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.
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