When beauty is more than skin deep

Discussion

Para-phenylenediamine is an aromatic amine derived from alanine and is an ingredient of kala pathar (black stone in Urdu), which is a component of some hair dyes. Para-phenylenediamine is a crystalline solid that is present as white lumps or flakes that darken upon exposure to air. Para-phenylenediamine is readily available for bulk purchase online and is widely used in hair dyes, black henna, fur dyes, plastic, photographic products, and printer inks.³ In developed countries, hair dye products contain a maximum of 2% PPD, but in developing countries, concentrations can range from 2% to 90% due to lack of standard regulations.⁴ In the United States, PPD was found to be present in 78% of 107 hair dyes from 10 major brands, of which 9% were marketed to men for use on facial hair.⁵

Para-phenylenediamine is converted to its active metabolite, benzoquinone diamine, by the cytochrome P450 system. Oxidation of this active metabolite leads to the formation of Bandrowski base, which can block cellular oxidation mechanisms and cause anaphylaxis.³ Metabolites of PPD are excreted in the urine. Reports of PPD toxicity resulting from intent to self-harm via oral ingestion of PPD-containing hair dyes have been increasing in many countries such as Egypt, Morocco, Sudan, India, and Pakistan.⁴ Clinical presentation includes cola-coloured urine; decreased urine output; severe face, neck, or tongue edema causing respiratory impairment and occasionally necessitating tracheostomy; rhabdomyolysis; renal impairment; and elevated liver transaminase levels.⁴ The mortality rate after acute oral ingestion was 14.5% in a meta-analysis⁴ and 36% in a case series.³ Para-phenylenediamine is nondialyzable and management of toxicity is supportive, as no specific antidote is available.

Topical PPD exposure through hair dyes and henna tattoos can lead to sensitization and allergic contact dermatitis.⁶ Para-phenylenediamine is considered a top contact allergen by the American Contact Dermatitis Society,⁷ and median prevalence of positive PPD patch test results ranges from 4% to 6.2% in North America, Europe, and Asia.⁶ Of importance, dermatologic exposure may lead to systemic absorption and toxicity. In one study, persons who self-applied hair dyes excreted greater than 200 times more aromatic diamines than hairdressers did, possibly due to less consistent use of protective gloves and long-sleeved clothing,⁸ excessive scalp exposure, and prolonged contact time.⁶ Intermittent, repeated exposure to low-concentration PPD may lead to PPD accumulation over time.⁹

The first case of PPD toxicity in humans was published in 1924, with symptoms including tongue edema, nausea, and gastric pain in an otherwise healthy, middle-aged hairdresser. Hair dye used in his salon was found to contain PPD. The patient experienced no further symptoms after avoiding further dye exposure.¹⁰ Chronic renal failure with vasculitis and crescentic glomerulonephritis was reported in 2 women after long-term topical use of PPD-containing hair dye.¹¹ Our patient experienced severe contact dermatitis and elevated liver enzyme levels 1 month after starting use of PPD-containing shampoo, with resolution of symptoms after discontinuation. We believe that our case is the first report of reversible drug-induced hepatitis secondary to use of hair dye shampoo containing PPD, but the prevalence may actually be higher due to lack of specific symptoms and underdiagnosis.

Para-phenylenediamine is a restricted ingredient on Health Canada’s Cosmetic Ingredient Hotlist, and hair dyes with PPD must display specific warnings and directions for safe use on the outer and inner product labels.¹² Nevertheless, further consumer education regarding risks associated with PPD-containing products is important. Our patient continued to use PPD-containing shampoo despite experiencing contact dermatitis and did not report use of this shampoo until after repeated questioning by his physician during subsequent visits; by that time his liver enzyme levels had been elevated for 5 months. With increased awareness and more specific questioning, the cause of his hepatotoxicity could have been identified much earlier. Furthermore, as the population ages, use of hair-darkening products may increase. These products are often advertised as being “natural,” “organic,” “pure,” “ammonia-free,” or “herbal” to suggest safety or minimal risk.^5,6 Patients are encouraged to check ingredient lists to identify PPD or other allergens. Many patients sensitized to PPD may be able to tolerate alternative permanent and semipermanent hair dyes, but there is a risk of cross-reactivity with other compounds that contain an amine group in their benzene ring.¹³ Wash in–wash out dyes are usually considered to be safe.⁶ Topical and systemic adverse reactions to PPD shampoo and other products should be reported to Health Canada’s postmarket surveillance program.¹⁴