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Review Article
ARTICLE IN PRESS
doi:
10.25259/IJDVL_745_2022

Dermatological adverse effects of hair dye use: A narrative review

Department of Dermatology, Venereology and Leprosy, Sri Manakula Vinayagar Medical College and Hospital, Madagadipet, Puducherry, India
Corresponding author: Dr. Kaliaperumal Karthikeyan, Department of Dermatology, Venereology and Leprosy, Sri Manakula Vinayagar Medical College and Hospital, Madagadipet, Puducherry, India. karthikderm@gmail.com
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This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Palaniappan V, Karthikeyan K, Anusuya S. Dermatological adverse effects of hair dye use: A narrative review. Indian J Dermatol Venereol Leprol doi: 10.25259/IJDVL_745_2022

Abstract

Hair dyeing is a popular practice dating back to ancient Egyptian times. Initially, hair dye use was restricted to concealing grey and white hairs of the elderly population. However, in recent times, its use is common among the younger generation as a fashion statement.

Hair dye contact dermatitis is a common dermatological condition encountered by dermatologists. It is a delayed type of hypersensitivity reaction that commonly affects the scalp and the vicinity of hair line and neck. Para-phenylenediamine (PPD), a synthetic aromatic amine is the most common allergen specifically implicated in hair dye contact dermatitis. Para-phenylenediamine was announced as the allergen of the year in 2006 by the American Contact Dermatitis Society. Contact allergy to para-phenylenediamine can occur in 0.1–2.3% of the general population. Epicutaneous patch testing is the gold standard test for the diagnosis of hair dye contact dermatitis. However, para-phenylenediamine carries a risk of cross-sensitivity and co-sensitization to other allergens.

Apart from contact dermatitis, hair dye use is also associated with various other cutaneous adverse effects such as pigmentary changes, hair loss, skin malignancies and autoimmune disorders. Due to the various adverse effects associated with hair dye use, it is prudent to look for safer alternatives to allergenic hair dyes. In this article, we review the epidemiology, cutaneous and systemic adverse effects associated with hair dye use, patch testing, preventive strategies to minimize the risk of hair dye contact dermatitis, and treatment aspects.

Keywords

Contact dermatitis
cosmetics
hair dye allergy
hair dye dermatitis
occupational dermatitis

Introduction

Hair colour is often linked to attractiveness and dark hair is a sign of youthfulness in most cultures. It is thus not a surprise that hair dyeing has become a multibillion-dollar industry involved in the production of various synthetic and natural dyes. In 2020, the global hair dye and colour industry was valued around 21.4 billion U.S. dollars and projected to be around 36.2 billion U.S. dollars by 2025. 1 However, the use of hair dyes is a major source of chemical exposure among the general population and can cause various adverse effects. In this article, we provide an overview of hair dyes and the potential adverse effects associated with their use.

History of hair colouring

The art of hair dyeing has been known since ancient Egyptian times when Ramesses II, pharaoh of the nineteenth dynasty of Egypt, had his hair applied with henna after death. 2 In ancient Greece, potassium solution rinse was used to bleach hair and then rubbed with a type of ointment composed of pollen and flower petals. 3 Colouring of hair in different shades such as black, green, red, gold were practiced in the past. 4 The first artificial hair dye was synthesized in a laboratory in 1856. 5 Para-phenylenediamine was initially described by German chemist Hofmann in 1863 and formulated for use in hair dye in the late 19th century. 6 Boonnevie recognized the implications of para-phenylenediamine exposure and recommended including it into the first standard series of patch test series allergen screening panel in 1939. 7

Classification and composition of hair dyes

Hair dyes are classified into three categories based on their chemical composition, namely, synthetic dyes, vegetable or herbal dyes and metallic dyes. Based on their oxidative nature, they are divided into oxidative dyes and non-oxidative dyes. According to the ability of hair dyes to penetrate the hair shaft, they can be divided into temporary, semi-permanent, demi-permanent and permanent hair dyes [Figure 1] 3 . The classification and features of various types of hair dyes are summarised in Table 1. 4,7,8 The various ingredients of hair dyes along with their functions are mentioned in Table 2. 3 The steps involved in different types of hair dyeing processes are depicted in Figure 2 3. Bleaching is a process that aids in achieving different shades of hair. 8 The mechanism of hair damage secondary to bleaching is shown in Figure 3 3. The process of hair colouring is shown in Figure 4. 3

Figure 1:
Penetration of hair dye in the hair shaft.
Table 1: Classification of synthetic hair dyes
Synthetic hair dyes
Characteristics Non-oxidative
Oxidative
Temporary Semi-permanent Permanent
Molecular weight High Low Low
Nature Anionic Cationic Cationic
Hydrogen peroxide Absent Present in lower concentration Present in higher concentration
Hair penetration On surface Diffuse cortex Diffuse cortex
Contact time 30 mins 10–40 mins 30–45 mins
Hair rinse resistance 3–6 rinses 5–6 rinses Resist wash
Nature of hair colour To add nuance More natural look Brown to black shade
Table 2: Ingredients and their characteristics of hair dye 3,89
Constituent Characteristics and function Commonly used agents
Coupling bases
  • Aromatic compounds derived from benzene substituted by at least two electron donor groups such as NH 2 and OH in ortho or para positions for easy oxidation and colour development

  • p-phenylenediamine

  • p-aminophenol

Reaction modifiers/couplers
  • Aromatic derivatives of benzene substituted by at least two electron donor groups such as NH 2 and OH in meta positions which does not present easy oxidation by H 2 O 2

  • Modifies colours with primary intermediaries and oxidants

  • Determines the final shade of colour

  • Phenols

  • Meta disubstituted phenylenediamines and phenyleneaminophenols

  • Resorcinol (1,3-dihydroxybenzene) derivatives

Alkalizing compound
  • Promotes proper pH value to initiate oxidation reaction

  • Removes the natural pigments present in hair

  • Ammonia (as ammonium hydroxide)

  • Monoethanolamine (for liquid forms)

  • Sodium silicate (for solid forms)

Oxidizing agent s
  • Two types of oxidizing agents used

  • Peroxides are unstable, require the stabilizers like sodium stannate and pentasodium pentetate

  • Used in the form of emulsion – creamy hydrogen peroxide

  • Hydrogen peroxide (when vehicle is water)

  • Sodium persulphate (when vehicle is powder)

Reducing agents
  • Added to oxidative hair dye formulations to delay the reaction between bases and reaction modifiers

  • To prevent the initiation of the reaction in the packaging tube during storage

  • Sodium metabisulphite

Dyes
  • Imparts colour to the hair dye

  • Responsible for allergenic reactions in many cases

  • O-nitro anilines

  • Aminonitrophenols and their ethers

  • Azo dyes

  • Nitrophenylamines

  • Nitrophenienediamines

  • Anthroquinone

Antioxidants
  • Avoid reaction before the addition of oxidant

  • Water-soluble antioxidant – prevents manipulation of bases and initiation of oxidation reaction by reaction modifiers

  • Oil-based antioxidant – used as a vehicle for emulsion hair dyes as it avoids yellowing of wax

  • Erythorbic acid – water based antioxidant

  • T-butyl quinone

Vehicles
  • Emulsion form of oxidative dyes are the highest selling hair dye product in the market

  • Emulsion

  • Gel

  • Powder

  • Solution (liquid)

Surfactants
  • To thicken the hair dye product solution for better handling, to get homogenous dye results,

  • Increase in concentration of surfactant increases the dye-formation in dye solution

  • To disperse dye molecules

  • Aids in the wetting of hair

  • Sodium lauryl sulphate

  • Sodium laureth sulphate

  • Disodium laureth sulfosuccinate

  • Disodium lauryl sulfosuccinate

  • Capramidopropylbetaine

  • Sodium lauroyl methyl isethionate

  • Cocamidopropyl betaine

  • Capryl/capamidopropyl betaine

  • Sodium cocoamphoacetate

Solvents
  • Increases the dyeing rate, establishment of equilibrium and hair wetting

  • Dispersion of dye molecules

  • Aids in the wetting of hair

  • Quaternium-80

  • Benzyl alcohol

  • Glycols

Emulsifiers
  • The ingredient which holds all other ingredients together

  • Oleth-23

  • Cetearyl Alcohol

Photoprotectors
  • Protection of hair against photodamage

  • Homoxalate

  • Octinosate

  • Octocrylene

  • Oxybenzone

Preservatives
  • Protects the product from oxidation

  • Protects against the contaminants such as moulds or bacteria

  • Parabens

  • Phenoxyethanol

Figure 2:
Various steps involved in hair dyeing.
Figure 3:
Mechanism of hair damage secondary to bleaching.
Figure 4:
Process of hair colouring.

Epidemiology of hair dye use and contact sensitivity

Population-based epidemiological studies have found para-phenylenediamine sensitivity in the general population to be 0.1–1%. 9 The prevalence of positive patch tests for para-phenylenediamine varies among dermatitis patients across the world, amounting to 11.5% in India, 6% in North America, 4.4% in Asia and 4.1% in Europe. Sensitization to para-phenylenediamine is more common in men than women in Asia, whereas it is the reverse in Europe. 10,11 In an Indian study, it was found that among hair dye users, the mean age of first-time hair dye use was 27 years, and 42% of respondents reported adverse events following its use. 12 Contact allergy to para-phenylenediamine can occur in 0.1–2.3% of the general population. 7 Two Indian studies have found para-phenylenediamine to be the commonest sensitizer among cosmetics. 13,14

Para-phenylenediamine

Para-phenylenediamine is a synthetic aromatic amine, a derivative of para-nitroaniline (coal–tar derivative) and is found in more than 1000 hair dye formulations. 15 It is an effective compound found in nearly 70% of the hair dyes available worldwide owing to its small molecular weight, high protein-binding capacity, potential to penetrate the hair shaft, rapid polymerization when oxidized and due to the natural colour imparted to hair. 6,16,17 Para-phenylenediamine is a Class I allergen on lymph node assay and a potential contact sensitizer even in low concentrations. 16,17

Contact sensitization to para-phenylenediamine often occurs due to various sources. Para-phenylenediamine is often used as a dye or antioxidant in various consumer and industry products such as fur, textiles, leather, rubber, paints, nylon stockings and industrial printing inks. Occupations which carry a high risk of contact with para-phenylenediamine are those of laboratory assistant, leather shop assistant, petrol pump attendant, masseur and jobs in the plastic, paper and cellulose manufacturing industries. 18

The metabolism of para-phenylenediamine was studied by Bandrowski and still has not been completely elucidated. The metabolism of para-phenylenediamine in skin roughly involves two major pathways: (1) oxidation pathway and (2) acetylation pathway. 19 The oxidative metabolites of para-phenylenediamine are the haptens that are responsible for para-phenylenediamine sensitization. Less than 1% of non-polymerised para-phenylenediamine undergoes acetylation in the epidermis without activating the T-cells and dendritic cells of sensitized individuals. The acetylation pathway gets saturated and increases the oxidative metabolites in the skin with exposure to large doses left for longer than the intended time of application and when carelessly applied, contaminating the nearby skin. 17 Apart from para-phenylenediamine, agents such as toluene-2,5-diamine, p-aminophenol, m-aminophenol, resorcinol, monoethanolamine, ammonium persulphates, ammonium thioglycolates, glyceryl thioglycolatesand sodium metabisulphite can produce contact dermatitis in hair dye users. 7,19

Natural hair dyes

Henna (Lawsonia inermis) is a shrub with an active dye lawsone (2-hydroxy-1,4-naphthoquinone). The dried leaves of henna are powdered and mixed with water or oil and hair dyes are prepared. 20,21 Natural henna is often mixed with coffee water or tea water overnight to make the colour more visible. The addition of natural substances such as vinegar, lemon oil and eucalyptus oil imparts different shades. 7,8 Brown henna contains indigo plant leaves, black henna has para-phenylenediamine whereas red henna has no additives, hence its lower allergenic potential. 20,21

Contact dermatitis to hair dye

Hair dye contact dermatitis is a delayed hypersensitivity reaction, with signs and symptoms observed after a latent period of several hours to days following the hair dye use. 6 It is common in the glabrous skin of the head and neck in the vicinity of the scalp (“rinse off areas”) [Figures 58]. Persons with mild hypersensitivity to hair dye can present only with dermatitis of the helices of ears and eyelids without affecting other facial areas or scalp. 22 In a study of 105 patients with hair dye contact dermatitis, 64.8% showed lesions over the direct contact sites (scalp, face, neck), while 36.2% had lesions over both direct and indirect contact sites (trunk, hand, upper extremities, lower extremities and feet) [Figures 9 and 10]. 23

Figure 5:
Allergic contact dermatitis to hair dye extending from anterior hairline to forehead.
Figure 6:
Allergic contact dermatitis associated with hair loss following hair dye use.
Figure 7:
Lichenoid changes after the use of hair dye.
Figure 8:
Vesiculation, oozing and crusting associated with hair dye use.
Figure 9:
A hair dye user with pigmentary changes over the face and prurigo-like lesions over the upper extremities with positive patch test for para-phenylene diamine. Differential diagnoses of Riehl’s melanosis and ashy dermatoses for the face were considered. Prurigo nodularis and hypertrophic lichen planus were considered for the upper limb lesions.
Figure 10:
Disseminated hair dye dermatitis in a 32-year-old female. Patch test was positive for para-phenylenediamine. A differential diagnosis of seborrheic dermatitis and photo-allergic contact dermatitis were also considered.

Even though dyeing is commonly performed on the hair-bearing scalp, the allergen load in that area is grossly decreased due to increased skin thickness, protective sebum production, greater absorption of allergens into scalp hair and moderation by hair follicle regulation which are likely to promote tolerance. 24,25 Among hairdressers, the most common sites for allergic contact dermatitis are the hands and arms [Figure 11]. In hairdressers, the cumulative effect from wet work results in irritant contact dermatitis with a defective skin barrier which in turn results in penetration of hair dye allergens. 26 The thin stratum corneum of the facial skin and the need for frequent dyeing of the beard make the site more susceptible to contact dermatitis [Figure 12]. 27

Figure 11:
Hairdresser with allergic contact dermatitis on the dorsa of hands. She showed a positive reaction to para-phenylenediamine on patch testing. A differential diagnosis of polymorphous light eruption was considered.
Figure 12:
Pigmentary contact dermatitis over the moustache region.

Hair dye contact dermatitis can produce symptoms such as redness, soreness, pruritus, dryness, pricking sensation, a burning or tingling sensation and discomfort. 23,28 Many patients may experience photosensitivity. 7 The signs observed include erythematous macules, patches, papules, plaques, vesicles, oozing, crusting, fissuring, lichenification, oedema, swelling, suppuration and ulceration at the affected sites. 23,29 Hair dye use can also produce split ends in hair dryness, lustreless hair, hair loss, paradoxical excessive greying and slowing of hair growth. 30 Oxidative hair dyes sometimes induce painful sensory irritation of the scalp. 31 The morphological patterns of hair dye contact dermatitis are mentioned in Table 3. 7,16 Patients with lichen simplex chronicus (LSC) with weak positive patch test reaction to para-phenylenediamine have shown improvement or complete clearing of the LSC lesions once they stopped using hair dye. 32 Hair dye used by a person can produce connubial contact dermatitis in the partner. 33

Table 3: Clinical patterns of hair dye contact dermatitis
  • Localized contact dermatitis over scalp, scalp margins, face and neck

  • Disseminated dermatitis

  • Airborne contact dermatitis

  • Eyelid eczema

  • Periorbital eczema

  • Irritant contact dermatitis

  • Photocontact dermatitis

  • Hand eczema

  • Nummular dermatitis

  • Chronic actinic dermatitis

  • Lichenoid lesions

  • Contact leukoderma

  • Lymphomatoid papulosis-like lesions

  • Erythema multiforme-like lesions

  • Prurigo nodularis-like lesions

  • Bullous contact dermatitis

  • Exudative erythema

There is a recent trend of using black henna tattooing as a form of temporary body art in younger individuals. In black henna, para-phenylenediamine is added to natural henna to reduce the application time, increase intensity of the colour, improve pattern recognition and make the tattoo last longer. Some of them are sensitized to para-phenylenediamine in the black henna tattoos, and later when they use hair dye, can develop delayed hypersensitivity reactions to it even at lower concentrations of para-phenylenediamine. 34,35

Type 1 hypersensitivity reactions to hair dye appears to occur after the process of oxidation. The reaction can manifest as urticaria, angioedema, rhinitis, asthma, bronchospasm and anaphylaxis [Figure 13]. 23,36

Figure 13:
Angioedema-like reaction following hair dye use

Diagnosis of allergic contact dermatitis to hair dye

Patch test

Epicutaneous patch testing is the gold standard modality to confirm the allergy to hair dye. 7 The patch test allergens to rule out hair dye allergy provided by Søsted et al. are mentioned in Table 4. 37 However, as para-phenylenediamine is the most commonly encountered allergen in hair dye, it is included in the Indian Standard Series of allergens. 6,17 The sensitivity of patch testing with para-phenylenediamine was found to be 87%. 38 Population-based epidemiological studies have shown that patch testing with the recommended standard concentration of 1% para-phenylenediamine can result in highly delayed patch test reactions from day 7 in 1.5% of patients, probably reflecting iatrogenic sensitizations. 39

Table 4: Patch test recommendations in suspected hair dye allergy (adapted from Søsted et al) 37

Para-phenylenediamine

Paratoluenediamine

p-Methylaminophenol

p-Aminophenol

4-Amino-2-hydroxytoulene

m-aminophenol

2,4-Diaminophenoxyethanol–HCl

4-Amino-m-cresol

1-Hydroxyethyl-4,5-diaminopyrazole sulphate

2-Amino-3-hydroxypyridine

2-Methylresorcinol

3-Nitro-p-hydroxyethyaminophenol

N,N’-Bis(2-hydroxyethyl)-p-phenylenediamine

4-Amino-3-nitrophenol

4-Chlororesorcinol

Resorcinol

1-Napthol

2,4,5,6-Tetraaminopyridine

2,7-Naphthalenediol

2-Amino-6-chloro-4-nitophenol

2-Methyl-5-hydroxyethylaminophenol

4-Hydroxypropylamino-3-nitrophenol

Acid Violet 43

Disperse Violet 1

HC Blue 2

HC Red 3

Picramic acid

The development of systemic anaphylactoid reaction 16 hours after a closed patch test with para-phenylenediamine has been reported. 40 Patients with a history of severe reaction to hair dyes can be tested with para-phenylenediamine 1% pet for 1 hour. The patch test conducted with standard 1% pet para-phenylenediamine in patients previously sensitized to black henna exposure often results in strong reactions. Hence, some centres are recommending tests with 0.3% para-phenylenediamine concentration. 6

Para-phenylenediamine may cross-react to other chemicals with an amine group on a benzene ring at the para position [Table 5]. 19 A retrospective study of 221 para-phenylenediamine patch test-positive patients found that severe patch test reactions (3+ rather than 1+ in international contact dermatitis research group (ICDRG) grading) have increased chances for cross-reactivity. 40 Polysensitization is common among para-phenylenediamine-allergic patients with stronger responses (2+ and 3+). 17 Carba mix, cobalt chloride, colophonium, methylchloroisothiazolinone, paraben mix and para-tertiary butylphenol formaldehyde resin are known to produce co-sensitization with para-phenylenediamine. 41

Table 5: Chemicals that can cross-react with para-phenylenediamine
Chemical Use
Para-toluenediamine sulphate Semipermanent hair dye, brown fur dyes, bleach-toner formula
Para-aminobenzoic acid Sunscreens, pesticides
Para-amino salicylic acid Antibiotics
N-isopropyl-N’-phenyl-p-phenylenediamine Antioxidant in rubber
Sulfonylureas, sulfonamides Medications
Azo dyes Textiles, food, leather, plastics, rubber, paints
Benzocaine, tetracaine, procaine Ester local anaesthetics
Thiazides Diuretic medications
Sesquiterpene-lactone mix Compositae family plants, cosmetics, topical medicaments
Hydroquinone Skin depigmentation agent
Pyrogallol Photographic developing agent
Black rubber mix Rubber industries

Hair dye manufacturers recommend open testing by applying a small amount of hair dye behind the ear for 48 hours and looking for any allergenic reaction. It is a good screening test, but often misses the late and weak positive reactions. 7 Repeated open application test (ROAT) had a sensitivity of 83.33% and specificity of 100% in patients with hair dye dermatitis in comparison to the patch test. 42 Para-phenylenediamine-specific lymphocyte activation test (LAT) is a potential alternative in vitro system in patients with severe allergic contact reactions to para-phenylenediamine. 39

Management of hair dye contact dermatitis

The withdrawal of the causative hair dye is the initial step in the management of hair dye contact dermatitis. In the case of acute severe hair dye contact dermatitis, the hair and scalp should be washed thoroughly to remove any surplus dye. Corticosteroids form the first-line treatment option in hair dye contact dermatitis. 6,7 Short courses of potent topical corticosteroids applied once or twice daily for 2–3 weeks are preferred for localized hair dye contact dermatitis. If more than 10% of the body surface area is involved, systemic prednisolone (1–2 mg/kg) for 7–10 days, followed by tapering over the next 7–10 days, is administered. Wet dressings and oral antihistamines for soothing, relieving pruritus and reducing redness are given. A sunscreen should be advised for patients with photosensitivity. 7

Adverse reactions due to hair dye use other than contact dermatitis

Hair dye–induced hyperpigmentation

Hair dyes are implicated in pigmentary alterations such as lichen planus pigmentosus and facial pigmented contact dermatitis [Figure 14]. 43,44 Earlier, Meghana et al. studied the pigmentary alterations of the face and neck in 118 hair dye users. Blotchy type (66.1%) followed by diffuse type (33.1%) of hyperpigmentation was commonly observed. In that study all the hair dye users had pigmentary alterations. The most frequently affected sites were the lateral forehead (88.3%), ear helix (88.3%) and central forehead (80.8%), an and zygomatic area (6.7%). 45 In that study, the most frequently Bishnoi et al. described 108 patients with acquired dermal hyperpigmentation of the face and scalp clinically and interface dermatitis histologically. Of them, 83.3% used hair dye and 36.1% tested positive for para-phenylenediamine. 46 Hair dye pigmentation has been reported to produce foreign body skull erosive granuloma. 47

Figure 14:
Riehl’s melanosis in a chronic hair dye user

Leukoderma

Initially, Taylor et al. in 1993 reported the ability of hair dyes to induce depigmentation. They described four patients who developed leukoderma of the scalp and hair following hair dye use. 48 In a study of 864 cases of chemical leukoderma, around 27.4% of the patients developed depigmentation at the hair dye application site. It was limited to the contact site in 73.7% of individuals and extended beyond in 26.3% of patients [Figure 15]. 49

Figure 15:
Contact leukoderma following hair dye use.

The chemical structure of para-phenylenediamine is similar to that of tyrosine which is probably converted by tyrosine-related protein 1 into compounds that are toxic to melanocytes resulting in its loss within skin and hair follicles, resulting in depigmentation of skin and hair. 50 The term “chemical-induced vitiligo” is often used to denote the depigmentation produced by chemicals like para-phenylenediamine. It cannot be clinically or histopathologically differentiated from vitiligo. 51

Hair dye–induced hair loss

Hair dye use has been reported to produce telogen effluvium, cicatricial (lichenoid) alopecia, alopecia totalis and milphosis. 5255 An in vivo mouse model identified hydrogen peroxide and monoethanolamine as the key causative ingredients in hair dye–induced hair loss. 56

Skin and other malignancies

The aromatic amine derivatives present in hair dyes are considered to be mutagenic. A large cohort study conducted in Sweden observed an increased risk of in situ carcinoma of the skin in the scalp and neck. 57 In a study of 160 cases of basal cell carcinoma on the head and neck, it was observed that the odds of developing it were more among hair dye users, particularly those who used darker shades. 58 A twofold increased risk of malignant melanoma in women using hair dye was noticed in a 37-year-old follow-up study. 59 A case of hair dye-induced intracranial communicating sebaceous carcinoma of the scalp which developed 10 years after hair dyeing has been reported. 60

In a large prospective cohort study of 1,17,000 personal hair dye users, increased incidence of breast carcinoma (oestrogen receptor-negative, progesterone receptor-negative, hormone receptor-negative), ovarian carcinoma and basal cell carcinoma was observed. Though evidence remains inadequate, individual or pooled relative risks were increased for malignancies such as lung carcinoma, prostate carcinoma and salivary gland carcinoma. 61 An increased incidence of non-Hodgkin’s lymphoma, particularly follicular lymphoma is also associated with permanent hair dye use. 62

Chemical burns

Severe chemical burns of the scalp following the application of hair dye requiring split-thickness skin graft are known. 63 In the United Kingdom, hairdressers have noticed chemical burns in their clients following hair dye application in those who recently recovered from COVID-19. 64

Hair dye use and systemic diseases

Exposure to para-phenylenediamine is postulated in the development of autoimmune phenomena, through various mechanisms such as apoptosis-mediated autoimmunity, molecular mimicry, immunological cross-reactivity and others, causing increased production of pro-inflammatory cytokines and immune complex formation. 65,66 Exacerbation of discoid cutaneous lupus erythematosus following hair dyes have been reported. 67 In addition, hair dye use has been associated with the development of systemic lupus erythematosus, rheumatoid arthritis, symmetrical polyarthritis and antinuclear antibody (ANA) positivity. 6871

Severe systemic toxicities following topical para-phenylenediamine exposure, resulting in rhabdomyolysis, kidney failure requiring haemodialysis, severe electrolyte derangements, severe anaphylaxis and myocardial infarction even resulting in death are reported. 72,73 A study on the effects of long-term para-phenylenediamine exposure among hairdressers found a high prevalence of haematuria (41.1%), proteinuria (26.4%), renal impairment (14%), hypertension (19.4%) and bronchospasm (22%). 74 In a case-control study, lenticular changes and early presbyopia were observed respectively in 89% and 7% of 200 hair dye users. 75 Gestational maternal hair dye use has been associated with low birth-weight children and the development of neuroblastoma, leukaemia and allergic rhinitis in the children at a later age. 7678

Hair dye poisoning

Para-phenylenediamine has been reported to be a suicidal poisoning agent owing to its easy availability in households, low cost and tolerable taste. It is associated with a high mortality rate (12 to 42%) due to the non-availability of specific antidotes. 79 The characteristic triad of hair dye poisoning is: (1) early angioneurotic oedema with stridor, (2) acute renal failure, and (3) rhabdomyolysis with chocolate-coloured urine. It can manifest as asphyxia, anuria or oliguria, metabolic acidosis, coagulation derangements, intravascular haemolysis, toxic myocarditis, arrhythmias, flaccid paralysis and gastrointestinal manifestations. 80

Preventive measures and safety regulations

Oxidative processes in the skin play a vital role in the activation of para-phenylenediamine and its derivatives. Hence, pre-treatment of the glabrous skin surrounding the scalp with topical anti-oxidants like vitamin C cream or emulsion and 0.07% astaxanthin emulsion (with >6000-fold stronger antioxidant action than vitamin C) has been reported to decrease the incidence of hair dye allergy in para-phenylenediamine-sensitive patients. 81,82  Patients with early, mild hair dye dermatitis have been advised in an article to use 0.05% clobetasol propionate foam applied twice daily over the affected area for 3 days before the next episode of hair colouring. 83

Hairdressers should be advised not to use disposable natural rubber latex gloves and polyvinylchloride gloves while handling hair dye products for more than 1 hour. However, neoprene gloves and 4-H gloves are recommended as they protect hairdressers from hair dyes and perm chemicals. 22,84 The strategies that can minimize the risk of development of contact dermatitis to hair dye are mentioned in Table 6. The recommended concentrations of para-phenylenediamine and toluene-2,5-diamine in hair dyes according to various regulations are mentioned in Table 7. 16,39

Table 6: Strategies to minimize hair dye contact dermatitis 7,17,90
  • Hair dye should be applied meticulously with minimal contact time

  • Patients should not get misled by the high-pitched advertisements and should look at all the contents of the hair dye

  • Use of hair foils or a highlight cap can minimize the risk of sensitization

  • The scalp should be rinsed well after hair dyeing

  • Immediate removal of hair dye if the adjacent area is contaminated

  • Application of petrolatum to prevent the lateral spread of hair dye and to shield scalp margins

  • Using lighter shades and less frequent dyeing will reduce the cumulative dose of dye on skin

  • At production levels, manufacturers should keep the para-phenylenediamine concentration at a minimal level

  • In patients with previous history of hair dye allergy, clear written advice should be given to look for allergenic ingredients

  • Patients with para-phenylenediamine allergy should be warned regarding potential cross reaction to other substances with para-group

  • Attention should be paid to all the “Caution” and “Warning” statements

  • Different hair dye products should never be mixed

  • Hair dressers should be educated about appropriate glove use and emollient use after work

  • General population should be encouraged to perform open patch testing before using hair dye

  • Pre-treatment of glabrous skin surrounding the scalp with topical antioxidants can minimise contact dermatitis

  • Silver nitrate as the colour additive is recommended to colour eyebrows and eyelashes.

  • Hair colouring should be carried out only by professional hairdressers.

  • Application of petrolatum on surrounding areas before dyeing the beard can prevent contact dermatitis in that region.

Table 7: Recommended concentration of para-phenylenediamine (PPD) and toluene-2,5-diamine in hair dyes
  • Para-phenylenediamine use in humans in “rinse off” products such as black hair dyes are approved for the US by the Food and Drug Administration irrespective of the concentration

  • The European Union Cosmetic Directive (EUCD) allows a maximum concentration of 6% para-phenylenediamine in hair dyes

  • EUCD allows a maximum concentration of 10% toluene-2,5-diamine in hair dyes

  • Bureau of Indian Standards (BIS) has set a maximum permissible limit of 30% and not less than 3% para-phenylenediamine after dilution of the powder form

  • BIS has set a maximum permissible limit of 4% and not less than 1.2% para-phenylenediamine after dilution of the oxidation liquid type.

  • In Australia, a warning label is required for para-phenylenediamine concentrations higher than 5%.

Safe alternatives to hair dye

In recent times, a newer para-phenylenediamine derivative 2-methoxymethyl-para-phenylenediamine (2-methoxymethyl-para-phenylenediamine) has been formulated and investigated for safer hair dye use. 85 The salient features of 2-methoxymethyl-para-phenylenediamine-based hair dyes are mentioned in Table 8. Venkatesan et al. introduced non-allergenic aromatic amine hair dyes as safe and efficient alternatives to para-phenylenediamine by introducing novel side chains to it. 86 One report has suggested hydroxyethyl-p-phenylenediamine sulphate (HPPS) as a potential alternative to para-phenylenediamine. 87 Natural botanical products that can be used for hair colouring are listed in Table 9. 88

Table 8: Salient features of 2-methoxymethyl-para-phenylenediamine (ME-PPD) based hair dye 85
  • Less allergenic para-phenylenediamine derivative secondary to its methoxy-methyl side chain

  • The peculiar side chain inhibits binding to the CD86 costimulatory molecule on antigen-presenting cells which is needed for T-cell activation

  • It creates a hapten complex that is poorly recognized by para-phenylenediamine-specific T cells

  • Attenuates the innate and adaptive immune response triggered by para-phenylenediamine

  • Maintains an equivalent hair colouring performance to para-phenylenediamine and toluene-2,5-diamine sulphate-based dyes

  • The concentration of ME-PPD needed to induce a local lymph node immune response is high (3–4%) as opposed to para-phenylenediamine (0–1%)

  • Relatively safe permanent hair dye for para-phenylenediamine-allergic patients

  • Allergic reaction even if encountered is expected to be less severe than that of para-phenylenediamine-based contact dermatitis

  • Minimal cross reaction rate (30%) in para-phenylenediamine patch test positive individuals

Table 9: Natural plant colourants used for hair dye applications
Colourant Plant origin
Lawsone Leaves of Lawsonia inermis L
Juglone Husk of Juglans regia L
Shikonin Roots of Lithospermum erythrorhizon
Alizarin Roots of Rubia tinctoria L
Benzoquinone Pyrus lindleyi Rehd
Gallotannin Parasitic aphids of Rhus chinensis Mill
Catechin Matcha tea
Cyanidin-3-o-rutinoside Fruit skins of Ribes nigrum L
Cyanidin-3-o-rutinoside Fruit of Morus nigra L
Cyanidin-3-o-rutinoside Beans of Phaseolus mungo
Cyanidin-3-o-rutinoside Fruit of Cleistocalyx nervosum Var. Paniala
Cyanidin-3-o-rutinoside Corn cobs of Zea mays L. Var.
Haematoxylin Heartwood of Haematoxylon campechianum
Quercetin Leaves of Tectona grandis Linn. F.
Acacetin Barque of Acacia farnesiana (Linn.) Willd
Indigo Leaves of Indigofera tinctorium
Curcumin Root of Curcuma longa Linn
Zeaxanthin Aerial parts of Eclipta alba L
Peridinin Fruit of Terminalia belerica Roxb
Lutein Flower of Tagetes erecta Linn

Conclusions

The use of hair dye has become quite common over the last few decades. It is a common sight for dermatologists to observe that many people continue to apply hair dye for various personal and social reasons even after developing an allergy to it. More scientific research should be carried out for the development of safer hair dyes. Till then, hair dyes will continue to be one of the most hazardous cosmetics used by mankind.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflict of interest

There is no conflict of interest.

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