Allergic contact dermatitis from Centella asiatica extract and fragrance allergens: Report of two patients from Turkey

The tropical plant Centella asiatica (Gotu kola, Indian pennywort), a member of the Umbelliferae family, and its triterpenic constituents, such as asiatic acid, its triglycoside asiaticoside and madecassic acid, are weak contact sensitizers.1 Topical preparations containing extracts of C. asiatica, have been used for decades for wound repair, particularly to treat chronic ulcers and surgical wounds, and for the prevention of cicatrization in keloids and hypertrophic scars.1 Due to its collagen-stimulating properties, C. asiatica is increasingly used in cosmetic products. Here, we present two rare patients with ACD from C. asiatica extract and other ingredients in an ointment, discussing the role of co-sensitization and the potential of aqua (aq.) as a better vehicle for patch testing with the extract. Patient 1, a 35-year-old non-atopic Turkish female with a blank history of allergy, presented with acute eczema on the surgical wound site of the suprapubic abdominal wall (Figure 1A) after using C. asiatica 1% ointment (Bayer Türk Kimya, İstanbul, Türkiye) twice daily for 3 weeks to the incision site to prevent scar formation. The patient had occasional prior use of C. asiatica products on the face, but without any complaints. Patient 2, a 20-year-old non-atopic Turkish female, developed acute eczema on the face after 3 days of using C. asiatica 1% ointment (Bayer Türk Kimya, İstanbul, Türkiye) twice daily for moisturising. She had a prior 2-week use of the same product on a burnt skin area. None of the patients had a history of fragrance allergy. They stopped using the ointment, and eczema healed with topical corticosteroids within 10 days. No new lesions occurred in a 2-month follow-up. The repeated open application test, conducted twice daily with C. asiatica 1% ointment on the volar anterior surface of the forearm in Patient 1, yielded a positive result on the third day. Results of patch testing according to the ESCD patch test guidelines2 are shown in Table 1 and Figure 1B–D. The patch test reactions were considered positive only when they showed crescendo- or plateau-positive patterns on at least two consecutive days (Table 1). Patch tests with C. asiatica extract 1%-5%–10% in aq. and pet. in 20 controls were negative. The presented patients were sensitised to C. asiatica extract and the fragrance ingredients (lavender oil, geranium oil) of the ointment. True positive patch test reactions were supported by crescendo- or plateau-positive patterns, and the use of dilution series. Similar to our findings, some of the patients sensitised with the C. asiatica extract in the literature3-7 showed co-sensitization to fragrance mix, lavender and geraniol.4, 6 The prolonged application of C. asiatica ointment on skin sites with an impaired epidermal barrier, such as a surgical incision site or burnt skin area (present report) or on the relatively thin skin of the ear4 might have contributed to an increased absorption to an otherwise weak contact sensitizer (C. asiatica) along with other ingredients of the ointment. The low sensitising capacity of C. asiatica extract was attributed to the high molecular weight of its three terpenic compounds.1 Although speculative, primary sensitization to fragrances could have occurred with the essential oil ingredients of the C. asiatica plant itself,8 potentially cross-reacting with the fragrance ingredients of the ointment. Patch testing with a serial dilution of C. asiatica extract in aq. induced stronger positive reactions than testing in pet. (Table 1). C. asiatica extract 2% in alcohol 70° was proposed as an alternative to patch testing the extract in pet.6, 9 However, aq. was not used as a vehicle in previous reports. Testing with a serial dilution is always better to differentiate a true positive reaction from an irritant reaction, as an irritant reaction will only appear at the highest concentration and abruptly vanish with lower concentrations.2 A true positive reaction, on the other hand, will gradually diminish with decreasing concentrations.2 In conclusion, the increasing use of C. asiatica extract in cosmetics emphasizes the need for proper patient evaluation regarding contact sensitization. We suggest testing with serial dilutions of the extract 1%-5%–10% in both pet. and aq. in addition to testing with the topical preparations itself and its ingredients. True positive patch test reactions to C. asiatica extract exist, particularly accompanied by co-sensitization to fragrance ingredients. Further investigation is needed to determine if the essential oil ingredients of the plant itself are the source of primary sensitization to fragrances. Verbal consent has been obtained from the patient for their clinical and patch test images to be included. Esen Özkaya: Conceptualization; investigation; writing – original draft; methodology; validation; visualization; writing – review and editing; software; formal analysis; data curation; supervision. İlkim Deniz Toprak: Investigation; writing – original draft; visualization; writing – review and editing; software; formal analysis; data curation. The authors declare no conflict of interest.