Celiac Disease Diagnosed after Uncomplicated Pregnancy in a Patient with History of Bulimia Nervosa

Celijaþna bolest dijagnostikovana posle nekomplikovane trudnoüe kod bolesnice sa anamnezom bulimije nervoze Abstract Introduction. The association between celiac disease and eating disorders has been very rarely reported. This is the first report on celiac disease associated with bulimia in this part of Europe. Case report. An adult female patient with history of bulimia and one uncomplicated pregnancy was admitted to the Gastroenterology Department, due to long lasting dyspeptic symptoms, constipation, major weight loss and fatigue. After positive serological screening, the diagnosis of celiac disease was confirmed with histopathology examination of duodenal biopsy specimen. Conclusion. Complicated interactions between celiac disease and bulimia can make them difficult to diagnose and treat. It is important to consider the presence of celiac disease in patients with bulimia and gastrointestinal symptoms.


Introduction
Celiac disease is an inflammatory condition of the small intestinal mucosa induced by gluten consumption in genetically susceptible individuals, leading to the spectrum of gastrointestinal manifestation.Previously, celiac disease was thought to be a disease of infancy, manifesting during the first years of life as the malabsorption syndrome with chronic diarrhea, abdominal distension, and failure to thrive.In the recent years it became increasingly evident that celiac disease can affect individuals of any age.Because of the variety of ways celiac disease can manifest itself in adults, it is often not still diagnosed.Psychiatric symptoms and disorders are commonly found in association with celiac disease 1,2 .Most reports concern the association between celiac disease and anxiety, irrita-bility and depression 3 .The association between celiac disease and eating disorders has been rarely reported in the literature 4 .Most of the case reports describe onset of anorexia nervosa in patients with already diagnosed celiac disease after the introduction of gluten free diet 5 .
We presented an adult patient with celiac disease and history of bulimia nervosa, in who celiac disease had been diagnosed after pregnancy.

Case report
A 27-year-old woman with a history of bulimia and one uncomplicated pregnancy was admitted to the Gastroenterology Department in 2010 due to long lasting dyspeptic symptoms, constipation, weight loss and fatigue.During childhood the patient suffered from mild underweight, nocturnal enuresis, and occult spina bifida.The patient had a late onset of menarche at the age of 15, followed by irregular, painful periods.Also, the patient had never been treated for infertility.Family history was negative for celiac disease or eating disorders.The patient's eating difficulties started in 2002, when she started binge eating and gained 10 kg in body weight (Figure 1 a).Then the patient started to use diet products, trained excessively for a few months and vomited and binge eating 3 to 4 times a week for the next 7 years in order to lose weight (Figure 1 a), fulfilling all the criteria of the Diagnostic and Statistical Manual (DSM-IV) for bulimia.Also, in 2002 the patient complained on dyspeptic symptoms and received Helicobacter pylori eradication therapy.As her dyspeptic symptoms had persisted she underwent upper gastrointestinal endoscopy which was normal findings.Celiac disease was not suspected as her duodenal mucosa had normal macroscopic appearance.Because of a long-lasting constipation in 2006 underwent colonoscopy and small bowel barium follow through test, which were both normal.In 2009, the patient got pregnant for the first time in her life and in the first trimester of pregnancy stopped her bulimic behavior.Routine pregnancy laboratory tests were within normal range.Pregnancy and childbirth were uncomplicated.During the next 12 months, prior to admission to hospital, the patient lost nearly 21 kg in weight (Figure 1 b) and experienced severe dyspeptic symptoms.Both weight loss and dyspeptic symptoms had begun soon after childbirth.The patient had not bulimic symptoms after pregnancy.Both psychiatrist and psychologist suspected a hidden bulimia relapse.Family history was negative for celiac disease or eating disorder.
Physical examination at admission revealed cachexia.Routine laboratory tests were within normal range.According to the standardized rating scale for eating disordersthe Bulimic Investigatory Test Edinburgh (BITE) 6 , the patient was in remission from bulimia.Bioimpedance analysis revealed a low level of body mass index (BMI) (15.1 kg/m 2 ) and total body fat (TBF) (8.6%).The screening serology test for celiac disease -IgA anti-transglutaminase antibodies was performed which were highly elevated -425.61RU/mL (< 20 RU/mL).Upper gastrointestinal endoscopy revealed atrophic macroscopic appearance in duodenum (Figure 2).Histopathology examination of duodenal biopsy specimen revealed type IIIb lesions according to the Marsh-Oberhuber classification.Osteodensitometry displayed a normal bone mineral density.

Fig. 2 -Endoscopic appearance of atrophic duodenal mucosa (with and without i-scan surface enhancement)
After diagnosing celiac disease, the patient was recommended to undergo strict life-long gluten free diet, and underwent cognitive behavioural psychotherapy performed by the psychologist for 20 weeks in order to prevent possible bulimia relapse.She was recommended to use paroxetine in combination with psychotherapy.
During 6-month follow-up the BMI of the patient improved (Figure 1 b) and IgA anti-transglutaminase antibodies were only slightly elevated (32.4 RU/mL).According to BITE, the patient had not relapsed into bulimia during the follow-up period.

Discussion
This paper presented an adult patient with celiac disease and previous history of bulimia nervosa and one uncomplicated pregnancy.To the best of our knowledge, this is the first case of celiac disease associated with an eating disorder in this part of Europe.According to the available sources, only 2 similar case reports, 1, 2 and one case series 4 have been reported so far.There is a strong clinical evidence for suspecting celiac disease early in our patient.
Celiac disease is an inflammatory condition of the small intestinal mucosa that is induced by ingestion of gluten in genetically susceptible individuals, leading to spectrum of gastrointestinal manifestations.It is one of the most common genetically conferred disorders reaching the prevalence of 1% in overall population.Many patients remained undiagnosed, either because of misdiagnosed, asymptomatic, latent, silent or potential celiac disease.It is known that a high proportion of adults with celiac disease has a prior history of psychiatric disorder even for years 3,7 .Also, it is known that undiagnosed celiac disease can lead to infertility in women.Bulimia nervosa is characterized by episodes of binge eating (uncontrolled consumption of a large amount of food in a relatively short period of time) followed by an inappropriate "compensation" such as forced vomiting, laxative or diuretic abuse, a subsequent fast or period of food restriction, or excessive exercising 8 .
The mechanisms involved in the pathogenesis of psychiatric disorders related to celiac disease are not well understood.Malabsorption of tryptophan, folic acid, and vitamin B6, known to occur in celiac disease, may lead to disturbances in brain serotonin function 9 .Decreased serotonin activity in the brain is associated with enhanced appetite, and thus may be related to bulimia 10 .Adult celiac patients taking a gluten-free diet showed an increase in the concentrations of serotonin metabolites in cerebrospinal fluid 11 .On the other hand, treatment-induced weight gain can act as a risk factor for altered eating behavior 12 .Studies evaluating the course of bulimia during pregnancy have reported an improvement in bulimic symptoms and a return to prepregnancy symptom levels or even a worsening of symptoms in the postpartum period 13,14 .A reason for improvement of bulimic symptoms during pregnancy may be found in the significant increase of serotonin concentration in the brain through pregnancy 15 .Pregnancy and delivery can trigger celiac disease in susceptible people for reasons that are not well-understood.
A long history of nonspecific gastrointestinal symptoms and low body weight, described in our patient, were neglected by physicians in the presence of bulimia and uncomplicated pregnancy.Furthermore, worsening of symptoms after pregnancy was mistakenly attributed to a hidden bulimia relapse.

Conclusion
Complicated interaction between celiac disease and bulimia can make the patient difficult both to diagnose and treat.It is important to consider the presence of celiac disease in patients with bulimia and gastrointestinal symptoms.Serological testing for celiac disease in patients with eating disorders may be useful.Further studies are needed to determine the true nature of the relationship between celiac disease and eating disorders, particularly bulimia.

Fig. 1 -
Fig. 1 -Body mass index (BMI) variations: a) before onset of bulimia , during binge phase , during purge phase^; b) at the beginning † and at the end of pregnancy ‡, at hospital admission*, and six months after introduction of gluten free diet ///