CLINICAL PRACTICE
CASE REPORT |
CINNAMON-INDUCED ORAL ERYTHEMA MULTIFORMELIKE SENSITIVITY REACTION
DONALD M. COHEN, D.M.D., M.S., M.B.A. and
INDRANEEL BHATTACHARYYA, D.D.S., M.S.D.
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ABSTRACT
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Background. Erythema multiforme, or EM, is a hypersensitivity reaction to agents such as herpes virus, drugs or foods. Oral EM-like reactions may be induced by cinnamon. It is important for dentists to recognize this condition.
Case Description. The authors report an unusual case of cinnamon-induced oral EM-like reaction in an older female patient. The disease manifested itself as chronic extensive surface ulcerations and lip swelling. The patient was treated repeatedly with topical and systemic steroids but responded to them only temporarily. The patient was cured when the offending agent—cinnamon—was eliminated from her diet.
Clinical Implications. Oral EM or EM-like reactions pose a diagnostic dilemma due to their varied etiologies and clinical manifestations. Correct diagnosis is essential for effective treatment. A negative skin test does not rule out an allergic reaction to food.
Erythema multiforme, or EM, is an acute, self-limiting mucocutaneous hypersensitivity syndrome.1–6 It exhibits a diverse etiology, often recurs, has unusual clinical features and is of uncertain pathogenesis.1,2 It usually exhibits distinctive skin or mucosal lesions that are characterized by a combination of bullae, papules, macules or ulcers. It most probably is an immunologically mediated process, although its cause is poorly understood. In about 50 percent of the cases, previously being infected with herpes simplex or Mycoplasma pneumoniae or being exposed to any one of a large variety of medications can be identified as a causative factor for developing EM.3–6 Other factors that have been linked to EM include malignancies, pregnancy, inflammatory bowel disease and exposure to sunlight.5 A few cases of oral EM-like reactions have been reported in people after contact with rubber, nickel, mouthwashes and certain foods such as margarine and benzoic acid (a food preservative).1,2,4,6–10
Cinnamon is a commonly used spice and flavoring agent derived from the bark of the Cinnamomum zeylanicum tree of the genus Lauraceae. This tree is native to eastern and southeastern Asia.11 The active ingredient in cinnamon is cinnamic aldehyde, which is a common contact allergen.3,4,6–9,11–18 Cinnamon is available in various forms such as powders, sticks and pastes.
There are no documented cases of oral EM related to cinnamon-flavored food in the English language literature; however, cinnamon-associated contact stomatitis has been well-documented.8–10,12–14 Terms such as plasma cell gingivitis, atypical gingivostomatitis or idiopathic gingivostomatitis have been used to describe sensitivity reactions to cinnamon-flavored chewing gum and toothpaste.6
Miller and colleagues12 presented 14 new cases of cinnamon-induced stomatitis with histologic features ranging from hyperkeratosis to lichenoid mucositis to marked perivasculitis. Their cases were localized mostly to the buccal mucosa, the area of contact with the offending agent. The lesions were nonulcerative, only mildly symptomatic and varied from leukoplakic to mildly erythroplakic. They suggested the term cinnamon stomatitis for such cases. Mihail16 reported a case of oral leukoplakia resulting from the use of cinnamon-flavored chewing gum.
Numerous reports of cinnamon-induced contact dermatitis of the skin have been published in the literature.1,7,11,18–20 Goh and Ng14 reported a case where a young Malay female developed bullous lesions on the skin of her knees and legs after rubbing ground cinnamon into scars she had in these areas. Nixon18 described a case in which the skin of a baker’s hands had florid dermatitis caused by contact with cinnamon.
Oral EM or EM-like reactions often present a diagnostic dilemma because of their ability to produce varied manifestations. Oral lesions induced by foods, flavoring agents or preservatives pose an additional challenge in identifying and eliminating the offending agent.6–8,10,12–14 In this article, we present a case of a cinnamon-induced oral EM-like reaction in a 66-year-old woman.
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CASE REPORT
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A 66-year-old woman came to one of us (D.M.C.) in February 1995 with a chief complaint of soreness associated with large ulcers that had been present in her mouth continuously for the past four months. She reported that similar lesions had occurred on and off for the last four years with only a few weeks’ respite between outbreaks. The ulcers were extremely uncomfortable and made it difficult for her to eat and function normally. The present outbreak coincided with the placement of a crown.
When we examined the patient, we found large areas of serpiginous ulcerations on the labial and buccal mucosa and on the ventral surface of the tongue, as well as that her lips were swollen (Figures 1
and 2). We carefully recorded her medical, dental and personal histories, including unusual habits. Her physician recently had treated her with acyclovir for 10 days for what he thought was a herpetic outbreak, but it was not helpful. She also had been prescribed a chlorhexidine mouthwash for the past four months, and this also failed to improve her condition. Her medical history was significant for hypertension, for which she had been taking reserpine, hydralazine and hydrochlorothiazide for the past 20 years. She also had taken 600 milligrams of ibuprofen per day for arthritis but discontinued it on her own.
We performed a biopsy of the buccal mucosa at the first appointment; it showed thickening of the epithelium (acanthosis) accompanied by intra- and intercellular edema. We noted small numbers of microvesicles beneath the epithelium and few necrotic epithelial cells (Civatte bodies). In addition, we observed transmigration of inflammatory cells into the lower regions of the epithelium with an indistinct epithelium–connective-tissue interface. The lamina propria exhibited extensive edema. Notably, numerous dilated vascular channels surrounded by neutrophils and lymphocytes were scattered throughout the connective tissue. The histologic features were considered to be compatible with EM.14 Indirect immunofluorescence assay of the biopsy tissue failed to reveal any significant immunoglobulin deposits.
We placed the patient on a regimen of 40 mg of prednisone (in tablet form) daily for five days, which dose then was reduced gradually over the next two weeks. She returned after one week, and we noted dramatic improvement in her condition. The erosions and ulcers in her mouth had healed completely. When the patient returned two weeks later, she had recurrent punctate ulcers on the left anterior buccal mucosa and hard palate. The area where the biopsy was performed appeared red and irritated. At this time, we placed the patient on a regimen of topical fluocinonide 0.05 percent gel.
She then was lost to follow-up for about five months. When she returned, she had multiple ulcers affecting diffuse areas of her mouth. A large ulcer measuring 2 x 1 centimeter was noted on the right side of the soft palate. We again placed her on a course of 40 mg of prednisone daily and asked her to report back in one week.
The patient failed to return again for about nine months. In May 1996, she returned, stating that she had been experiencing flare-ups of multiple ulcers all over her mouth for the past six months. She had been prescribed prednisone tablets by her physician, which helped to a small extent. She also had intermittent smaller lesions, which she had self-medicated with topical fluocinonide 0.05 percent gel. At this appointment, we found diffuse red areas with small ulcers on the anterior mucosal aspect of the upper lip and on the left buccal mucosa. We also observed a small ulcer on the ventral surface of the tongue. During this appointment, she reported consuming cinnamon-flavored bread pudding immediately before the onset of the latest outbreak and confessed to frequently using cinnamon-flavor ed sugar on bread and rolls, as well as drinking herbal tea with cinnamon daily. The current soreness in her mouth prevented her from having cinnamon, which she enjoyed.
Our working diagnosis at this stage was a cinnamon-induced EM-like reaction. We advised her to avoid cinnamon completely and once again prescribed 40 mg of prednisone tablets daily. She returned approximately one week later and the lesions were almost completely healed except for some residual soreness. We again prescribed topical fluocinonide 0.05 percent gel at this point. The patient was seen again after two weeks, and there was complete resolution of all the symptoms with no evidence of any lesions (Figure 3).
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Figure 3. Complete resolution of lip lesions after topical corticosteroid therapy and cessation of cinnamon use.
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We received a letter from the patient 18 months later indicating that she had been free of discomfort except for two or three minor outbreaks of oral ulcers that followed her eating in places in which she was not able to control her cinnamon intake. Subsequent investigation into each of these outbreaks revealed the ingestion of cinnamon or cinnamon-flavored products.
To rule out the possibility of a simple contact stomatitis, as opposed to EM, the patient was subjected to antigenic challenge using standard skin tests for cinnamon compounds, which included 5 percent cinnamic acid and 2 percent trans cinnamaldehyde. She tested negative for both agents at 72 hours.
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DISCUSSION
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Oral EM is a recently accepted clinical entity characterized by numerous and diffuse ulcerations and red patches and frequently is associated with lip swelling.3,21,22 Skin lesions often are absent or inconspicuous.21 Our patient had an unusual, severely debilitating EM-like reaction to cinnamon, which can be differentiated from contact stomatitis based on the following rationale.
- – Cases of contact stomatitis almost always test positive to antigenic skin challenges because the skin is a more reactive and reliable testing zone.23–25 On the other hand, EM is a systemic response, and antigenic skin tests may be negative.
- – EM often exhibits a wide range of signs and symptoms that include swelling and hemorrhagic crusting of lips, numerous and widespread ulcerations, and erosion and erythema of oral mucosa, which often are accompanied by profound pain and debilitation.1–3,6,22 In contrast, contact stomatitis is more localized with erythema, lichenoid change or ulcerations and usually is limited to the buccal mucosa and lateral border of the tongue.8,23–25 Often the patients complain only of a mild burning sensation as the primary symptom.8
- – Histopathologic features of contact stomatitis range from those similar to lichen planus to psoriasiform mucositis with prominent perivasculitis.23 EM is characterized by acanthosis and significant intra- and intercellular edema of the epithelium with inflammatory infiltration and tremendous edema of the lamina propria. The epithelial–connective tissue interface often is blurred, and perivasculitis is common. Though this constellation of histologic changes is not specific, it is suggestive of EM, and with clinical correlation a definitive diagnosis can be made.15
- – Contact dermatitis from food additives such as benzoic acid has been known to precipitate EM after patch testing or contact with the skin, and skin reactions to cinnamon often resemble EM-like reactions, including the development of bullous dermatitis and urticaria.7,8,17,19,20 The etiopathogenesis of EM is uncertain, with numerous precipitating or predisposing factors often making the diagnosis difficult. Chronic oral EM can be triggered by a hypersensitivity reaction to the herpes simplex virus, but other infectious agents, drugs and food also have been implicated (Box, "Predisposing Factors for Erythema Multiforme").1–7,21,22 The diagnosis of oral EM can be relatively simple when it also involves the skin; when limited to the oral cavity, however, numerous conditions and lesions should be considered in the differential diagnosis.1,3,4,21,22 A common condition confused with oral EM is acute herpetic gingivostomatitis.3,4,21 The main points that differentiate these conditions are that in herpetic stomatitis widespread gingival involvement is common, whereas oral EM rarely involves the gingiva except for occasional focal areas.6 Herpetic lesions are confined to the formation of vesicles that eventually rupture to form ulcers. EM has numerous lesions, including wide areas of erythema, swelling, punctate and large ulcerations, and even bullae. Both herpes and EM may be seen on any oral mucosal site, but herpes usually is seen in children and often is associated with fever and lymphadenopathy.6 EM usually is seen in young adults, and patients rarely have a fever or lymphadenopathy. Primary or acute herpetic gingivostomatitis may occur only once, whereas EM frequently recurs.6
Other conditions that we considered in our clinical differential diagnosis included bullous lichen planus, pemphigus vulgaris and benign mucous membrane pemphigoid.6 All of these conditions have characteristic histologic and immunological features that were not present in our case.
The most important step in the management of food- or flavoring-agent–induced oral erythema multiforme-like reactions is the identification and elimination of the offending agent.
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CONCLUSIONS
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The most important step in the management of food- or flavoring-agent–induced oral EM-like reactions is the identification and elimination of the offending agent. Maintaining a food diary and instituting an elimination diet may aid in the identification of the predisposing agent.7,8,17,23–25 Unless contraindicated by medical reasons, a brief course of systemic prednisone or topical corticosteroids such as fluocinonide or betamethasone usually is effective in controlling the disease.7,22
The importance of completely avoiding the precipitating agent needs to be stressed in patients with food-related reactions. All recurrences should be recorded diligently. Antigenic challenge using patch testing may help identify the offending agent or rule out contact stomatitis.9
A negative skin test and the profound clinical manifestations seen in this patient strongly suggest an EM-like reaction even in the absence of obvious skin lesions.7,21,25
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FOOTNOTES
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Dr. Cohen is a professor, University of Nebraska Medical Center, Department of Oral Biology, College of Dentistry, 40th and Holdrege, P.O. Box 830740, Lincoln, Neb. 68583-0740, e-mail "dcohen{at}unmc.edu". Address reprint requests to Dr. Cohen.
Dr. Bhattacharyya is an assistant professor, University of Nebraska Medical Center, Department of Oral Biology, College of Dentistry, Lincoln.
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REFERENCES
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