Oral and Lip Depigmentation Induced by Bael Leaves and Clove Phytochemicals

Dear Editor, Acquired depigmentation due to repeated or prolonged exposure to specific chemicals like hydroquinone, derivatives of phenols, catechols, etc., is known as chemical leucoderma.[1] Unlike vitiligo, it typically lacks an autoimmune basis and is generally limited to the site of contact. Phytochemicals derived from plants are recognized as emerging causes of leucoderma.[2] Two cases illustrate this phenomenon. Case 1: A 51-year-old female presented with progressing whitish discoloration of the lips for the past 2 weeks. A detailed history revealed that she has been chewing 2–3 bael leaves daily for the past one and a half months. On examination, the depigmentation involved the mucosal, vermillion, and cutaneous aspects of both upper and lower lips, extending to both oral commissures, gums, and buccal mucosae [Figure 1a]. Residual pigmentation was seen after everting the lower lip [Figure 1b]. We suspected leukoderma induced by bael leaves. Anemia, diabetes mellitus, and thyroid dysfunction were ruled out after blood investigation. A patch testing was done after taking written consent. Dilute bael leaves paste with saline (1 part of bael leaves powder and 10 parts saline), and saline-soaked empty chamber (control) was used [Figure 1c]. We took readings on day 2, day 4, and day 7 and advised delayed reading at 6 weeks. The patch test reading showed only slight erythema on day 2. There was no itching. The erythema later subsided on its own. The patient came back after 6 weeks with depigmentation at the site where bael patch was applied [Figure 1d].Figure 1: (a) Depigmentation on both upper and lower lips. (b) Depigmentation on the mucosal aspect of the lower lip with some islands of normal pigmentation seen. Involvement of both oral commissures and gum. (c) Bael paste is used for the patch test and bael leaves. (d) Depigmentation at the bael patch siteCase 2: A 78-year-old female presented with progressive white patches on her lips and surrounding skin and an apprehension of vitiligo for the past 2 months. Detailed history revealed that she had a habit of chewing one dried clove bud daily for a sensitive left upper molar for 1 year. She used to keep the crushed clove in the oral vestibule near this tooth for half an hour daily. On examination, there was depigmentation on the mucosal aspect of the upper and lower lips, extending outward on the vermillion, both lateral commissures and adjoining skin. The area of depigmentation was more on the left than the right side [Figure 2a]. The left oral commissure was totally depigmented. There was residual pigmentation on the outer aspect of the right commissure. Everting the lower lip showed depigmented gums [Figure 2b]. The left upper first molar tooth was affected [Figure 2c]. She had diabetes and hypothyroidism. The patient declined clove- patch test.Figure 2: (a) Depigmentation on lips, more on the left side. (b) Depigmentation on the mucosal aspect of the lower lip. Gums are also depigmented. (c) The affected left upper first molar tooth and depigmentation of the adjoining buccal mucosa.(d) Clove budsBoth the patients did not have any symptoms. There was no history of any prior application, eruption, and usage of toothpaste containing cinnamic aldehyde. No other lesions were seen elsewhere. They did not have a past or family history of vitiligo. Both of them refused a biopsy. Stopping the use of bael leaves/cloves [Figure 2d] halted the progression of depigmentation and spontaneous repigmentation started. This supported the diagnosis of phytochemical-induced leucoderma [Figure 3]. Both the patients were treated with tacrolimus 0.1% and were advised sun exposure.Figure 3: (a) Depigmentation of both lateral commissures and the inner aspect of the lips due to bael in case 1. (b) Repigmentation of both lateral commissures started, and an overall increase in pigmentation on the upper lip, after stopping bael. (c) Clove induced depigmentation of the left lateral commissure and extension to the adjoining skin in case 2. (d) Robust repigmentation on the lower lip near the lateral commissure and overall increased pigmentation on the lower lip after stopping cloveThere are reports of leucoderma on oral cavity, lip, and perioral area induced by cinnamic aldehyde-containing toothpaste and neem phytochemicals.[2] Our first case was diagnosed and confirmed by patch test as bael-induced leucoderma. The patch test in chemical vitiligo is not standardized. We did it with bael leaves paste. The erythema on day 2 could be because of pressure and the frictional effect of the unstandardized preparation. The delayed reading after 6 weeks was taken because it takes 4–6 weeks to shed the preformed melanin from epidermis.[2] Our second case had depigmentation due to chewing clove. The greater involvement of the left side, fulfillment of criteria for chemical leucoderma,[1] halting of progression, and beginning of repigmentation after stopping contact with clove confirmed clove as the culprit. Bael (Aegle marmelos) and cloves (Syzygicum aromaticus) are medicinal plants widely utilized for general health benefits and in dentistry respectively.[3,4] The main chemical constituents of clove is eugenol, a phenolic compound.[3] The phytochemicals in bael are rutin, quercetin, ellagic, gallic acid, marmelosin, and others.[4] Gallic acid, ellagic acid, and quercetin are the phenolic compounds present in both bael and clove.[3,4] Gallic acid and quercetin have tyrosinase inhibitory properties.[5] The pathogenesis of leucoderma in our cases could be direct melanocytotoxicity due to oxidative damage or tyrosinase inhibition with disruption in melanin synthesis in susceptible individuals.[2,5] In addition clove-induced depigmentation could be due to the targeting of senile, fragile susceptible melanocytes. Vitiligo and postinflammatory hypopigmentation were ruled out in our cases. The fulfillment of clinical criteria, patch test reading, and early and robust repigmentation on stopping the culprit agents ruled out vitiligo. The absence of a preceding dermatitis or eruption ruled out postinflammatory depigmentation. Chemical leukoderma is not always limited to the contact sites.[1] In our cases, the lesions were localized. These cases highlight the importance of obtaining a detailed history of exposure to herbal home remedies for accurate diagnosis. It also emphasizes the need for awareness among clinicians and patients regarding the potential harmful effects of so-called natural herbal usage. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their 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 author without the use of artificial intelligence technologies.