Herbal oral gel induced contact stomatitis along with desquamative gingivitis due to a coloring agent.

Report of a rare case of contact stomatitis manifesting as irregular erosions partially covered with pseudomembrane along with desquamative gingivitis in a 32-year-old female patient is presented. The patient was otherwise healthy and not taking any medication. She gave the history of using curcumin-based oral gel 2 days back. Allergy test to curcumin oral gel was found to be positive, which on detailed allergy testing proved to be the coloring agent, erythrosine present in the gel. Contrary to the popular belief some folk medicine preparations can lead to unwanted side effects due to the antigenic potential of ingredients present in them. In addition, every clinician, during differential diagnosis of oral lesions must bear in mind unwanted reactions to any local ointment.

INTRODUCTION

Skin and oral mucosa function as physical barriers to the outside environment and also play a biologic role in modulating interactions between the environment and the body. Different subjects develop a different degree of irritation when exposed to the same chemical or mechanical insult under the same conditions.

Allergic contact stomatitis is a rare disorder, which most clinicians are not familiar with. A wide variety of substances are known to elicit adverse oral mucosal reactions. Allergic stomatitis may present as immediate (type I) hypersensitivity or as a classic delayed (type IV) hypersensitivity immunologic reaction.[1] Virtually, every known drug and material is capable of inducing an allergic reaction.[2] Erythrosine is a coloring agent used in various pharmaceutical, food, and cosmetic industries. Allergy to erythrosine is rare; only one case in the literature has been documented till date. Authors in that case study speculated that the use of Erythrosine in the denture material was responsible for denture stomatitis.[3]

CASE REPORT

A 32-year-old female patient reported to the Department of Periodontology, Bhojia Dental College and Hospital, Baddi Himachal Pradesh with a chief complaint of pain, ulcers, and swelling on lips. She further complained of pain and sensitivity in gums, to whatever little she could take. The patient was, otherwise healthy and not taking any medication. No drug allergies were reported, and detailed medical history revealed no systemic disease. She reported a history of trauma 1-month back because of which she received injuries on her lips and sutures were given for the same on upper and lower labial mucosa by a private clinician and the medication given for the same had been stopped after 1-week of the accident. Sutures were removed after lignocaine gel application and after suture removal she was prescribed curcumin-based oral gel for local application at home. Subsequent to the use of the curcumin gel; after 1-day, she developed erythematous rashes all over the mucosa which later on progressed to multiple ulcers within 1–3 days. On examination, irregular erosions partially covered with pseudomembrane that involved both the lips and oral mucosa were observed with swelling on the lips. Erosions appeared as outlined, whitish, rough areas. Ulcerations were mostly covered by a yellow-white exudate and presented with an erythematous halo. Features of desquamative gingivitis, such as erythematous gingiva and discrete erosions were present involving both the arches. The eruption of lesions was not accompanied by any systemic symptoms, and none of the other parts of the body were involved. The lesions started to develop after two to three applications of curcumin ointment. The condition of the patient was quite disabling as she could not eat and swallow. She had difficulty while speaking too [Figures 1–3].

Figure 1

Ulcers on lower lip with desquamative gingivitis

Figure 3

Ulcers involving entire buccal mucosa

Ulcers on upper lip with desquamative gingivitis

Patient was advised to discontinue the topical application of curcumin-based oral gel, and the lesions were cleaned with povidone-iodine and saline at frequent visits. She was prescribed the systemic antihistaminic (pheniramine maleate), nonsteroidal anti-inflammatory drugs (paracetamol), and topical steroids (betamethasone valerate). Lesions subsided in 1-week after the treatment [Figures 4–6]. Patient was recalled for allergy tests after 15 days. Patch allergy test was performed on patient's arm using Finn chambers (Systopic Laboratories) for control (a), curcumin (b), curcumin-based oral gel (c) and lignocaine oral gel (d). After 4 days, patch was removed, and allergy test for c was found to be positive [Figures 7 and 8].

Figure 4

Healing after 15 days

Figure 6

Healed gingival and labial mucosa after 15 days

Figure 7

First allergy test done with a, b, c, d

Figure 8

Results of first allergy test after 4 days

After confirmation of the allergy, individual ingredients of the curcumin-based ointment were procured and the patch test was repeated again on patient's arm with individual ingredients (ROHA Dyechem Pvt. Ltd., Curcumin, Titanium Dioxide, Brilliant Blue FCF, Erythrosine) after 1-month. Six chambers of the strip were numbered from 1 to 6. Curcumin oral gel (1), curcumin (2), erythrosine (3), brilliant blue FCF (4), titanium dioxide (5) and control (6), respectively, from 1 to 6. Curcumin (2), erythrosine (3), brilliant blue FCF (4), titanium dioxide (5) were mixed with sterile water for the patch test. After 4 days, the patch was removed, and again it confirmed the allergy to curcumin-based oral gel and along with this erythrosine (3) was also found to be positive for allergy. Hence, it confirmed the allergy to coloring agent added to the ointment [Figures 9–11].

Figure 9

Possible allergens, sterile water, and finn chambers used in second allergy test

Figure 11

Results of second allergy test confirming allergy to 1 and 3

Loaded Finn chambers secured on patient's arm

DISCUSSION

Differential diagnosis of multiple oral ulcers may include aphthous ulcers major, erosive lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris. Multiple oral ulcers may be classified as acute, recurrent and/or chronic. The most common causes of rapid-onset oral ulcers include acute necrotizing ulcerative gingivitis, allergies, acute herpetic gingivostomatitis, and erythema multiforme. Clinical criteria which are most useful in identifying the cause of oral ulcers are vesicles or bullae, which may not be seen because they rupture rapidly in the oral environment. Complete history is essential to come to the accurate diagnosis. In some cases, diagnosis depends upon culture or biopsy, particularly with the application of immunofluorescence to the surgical specimen.

Contact stomatitis is an inflammation of the oral mucosa caused by external substances. It can be caused by a variety of substances, which can act as allergic agents. These substances include dental materials, preservatives and flavoring and coloring agents in foods or oral hygiene products. Dental therapeutic agents e.g., alcohol, antibiotics, chloroform, iodine, phenol, procaine, and volatile oils are some of the agents which can cause contact stomatitis. Cinnamon oil used in various preparations such as gum candy, mouthwashes, and mouth freshener has also been reported to cause allergic reactions.[4] Oral mucosa is less commonly prone to contact allergic reactions, when compared to skin, though the latter is exposed to a wide variety of antigenic stimuli.[5]

Therapeutic benefits of curcumin are very popular in folk medicine for the treatment of various oral and skin conditions. Though, the allergy to curcumin is unlikely still it was suspected as a possible allergen as it was the principal ingredient in the ointment. Sensitivity to certain products can go unnoticed for years. Coloring agents used in the preparations of medicines can be the possible allergens.[678] Erythrosine (FD and C Red No. 3, disodium salt of 2,4,5,7-tetraiodofluorescein); is used extensively as a color additive in foods, drugs, and cosmetics.[910] Erythrosine was able to provoke an experimental iodine allergy in guinea pigs.[11] In a study done on pregnant rats, the authors observed that erythrosine increased the number of mast cells and stimulated the degranulation of these cells, suggesting that erythrosine may play an inductive role in atopic diseases.[10] A case study has been reported, in which a patient suffered from hypersensitivity to denture materials. Authors reported that this could be due to the use of Erythrosine in the denture material, but was not completely clear from the study.[3] The present case report emphasizes antigenic potential of coloring agents used in various preparations and suggests that these should be used carefully as topical agent in the treatment of oral diseases. Furthermore, it highlights the fact that contact stomatitis should be taken into account in the differential diagnosis of the oral lesions. We believe that people must be informed about the effects of any additives as a formal regulation.