Anorexia Nervosa

Etiology

The success of many professions depends on a person's weight. Models and actors portray a level of thinness that is difficult to attain, and it is enhanced by make-up and photographic alterations. Athletes in sports such as ballet, long-distance running, and martial arts are pressured to maintain lean body weights to outperform the competition. Media outlets promote diet secrets and weight loss tips in excess. Populations such as maturing females identify thin body types with increased self-esteem and link weight loss with self-control.[4][5]

Epidemiology

Anorexia nervosa is more common in females than males. Onset is late adolescence and early adulthood. Lifetime prevalence is 0.3% to 1% (European studies have demonstrated a prevalence of 2% to 4%), irrespective of culture, ethnicity, and race. Risk factors for eating disorders include childhood obesity, female sex, mood disorders, personality traits (impulsivity and perfectionism), sexual abuse, or weight-related concerns from family or peer environments.[6][7][8]

Pathophysiology

Studies demonstrate biological factors play a role in the development of anorexia nervosa in addition to environmental factors. Genetic correlations exist between educational attainment, neuroticism, and schizophrenia. Patients with anorexia nervosa have altered brain function and structure there are deficits in neurotransmitters dopamine (eating behavior and reward) and serotonin (impulse control and neuroticism), differential activation of the corticolimbic system (appetite and fear), and diminished activity among the frontostriatal circuits (habitual behaviors). Patients have co-morbid psychiatric disorders such as major depressive disorder and generalized anxiety disorder.

History and Physical

Patients will report symptoms such as amenorrhea, cold intolerance, constipation, extremity edema, fatigue, and irritability. They may describe restrictive behaviors related to food like calorie counting or portion control, and purging methods, for example, self-induced vomiting or use of diuretics or laxatives. Many exercise compulsively for extended periods of time. Patients with anorexia nervosa develop multiple complications related to prolonged starvation and purging behaviors.

Evaluation

Workup includes a thorough medical history (comprehensive review of systems, family and social history, medications including nonprescribed, past medical and psychiatric history, prior abuse) and physical exam (looking for complications above). Basic labs include coagulation panel, complete blood count, complete metabolic profile, 25-hydroxyvitamin D, testosterone (males), thyroid-stimulating hormone, and urine testing (beta-hCG [females] and drugs, either illicit or prescription). An electrocardiogram is recommended to assess for life-threatening arrhythmias. Additional studies may be necessary if BMI is less than 14 kg/m, for example, echocardiogram in patients with hemodynamic compromise (dyspnea, murmurs, syncope) or computed tomography of the abdomen to rule out superior mesenteric artery syndrome or amenorrhea more than 9 months (dual-energy x-ray absorptiometry).[9][8]

Complications of anorexia nervosa are listed:

• Cardiovascular: bradycardia, dilated cardiomyopathy, electrolyte-induced arrhythmias, hypotension, mitral valve prolapse, pericardial effusion
• Constitutional: arrested growth, hypothermia, low body mass index (BMI), muscle wasting
• Dermatologic: carotenoderma, lanugo, xerosis
• Endocrine: hypothalamic hypogonadism, osteoporosis
• Gastrointestinal: constipation (laxative abuse), gastroparesis
• Hematologic: cytopenias (inc. normocytic anemia), bone marrow hypoplasia/aplasia
• Neurologic: brain atrophy, peripheral neuropathy (mineral and vitamin deficiencies)
• Obstetric: antenatal and postnatal complications
• Psychiatric: depression, impaired concentration, insomnia, irritability
• Renal and electrolytes: hypokalemic metabolic acidosis or alkalosis (laxative or diuretic abuse, resp.), prerenal renal failure, refeeding syndrome.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) provides the diagnostic criteria for anorexia nervosa (A-C). It classifies the disease by type, status, and severity.

Of note, amenorrhea has been removed from the DSM-5 criteria. Patients who meet the new criteria and continue to menstruate have similar outcomes as those who do not.

Other eating disorders have similar features to anorexia nervosa. Avoidant or restrictive food intake disorder involves food restriction with failure to meet the nutritional need. While patients are often underweight, this disturbance does not meet diagnostic criteria for anorexia nervosa. Individuals with binge eating disorder eat excessive amounts of calories in a short period with a lack of self-control but do not display compensatory behaviors such as purging or restriction. Patients with bulimia nervosa will binge and purge without a corresponding low BMI. Pica refers to chronic ingestion of nonfood substances and may be a manifestation of underlying medical or psychiatric condition. For example, patients with anorexia nervosa may eat toilet paper when they are hungry. Rumination disorder occurs when patients repeatedly regurgitate food for one month when no other medical condition can be identified and does not occur solely during the course of another eating disorder. Other specified feeding or eating disorder refers to conditions with symptoms that impair functioning but do not meet criteria for a specific eating disorder, for example, patients who meet criteria for anorexia nervosa but have BMI more than 18.5 kg/m are classified as “atypical anorexia nervosa.”

Major depressive disorder can cause anorexia and weight loss. However, patients are not obsessed with body habitus. Patients with obsessive-compulsive disorder may have food rituals but maintain a normal weight. Patients who abuse stimulants such as cocaine and methamphetamine experience weight loss through increased metabolism and concentrated efforts to obtain illicit substances rather than consume calories.

Medical conditions can cause weight loss. Examples are celiac disease, hyperthyroidism, inflammatory bowel disease, malignancy, poorly controlled diabetes mellitus, primary adrenal insufficiency, and tuberculosis. The diagnosis will come from the history and physical examination. Order labs as dictated by the clinical picture.

Treatment / Management

Treatment for anorexia nervosa is centered on nutrition rehabilitation and psychotherapy. Patients who need inpatient treatment have the following characteristics:

• Existing psychiatric disorders requiring hospitalization
• High risk for suicide (intent with highly lethal plan or failed attempt)
• Lack of support system (severe family conflict or homelessness)
• Limited access (lives too far away to participate in a daily treatment program)
• Medically unstable (bradycardia, dehydration, hypoglycemia or poorly controlled diabetes, hypokalemia or other electrolyte imbalances indicative of refeeding syndrome, hypothermia, hypotension, organ compromise requiring acute treatment)
• Poorly motivated to recover (uncooperative, preoccupied with intrusive thoughts)
• Purging behaviors that are persistent, severe, and occur multiple times a day
• Severe anorexia nervosa (less than 70% of ideal body weight or acute weight loss with food refusal)
• Supervised feeding and/or specialized feeding (nasogastric tube) required
• Unable to stop compulsively exercising (not a sole indication for hospitalization).

Outpatient treatment includes intensive therapy (2 to 3 hours per weekday) and partial hospitalization (6 hours per day). Pediatric patients benefit from family-based psychotherapy to explore underlying dynamics and restructure the home environment.

Refeeding syndrome can occur following prolonged starvation. As the body utilizes glucose to produce molecules of adenosine triphosphate (ATP), it depletes the remaining stores of phosphorus. Also, glucose entry into cells is mediated by insulin and occurs rapidly following long periods without food. Both cause electrolyte abnormalities such as hypophosphatemia and hypokalemia, triggering cardiac and respiratory compromise. Patients should be followed carefully for signs of refeeding syndrome and electrolytes closely monitored.

Pharmacotherapy is not used initially. For acutely ill patients who do not respond to initial treatment, olanzapine is a first-line medication. Other antipsychotics have not demonstrated similar effects on weight gain. For patients who are not acutely ill but have co-morbid psychiatric conditions such as generalized anxiety disorder or major depressive disorder, combination therapy with selective serotonin reuptake inhibitors (SSRIs) and therapy is best. Patients who do not respond to SSRIs may need a second-generation antipsychotic. Tricyclic antidepressants (TCAs) are less preferred due to concerns about cardiotoxicity, especially in malnourished patients. Bupropion is contraindicated in patients with eating disorders due to the increased risk of seizures.[10][11][12](A1)

Differential Diagnosis

• Cancer
• Chronic mesenteric ischemia
• Achalasia
• Malabsorption
• Hyperthyroidism
• Irritable bowel syndrome
• Celiac disease

Prognosis

Remission in AN varies. Three-fourths of patients treated in out-patient settings remit within 5 years and the same percentage experience intermediate-good outcomes (including weight gain). Relapse is more common in patients who are older with a longer duration of disease or lower body fat/weight at the end of treatment, have co-morbid psychiatric disorders, or receive therapy outside of a specialized clinic. Patients who achieve partial remission often develop another form of eating disorder (ex. bulimia nervosa or unspecified eating disorder).

All-cause mortality is greater in AN compared to the rest of the population. It has one of the highest mortality rates of all eating disorders due to medical complications, substance abuse, and suicide. Patients with AN have increased rates of suicide and this accounts for 25% of deaths associated.

Complications

• Amenorrhea
• Delayed puberty
• Hypercarotenemia
• Hypothermia
• Hypoglycemia
• Osteoporosis
• Failure to thrive 
• Cardiomyopathy
• Bradycardia
• Arrhythmias
• Renal failure
• Constipation
• Peripheral neuropathy
• Pancytopenia
• Infertility