According to the National Eating Disorders Association, the diagnostic criteria for AN, adapted from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are described as follows.
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES: ANOREXIA NERVOSA
Restriction of energy intake relative to requirements leading to low body weight in the context of age, sex, physical health, and developmental trajectory.
Strong fear of gaining weight or becoming fat, even though underweight.
Disturbance in the way one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or denial of the seriousness of current low body weight.
There are two major types of AN. In the restricting type, patients do not regularly engage in binge eating or purging. In the binge-purge type, AN is combined with binge eating or purging behavior, or both. Distinguishing between the two is important as they carry different implications for prognosis and treatment. Although patients may not demonstrate all features of AN, they may still exhibit the deleterious symptoms associated with AN. A third form—atypical AN—exists as well, accounting for 18% of all ED diagnoses in one study. These individuals demonstrate typical AN behavior but are within or above normal weight.
Clinicians should recognize the early symptoms and signs of AN because early intervention may prevent the full-blown syndrome from developing. Patients may show some typical AN behaviors, such as reduction in dietary fat and intense concern with body image, even before weight loss or amenorrhea occurs.
Making the diagnosis of AN can be challenging because adolescents may try to conceal their illness. Assessing the patient’s body image is essential to determining the diagnosis. Table 6–1 lists screening questions that help tease out a teenager’s perceptions of body image. Other diagnostic screening tools (eg, EDs Inventory) assess a range of eating and dieting behaviors. Parental observations are critical in determining whether a patient has expressed dissatisfaction over body habitus and which weight loss techniques the child has used. If the teenager is unwilling to share his or her concerns about body image, the clinician may find clues to the diagnosis by carefully considering other presenting symptoms or signs. Weight loss from a baseline of normal body weight is an obvious red flag for the presence of an ED. Additionally, AN should be considered in any girl with secondary amenorrhea who has lost weight.
Table 6–1.Screening questions to help diagnose anorexia and bulimia nervosa. ||Download (.pdf) Table 6–1. Screening questions to help diagnose anorexia and bulimia nervosa.
How do you feel about your body?
Are there parts of your body you might change?
When you look at yourself in the mirror, do you see yourself as overweight, underweight, or satisfactory?
If overweight, how much do you want to weigh?
If your weight is satisfactory, has there been a time when you were worried about being overweight?
If overweight (underweight), what would you change?
Have you ever been on a diet?
What have you done to help yourself lose weight?
Do you count calories or fat grams?
Do you keep your intake to a certain number of calories?
Have you ever used nutritional supplements, diet pills, or laxatives to help you lose weight?
Have you ever made yourself vomit to get rid of food or lose weight?
Physical symptoms and signs are usually secondary to weight loss and proportional to the degree of malnutrition. The body effectively goes into hibernation, becoming functionally hypothyroid (euthyroid sick) to save energy. Body temperature decreases, and patients report being cold. Bradycardia develops, especially in the supine position. Dizziness, light-headedness, and syncope may occur as a result of orthostasis and hypotension secondary to impaired cardiac function. Left ventricular mass is decreased, stroke volume is compromised, and peripheral resistance is increased, contributing to left ventricular systolic dysfunction. Patients can develop prolonged QTc syndrome and increased QT dispersion (irregular QT intervals), putting them at risk for cardiac arrhythmias. Peripheral circulation is reduced. Hands and feet may be blue and cool. Hair thins, nails become brittle, and skin becomes dry. Lanugo develops as a primitive response to starvation. The gastrointestinal (GI) tract may be affected; inability to take in normal quantities of food, early satiety, and gastroesophageal reflux can develop as the body adapts to reduced intake. The normal gastrocolic reflex may be lost due to lack of stimulation by food, causing bloating and constipation. Delayed gastric emptying may develop. Nutritional rehabilitation improves gastric emptying and dyspeptic symptoms in AN restricting type, but not in those who vomit. Neurologically, patients may experience decreased cognition, inability to concentrate, increased irritability, and depression, which may be related to structural brain changes and decreased cerebral blood flow.
Determining BMI is critical for assessing degree of malnutrition. A gown-only weight after urination is the most accurate way to assess weight. Patients tend to wear bulky clothes and may hide weights in their pockets or drink excessive fluid (water-loading) to trick the practitioner. BMI below the 25th percentile indicates risk for malnutrition and below 5th percentile indicates significant malnutrition. Median body weight (MBW) should be calculated as it serves both as the denominator to determine what percent weight an individual is and to provide a general goal weight during recovery. MBW for height is calculated by using the 50th percentile of BMI for age.
A combination of malnutrition and stress causes hypothalamic hypogonadism. The hypothalamic-pituitary-gonadal axis shuts down as the body struggles to survive, directing finite energy resources to vital functions. This may be mediated by the effect of low serum leptin levels on the hypothalamic-pituitary axis. Pubertal development and skeletal growth may be interrupted, and adolescents may experience decreased libido.
Amenorrhea will continue to be an important clinical sign that the body is malnourished. Amenorrhea occurs for two reasons. The hypothalamic-pituitary-ovarian axis shuts down under stress, causing hypothalamic amenorrhea. In addition, adipose tissue is needed to convert estrogen to its activated form. When weight loss is significant, there is not enough substrate to activate estrogen. Resumption of menses occurs only when both body weight and body fat increase.
Approximately, 73% of postmenarchal girls resume menstruating if they reach 90% of MBW. An adolescent female needs about 17% body fat to restart menses and 22% body fat to initiate menses if she has primary amenorrhea. Some evidence suggests that target weight gain for return of menses is approximately 1 kg higher than the weight at which menses ceased.
All organ systems may suffer some degree of damage in the anorexic patient, related to both severity and duration of illness (Table 6–2). Initial screening should include complete blood count with differential; serum levels of electrolytes, blood urea nitrogen, creatinine, phosphorus, calcium, magnesium, and thyroid-stimulating hormone; liver function tests; and urinalysis. Increase in lipids, likely due to abnormal liver function, is seen in 18% of those with AN, with subsequent return to normal once weight is restored. An electrocardiogram (ECG) should be performed, because significant ECG abnormalities may be present, most importantly prolonged QTc syndrome. Bone densitometry should be done if illness persists for 6 months, as patients begin to accumulate risk for osteoporosis.
Table 6–2.Laboratory findings: anorexia nervosa. ||Download (.pdf) Table 6–2. Laboratory findings: anorexia nervosa.
Increased blood urea nitrogen and creatinine secondary to renal insufficiency
Decreased white blood cells, platelets, and less commonly red blood cells and hematocrit secondary to bone marrow suppression or fat atrophy of the bone marrow
Increased AST and ALT secondary to malnutrition
Increased cholesterol, thought to be related to altered fatty acid metabolism
Decreased alkaline phosphatase secondary to zinc deficiency
Low- to low-normal thyroid-stimulating hormone and thyroxine
Decreased follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone secondary to shutdown of hypothalamic pituitary-gonadal axis
Abnormal electrolytes related to hydration status
Decreased insulin-like growth factor
Decreased urine specific gravity in cases of intentional water intoxication
If the diagnosis is unclear (ie, the patient has lost a significant amount of weight but does not have typical body image distortion or fat phobia), the clinician must consider the differential diagnosis for weight loss in adolescents. This includes inflammatory bowel disease, diabetes, hyperthyroidism, malignancy, depression, and chronic infectious disease such as human immunodeficiency virus (HIV). Less common diagnoses include adrenal insufficiency and malabsorption syndromes such as celiac disease. The history and physical examination should direct specific laboratory and radiologic evaluation.
Table 6–3.Complications of anorexia and bulimia nervosa, by mechanism. ||Download (.pdf) Table 6–3. Complications of anorexia and bulimia nervosa, by mechanism.
Postural hypotension (WL/MN, SIV, LX)
Arrhythmia, sudden death (WL/MN, SIV, LX)
Congestive heart failure (during refeeding) (WL/MN)
Pericardial effusion (WL/MN)
Mitral valve prolapse (WL/MN)
ECG abnormalities (prolonged QT, low voltage, T-wave abnormalities, conduction defects) (WL/MN)
↓ LH, FSH (WL/MN)
↓ T3, ↑ rT3, ↓ T4, TSH (WL/MN)
Irregular menses (WL/MN, B/P)
Growth retardation (WL/MN)
Delayed puberty (WL/MN)
Decreased libido (WL/MN)
Dental erosion (SIV)
Parotid swelling (SIV)
Esophagitis, esophageal tears (SIV)
Delayed gastric emptying (WL/MN, SIV)
Gastric dilation (rarely rupture) (SIV)
Constipation (WL/MN, LXA)
Superior mesenteric artery syndrome (WL/MN)
↑ Liver function tests (fatty infiltration of the liver) (WL/MN)
Dehydration (WL/MN, SIV, LXA, DU)
Hypokalemia (SIV, LXA, DU)
Hyponatremia (SIV, LXA, DU, WL/MN)
Hypocalcemia (WL/MN, SIV)
Cortical atrophy-white and gray matter (WL/MN)
Peripheral neuropathy (WL/MN)
Seizures (WL/MN, SIV, LXA)
Thermoregulatory abnormalities (WL/MN)
↓ REM and slow-wave sleep (All)
A. Short-Term Complications
Patients may have difficulty tolerating even modest quantities of food when intake increases; this usually resolves after the patients adjust to larger meals. Gastric emptying is poor. Pancreatic and biliary secretion is diminished.
2. Superior mesenteric artery syndrome
As patients become malnourished, the fat pad between the superior mesenteric artery and the duodenum shrinks and compression of the transverse duodenum may cause obstruction and vomiting, especially with solid foods. The upper GI series shows to-and-fro movement of barium in the descending and transverse duodenum proximal to the obstruction. Treatment involves a liquid diet or nasoduodenal feedings until restoration of the fat pad has occurred, coincident with weight gain.
Patients may be very constipated. Two mechanisms contribute—loss of the gastrocolic reflex and loss of colonic muscle tone. Typically stool softeners are not effective because the colon has decreased peristaltic amplitude. Agents that induce peristalsis, such as bisacodyl, as well as osmotic agents, such as polyethylene glycol-electrolyte solution (MiraLax), are helpful. Constipation can persist for up to 6–8 weeks after refeeding. Occasionally enemas are required.
This syndrome is described in the Treatment section.
The degree of malnutrition correlates with increasing prevalence of pericardial effusion. One study demonstrated that 22% of those with AN had silent pericardial effusions, with 88% of effusions resolving after weight restoration.
B. Long-Term Complications
Approximately 50% of females with AN have reduced bone mass at one or more sites. The lumbar spine has the most rapid turnover and is the area likely to be affected first. Teenagers are particularly at risk as they accrue 40% of their bone mineral during adolescence. Low body weight is most predictive of bone loss. The causes of osteopenia and osteoporosis are multiple. Estrogen and testosterone are essential to potentiate bone development. Bone minerals begin to resorb without estrogen. Elevated cortisol levels and decreased insulin-like growth factor-1 also contribute to bone resorption. Amenorrhea is highly correlated with osteoporosis. Studies show that as few as 6 months of amenorrhea is associated with osteopenia or osteoporosis. Males have similar bone loss related to their degree of malnutrition, likely due to decreased testosterone and elevated cortisol.
The most effective treatment for bone loss in girls with AN has been regaining sufficient weight and body fat to restart the menstrual cycle. Studies do not support the use of hormone replacement therapy delivered orally to improve bone recovery; however, one randomized controlled trial demonstrated that physiologic doses of estrogen, delivered transdermally, over 18 months did improve bone density. Clinicians may consider transdermal estrogen treatment if patients are recalcitrant to intervention and do not restore weight in a timely manner. Bisphosphonates show moderate positive effectiveness for adults with AN, but not for adolescents. Use of dehydroepiandrosterone in combination with oral contraceptive pills is shown to maintain bone mineral density in adolescents with AN compared to controls, though this treatment approach has not been adopted as standard of care.
As malnutrition becomes pronounced, brain tissue—both white and gray matter—is lost, with a compensatory increase in cerebrospinal fluid in the sulci and ventricles. Follow-up studies of weight-recovered anorexic patients show a persistent loss of gray matter, although white matter returns to normal. Functionally, there does not seem to be a direct relationship between cognition and brain tissue loss, although studies have shown a decrease in cognitive ability and decreased cerebral blood flow in very malnourished patients. Making patients and family aware that brain tissue can be lost may improve their perception of the seriousness of this disorder.
3. Effects on future children
This area has just recently been studied. Findings suggest that there may be feeding issues for infants who are born to mothers who have a history of either AN or BN. Infants born to mothers with a history of AN have more feeding difficulties at 0 and 6 months and tend to be lower weight (30th percentile on average). Infants born to mothers with current or past BN are more likely to be overweight and have faster growth rates than controls. Pediatricians should ascertain an ED history from mothers of patients who are having feeding issues.
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Patients with EDs are at a higher risk of death than the general population and those with AN have the highest risk of dying among those with EDs. Meta-analysis estimates the standardized mortality ratio associated with AN to be 5.9. Death in anorexic patients is due to suicide, abnormal electrolytes, and cardiac arrhythmias.
Factors that determine treatment interventions are severity of illness, duration of illness, specific manifestations of disease, previous treatment approaches and outcomes, program availability, financial resources, and insurance coverage. Treatment options include outpatient management, day treatment hospitalization, inpatient medical or psychiatric hospitalization, and residential treatment. The key to determining level of intervention is the degree of malnutrition, the rapidity of weight loss, the degree of medical compromise, and the presence of life-threatening electrolyte abnormalities. No absolute criteria determine level of intervention. The practitioner must examine the degree of medical compromise and consider immediate risks and the potential for an individual to reverse the situation on his or her own. Treatment is costly. Many patients do not have insurance benefits that adequately cover the cost of treatment, leaving parents and practitioners with profound dilemmas as to how to best provide treatment in the face of financial constraints. Legally, however, EDs are now recognized as a parity mental health diagnosis similar to the other biologically based mental health illnesses in many states, which has increased the ease of obtaining insurance coverage.
A multidisciplinary approach is most effective and should include medical monitoring, nutrition therapy, and individual and family psychotherapy by experienced practitioners. Family therapy is an important means of helping families understand the development of the disease and addressing issues that may be barriers to recovery. Both types of psychotherapy are encouraged in most treatment programs, and recovery without psychotherapy is unusual. The average length of psychotherapy is roughly 6–9 months, although some individuals continue therapy for extended periods. Adjunctive modalities include art and horticulture therapy, therapeutic recreation, and massage therapy.
Manualized family therapy, developed in Britain by Maudsley and adapted by Lock and LeGrange, has shifted the therapeutic approach to adolescents with AN. Traditional therapy allowed the adolescent to control his or her eating and the parents to remain uninvolved with the food portion of recovery. The manualized approach gives power and control back to parents.
Treatment is prescribed for 20 weekly sessions. The first 10 weeks are devoted to empowering parents, putting them in control of their child’s nutrition and exercise. Parents are educated about the dangers of malnutrition and are instructed to supervise each meal. The next phase, sessions 11–16, returns control over eating to the adolescent once he or she accepts the demands of the parents. The last phase of treatment, sessions 17–20, occurs when the patient is maintaining a healthy weight and shifts the focus away from the ED, examining instead the impact that the ED has had on establishing a healthy adolescent identity. This approach is reported to result in good or intermediate outcomes in 90% of treated adolescents.
Careful instruction in nutrition helps the teenager and family dispel misconceptions about nutrition, identify realistic nutritional goals, and normalize eating. Initially, nutrition education may be the most important intervention as the teenager slowly works through his or her fears of fat-containing foods and weight gain. The teenager begins to trust the nutrition therapist and restore body weight, eventually eating in a well-balanced, healthy manner.
Table 6–4 lists the criteria for hospital admission generally used in the medical community. It is usually quite difficult for a patient who is losing weight rapidly (> 2 lb/wk) to reverse the weight loss because the body is in a catabolic state.
Table 6–4.Criteria for hospitalization for eating disordered patients. ||Download (.pdf) Table 6–4. Criteria for hospitalization for eating disordered patients.
One or more of the following justify hospitalization:
Body weight: < 75% median body weight.
Electrolyte disturbance (hypokalemia, hyponatremia, hypophosphatemia)
ECG abnormalities (prolonged QTC, severe bradycardia)
Supine heart rate < 45 beats/min
Symptomatic hypotension or syncope
Failure of outpatient management
Acute food refusal
Uncontrolled bingeing and purging
Acute medical complications of malnutrition (syncope, seizures, cardiac failure, pancreatitis)
Comorbid psychiatric or medical condition that prohibits or limits appropriate outpatient treatment (severe depression, suicidal ideation, obsessive-compulsive disorder, type 1 diabetes)
Goals of hospitalization include arresting weight loss and stabilizing hemodynamics. Nutrition is the most vital inpatient medicine. Clinicians can safely begin with a meal plan containing approximately 250 kcal more than the patient has been routinely eating, which can usually be accomplished orally. Studies suggest that meal plans can begin with as high as 1750 kcal regardless of baseline intake. Meal plans should be well balanced with appropriate proportions of carbohydrate, protein, and fat. Oral meals are usually tolerated, although it is important to be supervised by medical staff. If the patient resists, nasogastric or intravenous alimentation can be used. Aside from caloric needs, the clinician needs to consider the patient’s hydration and include the appropriate amount of fluid with the meal plan. Dehydration should be corrected slowly. The oral route is usually adequate. Aggressive intravenous fluid administration should be avoided because left ventricular mass is compromised and a rapid increase in volume may not be tolerated. Regulating fluid intake is important, because water intoxication can contribute to abnormal electrolytes and falsified weights.
During the initial introduction of food, the clinician should monitor the patient for refeeding syndrome, a phenomenon that occurs if caloric intake is increased too rapidly. Signs of refeeding syndrome are decreased serum phosphorus (as the body resumes synthesis of adenosine triphosphate), decreased serum potassium (as increased insulin causes K+ to shift from extracellular fluid into K+-depleted cells), and, rarely, edema related to fluid shifts or congestive heart failure.
Although specific guidelines do not exist, many practitioners begin phosphorus supplementation if patients are severely malnourished (< 70% MBW) or their intake has been consistently less than 500 kcal/day.
Caloric intake can be increased 250 kcal/day as long as refeeding syndrome does not occur. Weight goals vary depending on programmatic approach. Typically, intake is adjusted to reach a goal of 0.1–0.25 kg/day weight gain.
Overnight monitoring for bradycardia is helpful in assessing degree of metabolic compromise. Usually the more rapid and severe the weight loss, the worse the bradycardia. Improving bradycardia correlates with weight recovery. Orthostatic hypotension is most severe around hospital day 4, improving steadily and correcting by the third week of nutritional rehabilitation. An ECG should be obtained because the patient is at risk for prolonged QTc syndrome and junctional arrhythmias related to the severity of bradycardia.
It usually takes 2–3 weeks to reach the initial goals of hospitalization—steady weight gain, toleration of oral diet without signs of refeeding syndrome, corrected bradycardia (heart rate > 45 beats/min for three consecutive nights), and correction of orthostasis. Specific weight criteria are used by many programs when considering discharge. This depends partly on admission weight. Ideally a patient gains at least 5% of his or her MBW. Some programs set discharge at 80%, 85%, or 90% MBW. Patient outcomes are improved with discharge at a higher body weight. Some evidence exists that patients do better if discharged at 95% MBW. In many practitioners’ experience, relapse rates are high if patients are discharged at less than 75% MBW.
Practitioners frequently use psychotropic medications for treatment of AN, despite the lack of evidence supporting efficacy. Several open-label trials suggest that atypical antipsychotics (risperidone, olanzapine, quetiapine) may be helpful. One review found that olanzapine (2.5–15 mg/day) was associated with improved body weight, decreased delusional thinking, improvement in body image, and decreased agitation and premeal anxiety. However, a randomized controlled trial did not show any difference in outcomes between risperidone and placebo.
SSRIs repeatedly have been shown to not be helpful in the initial therapy of AN. A recent study showed that use of SSRIs may decrease bone mineral density when used in malnourished patients. However, once the patient has achieved approximately 85% MBW, SSRIs (fluoxetine, citalopram, or sertraline) may help prevent relapse.
Zinc deficiency is common in AN, and several studies support its use as a supplement during the initial phases of treatment. Because zinc deficiency adversely affects neurotransmitters, administering zinc helps restore neurotransmitter action to baseline. Additionally, zinc may restore appetite and improve depressive mood. Zinc should be administered for approximately 2 months from the beginning of therapy, with at least 14 mg of elemental zinc daily.
Because of global nutritional deficits, a multivitamin with iron is also recommended daily. Symptomatic treatment for constipation and reflux should be used appropriately until symptoms resolve.
Not all patients with AN require inpatient treatment, especially if parents and clinicians recognize the warning signs early. These patients can receive treatment as outpatients, employing the same multidisciplinary team approach. Manualized family-based treatment is ideal for the outpatient setting if a trained therapist is available. Appropriate nutrition counseling is vital in guiding a patient and family through the initial stages of recovery. As the nutrition therapist is working at increasing the patient’s caloric intake, a practitioner needs to monitor the patient’s weight and vital signs. Often, activity level needs to be decreased to help reverse the catabolic state. A reasonable weight gain goal may be 0.2–0.5 kg/wk. If weight loss persists, careful monitoring of vital signs, including supine heart rate, is important in determining whether an increased level of care is needed. Concomitantly, the patient should be referred to a psychotherapist and, if indicated, assessed by a psychiatrist.
E. Treatment Goals and Outcomes
Goals of treatment include reaching a healthy body weight, elimination of medical sequelae, and resumption of menses. Symptoms can wax and wane over an extended period for several years. Approximately 50% of adolescents recover in a relatively short period of time. Thirty percent may take several years to get back to a state of health, although symptoms may reappear on occasion. About 20% of adolescents can go on to develop chronic, unremitting AN.
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