatch test reactions to plants were of efinite relevance; however, almost all of the reactions cause by pesticies were of unknown relevance. Nine of 15 (60%) of the positive photopatch test reactions to antibacterial agents were cause by Fentichlor. When the reactions to Fentichlor are exclue, the percentage of reactions to antimicrobial agents i not increase. Fentichlor was a component of antibacterial creams in the 1960s; however, it is no longer present in topical preparations in the Unite States. Although PACD to Fentichlor was etecte in retrospective stuies in Europe in the 1980s an 1990s, 8,10 reports of PACD to Fentichlor have been rare. In a report in 1979, 4 patients with PACD to Fentichlor became persistent light reactors. 17 Three of the exposures were cause by a hair cream that containe Fentichlor; the fourth exposure was cause by an inustrial exposure. Aitional cases were reporte in an iniviual in France, who was expose to soap, 18 an in a service engineer in the Unite Kingom, who was expose to a cooling system liqui. 19 Although cross-reactivity between bithionol an Fentichlor has been ocumente, 20,21 bithionol accounte for 3 of 16 (19%) of the positive photopatch test reactions to antimicrobial agents in our stuy. Only one of our patients ha positive reactions to both Fentichlor an bithionol. In a stuy in 2002, 22 patients who ha photoallergy to

5 JAM ACAD DERMATOL VOLUME 62, NUMBER 4 Victor, Cohen, an Soter 609 Table III. Allergens eliciting positive photopatch test reactions Sunscreens Antimicrobial agents Meications Fragrances PABA 4 (5.8%) Fentichlor 9 (13%) Promethazine Musk ambrette 9 (13%) 6 (8.7%) Oxybenzone Bithionol Chlorpromazine 6-Methylcoumarin 4 (4.3%) 2 (3.0%) Benzophenone-4 Sulfanilamie Diphenhyramine Sanalwoo oil 2 (3.0%) Parsol 1789 Chlorhexiine Octylimethyl Dichlorophen PABA 2 (3.0%) Paimate O PABA, p-aminobenzoic aci. No of positive patch test reactions (percent of total). Plants an plant erivatives Diallylisulfie Alantolactone Arnica montana Pyrethrum Sesquiterpene lactone mix Tanacetum vulgare Pesticies Folpet Captan 2 (3.0%) Captafol Table IV. Summary of photopatch test stuies Location n Stuy perio Most frequent allergens Scaninavia Musk ambrette, PABA, promethazine, chlorpromazine Unite States 6 (Minnesota) Chlorpromazine, musk ambrette, promethazine Unite Kingom Sunscreens, chlorpromazine, promethazine, musk ambrette Unite States 4 (New York) Sunscreens, antimicrobial agents, fragrances Austria, Germany, Switzerlan Tiaprofenic aci, Fentichlor, carprofen, 4-isopropyl-ibenzoylmethane Unite States 3 (New York) Sunscreens, fragrances, antimicrobials agents Netherlans Chlorpromazine, promethazine, musk ambrette Austria, Germany, Switzerlan Fentichlor, carprofen, chlorpromazine, 2-hyroxy-4-methoxybenzophenone Australia Oxybenzone, benzophenone-4 France Sesquiterpene lactone, ketoprofen, benzophenone, ibenzoylmethane Inia Musk ambrette, chlorpromazine, promethazine, balsam of Peru Netherlans Eusolex 8020, Parsol 1789, benzophenone-3 Unite Kingom an Europe Benzophenone-3 Unite States Meications, sunscreens, fragrances, antiseptics Italy Ketoprofen, piroxicam, promethazine, octocrylene PABA, p-aminobenzoic aci. ketoprofen were teste to Fentichlor an halogenate salicylanilies among other allergens. Of the 9 patients teste, all ha positive reactions to Fentichlor, an 4 ha positive reactions to the halogenate salicylanilies. The positive reactions to ketoprofen, Fentichlor, an the salicylanilies were interprete by the authors as cross-reactions to a common metabolite. This hypothesis is not reaily applicable to our patient population, owing to the infrequent use of topical nonsteroial antiinflammatory rugs in the Unite States. Although one of our patients ha positive reactions to both Fentichlor an bithionol, the importance of photoallergy to Fentichlor in our patients is unclear. A Worl Wie Web site search for commercial proucts currently available in the Unite States that contain Fentichlor yiele only a prouct from Nipa Harwicke Inc (Wilmington, DE) that is use in water cooling systems. It remains unknown if positive test reactions to Fentichlor represent a primary allergic response or a cross-reaction with other chemical compouns. A recent stuy from the Unite States showe that 9% of the PACD reactions were cause by Fentichlor. 15 Our stuy emonstrates both the changing nature of reactions to photoallergens an the fact that continue an vigilant observation is necessary to maximize the relevance of photopatch test allergen series.

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