Anorexia nervosa

                                Anorexia nervosa (AN) is a psychiatric disorder with severe physiologic consequences, characterized by the inability or refusal to maintain a minimally normal weight. Patients have a profoundly disturbed body image as well as an intense fear of weight gain despite being moderately to severely underweight.^[1]

Diagnostic criteria for anorexia nervosa in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) include the following^[2] :

• A refusal to maintain body weight at or above a minimally normal weight for age and height (usually less than 85% of ideal body weight)
• Intense fear of gaining weight or becoming fat
• Disturbance in the way one's body weight or shape is experienced, with denial of current low body weight
• Amenorrhea in postmenarchal females of at least 3 menstrual cycles

Anorexia nervosa may be further divided into 2 subtypes:

 (1) restricting, in which severe limitation of food intake is the primary means to weight loss

(2) binge-eating/purging type, in which there are periods of food intake that are compensated by self-induced vomiting, laxative or diuretic abuse, and/or excessive exercise.

Formal recommendations have been made to remove the amenorrhea criterion and the subtype distinctions from the criteria for anorexia nervosa in the upcoming DSM-V.^[3] In addition, numerous studies have demonstrated subthreshold eating disorders either alone or coexistent with other psychiatric diagnoses, suggesting the diagnostic criteria may need to be expanded, and there may be a higher prevalence of anorexia nervosa than previously thought.^[4]

Patients may or may not carry a diagnosis of anorexia nervosa when presenting to an emergency department for acute care, and other physiologic causes of malnutrition, weight loss, and amenorrhea must be ruled out before making the diagnosis.

Patients with anorexia nervosa often display other personality traits such as a desire for perfection, academic success, lack of age-appropriate sexual activity, and a denial of hunger in the face of starvation. Psychiatric characteristics include excessive dependency needs, developmental immaturity, social isolation, obsessive-compulsive behavior, and constriction of affect. Many patients also have comorbid mood disorders, with depression and dysthymic disorder being most prevalent.^{[5, 6, 7]}

Pathophysiology

Anorexia nervosa is the result of a complex interplay between biological, psychological, and social factors, which tend to affect women more than men, and adolescents more than older women. Some evidence suggests a higher rate of the disorder in monozygotic twins than in dizygotic twins, which may indicate a biologic predisposition.^[8]

Psychologically, prepubescent patients who subsequently develop anorexia nervosa have a high incidence of premorbid anxiety disorders. The onset of the disorder during puberty has led to the theory that, by exerting control over food intake and body weight, adolescents are attempting to compensate for a lack of autonomy and selfhood.

Individuals with anorexia nervosa maintain a lifelong increased incidence of anxiety, depressive disorders, and obsessive-compulsive disorder. Neurobiologists hypothesize that disruption of serotonergic pathways in the brain mediate the development of anorexia nervosa and may account for the frequent coexistence of other psychological disturbances.^[9]

The patient's altered body image results in a perception of fatness despite being normal or underweight. Attempts to correct this flaw through food restriction or purging lead to progressive malnutrition and eventually starvation. Modern preoccupation with slenderness and beauty in the Western world may contribute to the mindset of thinness as a valued quality in adolescents; however, this link has not been proven. A subset of adolescents who are temperamentally incapable of dealing with age-appropriate challenges without extreme reward-seeking behavior (thinness) may be susceptible to anorexia nervosa.^[10]

Malnutrition subsequent to self-starvation leads to protein deficiency and disruption of multiple organ systems. In addition to hypoglycemia and vitamin deficiencies, starvation results in release of endogenous opioids, hypercortisolemia, and thyroid function suppression.

Neuroendocrine disturbances result in delayed puberty, amenorrhea, anovulation, low estrogen states, increased growth hormone, decreased antidiuretic hormone, hypercarotenemia, and hypothermia.^[11] Decreased gonadotropin levels and hypogonadism may occur among males who are affected.

Cardiovascular effects include mitral valve prolapse, supraventricular and ventricular dysrhythmias, long QT syndrome, bradycardia, orthostatic hypotension, and shock due to congestive heart failure.^{[12, 13]}

Renal disturbances include decreased glomerular filtration rate (GFR), elevated blood urea nitrogen (BUN), edema, acidosis with dehydration, hypokalemia, hypochloremic alkalosis with vomiting, and hyperaldosteronism.

Gastrointestinal findings include constipation, delayed gastric emptying, and gastric dilation and rupture when binge eating. Patients who induce vomiting develop dental enamel erosion, palatal trauma, enlarged parotids, esophagitis, Mallory-Weiss lesions, and elevated transaminase levels. Cases of superior mesenteric artery (SMA) syndrome from loss of intraperitoneal fat in AN as well as gastric rupture from bingeing and purging, leading to pneumothorax and pneumoperitoneum, have been reported.^{[14, 15]}

Etiology

Anorexia nervosa is a complex combination of biological, psychological, and social factors, which have devastating physical and mental consequences.

Twin studies suggest there is a 50-80% genetic contribution, which, when combined with a high-risk environment, predisposes to the development of anorexia nervosa. This places anorexia nervosa with a similar heritability estimate to that of bipolar disorder and schizophrenia.

A psychological profile often demonstrates premorbid anxiety disorders as well as more severe affective disorders such as major depression and dysthymic disorder. Patients may also have symptoms of obsessive-compulsive disorder, with rigid and ritualistic eating behaviors.

Epidemiology

The lifetime prevalence of anorexia nervosa in the United States is estimated at 0.3-1%; however, some studies have shown rates as high as 4% among women. The rates among men are estimated at 0.1%. As many as 5% of young women exhibit symptoms of anorexia but do not meet full diagnostic criteria, and some studies show disordered eating behavior in 13% of adolescent girls in the United States.^{[5, 6, 7, 16, 17]}

Internationally, anorexia nervosa is found in all developed countries and in all socioeconomic classes at similar rates (0.3-1% in women, 0.1% in men) as well as in developing countries such as China and Brazil.^[7]

Racial, sexual, and age-related differences in incidence

Anorexia nervosa is significantly more frequent in white populations than in people of other races, but it has been reported among all races. A link between socioeconomic class and prevalence of eating disorders has not been demonstrated in the literature.

Female-to-male ratio is 10-20:1 in developed countries. In some professions, the frequency is much higher among men (wrestling, running, modeling) than the general male population.

Anorexia nervosa has been observed in both the very young and very old, but the disorder is primarily a phenomenon of puberty and early adulthood. Eighty-five percent of patients have onset of the disorder between the ages of 13 and 18 years.^{[5, 16, 17, 18]} Patients who are older at the time of onset of the disorder have a worse prognosis.

Prognosis

The prognosis for recovery from anorexia nervosa is multi-factorial. Overall, the prognosis has not changed much over the past 50 years.^{[1, 19]} Approximately 50% of patients will recover with treatment and maintain a normal weight but often not without relapses and with the aid of multiple treatment modalities.

In one large meta-analysis, 47% of patients fully recovered; 33% improved somewhat; and 20% developed chronic, relapsing anorexia.^[20] Patients with later age at onset of the disorder, binge-purge behavior, and concurrent mood disorders have a worse prognosis for full recovery.

Anorexia nervosa has one of the highest mortality rates of all psychiatric disorders, with rates reported from 4-18%.^{[16, 20, 21]} Patients with restricting subtype tend to be more refractory to treatment and are at high risk of death.^[22] Mortality is often due to suicide and less frequently due to complications of starvation.^{[20, 21]}

History

Patients with anorexia nervosa may present to the emergency department (ED) with extreme weight loss, food refusal, dehydration, weakness, acute abdominal pain, or shock. They are frequent users of the emergency department, and, as a result, emergency physicians should be screening for both subclinical and overt clinical evidence of anorexia nervosa in adolescents. Many present at the urging of family members or friends and are in deep denial of their malnutrition and illness.

Patients should be questioned about their current weight, highest weight, lowest weight, exercise habits, and menstrual cycles. Further questioning should inquire with regard to eating habits, presence or absence of self-induced vomiting/binge eating, and use of laxatives.

Major depression and dysthymic disorder have been reported in up to 50% of patients with anorexia nervosa. Patients should be asked about early morning awakening, tearfulness, and thoughts of suicide or a plan for it.

Review of systems is often positive for constipation, early satiety, hypothermia, nausea, hair loss, and fatigue.

Physical Examination

Patients with anorexia nervosa may present anywhere along the spectrum of weight loss. They may attempt to hide their weight loss by wearing bulky clothing or many layers.

Physical examination may reveal hypothermia, peripheral edema, thinning hair, and obvious emaciation.

Behaviorally, a patient may demonstrate a flat affect and display psychomotor retardation, especially in the later stages of the disease. Cases of acute psychosis in anorexia nervosa from Wernicke-Korsakoff syndrome due to severe thiamine deficiency have been reported.^[23]

Vital sign abnormalities may include hypothermia, bradycardia, and hypotension.

Cardiac examination may reveal the mid-systolic click of mitral valve prolapse.

Patients with purging behavior may have parotid gland hypertrophy, dental enamel erosion and, in extreme cases, seizures from electrolyte disturbances.

Dermatologic examination reveals dry skin, lanugo (a fine, downy covering of hair on the extremities), and poor skin turgor.^[24]

Complications

Patients with anorexia nervosa are at risk for complications related to nutritional and electrolyte imbalances, as well as long-term social and interpersonal difficulties due to their disorder. Physiologic complications involve nearly every organ system.

Fluid and electrolyte imbalances include hypokalemia, hyponatremia, hypochloremia, metabolic alkalosis, elevated blood urea nitrogen (BUN), decreased glomerular filtration rate (GFR), and ketonuria. Cardiovascular complications range from bradycardia, orthostatic hypotension, prolonged QT interval, low voltage, and mitral valve prolapse, to frank congestive heart failure and life-threatening dysrhythmias.

Gastrointestinal effects include constipation, bloating, early satiety, parotid gland hypertrophy, delayed gastric emptying, Mallory-Weiss tears, esophageal or gastric perforation, fatty liver infiltration, gallstones, and pancreatitis. Hematologic findings include anemia, leukopenia, thrombocytopenia, and impaired immunity. Endocrine problems due to starvation involve growth retardation, delayed puberty, amenorrhea, depressed T3 levels, hypercortisolemia, and diabetes insipidus.

Dermatologic complications include acrocyanosis, hypercarotenemia, brittle hair and nails, hair loss, lanugo, and pitting edema.

Neurologically, patients may develop peripheral neuropathy, seizures, and cortical atrophy. Psychologically, patients are at risk for isolation, depression, and suicide in addition to their disordered thought patterns regarding food and weight.

Differentials

• Adrenal Insufficiency and Adrenal Crisis
• Alcohol and Substance Abuse Evaluation
• Anxiety
• Depression and Suicide
• Hyperthyroidism, Thyroid Storm, and Graves Disease
• Hypokalemia
• Mitral Valve Prolapse
• Pediatrics, Dehydration
• Pediatrics, Diabetic Ketoacidosis
• Sinus Bradycardia

Approach Considerations

The emergency department workup of a patient with possible anorexia nervosa should include a basic medical evaluation as well as urgent or timely outpatient psychiatric evaluation. If the patient has not been previously diagnosed with anorexia nervosa, a thorough medical evaluation should seek other metabolic or gastrointestinal causes of severe weight loss.

No definitive diagnostic tests are available for anorexia nervosa. However, given the multi-organ system effects of starvation, a thorough medical evaluation is warranted. Basic tests include physical and mental status evaluation, complete blood cell count, a metabolic panel, urinalysis, a pregnancy test in females of childbearing age, and an electrocardiogram (ECG).

A chemistry panel should be assessed for hypokalemic, hypocalcemic metabolic alkalosis caused by vomiting. Ionized calcium levels should detect hypocalcemia. Hyponatremia may be seen due to excess water intake. The serum phosphorus level may be low; levels less than 0.8 mmol/L should be repleted.

Liver function test results may be slightly elevated. Albumin and protein levels are usually normal, however.

A complete blood count may reveal a mild leukopenia secondary to margination as well as thrombocytopenia. Hemoglobin may be elevated with extreme dehydration, but is generally normal.

Fecal occult blood may be indicative of esophagitis, gastritis, or repetitive colonic trauma from laxative abuse. Thyroid function tests, prolactin, and serum follicle-stimulating hormone levels can differentiate anorexia nervosa from alternative causes of primary amenorrhea.

ECG is helpful in evaluating the severity of malnutrition and risk for dysrhythmias in patients with metabolic abnormalities. ECG findings are nonspecific but may include bradycardia and prolonged QT interval.^{[13, 24]}

Imaging studies are rarely necessary in the ED. However, a chest radiograph may reveal rib fractures from repetitive vomiting in the presence of hypocalcemia. Patients may also show evidence of osteopenia. Radiographic evidence of emphysematous changes is present on the chest CT scan of patients with anorexia^[25] ; however, these changes resolve with refeeding and weight normalization, unlike those seen in chronic obstructive pulmonary disease.

Approach Considerations

Metabolic abnormalities in patients with anorexia nervosa should be corrected as needed, with oral or parenteral treatment depending on the patient's mental status and decision to cooperate. Hospital admission may be indicated for patients who are extremely ill, have cardiac dysrhythmias, or have severe metabolic abnormalities. Most patients will be admitted to medical facilities for re-feeding, referred to psychiatric facilities and counseling if medically stable, or be managed on an outpatient basis.

It is not necessary to begin parenteral nutrition in the emergency department; the focus should be on stabilization of acute abnormalities while an inpatient team including nutrition specialists can determine a re-feeding schedule. The process of re-feeding must be undertaken slowly, with modest increases in metabolic demands to avoid heart failure and a "re-feeding syndrome" that includes life-threatening dysrhythmias and hypophosphatemia. Ideal weight gain should occur at a rate of 1-2 lbs per week.

Inpatient treatment in a medical facility should always include psychiatric consultation for ongoing treatment of the underlying anorexia nervosa while addressing the acute medical complications of malnutrition.

Acute pharmacologic treatment of anorexia nervosa is rarely required, and cases of extreme altered mental status or psychosis should prompt a search for underlying profound metabolic disorders. The psychopharmacology of anorexia nervosa should be determined in consultation with a psychiatrist.

As with all psychiatric and behavioral emergencies, care must be taken to prove and document competency upon discharge. Many patients with anorexia nervosa may have additional psychopathology, which leaves them incapacitated during an anorexic crisis. If doubt remains, the patient must be admitted for more thorough psychiatric and physiologic monitoring or discharged in the care of a competent caretaker.

Transfer to an inpatient psychiatric facility may be the disposition for patients who are medically safe for discharge but who require aggressive inpatient psychiatric treatment of their disorder.

Indications for Hospital Admission

Life-threatening or potentially lethal abnormalities require admission. Indications for hospitalization include the following:

• Bradycardia or other cardiac dysrhythmias
• Severe electrolyte abnormalities, especially of potassium, sodium, and phosphorus levels
• Altered mental status or suicidality
• Extremely low body weight
• Failure of outpatient treatment

Consultations

Most cases of anorexia nervosa encountered in the emergency department will be appropriate for outpatient management if close, planned follow-up is arranged prior to discharge. Consultation with the pediatrician or primary care physician is necessary to arrange follow-up. Urgency of follow-up depends on the patient's condition and how soon the laboratory study results will need to be reevaluated.

Psychiatric consultation in the emergency department should be considered for patients expressing suicidality, psychosis, or severely disordered thinking. Outpatient psychiatric follow-up is necessary and may be arranged either from the ED or by the primary care provider.

Long-Term Monitoring

Close follow-up with the primary care physician is very important.

Patients with anorexia nervosa should have their weight and electrolytes checked within a week of their emergency department visit.

Outpatient psychiatric treatment should be arranged as soon as possible from either the emergency department or a primary care referral.

Medication Summary

Medical therapy in the emergency department consists of electrolyte repletion and stabilization. Multiple studies have failed to show an overall benefit for pharmacologic treatment of anorexia nervosa with psychiatric medications. However, most patients who recover will be treated with a multidisciplinary approach that includes medication, psychotherapy, nutritional counseling, and frequent medical evaluations.^{[26, 27]}

The most common class studied is selective serotonin reuptake inhibitors (SSRIs), which have been shown to be beneficial in patients with bulimia nervosa but not anorexia. However, since many patients with anorexia have concurrent mood disorders, medication may be of benefit.

Electrolytes

Class Summary

Electrolyte repletion is necessary in patients with profound malnutrition, dehydration, and purging behaviors. Repletion may be done orally or parenterally, depending on the patient’s clinical state.

Potassium chloride

Potassium is essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion or GI loss or because of low intake. Depletion usually results from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea (if associated with vomiting), or inadequate replacement during prolonged parenteral nutrition.

Potassium depletion sufficient to cause 1 mEq/L drop in the serum potassium level requires a loss of approximately 100-200 mEq of potassium from the total body store.

Calcium gluconate

Calcium gluconate moderates nerve and muscle performance and facilitates normal cardiac function. It can be given IV initially, and then calcium levels can be maintained with a high-calcium diet. Some patients require oral calcium supplementation. The 10% IV solution provides 100 mg/mL of calcium gluconate that equals 9 mg/mL (0.46 mEq/mL) of elemental calcium. One 10-mL ampule contains 93 mg of elemental calcium

Potassium phosphate

For severe hypophosphatemia (< 1 mg/dL), parenteral preparations of phosphate should be used for repletion. IV preparations are available as sodium or potassium phosphate (K2PO4). Response to IV serum phosphorus supplementation is highly variable and is associated with hyperphosphatemia, and hypocalcemia. The rate of infusion and choice of initial dosage should be based on severity of hypophosphatemia and presence of symptoms. Serum phosphate and calcium should be monitored closely.

For less severe hypophosphatemia (1-2 mg/dL), PO phosphate salt preparations can be used. PO preparations are available as sodium or potassium phosphate in capsule or liquid form. Neutra-Phos packets contain 250 mg of phosphorus/packet. Tablets contain 250, 125.6, or 114 mg each. Liquid preparations are available as 250 mg/75 mL.