Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS

Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS

Accepted Manuscript Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS Rene Panico, Eduardo Piemonte, Jerónimo Lazos, Gerardo Gilliga...

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Accepted Manuscript Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS Rene Panico, Eduardo Piemonte, Jerónimo Lazos, Gerardo Gilligan, Anibal Zampini, Héctor Lanfranchi PII:

S0022-3956(17)30663-5

DOI:

10.1016/j.jpsychires.2017.09.022

Reference:

PIAT 3219

To appear in:

Journal of Psychiatric Research

Received Date: 12 June 2017 Revised Date:

17 September 2017

Accepted Date: 21 September 2017

Please cite this article as: Panico R, Piemonte E, Lazos Jeró., Gilligan G, Zampini A, Lanfranchi Hé., Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS, Journal of Psychiatric Research (2017), doi: 10.1016/j.jpsychires.2017.09.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS

Rene Panico, DDS, PhD1; Eduardo Piemonte, DDS, PhD1; Jerónimo Lazos, DDS, Cert.Perio1; Gerardo Gilligan, DDS1, Anibal Zampini, MD2; Héctor Lanfranchi, DDS,

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PhD3.

Oral Medicine Department, Dentistry College, Universidad Nacional de Córdoba,

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Av. Haya de la Torre s/n, Ciudad Universitaria, Córdoba, Argentina.

Medical Director and Head, Anorexia and Bulimia Fight Association Institute,

Córdoba, Argentine.

Oral Medicine Department, Dentistry College, Universidad de Buenos Aires,

Buenos Aires, Argentina

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Corresponding author: Rene Panico, Figueroa Alcorta 46, 1st A, Tel: +54 351

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4226475, E-mail: [email protected]

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Abstract Word Count: 187

Main Text Word Count: 2487

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Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS

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Running title: Oral mucosal lesions in eating disorders

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Keywords: eating disorders; anorexia nervosa; bulimia nervosa; eating

4

disorders not otherwise specified; oral manifestations.

5 Abstract

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Objectives: The aim of this study is to describe oral lesions in patients with

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eating disorders (ED), including Anorexia Nervosa (AN), Bulimia Nervosa (BN)

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and eating disorders not otherwise specified (EDNOS).

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Material and methods: A prospective case-control study was carried out from

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April 2003 to May 2004. Inclusion criteria for the study group were individuals

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with a diagnosis of ED; age and sex-matched individuals without ED were

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included as controls. Clinical data regarding ED, medical complications and oral

14

examination were performed by previously calibrated professionals.

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Results: Study group (n=65) presented 46 cases of BN (71%), 13 of EDNOS

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(20%) and 6 of AN (9%); also, 94% (n=61) showed oral lesions. The most

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common were: labial erythema, exfoliative cheilitis, orange-yellow palate,

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hemorrhagic lesions, lip-cheek biting and non-specific oral atrophies. Only two

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patients of the study group had dental erosions, and no case of major salivary

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gland swelling was found.

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Conclusions: ED display a wide array of oral mucosal lesions that can be

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regarded as their early manifestations. The dentist could be the first

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professional to detect symptoms of eating disorders, potentially improving early

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detection and treatment of ED.

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ACCEPTED MANUSCRIPT Introduction

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Eating disorders (ED) are characterized by a morbid concern about weight and

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shape that triggers various distorted behaviors: food restriction, fear of weight

4

gain, distorted body image perception and endocrinal disorders (El Ghoch et al,

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2013). According to the Diagnostic and Statistical Manual of mental disorders

6

(DSM IV) ED are classified in eating disorders not otherwise specified (EDNOS)

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and specific ED (American Psychiatric Association, 1994). In the last group,

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Anorexia nervosa (AN) and Bulimia nervosa (BN) are common, affecting

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adolescents and young adults regardless of ethnic groups, and most of the

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cases are females (Nicholls and Viner, 2005). AN typically has malnourishment

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and severe food restriction, while BN displays a vicious cycle of binge eating

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plus

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laxatives/diuretic and exercise). On the other hand, EDNOS is referred as

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eating behaviors that do not fulfill the criteria for a specific disorder (Brady,

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1980; Winkler et al, 2014). Overall, ED patients display a profound impairment

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of functional limitations (Reas et al, 2016)

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ED could include a wide array of symptoms, having a deep impact on everyday

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life, and are associated with high morbidity and mortality, arising mainly from

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undereating and purging (Winkler et al, 2014). Some of the main clinical

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manifestations include malnutrition, endocrine alterations (hypothalamic-

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pituitary-gonadal), amenorrhea, dehydration, electrolytic imbalance. More

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advanced cases could also show depressive symptoms, low basal metabolic

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rate, hypothermia, decreased blood pressure, muscle weakness and a higher

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risk of circulatory collapse (Reyes-Rodríguez et al, 2010).

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A limited number of studies have investigated the impact of ED on oral health,

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and a wide array of symptoms is mentioned (Romanos et al, 2012). Enamel

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erosion is extensively described in patients with ED with self-induced vomiting,

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(Forney et al, 2016). Dental lesions in BN have been shown to be associated

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with vomiting behavior, and with the severity of the disorder. It appears to be a

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consequence of chronic and repeated regurgitation of gastric contents, which

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produces a critical decrease in oral pH, thus facilitating tooth demineralization

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(Brown and Bonifazi, 1993). Although it has been described mild gingivitis

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associated with ED, these patients usually maintain good oral hygiene, with low

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caries and plaque index (Frydrych et al, 2005). It has been noted that ED

behaviors

(induced

vomiting,

excessive

use

of

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ACCEPTED MANUSCRIPT patients could develop a higher auditory or contact sensitivity during common

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dental treatments, and this might also play a role in their oral status (Romanos

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et al, 2012). Some of the oral manifestations of ED may include salivary gland

4

swelling, cheilitis and/or dry cracked lips, burning tongue, tongue thrusting and

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overall oral mucosa irritation have been reported as common in patients with

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ED (Abrams and Ruff, 1986; Johansson et al, 2012). Nonetheless, none of

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these lesions are pathognomonic or specific of ED.

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The salivary glands enlargement affects mainly the Parotid gland, and

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occasionally the submaxillary glands, and could be recurrent and asymptomatic.

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The pathogenesis of this alteration is not clear, but it may include higher

11

carbohydrate intake, gastric content irritation, and malnutrition. Salivary biopsies

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showed a fairly normal tissue with minor inflammation (Spigset, 1991).

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Oral mucosa in ED patients has shown erythema/atrophic lesions as a result of

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chronic irritation by gastric fluids. Usually, throat, palatal and even gingival pain

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could be found in cases of self-inducing vomiting. Stimulation of gag reflex often

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produces erosions in oral mucosa through mechanical irritation of fingers or

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objects used to that end (Forney et al, 2016). Exfoliative and angular cheilitis

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are associated with vitamin deficiencies, dehydration, loss of electrolytes and

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overall metabolic alterations (Grinspan, 1976; Abrams and Ruff, 1986; Brown

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and Bonifazi, 1993).

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However, oral lesions of ED have not been properly systematized, and most of

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the references dealing with this are reviews(Lo Russo et al, 2008; Romanos et

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al, 2012). Indeed, there is relatively scarce and contradictory information

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regarding oral complications(Johansson et al, 2012). Therefore, the aim of this

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study was to depict oral lesions in patients with eating disorders and to analyze

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the association between those lesions and ED.

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Material and Methods

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A prospective case-control study was carried out from April 2003 to May 2004;

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all patients gave their informed consent previously. This study was approved by

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the Research and Ethics Committee of the Cordoba Health Ministry, in

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accordance with the Declarations of Nüremberg, Helsinki, and Tokyo of the

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World Medical Association.

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ACCEPTED MANUSCRIPT Inclusion criteria for the study group were individuals with a diagnosis of eating

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disorder (both specific and/or not specified), according to the Diagnostic and

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Statistical Manual of mental disorders (American Psychiatric Association, 1994).

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The sample was derived from patients of the Anorexia and Bulimia Fight

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Association Institute (Córdoba, Argentine). In order to minimize the effect of ED

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therapy, cases of more than a month of treatment were excluded. Age and sex-

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matched individuals without ED were used as a control, excluding those who

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had restrictive dietary or purgative behaviors (laxative or diuretic abuse, induced

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vomiting) and/or physical exercise more than three times in a week.

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Oral examination was performed by two previously calibrated odontologists (RP

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and EP) through visual inspection and palpation of the oral mucosa. The

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professionals involved in the clinical exam belong to the Oral Medicine

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Department, with training in identification and treatment of oral mucosal

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diseases. The final diagnosis oral mucosal lesions were reached through

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consensus of the two examiners; in cases of disagreement, the diagnosis was

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defined by a third party (JL).

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form (sociocultural, genetic, environmental, anthropometric, medical and

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dental), that included detailed information regarding the type of ED and

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purgative/restrictive behaviors. Oral lesions and potentially irritating mechanical

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factors -dental, prosthetic and/or functional-(Piemonte et al, 2010) and dental

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erosion were also registered.

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Statistical Analysis

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Chi-square and Fisher’s exact test were used to evaluate categorical variables

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in control and ED groups, while T-Test was used for quantitative variables,

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setting a p-value ≤0.5 for statistical significance.

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Results

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Initially, 81 female patients with ED were enrolled, but 16 were screened out

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because they refused oral inspection. Thus, study group were 65 ED

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individuals: 46 had BN (71%), 13 of EDNOS (20%) and 6 of AN (9%, 3

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restrictive and 3 purgatives), with a mean age of 21.6 years (12-32); whereas

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control group (n=65) had a mean age of 23.21 years (14-31). Amenorrhea was

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found more in the study group (OR 14.9, CI 95% 6-37, p<0.0001). Although

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amenorrhoea is a criterion defined by DSM IV for anorexia nervosa, it had no

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Clinical data were registered in a specific clinical

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ACCEPTED MANUSCRIPT statistically significant differences on BN, AN and EDNOS. Self-induced

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vomiting, diuretic/laxative use, and binge eating were higher in BN (Table 1).

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The mean vomiting per day was 2.4 for patients with ED, and 3.11, 0.38 y 1, for

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bulimia nervosa, EDNOS and anorexia nervosa, respectively. According to T-

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Test, these results were statistically significant between bulimia nervosa and

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EDNOS (p<0,0001), bulimia nervosa and anorexia nervosa (p=0.012); but not

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significant between EDNOS and anorexia nervosa (p=0.2).

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In the study group 94% (n=61) showed oral lesions (a total of 112 lesions),

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while in control group had 18.5% (n=12, 15 lesions). Considering the most

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common oral lesions in the study group, there was a statistically significant

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difference with control (OR 50.8 CI 95% 15.8-162.9, p<0.0001). The most

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common oral lesions were labial erythema, exfoliative cheilitis, orange-yellow

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palate, hemorrhagic lesions, lip-cheek biting and non-specific oral atrophies

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(Figs 1-2). All these lesions presented statistically significant differences

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between the study group and the control group (Table 2). No case of major

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salivary gland swelling was found.

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Analysis of the type of ED presented no significant differences among the oral

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lesions, the exception being made for labial erythema, which was more

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common in BN than AN or EDNOS (p=0.0098). Moreover, considering all the

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oral lesions together, they were related only to purging habits (OR 6, CI 95%,

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1.06-34.12, p=0.0414). However, considering the oral lesions independently,

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only labial erythema displayed a statistically significant association with self-

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induced vomiting (OR 4, CI 95%, 1.08-14.77, p=0.0396) and diuretic/laxative

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use (OR 7.89, CI 95%, 2.18-28.56, p=0.0012). The relationship between

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vomiting per day and the presence of specific lesions on the buccal mucosa

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was analyzed by quantitative (Table 3) and qualitative (Table 4) tests. In both

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cases, only labial erythema was associated with a higher frequency of vomiting

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per day. Only two patients of the study group had dental erosions, whereas the

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control group had none.

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In 22 individuals (34%) an orange-yellow palate (hard and soft) was found,

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where the individuals acknowledged intake of high-carotene supplements.

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Discussion

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ACCEPTED MANUSCRIPT There is scarce information about oral mucosal changes in patients with ED,

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and our work shows interesting results, particularly in relation to the different

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lesions found. This suggests that oral lesions in ED could be related both to

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local –mainly irritative- and systemic factors.

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Given the marked difference in oral mucosal lesions occurrence comparing

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control to study groups, it is apparent that those could be regarded as very

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common findings in ED. Remarkably, there has been a dearth of papers

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regarding oral lesions in ED, and the existing studies focus mainly on dental

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tissue alterations (Ximenes et al, 2010).

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Since in our study BN was more common (71%), it would be logical finding

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more oral lesions, because of potentially harmful habits, e.g. self-induction of

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vomiting could injure hard and soft palate, tongue dorsum, and lips, through

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mechanical and also chemical irritation. Indeed, labial erythema was found

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more on BN than other ED (p=0.0013), and the rest of oral lesions showed no

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significant difference in AN, BN or EDNOS. Also, given that we used DSM IV

16

diagnostic criteria, all AN patients would be expected to have experienced

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amenorrhea.

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Labial erythema is an oral symptom that has not been previously described in

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ED patients and its clinical significance is unknown. It is seen primarily in the

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vermillion border of the lips, where it converges with lip mucosa, on both upper

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and lower parts, being slightly more common on the lower lip. The magnitude of

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the affected area and redness are variable, ordinarily in association with

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exfoliative cheilitis in severe cases. Observing at higher magnification, this

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erythema describes a red linear pattern, parallel between them and

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perpendicular to the major axis of the lip, which offers a fence or palisading

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aspect. For ethical reasons, a biopsy of those lesions could not be carried out,

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and consequently, its histological features are unknown. However, given that

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labial erythema was in relation with self-induced vomiting, irritative causes could

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explain this particular oral lesion, both mechanical (biting) and chemical (gastric

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regurgitation).

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The higher occurrence of exfoliative cheilitis in ED patients could be in relation

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to systemic factors. Among them, dehydration and undernourishment should be

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emphasized. Besides, individuals with ED usually have emotional discharge

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ACCEPTED MANUSCRIPT behaviors, like lip biting, which has been shown in association to exfoliative

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cheilitis (Almazrooa et al, 2013). Hence, this lesion could be regarded as a

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clinical indicator of psychological disorders such as ED.

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Oral areas with thinner mucosa, such as soft palate, allow a better visualization

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of the connective tissue color. Therefore, a higher orange-yellow coloration is

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easily identifiable in those parts. This situation is due to carotenemia, an

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increased level of serum carotene, which is known to cause discoloration of the

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skin and has been described in relation with ED (Takita et al, 2006). Also,

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carotenoids are fat-soluble, and probably the soft palate is an anatomical

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location with higher affinity for lipid-based substances (Harden et al, 2012). It is

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of interest pointing out that all cases of orange-yellow palate in this study were

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associated with a diet rich in carotenoids (such as carrots) or consumption of

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supplements of vitamin-A analogs.

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Oral hemorrhagic lesions (petechiae, ecchymosis, and hematoma) are

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produced by a coagulopathy disorder or, more ordinarily, by soft tissue injury,

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leading to vessel damage with extravasation of erythrocytes (Silverman et al,

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2002). ED patients often use hard elements to induce gag reflex, in addition to

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duration, strength, and frequency of purging incidents, all which could explain

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the onset of this hemorrhagic lesions on the palate. Similar but smaller lesions

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were also found in buccal mucosa, possibly to mechanical irritation due to a

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functional factor, like cheek biting.

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AN and BN are typically associated with psychological disorders including self-

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harm behaviors, such as skin cutting or burning, reopening wounds and much

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more self-injuries (Olatunji et al, 2015). Chronic rubbing or friction against an

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oral mucosal surface, also known as Morsicatio buccarum, is within those

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lesions (Regezi et al, 2012). Repetitive cheek/lip biting, along with hemorrhagic

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lesions could be seen as objective signs of emotional disturbances distinctive of

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ED.

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The non-specific oral atrophies that were seen on palate probably have a

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traumatic cause during vomit induction, although the effect of acidity and

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malnutrition could alter epithelial turnover, enabling mucosal damage (Robb et

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al, 1995).

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ACCEPTED MANUSCRIPT It is noteworthy that salivary gland swelling was not found in our study, which is

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in dissonance with current literature of oral manifestations of ED. This could be

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because this specific sign occurs on late stages of ED, and therefore the

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aforementioned lesions (labial erythema, exfoliative cheilitis, orange-yellow

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palate) may take less time to develop, and could be regarded as early

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symptoms.

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Most of the papers dealing with ED emphasize dental erosions as one of the

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most outstanding oral symptoms. However, in our study, only two patients of

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study group presented such lesions. It may be that patients with ED of our study

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were stricter towards oral hygiene maintenance as compared to healthy

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controls. Thus, dental decalcifying possibly is not an early symptom of ED.

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As we could not record the ED evolution time in all cases, it is not possible to

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determine with certainty if the oral lesions that we found are actually associated

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with early developed ED. However, the oral mucosal lesions described in our

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study need less time to become clinically noticeable and may be discovered

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even in early cases. This stresses the relevance of the oral mucosal lesions as

17

early signs of ED, since early detection and management may contribute to

18

better outcomes (Yeo and Hughes, 2011).

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Finally, the inability to perform a biopsy on some lesions (e.g. labial erythema)

20

hindered the understanding of the underlying pathological pathways. Moreover,

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the rejection of some patients to undergo oral inspection reduced our study

22

group, and we could not measure its impact on the outcome. Also, control group

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sample could have been larger, even though the differences in oral lesions were

24

so prominent that this might not affect results.

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Conclusions

26

ED display a wide array of alterations on the patient, which usually includes

27

several oral mucosal lesions, prompted by both local and systemic factors. In

28

our study, some mucosal lesions, such as labial erythema, orange-yellow

29

palate, and exfoliative cheilitis were even more common than dental erosion

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and can be regarded as common manifestations of ED.

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Health professionals could detect oral symptoms of eating disorders, so a

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thorough oral-dental examination may offer valuable information in a routine

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ACCEPTED MANUSCRIPT check-up. The presence of lesions on the oral mucosa, particularly labial

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erythema, exfoliative cheilitis and orange-yellow palate in young individuals,

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could indicate an ED. Furthermore, the identification of labial erythema could be

4

a sign of vomiting, being valuable not only to identify an ED but also a vomiting

5

behavior.

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Early detection of ED is important to prevent its somatic and psychological

7

complications, hence the important role of health professionals, -particularly the

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dentist- in the identification of oral lesions in relation to ED.

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9 References

11 12

Abrams RA, Ruff JC (1986). Oral signs and symptoms in the diagnosis of bulimia. J Am Dent Assoc 113: 761–764.

13 14 15

Almazrooa SA, Woo S-B, Mawardi H, Treister N (2013). Characterization and management of exfoliative cheilitis: a single-center experience. Oral Surg Oral Med Oral Pathol Oral Radiol 116: e485-489.

16 17

American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders. 4th ed.

18 19

Brady WF (1980). The anorexia nervosa syndrome. Oral Surg Oral Med Oral Pathol 50: 509–516.

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Brown S, Bonifazi DZ (1993). An overview of anorexia and bulimia nervosa, and

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the impact of eating disorders on the oral cavity. Compendium 14: 1594,

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1596–1602, 1604–1608; quiz 1608.

EP

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El Ghoch M, Soave F, Calugi S, Dalle Grave R (2013). Eating Disorders, Physical Fitness and Sport Performance: A Systematic Review. Nutrients 5: 5140–5160.

26 27

Forney KJ, Buchman-Schmitt JM, Keel PK, Frank GKW (2016). The medical complications associated with purging. Int J Eat Disord 49: 249–259.

28 29

Frydrych AM, Davies GR, McDermott BM (2005). Eating disorders and oral health: a review of the literature. Aust Dent J 50: 6–15; quiz 56.

30 31

Grinspan D (1976). Enfermedades de la boca: Semiología, patología, clínica y terapéutica de la Mucosa bucal. Volume III. Mundi: Buenos Aires.

32 33

Harden SA, Sheikh A, Brown RS (2012). Orange-yellow tongue and palate: case report. Dent Today 31: 78, 80-81.

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ACCEPTED MANUSCRIPT Johansson A-K, Norring C, Unell L, Johansson A (2012). Eating disorders and oral health: a matched case-control study. Eur J Oral Sci 120: 61–68.

3 4 5

Lo Russo L, Campisi G, Di Fede O, Di Liberto C, Panzarella V, Lo Muzio L (2008). Oral manifestations of eating disorders: a critical review. Oral Dis 14: 479–484.

6 7

Nicholls D, Viner R (2005). Eating disorders and weight problems. BMJ 330: 950–953.

8 9 10

Olatunji BO, Cox R, Ebesutani C, Wall D (2015). Self-harm history predicts resistance to inpatient treatment of body shape aversion in women with eating disorders: The role of negative affect. J Psychiatr Res 65: 37–46.

11 12 13 14

Piemonte ED, Lazos JP, Brunotto M (2010). Relationship between chronic trauma of the oral mucosa, oral potentially malignant disorders and oral cancer: Chronic trauma of the oral mucosa. Journal of Oral Pathology & Medicine 39: 513-517.

15 16 17 18

Reas DL, Stedal K, Lindvall Dahlgren C, Rø Ø (2016). Impairment due to eating disorder pathology: Identifying the cut-off score on the Clinical Impairment Assessment in a clinical and community sample. Int J Eat Disord 49: 635–638.

19 20

Regezi JA, Sciubba JJ, Jordan RCK (2012). Oral pathology clinical pathologic correlations. Elsevier/Saunders: St. Louis, Mo.

21 22 23

Reyes-Rodríguez ML, Franko DL, Matos-Lamourt A, et al (2010). Eating Disorder Symptomatology: Prevalence among Latino College Freshmen Students. J Clin Psychol 66: 666–679.

24 25

Robb ND, Smith BG, Geidrys-Leeper E (1995). The distribution of erosion in the dentitions of patients with eating disorders. Br Dent J 178: 171–175.

26 27

Romanos GE, Javed F, Romanos EB, Williams RC (2012). Oro-facial manifestations in patients with eating disorders. Appetite 59: 499–504.

28 29

Silverman S, Eversole LR, Truelove EL (2002). Essentials of oral medicine. Bc Decker: Hamilton.

30 31

Spigset O (1991). Oral symptoms in bulimia nervosa. A survey of 34 cases. Acta Odontol Scand 49: 335–339.

32 33 34

Takita Y, Ichimiya M, Hamamoto Y, Muto M (2006). A case of carotenemia associated with ingestion of nutrient supplements. J Dermatol 33: 132– 134.

35 36 37

Winkler LA-D, Christiansen E, Lichtenstein MB, Hansen NB, Bilenberg N, Støving RK (2014). Quality of life in eating disorders: a meta-analysis. Psychiatry Res 219: 1–9.

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ACCEPTED MANUSCRIPT 1 2

Ximenes R, Couto G, Sougey E (2010). Eating disorders in adolescents and their repercussions in oral health. Int J Eat Disord 43: 59–64.

3 4

Yeo M, Hughes E (2011). Eating disorders - early identification in general practice. Aust Fam Physician 40: 108–111.

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6 7 Figure legends

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Figure 1. a) Hemorrhagic lesions on the hard palate; b) Labial erythema

10

associated with Exfoliative cheilitis; c) Orange-yellow pigmentation on the soft

11

palate.

12

Figure 2. a) Non-specific atrophies and desquamation on the palate (soft and

13

hard); b) Cheek biting (Morsicatio Buccarum); c) Chronic exfoliative cheilitis.

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Tables

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Table 1: Distribution of medical complications.

p-value

Amenorrhea

6 (100%)

7 (54%)

31 (67%)

4.01

0.13

Laxative and diuretic use

4 (66%)

4 (31%)

36 (78%)

10.46

0.0054

3 (50%)

3 (23%)

44 (95%)

32.77

<0.0001

4 (66%)

6 (46%)

42 (91%)

13.65

0.0011

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Self-induced vomiting

Binge eating

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X2

n=13

Bulimia nervosa n=46

EDNOS

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Anorexia nervosa n=6

Table 2: Oral lesions among groups. Lesion Exfoliative cheilitis Labial erythema

Control (n=65)

Eating Disorders (n=65)

p-value*

Bulimia nervosa (n=46)

EDNOS (n=13)

Anorexia nervosa (n=6)

p

7 (10.7%)

28 (43%)

0.000014

18 (39%)

6 (46%)

2 (33%)

0.84

0 (0%)

28 (43%)

<0.00001

25 (54%)

1 (8%)

3 (50%)

0.0098



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ACCEPTED MANUSCRIPT Orange1 (1.5%) 23 (35%) yellow palate Hemorrhagic 3 (4.6%) 17 (26%) lesions Cheek/lip 4 (6.1%) 12 (18%) biting Non-specific 0 (0%) 5 (7.7%) oral atrophies * p-value according to Fisher´s exact test † 2 p-value according to X

<0.00001

13 (28%)

6 (46%)

2 (33%)

0.47

0.00062

11 (24%)

3 (23%)

3 (50%)

0.37

0.036

8 (17%)

3 (23%)

1 (16%)

0.89

0.028

4 (8.7%)

0 (0%)

1 (5%)

0.4

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Table 3: Self-induced vomiting according to oral lesions Without lesion With lesion p-value* n vomits/day n vomits/day 0.03 Labial erythema 37 1.89 28 3.00 Exfoliative cheilitis 39 2.21 26 2.62 0.43 Orange-yellow palate 44 2.34 21 2.43 0.87 Hemorrhagic lesions 48 2.25 17 2.71 0.52 Cheek/lip biting 53 2.17 12 3.25 0.1 Non-specific oral atrophies 60 2.25 5 3.8 0.1 *P-value according to T Test

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0.91 0.29 0.45 0.23 0.42

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Table 4: Relationship between oral lesions and vomits per day Vomits /day* OR CI 95% 1-2 3 or + Labial erythema No 25 12 2.78 1.02-7.54 Yes 12 16 Exfoliative cheilitis No 22 17 0.95 0.35-2.54 Yes 15 11 Orange-yellow palate No 27 17 1.75 0.62-4.89 Yes 10 11 Hemorrhagic lesions No 26 22 0.64 0.21-1.96 Yes 11 6 Cheek/lip biting No 32 21 2.13 0.62-7.28 Yes 5 7 Non-specific oral 0.38No 32 25 2.1 atrophies 11.51 Yes 2 3 *Categorized according to mean value=2.4 vomits/day † According to X2

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ACCEPTED MANUSCRIPT Figures

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Figure 1. a) Hemorrhagic lesions on the hard palate; b) Labial erythema associated

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with Exfoliative cheilitis; c) Orange-yellow pigmentation on the soft palate.

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Figure 2. a) Non-specific atrophies and desquamation on the palate (soft and hard); b)

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Cheek biting (Morsicatio Buccarum); c) Chronic exfoliative cheilitis.

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Conflict of interest: none.

Fundings

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public, commercial, or not-for-profit sectors.

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This research did not receive any specific grant from funding agencies in the