Route Of Exposure

Allergen Exposure

True cinnamon is the dried or powdered inner bark of the Cinnamomum zeylanicum tree and has been used as a spice and in perfume and incense for over 5000 years. True cinnamon is a native of Sri Lanka and was a monopoly product of that country before sources developed on the neighbouring Malabar Coast of India, and in Myanmar (Burma), South America and the West Indies. True cinnamon should be distinguished from the closely related Cassia (Chinese cinnamon, used in China long before true cinnamon but now considered an inferior substitute), which is obtained from Cinnamomum cassia, grown in China. True cinnamon has been replaced almost entirely by Cassia in many markets and is not often used – nor are consumers often aware of the difference. Cassia is thicker, darker, more pungent and rougher in appearance, with a less subtle flavour. It is the main source of Cinnamon oil.

Cinnamon of both kinds comes from bushy, 6-8 m tall evergreen trees, cultivated as low bushes to ease the harvesting process. The spice is obtained by drying the central part of the bark and is marketed as stick cinnamon or in powdered form. The waste and other parts are used for oil of cinnamon, a medicine and flavouring.

Cinnamon of both kinds has an agreeable and delicate fragrance and a sweetly pungent taste. It is therefore used as a spice (whole or ground) and as a flavouring agent for various types of products such as confectionery, pharmaceutical preparations, sausage, eggnog, oriental curries, chewing gum, toothpaste, and mouth washes. It helps to create flavours of apple, plum, vanilla, etc., as well as of cinnamon. It may be an ingredient in beverages such as cola drinks, vermouth and bitters. It is used in cosmetics, and has carminative and anti-diarrhoea properties in drugs as well. Oil of cinnamon is used as a flavourant and a scent in perfumes. It is a stimulant, digestive, antiseptic and fungitoxic, and so is also often used in drugs.

From a phytochemical viewpoint, cinnamon is a uniquely interesting plant. The volatile oils obtained from the bark, leaf, and root bark vary significantly in chemical composition. Each oil has a different primary constituent: cinnamic aldehyde (or cinnamaldehyde) (in the bark oil), eugenol (in the leaf oil), and camphor (in the root-bark oil). Other components are eugenol acetate, and small amounts of aldehydes, ketones, alcohols, esters and terpenes.

The oil distilled from the bark and leaves of the true cinnamon tree constitutes a minor part of the industry in Sri Lanka. The cinnamon oil of commerce is usually obtained from C. cassia. As much as 68% of the oil consists of cinnamic aldehyde, which is a powerful irritant that can blister the tongue. Powdered Cinnamon contains only about 1% of the aldehyde and is not an irritant under ordinary circumstances.

Cinnamic aldehyde has been identified as the active fungitoxic constituent of oil of cinnamon and may result in allergic as well as irritant reactions. Used as a flavourant in toothpaste, it can result in stomatitis, cheilitis, glossitis, gingivitis, perioral dermatitis and immediate hypersensitivity. The most common allergens causing cheilitis are reported to include fragrance mix (mainly cinnamic aldehyde, oak moss, and isoeugenol).

Eugenol, along with carvone and linalool (which are also components of cinnamon oil), is stable to heat. In contrast, starting at approximately 60 degrees C, pure cinnamaldehyde undergoes a temperature-dependent transformation to benzaldehyde under the influence of the heat. Eugenol (both pure and in cinnamon oil), when added to pure cinnamaldehyde, protects the aldehyde against heat destruction.

The processing of cinnamon is multi-faceted, labour-intensive and largely unmechanised. It involves peeling, scraping, drying, sorting, bleaching, bundling, re-sorting, re-bundling, and refuse recycling (mainly for oil production). Some cinnamon sticks are cut with a circular saw. There is considerable exposure of workers to the cinnamon dust and the aromatic oils, as well as to the sulphur dioxide used in bleaching.

Cinnamaldehyde has also been used as a filtering agent, a rubber-reinforcing agent, a brightener in electroplating processes, an animal repellent, and an insect attractant.

Clinical Relevance

Allergen Description

No allergens from this spice have yet been characterised.

Potential Cross Reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected. In both laboratory and clinical studies it is usually unclear whether the substance in question is true cinnamon or Chinese cinnamon. While it should by no means be assumed that the two are equivalent where allergy is concerned, a clarification of their differences must await further research.

Although cross-reactivity between Balsam of Peru and cinnamon has not been established, allergy to cinnamon is frequently encountered in individuals allergic to Balsam of Peru.

In animal studies, a certain degree of cross-reactivity between cinnamaldehyde, cinnamyl alcohol and cinnamic acid was demonstrated. Animals sensitised to cinnamyl alcohol reacted to cinnamyl alcohol and cinnamaldehyde, but not to cinnamic acid. Compared to the challenge concentration for cinnamaldehyde, an approximately 15-times higher concentration of cinnamyl alcohol and a 25-times higher concentration of cinnamic acid were required to induce positive reactions in animals sensitised to cinnamaldehyde. The study suggests that cinnamaldehyde is the ‘true’ allergen, while cinnamyl alcohol and cinnamic acid are transformed in the skin to cinnamaldehyde before contact allergic reactions can occur.

Clinical Experience

IgE-mediated reactions

Cinnamon may commonly induce symptoms of food allergy in sensitised individuals.

Cinnamon oil has been known as a contact allergen since the 19th century, when sucking on cinnamon-soaked toothpicks was found to cause contact dermatitis. Two components of cinnamon are known to be sensitising: cinnamon oil and cinnamic aldehyde. Cinnamic aldehyde is the most common of the allergenic constituents. Cinnamic aldehyde and related chemicals are used widely; patients with cinnamon allergy may be exposed to many sources.

Contact and systemic contact-type dermatitis reactions to spices such as cinnamon may well be overlooked. Positive skin-specific IgE tests to cinnamon may be reported during investigation of other food allergies, but the clinical implications may not be evident. The most common reactions described are those of allergic contact dermatitis or irritant contact dermatitis. Although immediate hypersensitivity reactions are possible, many reported allergic contact dermatitis cases occur as a result of delayed type IV reactions.

Perioral dermatitis as a result of cinnamon has been reported. Cinnamon used as an odour-neutralising agent in shoe insoles was reported to be responsible for a case of allergic contact dermatitis. Bullous contact allergy from cinnamon in a young Malay female as a result of contact allergy to cinnamic aldehyde in cinnamon has been described.

In an early report, a newly formulated ‘spicy’ toothpaste containing cinnamon as a flavouring agent was the cause of oral symptoms in 8 patients referred to clinics in England, and in a further 8 patients discovered subsequently. Positive reactions were obtained with 1% cinnamic aldehyde in 15 out of 16 patients tested. Subsequently, a number of reports have described adverse reactions to cinnamon in toothpaste, from acute contact sensitivity to cinnamon-induced stomatitis. Reports have implicated cinnamon or a component of cinnamon: a patient had acute stomatitis and dermatitis due to a popular toothpaste containing cinnamon oil flavor. Cheilitis caused by cinnamon oil in toothpaste has been described, but may result from irritation rather than an allergic mechanism. Contact dermatitis following oral administration of cinnamon oil has been reported.

In still more reports, patients sensitive to cinnamic aldehyde in a toothpaste have been described. In a report of 37 cases of cinnamon-induced contact stomatitis, the most common cause was toothpaste; other causes were chewing gum and foods. Although various clinical findings were described, the most commonly affected site was the gingiva, which showed diffuse or generalised erythema and epithelial sloughing.

A Finnish study on toothpaste composition concluded that toothpastes are not entirely safe to use, because almost 50% of the 48 products studied contained a total of some 30 compounds widely recognised as allergens. The most common allergens in toothpastes are flavourants (e.g. cinnamic aldehyde, cinnamon oil and peppermint) and preservatives. Symptoms include stomatitis, cheilitis, glossitis, gingivitis, perioral dermatitis and immediate hypersensitivity.

Cinnamon is often a component of chewing gum. Two cases of cheilitis caused by cinnamon oil in bubble gum have been reported. Oral lesions may take on a more sinister presentation: an oral lesion that was clinically thought to be a squamous cell carcinoma was found to have resulted from cinnamon oil in chewing gum. The case is unusual because of the leukoplakia noted; all other previously reported cases described erythematous patches only.

Non-IgE-mediated allergic contact stomatitis to cinnamon found in chewing gum was described in a 39-year-old female referred with the diagnosis of angioedema. She reported recurrent swelling of the cheeks with intermittent pain and burning sensations every 1-2 weeks for more than 6 months. Urticaria was never present. The swelling often began in the evenings and spontaneously resolved overnight. Systemic antihistaminic therapy did not help. Specific-IgE assessments were negative for cinnamon. Patch tests were positive to fragrance- mix: its individual components revealed a positive test to cinnamic alcohol and cinnamic aldehyde. She recalled having chewed several cinnamon-flavoured chewing gums some hours before the start of the symptoms. After omission of the chewing gums, there was no recurrence.

A 37-year-old woman was described with a year history of episodic, painful palatal and buccal blisters and erosions without cheilitis, attributed to exposure to cinnamon-flavoured breath mints. Patch tests were positive for cinnamic aldehyde.

In view of the irritant and allergic nature of cinnamic aldehyde and the reported sensitivity reactions to it, it is not unreasonable to expect cinnamon processors and workers having contact with cinnamon at further stages to exhibit occupational ill effects. Cinnamon is well known to cause dermatitis in bakers and confectioners. Some occupations seen as particularly susceptible are in the food industry, for example bakers, bakery workers, and other individuals working with spices. Occupational allergic contact dermatitis has been described. Allergic hand dermatitis occurred in a 50-year-old baker with a 3-month history of rash, which began on both palms and spread to the dorsum of the right hand.

In a study investigating 40 workers with an average of 4 years' service in the cinnamon processing industry, 35 workers (87.5%) had symptoms, including asthma (22.5%), irritation of the skin (50%), loss of hair (37.5%), and smarting of eyes while at work (22.5%). Loss of weight (65%) was the most common finding. Sweating while doing manual work is common, and many workers experienced itching or a burning sensation when cinnamon dust settled on the sweat. The authors suggest that cinnamic aldehyde may dissolve in sweat and cause this irritation.

In 70 workers in a Swedish spice factory investigated by questionnaire regarding skin symptoms, pruritus and skin irritation (particularly from cinnamon powder) were common. Patch test reactions to cinnamic aldehyde were found in 11 of 25 factory workers, but in several cases the nature of the reactions was difficult to evaluate. On skin-specific IgE investigation, 6 of 25 workers reacted to cinnamic aldehyde.

Occupational allergic contact dermatitis from essential oils containing eugenol, oil of Cinnamon and oil of Cloves has been reported in a physiotherapist.

Six patients with delayed contact allergy to Cinnamon were reported from two dermatological clinics in Helsinki. In four patients, cinnamon was the main cause of occupational allergic contact dermatitis (ACD): 3 had dermatitis on their hands and one patient on the face and neck. In the latter case, the exposure was shown to be as a result of airborne contact with cinnamon. The fifth patient was occupationally sensitised to Cinnamon, but it was not the main cause of his hand dermatitis. In the sixth patient, Cinnamon allergy was considered to derive from cross-allergy to fragrances. Five of the patients reacted to cinnamal separately and in fragrance mix I. None of the six patients experienced immediate-type cinnamon allergy. (39

Other reactions

Oral lesions induced by contact with cinnamon flavouring agents may be unrecognised by many clinicians. In a report on 10 patients with these lesions, it was stated that most patients had a "burning sensation" as their primary symptom. Clinically, lesions appeared as erythematous patches with varying degrees of superimposed keratosis or ulceration, or both. The lesions were usually confined to the buccal mucosa and lateral border of the tongue. The offending agent was almost always cinnamon-flavoured chewing gum, and symptoms typically resolved within 1 to 2 days of discontinuing the product containing cinnamon. Other symptoms may include painful sores, inflamed taste buds and an overall burning sensation. Stomatitis as a result of cinnamon has been described in 14 patients: 10 cases were first detected on the basis of histopathologic changes, which included hyperkeratosis, chronic lichenoid mucositis with plasmacytic infiltration, and marked chronic perivasculitis.

Cinnamon has resulted in erythema multiforme, which manifested as chronic extensive surface ulcerations and lip swelling. The authors state that a negative skin test does not rule out an allergic reaction to food.

Animal studies have indicated that cinnamon dust may also have a non-allergic damaging effect on lung tissue. Histopathological effects of a single intratracheal dose of respirable cinnamon dust, cinnamon dust extract, and cellulose dust on the lungs of rats were studied sequentially 1 day, 7 days and 1 month after treatment. Exposure to respirable cinnamon and cellulose dusts resulted in alveobronchiolitis at the end of the first and seventh day, and fibrotic changes by the end of the first month. As the extract of cinnamon dust caused no histopathological alterations, it is assumed that the cellulose content of cinnamon dust was responsible for the histological reactions.

Trans-cinnamaldehyde (closely related to cinnamic aldehyde) was nominated for study by the US Food and Drug Administration based on its widespread use as a flavour and fragrance ingredient, and its structural similarity to cinnamyl anthranilate and 3,4,5-trimethoxy cinnamaldehyde, two known rodent carcinogens.