Anorexia Nervosa

Primer

Anorexia nervosa (AN) is an eating disorder characterized by a fear of gaining weight, strong desire to be thin, and food restriction, which results in low weight. It is the highest mortality psychiatric illness with a mortality rate of 10%.

Epidemiology

In the United States, the 12-month prevalence of anorexia nervosa in young females is approximately 0.4%.^[1]
- The incidence in low- and middle-income countries is significantly lower (see Cultural section).
Anorexia nervosa predominantly affects females (10:1 female-to-male ratio).^[2]
It most commonly begins during adolescence or young adulthood
- Very rarely, it can begin before puberty or after age 40.^[3]

Prognosis

Anorexia nervosa is associated with physiological disturbances, including amenorrhea and vital sign abnormalities.
- Although most physiological disturbances from malnutrition are reversible with nutritional rehabilitation, some are not completely reversible (e.g. - loss of bone mineral density).
The prognosis for anorexia nervosa is highly variable.
- Some individuals will recover fully after a single episode, while others experience a chronic course over many years.
- Hospitalization may be needed to restore weight and to treat medical complications.
On average, most individuals with anorexia nervosa experience remission within 5 years of presentation, but overall remission rates are lower in those who have a history of hospitalization.
The crude mortality rate (CMR) for anorexia nervosa is approximately 5% per decade.
- Death most commonly results from medical complications or from suicide.
- Suicide risk is significantly elevated in anorexia nervosa.^[4]

Comorbidity

Bipolar, depressive, and anxiety disorders are most comorbid.^[5]
Many individuals may have an anxiety disorder or symptoms prior to onset of their eating disorder.
OCD is more common in those with restricting type, while alcohol use disorder and other substance use disorders is more common in those with binge-eating/purging type.^[6]

Risk Factors

Anxiety disorders and obsessional traits in childhood are risk factors.^[7]
Triggers for anorexia include stressful life events, such as leaving home for college.
Genetically, there is an increased risk of anorexia nervosa and bulimia nervosa among first-degree biological relatives of individuals with the disorder.
- Concordance rates for anorexia nervosa in monozygotic twins are significantly higher than those for dizygotic twins

Cultural

Anorexia nervosa is most prevalent in post-industrialized, high-income countries including Canada, the United States, many European countries, Australia, New Zealand, and Japan.^[8]
Historical and cross-cultural variability in the prevalence of anorexia nervosa supports its association with cultures and settings in which thinness is valued.
Occupations and jobs that encourage thinness, such as modeling, elite athletics, and dancers,^[9] are associated with increased risk.

DSM-5 Diagnostic Criteria

Criterion A

Restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. Significantly low weight is defined as a weight that is less than minimally normal or, for children and adolescents, less than that minimally expected.

Mnemonic

The mnemonic “individuals with anorexia want to get RID of their weight” can be used to remember the core features of anorexia.

R - Restriction of intake leading to significantly low body weight
I - Intense fear of weight gain
D - Disturbance in perception of one's weight or body image

Criterion B

Intense fear of gaining weight or of becoming fat, or persistent behaviour that interferes with weight gain, even though at a significantly low weight.

Criterion C

Disturbance in the way in which one's bodyweight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight.

See also: DSM-IV to DSM-5 Changes for Anorexia Nervosa

Specifiers

Type Specifier

Restricting type: During the last 3 months, the individual has not engaged in recurrent episodes of binge eating or purging behaviour (i.e. - self-induced vomiting or the misuse of laxatives, diuretics, or enemas). This subtype describes presentations in which weight loss is accomplished primarily through dieting, fasting, and/or excessive exercise.
Binge-eating/purging type: During the last 3 months, the individual has engaged in recurrent episodes of binge eating or purging behaviour (i.e. - self-induced vomiting or the misuse of laxatives, diuretics, or enemas).

Remission Specifier

Specify if:

In partial remission: After full criteria for anorexia nervosa were previously met. Criterion A (low body weight) has not been met for a sustained period, but either Criterion B (intense fear of gaining weight or becoming fat or behavior that interferes with weight gain) or Criterion C (disturbances in self-perception of weight and shape) is still met.
In full remission: After full criteria for anorexia nervosa were previously met, none of the criteria have been met for a sustained period of time.

Severity Specifier

The minimum level of severity is based, for adults, on current body mass index (BMI) (see below) or, for children and adolescents, on BMI percentile. The ranges below are derived from World Health Organization (WHO) categories for thinness in adults; for children and adolescents, corresponding BMI percentiles should be used. The level of severity may be increased to reflect clinical symptoms, the degree of functional disability, and the need for supervision.

Mild: BMI ≥ 17 kg/m²
Moderate: BMI = 16 to 16.99 kg/m²
Severe: BMI = 15 to 15.99 kg/m²
Extreme: BMI < 15 kg/m²

Note: a BMI = 18.5 kg/m² has been used by the WHO and Centers for Disease Control and Prevention (CDC) as the lower limit of normal body weight. Therefore, most adults with a BMI at or above this number would not be considered to have a significantly low body weight).^[10]

Signs and Symptoms

Often, individuals come to professional attention via family members who are concerned about seeing weight loss (or failure to make expected weight gains).
- It is rare for individuals with anorexia nervosa to complain of weight loss and seek clinical attention, and they frequently lack insight or deny the problem.
- If individuals do seek help on their own, it is usually due to distress over the somatic and/or psychological sequelae of starvation.^[11]
Individuals with anorexia nervosa, binge-eating/purging type can binge eat and also purge through self-induced vomiting or the misuse of laxatives, diuretics, or enemas.
- However, some individuals will not binge eat but will regularly purge after eating small amounts of food.
- The crossover between the two subtypes over the course of the disorder can be common.
- Thus, the subtype specifiers should be used to describe current symptoms rather than longitudinal course.
Obsessive-compulsive symptoms, both related and unrelated to food, are often prominent. Most individuals are preoccupied with thoughts of food, and some may collect recipes or hoard food.

BMI Calculation

See also: Centers for Disease Control and Prevention (CDC) BMI Percentile Calculator for Child and Teen

For children and adolescents, determining a BMI-for-age percentile is useful. Similar to adults, it is not possible to give definitive standards for judging whether a child or adolescent's weight is significantly low. This is because variations in developmental trajectories among youth limit the utility of simple numerical guidelines.
The CDC has used a BMI-for-age below the 5th percentile as suggesting underweight.
- However, children and adolescents with a BMI above this cut off may still be judged to be significantly underweight if there is failure to maintain their expected growth trajectory
Thus, to determine whether Criterion A or anorexia nervosa is met, the clinician needs to consider not just the numerical guidelines, but also the individual's body build, weight history, and any physiological changes (e.g. - amenorrhea).^[12]

Screening and Rating Scales

Eating Disorder Scales

Name	Rater	Description	Download
Eating Disorder Diagnostic Scale (EDDS)	Patient	A 22-item self-report scale for individuals between 13 to 65 years old that screens for anorexia nervosa, bulimia nervosa, and binge-eating disorder.	Link

The SCOFF Questionnaire

The SCOFF is a simple 5-question screening questionnaire for anorexia and validated in specialist and primary care setting (sensitivity of 100% and specificity of 90%).^[13] Though not diagnostic, a score of 2 or more positive answers should raise your index of suspicion of a case, highlighting need for more detailed history.

S: Do you ever make yourself sick because you feel uncomfortably full?
C: Do you worry you have lost control over how much you eat?
O: Have you recently lost more than one stone [14 pounds/6.4kg] in a 3 month period?
F: Do you believe yourself to be fat when others say you are too thin?
F: Would you say that food dominates your life?

Pathophysiology

Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have shown a range of neuroanatomical abnormalities.^[14] The degree to which these findings reflect changes associated with malnutrition versus primary abnormalities associated with the disorder is unclear.

Differential Diagnosis

Other possible causes of either significantly low body weight or significant weight loss should be considered in the differential diagnosis of anorexia nervosa, especially when the presenting features are atypical (e.g., onset after age 40 years).

Medical conditions
- Medical conditions such as gastrointestinal disease, hyperthyroidism, occult malignancies, and acquired immunodeficiency syndrome (AIDS) can present with serious weight loss
- However, individuals with these disorders usually do not have a disturbance in the way their body weight or shape is experienced or the intense fear of weight gain seen in anorexia nervosa. Acute weight loss associated with a medical condition can occasionally be followed by the onset or recurrence of anorexia nervosa, which can initially be masked by the comorbid medical condition. Rarely, anorexia nervosa can develop after bariatric surgery for obesity.
Major depressive disorder (MDD)
- In MDD, severe weight loss can occur, but most individuals do not have either a desire for excessive weight loss or an intense fear of gaining weight.^[15]
Schizophrenia
- Individuals with schizophrenia may have odd eating behaviours and occasionally have significant weight loss. However, they rarely show the fear of gaining weight and the body image disturbance seen in anorexia nervosa.
Substance use disorders
- Individuals with substance use disorders may have low weight due to poor intake but generally do not have a fear gaining weight or body image disturbance. Individuals who abuse substances that reduce appetite (e.g. - cocaine, stimulants) and who also have a fear of weight gain should be evaluated for the possibility of comorbid anorexia nervosa, since substance use can be a persistent behaviour that interferes with weight gain (Criterion B).

Social anxiety disorder, obsessive-compulsive disorder (OCD), and body dysmorphic disorder (BDD)
- Some of the features of anorexia nervosa overlap with the criteria for social phobia, OCD, and BDD. Specifically, individuals may feel humiliated or embarrassed to be seen eating in public, as in social phobia. They may have obsessions and compulsions related to food as seen in OCD. Or, they may be preoccupied with an imagined defect in their bodily appearance, as seen in BDD. If the individual with anorexia nervosa has social fears that are limited to eating behavior alone, the diagnosis of social anxiety disorder should not be made. However, if the social fears unrelated to eating behavior (e.g. - excessive fear of speaking in public) they may warrant an additional diagnosis of social phobia. Similarly, OCD should be considered only if the individual exhibits obsessions and compulsions unrelated to food (e.g. - an excessive fear of contamination), and an additional diagnosis of BDD should be considered only if the distortion is unrelated to body shape and size (e.g. - preoccupation that one's nose is too big).^[16]
Bulimia nervosa
- Individuals with bulimia nervosa have recurrent episodes of binge eating, engage in inappropriate behavior to avoid weight gain (e.g. - self-induced vomiting), and are also overly concerned with body shape and weight. However, unlike in anorexia nervosa, binge-eating/purging type, individuals with bulimia nervosa maintain a body weight at or above a minimally normal level.^[17]
Avoidant/restrictive food intake disorder (ARFID)
- Individuals with ARFID may have significant weight loss or nutritional deficiency, but do not have a fear of gaining weight or of becoming fat, nor do they have a disturbance in the way they experience their body shape and weight.

Investigations

Various metabolic and bloodwork disturbances can occur in anorexia nervosa. Self-induced vomiting and/or misuse of laxatives, diuretics, and enemas can cause a number of disturbances that lead to abnormal laboratory findings. However, some individuals with anorexia nervosa exhibit no laboratory abnormalities.
Hematology
- Leukopenia (decreased white blood cells, WBC) is common
- Elevated lymphocytes can occur
- Mild anemia can occur, thrombocytopenia and, rarely, bleeding problems
Electrolytes are typically all decreased, resulting in:
- Hyponatremia
- Hypophosphatemia
- Hypomagnesmia
- Hypokalemia
- Hypocalcemia
- Hypozincemia
- Self-induced vomiting may lead to metabolic alkalosis (elevated serum bicarbonate), hypochloremia, and hypokalemia; laxative abuse may also cause a mild metabolic acidosis.
Endocrine
- Serum thyroxine (T4) levels are usually in the low-normal range; triiodothyronine (T3) levels are decreased, while reverse T3 (rT3) levels are elevated.
Cholesterol
- Hypercholesterolemia is common
Liver enzymes
- Hepatic enzyme levels may be elevated
Elevated serum amylase^[18]
Reproductive hormones
- Females have low serum estrogen levels, whereas males have low levels of serum testosterone.
Growth hormone (GH)
- Increased^[19]
Cortisol
- Increased^[20]
Gonadotropin releasing hormone (GnRH)
- Decreased^[21]
Leptin
- Decreased

Bone Density

Low bone mineral density, with specific areas of osteopenia or osteoporosis, is often seen. The risk of fracture is significantly elevated.^[22]

ECG

Sinus bradycardia is common, and, rarely, arrhythmias are noted. Significant prolongation of the QTc interval is observed in some individuals.^[23]

Physical Exam

Most of the physical signs and symptoms of anorexia nervosa are due to starvation.
Amenorrhea is commonly present and appears to be an indicator of physiological dysfunction.
- In prepubertal females, menarche maybe delayed.
There may be complaints of cold intolerance, hypothermia, and lethargy.
Cardiovascular changes include hypotension, bradycardia, dizziness, cyanotic hands and feet, edema.
- Some develop peripheral edema, especially during weight restoration or upon cessation of laxative and diuretic abuse.
Genitourinary changes include: polyuria
Gastrointestinal changes may include: constipation, non-focal abdominal pain,
Dermatological changes include: lanugo (a fine downy body hair), brittle hair and nails, dry or yellow skin (associated with hypercarotenemia),
Rarely, petechiae or ecchymoses, usually on the extremities, may indicate a bleeding disorder (e.g. - thrombocytopenia).
As may be seen in individuals with bulimia nervosa, individuals with anorexia nervosa who self-induce vomiting may have hypertrophy of the salivary glands, particularly the parotid glands, as well as dental enamel erosion.
Some individuals may have scars or calluses on the dorsal surface of the hand from repeated contact with the teeth while inducing vomiting.

Treatment

Hospitalization

To avert potentially irreversible effects on physical growth and development, many children and adolescents require inpatient medical treatment, even when weight loss, although rapid, has not been as severe as that suggesting a need for hospitalization in adult patients
Hospitalization should occur before the onset of medical instability as manifested by abnormalities in vital signs:
- Orthostatic hypotension with an increase in pulse of 20 bpm
- Drop in standing blood pressure of 20 mmHg
- Bradycardia <40 bpm
- Tachycardia >110 bpm
- Inability to sustain core body temperature

Refeeding

Refeeding syndrome can occur in significantly malnourished patients when they have a sudden increase in calorie intake.
The mechanism is that increased caloric intake leads to increased insulin release, which leads to hypophosphatemia, decreased potassium, and decreased magnesium.
This series of metabolic chances can lead to cardiac complications, rhabdomyolysis, and seizures.
During the refeeding process, serum glucose may rise, while B1 vitamin thiamine may fall
- Thus, there is a risk for Wernicke's encephalopathy, and individuals should receive IV thiamine during refeeding as well.

Medication

Psychological

Once weight-gain has restarted, various forms of psychotherapy have been found to be effective for treatment of anorexia, including:^[24]^[25]

Individual therapy (CBT, IPT, and psychodynamic approaches)
Group therapy (CBT, IPT, and psychodynamic approaches)
Family-Based Therapy (Maudsley) for children and adolescents

Guidelines

See also: Psychiatry Clinical Practice Guidelines (CPGs)

Eating Disorder Guidelines

Guideline	Location	Year	PDF	Website
International Comparison (Curr Opin Psychiatry)	International	2017	-	Link
Canadian Clinical Practice Guidelines (Children and Adolescents)	Canada	2020	-	Link
National Institute for Health and Care Excellence (NICE)	UK	2017	-	Link
American Psychiatric Association (APA)	USA	2006, 2012	-	• Guideline (2006) • Guideline Watch (2012) • Quick Reference

Resources

Research

¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁴⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁵⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁶⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁷⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁸⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁹⁾ Arcelus, J., Witcomb, G. L., & Mitchell, A. (2014). Prevalence of eating disorders amongst dancers: a systemic review and meta‐analysis. European Eating Disorders Review, 22(2), 92-101.

¹⁰⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹³⁾ http://cedd.org.au/wordpress/wp-content/uploads/2014/09/The-SCOFF-Questionnaire-SCOFF.pdf

¹⁴⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁵⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁶⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁷⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁸⁾ Wolfe, B. E., Jimerson, D. C., Smith, A., & Keel, P. K. (2011). Serum amylase in bulimia nervosa and purging disorder: Differentiating the association with binge eating versus purging behavior. Physiology & behavior, 104(5), 684-686.

¹⁹⁾ Misra, M., & Klibanski, A. (2014). Endocrine consequences of anorexia nervosa. The lancet Diabetes & endocrinology, 2(7), 581-592.

²⁰⁾ Misra, M., & Klibanski, A. (2014). Endocrine consequences of anorexia nervosa. The lancet Diabetes & endocrinology, 2(7), 581-592.

²¹⁾ Schorr, M., & Miller, K. K. (2017). The endocrine manifestations of anorexia nervosa: mechanisms and management. Nature reviews endocrinology, 13(3), 174.

²²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁴⁾ Yager, Joel, et al. Practice guideline for the treatment of patients with eating disorders. American Psychiatric Association, 2006. Third Edition

²⁵⁾ Guideline Watch for the Practice Guideline for the Treatment of Patients With Eating Disorders 11

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