Secondary Logo

Journal Logo

Invited Reviews

Gastrointestinal Manifestations of Eating Disorders

Bern, Elana M.; Woods, Elizabeth R.; Rodriguez, Leonel

Author Information
Journal of Pediatric Gastroenterology and Nutrition: November 2016 - Volume 63 - Issue 5 - p e77-e85
doi: 10.1097/MPG.0000000000001394
  • Free

Abstract

What Is Known

  • Eating disorders are often associated with gastrointestinal symptoms originating from the oral cavity, salivary glands, gastrointestinal tract, pancreas, and liver.

What Is New

  • This is a critical and comprehensive review of the literature on the oral, salivary, and gastrointestinal manifestations of eating disorders.

Eating disorder is a term that includes several psychiatric illnesses affecting an individual's body image and relation to food. The medical complications of eating disorders may involve virtually all body systems and may be of life-threatening severity. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) published in May 2013 revised the diagnostic criteria for eating disorders in an attempt to better characterize individuals having a pathologic relation with food (1). Eating disorders now include not only anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), but also pica, rumination, and avoidant/restrictive food intake disorder (ARFID) (1). Patients with AN typically practice an obsessive restriction of food and sometimes engage in intensive physical activity to achieve weight control. Patients with BN and BED typically engage in episodic binge eating with subsequent purging by self-induced emesis and/or laxative abuse (1). AN and BN/BED are not mutually exclusive diagnoses and many patients have elements of both. The literature suggests that AN and BN/BED are a result of both psychological and environmental factors in an individual with a genetic predisposition (2). The new diagnostic classification of ARFID is distinguished from classically defined AN, BN, and BED as an eating or feeding disturbance occurring in the absence of concerns about weight or body image (1).

The medical complications of eating disorders may involve virtually any body system and may be of life-threatening severity. In this review, we will focus on the gastrointestinal (GI) tract complications of eating disorders including those arising in the oral cavity, salivary glands, GI tract, pancreas, and liver (Table 1). Although most current literature on the GI manifestations of eating disorder are based upon studies of patients with AN, BN, and BED only, it is likely that similar manifestations would occur in patients with pica, rumination, and ARFID if nutritional health is severely impacted.

Table 1
Table 1:
Gastrointestinal manifestations of eating disorders

ORAL AND SALIVARY MANIFESTATIONS

The oral manifestations of eating disorders most commonly arise as a consequence of nutritional deficiencies and chronic self-induced vomiting. The symptoms may be exacerbated by use of certain medications, lack of personal hygiene, and anomalous eating habits. The teeth, oral cavity, perioral tissue, and salivary glands all may be affected. The most common dental complications are erosions, caries, and periodontal disease (3,4).

Dental erosion, or perimylolysis, occurs in BN primarily on the palatal lingual surfaces of the maxillary teeth and results from purging behaviors (5,6). With chronic acid exposure from emesis, the affected teeth display a uniform, polished surface, which is in contrast to the sharply cut angled teeth seen with mechanical wear (5,7). Erosion of the enamel becomes apparent to inspection after approximately 2 years of regular emesis (8). These patients often consume acidic fluids such as sports drinks, caffeinated and carbonated beverages as well as sweetened foods, liquids, and chewing gum in their efforts to support excessive exercise, boost energy levels, and suppress appetite (5,6). The sugar and acid exposure can further promote tooth erosion and decay. The clinician may be able to distinguish between dental erosion associated with BN and that associated with chronic gastroesophageal reflux. Reflux-associated erosion typically involves the lingual and occlusal surfaces of the posterior teeth, whereas purging behaviors more often cause erosion of the lingual surfaces of the anterior teeth (9).

Gingival inflammation and periodontitis, which present with pain and erythema of the gums, are relatively uncommon problems in children. When these symptoms present, therefore, an eating disorder should be considered in the differential diagnosis (5). Palatal erythema and ulcers, especially the soft palate, can arise in individuals with purging behavior as a result of chronic acid exposure and the repeated trauma of digital induction of purging (5,10,11). Cheilosis, a stomatitis characterized by pallor and maceration of the mucosa at the angles of the mouth, can be seen in patients with BN (5).

Nutritional deficiencies resulting from eating disorders may cause perioral and periodontal disease. Vitamin C deficiency can be associated with impaired collagen synthesis and gingival inflammation (5,12). Deficiency of the B vitamins, particularly B1, B6, and B12, important in epithelial cell turnover, can present with mucosal atrophy, atrophic glossitis and glossodynia (burning sensation of the tongue) (5,13). Severe protein calorie malnutrition may cause immune dysfunction and predispose to oral opportunistic infections including oral candidiasis (14,15). The gastroenterologist should be cognizant of the oral pathologies that may occur in patients with eating disorders and early referral to a dentist is often indicated.

Dental injury can be exacerbated in patients with eating disorders by a reduction in salivary flow (5). Bulimic patients may develop sialadenosis, a noninflammatory enlargement of the salivary glands (mainly the parotids) as a result of repetitive vomiting. Despite the covert nature of bulimia, cosmetic concerns over facial swelling from enlarged parotids may encourage some patients with bulimia to seek medical care. Parotid swelling may be symmetric or unilateral. It may initially be intermittent presenting 3 to 6 days after a binge-purge episode, but it may become persistent in long-standing disease (8).

Sialadenosis is thought to result from a peripheral autonomic neuropathy, which causes an increase in salivary acinar protein synthesis and/or a disruption in release of secretory granules. The acinar cells become engorged with zymogen granules, which result in parotid hypertrophy and impairment of salivary secretion (16). Donath and Seifert (17,18) have described degenerative changes in the myoepithelial cells and postganglionic sympathetic neurons, which regulate salivary synthetic and secretory processes and suspect that these changes cause sialadenosis. Sialadenosis is characterized by diminished parotid salivary flow rate. Salivary flow rate may be further reduced by antidepressant medications (5,19). Salivary electrolyte and immunoglobulin levels are usually normal in eating disorder patients (8,20). Serum salivary amylase level is elevated in 10% to 20% of patients with sialadenosis and usually normalizes within weeks if purging behavior ceases (8).

Necrotizing sialometaplasia has been reported in association with bulimia. It is a self-limiting, necrotizing process involving the minor salivary glands, most commonly those of the hard palate (21). This disorder can resemble a malignant palatal tumor visually and on histology is characterized by necrosis and squamous metaplasia of the salivary glands (22,23). The condition is thought to arise as a result of palatal ischemia, possibly from chronic exposure to ice chips or chronic vomiting (23).

GASTROINTESTINAL MANIFESTATIONS

Gastrointestinal symptoms in patients with eating disorders present a difficult clinical problem for the gastroenterologist. The clinician must attempt to distinguish between true organic disease, complications secondary to untreated eating disorder, and pure functional GI disorders. Symptoms may be very suggestive of organic disorders such as achalasia, celiac disease, eosinophilic gastroenteritis, inflammatory bowel disease or peptic ulcer, leading to extensive and confusing investigations to rule out these diagnoses (24–28). On the other hand, the GI symptoms may be complications of the underlying eating disorder arising from the impact of malnutrition and/or chronic emesis or laxative abuse. Patients with functional GI disorders such as irritable bowel syndrome or functional constipation also have many symptoms suggestive of an eating disorder (29). Although the patient with AN is often malnourished to the point that consideration of eating disorder is obvious, the patient with BN or BED may not be so easily recognized because of the secrecy of the symptoms and the absence of severe undernutrition (30). Many bulimic patients eat alone to conceal their binging habits and are unlikely to seek treatment unless encouraged. Some individuals self-identify as so-called pragmatic bulimics, that is, individuals who do not engage in bulimic behaviors frequently enough to consider themselves affected (8,31). GI symptoms can be difficult to treat and may interfere with the rehabilitation of these patients, especially patients with AN, in whom they may serve as a justification for food refusal.

ESOPHAGUS

Dysphagia and heartburn are common complaints in patients with AN and BN. Patients with emesis as a result of achalasia, esophageal inflammation, stricture, motility disorders, and gastroesophageal reflux disease can strongly resemble patients with bulimia and may require specific diagnostic evaluations and therapy (25,32,33).

In patients with repeated self-induced vomiting, frequent contact of the esophageal mucosa with regurgitated acidic gastric contents may cause esophageal inflammation and even dysplasia. Gastroesophageal reflux disease is an organic diagnosis regularly considered in the differential of these patients, however, a link between gastroesophageal reflux and BN remains unclear (33). Mallory-Weiss tears may occur (8,34). Kiss et al (35) performed upper GI endoscopy in 37 long-standing bulimic patients of mean age 24.3 ± 0.8 years and average duration of symptoms 61 ± 7 months. They found normal endoscopic appearance of stomach and esophagus in 23 patients. Eight patients had esophageal erythema, 2 had hiatus hernia, 6 had gastritis, 3 had duodenitis, and 1 had a gastric polyp. There are rare case reports of esophageal cancer, primarily adenocarcinoma, in young adults with bulimia, the youngest being 27 years old at diagnosis (33,36).

In most studies, esophageal motility is reported to be normal in BN and AN (32,37,38). Nickl et al (37) evaluated young adults with stable BN, and Benini et al (38) evaluated inpatients with AN exhibiting both binging/purging and restrictive disease activity. In both studies, esophageal complaints included dysphagia, heartburn, and regurgitation. Nickl's study evaluated esophageal motility in 12 young adults, 8 with BN and 4 with AN with bulimic features with a mean disease duration of 94 months comparing them with sex-matched controls. Esophageal motility was normal in all 24 subjects and controls despite reports of dysphagia and/or odynophagia in 1 control subject and 8 of the eating disorder patients (37). Benini et al also studied a younger group of hospitalized, malnourished inpatients during hospitalization and again after 22 weeks of nutritional rehabilitation, comparing them to age- and sex-matched controls. The inpatients with restrictive behaviors were younger (19.9 ± 0.7 vs 25.4 ± 1.1 years) and more malnourished (body mass index [BMI] 13.2 ± 0.6 vs 15.5 ± 0.7 kg/m2) than those with purging behaviors. Esophageal manometry was within the normal range in all patients except one with nutcracker esophagus. The resting lower esophageal sphincter pressures were higher in restricters than purgers (32.1 ± 4.6 vs 14.9 ± 2.2), but all values were within the normal range. Postdeglutitive peristalsis was normally propagated but was of significantly higher amplitude in the distal esophagus of patients compared with controls. In the majority of patients, both those with restrictive and binge-eating/purging behaviors, the esophageal complaints of dysphagia, heartburn, and/or regurgitation did not improve following nutritional rehabilitation (38).

There is a high prevalence of functional gastrointestinal disorders in patients with eating disorders. In 2015, Wang and colleagues (29) evaluated 100 women admitted for restrictive eating and/or purging behaviors using the Rome III classification of functional gastrointestinal disorders (39). One-third of the patients had functional esophageal complaints of at least 6 months duration, including heartburn in 22%, chest discomfort in 8%, and dysphagia in 6%. There are rare reports of oropharyngeal dysphagia with aspiration in severely malnourished patients with AN, presumably secondary to nutritionally mediated oropharyngeal muscle wasting (40).

A rare but serious esophageal complication of bulimia is esophageal rupture (Boerhaave syndrome). Patients may present with severe chest pain, painful swallowing, tachypnea, tachycardia, and pneumomediastinum. Early diagnosis is crucial. Surgery may be required, and without prompt attention, mortality is significant (41).

The practitioner should consider regular surveillance endoscopy in patients suspected of chronic purging behavior to identify those with persistent esophageal inflammation and (rarely) dysplasia. Routine monitoring of esophageal motility is not recommended in patients with well-documented bulimia. However, if the symptoms of a bulimic patient are atypical, e.g. persistent frequent emesis, nocturnal emesis, persistent cough, or emesis occurring in a public place, then evaluation for underlying organic disease, including esophageal motor disorders, should be considered (25,32). Addressing functional symptoms directly is important, as esophageal complaints often do not improve solely with weight recovery and nutritional rehabilitation (38).

STOMACH

Bloating, nausea, epigastric discomfort, and fullness are common complaints in AN and BN. The complaints may be a result of impaired gastric motility or may be purely functional (42). In Wang's study referenced above (29), functional gastroduodenal complaints included postprandial distress syndrome (45%), cyclic vomiting syndrome (17%), aerophagia/excessive belching (14%), nausea (10%), and rumination syndrome (7%).

Gastric emptying of solids is commonly delayed in patients with eating disorders, primarily in the setting of nutritional compromise (43–45). The literature is replete with evidence for gastroparesis in malnourished adults with AN (45–48). Studies in the pediatric population are limited and the evidence for gastroparesis is not conclusive. Diamanti et al (49) evaluated gastric myoelectrical activity with electrogastrography and gastric emptying with scintigraphy in 28 adolescent patients with eating disorders (18, AN; 10, BN) comparing results to healthy volunteers. They found a significantly higher rate of abnormal myoelectrical activity in patients with BN compared with AN and controls. The delay in gastric emptying was greater in BN than in AN patients. A more recent study by Perez et al (50) evaluated gastric emptying and accommodation using ultrasonography in 16 adolescents with AN compared with 22 controls. They found no differences in gastric emptying between AN and controls while gastric accommodation was significantly impaired in patients with AN. Complaints of upper GI dysfunction are common in patients with BN. The literature includes reports of impaired postprandial cholecystokinin release, altered satiety, increased gastric capacity, and diminished gastric relaxation in adults with BN (42,51,52). Although some studies describe delayed gastric emptying in BN, not all studies agree (32,47,48,53).

The mechanism of gastroparesis in individuals with AN and BN is not well understood and likely multifactorial. Smooth muscle atrophy may result from protein malnutrition. Metabolic and hormonal imbalance can develop as a result of poor nutrition, centrally mediated stress reactions, vomiting, or laxative abuse. Gastric dysrhythmia resulting from impaired autonomic function may produce antral hypomotility with delay in the grinding of solid food before transport into the duodenum (46,47,54).

The relation between nutritional rehabilitation, resolution of bulimic activity, and gastric emptying is variable. In some patients, nutritional rehabilitation and weight gain are associated with improved gastric emptying and stomach functioning (43,46,55). The threshold of nutritional deprivation at which gastroparesis begins and the level of renutrition required to initiate improvement are, however, not clear (56). Mechanisms postulated to improve gastric emptying in eating disorders may include the physical presence of food in the stomach, improved nutritional status, or rebalanced metabolic/hormonal mechanisms associated with nutritional and psychological gains (42,43,47,54). The clinician should consider the pros and cons of evaluating gastric emptying in patients with eating disorders as patient reported complaints have not been found to correlate well with the results of gastric emptying studies (47,54).

Bethanocol chloride, cisapride, domperidone, metoclopromide, and erythromycin all shorten gastric emptying time (55,57–60) and all have been used to treat eating disorder patients with presumed delay in gastric emptying. Adverse reactions, including cardiac arrhythmias and neurologic sequelae should be considered before prescribing these medications, particularly in AN where there is a risk of electrolyte imbalance and cardiac pathology (55,57–61). Nutritional rehabilitation is the safest and most efficacious therapy for gastroparesis in patients with AN. Intolerance of nutritional rehabilitation with dyspeptic symptoms may, however, hinder nutritional therapy. In a retrospective study, Rodriguez et al (62) noted improved symptoms in 55% of children treated with cyproheptadine for refractory upper GI complaints. The authors proposed that cyproheptadine diminished dyspeptic symptoms in part by increasing gastric accommodation. In light of the study by Perez et al (50), which noted impaired gastric accommodation in adolescents with AN, further study of the administration of cyproheptadine simultaneous with nutritional rehabilitation should be considered (62,63). Treating constipation in the eating disorder patient with gastric retention is essential as rectal distention may reflexively inhibit gastric emptying (54,64).

Delayed gastric emptying associated with eating disorders can have severe consequences. Gastric bezoars may accumulate (Fig. 1). Gastric dilation with or without bezoar may be severe enough to produce gastric necrosis and perforation (65). Gastric bezoar has been reported as a result of excessive ingestion of vegetables in a setting of delayed gastric emptying (65). Acute gastric outlet obstruction may be caused by gastric bezoar, superior mesenteric artery (SMA) syndrome, or duodenal ileus (66,67). Gastric smooth muscle atrophy and disturbances in gastric autonomic function may also lead to gastric distension (42). In some cases of severe gastric distension, intragastric pressure may eventually exceed gastric venous pressure, culminating in necrosis of the stomach wall (68). A high index of suspicion for acute gastric distension/gastric rupture is needed, particularly in patients after an episode of binge overeating. These patients may present initially with vague, mild abdominal pain, and gradual progressive abdominal distension. Emesis may not occur because of gastric atony. Ultimately, gastric necrosis with perforation, peritonitis, subcutaneous emphysema, and shock may ensue if the condition is untreated (69,70). Direct questioning of the patient about bulimic behaviors is critical. The diagnosis of gastric rupture can be confirmed with abdominal imaging or during emergent laparotomy. Treatment includes nasogastric tube decompression of the stomach, rehydration and correction of electrolyte disturbances. Occasionally, nasogastric decompression is not possible because of the presence of large retained food items, in which case endoscopic intervention or gastrostomy and surgical decompression may be necessary. A comprehensive evaluation of the patient is essential as systemic complications have included vascular compromise with lower extremity ischemia (66,71). The mortality rate of gastric perforation is reported to be as high as 60% to 80% (66,70).

FIGURE 1
FIGURE 1:
Severe gastric dilatation in a 26-year-old woman with anorexia nervosa, binge-purge subtype. Coronal CT image shows marked distention of the stomach after ingestion of 4 boxes of semi-cooked pasta. The visualized pasta shells exhibit high attenuation as a result of iodine fortification. (Courtesy of Laura Avery, MD, Massachusetts General Hospital, Boston, MA with permission from Radiographics.) (85).

SMALL AND LARGE INTESTINE

In Wang's study of functional GI complaints in inpatients with eating disorders, 53% were identified as having irritable bowel syndrome, functional bloating, or constipation. Anorectal complaints occurred in 16% (29).

Few studies have examined small bowel transit and motility in patients with eating disorders. Hirakawa et al (72) measured gastrocecal transit in malnourished patients and controls with AN using lactulose hydrogen breath test. Duodenocecal transit time was also examined in several of the patients with AN to assess the impact of gastroparesis on gastrocecal transit time. Transit time was significantly prolonged in patients with AN compared with controls (117 ± 31 vs 81 ± 33 minutes, P < 0.02) and the duodenocecal transit time in the 3 patients with AN tested was longer than the average orocecal transit time in healthy controls. In a similar study, Kamal and colleagues (73) observed a trend toward delay in the orocecal transit time in patients with AN (mean BMI 15.1 ± 2.2 kg/m2) and BN (mean BMI 22.9 ± 6.5 kg/m2) compared with controls that did not reach statistical significance. No studies currently available have evaluated small bowel peristalsis in these patients.

The impact of nutritional compromise on the GI tract has been extensively studied in animal models. In the setting of acute starvation, the small bowel responds with alteration of nutrient and ion transport, reduction in absorptive surface area with apoptosis and reduced cell proliferation and migration along the crypt-villus axis, and increased permeability to macromolecules. This scenario predisposes the host to nutrient malabsorption, bacterial translocation, and sepsis (74–77). Alternatively, the response of the small intestine to chronic malnutrition can be viewed as an adaptive response. Mucosal cell turnover and crypt to villous tip migration rate decrease. The ratio of villous cells to crypt cells increases, presumably increasing the absorptive capacity of the intestine. Human studies of AN support the proposition that the intestine in restrictive eating disorders has preserved absorptive capacity as does the gut in chronic undernutrition of other etiologies. Monteleone et al (78) examined intestinal permeability in a group of young women with AN comparing them with controls. Intestinal permeability was estimated by the lactulose (L) to mannitol (M) excretion ratio. Lactulose is absorbed paracellularly via intercellular tight junctions and mannitol is absorbed transcellularly. Both are excreted in the urine. In conditions with increased permeability, the L:M excretion ratio is increased because of relatively greater absorption of lactulose (79). The authors noted a reduced intestinal permeability in AN compared with controls, which may explain the low prevalence of sepsis in these patients (75,78). Martinez-Olmes et al (80) examined intestinal absorption in women admitted for AN and severe malnutrition at admission and after nutritional rehabilitation by d-xylose absorption test (81) and C-13 triglyceride breath test (82,83). Intestinal absorption was fully preserved throughout the study, including upon admission. Intestinal disaccharidases have not been examined in this population.

SMA syndrome is a complication of patients with AN who have experienced rapid weight loss. The loss of the normal mesenteric fat pad between the abdominal aorta and SMA results in entrapment of the third part of the duodenum between the SMA and aorta producing obstructive symptoms (84–86). SMA syndrome may present in an acute or chronic manner with food intolerance, postprandial abdominal pain and distension, vomiting which can be bilious, and weight loss. The pain is typically relieved by assuming the prone, knee-chest, or left lateral decubitus position, which relieves tension at the aortomesenteric angle (87). Diagnosis is confirmed with fluoroscopy or cross-sectional imaging (84). Figure 2 displays fluoroscopic evidence of abrupt cessation of flow of contrast before the third portion of the duodenum in an adolescent with SMA syndrome. Computerized tomography and magnetic resonance studies provide a measure of the angle and distance between aorta and SMA. The normal range for the aortomesenteric angle is 38 to 65 degrees. The normal range for aortomesenteric distance is 10 to 28 mm. An aortomesenteric angle <22 to 25 degrees and aortomesenteric distance <8 mm correlate well with the occurrence of SMA syndrome (85–87). Postpyloric enteral feeding promotes restoration of the retroperitoneal fat and leads to resolution of symptoms in most cases (88). A review of reported cases of SMA syndrome in eating disorders (66) found that 73% of cases responded to conservative therapy whereas 29% required surgical intervention.

FIGURE 2
FIGURE 2:
Upper gastrointestinal series on a 14-year-old female with history of anorexia nervosa and superior mesenteric artery syndrome presenting with refractory vomiting. Note the sudden and abrupt cessation of contrast flow in the second portion of the duodenum (arrow).

Many factors contribute to the development of constipation in patients with eating disorders. Malnutrition causes smooth muscle atrophy and electrolyte abnormalities, especially hypokalemia. Malnourished patients are at risk for low triiodothyronine (T3) sick euthyroid syndrome (89). Purging by emesis or laxative abuse can induce hypokalemia (90). Antidepressants, particularly tricyclic antidepressants, may delay intestinal transit (91). Colon transit studies have demonstrated delayed colonic transit in the majority of malnourished AN inpatients. Kamal et al (73) reported delayed whole gut transit in AN patients versus controls (66.6 ± 29.6 vs 38 ± 19.6 hours). Chun and colleagues (94) reported whole gut transit time of 86.6 ± 17.8 hours in AN vs 28 ± 8.6 hours in controls. Chiaroni and colleagues (95) reported delayed transit in 8 of 12 AN patients. In the majority of the patients studied pre- and postnutritional therapy, the colonic transit times normalized. Many patients still, however, complained of a subjective sensation of constipation (94,95). Kamal et al (73) also reported that whole gut transit time was delayed in patients with BN compared to controls despite their normal BMI.

Studies of anorectal manometry in patients with AN have shown consistent differences compared with controls. Chiarioni et al (95) found that 42% of patients exhibited pelvic floor dysfunction with inability to expel a rectal balloon versus none in the control group. Mean resting external anal sphincter pressure is significantly reduced in AN versus controls (50.6 ± 19 vs 83.1 ± 24.4 mmHg). Threshold for the urge to defecate is higher in AN than controls (121 ± 86.5 vs 58.3 ± 19.5 mL). After refeeding, colonic transit normalized, but anorectal manometry remained abnormal, suggesting a persistent anorectal and pelvic floor dysfunction. Rarely, rectal prolapse with full-thickness protrusion of the rectal wall through the anal canal occurs in patients with AN and may necessitate surgical correction (66).

Patients with eating disorders use laxatives not only to relieve the symptoms of constipation and abdominal fullness, but also in an attempt to promote weight loss and “purification” through the expulsion of stool (96). The loss of weight after laxative use is almost entirely a result of water loss, not nutrient malabsorption. Nutrient malabsorption estimated by bomb calorimetry during laxative use has been estimated by one source at approximately 12% (92).

Laxatives should be used sparingly for constipation in patients with an eating disorder because of the potential for abuse. Evidence for the efficacy of laxatives during nutritional rehabilitation in patients with AN is sparce. The literature suggests that nutritional rehabilitation is effective in improving GI transit in most individuals. Unfortunately, however, despite improvement in BMI and whole intestinal transit, most patients with AN continue to complain of a sensation of constipation (73,94,95).

The prevalence of laxative abuse in patients with BN and AN has been reported to be as high as 75% (93,97,98). The abuse is often concealed by the patient, making true estimates difficult to obtain. Excessive use of most stimulant laxatives is associated with electrolyte and acid-base imbalance. Potassium is the primary electrolyte in stool water (70–90 mmol/L), with lower concentrations of sodium and chloride (93). Hypokalemia can induce muscle, renal, and cardiac injury (93,99). Hypermagnesemia with neuromuscular injury can occur with magnesium containing laxative abuse (100). Laxative abuse can trigger secondary hyperaldosteronism in response to chronic dehydration. Acute cessation of laxative intake can thus precipitate severe water and sodium retention with consequent cardiac and pulmonary fluid overload (93).

The morbidities associated with laxative abuse have changed over time as the active ingredients have been modified. In the past, concerns were raised about the ingredients in commonly used stimulant laxatives, including diphenylmethane derivatives (bisacodyl), castor oil, and anthraquinones (senna and cascara). The mode of action of stimulant laxatives is to alter fluid and electrolyte transport and/or motility in the intestines. Concern was raised about development of cathartic colon with overuse of these laxatives. Cathartic colon presented as severe colonic inertia associated with loss of colonic myenteric neurons, atrophy of smooth muscle, loss of haustrations, decreased volume and numbers of interstitial cells of Cajal, and loss of enteric neurons (101–104). It is currently believed that cathartic colon is most likely related to undefined toxic compounds previously present in laxatives, including the neurotoxin podophyllum (105–107), or an underlying undiagnosed motility disorder involving the myenteric plexus (93,107–109). Furthermore, phenolphthalein was the active ingredient in many over-the-counter laxatives. In 1997, the US Food and Drug Administration banned the use of phenolphthalein, as studies in animals exposed to high doses revealed an association with cancer and with genetic mutations in gametes (107,110,111).

Currently, the only significant pathologic entity associated with laxatives is mucosal damage induced by castor oil and anthranoid derivatives. Castor oil can injure intestinal epithelial cells (112). Anthraquinone-derived laxatives, when used chronically, can induce a reversible melanosis coli and gastric melanosis, a brownish pigmentation easily observed on endoscopy and colonoscopy (113). Melanosis coli (Figs. 3 and 4) results from the accumulation of lipofuscin in the macrophages of the lamina propria during cellular apoptosis (103). The finding appears to be benign with no evidence for genetic or malignant potential (114–116). The retained pigment does not extend to the muscle layers or the enteric plexuses, and it is thought to lessen and disappear when the offending agent is removed (103).

FIGURE 3
FIGURE 3:
Melanosis Coli-pigmented colonic mucosa. (Courtesy of Victor Fox, MD, Boston Children's Hospital, Boston, MA.)
FIGURE 4
FIGURE 4:
Melanosis Coli: Lipofuscin pigment laden macrophages-light micrograph 1000 × 3.

Necrotizing colitis is a rare complication in patients with severe malnutrition from AN. A very high index of suspicion is required to make this diagnosis. The initial complaint is usually abdominal pain early in refeeding therapy (117). Necrotizing colitis has been reported to develop even when refeeding is introduced cautiously. Patients may have diminished bowel sounds, abdominal distension and tenderness, hematochezia, and apparent delayed gastric emptying with emesis and gastric residuals. Later, radiologic findings include pneumatosis intestinalis involving small and large bowel, portal venous air and pneumoperitoneum. Intestinal dilatation and bowel wall thickening occur. The pathogenesis of necrotizing colitis in AN is thought to be similar to that of infant necrotizing enterocolitis. Proposed risk factors include starvation-induced intestinal hypoperfusion with hypoxic-ischemic bowel injury, intestinal dysmotility, and compromised intestinal mucosal integrity. Alterations to the intestinal microbiome and bacterial translocation have not been evaluated as possible causes in AN (117).

PANCREAS

Noninflammatory fibrotic injury to the pancreas has been observed in humans and in animals with protein-calorie malnutrition. Pancreatic histology in these cases reveals acinar cell atrophy, disorganization of the acinar pattern, stellate cell activation, reduction in the number of zymogen granules, and fibrosis of variable severity, which can involve the entire pancreas. Damage to all pancreatic organelles is seen in children dying of protein calorie malnutrition (118,119). Duodenal aspirates of severely malnourished children exhibit functional pancreatic compromise with reduced amylase, lipase, and trypsin levels. The secretion of bicarbonate and water is usually normal as ductular function is usually preserved (120). In the majority of reported cases, pancreatic exocrine dysfunction resolves with nutritional rehabilitation (119,120). Martinez-Olmos et al (80) measured pancreatic exocrine function in a small group of chronically malnourished AN patients using 2 noninvasive tests of pancreatic function, 13C-labeled triglyceride breath test (82,83) and fecal elastase (121,122). The 13C-labeled triglyceride breath test assesses lipase activity and fecal elastase 1 is a general measure of pancreatic exocrine function. Fecal elastase is not affected by GI motility or small bowel malabsorption (121,122). The authors’ normal findings in these women contrasts with the abnormalities noted in other studies of malnourished patients and may relate to the small size of the study or to the relative lack of sensitivity of the study tests they used to detect mild pancreatic insufficiency (80,83,121–123).

Acute pancreatitis has been reported in patients with AN. Proposed mechanisms include malnutrition related microlithiasis, ischemia, and/or structural damage. Ischemic injury to the pancreas may occur with fluid shifts and cardiac compromise during nutritional rehabilitation. Duodenal dysmotility may promote retrograde flow of duodenal contents into the pancreatic duct, initiating an inflammatory cascade, and pancreatic autolysis (124). Serum amylase levels can be elevated in patients with BN, but this is more commonly of salivary, not pancreatic, origin. Serum lipase and pancreatic isoamylase levels are more sensitive and specific indicators of pancreatitis in patients with an eating disorder (66,125).

LIVER

Hepatic injury occurs in both BN and AN. In obese individuals with binging, nonalcoholic fatty liver disease has been seen (126). In patients with malnutrition, liver injury ranging from asymptomatic elevation of hepatic transaminases to hepatic failure has occurred both during the malnourished state and upon nutritional rehabilitation. In 1 study of patients presenting to an eating disorder clinic, approximately 4% had elevated hepatic transaminases. Many of the subjects in this study, however, had comorbidities that may have contributed to the elevated transaminases (127). In another study of patients hospitalized for AN, more than one-third had elevated hepatic transaminases (128). Although abnormal transaminases in most malnourished patients normalize with nutritional rehabilitation, hepatitis, and acute fatty liver can develop during refeeding and rarely progress to hepatic failure.

The severity of malnutrition is a strong predictor of the risk of liver injury in patients hospitalized with AN (129). In AN, liver injury often occurs as a result of starvation-induced autophagy. Autophagy is a normal homeostatic cell process, which in health allows for recycling damaged or aged cell components. The phagophore consumes a portion of the cytoplasm including aging organelles to form an autophagosome. Fusion of a lysosome with the autophagosome creates an autolysosome. Material in the autolysosome is degraded by lysosomal hydrolases and the breakdown products are released into the cytoplasm (130,131). Malnutrition in AN causes a compensatory augmentation of autophagy to promote nutrient preservation and protect hepatocytes. When starvation is severe and chronic (BMI ≤ 13 kg/m2), excessive activation of autophagy can lead to hepatocyte cell death and liver insufficiency (130). This form of acute liver insufficiency is unique in that the liver does not exhibit necrosis or apoptosis but instead, electron microscopy reveals numerous autophagosomes with reduction of organelles and glycogen (130,132). In some patients with AN, the liver may incur hypoxic injury as a result of low cardiac output and hepatic hypoperfusion. Decreased cardiac output may occur as a result of cardiac muscle atrophy and electrolyte-induced arrhythmias and may be exacerbated during refeeding syndrome (133).

CONCLUSION

Eating disorders, including AN and BN, can present with a wide range of oral, salivary, and GI manifestations. The clinician must determine whether the complaints are organic in and of themselves, whether they represent complications of the eating disorder, or whether they are primarily functional. It is often the case that the complaints represent a combination of these 3. The secrecy enshrouding symptoms experienced by patients with eating disorders is a major problem that often prevents obtaining a reliable history. Diagnostic evaluations should be carefully selected and testing should not delay the introduction of nutritional therapy when an eating disorder is suspected as the oral, salivary, and GI complications are often reversible with nutritional rehabilitation.

REFERENCES

1. American Psychiatric AssociationDiagnostic and Statistical Manual of Mental Disorders. 5th ed.Arlington, VA:American Psychiatric Association; 2013.
2. Culbert KM, Racine SE, Klump KL. Research review: what we have learned about the causes of eating disorders—a synthesis of sociocultural, psychological, and biological research. J Child Psychol Psychiatry 2015; 56:1141–1164.
3. Johansson AK, Norring C, Unell L, et al. Eating disorders and oral health: a matched case-control study. Eur J Oral Sci 2012; 120:61–68.
4. Romanos GE, Javed F, Romanos EB, et al. Oro-facial manifestations in patients with eating disorders. Appetite 2012; 59:499–504.
5. Lo Russo L, Campisi G, Di Fede O, et al. Oral manifestations of eating disorders: a critical review. Oral Dis 2008; 14:479–484.
6. Imfeld T Dental erosionDefinition, classification and links. Eur J Oral Sci 1996; 104 (2 pt 2):151–155.
7. McIntyre JM. Erosion. Aust Prosthodont J 1992; 6:17–25.
8. Mehler PS. Medical complications of bulimia nervosa and their treatments. Int J Eat Disord 2011; 44:95–104.
9. Preetha A, Sujatha D, Patil BA, et al. Oral manifestations in gastroesophageal reflux disease. Gen Dent 2015; 63:e27–e31.
10. Mueller JA. Eating disorders: identification and intervention. J Contemp Dent Pract 2001; 2:98.
11. Sedghizadeh PP. Images in clinical medicine. Bulimia nervosa. N Engl J Med 2013; 368:1238.
12. Christopher K, Tammaro D, Wing EJ. Early scurvy complicating anorexia nervosa. South Med J 2002; 95:1065–1066.
13. Flores IL, Santos-Silva AR, Coletta RD, et al. Widespread red oral lesions. J Am Dent Assoc 2013; 144:1257–1260.
14. Lu SY, Wu HC. Initial diagnosis of anemia from sore mouth and improved classification of anemias by MCV and RDW in 30 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98:679–685.
15. Paillaud E, Merlier I, Dupeyron C, et al. Oral candidiasis and nutritional deficiencies in elderly hospitalised patients. Br J Nutr 2004; 92:861–867.
16. Mandel L. Salivary gland disorders. Med Clin North Am 2014; 98:1407–1449.
17. Donath K, Seifert G. Ultrastructural studies of the parotid glands in sialadenosis. Virchows Arch A Pathol Anat Histol 1975; 365:119–135.
18. Coleman H, Altini M, Nayler S, et al. Sialadenosis: a presenting sign in bulimia. Head Neck 1998; 20:758–762.
19. Scully C, Bagan JV. Adverse drug reactions in the orofacial region. Crit Rev Oral Biol Med 2004; 15:221–239.
20. Riad M, Barton JR, Wilson JA, et al. Parotid salivary secretory pattern in bulimia nervosa. Acta Otolaryngol 1991; 111:392–395.
21. Solomon LW, Merzianu M, Sullivan M, et al. Necrotizing sialometaplasia associated with bulimia: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103:e39–42.
22. Kaplan I, Alterman M, Kleinman S, et al. The clinical, histologic, and treatment spectrum in necrotizing sialometaplasia. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114:577–585.
23. Gilowski L, Wiench R, Polakiewicz-Gilowska A, et al. Necrotizing sialometaplasia of the palatal mucosa in patient with history of anorexia: review and case report. Am J Otolaryngol 2014; 35:400–401.
24. Gryboski JD. Eating disorders in inflammatory bowel disease. Am J Gastroenterol 1993; 88:293–296.
25. Reas DL, Zipfel S, Ro O. Is it an eating disorder or achalasia or both? A literature review and diagnostic challenges. Eur Eat Disord Rev 2014; 22:321–330.
26. Leffler DA, Dennis M, Edwards George JB, et al. The interaction between eating disorders and celiac disease: an exploration of 10 cases. Eur J Gastroenterol Hepatol 2007; 19:251–255.
27. Jenkins AP, Treasure J, Thompson RP. Crohn's disease presenting as anorexia nervosa. Br Med J (Clin Res Ed) 1988; 296:699–700.
28. Bern EM, O’Brien RF. Is it an eating disorder, gastrointestinal disorder, or both? Curr Opin Pediatr 2013; 25:463–470.
29. Wang X, Luscombe GM, Boyd C, et al. Functional gastrointestinal disorders in eating disorder patients: altered distribution and predictors using ROME III compared to ROME II criteria. World J Gastroenterol 2014; 20:16293–16299.
30. Oberne A, DeBate R. Self-induced vomiting as a function of bulimia nervosa increases the risk for oral health issues. J Evid Based Dent Pract 2014; 14:195–196.
31. Pettersen G, Rosenvinge JH, Ytterhus B. The “double life” of bulimia: patients’ experiences in daily life interactions. Eat Disord 2008; 16:204–211.
32. Kiss A, Bergmann H, Abatzi TA, et al. Oesophageal and gastric motor activity in patients with bulimia nervosa. Gut 1990; 31:259–265.
33. Denholm M, Jankowski J. Gastroesophageal reflux disease and bulimia nervosa—a review of the literature. Dis Esophagus 2011; 24:79–85.
34. Rothstein SG. Reflux and vocal disorders in singers with bulimia. J Voice 1998; 12:89–90.
35. Kiss A, Wiesnagrotzki S, Abatzi TA, et al. Upper gastrointestinal endoscopy findings in patients with long-standing bulimia nervosa. Gastrointest Endosc 1989; 35:516–518.
36. Shinohara ET, Swisher-McClure S, Husson M, et al. Esophageal cancer in a young woman with bulimia nervosa: a case report. J Med Case Rep 2007; 1:160.
37. Nickl NJ, Brazer SR, Rockwell K, et al. Patterns of esophageal motility in patients with stable bulimia. Am J Gastroenterol 1996; 91:2544–2547.
38. Benini L, Todesco T, Frulloni L, et al. Esophageal motility and symptoms in restricting and binge-eating/purging anorexia. Dig Liver Dis 2010; 42:767–772.
39. Drossman DA, Dumitrascu DL. Rome III: New standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006; 15:237–241.
40. Holmes SR, Gudridge TA, Gaudiani JL, et al. Dysphagia in severe anorexia nervosa and potential therapeutic intervention: a case series. Ann Otol Rhinol Laryngol 2012; 121:449–456.
41. Overby KJ, Litt IF. Mediastinal emphysema in an adolescent with anorexia nervosa and self-induced emesis. Pediatrics 1988; 81:134–136.
42. Hadley SJ, Walsh BT. Gastrointestinal disturbances in anorexia nervosa and bulimia nervosa. Curr Drug Targets CNS Neurol Disord 2003; 2:1–9.
43. Rigaud D, Bedig G, Merrouche M, et al. Delayed gastric emptying in anorexia nervosa is improved by completion of a renutrition program. Dig Dis Sci 1988; 33:919–925.
44. Holt S, Ford MJ, Grant S, et al. Abnormal gastric emptying in primary anorexia nervosa. Br J Psychiatry 1981; 139:550–552.
45. McCallum RW, Grill BB, Lange R, et al. Definition of a gastric emptying abnormality in patients with anorexia nervosa. Dig Dis Sci 1985; 30:713–722.
46. Abell TL, Malagelada JR, Lucas AR, et al. Gastric electromechanical and neurohormonal function in anorexia nervosa. Gastroenterology 1987; 93:958–965.
47. Hutson WR, Wald A. Gastric emptying in patients with bulimia nervosa and anorexia nervosa. Am J Gastroenterol 1990; 85:41–46.
48. Robinson PH, Clarke M, Barrett J. Determinants of delayed gastric emptying in anorexia nervosa and bulimia nervosa. Gut 1988; 29:458–464.
49. Diamanti A, Bracci F, Gambarara M, et al. Gastric electric activity assessed by electrogastrography and gastric emptying scintigraphy in adolescents with eating disorders. J Pediatr Gastroenterol Nutr 2003; 37:35–41.
50. Perez ME, Coley B, Crandall W, et al. Effect of nutritional rehabilitation on gastric motility and somatization in adolescents with anorexia. J Pediatr 2013; 163:867.e1–872.e1.
51. Geracioti TD Jr, Liddle RA. Impaired cholecystokinin secretion in bulimia nervosa. N Engl J Med 1988; 319:683–688.
52. Geliebter A, Hashim SA. Gastric capacity in normal, obese, and bulimic women. Physiol Behav 2001; 74:743–746.
53. Devlin MJ, Walsh BT, Guss JL, et al. Postprandial cholecystokinin release and gastric emptying in patients with bulimia nervosa. Am J Clin Nutr 1997; 65:114–120.
54. Benini L, Todesco T, Dalle Grave R, et al. Gastric emptying in patients with restricting and binge/purging subtypes of anorexia nervosa. Am J Gastroenterol 2004; 99:1448–1454.
55. Dubois A, Gross HA, Richter JE, et al. Effect of bethanechol on gastric functions in primary anorexia nervosa. Dig Dis Sci 1981; 26:598–600.
56. Szmukler GI, Young GP, Lichtenstein M, et al. A serial study of gastric emptying in anorexia nervosa and bulimia. Aust N Z J Med 1990; 20:220–225.
57. Stacher G, Abatzi-Wenzel TA, Wiesnagrotzki S, et al. Gastric emptying, body weight and symptoms in primary anorexia nervosa. Long-term effects of cisapride. Br J Psychiatry 1993; 162:398–402.
58. Stacher G, Peeters TL, Bergmann H, et al. Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa. Gut 1993; 34:166–172.
59. Russell DM, Freedman ML, Feiglin DH, et al. Delayed gastric emptying and improvement with domperidone in a patient with anorexia nervosa. Am J Psychiatry 1983; 140:1235–1236.
60. Saleh JW, Lebwohl P. Metoclopramide-induced gastric emptying in patients with anorexia nervosa. Am J Gastroenterol 1980; 74:127–132.
61. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol 2013; 108:18–37.
62. Rodriguez L, Diaz J, Nurko S. Safety and efficacy of cyproheptadine for treating dyspeptic symptoms in children. J Pediatr 2013; 163:261–267.
63. Halmi KA, Eckert E, LaDu TJ, et al. Anorexia nervosa: treatment efficacy of cyproheptadine and amitriptyline. Arch Gen Psychiatry 1986; 43:177–181.
64. Tjeerdsma HC, Smout AJ, Akkermans LM. Voluntary suppression of defecation delays gastric emptying. Dig Dis Sci 1993; 38:832–836.
65. Birmingham CL, Cardew S, Gritzner S. Gastric bezoar in anorexia nervosa. Eat Weight Disord 2007; 12:e28–e29.
66. Norris ML, Harrison ME, Isserlin L, et al. Gastrointestinal complications associated with anorexia nervosa: a systematic review. Int J Eat Disord 2016; 49:216–237.
67. Mascolo M, Dee E, Townsend R, et al. Severe gastric dilatation due to superior mesenteric artery syndrome in anorexia nervosa. Int J Eat Disord 2015; 48:532–534.
68. Edlich RF, Borner JW, Kuphal J, et al. Gastric blood flow. I. Its distribution during gastric distention. Am J Surg 1970; 120:35–37.
69. Abdu RA, Garritano D, Culver O. Acute gastric necrosis in anorexia nervosa and bulimia. Two case reports. Arch Surg 1987; 122:830–832.
70. Jennings KP, Klidjian AM. Acute gastric dilatation in anorexia nervosa. Br Med J 1974; 2:477–478.
71. Van Eetvelde E, Verfaillie L, Van De Winkel N, et al. Acute gastric dilatation causing acute limb ischemia in an anorexia nervosa patient. J Emerg Med 2014; 46:e141–e143.
72. Hirakawa M, Okada T, Iida M, et al. Small bowel transit time measured by hydrogen breath test in patients with anorexia nervosa. Dig Dis Sci 1990; 35:733–736.
73. Kamal N, Chami T, Andersen A, et al. Delayed gastrointestinal transit times in anorexia nervosa and bulimia nervosa. Gastroenterology 1991; 101:1320–1324.
74. Ferraris RP, Carey HV. Intestinal transport during fasting and malnutrition. Annu Rev Nutr 2000; 20:195–219.
75. Chappell VL, Thompson MD, Jeschke MG, et al. Effects of incremental starvation on gut mucosa. Dig Dis Sci 2003; 48:765–769.
76. Winter TA, Lemmer ER, O’Keefe SJ, et al. The effect of severe undernutrition, and subsequent refeeding on digestive function in human patients. Eur J Gastroenterol Hepatol 2000; 12:191–196.
77. Welsh FK, Farmery SM, MacLennan K, et al. Gut barrier function in malnourished patients. Gut 1998; 42:396–401.
78. Monteleone P, Carratu R, Carteni M, et al. Intestinal permeability is decreased in anorexia nervosa. Mol Psychiatry 2004; 9:76–80.
79. Juby LD, Rothwell J, Axon AT. Lactulose/mannitol test: an ideal screen for celiac disease. Gastroenterology 1989; 96:79–85.
80. Martinez-Olmos MA, Peino R, Prieto-Tenreiro A, et al. Intestinal absorption and pancreatic function are preserved in anorexia nervosa patients in both a severely malnourished state and after recovery. Eur Eat Disord Rev 2013; 21:247–251.
81. Craig RM, Atkinson AJ Jr. D-Xylose testing: a review. Gastroenterol 1988; 95:223–231.
82. Watkins JB, Klein PD, Schoeller DA, et al. Diagnosis and differentiation of fat malabsorption in children using 13C-labeled lipids: trioctanoin, triolein, and palmitic acid breath tests. Gastroenterology 1982; 82 (5 Pt 1):911–917.
83. Dominguez-Munoz JE, Iglesias-Garcia J, Vilarino-Insua M, et al. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2007; 5:484–488.
84. Rabie ME, Ogunbiyi O, Al Qahtani AS, et al. Superior mesenteric artery syndrome: clinical and radiological considerations. Surg Res Pract 2015; 2015:628705.
85. Bowden DJ, Kilburn-Toppin F, Scoffings DJ. Radiology of eating disorders: a pictorial review. Radiographics 2013; 33:1171–1193.
86. Unal B, Aktas A, Kemal G, et al. Superior mesenteric artery syndrome: CT and ultrasonography findings. Diagn Interv Radiol 2005; 11:90–95.
87. Merrett ND, Wilson RB, Cosman P, et al. Superior mesenteric artery syndrome: diagnosis and treatment strategies. J Gastrointest Surg 2009; 13:287–292.
88. Adson DE, Mitchell JE, Trenkner SW. The superior mesenteric artery syndrome and acute gastric dilatation in eating disorders: a report of two cases and a review of the literature. Int J Eat Disord 1997; 21:103–114.
89. Stoving RK, Hangaard J, Hansen-Nord M, et al. A review of endocrine changes in anorexia nervosa. J Psychiatr Res 1999; 33:139–152.
90. Crow SJ, Salisbury JJ, Crosby RD, et al. Serum electrolytes as markers of vomiting in bulimia nervosa. Int J Eat Disord 1997; 21:95–98.
91. Gorard DA, Libby GW, Farthing MJ. Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome. Aliment Pharmacol Ther 1994; 8:159–166.
92. Bo-Linn GW, Santa Ana CA, Morawski SG, et al. Purging and calorie absorption in bulimic patients and normal women. Ann Intern Med 1983; 99:14–17.
93. Roerig JL, Steffen KJ, Mitchell JE, et al. Laxative abuse: epidemiology, diagnosis and management. Drugs 2010; 70:1487–1503.
94. Chun AB, Sokol MS, Kaye WH, et al. Colonic and anorectal function in constipated patients with anorexia nervosa. Am J Gastroenterol 1997; 92:1879–1883.
95. Chiarioni G, Bassotti G, Monsignori A, et al. Anorectal dysfunction in constipated women with anorexia nervosa. Mayo Clin Proc 2000; 75:1015–1019.
96. Kovacs D, Palmer RL. The associations between laxative abuse and other symptoms among adults with anorexia nervosa. Int J Eat Disord 2004; 36:224–228.
97. Steffen KJ, Mitchell JE, Roerig JL, et al. The eating disorders medicine cabinet revisited: a clinician's guide to ipecac and laxatives. Int J Eat Disord 2007; 40:360–368.
98. Turner J, Batik M, Palmer LJ, et al. Detection and importance of laxative use in adolescents with anorexia nervosa. J Am Acad Child Adolesc Psychiatry 2000; 39:378–385.
99. Slung PH, Carey WD. Clinical features and follow-up of surreptitious laxative users. Cleve Clin Q 1984; 51:167–171.
100. Qureshi T, Melonakos TK. Acute hypermagnesemia after laxative use. Ann Emerg Med 1996; 28:552–555.
101. He CL, Burgart L, Wang L, et al. Decreased interstitial cell of cajal volume in patients with slow-transit constipation. Gastroenterology 2000; 118:14–21.
102. Wedel T, Spiegler J, Soellner S, et al. Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon. Gastroenterology 2002; 123:1459–1467.
103. Wald A. Is chronic use of stimulant laxatives harmful to the colon? J Clin Gastroenterol 2003; 36:386–389.
104. Ewe K. The physiological basis of laxative action. Pharmacology 1980; 20 (suppl 1):2–20.
105. De Ponti F, De Giorgio R. The cathartic colon? Aliment Pharmacol Ther 2002; 16:643–644.
106. Fioramonti J, Bueno L. Toxicity of laxatives: how to discriminate between myth and fact? Eur J Gastroenterol Hepatol 1995; 7:5–7.
107. Muller-Lissner S. What has happened to the cathartic colon? Gut 1996; 39:486–488.
108. Krishnamurthy S, Schuffler MD, Rohrmann CA, et al. Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus. Gastroenterology 1985; 88 (1 pt 1):26–34.
109. De Giorgio R, Stanghellini V, Barbara G, et al. Primary enteric neuropathies underlying gastrointestinal motor dysfunction. Scand J Gastroenterol 2000; 35:114–122.
110. Dunnick JK, Hailey JR. Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems. Cancer Res 1996; 56:4922–4926.
111. Coogan PF, Rosenberg L, Palmer JR, et al. Phenolphthalein laxatives and risk of cancer. J Natl Cancer Inst 2000; 92:1943–1944.
112. Gaginella TS, Haddad AC, Go VL, et al. Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells. J Pharmacol Exp Ther 1977; 201:259–266.
113. Mitty RD, Wolfe GR, Cosman M. Initial description of gastric melanosis in a laxative-abusing patient. Am J Gastroenterol 1997; 92:707–708.
114. van Gorkom BA, de Vries EG, Karrenbeld A, et al. Review article: anthranoid laxatives and their potential carcinogenic effects. Aliment Pharmacol Ther 1999; 13:443–452.
115. Siegers CP. Anthranoid laxatives and colorectal cancer. Trends Pharmacol Sci 1992; 13:229–231.
116. Nusko G, Schneider B, Schneider I, et al. Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case-control study. Gut 2000; 46:651–655.
117. Diamanti A, Basso MS, Cecchetti C, et al. Digestive complication in severe malnourished anorexia nervosa patient: a case report of necrotizing colitis. Int J Eat Disord 2011; 44:91–93.
118. Shaper AG. Chronic pancreatic disease and protein malnutrition. Lancet 1960; 1:1223–1224.
119. Pitchumoni CS. Pancreas in primary malnutrition disorders. Am J Clin Nutr 1973; 26:374–379.
120. Barbezat GO, Hansen JD. The exocrine pancreas and protein-calorie malnutrition. Pediatrics 1968; 42:77–92.
121. Naruse S, Ishiguro H, Ko SB, et al. Fecal pancreatic elastase: a reproducible marker for severe exocrine pancreatic insufficiency. J Gastroenterol 2006; 41:901–908.
122. Dominici R, Franzini C. Fecal elastase-1 as a test for pancreatic function: a review. Clin Chem Lab Med 2002; 40:325–332.
123. Dominguez-Munoz JE, Hieronymus C, Sauerbruch T, et al. Fecal elastase test: evaluation of a new noninvasive pancreatic function test. Am J Gastroenterol 1995; 90:1834–1837.
124. Keane FB, Fennell JS, Tomkin GH. Acute pancreatitis, acute gastric dilation and duodenal ileus following refeeding in anorexia nervosa. Ir J Med Sci 1978; 147:191–192.
125. Muniraj T, Dang S, Pitchumoni CS. Pancreatitis or not? Elevated lipase and amylase in ICU patients. J Crit Care 2015; 30:1370–1375.
126. Lelli L, Castellini G, Gabbani T, et al. Associations between liver enzymes, psychopathological and clinical features in eating disorders. Eur Eat Disord Rev 2014; 22:443–447.
127. Mickley D, Greenfeld D, Quinlan DM, et al. Abnormal liver enzymes in outpatients with eating disorders. Int J Eat Disord 1996; 20:325–329.
128. Tomita K, Haga H, Ishii G, et al. Clinical manifestations of liver injury in patients with anorexia nervosa. Hepatol Res 2014; 44:E26–31.
129. Nagata JM, Park KT, Colditz K, et al. Associations of elevated liver enzymes among hospitalized adolescents with anorexia nervosa. J Pediatr 2015; 166:439.e1–443.e1.
130. Kheloufi M, Boulanger CM, Durand F, et al. Liver autophagy in anorexia nervosa and acute liver injury. Biomed Res Int 2014; 2014:701064.
131. Rautou PE, Mansouri A, Lebrec D, et al. Autophagy in liver diseases. J Hepatol 2010; 53:1123–1134.
132. Rautou PE, Cazals-Hatem D, Moreau R, et al. Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy. Gastroenterology 2008; 135:840–848.48.e1-3.
133. Fuhrmann V, Kneidinger N, Herkner H, et al. Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med 2009; 35:1397–1405.
Keywords:

anorexia nervosa; bulimia nervosa; complications of eating disorders; gastrointestinal complications; weight loss

Copyright 2016 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.