Fig 3 - uploaded by Hiroyasu Endo
Content may be subject to copyright.
Source publication
It has been reported that clinical changes due to hypersensitivity reactions to various foods, preservatives, and oral hygiene products may be consistent with the characteristic signs of orofacial granulomatosis (OFG). The objective of this study was to examine 37 well-documented cases of cinnamon-induced contact stomatitis for clinical and histolo...
Contexts in source publication
Context 1
... are in agreement with this conclusion (17,18), in some cases, eliminating provoking factors clearly led to remission of OFG signs and symptoms (3,9-14). Reported provoking factors of OFG are cocoa (16), cinnamon (3,9), carvone (9), piperiton (9), aspartate(14), carmoisine (11), sunset yellow (11), monosodium glutamate (11,13), sodium benzoate (12) and tartrazine (12). A few case reports have described OFG as a hypersensitivity reaction to dental restorative metals and remission after removal of the materials (7,15,19). Cinnamon is a common flavoring agent contained in toothpaste, foods, and chewing gum and is known to occasionally cause contact allergic stomatitis (20-22). In a previous paper, we reported on characteristic clinical symptoms, diagnosis, and treatment in 37 cases of cinnamon-induced contact stomatitis (20). Characteristic clinical symptoms of OFG were observed in the lips, gingiva, and buccal mucosa in some cases (20). These characteristics have rarely been described in other papers reporting on cinnamon-induced contact stomatitis. The objective of this study was to examine 37 well-documented cases of cinnamon-induced contact stomatitis for clinical and histological features consistent with a diagnosis of OFG. The subjects were 37 patients diagnosed with cinnamon- induced contact stomatitis, as described in a previous paper (20). Briefly, we examined the patient records from the database of the Stomatology Center at Baylor College of Dentistry and identified 65 cases from 1985 through 1998 that were classified as cinnamon-induced contact stomatitis. The records examined contained information such as the types of oral hygiene products being used by the patients and the frequency of gum chewing. Patients kept food diaries for 1 to 2 weeks, and the contents of their diets were evaluated if necessary. In some cases, evaluation included patch tests and biopsies. In 37 of these 65 cases, causative cinnamon flavoring agents were identified, and signs and symptoms subsided after discontinuing the use of the agents. These 37 cases were used in the present study. Of these 37 cases, five were males and 32 were females ranging in age from 20 to 80 years with an average age of 48.4+/-15.2 years. All 37 patients were examined for clinical features of OFG. Those with such features were analyzed in more detail. Selection of the OFG cases from patient records was based on re- corded clinical symptoms or biopsy reports (1,8,9,22). The diagnostic criteria were lip swelling, erythema in the gingiva and oral mucosa, localized edema, or tissue enlargement. The histologic presence of non-caseating granulomas or multinucleated giant cells in biopsy reports was considered to be characteristic of OFG. Of the 37 patients diagnosed with cinnamon-induced contact stomatitis, 12 (32%) showed characteristics of OFG (Table 1). The 12 patients included two males and ten females aged 20 to 65 years with an average age of 45.1+/- 14.8 years. The cinnamon-containing causative agents were toothpaste and foods. One case was caused by cinnamon- flavored chewing gum. The most common site of clinical signs and symptoms was the gingiva (9 cases, or 75% of the OFG group), followed by the lips (6 cases) and the tongue (6 cases). The clinical symptoms described were erythematous gingiva (8 cases), lip swelling (6 cases), and edematous gingiva (5 cases) (Table 1, Figures 1 and 2). Other characteristic clinical signs described were a granular gingival surface (3 cases, Figure 3), gingival hyperplasia (1 case), and cobblestone enlargement of the buccal mucosa (1 ...
Context 2
... clinical symptoms described were erythematous gingiva (8 cases), lip swelling (6 cases), and edematous gingiva (5 cases) ( Table 1, Figures 1 and 2). Other characteristic clinical signs des- cribed were a granular gingival surface (3 cases, Figure 3), gingival hyperplasia (1 case), and cobblestone enlargement of the buccal mucosa (1 case). ...
Citations
... Te etiology of OFG remains to be elucidated; however, allergy is suspected to be a contributing factor [3,[17][18][19]. Studies reveal that people with a history of allergic diseases such as hay fever, bronchial asthma, and atopic dermatitis are more likely to develop OFG (12-60%) than those without such a history (up to 15%) [10,20,21]. ...
... In our cases, two of the four patients had allergy or allergic diseases; however, both had a favorable prognosis after treatment. Research also suggests that contact sensitivity to food additives, including cinnamon, cacao powder, and benzoate, may be associated with the onset of OFG [17,[21][22][23]. Interestingly, 32% of patients with allergic cheilitis due to cinnamon powder showed clinical features and pathological fndings similar to those of patients with OFG [17]. ...
... Research also suggests that contact sensitivity to food additives, including cinnamon, cacao powder, and benzoate, may be associated with the onset of OFG [17,[21][22][23]. Interestingly, 32% of patients with allergic cheilitis due to cinnamon powder showed clinical features and pathological fndings similar to those of patients with OFG [17]. Moreover, OFG may develop from delayed hypersensitivity to dental materials such as amalgam, which contains inorganic mercury [21,24]. ...
Orofacial granulomatosis (OFG) is a rare disease entity characterized by nonnecrotizing granulomatous inflammation in the oral and maxillofacial regions, typically characterized by recurrent or persistent edema, primarily in the lips and occasionally in the gingiva. OFG is often associated with Crohn’s disease and sarcoidosis, and an accurate diagnosis requires systemic examination of patients. Pediatric patients possess unique oral conditions where dental plaque rapidly forms, especially during tooth replacement due to tooth crowding. Moreover, controlling oral hygiene can be challenging, rendering it difficult to distinguish plaque-induced gingivitis from nonplaque-induced gingivitis. We elucidate the reports of pediatric patients who developed OFG in the lips and/or gingiva alone, which was well controlled through corticosteroid treatment. The patients demonstrated recurrent lips and/or gingival swelling with redness, which failed to improve despite oral health care and treatment with antibiotics and/or corticosteroid ointment. Incision biopsy was performed, which demonstrated granulomatous inflammation. Further systemic examination ruled out Crohn’s disease and sarcoidosis and confirmed OFG diagnosis. Corticosteroid treatment orally or through gargling was administered to the patients, which provided improvement of symptoms after 1 month. As OFG may be associated with intractable diseases, monitoring the patient regularly is crucial. Pediatric patients with OFG require a collaborative approach with pediatricians and pediatric dentists to manage their oral and overall health.
... After this fulltext review, 26 studies did not meet the criteria and were excluded (eTable 2, available online at the end of this article); hence, we included 13 studies for data analysis. 1,[13][14][15][16][17][18][19][20][21][22][23][24] The flow diagram of this search is depicted in Figure 3. ...
... In fact, this agent has been shown to be an irritant and sensitizer in high concentrations. 4,7,8,[18][19][20]22 Considering these facts, we would recommend that toothpastes containing cinnamon as a flavoring should be labeled properly to warn people who are highly predisposed to hypersensitivity reactions. Hypersensitivity responses to R-carvone and Scarvone also were identified in the scoping review. ...
... To rule them out, laboratory tests or a chest radiograph in the case of sarcoidosis should be requested. 22 Lupus and HIV also should be considered in the differential diagnosis. Erythematous gingival lesions such as gingivitis, red macules, and telangiectasias have been observed in patients with lupus. ...
... Regarding the toxicity data, some clinical studies reported that the most common adverse events after cinnamon consumption were gastrointestinal problems in patients with diabetes (Altschuler et al., 2007;Crawford, 2009), Helicobacter infection (Nir et al., 2000), polycystic ovarian syndrome (Kort and Lobo, 2014b) and seasonal allergies (Walanj et al., 2014). Dermatitis (Calnan, 1976;Ackermann et al., 2009;Isaac-Renton et al., 2015) and steatites (Miller et al., 1992;Endo and Rees, 2007) were also reported in some case reports. A systematic review of clinical trials and case reports/series on side effects associated with the use of cinnamon in humans indicated that no important difference obtained between cinnamon treated and control group in most cases (Food and Administration, 2005;Hajimonfarednejad et al., 2018b). ...
The genus Cinnamomum includes a number of plant species largely used as food, food additives and spices for a long time. Different traditional healing systems have used these plants as herbal remedies to cure diverse ailments. The aim of this comprehensive and updated review is to summarize the biodiversity of the genus Cinnamomum, its bioactive compounds, the mechanisms that underlie the pharmacological activities and molecular targets and toxicological safety. All the data in this review have been collected from databases and recent scientific literature including Web of Science, PubMed, ScienceDirect etc. The results showed that the bioactive compounds of Cinnamomum species possess antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer and neuroprotective effects. The preclinical (in vitro/in vivo) studies provided the possible molecular mechanisms of these action. As a novelty, recent clinical studies and toxicological data described in this paper support and confirm the pharmacological importance of the genus Cinnamomum. In conclusion, the obtained results from preclinical studies and clinical trials, as well as reduced side effects provide insights into future research of new drugs based on extracts and bioactive compounds from Cinnamomum plants.
... First approach is of behavioural strategies, which includes abortion of parafunctional habits (clenching, bruxism, tongue thrusting), replacement of potentially irritating oral healthcare products such as alcohol containing mouthwashes with non-alcohol containing alternatives and the use of oral healthcare products (tooth paste, tooth whitening gels, anticalculus agents) without added flavouring agents (cinnamon) or irritating components (sodium lauryl sulphate) 5 . Patients are advised to discontinue use of breath fresheners 28 . Local irritants such as ill fitting dentures, sharp restoration edges and sharp edges of dentition are corrected. ...
Burning Mouth Syndrome (BMS) is a neurosensory disorder that affects the oral mucosa by causing a burning or stinging pain of varying degrees in different individuals. It is difficult to diagnose the condition as it does appear in conjunction with any clinical or laboratory abnormalities. The psychological and psychiatric issues involved along with the oral symptoms make oral healthcare provision in such individuals a challenging task. This review presents the oral healthcare provider an insight into the peculiar nature of BMS and the oral healthcare management of patients with BMS.
... Eugenol produces a possible irritation effect on the periapical tissues and could lead to necrosis of bone and cementum and to an alteration of the eruption of permanent teeth [52]. Reports of allergic contact dermatitis and stomatitis as a result of cinnamon EOs are rare [53,54], which could lead to orofacial granulomatosis [55]. In vivo studies reported a lack of significant side effects on the liver and kidneys, no hypersensitivity, and a wide therapeutic range of C. zeylanicum [56,57]. ...
Dental medicine is one of the fields of medicine where the most common pathologies are of bacterial and fungal origins. This review is mainly focused on the antimicrobial effects of cinnamon essential oil (EO), cinnamon extracts, and pure compounds against different oral pathogens and the oral biofilm and the possible effects on soft mouth tissue. Basic information is provided about cinnamon, as is a review of its antimicrobial properties against the most common microorganisms causing dental caries, endodontic and periodontal lesions, and candidiasis. Cinnamon EO, cinnamon extracts, and pure compounds show significant antimicrobial activities against oral pathogens and could be beneficial in caries and periodontal disease prevention, endodontics, and candidiasis treatment.
... Even restriction diets were employed in the treatment of OFG with response rates up to 72 % of patients. Cinnamon -, benzoate -free or low phenolic acid diets were administered with good clinical response rates [39][40][41]. Because of the rarity of the disease entity only small case series exist in the published literature. ...
Background and objective:
Melkersson Rosenthal syndrome (MRS) is a rare disorder of unknown etiology and comprises the triad: orofacial edema, recurrent facial paralysis and lingua plicata. In the current literature confusing heterogeneity exists, mixing together the historically grown terms cheilitis granulomatosa or granulomatous cheilitis, Melkersson Rosenthal syndrome and the umbrella term orofacial granulomatosis (OFG).
Methods:
We provide a systematic review comprising all three disease entities of orofacial granulomatosis using the computerized database "Pubmed Medline" entering the key words "orofacial granulomatosis" (141 references), "Melkersson-Rosenthal syndrome" (207 references), "granulomatous cheilitis" or "cheilitis granulomatosa" (102 references) back to 1956. Full text journals and case studies were included, and data synthesis was performed individually.
Results:
Etiology remains unclear for all three disease entities. Etiological relatedness to chronic inflammatory bowel disease is under discussion and effectiveness was found for different treatments, e.g. local triamcinolone injections, antibiotics, surgical interventions, TNF alpha blockers or exclusive enteral nutrition. No randomized controlled trial concerning the therapy of orofacial granulomatosis was found. As a consequence, therapeutic conclusions are drawn mainly from small case series, thus limiting the evidence of therapeutic interventions.
Conclusions:
OFG with the sub-entities MRS and cheilitis granulomatosa is an etiological obscure disease process with various possible therapeutic interventions potentially alleviating the disease course but to broaden treatment knowledge further study in randomized controlled trials are needed.
... All cases were healthy except for one with obesity and fibromyalgia [75]. Dermatitis (3 studies) [75,76,80] and stomatitis (2 studies) [77,81] were the most common reported reactions. Almost all cases were asymptomatic after the elimination of cinnamon. ...
Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored.
... Localized or generalized DG is sometimes elicited by contact hypersensitivity reactions to various foodstuffs, preservatives, oral hygiene products, and dental restorative materials [11,25,[35][36][37][38][39]81]. Toothpaste hypersensitivity reactions may occur in various oral or perioral sites, but the gingiva was the most common site of onset [24,35,36,39,81] (Figure 23). ...
... Localized or generalized DG is sometimes elicited by contact hypersensitivity reactions to various foodstuffs, preservatives, oral hygiene products, and dental restorative materials [11,25,[35][36][37][38][39]81]. Toothpaste hypersensitivity reactions may occur in various oral or perioral sites, but the gingiva was the most common site of onset [24,35,36,39,81] (Figure 23). Erythema has been expressed as a "velvet-like appearance of the gingiva" or "fiery red gingiva" [35]. ...
... However, if a biopsy is performed, these lesions present with non-specific histopathologic findings with submucosal perivascular inflammatory cell infiltration [11,35,36]. The existence of focal granulomatous inflammation and/or multinucleated giant cells in the deep layer of the lamina propria was also described in some cases studying contact hypersensitivity stomatitis [25,81]. DIF is not indicated because it is routinely negative [11]. ...
... However, as previous studies have shown, reactions following local dental anesthetics have, in most cases, a psychogenic origin [51]. Montebugnoli et al. [52] reported that psychologic stress contributes to the development of Table 1 Clinical presentation of contact allergy to dental materials and differential diagnosis [1,15,23,29,38,39,[53][54][55][56][57] ...
... chocolate, the investigation of the cause is challenging [55]. In addition, dental products such as toothpaste including mint, eugenol or cinnamaldehyde are potential allergens, leading, as reported, from local reaction up to orofacial granulomatosis [56]. ...
Allergic reactions of the oral mucosa are associated with diverse symptoms and can severely affect patients’ quality of life. Oral mucosa changes such as stomatitis or lichenoid reactions can be the first evidence of a contact allergy, with oral lichenoid reactions after contact with dental restorations, especially amalgam fillings, being among the most common clinical reactions. Additives in foods and oral hygiene products may also cause allergic mucosal reactions. Subjective symptoms, such as pain, burning feeling, or dryness of the oral mucosa, as well as cheilitis or lip and facial swelling, may not only have an allergic component but may also be associated with other diseases that have to be excluded. A complete and thorough clinical examination of the oral mucosa is the first step in the diagnosis of a contact allergy. A detailed history of the patient’s oral care products, drugs, and dental materials is both essential and helpful for the clinician. As a result of the presence of mucosal changes, a patch test can be used for the diagnosis of contact allergy of delayed type. Although the patch test is the standard diagnostic tool for such types of contact allergy, proper interpretation of patch-test results and their clinical relevance can be challenging. As the number of patients with allergies resulting from different materials increases over the years, and a larger number of different dental materials are found to induce an allergy, it is essential for dentists to be aware of the possible allergic reactions to dental materials. Thus, we aimed to develop a systematic approach for contact allergy of the oral cavity, focusing not only on clinical manifestations and diagnosis but also on management and prediction of the risk of oral allergic reactions. A multidisciplinary approach for patients with an oral allergy is essential, with participation of physicians of different specialties, including dentists, allergists and dermatologists.
... The other oral and facial manifestations include oral ulcers, fissured tongue, mucosal tags, gingival enlargement, facial nerve palsy, facial swelling and cervical lymphadenopathy [2,8]. Our case mimicked some of the cases studied by Endo et al. and Gale et al., in that; gingival hyperplasia was the sole manifestation [10]. ...
... There are a number of theories, both genetic and immunological, which attempt to explain the course and clinical outcome of this disease [6]. Current research in OFG supports an immunologic or allergen triggering factor as the chief aetiological basis [10]. ...
... The immunohistochemical evaluation showing a predominance of CD3+ T cells support a diagnosis of OFG without systemic Crohn's disease. It has also been suggested that IgE-expressing B cells (CD20+) in the submucosa of OFG patients play an important role in the pathogenesis and provide a link to type IV hypersensitivity, particularly in cases of OFG without CD in young individuals [10]. This may be reflected by the high expression of CD138+ plasma cells. ...
