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Home , Anorexia (symptom), Bulimia nervosa, Hypokalemia

AED INVITED LITERATURE REVIEW

Medical Complications of and Their Treatments

Philip S. Mehler, MD* ABSTRACT Results: Extensive and detailed review Objective: To present a cogent and of the medical complications of bulimia practical review of the medical complica- nervosa. VC 2010 by Wiley Periodicals, tions and their treatment in patients Inc. with bulimia nervosa. Keywords: bulimia; medical; compli- Method: Thorough review of the medi- cations; ; pseudo-barters cal literature from 1990 to current in regards to the medical complications of bulimia nervosa and the therapeutic inter- vention that are effective to treat them. (Int J Eat Disord 2011; 44:95–104)

Introduction be healthy and can more easily hide their disorder. It is not uncommon for patient with bulimia nerv- Although DSM-V will likely provide some new defi- 1 osa to engage in bulimic purging behaviors for nitions for bulimia nervosa, currently the purging many years before seeking medical attention. subtype is by far the more common diagnostic cat- To maximize the utility of this review, the manu- egory. The types of compensatory purging behav- script is divided into four main sections: the spe- iors, which individuals engage in most frequently, cific medical complications that emerge as a result include self-induced , or the misuse of lax- of self-induced vomiting, abuse, and diu- atives or . There are numerous potentially retic abuse, followed by the fourth section devoted serious medical complications that directly ema- to the therapeutic interventions available to effec- nate from the specific mode and frequency of purg- tively treat these complications. ing that is utilized. Indeed, use of health services are markedly higher for patients with bulimia nerv- osa both in the 12 months leading up to, and in the 12 months following the index visit, probably reflecting, in part, the broad range of medical com- Self-Induced Vomiting plications present as a result of the purging behav- iors.2 In this review, the medical complications of There are a number of oral and gastrointestinal bulimia nervosa will be discussed along with their complications that develop as a result of engaging treatments to help clinicians caring for these in self-induced vomiting. Most patients with buli- patients achieve the most optimal overall results. mia nervosa induce vomiting with their finger, but This is especially important because symptoms of some use ipecac. As the illness progresses, many bulimia nervosa are relatively longstanding and the can vomit reflexively without mechanical stimula- 5-year recovery rate is only in the 50% range.3 tion. Oral complications of bulimia are primarily Thus, the medical complications are of relevance related to the chronic regurgitation of acidic gastric for many years during the course of treatment. contents. Cheilosis, a form of stomatitis character- Although the emaciated state of the patient with ized by and maceration of the mucosa at the angels of the mouth, is seen in some patients with nervosa immediately suggests that diag- 4 nosis, patients with bulimia nervosa may appear to bulimia nervosa. In severe cases, linear fissures can occur, which may form scars on healing. In

Accepted 11 February 2010 addition to the associated with cheilosis, *Correspondence to: Philip S. Mehler, Denver Health Medical patients may complain of pharyngeal soreness Center, Denver, Colorado. E-mail: [email protected] related to the chronic irritation created in the back Denver Health Medical Center, Denver, Colorado of the throat from acidic stomach contents. Given Published online 7 May 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/eat.20825 that dentists may be the first medical providers to VC 2010 Wiley Periodicals, Inc. assess the oral effects of bulimia nervosa, they may

International Journal of Disorders 44:2 95–104 2011 95 MEHLER be key in the timely diagnosis of bulimia nervosa after a bingeing-purging episode, and thus the con- and its treatment.5 Oral-dental problems associ- nection to bulimia may not be obvious. ated with self-induced vomiting can be manifested Sialographic computed tomographic scanning of as early as 6 months following the initiation of self- the parotids will demonstrate enlarged glands. His- induced vomiting. The most common dental com- tologically, parotid biopsy specimens are normal plications include dental erosions, dental caries, except for acinar size, which is increased because and periodontal . The dental erosions of an increased number of secretion granules.15 Pa- involve erosion of the enamel on the lingual surface rotid salivary flow rates are reduced, but there are of maxillary teeth that manifest as a smooth no derangements of salivary or immu- unnatural glossy appearance noticeable with illu- noglobulin levels. mination of the teeth during an examination of the The pathogenesis of parotid swelling in bulimia oral cavity.6 This is referred to as peri- is unclear.16 Some investigators think that the swel- myolysis. Enamel erosion is a common manifesta- ling is a direct result of , which often tion of bulimia. The loss of dentin and tooth involves highly caloric foods consumed in very enamel is seen initially only on the lingual surface but can also involve palatal and posterior occlusal large quantities over short periods. Others postu- surfaces of the maxillary teeth.7 Usually, the lower late that chronic regurgitation of acidic gastric con- anterior teeth have not had significant damage, tents is responsible. Still others believe that pancre- likely because of protective tongue movements.8 It atic proteolytic enzymes brought into the mouth is thought that visible enamel destruction occurs during vomiting stimulate lingual taste receptors; after about 2 years of regular episodes of vomiting. increased autonomic stimulation would thus cause 17 The severity and rate of enamel loss may be related the salivary glands to swell. to a multiplicity of factors, such as duration of buli- In association with sialadenosis, serum mia, frequency of purging, types of food consumed, levels are elevated in 10–20% of patients. Fractiona- quality of tooth structure, and .9 tion of the amylase confirms that it is of salivary Patients with severe cases complain of thermal and not pancreatic origin. Elevated levels are com- tooth sensitivity because of the exposed dentin. mon in patients reporting more frequent binge eat- Gum disease (gingivitis) is also a direct result of ing and vomiting. Amylase levels will usually return chronic irritation from the acidic gastric contents to normal a few days to weeks after cessation of and occurs as pain and erythematous gums. These vomiting. patients also appear to have more periodontitis.10 Esophageal complications run the spectrum There is controversy about whether patients with from mild esophagitis to life-threatening esopha- bulimia have a greater incidence of dental caries.11 geal rupture. Esophagitis, esophageal erosions, It is known that patients with bulimia often binge ulcers, and bleeding are thought to be secondary to on high-carbohydrate foods, but they are often fas- the frequent contact of the esophageal mucosa tidious in the care of their teeth. Older studies, with the regurgitated acidic gastric contents. Thus, however, have suggested an increased risk of caries patients with bulimia nervosa often complain of in patient with bulimia.12 However, the caries that heartburn and acid-reflux symptoms.18 However, patients with bulimia seem to develop include a esophageal motility is normal in bulimia nervosa predisposition to cervical caries and leathery and gastric emptying is not delayed as it often is in lesions of dentine leaving extensive areas of enamel .19 Frequent complaints of sore undermined.13 throat and hematemesis are noted. The latter is Another oral complication associated with usually the result of Mallory-Weiss tears at the gas- repeated self-induced vomiting is sialadenosis (hy- tro-esophageal junction and usually only cause pertrophy of the salivary glands). The intensity of minor gastrointestinal bleeds that are self-limited. this seems to correlate with the severity of enamel Spontaneous reflux of acidic gastric contents into erosions. Painless unilateral or bilateral swelling of the lower can also occur due to laxity of the salivary glands has been reported in 10–50% of the lower esophageal sphincter after months of patients, depending on the frequency of vomiting. repeated vomiting. Similarly, among patients with Initially intermittent, the swelling tends to persist long-standing bulimia nervosa, esophageal stric- as the patient becomes chronically bulimic. tures with resultant dysphagia have been reported. Involvement of the parotid glands is most com- Although Barrett’s esophagus, which is the mon, but some patients will demonstrate subman- replacement of normal squamous epithelium with dibular gland involvement as well.14,15 Clinically, columnar epithelium as a result of chronic gastro- the swelling is generally most pronounced 3–6 days esophageal reflux, has been reported in patients

96 International Journal of Eating Disorders 44:2 95–104 2011 MEDICAL COMPLICATIONS OF BULIMIA with bulimia, it is unclear if this condition has an lar toxicity is not clearly defined, but the alkaloid is increased prevalence among bulimic patients. The known to depress glycolysis, inhibit the Krebs cycle, diagnosis of Barrett’s esophagus is important with a resultant decrease in adenosine triphosphate because approximately 10% of cases will eventually formation, and induce neuromuscular blockade by progress to often fatal adenocarcinoma of the means of tubocurarinelike effect. The neuromyop- esophagus. It is recommended that patients with athy, in contrast to the cardiomyopathy, is generally known Barrett’s esophagus should have periodic reversible. surveillance endoscopies to screen for early adeno- carcinoma. Therefore, if a patient with bulimia, who purges through self-induced vomiting, has severe dyspepsia that is not well controlled with a Laxative Abuse proton-pump inhibitor or other common treat- ment for acid-reflux, a referral should be made for Like self-induced vomiting, laxative abuse remains an upper endoscopy procedure.20 a fairly common mode of purging for patients with A serious, albeit rare, esophageal complication of bulimia nervosa, and like self-induced vomiting it bulimia is (Boerhaave’s syn- has a unique set of medical complications related drome). The first reported case, by Boerhaave in to it. Of note, they are not a effective method to 1724, described the death of Baron John Van Wass- lose weight because most caloric absorption has ner, who suffered a ruptured esophagus after self- occurred before the site in the bowel where laxa- tives act.24 Only 10–12% of ingested calories are induced emesis. Although this condition is rare, 25 mortality is high, reaching approximately 20%. lost as a result of laxative use, because Classically, patients will have severe chest pain, have little effect on the small intestine, the primary site of caloric absorption. painful swallowing, tachypnea and , and a left-sided pleural effusion on chest radiogra- Laxatives can be grouped into five major classes phy.21 Early diagnosis is crucial, as prompt depending on their mechanism of action: bulk lax- is usually curative. atives, osmotics, surfactants, emollients, and . Of the various classes of laxatives, the Some patients induce emesis by inserting their ones most abused by patients with bulimia, and fingers into the throat; abrasions and on the ones associated with most of the medical com- the dorsum of the hand and knuckles (Russell’s plications, are the laxatives including sign) may result and is the most characteristic der- 22 compounds containing phenolphthalein, cascara, matologic sign of vomiting. Other patients use a bisacodyl, or anthraquinone. They act rapidly and spoon or toothbrush, and still others can merely directly to stimulate colonic motility, producing a turn the neck and spontaneously vomit. These large volume of watery .26 patients have also been reported to use a variety of The medical complications of laxative abuse can chemical agents to vomit including soap solutions. be divided into two main categories. The effects on Ipecac syrup is mainstay for treatment of acute the gastrointestinal system and the systemic overdoses of certain toxins. It may also be abused effects, predominantly and electrolyte by patients with bulimia nervosa; in this setting, it disturbances. The latter effect will be discussed can be toxic or even fatal. Ipecac has five alkaloid later as a general review of all the electrolyte distur- constituents (the major ones are emetine and bances that emanate from the different modes of cephaeline), all of which are toxic to cardiac and purging. The gastrointestinal effects of laxative . A 30-mL bottle of ipecac contains abuse include melanosis coli, cathartic colon, and 21 mg of emetine. Because of ipecac’s long half-life functional impairment. Melanosis coli is a dark (56 h), repeated ingestions can result in potentially brown discoloration of the colonic mucosa. Micro- fatal cumulative dose of emetine, variously scopic melanosis can be seen in about half of reported to be between 500 and 1,200 mg. An irre- patients taking anthraquinone-based laxatives.27 versible cardiomyopathy with resultant symptoms There is no indication that melanosis coli has any of congestive heart failure, ventricular , significant pathophysiologic consequences, and sudden death may follow.23 although there have been reports that phenol- The neuromuscular manifestations of an eme- phthalein-containing laxatives are carcinogenic in tine overdose are predictably muscle , laboratory animals. Thus, they were withdrawn pain, and stiffness. Of note, the serum creatinine from the market about 10 years ago. phosphokinase (CPK) value may be elevated or The cathartic colon syndrome is a much more normal. The mechanism of emetine neuromuscu- serious entity, involving loss of normal colonic peri-

International Journal of Eating Disorders 44:2 95–104 2011 97 MEHLER stalsis because of long-term habituation to stimu- FIGURE 1 Idiopathic cyclical edema. [Color figure can 28 be viewed in the online issue, which is available at lant laxatives. The result is a dilated, atonic colon, wileyonlinelibrary.com] typically defined on the basis of radiologic findings. Barium enema studies reveal that the colon loses the normal haustral markings and is dilated. These changes arise from inflammation of the mucosa, alterations in the muscular layers of the colon, and degeneration and damage to the enteric and Auer- bach’s plexi caused by a direct toxic effect from stimulant laxatives.29 Microscopically, the colon shows thinning of the microvilli and abnormalities diuretics. Often, the initial stimulus to take diu- within cytoplasmic organelles. As a result of these retics is the normal fluctuation of weight from the changes, slowed or absent transit occurs through fluid retention many women experience as part of some or all segments of the colon, leading to hard, the premenstrual syndrome. Diuretics, either over- infrequently passed stools and, occasionally, a state the-counter or prescribed, are taken for sympto- of totally refractory . The colon is thus matic relief. The resultant stimulates relegated to an inert tube, incapable of propagating the renin-angiotensin- system, which fecal matter with resultant obstipation. There is in turn causes rebound salt and water retention. marked variation in individual susceptibility to Then, discontinuing the diuretics precipitates a these effects of stimulant laxatives. With truly pro- reflexive state of fluid retention because of the longed abuse of these laxatives, the cathartic colon unopposed effects of the renin-angiotensin-aldo- syndrome is potentially irreversible. Loss of normal sterone axis. This leads to a vicious circle of further colonic function can become so severe that surgical abuse to eliminate the edema. This pattern colectomy and insertion of an ostomy bag is of edema was referred to as idiopathic because needed to treat intractable constipation. Unfortu- there was no associated cardiac, hepatic, or renal nately, it is impossible to predict or advise patients disease.34 However, Bihun et al.35 showed a strong at what point in their history of laxative abuse this correlation between idiopathic edema and eating may occur. However, it is known that tolerance to disorders after surveying university students with the effects of stimulant laxatives does occur. Larger computerized self-report questionnaire. Women doses are then required to achieve the same desired with symptoms of ‘‘idiopathic edema’’ had a 70% effect. Therefore, more exposure occurs that increased risk of having abnormal eating behaviors increases the risk for the cathartic colon syn- compared with women without symptoms of 30 drome. edema. Therefore, it should no longer be sufficient A history of prolonged laxative use may also pro- to relegate this distressing complaint of normal duce a more innocuous reflex constipation. This cyclic edema to a specific diagnostic category and constipation can be bothersome during withdrawal then to treat with diuretics rather than searching from laxatives, making it difficult to terminate laxa- for the likely etiology, and advising conservative tive abuse, but it is usually transient. Of note, many treatment with salt restriction, leg elevation, and patients who abuse laxatives also engage in other patience (Fig. 1). 31 purging methods including enemas. Rectal pro- The spectrum of medical complications associ- lapse is a very disturbing and rare complication of ated with abuse of diuretics primarily involves re- 32 laxative abuse. Through laboratory testing there sultant abnormalities of fluid and . are ways, utilizing thin layer chromatography, to Indeed, laxative abuse, self-induced vomiting, and 33 test for surreptitious laxative abuse. diuretic abuse all cause fluid and electrolyte abnor- malities, although the specific spectrum of said abnormalities is somewhat unique to each of the three purging modes.36 (Table 1) The most com- Diuretic Abuse mon electrolyte abnormalities seen in patients with bulimia nervosa who purge via self-induced vomit- Diuretics are less frequently used by patients with ing or diuretic abuse are , hypochlore- bulimia nervosa than are laxatives. They too are mia, and an elevated serum bicarbonate level or ineffective at preventing . The tempo- metabolic .37,38 A study of 945 patients rary loss of 2–4 pounds with consequent dehydra- who met criteria for eating disorders found that 43 tion from the is followed by reflex fluid patients (4.6%) were hypokalemic. The majority of retention, weight gain, and the impulse to continue the hypokalemic population was found to have

98 International Journal of Eating Disorders 44:2 95–104 2011 MEDICAL COMPLICATIONS OF BULIMIA

TABLE 1. Electrolyte levels usually associated with purging Serum Levels Urine Levels Method of purging Chloride Bicarbonate pH Sodium

Vomiting Increased, decreased Decreased Decreased Increased Increased Decreased Decreased Decreased or normal Laxatives Increased or normal Decreased Increased or Decreased or Decreased or Decreased Decreased Normal or decreased increased increased decreased Diuretics Decreased or normal Decreased Decreased Increased Increased Increased Increased Increased

lower mean weight, lower , and to stimulates the -based renin-angioten- purge via self-induced vomiting, or misuse of diu- sin-aldosterone system, leading to hypokalemia retics.39 This 5% rate of hypokalemia in patients and a . Other well-documented with who self-induce vomitus or metabolic side effects of include hyper- abuse diuretics have been validated in subsequent glycemia, hyperuricemia, hyperlipidemia (mainly studies,40 although some studies have reported a triglycerides), , and hypercalcemia. 41 prevalence of up to 20%. Loop diuretics include , torsemide, Although hypokalemia is the most common elec- and ethacrynic acid. In contrast to thiazides, they trolyte abnormality seen in the bulimic population, act on the kidney in the thick ascending loop of other abnormalities include an elevated serum bi- Henle and therein inhibit the reabsorption of so- carbonate level (alkalosis), , and hy- dium. As with diuretics, the loss of sodium ponatremia. An increase in serum bicarbonate, like in the urine and reduction of edema, and decrease hypokalemia, is more likely to be seen in patients in plasma volume leads to activation of the renin- with self-induced vomiting or diuretic abuse on a angiotensin-aldosterone system and the secondary regular basis. The most severe cases of metabolic , which results in hypokalemia alkalosis, with serum bicarbonate levels greater and metabolic alkalosis. Other side effects of loop then 40 mmol/L, are almost always due to vomit- diuretics include hypomagnesemia, , ing. Acute diarrhea associated with laxative abuse and hyperuricemia. results in a hyperchloremic . Lastly, potassium-sparing diuretics include spiro- As mentioned earlier, hypokalemia occurs in nolactone, , and . Unlike thia- approximately 5% of patients with bulimia and zide or loop diuretics, this class of is may predispose them to cardiac arrhythmias. Given unique in that it causes loss of sodium and water its low sensitivity, screening for hypokalemia can- without causing a loss of potassium. Thus, the class not be recommended as a means of detecting buli- name, potassium-sparing diuretics. Accordingly, mia. However, the finding of hypokalemia in an the main potential side effects of potassium spar- otherwise healthy young woman is highly specific ing diuretics are and metabolic aci- for bulimia nervosa. Urine electrolytes may be use- dosis, the antithesis of those seen with the other ful predictors of bulimic behaviors.41,42 Also, mea- two classes of diuretics. surement of urinary potassium levels may be use- The electrolyte abnormalities seen in patients ful; a value of less than 10 mmol/L in a ‘‘spot’’ urine taking chronic diuretic therapy are described earlier. specimen usually suggests a gastrointestinal cause One additional and very important complication, of potassium loss. The patient with purely restricting pseudo-, has been increasingly anorexia nervosa is not at risk for any metabolic ab- recognized in the bulimic population.45 In 1962, normality, acid-base disturbance, or hypokalemia.43 Bartter et al.46 described two children with a syn- The three most commonly used classes of diu- drome characterized by hypokalemia, metabolic retics, available by prescription, are thiazide, loop, alkalosis, hyperaldosteronism, normal blood pres- and potassium-sparing diuretics.44 Thiazide diu- sure, and hyperplasia of the kidney’s juxtaglomeru- retics include , , lar apparatus. Subsequently, this was histologically and . The mechanism of action of thia- shown to be secondary to hyperplasia of the kidney’s zide diuretics is inhibition of sodium chloride reab- zona glomerulosa. This syndrome, named Bartter’s sorption in the distal renal tubule resulting in loss syndrome, after publication of his seminal article, 47 of sodium in the urine, and thus a decrease in has now been liked to deficient chloride channels. extracellular volume and a reduction in peripheral The same pathophysiological changes, namely edema. However, this same volume contraction hypokalemia, hypochloremia, alkalosis, and hyper-

International Journal of Eating Disorders 44:2 95–104 2011 99 MEHLER aldosteronism with hyperplasia of the juxtaglomer- of women with bulimia have improvement in ular apparatus, is seen with chronic laxative and di- symptoms during pregnancy, but an exacerbation uretic abuse as well as self-induced vomiting, and of symptoms after delivery is common.55 has been named secondary or pseudo-Bartter syn- A particularly difficult combination to effectively 48 drome. Unlike Bartter syndrome, pseudo-Bartter treat is the coexistence of bulimia nervosa and in- is characterized by lack of intrinsic pathology in the sulin dependent diabetes mellitus (type 1). renal tubules and thus normal urinary chloride Whether or not there is an increased prevalence of level. Pseudo-Bartter syndrome resolves once the bulimia among women with type 1 diabetes or offending agent or behavior has been discontinued merely an overlap of two common problems and the state of volume contraction has been remains controversial.56 Multiple studies have restored to normal. shown that 30–50% of young women with type 1 di- There is pathophysiology over activation of the abetes engage in behaviors for renin-angiotensin-aldosterone system in the weight control. Binge eating is the most common bulimic population who excessively purge. Nor- form of disordered behavior in such patients and mally, the main function of this system is to main- has been reported in up to 50% of diabetic women. tain plasma volume in the face of clinical situations Also common and more insidious is the reduction that are associated with dehydration. The juxtaglo- of dose or omission of insulin to induce an merular apparatus senses a decrease in circulating osmotic diuresis with glycosuria and . volume as a result of purging and responds by This has been termed ‘‘insulin purging.’’ Insulin secreting renin that results in increased production omission has been found in 30–40% of women with of angiotensin I and II, which stimulates the adre- type 1 diabetes and occurs not only in younger nal glands to produce aldosterone. Aldosterone women but also has been identified in diabetic acts in the distal tubule and the collecting duct to women up to age 60.57,58 reabsorb sodium in exchange for potassium and Binge eating and insulin omission have been hydrogen. The excreted hydrogen results in an clearly related to an increased risk of poor meta- increase in bicarbonate absorption thus contribut- bolic control and diabetes-related complications. ing to the overall state of metabolic alkalosis. Ab- Diabetic women who engage in these behaviors rupt cessation of any of the three common modes have been shown to have higher glycosylated he- of purging thus results in severe edema formation moglobin levels, increased episodes of hypoglyce- due to the ambient high levels of aldosterone, with mia and resulting hospitalizations for diabetic resultant avidity towards sodium reabsorption in ketoacidosis (DKA), growth retardation and puber- the absence of compensatory purging behaviors. tal delay in adolescence, and increased microvas- Therefore, with rapid rehydration along with the cular complications, particularly retinopathy. Thus, abrupt cessation of purging behaviors, patients can whereas there relative risk of women with type 1 di- become markedly edematous. This condition has abetes developing eating disorders continues to be been termed pseudo-idiopathic edema or pseudo- debated, the potential harmful effects that binge Bartter’s syndrome.49,50 eating and purging can have on a diabetic person’s Before moving onto the treatment of the afore- glucose control is universally acknowledged. mentioned litany of medical complications of buli- Disordered eating behaviors, therefore, have mia, it is worth noting a few additional miscellane- more serious consequences for women with con- ous findings. One notable absent finding, in con- comitant type 1 diabetes than for otherwise healthy trast to patient with anorexia nervosa,51 is that women. Whether such diabetic women actually are strictly normal weight patients with bulimia nerv- more likely to develop bulimia or whether or not osa do not have problems with , unless they meet the strict DSM-IV criteria for bulimia is there is a history of anorexia nervosa.52 Also, in not the salient issue. A high index of suspicion for contrast with anorexia nervosa, the complete blood disordered eating behaviors should be maintained count (CBC) is not abnormal in patients with buli- for all women with type 1 diabetes, and screening mia nervosa.53 questionnaires for the detection of covert eating However, there are some endocrine abnormal- disorders should be considered in women with ities found in patient with bulimia nervosa. poor glycemic control, multiple episodes of DKA, Although irregular menses, which fertility, or an unusually rapid progression of microvascular are common during episodes of active bulimia, the complications. future ability to conceive is not impaired in Many authors have suggested that the nature of patients who recover from bulimia.54 The majority diabetes and its management may put patients at

100 International Journal of Eating Disorders 44:2 95–104 2011 MEDICAL COMPLICATIONS OF BULIMIA risk for disordered eating behaviors. Chronic die- be safe, even when used on a long-term basis. It is tary restraint, an emphasis on food, family dynam- important to remember that these ics associated with chronic childhood illness, work best if taken on an empty stomach followed weight gain associated with tight glycemic control, by food ingestion about 30 min after taking the and the convenience of a powerful means of weight medication. It has also been demonstrated that loss (insulin omission) may all predispose patients empirical treatment with a proton-pump inhibitor with type 1 diabetes to abnormal weight-related is cost-effective compared with endoscopy-ori- behaviors. These women may, therefore, require an ented treatment of reflux disease.62 If alarm symp- individualized approach to treatment that differs toms such as dysphagia, bleeding , or per- from typical treatment for bulimia. sistent dyspepsia exist, further work up with an upper endoscopy is needed. Of note, symptom se- verity does not predict the occurrence of Barrett’s esophagus, but chronicity does.63 There is no cur- rent test other than endoscopy to establish the di- agnosis, which is indicated in patients with long- Treatment standing frequent reflux symptoms, especially in Most of the medical complications of bulimia nerv- patients older than 45 years of age. The prokimetic osa are treatable. In the absence of clinical trials, agent metaclopramide, 2.5–5.0 mg 30 min before suggested therapies for these complications are meals, may occasionally be worth considering as a largely based on clinical experience. means of decreasing the frequency of vomiting; presumably, it acts on the central ‘‘emetic center’’ Oral Complications and also by increasing the tone of the lower esoph- 64 Gentle brushing and use of a fluoride mouth ageal sphincter. rinse immediately after purging may prevent caries. It is difficult to treat laxative dependence. Sialadenosis responds to a combination of absti- Patients must be counseled about the ineffective- nence from vomiting, the application of heat, and ness of stimulant laxatives for weight loss. The res- sucking of tart candies. If the sialadenosis has not toration of bowel function is the norm after laxative begun to recede after a few weeks, oral pilocarpine use has been discontinued, but it may take several 65 (5 mg three times per day) may decompress the weeks. Ample hydration, a high-fiber , and glands.59 Because of the despair from the facial moderate amounts of exercise should be encour- swelling in patients who already have a distorted aged, as long as the patient does not have a history , a cautious trial of pilocarpine may be of excessive exercise as a means of controlling worthwhile. Pilocarpine is a parasympathetic mus- weight. If constipation persists for more than a few carinic receptor agonist that increases secretion days, a glycerin suppository or a nonstimulating from salivary glands. Total dosage of pilocarpine osmotic laxative such as lactulose may be useful; 66 for treatment of sialadenosis in these patients is stool softeners are of little value. From the outset not known, but it may be limited by adverse effects it is important to reiterate to the patient who is that include flushing, profuse sweating, bradycar- ‘‘detoxing’’ from stimulant laxatives that normal dia, and . It is presumed that the bowel function, as defined by the Rome criteria, is increased flow of saliva serves to decompress the surprisingly anything more than two bowel move- swollen glands. Noninvasive interventions are ments per week. A recent metaanalysis suggested strongly recommended because performing facial that there is little credible evidence to support surgery in patients affected by bulimia as a conse- many of the drugs that are commonly used in the quence of altered body image may represent a seri- treatment of constipation, especially when it is a 67 ous risk. Tooth sensitivity may be treated with fluo- result of chronic stimulant laxative abuse. rinated or desensitizing toothpastes.60 Pseudo-Bartter’s Syndrome Gastrointestinal Complications The leg edema, which may be associated with Reflux symptoms respond to all of the proton- abrupt cessation of laxatives and caused by pump inhibitors. In patients with reflux, treatment pseudo-Bartter’s syndrome, is treated with salt with proton pump inhibitors, such as esomepra- restriction (less than 3 g per day), elevation of the zole, is more effective for healing esophagitis and legs, and patience; loop diuretics will only exacer- improving symptoms, than are other forms of ther- bate the problem. An aldosterone antagonist, such apy such as -2 receptors antagonists such as (25–50 mg per day), may be given as ranitidine.61 Proton pump inhibitors appear to for 1–2 weeks after cessation of laxative abuse, at

International Journal of Eating Disorders 44:2 95–104 2011 101 MEHLER which point the propensity towards edema forma- ably.68 Once euvolemia has been restored, if there tion symptoms will probably have resolved. Such is ongoing frequent purging, the electrolytes should treatment is particularly worth considering if the also be monitored; long-term potassium supple- distress of having edema is thought likely to precip- mentation may be needed. itate a relapse of bulimia and laxative abuse. Thia- However, the efficacy of potassium repletion is zide diuretics in this scenario would worsen both abrogated unless there is concomitant normaliza- hypokalemia and metabolic alkalosis by continuing tion of the hypovolemic state. Once normalization to stimulate the renin-angiotensin-aldosterone sys- is achieved and the metabolic alkalosis is corrected tem. Similarly, loop diuretics would also provide a to inactivate the renin-angiotensin-aldosterone continuous stimulus for aldosterone production axis, potassium repletion can be successful. An and consequently aggravate the hypokalemia, met- additional cause of refractory potassium repletion abolic alkalosis, and edema formation after the is the presence of undetected concomitant magne- was discontinued. Accordingly, the di- sium deficiency, which may also occur as a result uretic of choice in a patient with pseudo-Bartter of diuretic abuse.69 syndrome induced-edema, related to abrupt cessa- There is an additional important point about the tion of purging behaviors, is spironolactone. treatment of hypovolemia due to either excessive Spironolactone acts by competitively inhibiting vomiting, diuretic abuse, or laxative abuse. Because the action of aldosterone in the distal tubule. As the renin-angiotensin is chemically activated in mentioned earlier, the driving mechanism for the patients who purge excessively, if these patients are findings in pseudo-Bartter’s syndrome, is activation given intravenous in the same rapid infusion of the renin-angiotensin-aldosterone system lead- manner as typically given to someone presenting to ing to a state of hyperaldosteronism. This overpro- an emergency room seeking treatment for acute duction of aldosterone may take 2–3 weeks to dehydration, they are at risk for massive edema for- resolve once treatment is initiated. Spironolactone mation after just a few liters of saline due to their provides relevant treatment on three levels: it halts salt-avid state from the pseudo-Bartter syndrome. the action of aldosterone while the renin-angioten- Therefore, it is important to alert the emergency sin-aldosterone system is still stimulated, it pro- room, when a patient with bulimia is being referred vides mild diuresis, and it aids in the correction in for their dehydration, to administer intravenous sa- its role of a potassium-sparing diuretic. line slowly, at a rate of perhaps 50–100 mL/h to avert The main therapies that may be necessary to the possibility of severe edema formation and a treat diuretic abuse include the aforementioned future reticency to revisit an emergency department ones needed to negate edema formation which can if the need arises because of a fear of a recurrence of similarly be seen with abrupt cessation of diuretic the edema and the consternation inherent thereof. abuse. Since the pathophysiology of edema forma- In summary, because the patient with bulimia tion after cessation of diuretic abuse is exactly the nervosa may go unrecognized in healthcare set- same as with abrupt cessation of excessive self- tings and because their symptoms are relatively induced vomiting or laxative abuse, the treatments longstanding, it is important to be vigilant about are also similar. the detection of bulimia in young patients with the aforementioned medical complications.70 Most of the medical complications of bulimia nervosa are Electrolyte Complications readily treatable, but do require familiarity with the The treatment of marked hypokalemic metabolic therapeutic interventions, to maximize their effi- alkalosis requires volume repletion (with intrave- cacy and help facilitate recovery. nous normal saline), to turn off the renin-angioten- sin system. Normalization of volume status is needed for effective potassium repletion. A general principle is that every decrease of 1 mmol per liter in the serum potassium level represents a loss of References 150 mmol in the total body potassium level. Oral 1. van Hoeken D, Veling W, Sinke S, Mitchell JE, Hoek HW. The va- potassium chloride is generally preferred for potas- lidity and utility of subtyping bulimia nervosa. Int J Eat Disord sium repletion. Typically, potassium is adminis- 2009;42:595–602. tered in a split dose of 40–80 mEq per day for a few 2. Striegel-Moore RH, Debar L, Wilson GT, Dickerson J, Rosselli F, Perrin N, et al. Health service use in eating disorders. Psychol days. The potassium level should initially be moni- Med 2008;38:1465–1474. tored closely during replacement therapy because 3. Keski-Rahkonen A, Hoek HW, Linna MS, Raevuori A, Sihvola E, the required amount cannot be calculated reli- Bulik CM, et al. Incidence and outcomes of bulimia nervosa:

102 International Journal of Eating Disorders 44:2 95–104 2011 MEDICAL COMPLICATIONS OF BULIMIA

A nationwide population-based study. Psychol Med 28. Xing JH, Soffer EE. Adverse effects of laxatives. Dis Colon Rectum 2009;39:823–831. 2001;44:1201–1209. 4. Ximenes R, Couto G, Sougey E. Eating disorders in adolescents 29. Mehler PS. Constipation: Diagnosis and treatment in eating dis- and their repercussion in oral health. Int J Eat Disord orders. Eating Disord 1997;5:41–45. 2010;43:59–64. 30. Joo JS, Ehrenpreis ED, Gonzales L, Kaye M, Breno S, Wexner SD, 5. DeBate RD, Tedesco LA, Kerschbaum WE. Knowledge of oral et al. Alterations in colonic anatomy induced by chronic stimu- and physical manifestation of anorexia and bulimia nervosa lant laxatives: The cathartic colon revisited. J Clin Gastroenterol among dentists and dental hygienists. J Dent Educ 2005;69: 1998;26:283–286. 346–354. 31. Bryant-Waugh R, Turner H, East P, Gamble C, Mehta R. Misuse 6. Studen-Pavlovich D, Elliott MA. Eating disorder in women’s oral of laxatives among adult outpatients with eating disorders. health. Dent Clin N Am 2001;45:491–511. Prevalence and profiles. Int J Eat Disord 2006;39:404–409. 7. Altschuler BD, Dechow PC, Waller DA, Hardy BW. An investiga- 32. Malik M, Stratton J, Sweeney WB. Rectal prolapse associated tion of oral pathologies occurring in bulimia nervosa. Int J Eat with bulimia nervosa: Report of seven cases. Dis Colon Rectum Disord 1990;9:191–199. 1997;40:1382–1385. 8. Christensen GJ. Oral care for patients with bulimia nervosa. 33. Shelton JH, Santa Ana CA, Thompson DR, Emmett M, Fordtran J Am Dent Assoc 2002;133:1689–1691. JS. Factitious diarrhea induced by stimulant laxatives; accuracy 9. Touyz SW, Liew VP, Tseng P, Frisken K, Williams H, Beumont PJ. of diagnosis by a clinical reference laboratory using thin layer Oral and dental complications in eating disorders. Int J Eat Dis- chromatography. Clin Chem 2007;53:85–90. ord 1993;14:341–347. 34. Berezeller PH. Idiopathic edema. Hosp Pract 1994;29:115–118. 10. Little JW. Eating disorders: Dental implications. Oral Surg Oral 35. Bihun JA, McSherry J, Marciano D. Idiopathic edema in eating Med Oral Pathol Oral Radiol Endod 2002;93:138–143. disorders: Evidence of an association. Int J Eat Disord 1993;14: 11. de Moor RJ. Eating disorder-induced dental complications. 197–200. J Oral Rehabil 2004;31:725–732. 36. Mehler PS. Clinical practice. Bulimia nervosa. N Engl J Med 12. Brewer TL. The necessity for dental awareness of the presenting 2003;349:875–881. of bulimia nervosa. J Okla Dent Assoc 37. Crow SJ, Salisbury JJ, Crosby RD, Mitchell. Serum electrolytes as 1987;78:24–27. markers of vomiting in bulimia nervosa. Int J Eat Disord 13. Robb ND, Smith BG. Anorexia and bulimia nervosa (the eating 1997;21:95–98. disorders): Conditions of interest to the dental practitioner. 38. Wolfe BE, Metzger ED, Levine JM, Jimerson DC. Laboratory J Dent 1996;24:7–16. screening for electrolyte abnormalities and anemia in bulimia 14. Mandel L, Abai S. Diagnosing bulimia nervosa with parotid nervosa: A controlled study. Int J Eat Disord 2001;30:288–293. gland swelling. J Am Dent Assoc 2004;135:613–616. 39. Greenfeld D, Mickey D, Quinlan DM, Roloff P. Hypokalemia in 15. Mignogna MD, Fedele S, Russo L. Anorexia/bulimia—Related outpatients with eating disorders. Am J 1995;152: sialadenosis of palatal minor salivary glands. J Oral Pathol Med 60–63. 2004;33:441–442. 40. Wolfe BE, Metzger ED, Levine JM, Jimerson DC. Laboratory 16. Park KK, Tung RC, de Luzuriaga AR. Painful parotid hypertrophy screening for electrolyte abnormalities in bulimia nervosa. Int J with bulimia: A report of medical management. J Drugs Der- Eat Disord 2001;30:288–293. matol 2009;8:577–579. 41. Miller KK, Grinspoon SK, Ciampa J, Hier J, Herzog D, Klibanski 17. Coleman H, Altini M, Nayler S, Richards A. Sialadenosis: A pre- A. Medical findings in outpatients with anorexia nervosa. Arch senting sign in bulimia. Head Neck 1998;20:758–762. Intern Med 2005;165:561–566. 18. Mendell DA, Logemann JA. Bulimia and swallowing; cause for 42. Crow SJ, Rosenberg ME, Mitchell JE, Thuras P. Urine electrolytes concern. Int J Eat Disord 2001;30:252–258. as markers of bulimia nervosa. Int J Eat Disord 2001;30:279– 19. Nickl NJ, Brazer SR, Rockwell K, Smith JW. Patterns of esopha- 287. geal mortality in patients with bulimia. Am J Gastroenterol 43. Mehler PS. Diagnosis and care of patients with anorexia nerv- 1996;91:2544–2547. osa. Ann Intern Med 2001;134:1048–1059. 20. Mehler PS, Weiner KL. Frequently asked medical questions 44. Ernst ME, Moser M. Use of diuretics in patients with hyperten- about eating disorder patients. Eating Disord 1994;2:22–26. sion. N Engl J Med 2009;361:2153–2164. 21. Mitchell JE, Seim HC, Colon P, Pomeroy C. Medical complica- 45. Mitchell JE, Pomeroy C, Seppala M, Huber M. Pseudo-Bartter’s tions and medical management of bulimia. Ann Intern Med syndrome, diuretic abuse, idiopathic edema, and eating disor- 1987;107:71–76. ders. Int J Eat Disord 1988;7:225–237. 22. Strumia R. Dermatologic signs in patients with eating disorders. 46. Bartter FC, Pronove P, Gill JR Jr, MacCardle RC. Hyperplasia of Am J Clin Dermatol 2005;6:165–173. the juxtaglomerular complex with hyperaldosteronism and 23. Ho PC, Dweik R, Cohen MC. Rapidly reversible cardiomyopathy hypokalemic alkalosis. A new syndrome. Am J Med 1962;33: associated with chronic ipecac ingestion. Clin Cardiol 811–828. 1998;21:780–783. 47. Proesmans W. Threading through the mizmaze of Bartter syn- 24. Steffen KJ, Mitchell JE, Roerig JL, Lancaster KL. The eating disor- drome. Pediatr Nephrol 2006;21:896–902. ders cabinet revisited: A clinician’s guide to ipecac 48. Amirlak I, Dawson KP. Bartter syndrome: An overview. QJM and laxatives. Int J Eat Disord 2007;40:360–368. 2000;93:207–215. 25. Turner J, Batik M, Palmer LJ, Forbes P, McDermott BM. Detec- 49. Meyers AM, Feldman C, Sonnekus MR. Chronic laxative abusers tion and importance of laxative use in adolescents with ano- with pseudo-idiopathic edema and autonomous pseudo-Bart- rexia nervosa. J Am Acad Child Adolesc Psychiatry 2000;39:378– ters syndrome. S Afr Med J 1990;78:631–636. 385. 50. Zeier MG. Excessive fluid gain in a chronic laxative abuser: 26. Ramkumar D, Rao SS. Efficacy and safety of traditional medical Pseudo-idiopathic edema. Nephrol Dial Transplant 2002;17: therapies for chronic constipation: A systematic review. Am J 161–162. Gastroenterol 2005;100:936–971. 51. Mehler PS, MacKenzie TD. Treatment of osteopenia and osteo- 27. Ahmed S, Gunaratnam NT. Melanosis coli. N Engl J Med porosis in anorexia nervosa. A systematic review of the litera- 2003;349:1349. ture. Int J Eat Disord 2009;42:195–201.

International Journal of Eating Disorders 44:2 95–104 2011 103 MEHLER

52. Zipfel S, Seibel MJ, Lowe B, Beaumont PJ, Kaperk C, Herzog W. 61. Pinxteren B, Numans M, Lau J, de Wit N, Hungin APS, Bonis Osteoporosis in eating disorders; a follow up study of patients PAL. Short-term treatment of gastroesophageal disease. J Gen with anorexia nervosa and bulimia. J Clin Endocrinol Metab Intern Med 2003;18:755–763. 2001;86:5227–5233. 62. Giamini EG, Zentilin P, Dulbecco P, Bigneri S, Scarlata P, Savar- 53. Cleary BS, Gaudiani JL, Mehler PS. Interpreting the complete ino V. Management strategy for patient with reflux disease: A blood count in anorexia nervosa. Eat Disord: J Treatment Prev comparison between empirical treatment and endoscopy-ori- 2010;18:37–41. ented treatment. Am J Gastroenterol 2008;103:267–275. 54. Crow SJ, Thomas P, Keel PK, Mitchell JE. Long-term menstrual 63. Spechler SJ. Barrett’s esophagus. N Engl J Med 2002;346:836–842. and reproductive functions in patients with bulimia nervosa. 64. Wood GJ, Shega JW, Lynch B, vonRoenin JH. Management of in- Am J Psychiatry 2002;159:1048–1050. tractable and vomiting. JAMA 2007;298:1196–1207. 55. Conrad R, Schablewski J, Schilling G, Liedke R. Worsening of 65. Colton P, Woodside DB, Kaplan AS. Laxative withdrawal in eat- symptoms of bulimia nervosa during pregnancy. Psychoso- ing disorders: Treatment protocol and 3 to 20 month follow matics 2003;44:76–78. up. Int J Eat Disord 1997;25:311–317. 56. Rodin GM, Daneman D. Eating disorders and IDDM: A problem- 66. Tramonte SM, Brand MR, Mulrow CD, Amato MG, OKeefe ME, atic association. Diabetes Care 1992;15:1402–1407. Ramirez G. The treatment of chronic constipation in adults. A 57. Polonsky WH, Anderson BJ, Lohrer PA, Aponte JE, Jacobson AM, systematic review. J Gen Intern Med 1997;12:15–24. Cole CF. Insulin omission in women with IDDM. Diabetes Care 67. Jones MP, Talley NJ, Nayts G. Lack of objective evidence of effi- 1994;17:1178. cacy of laxatives in chronic constipation. Dig Dis Sci 58. Rydal AC, Rodin GM, Olmsted MP, Devenyi RG, Daneman D. Dis- 2002;47:2222–2230. ordered eating behavior and microvascular complications in 68. Gennari FJ. Hypokalemia. N Engl J Med 1998;339:451–458. young women with insulin-dependent diabetes mellitus. N 69. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. Engl J Med 1997;336:1849. A consequence of deficiency. Arch Intern Med 59. Mehler PS, Wallace JA. Sialadenosis in bulimia; a new treat- 1992;152:40–45. ment. Arch Otolaryngol Head Neck Surg 1993;119:787–788. 70. Keski-Rahkomen A, Hoek HW, Linna MS, Raevuori A, Sihvola E, 60. Trowbridge HO, Silver DR. A review of current approaches to in- Bulik CM, et al. Incidence and outcome of bulimia nervosa: A office management of tooth hypersensitivity. Dent Clin North nationwide population-based study. Psychol Med 2009;39:823– Am 1990;34:561–581. 831.

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