THE TEMPORARY paint-on tattoo,

OSERVATION Clinicopathologic Features of Skin Reactions to Temporary Tattoos and Analysis of Possible Causes Wen-Hung Chung, MD; Ya-Ching Chang, MD; Lih-Jen Yang, MD; Shuen-Iu Hung, PhD; Wen-Rou Wong, MD; Jing-Yi Lin, MD; Heng-Leong Chan, MD ackground: Recently, temporary paint-on tattoos have become increasingly popular as a safe alternative to permanent tattoos in Asia and other regions. The most common dye for such temporary tattoos is henna, a vegetable dye. Henna is considered to possess low allergenicity because the incidence of allergic contact dermatitis to henna has rarely been reported. However, recently, allergic reactions to henna used in temporary tattoos have been reported frequently. Observations: Ten patients developed inflamed skin eruptions after receiving temporary paint-on tattoos in either Thailand or Indonesia. The 6 patients who were patch tested all exhibited moderate to strong positive reactions to p-phenylenediamine (1% in petrolatum). Four of the 6 patients were then tested with commercial black henna obtained from Thailand, and all 4 had strong positive reactions. A skin biopsy specimen showed lichenoid dermatitis. Mass spectrometry analysis of commercial black henna for molecular weight revealed a major peak at the mass-charge ratio of 108.1, which corresponds to the molecular weight of p-phenylenediamine. Conclusions: The most likely causative agent for the lichenoid reaction associated with use of commercial black henna for temporary tattooing, currently popular in Southeast Asia, is p-phenylenediamine. With the increased popularity of temporary paint-on tattoos, clinicians should be aware of the possible associated complications. Arch Dermatol. 2002;138:88-92 From the Department of Dermatology, Chang Gung Memorial Hospital (Drs Chung, Chang, Yang, Wong, Lin, and Chan), and the Institute of Microbiology and Immunology, National Yang-Ming University (Dr Hung), Taipei, Taiwan. THE TEMPORARY paint-on tattoo, derived from the art of henna used in India, the Arab world, and Africa for many traditional ceremonies, 1 has gained increasing popularity recently. Henna is a material obtained from the dried leaves of a shrub (Lawsonia inermis) found in dry tropical and subtropical zones, including North Africa, India, Sri Lanka, and the Middle East. Henna has been used worldwide as a hair dye and as a component of some shampoos, and it also has a variety of other cosmetic uses. 1 Contact dermatitis to henna has been previously reported, 2-4 but its incidence seems to be low. However, recently, allergic reactions to henna used in temporary tattoos have been reported frequently. 5-10 Although temporary tattoos are not so popular in Taiwan, several people have been observed at Chang Gung Memorial Hospital, Taipei, to have experienced a contact allergy arising from application of temporary tattoos. The patients received tattoos while they were traveling in Thailand or ali. In this article, we describe 10 patients who developed unusual skin reactions after application of temporary paint-on tattoos. Furthermore, we analyze the agent responsible for such unusual allergic reactions, derived from commercial black henna. RESULTS Three patients experienced a moderate to intense pruritic and burning sensation on the tattooed areas 2 days after tattoo application, and the remaining 7 experienced only mild pruritus during the first week subsequent to tattooing. Most patients did not notice any abnormal eruptions from the tattooed areas until the black discoloration began to fade. Most lesions exhibited raised, erythematous eruptions along the designs of the specific tattoos, with or without blister formation in the early stages (Figure 1). For most patients, treatment with or without oral s in addition to antihistamines and potent topical s led to variation in response or resolution. Postinflammatory hyperpigmentation at the former tattoo site was subsequently noted for most patients. Clinical presentation, treatment, and follow-up data are summarized in Table 1. Six patients patch tested with the European standard series all revealed moderate (++ [erythema, infiltration, papules, vesicles]) to strong (+++ [intense ery- 88

PATIENTS AND METHODS From February 7, 2000, to August 23, 2000, ten patients seen at the dermatology clinic (Chang Gung Memorial Hospital) had pruritic, burning, inflamed, and edematous skin reactions after application of temporary paint-on tattoos in Thailand or ali. The following data were collected: sex, age, dye color, country or location of tattoo application, onset of eruption subsequent to application, allergy history, clinical appearance of allergic reaction along tattooed areas, treatment, and follow-up. Six of the 10 patients agreed to undergo patch testing with the European standard series (Chemotechnique Diagnostics, Tygelsjö, Sweden). Four of the 6 patients were also tested with natural henna and commercial black henna obtained from Thailand, at 10% and 20% aqueous solutions and also as pure powder. Ten control subjects were also patch tested with natural and commercial henna. The substances were applied, using an IQ Chamber (Inert Quadrate & Ideal Quick Test Chamber unit; Chemotechnique Diagnostics), to the upper back and remained there for 48 hours. Readings were taken after 72 hours. Reactions were scored according to the scale recommended by the International Contact Dermatitis Research Group. Thesampleofcommercialblackhennawasobtained from a local artisan in Thailand where most of our patientsreceivedtemporarytattoosduringtheirtrips.naturalpowderedhenna(conceptstudio,india)wasobtained fromalocaltaipeibeautician. Thesehennasampleswere analyzedusingmassspectrometryinelectronimpactand fast atom bombardment modes. A skin biopsy sample was obtained from the eruption of the tattooed area on patient 8 a week after tattoo application. 1 2 Figure 2. Results of patch tests. Patient 8, similar to the 5 other patients tested, had a positive reaction to 1% p-phenylenediamine (PPD) in petrolatum. In addition, this patient also showed a strong positive reaction to commercial black henna. 1 indicates natural henna powder ( ); 2, commercial black henna powder (+++ [intense erythema, infiltration, and coalescing vesicles]); 3 and 4, natural henna, 10% and 20% aqueous solutions, respectively ( ); 5 and 6, commercial black henna, 10% and 20% aqueous solutions, respectively (++ [erythema, infiltration, papules, vesicles]); and 7, PPD (++). 3 4 5 6 7 A Figure 1. Skin lesion samples from patient 6 (A) and patient 9 () demonstrating erythematous or violaceous, raised (lichenoid) eruptions along the designs of the tattoos, with or without associated vesicle formation in the early stages. Figure 3. Skin biopsy sample from the eruption of a tattooed area (patient 8) revealing hyperkeratosis, parakeratosis, and acanthosis of the epidermis with exocytosis and dermal perivascular lymphocytic infiltrate with the destruction of the basal layer that caused pigmentary incontinence, indicating a lichenoid dermatitis (hematoxylin-eosin, original magnification 100). thema, infiltration, coalescing vesicles]) reactions to p- phenylenediamine (PPD) (1% in petrolatum). Four of the 6 patients were also tested with commercial black henna and demonstrated moderate or strong positive reactions to 10% aqueous solution and strong positive reactions to 20% aqueous solution and pure black henna powder (Figure 2). Only patient 1 exhibited a positive reaction to natural powdered henna (+ [erythema, infiltration, possibly papules] to 10% aqueous solution and moderate [++] to 20% aqueous solution and pure powder). In addition, of these 6 patients, 2 had a positive reaction to nickel, 1 to cobalt, and 1 to thiuram mix. All results of control patch testing for natural henna and commercial black henna were negative. Results of patch testing are summarized in Table 2. 89

Table 1. Clinical Presentation, Treatment, and Follow-up for 10 Patients With Reactions to Temporary Tattoos* Patient No./ Sex/Age, y Country of Tattoo Application Onset of Eruption 1/M/26 Thailand Slow, 2 wk None Itchy, erythematous, edematous 2/F/22 ali, Indonesia Acute, 2 d Rubber, hair dye Allergy History Clinical Appearance Treatment Follow-up Itchy, erythematous, and eczematous eruption Topical and oral s, antihistamines Topical and oral s, antihistamines Topical Gradual remission in 4 mo, Gradual remission in 5 mo, 3/M/24 ali, Indonesia Slow, 1 wk None Itchy, violaceous, and raised Resolved in 1 mo, 4/M/28 Thailand Acute, 2 d None Itchy, erythematous, papular Topical Resolved in 2 wk eruption (eczematous) 5/M/28 Thailand Slow, 1 wk None Itchy, erythematous papules and Antihistamines, topical Resolved in 3 mo, raised eruption 6/M/28 Thailand Slow, 1 wk None Itchy, violaceous, and raised Antihistamines, topical Resolved in 2 mo, eruption; vesicles (+) (lichenoid) 7/F/18 Thailand Acute, 2 d None Itchy, erythematous eruption with Antihistamines, topical Lost to follow-up residual black coloring; vesicles (+) 8/F/22 Thailand Slow, 1 wk None Itchy, erythematous, and raised Antihistamines, topical Complete remission in 3 mo 9/F/20 Thailand Slow, 1 wk None Itchy, erythematous eruption Topical Residual hyperpigmentation remained for 6mo 10/M/22 Thailand Slow, 2 wk None Itchy, erythematous, and raised Topical Residual hyperpigmentation remained for 5mo *+ Sign indicates with clinical manifestation. Table 2. Results of Patch Testing* Natural Henna lack Henna Patient No. 10% aq soln 20% aq soln Pure Powder 10% aq soln 20% aq soln Pure Powder PPD Other Allergens 1 + ++ ++ ++ +++ +++ +++ 2 +++ +++ +++ +++ Nickel ++ Thiuram mix + 5 +++ +++ +++ ++ 7 ++ ++ +++ ++ Cobalt +++ 9 NA NA NA NA NA NA ++ 10 NA NA NA NA NA NA ++ Nickel + *Six patients were patch tested with the European standard series; 4 of these were also tested with natural powdered henna and commercial black henna. aq soln indicates aqueous solution; PPD, p-paraphenylenediamine (1% in petrolatum); +, erythema, infiltration, possibly papules; ++, erythema, infiltration, papules, vesicles; +++, intense erythema, infiltration, coalescing vesicles;, negative reaction; and NA, not available. A skin biopsy sample taken from the eruption of the tattooed area of patient 8 revealed hyperkeratosis, parakeratosis, hypergranulosis, and acanthosis of the epidermis, with exocytosis and scattered dyskeratotic cells. There was a dermal perivascular lymphocytic infiltrate with destruction of the basal layer that caused pigmentary incontinence, indicating a lichenoid dermatitis (Figure 3). The electron impact mass spectrometry spectrum of the commercial black henna sample demonstrated a major peak at an m/z ratio (mass-charge) of 108.1, which corresponds exactly to the molecular weight of PPD. The fast atom bombardment mass spectrometry spectrum of natural henna showed a series of complex peaks, demonstrating a clear difference from commercial black henna (Figure 4). COMMENT Recently, allergic reactions caused by temporary henna tattoos have been described in several articles in the English-language literature (Table 3). Although henna was described as a commonly used paint-on dye in most of those articles, some researchers 7,8 found that use of a variety of additives intended to provide variable coloration, especially PPD, was the principal cause responsible for eliciting the allergic reaction associated with henna-containing tattooing. Natural henna, containing an active agent of lawsone (2-hydroxy-1,4- naphthoquinone), is grayish green; all other colors obtained with henna are due to the addition of other agents. 1 Cross-reactivity between lawsone and PPD is not likely to occur owing to their different chemical structures (Figure 5). Henna can be used in combination with other materials, such as PPD, lemon juice, or beet juice, to produce more intense coloration and to reduce dye fixation time. 1 To our knowledge, no previous reports concerning temporary tattoo allergy analyzed the actual allergen(s) from commercial paint-on dyes directly, despite their similar positive results to PPD by using patch testing. To elicit the 90

Table 3. Summary of Reported Allergic Reaction(s) to Temporary Paint-on Tattoos Reported in the English-Language Literature Cases, No. Country of Tattoo Application Patch Test: Positive Results (Positive Cases/Tested Cases) Study Clinical Description Follow-up O rien and 2 ali, Indonesia Weeping red, raised reaction in Not available Resolved in a few weeks McColl, 9 1999 an exact pattern of the tattoo Nixon and 4 ali, Indonesia Severe dermatitis p-phenylenediamine, Not available Orchard, 10 1999 aminoazobenzene, disperse yellow 3, 4-aminophenol, disperse orange 1, black rubber mix, and diaminotoluenesulfate (1/1) Lewin, 5 1999 1 Canada Itchy inflammation Not available Keloid scarification persisted for 8wk Lestringant et al, 7 14 United Arab Lichenoid reaction along the p-phenylenediamine (3/6), scented Not available 1999 Emirates initial drawing pattern oily additive (3/6), plain henna (1/1) Lyon et al, 6 2000 1 United States Itchy small papules, Not available Gradual improvement in erythematous and raised several weeks eruption along the design of the tattoo Rubegni et al, 8 2000 Sidbury and Storrs, 18 2000 Le Coz et al, 19 2000 *Pathologic finding of biopsy. 1 Zanzibar, Tanzania 1 Zanzibar, Tanzania 4 France, Egypt, United States Red palpable skin reaction (lichenoid dermatitis*) Extremely pruritic, red, vesicular, and exudative eruption Itchy, edematous, or eczematous eruption, with or without crusting, scaling, and vesicle formation p-phenylenediamine and plain henna (1/1) p-phenylenediamine and henna powder (1/1) p-phenylenediamine (3/3); p-toluenediamine, p-aminophenol, p-aminoazobenzene, o-nitro-p-phenylenediamine, disperse orange 3, and tixocortol pivalate (1/3) Resolved in 1 wk Gradual resolution in 2-3 wk, with residual postinflammatory hyperpigmentation Resolved with or without residual pigmentation; 1 had a depigmented scar that recurred spontaneously 100 A 108.1 (PPD) Relative Abundance, % 80 60 40 80.0 20 53.0 67.0 91.0 119.1 149.0 167.0 199.1 223.1 239.2 100 200 300 400 m/z 279.1 295.3 320.3 346.3 371.3 100 69.7 Relative Abundance, % 80 60 40 55.9 81.6 184.1 20 121.2 165.1 50 100 150 200 250 300 350 400 m/z Figure 4. A, The electron impact mass spectrometry spectrum of commercial black henna depicting a major peak at an m/z (mass-charge) ratio of 108.1, corresponding exactly to the molecular weight of p-phenylenediamine (PPD) (1% in petrolatum)., The fast atom bombardment mass spectrometry spectrum for natural henna as a series of complex peaks. 91

A NH 2 NH 2 p-phenylenediamine 0 0H 2-Dihydroxy-1,4-naphthoquinone Figure 5. The chemical structures of p-phenylenediamine (A) and lawsone, the active ingredient of henna (). 0 principal allergen responsible for the unusual reactions to commercial black henna, popular for tattooing in Southeast Asia, a sample of commercial black henna powder was obtained from a local artisan in Thailand. However, mass spectrometry of the commercial black henna revealed only PPD as the major ingredient (molecular weight, 108.1) and not lawsone (molecular weight, 174.2), the active agent of henna. This analysis also revealed that the principal ingredient of commercial black henna is more likely a synthetic dye, as indicated by the presence of 2 simple major peaks, compared with natural henna, which contains a series of complex peaks. Although lichenoid reactions to permanent tattoos, especially red dye, have been well known, 11-13 a lichenoid reaction to a paint-on tattoo has rarely been reported. Lestringant et al 7 in 1999 described a clinical lichenoid eruption due to tattooing with a henna mixture. Rubegni et al 8 recently reported a histopathologic finding of lichenoid dermatitis caused by an allergic reaction to a temporary tattoo. According to the results of patch tests, both these groups indicated that the possible causative factors of lichenoid reaction to temporary tattooing were the contained additives of dyes, especially PPD. In this study, most of the clinical appearances and the pathologic finding also demonstrated a lichenoid reaction associated with allergic reaction to temporary tattooing, and the results of patch tests in our 6 patients all revealed strong positive reactions to PPD. Furthermore, as a result of mass spectrometry analysis of the commercial dyes used for temporary tattooing, we speculate that PPD is the major ingredient of commercial black henna and that the causative agent responsible for most lichenoid reactions arising from tattooing is PPD, not henna itself. uckley, 14 in 1958, described lichenoid eruptions after contact dermatitis among photographic operators who handled a certain PPD. He further classified such cases into 2 groups according to their clinical course, these being an acute and a subacute type. The clinical features described by uckley are similar to our findings. In our study, the clinical course may also be divided into 2 groups: (1) an acute response to temporary tattooing, typically presenting with intense eczematous responses within 1 to 2 days of tattooing, and (2) a subacute response, that is, developing lichenoid eruptions slowly in 1 to 2 weeks. p-phenylenediamine has been used as a permanent or semipermanent chemical hair dye for a long time, and allergic contact dermatitis from PPD has been reported in hair dye users and hairdressers. 15,16 Recently, PPD-containing hair dye has been reported 17 to be implicated as a causative agent in a series of lichenoid eruptions experienced by users of specific hair dye preparations. All the lesions demonstrated by our patients disappeared subsequent to treatment with antihistamines and potent topical s, with or without oral s; however, the clinical responses were notably different. Some lesions subsided within a few weeks, and others required several months to subside despite use of short-course oral s. Most of our patients exhibited remnant postinflammatory hyperpigmentation. Although we speculate that the high incidence of residual hyperpigmentation may be due to Asian skin type, a prolonged residual pigmentary phase after an intense lichenoid dermatitis following contact with PPD-containing color developer has also been described by uckley. 14 Henna was considered to be the paint-on dye causing allergic reactions in some previous reports 5,6 ; however, the results of our study reveal that the most likely allergen of tattooing dye, especially black henna popular in Southeast Asia, is PPD, not henna itself. With the increased popularity of temporary paint-on tattoos, clinicians should be aware of the complications associated with the use of paint-on dyes, especially those containing PPD. Accepted for publication May 16, 2001. We thank Hui Chung-Yee, MD, for patient referral and to Jennifer C. Lee, MD, for reviewing and editing this manuscript. Corresponding author and reprints: Ya-Ching Chang, MD, Department of Dermatology, Chang Gung Memorial Hospital, 199, Tun Hwa North Road, Taipei, Taiwan (e-mail: hsula@ms11.hinet.net). REFERENCES 1. Natow AJ. Henna. Cutis. 1986;38:21. 2. Wantke F, Götz M, Jarisch R. Contact dermatitis due to henna, Solvent Red 1 and Solvent Red 3: a case report. Contact Dermatitis. 1992;27:346-347. 3. Nigam PK, Saxena AK. Allergic contact dermatitis from henna. Contact Dermatitis. 1988;18:55-56. 4. Pasricha JS, Gupta R, Panjwani S. Contact dermatitis to henna (Lawsonia). Contact Dermatitis. 1980;6:288-289. 5. Lewin PK. Temporary henna tattoo with permanent scarification [letter]. CMAJ. 1999;160:310. 6. Lyon MJ, Shaw JC, Linder JL. Allergic contact dermatitis reaction to henna. Arch Dermatol. 2000;136:124-125. 7. Lestringant GG, ener A, Frossard PM. 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