Raluca Miulescu¹, Cristiana Voicu², Adriana Diaconeasa³, Anca E. Chiriac^{4, 5}, Anca Chiriac^5-7*, Uwe Wollina⁸

1 Pediatric Hospital, Ploiesti, Romania
2 Department of Dermatology, MedLife Medical System, Bucharest, Romania
3 Dermatology Ambulatory Care Center, “Grigore Alexandrescu” Clinical Emergency Hospital for Children, Bucharest, Romania
4 Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
5 Department of Dermatology, Nicolina Medical Center, Iasi, Romania
6 Apollonia University, Iasi, Romania
7 Romanian Academy, P. Poni Institute of Macromolecular Chemistry, Iasi, Romani Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Academic Teaching Hospital, Dresden, Germany
8* Corresponding author: ancachiriac@yahoo.com

Introduction

Acne is a common disorder during adolescence and adulthood seen worldwide. The disease has a negative impact on wellbeing. Treatment according to current guidelines includes topical and systemic medical drugs, and energy-based devices [1].

In addition, OTC products are often used in adjunct. OTC acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment [2].

Nonprescription acne treatments may be responsible for adverse events as are prescription drugs. Possible they are underreported.

Discoloration of hair, nails and skin have occasionally been observed using oral minocycline [3]. Discoloration by topical acne treatment, however, is an uncommon adverse event.

Fig. 1. Patient #1. (a) Initial presentation with yellowish discoloration. (b) After one month with partial remission.
(c) After 3 months with complete remission.

Case reports

We would like to draw attention on an underreported adverse event using a topical OTC product for acne. We observed three female adolescent patients (13-16-year-old) presenting with a yellow skin discoloration after using Acne Out Active Lotion (Biotrade Cosmeceuticals Ltd., Sofia, Bulgaria).

Fig. 2: Patient #2. (a-d) Initial presentation with yellowish discoloration. (c, d) Examination under Wood’s light.

The discoloration is observed not on the face, but on the hands, especially palms, after applying the product on the face and if the hands are not quickly washed up. Yellow discoloration has not been observed in all patients using the product. The discoloration was easily recognizable under Wood light. The affected skin presented also a hyperlinearity (Figs. 1-3). The patients did not suffer from pruritus or burning sensations. There was no correlation to the type and severity of acne (Tab. 1). Follow-up of patients was 2 to 3 months. The discoloration improved in 2 and disappeared in one. None of the patients had a pre-existing hand dermatitis.

This is an uncommon adverse event of a topical product for acne skin, not yet reported in the medical literature.

Fig. 3: Patient #2 after one months. Partial remission (a & b).

Fig. 4. Patient #3. Initial presentation on the back of the hands (a) and the palms (b) with yellowish discoloration.

Discussion

Acne-out lotion contains among other substances hexamethylenetetramine (methenamine) (Tab. 2). The substance has antimicrobial activity that can explain the favourable effect in acne, but also can raise the caution about skin discoloration [4, 5]. Furthermore, topical methenamine has been used in focal hyperhidrosis as an antiperspirant [6].

Methenamine is a potential formaldehyde releaser [7]. Transdermal absorption of formaldehyde from cosmetics has been investigated on pig ear skin and found to be low [8]. However, concentrations as low as 200 – 300 p.p.m. of free formaldehyde in cosmetic products can induce contact dermatitis in short-term use on normal skin [9]. Excessive exposure to solid methenamine or its vapor has been reported to cause dermatitis and respiratory allergies [10-12]. The yellowish discoloration of skin (only the palmar area and fingers) is the most remarkable clinical sign. It occurred only in areas with rough skin. Yellowish discoloration is known from formaldehyde in nail hardeners (chromonychia) [13]. It is unknown, why only the hands had been affected and not the more sensitive facial skin.

We present a few cases of yellowish skin after using Acne Out Active Lotion, an unwanted adverse event. The clinical features with hyper linearity of affected skin suggest a component of irritant contact dermatitis.