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Background: The textile dye mix (TDM) 6.6% pet. contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM-positive patients is DO 3. Around 85% of p-phenylenediamine (PPD)-allergic dermatitis patients have shown positive patch test reactions to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of frequent, strong reactions to TDM 6.6% and PPD., Objectives: To study if DO 3 can be omitted from a TDM., Methods: Patch tests were performed on 2250 dermatitis patients with TDM 6.6%, TDM 5.6% pet., TDM 7.0% pet., and PPD 1.0% pet.; 122 patients were also patch tested with DO 3 1.0% pet., Results: Among the 2250 patients patch tested, contact allergy prevalence to TDM 6.6% was 2.4%, to TDM 5.6% 1.8%, and to TDM 7.0% 2.0%. Of the 54 TDM 6.6%-positive patients, 55.6% reacted to PPD; as much as 42.2% of PPD-allergic women and 50% of PPD-allergic men reacted to TDM 6.6%. Of the 17 DO 3-positive patients, 94.1% showed a positive reaction to PPD., Conclusion: Results indicate that DO 3 can probably be omitted from TDM, but patch testing with TDM 6.6%, TDM 7.0%, DO 3 1.0%, and PPD 1.0% simultaneously is needed to finally decide whether it is possible or not., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Solvent Orange (SO) 60 is a perinone-type dye that is often used in plastic materials such as spectacle frames and has been shown to cause contact allergy. The first case of SO 60 allergic contact dermatitis caused by spectacle frames was reported in 1999, and the second in 2011. We have recently seen 10 patients, of whom 6 developed dermatitis in the retroauricular/temporal area after wearing plastic spectacles., Objectives: To report the cause of the dermatitis in the 10 patients and to describe our first case with occupational SO 60 contact allergy., Methods: In this retrospective study, patch test results of 10 patients, tested with the Swedish baseline series and our specific spectacle and/or plastic series, including SO 60 1.0% pet., in 2011-2017 were analysed., Results: Ten patients, 2 males and 8 females, aged 43 to 71 years, reacted positively to SO 60 1.0% pet., namely, 4 pensioners, 2 nurses, 1 office worker, 1 teacher, 1 shop assistant, and 1 unemployed person. Four of the patients had an atopic history. Patch test reactions varied from + to +++; some had spread >20 cm outside the test area in terms of erythematous, infiltrated skin with papules. Retesting of patient no. 1 with serial dilutions of SO 60 in acetone showed positive reactions down to 1 ppm. Three patients reacted to the extracts of their earpieces. Gas chromatography-mass spectrometry was used to confirm the presence of SO 60 in 2 earpieces., Conclusions: SO 60 should be included in any spectacle patch test series that may be used. If there is a strong suspicion of contact allergy to SO 60 before patch testing, lowering the test concentration from 1.0% to 0.01% should be considered., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Concern about causing active sensitization when patch testing is performed with p-phenylenediamine (PPD) 1% pet. has led to a recommendation to use PPD 0.3% pet. as a potentially safer preparation. However, the dose per area of allergen delivered, and hence the risk of active sensitization, depend on the amount dispensed into the patch test chamber, which can vary widely., Objective: To evaluate whether patch testing with equivalent doses of different concentrations of PPD in pet. is associated with similar outcomes., Methods: Seventeen known PPD-sensitive subjects were patch tested with different volumes and concentrations of PPD in pet. that deliver the same allergen dose per unit area (6 mg of PPD 1% pet. and 20 mg of PPD 0.3% pet. in Finn Chambers®, both equivalent to ∼ 0.09 mg/cm 2 )., Results: Eleven patients (65%) had positive reactions to both doses; 4 patients (24%) had negative results [percentage agreement of 88% (15/17)]. One patient each had a positive reaction to only one dose., Conclusions: The 88% concordance suggests that dose per unit area is more important in determining reactions to allergens than the excipient volume dispensed. Patch testing with a smaller volume of 1% PPD may be a reasonable alternative to testing with 20 mg of 0.3% PPD., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hair dyes represent one of the most important causes of allergic contact dermatitis resulting from the use of cosmetic products. The principal causative chemistry is associated with oxidation products of p-phenylenediamine (PPD) and closely related substances., Objectives: To examine whether prior application of the antioxidant vitamin C to the skin was able to reduce the cutaneous allergic response to PPD., Methods: Twenty eight volunteers with a proven history of contact allergy to PPD were recruited. Each was tested with a range of PPD doses and PPD-containing hair dye on untreated skin and skin pretreated for 10 min with a vitamin C formulation., Results: Pretreatment of skin sites with vitamin C led to a reduction in the intensity, or even ablation, of the cutaneous allergic reaction to PPD in ∼75% of cases as compared with untreated skin., Conclusions: The results suggest that treatment of the skin adjacent to the hair-bearing area with antioxidant could form part of a strategy to reduce the burden of cosmetic allergic contact dermatitis caused by hair dyeing., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Penetration, autoxidation and N-acetylation of p-phenylenediamine (PPD) have been studied in vitro and ex vivo. However, a clear understanding of in vivo PPD penetration and the formation of PPD derivatives is lacking., Objectives: To obtain insights into the in vivo penetration, clearance and formation of PPD derivatives in human skin., Methods: Patch test chambers containing PPD 1% pet. were applied to the forearms of two human volunteers, with increasing application times. Non-invasive Raman microspectroscopy was used for detection of PPD (derivatives) in skin at several follow-up times., Results: Application of a PPD 1% pet. patch for 30 min resulted in substantial amounts of PPD in the stratum corneum of 90 mg PPD/g keratin. PPD contents were highest after three applications for 1 h each (330 mg PPD/g keratin), followed by single applications for 2 h 40 min, 2 h, and 23 h. The PPD half-time in the skin was 3 h. No spectral contributions of Bandrowski's base, monoacetyl-PPD and diacetyl-PPD were detected., Conclusions: We have gained insights into the in vivo penetration of PPD in human skin by using non-invasive Raman spectroscopy. Penetration into the skin was fast, and the PPD concentrations detected in the stratum corneum were high. PPD was detected in both the stratum corneum and the viable epidermis. Oxidized or acetylated PPD derivatives could not be detected., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Henna, the dried and powdered leaf of Lawsonia inermis, is widely used as a dye for the skin, hair, and nails, and as an expression of body art, especially in Islamic and Hindu cultures. As it stains the skin reddish-brown, it is also called red henna. Black henna is the combination of red henna with p-phenylenediamine (PPD), and is used for temporary 'black henna tattoos'. This article provides a full review of the side-effects of topical application of red and black henna, both cutaneous (allergic and non-allergic) and systemic. Red henna appears to be generally safe, with rare instances of contact allergy and type I hypersensitivity reactions. In children with glucose-6-phosphate dehydrogenase deficiency, topical application of henna may cause life-threatening haemolysis. Black henna tattoos will induce contact allergy to its ingredient PPD at an estimated frequency of 2.5%. Once sensitized, the patients may experience allergic contact dermatitis from the use of hair dyes containing PPD. There are often cross-reactions to other hair dyes, dyes used in textiles, local anaesthetics, and rubber chemicals. The sensitization of children to PPD may have important consequences for health and later career prospects. Systemic toxicity of black henna has been reported in certain African countries., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: p-Phenylenediamine (PPD) is the primary patch test screening agent for hair dye contact allergy, and approximately 100 different hair dye chemicals are allowed., Objectives: To examine whether PPD is an optimal screening agent for diagnosing hair dye allergy or whether other clinically important sensitizers exist., Methods: Two thousand nine hundred and thirty-nine consecutive patients in 12 dermatology clinics were patch tested with five hair dyes available from patch test suppliers. Furthermore, 22 frequently used hair dye ingredients not available from patch test suppliers were tested in subgroups of ~500 patients each., Results: A positive reaction to PPD was found in 4.5% of patients, and 2.8% reacted to toluene-2,5-diamine (PTD), 1.8% to p-aminophenol, 1% to m-aminophenol, and 0.1% to resorcinol; all together, 5.3% (n = 156). Dying hair was the most frequently reported cause of the allergy (55.4%); so-called 'temporary henna' tattoos were the cause in 8.5% of the cases. p-Methylaminophenol gave a reaction in 20 patients (2.2%), 3 of them with clinical relevance, and no co-reaction with the above five well-known hair dyes., Conclusions: Hair dyes are the prime cause of PPD allergy. PPD identifies the majority of positive reactions to PTD, p-aminophenol and m-aminophenol, but not all, which justifies additional testing with hair dye ingredients from the used product., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Simultaneous contact allergies to Disperse Orange 1, 4-nitroaniline and p-aminodiphenylamine (PADPA), as well as to other disperse azo dyes and to p-phenylenediamine (PPD), have been reported. Cross-reactivity is one of the possible explanations for simultaneous reactions between PPD and disperse azo dyes. Some metabolites from the azo reduction of these disperse azo dyes could be sensitizers, as human skin bacteria produce azo reductases., Objectives: To investigate the sensitizing capacity of Disperse Orange 1, PADPA and 4-nitroaniline, and the cross-reactivity between these substances and Disperse Yellow 3, its potential metabolites from azo reduction (4-aminoacetanilide and 2-amino-p-cresol), and PPD., Method: The guinea-pig maximization test was used., Results: It was found that both Disperse Orange 1 and PADPA are strong sensitizers and cross-react with each other. We were unable to sensitize guinea-pigs with 4-nitroaniline tested in equimolar concentrations to Disperse Orange 1., Conclusions: The results indicate that patients sensitized primarily to Disperse Orange 1 will also react to PADPA, which can be found mainly in hair dyes. PPD, 4-nitroaniline, 4-aminoacetanilide, 2-amino-p-cresol and Disperse Yellow 3 did not show any cross-reactivity with Disperse Orange 1 or PADPA., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Being a contact allergen of general relevance, p-phenylenediamine (PPD) is patch tested in the baseline series. However, PPD 1% in petrolatum may actively sensitize. Patch testing with PPD at 0.35% pet. proved to be safe, as far as active sensitization is concerned., Objectives: To determine whether PPD 0.3% pet. reliably detects PPD sensitization., Methods: Patch testing with PPD 0.3% pet. and 1% pet. synchronously was performed in consecutive patients in a multicentre study within the Information Network of Departments of Dermatology., Results: Altogether, 2042 patients were patch tested. PPD 1% pet. yielded 6.0% positive reactions (n = 123), and PPD 0.3% pet. yielded 4.7% (n = 95). The synchronous reproducibility of PPD reactions was similar as known from parallel patch tests with identical PPD concentrations. The diagnostic properties of PPD 0.3% pet. expressed as reaction index and positivity ratio were good. Of the 123 patients reacting to PPD 1% pet., 32 (26%) had no positive reaction to PPD 0.3% pet. In 22 of these 32 patients (69%), no clinical relevance could be found., Conclusions: As patch testing with PPD 0.3% pet. is reliable according to our results, we recommend replacing PPD 1% pet. in the baseline series with PPD 0.3% pet., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In recent years, cosmetic tattoos [permanent make-up (PMU)] on eyelids, eyebrows and lips have become increasingly popular. However, most colorants are manufactured for non-medical purposes, without any established history of safe use in humans., Objectives: To investigate severe adverse reactions, such as swelling, burning, and the development of papules, of the lips and the surrounding area in 4 patients who had had at least two PMU procedures on their lips., Patients, Materials and Methods: Adverse skin reactions were examined with patch and prick testing of the colorants. In addition, skin biopsies were taken in the centre of the prick test for histology. One patient declined prick testing., Results: Beauticians tended to use various PMU products, but all contained Pigment Red 181 (CI 73360). All patients tested showed a clear delayed reaction to Pigment Red 181 or the tattoo ink, or both, after prick testing. Histology indicated an allergic reaction. Each lip lesion slowly abated after several months of topical or systemic therapy with steroids in combination with tacrolimus, but none has yet completely resolved., Conclusions: In light of the severe and often therapy-resistant skin reactions, we strongly recommend the regulation and control of the substances used in PMU colorants., (© 2010 John Wiley & Sons A/S.)

Often barrier creams (BC) do not fulfil their protecting behaviour, even when promised by the manufacturers. Therefore, it is of great importance to develop standardized in vivo techniques to prove the potency of BC in humans. In the present study, 3 promising techniques for the analysis of BC were evaluated: laser scanning microscopy, laser doppler flowmetry, and the tape-stripping procedure. Sodium fluorescein and glycerol trinitrate acted as hydrophilic model-penetrating substances. By means of these methods, 3 different BC were tested and compared for their potency. The investigations showed that primarily the tape-stripping procedure and also the laser scanning microscopy are promising tools for the evaluation of BC. In contrast, the laser doppler flowmetry represents a less feasible technique. In addition, the evaluation of BC showed that Vaseline enfolds a 100% barrier on the skin surface for the penetration of a hydrophilic dye, whereas BC1 only partially showed a protective effect and BC2 exhibited almost no potency. In conclusion, it can be referred that laser scanning microscopy and the tape-stripping procedure represent 2 non-invasive in vivo techniques, which enable a fast investigation concerning the potency of BC.

The reservoir function and the barrier function are important properties of the skin. The reservoir function is dependent on the barrier function which, however, needs support by protective measures, in particular under working conditions. Barrier creams represent a possibility to protect the skin. In the present study, a method was developed to investigate the effectiveness of reservoir closure by different formulations. Patent Blue V in water was used as a model penetrant. Its penetration, with and without barrier cream treatment, was analyzed by tape stripping in combination with UV/VIS spectroscopic measurements. The investigations showed that the stratum corneum represents a reservoir for topically applied Patent Blue V in water. Furthermore, the barrier investigations showed that vaseline and bees wax form a 100% barrier on the skin surface. The third barrier cream, containing waxes and surfactant, only partially showed a protective effect against the penetration of Patent Blue V in water. Strong interindividual differences were observed for this barrier product. In conclusion, it was assumed that the application of barrier creams cannot replace other protective measures and should be maximally used to inhibit low-grade irritants or in combination with other protectants or in body areas where other protective measures are not applicable.

Allergic contact dermatitis from moderate and weak contact sensitizers is generally studied with guinea pigs, since they are readily sensitized to contact allergens. Mice, by contrast, are poor responders to weak contact allergens. However, the variety of in vitro murine systems as well as murine specific reagents make mice the preferable species. With the use of vitamin A supplementation, 2 protocols were developed which sensitized CBA/J female mice to paraphenylenediamine. Mice were sensitized by 5 daily topical applications to shaven dorsal skin. Alternately, mice were sensitized by 2 intraperitoneal injections of antigen pulsed spleen cells. Sensitization to paraphenylenediamine was determined by ear swelling following topical application. Vitamin A supplementation was found to be essential for optimum response. Lymph node and spleen cells from sensitized mice were capable of proliferating to paraphenylenediamine in vitro. With the use of vitamin A supplementation and intraperitoneal injection, CBA/J mice were also sensitized to a number of compounds structurally related to paraphenylenediamine, including the ortho- and meta-derivatives of paraphenylenediamine, as well as hydroquinone and resorcinol. These new protocols, combined with vitamin A supplementation, expand the use of mice to study moderate sensitizers with minimal animal utilization.