Dear Editor, Para-phenylenediamine (PPD) is a strong contact allergen, with a prevalence of allergic contact dermatitis (ACD) to PPD being reported in up to 4% in patch-tested individuals.1 Its allergenicity stems from rapid self-oxidation, forming reactive compounds like the Brandowski base and benzoquinone, which activate CD4+ and CD8+ T cells, triggering a Th2-mediated response.1,2 While keratinocytes acetylate about 80% of PPD into non-immunogenic forms, the remaining fraction undergoes oxidation, tipping the balance toward sensitization.3 This dual metabolic fate-acetylation versus oxidation-determines its immunologic outcome. The oxidative pathway’s dominance is key to PPD’s ability to induce delayed-type hypersensitivity reactions in genetically predisposed individuals.3 A 40-year-old female homemaker, with no known comorbidities (hypertension, diabetes, renal disease), presented to the dermatology outpatient department with a 2–3-day history of facial swelling accompanied by erythematous, pruritic, and burning lesions involving the scalp and face. The rash initially developed on the forehead and frontal hairline and rapidly progressed within 24–48 hours to involve the frontal scalp, both ears, retroauricular areas, and nape of the neck. By the second day, the lesions on the forehead had evolved into erythematous plaques with loosely adherent scaling. The patient reported mild to moderate pruritus and burning in the involved areas. Within hours of rash onset, she developed sudden-onset facial edema, initially on the left periorbital region, subsequently involving the right periorbital area, the malar area, the lips, and the ear lobules, but not involving the tonsils, mucosa, or tongue. The swelling was not associated with other constitutional symptoms. She reported intermittent use of a commercially available hair dye, which contains natural henna, barium peroxide, and less than 3% PPD, over the past 2 years. The most recent application occurred 1 day prior to symptom onset. She denied any history of similar reactions, other known dermatological issues, drug allergies, or photosensitivity. No vesiculobullous lesions were observed. Minimal symptomatic relief was noted with the self-application of coconut oil. On examination, well-demarcated erythema was noted on the frontal scalp, periorbital regions, malar areas, jawline, ears, retroauricular regions, and nape of the neck, with prominent non-pitting edema of the eyelids and periorbital tissues Figure 1a-c. A clinical diagnosis of ACD and angioedema-like facies due to PPD was made, for which she was initiated on tapering doses of oral methylprednisolone (started at a dose of 0.5 mg/kg/day, tapered by 10 mg every 3 days, over a span of 9 days) along with a mid-potent topical corticosteroid (mometasone 0.1%) for 1 week, leading to complete clinical remission within 7–10 days Figure 1d-f.Figure 1: (a-c) Angioedema-like facies with erythema on the face at the time of presentation (d-f): Reduction in angioedema-like facies and erythema after 7 days of starting treatment (g-i): Positive patch test at 48-hour, 96-hour, and day 7 readings in the 12th patch test chamber chamber (P-phenylenediamine)Patch testing with the Indian Standard Series revealed a positive reaction to PPD (+1) on days 2, 4, and 7 (as per International Contact Dermatitis Research Group (ICDRG) criteria) Figure 1g-i. Serum IgE and absolute eosinophil count (AEC) were elevated. The patient was advised strict avoidance of PPD and ammonium salt-containing hair products and counseled to switch to PPD-free hair dye alternatives. We reviewed the pathomechanisms of PPD causing depigmentation, ACD, and angioedema-like facies and summarized them in Figure 2.Figure 2: The pathomechanisms of P-phenylenediamine causing depigmentation, allergic contact dermatitis, and angioedema-like facies. ACD, allergic contact dermatitis; PPD, para-phenylenediamine; ROS, reactive oxygen species; TRP-1, tyrosinase-related protein-1An IgE-mediated mechanism has been implicated in PPD-induced immediate hypersensitivity reactions, including anaphylaxis.4 Skin testing showed a wheal-and-flare response to an oxidized PPD derivative, N′N′-bis-(4-aminophenyl)-2,5-diamino-1,4-quinonediimine, and passive serum transfer confirmed IgE involvement.4 Frosch et al.4 identified PPD, glyceryl thioglycolate, and ammonium persulfate as leading allergens among hairdressers, with both delayed- and immediate-type reactions, including asthma, rhinitis, and urticaria commonly reported.4 These findings highlight that both T-cell and IgE pathways contribute to PPD reactions and that oxidative metabolites can induce systemic responses, including angioedema and even anaphylaxis, in sensitized individuals.4 PPD, which is structurally similar to tyrosine, competes with tyrosine for hydroxylation by tyrosinase and interferes with melanin synthesis. Similarly, tyrosinase-related protein 1 converts phenols and catechols into semiquinone-free radicals and reactive oxygen species that cause oxidative stress on melanocytes, which may lead to loss of melanocytes within the skin and hair follicles, resulting in skin depigmentation and greying of hair.5 ACD due to PPD is a well-documented entity, with facial and neck edema frequently reported. In our case, the presentation with angioedema-like facies and elevated serum IgE and AEC raised the possibility of an IgE-mediated component, potentially representing a localized anaphylactoid reaction. Patch testing confirmed sensitivity to PPD. This case highlights the multifaceted pathogenesis of PPD reactions-spanning T-cell and IgE-mediated pathways- and reinforces that early detection and public awareness are vital to prevent severe allergic sequelae. Authors’ contributions We confirm that all authors have read and approved the manuscript for submission. All authors meet authorship criteria, and the manuscript represents honest work. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.
Ashwini et al. (Mon,) studied this question.