AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

Background

Anorexia nervosa is an eating disorder characterized by a weight loss of at least 15% of expected body weight,¹ a devastating fear of weight gain, relentless dietary habits preventing weight gain, and a disturbance in the way in which body weight and shape are experienced. It has potentially life-threatening physiologic effects as well as enduring psychological disturbance.

Although anorexia nervosa is often heralded by a desire to lose an insignificant amount of weight through dieting, once the weight loss is in progress, immunological and hormonal factors that may play a role in the malignant spiral down and maintenance of anorexia nervosa include leptins (involved with signally satiety) as well as alpha melanocyte stimulating hormone.²

According to the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV), anorexia nervosa is defined as "the refusal to maintain body weight about 85% of predicted, an intense fear of gaining weight, undue influence of body shape or weight on self image, and missing at least 3 consecutive menstrual periods."³ An increase in morbidity and mortality is present in anorexia nervosa compared with other psychiatric disorders.

Pathophysiology

Anorexia nervosa is a disease that affects all organ systems. The principal systems affected are the cardiovascular and the endocrine systems. However, complications from other systems, including the GI, renal, reproductive, neurologic, orofacial, dermatologic and hematologic, are noted as well.

Frequency

United States

The prevalence of anorexia nervosa is 1%, with a bimodal pattern of onset, occurring in people aged 14 and 18 years. A point prevalence study performed in Rochester, Minnesota showed a prevalence of 145 and 113 cases per 100,000 people in 1988 and 1991, respectively. The disease is more common in industrialized countries where food is abundant and an emphasis is placed on a slender body shape and an overall thin appearance.

Although more common in women, with a female-to-male ratio of 10:1, approximately 10% of cases involve men. Gay and bisexual males are more likely to have an eating disorder than heterosexual males but they are more likely to have bulimia than anorexia.⁴

Anorexia nervosa is found mainly in the white (>95%) adolescent (>75%) populations of the middle and upper socioeconomic classes, although it can be observed in either sex and in people of any race, age, or social stratum.⁵

No influences have been found with respect to the month or season of birth.⁶

A 7% increased incidence in first-degree relatives may be related to an area on chromosome 1p at the DF1153721 locus.⁷

According to Mehler in 1997, certain groups are especially at risk, including dancers, long-distance runners, skaters, models, actors, wrestlers, gymnasts, flight attendants, college sorority members, and others for whom thinness is emphasized and overly rewarded.⁸

International

As mentioned above, anorexia nervosa is observed mostly in industrialized countries. However, a study performed in suburban London reported a prevalence of only 20.2 cases per 100,000 people, a much smaller figure than that observed in the United States.⁹

Mortality/Morbidity

Prognosis is guarded, and poor outcome is associated with longer duration of illness, late onset of illness, and more severe weight loss. Morbidity rates range from 10-20%; only 50% of patients completely recover. Of the remaining 50%, 20% remain emaciated, and 25% are thin.¹⁰ The remaining 10% become overweight or die of starvation.

The following are prognostic factors and how they affect anorexia nervosa:

• Onset of anorexia nervosa before adulthood carries a more favorable outcome. However, onset at an age younger than 11 years is a poor prognostic factor.
• Although the degree of weight loss at the clinically noted onset of the involvement of the patient's organic systems is not predictive of outcome, a high weight loss at presentation predicts a poor outcome.
• Both a short duration of involvement of the patient's organic systems before admission and a short inpatient treatment period are associated with a favorable outcome.
• A good relationship between the parent and child tends towards a more favorable outcome. Bryant-Waugh et al found a poor prognosis for patients from one-parent families, from families in which parents had been married before, and from families in which several generations lived together.¹¹

Race

As mentioned earlier, no discrimination in race with respect to anorexia nervosa is observed, although the disease is observed more often in white adolescents than in black adolescents.

Sex

A predominance of anorexia nervosa in females is observed. Studies have reported a 10:1 female-to-male ratio. Treatment plans remain the same for both sexes.

Age

Although it is more frequently observed in the adolescent age group, anorexia nervosa has no age restrictions and can be observed in the young child and adult as well. Onset in both of the latter groups carries a poor prognosis.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

History

Obtain patient history with the goal of developing a treatment plan and not with the thought of merely ruling out an eating disorder. With medical assessment, focus on the medical complications of altered nutrition. Seek a careful history detailing weight changes, dietary patterns, and excessive exercise. Determine weight and height.

A review of systems may reveal many positive responses. The following are symptoms commonly observed in patients with anorexia nervosa:

• Physical health concerns
• Mental health concerns
• Amenorrhea
• Concentration concerns
• Cold hands or feet
• Decision-making concerns
• Constipation
• Irritability
• Dry skin or hair loss
• Depression¹²
• Headaches
• Social withdrawal
• Fainting or dizziness
• Obsessiveness (food)
• Lethargy

Physical

Focus the physical examination on the changes commonly observed in anorexia nervosa. Vital sign changes include hypotension, bradycardia, and hypothermia. Other changes include dry skin, hypercarotenemia, lanugo body hair, acrocyanosis, atrophy of the breasts, and swelling of the parotid and submandibular glands. ECG reveals a prolonged cardiac output (QT) interval,¹³ and echocardiography (ECHO) reveals a decreased ventricular mass and mitral valve prolapse (see Other Tests). GI signs include intestinal dilation from constipation and diminished intestinal motility.

Mental health assessment

When performing a mental health assessment, focus on making a diagnosis, identifying concurrent emotional-behavioral illnesses, evaluating for the risk of suicide,^{14, 15} and exploring the psychosocial context of the symptoms.

The following are characteristic signs of inadequate energy (caloric) intake observed in patients with anorexia nervosa that are due to starvation-induced changes:

• Positive
• • Hypothermia
  • Acrocyanosis
  • Resting bradycardia (resting heart rate often 40-49 beats per minute)
  • Hypotension
  • Orthostatic lowered blood pressure or pulse
  • Loss of muscle mass
  • Low blood glucose (impaired insulin clearance)
  • Low parathyroid hormone levels
  • Elevated liver function
  • Low WBC count
• Negative
• • Normal fundi or visual fields
  • No organomegaly
  • No lymphadenopathy

Causes

Anorexia nervosa is a complex condition based on various biologic, psychologic, and social issues. As such, referring to anorexia nervosa as a developmental condition rather than a mental condition is preferable. Therefore, commenting about predisposing, precipitating, and perpetuating factors is more useful than commenting about actual causes.

• Predisposing factors include the following factors that make a patient more vulnerable to developing an eating disorder:
• • Female sex
  • Family history of eating disorders¹⁶
  • Perfectionistic personality
  • Difficulty communicating negative emotions
  • Difficulty resolving conflict
  • Low self-esteem
• Precipitating factors relate most often to developmental tasks that cause intense intrapsychic conflict and unconscious feelings of anxiety related to developing into a mature sexual person; these factors interact with physiological and biological factors.
• • In individuals aged 10-14 years, these factors are related to sexual development and menarche, which is associated with a spurt in weight gain. Societal influences intensify the fear of becoming "fat." This feeling is often intensified by a peer group that comments in a rejecting fashion. These individuals often diet and receive peer acceptance for weight loss; this emotional reinforcement combined with the physiological response of the body to the sudden loss of weight (when >5 lb) intensifies the likelihood of continued weight loss. Sudden weight loss with loss of fat causes a decrease in body temperature, which physiologically causes a subjective feeling of chills; this discomfort is relieved by increased physical activity, which causes further weight loss. The continuous downward spiraling of weight loss then causes secondary amenorrhea and loss of secondary sexual characteristics, which further worsens weight loss.
  • In individuals aged 15-16 years, precipitating factors stem from independence and autonomy struggles. Ambivalence about growing up is present, and an abnormal transition from dependence to interdependence rather than independence occurs.
  • In individuals aged 17-18 years, identity conflicts are more common. These patients do not make healthy transitions from leaving home to going to college or getting married.
• Perpetuating factors maintain the eating disorder.
• • Biologic issues refer to the signs and symptoms of starvation and to the aspects involved in refeeding the malnourished patient.
  • Psychologic issues encompass the coping strategies engendered by the eating disorders. According to Kreipe et al in 2000, the treating clinician may threaten the homeostatic balance that has been achieved within the family system secondary to dealing with the patient with anorexia; negative emotions, such as anger and denial, may be directed at the clinician.¹⁷

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

Other Problems to be Considered

Inflammatory bowel disease
Cancer
Chronic undiagnosed organic disease (infectious, congenital, or metabolic)
Osteoporosis
Osteopenia
Myeloma
Cardiac valvular disease
Pellagra
Occult infection (if heart rate is normal or elevated)
Sheehan syndrome
Cataracts
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS)¹⁸
Rash (due to low zinc)¹⁹

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

Lab Studies

Because an eating disorder is a clinical diagnosis, no specific diagnostic tests are available. However, perform the following laboratory tests to evaluate the patient:

• Obtain a CBC count with erythrocyte sedimentation rate (ESR).
• Perform urinalysis.
• Obtain blood chemistries analysis.
• Hyponatremia reflects excess water intake or the inappropriate secretion of antidiuretic hormone (ADH).
• Hypoglycemia is observed secondary to lack of glucose precursors in the diet or low glycogen stores.
• Renal function is generally normal except in the case of dehydration when the BUN level may be elevated.
• A hypokalemic hypochloremic metabolic alkalosis is observed with vomiting, and acidosis is observed in cases of laxative abuse.
• Protein and albumin are surprisingly normal because, although the amount of food intake is restricted, it usually contains high-quality proteins.
• Liver function test results are minimally elevated, but levels encountered in patients with active hepatitis are not observed.
• Dramatic elevations in cholesterol are observed in cases of starvation. This elevation may be secondary to (1) decrease in triiodothyronine (T3) levels, (2) low cholesterol binding globulin, and (3) leakage of intrahepatic cholesterol.
• Leukopenia, secondary to increased margination, and thrombocytopenia are observed. The leukopenia is not a sign that the patient is at an increased risk for infection.
• Hemoglobin levels are typically normal, although elevations are observed in states of dehydration. If anemia is observed, it is not due to menstrual blood loss because these patients are usually amenorrheic. In such cases, further investigation is warranted.
• The ESR is normal. Elevations should prompt a search for an organic etiology as noted above.

Other Tests

• Cardiovascular complications account for most of the morbidity and mortality associated with this condition.
• An ECG is helpful in evaluating for a prolonged QT interval. ECG findings may include low voltage, prolonged QTc, and nonspecific T-wave changes.¹³ In patients taking drugs with a prolonged QT, potential harmful dysrhythmias are possible.

Staging

Anorexia nervosa can be divided into an early or mild stage and an established stage.^{17, 20}

• Early or mild stage is defined by the following:
• • Mildly distorted body image
  • Weight 90% or less of average weight for height
  • No symptoms or signs of excessive weight loss
  • Use of potentially harmful weight-control methods or a strong drive to lose weight
• Established or moderate stage features include the following:
• • Definitely distorted body image that has not diminished with weight loss
  • Weight goal less than 85% of average weight for height associated with a refusal to gain weight
  • Symptoms or signs of excessive weight loss associated with a denial that any problems is present
  • Unhealthy means to lose weight, such as eating fewer than 1000 calories per day, purging, or excessive exercise

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

Medical Care

The medical modality is geared toward correcting and preventing the complications of anorexia nervosa.

• Monitoring of weight, vital signs, and serum electrolyte levels is important.
• Weight gain is a primary goal of treatment. Weight gain should not be excessive because rapid refeeding can lead to excessive bloating, edema, and, rarely, congestive heart failure (CHF).
• Outpatient treatment should only be done with very close monitoring, such as weekly weight measurement wearing only a gown.
• Family therapy should only be performed conjointly if the level of expressed emotion is not excessive;²¹ simultaneous sessions can be more productive because if patients feel intense negative emotions from their families they are more likely to be noncompliant with treatment.
• Tube feeding often must be initiated on an inpatient basis when the patient's weight is less than or at 85% of expected weight because outpatient refeeding can be too uncomfortable and the weight gain can be too rapid for the patient to tolerate, sabotaging treatment.
• Prolongation of the QT interval is a contraindication for the use of tricyclic antidepressants because a prolonged QT may increase the risk of ventricular tachycardia and death.
• No treatment is needed for the euthyroid sick syndrome.
• Estrogen has no established effect on bone density in patients with anorexia nervosa, and vitamin supplementation with calcium should be started.
• Those at risk medically or psychiatrically require inpatient treatment. Indications for inpatient treatment include the following:
• • Low weight (£85% of expected weight) or rapid weight loss
  • Lack of any weight gain
  • Significant edema
  • Severe electrolyte imbalance (life-threatening risks created by sodium and potassium derangements)
  • Temperature less than 36ºC
  • Pulse less than 45 beats per minute
  • Altered mental status or other signs of severe malnutrition
  • Cardiac disturbances or other acute medical disorders
  • Psychosis or a high risk of suicide
  • Symptoms refractory to outpatient treatment
• Individuals with anorexia nervosa may respond best to family therapy. Psychodynamic psychotherapy in combination with behavioral strategies is indispensable. Psychopharmacologic therapy is generally not helpful, although fluoxetine may stabilize recovery in patients who have already attained 85% of their weight.

Consultations

The approach to the treatment of individuals with anorexia nervosa is multidisciplinary. Consultations with specialists in adolescent medicine, nutrition, psychiatry or behavioral-developmental pediatrics, and psychology may be required.

Various psychological therapies have proven helpful in treating patients with anorexia nervosa, including the following:^{22, 23, 24}

• Individual therapy (insight-oriented)
• Cognitive analytic therapy
• Cognitive behavior therapy
• Interpersonal therapy
• Motivational enhancement therapy
• Dynamically informed therapies
• Group therapy
• Family therapy
• Conjoint therapy
• Separated family therapy
• Multifamily groups
• Relatives and caregiver support groups

Tube refeeding does not impair efficacy of any psychological therapies.²⁵

Diet

Nutrition is an important part of the treatment for the individual with anorexia nervosa. A nutritionist or dietitian should be an integral part of the treatment plan because the well-recognized refeeding syndrome can occur during the early stages of refeeding the patient with anorexia. This syndrome encompasses cardiovascular collapse; starvation-induced hypophosphatemia; and dangerous fluctuations in potassium, sodium, and magnesium levels.

• According to Becker at al in 1999, for adequate weight gain, the patient or family requires some "education on nutrition, adjustment of caloric and nutritional intake, and limitations on exercise and other modifications of behavior. Enteral or parenteral nutrition is reserved for patients with severe undernutrition that has been refractory to treatment by these methods."²⁶
• In the moderate stage of anorexia nervosa, in addition to the above recommendations, providing structure to daily activities is necessary. This includes eating 3 meals a day. Also, parents should ensure that healthy food is available, but the patient should assume all responsibility for eating.
• In 1997, Mehler et al proposed the following strategies to avoid the refeeding syndrome to avoid pitfalls during the refeeding period:⁸
• • Identify patients at risk.
  • Measure serum electrolyte levels and correct abnormalities before refeeding.
  • Obtain serum chemistry values every 3 days for the first 7 days and then weekly during the rest of refeeding.
  • Attempt to increase daily caloric intake slowly by 200-300 kcal every 3-5 days until sustained weight gain of 1-2 pounds per week is achieved.
  • Monitor the patient carefully for development of tachycardia²⁷ or edema.
• Monitor for pellagra and administer niacin supplementation if needed.²⁸

Activity

Limited physical activity (eg, sports, exercise classes) is recommended. By limiting activity, energy expenditure is limited, thus assuring a balanced weight. Limitation of activity may also motivate the patient to maintain healthy eating habits in order to ensure a rapid return to favorite activities. Note that the disadvantage of curtailing activity is the removal of the patient's coping mechanism to deal with stress.

• Anorexia nervosa is based on caloric restriction and increased caloric expenditure that leads to excess exercise to control weight. Previous studies have described the use of exercise programs for hospitalized inpatients in which exercise was exchanged for weight gain and compliance. However, no guidelines were set forth in terms of type, intensity, and duration of exercise.
• A study by Thein et al (2000) looked at a standard program designed for outpatient use, graduated in type of exercise, duration, and level of activity.²⁹ Without structure, patients could be exercising in potentially harmful ways and at very high intensities. This study showed that both the exercise and the control groups increased in body mass index (BMI) and body fat percentage. However, quality of life was increased in the exercise group, whereas the control group showed a decrease in all aspects of quality-of-life measures, although the difference was not statistically significant.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

The use of medication for individuals with anorexia nervosa is limited to the treatment of medical complications. To treat osteopenia and to prevent further bone loss, dietary calcium (1000-1500 mg/d) and vitamin D (400 IU) are recommended. Estrogen replacement in the form of oral contraceptives has also been recommended for the treatment of osteopenia, although the benefits and minimal effective dose have not been established.

In anorexia nervosa, bone density is compromised, which can lead to an increase in fractures and early osteoporosis. The intake of calcium and other macronutrients that normally strengthen bone decreases because of poor nutrition. Studies of dehydroepiandrosterone (DHEA) using 50 mg, 100 mg, and 200 mg have reported a decrease in bone resorption, an increase in bone formation markers, and a possible association with resumption of menses (53%).³⁰

The antiosteolytic and anabolic effects of DHEA have been noted to be secondary to the androgenic effects on bone mass and not secondary to the estrogenic effects, as was previously thought. Potential adverse effects include mild acne; decreases in cholesterol, high-density lipoprotein (HDL) and sex hormone binding globulin (SHBG) levels; insulin resistance, and hirsutism.

Limitations of the study by Gordon et al included the small size, a question of compliance, and the self-reporting of activity levels and nutritional intake; no response relationship between the doses of 50 mg, 100 mg, or 200 mg was clear.³⁰

Pharmacotherapy is generally not effective. In patients with anorexia nervosa who have already attained 85% of their expected weight, fluoxetine has been used to stabilize recovery. Zinc and cyproheptadine have not been useful.

Antidepressive and neuroleptic agents, although not reported to be effective, have a limited use in patients who have mood changes associated with anorexia nervosa. Their use is limited in patients with inadequate nutrition.

Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred over the other classes of antidepressants.³¹ Because the adverse effect profile of SSRIs is less prominent, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered in the treatment of a child or adolescent with a mood disorder.

Physicians are advised to be aware of the following information and use appropriate caution when considering treatment with SSRIs in the pediatric population:

• In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
• In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (both ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
• However, a recent study of more than 65,000 children and adults treated for depression between 1992 and 2002 by the Group Health Cooperative in Seattle found that suicide risk declines, not rises, with the use of antidepressants.³² This is the largest study to date to address this issue.
• Currently, evidence does not support an increased risk of suicide in patients with obsessive-compulsive disorder (OCD) and other anxiety disorders who are treated with SSRIs.

Part of the pathophysiology of anorexia nervosa is a delay in gastric emptying, which can perpetuate the disorder by limiting the quantity of food that can be eaten. A study of cisapride (Propulsid) to improve gastric emptying did not show enhancement, but the patients did report a greater improvement in subjective symptoms during a meal.³³ However, in 2000, cisapride use in patients with anorexia nervosa or bulimia was advised against because of serious cardiac events associated with the drug (ie, serious arrhythmias associated with prolonged QTc) and the risk of cardiovascular-related events in patients with eating disorders.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

Further Inpatient Care

• Inpatient management should be approached in such a way as not to seem like punishment to the patient in order to preserve self-esteem and to prevent suicidality and hopelessness.
• The goals of inpatient therapy should be fully discussed with the family and the patient.
• The discussion elements should include development of a healthy meal plan, addressing underlying conflicts (low self-esteem, planning new coping strategies), and enhancing communication skills.
• Randomized controlled trials show that cognitive behavior therapy is very effective, especially in the setting of tube feeding.³⁴
• In a study by McIntosh et al that compared 3 psychotherapies, interpersonal psychotherapy and family therapy were also reported to be effective when the expressed emotion was not negative.³⁵
• • Some patients who received nonspecific management appeared to have as good or better an outcome as those who received the other therapies
  • Interpersonal psychotherapy was the least effective.
  • Cognitive behavior therapy outcomes were not as effective because of the large amount of psychoeducational material, large skills acquisition, and "the inability to generate alternatives to fixed cognition stemming from the cognitive rigidity of anorexia nervosa patients."³⁵
  • Nonspecific management may be more successful because the therapy is provided by experienced clinicians, is practiced according to a detailed treatment manual, and institutes psychoeducation with a strong focus on normalizing eating with approaches such as smart food selection and quantities needed to gain weight. The rest of the sessions were based on issues presented by the patient. Key features of this type of therapy may include the nonspecific factor of empathy and therapeutic alliance. Because this is the first time this nonspecific management was studied, a replication of this study may be necessary
• Family involvement is a vital part of the process in the treatment of anorexia nervosa. Family group psychotherapy has been shown to be more cost-effective than family therapy and equally useful (weight gain measurements).³⁶
• Robin et al studied the effect of family relations on behavioral family systems therapy (BFST) versus ego-oriented individual therapy (EOIT) as treatment modalities for adolescents with anorexia nervosa.³⁷ Although the difference was not statistically disparate, the results demonstrated a greater improvement in BMI in the BFST group. In addition, in this group, the mothers showed a decrease in negative communication and an increase in positive communication, whereas the mothers in the other group did not.
• Indications for hospital admission include the following:
• • Physiologic decompensation
  • • Temperature less than 36°C
    • Pulse less than 45 beats per minute
    • Orthostatic differential greater than 30/min
    • Altered mental status, fainting, or other signs of significant malnutrition
    • Rapid or excessive weight loss that cannot be curtailed as an outpatient
  • Complications of weight control habits
  • • Inability to break the cycle of disordered eating as outpatient
    • Inability to initiate effective outpatient psychotherapy¹⁷

Further Outpatient Care

• Patients with anorexia nervosa may respond best to family therapy. Psychodynamic psychotherapy in combination with behavioral strategies is indispensable. Remember that anorexia nervosa is associated with suicide.
• For patients with the mild stage of anorexia nervosa, reevaluate in 1-2 months to check that the weight is not decreasing, that health is maintained, and that the patients have not developed bad eating habits. Surveillance is required to ensure that the patient has not progressed to the moderate stage.

Complications

• Most complications are secondary effects from starvation. Complications of anorexia nervosa include the following:
• • Orofacial - Dental caries
  • Cardiovascular³⁸
  • • Hypotension
    • Prolonged QT
    • Arrhythmias
    • Cardiomyopathy
  • GI
  • • Delayed gastric emptying
    • Decreased intestinal mobility
    • Constipation
  • Endocrine and metabolic
  • • Hypokalemia
    • Hyponatremia
    • Hypoglycemia
    • Hypothermia
    • Euthyroid sick syndrome
    • Hypercortisolism
    • Amenorrhea
    • Delay in puberty
    • Arrested growth
    • Osteoporosis
  • Renal - Renal calculi
  • Reproductive
  • • Infertility
    • Low birth weight infant
  • Integumentary
  • • Dry skin and hair
    • Hair loss
    • Lanugo body hair
  • Neurologic
  • • Peripheral neuropathy
    • Ventricular enlargement
  • Hematologic
  • • Anemia
    • Leukopenia
    • Thrombocytopenia
• Cardiac complications are the most common cause of death; the mortality rate is about 10%.
• • Cardiac effects include profound bradycardia, hypotension, decreased size of cardiac silhouette, and decreased left ventricular mass associated with abnormal systolic function. Patients with anorexia report fatigue and have an attenuated blood pressure response to exercise and reduction in maximal work capacity. An increased incidence of mitral valve prolapse without significant mitral regurgitation is also observed. Low potassium-dependent QT prolongation increases risk of ventricular arrhythmia.³⁹
  • Vital signs reflect hypotension with systolic pressures as low as 70 mm Hg and sinus bradycardia with heart rates as low as 30-40 beats per minute. These changes are a response to a decrease in basal metabolic rate. The mechanism may be due to an autonomic imbalance in heart rate regulation with increases in vagal activity and a reduction in sympathetic activity. These changes are physiologic cardiovascular responses, and treatment is unnecessary unless negative clinical sequelae are present. If ECG is performed, evidence of sinus bradycardia, ST-segment elevation, T-wave flattening, low voltage, and rightward QRS axis is apparent. All the aforementioned changes are clinically insignificant. The frequency of rhythm disturbances is most concerning, especially QT interval prolongation that may be an indication for those at risk for cardiac arrhythmias and sudden death.
  • Cardiac decompensation is greatest during the initial 2 weeks of refeeding when the myocardium cannot withstand the stress of an increased metabolic demand. If the daily weight gain is 0.2-0.4 kg, then complications are limited.
• Foremost in the gamut of endocrinologic complications is amenorrhea, which is actually part of the diagnostic criteria of anorexia nervosa.
• • Amenorrhea results from disorders in the hypothalamic-pituitary-ovarian axis in which levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are low despite low levels of estrogen. Reversion to the prepubertal state occurs; the LH response to gonadotropin-releasing hormone (GnRH) is blunted. This blunted response is insufficient to maintain menstrual integrity, and amenorrhea results.
  • Weight loss and emotional instability play a role in amenorrhea, although persistence of amenorrhea has been observed in some patients despite a return to baseline weight.
  • Amenorrhea persists in 5-44% of patients in whom weight gain has been documented. The explanation for this wide range has not been elucidated.
• Other changes related to endocrine function include a reduction in fertility, multiple small follicles in the ovaries, and decreased uterine volume and atrophy.
• Thyroid function is also affected, with laboratory data revealing a decrease in T3, thyroxine (T4), and an increase in reverse T3. These changes are characteristic of the euthyroid sick syndrome. Similar to the cardiac changes, these represent an adaptive mechanism and hormonal replacement is not necessary.
• An associated impaired release in vasopressin consistent with diabetes insipidus is present. This defect is of the neurogenic type; concentration of urine is observed after administering vasopressin. This affects 40% of those with anorexia nervosa and is reversible with weight gain.
• Osteopenia is a serious complication. Both cortical and trabecular bone are affected, and osteopenia persists despite estrogen therapy. Low levels of progesterone (accelerates remodeling) formation and decreased insulinlike growth factor-1 (IGF-1) levels, which stimulate type 1 collagen biosynthesis, contribute to bone loss. No established treatment is available; however, 1000-1500 mg/d of dietary calcium and 400 IU of vitamin D is recommended to prevent further bone loss and to maximize peak bone mass. Although exercise and hormonal replacement therapy have some benefit in perimenopausal women, exercise may be deleterious in patients with anorexia nervosa who have amenorrhea, and hormonal replacement may induce premature closure of bone epiphysis. Treatment with bisphosphates is not indicated in adolescents.⁴⁰
• Patients with anorexia nervosa have fewer GI complications than those with bulimia. Constipation is common. In addition, they still have prolonged GI transit, alterations in antral motility, and gastric atrophy. Prokinetic agents may accelerate gastric emptying, and the relief from gastric bloating can accelerate resumption of normal eating habits.
• Cerebral atrophy and loss of brain volume may be observed. Generalized muscle weakness is the most common neurologic symptom.
• Patients with anorexia nervosa typically have dry scaly skin, brittle hair and nails, and increased lanugo-type body hair.
• An increase in BUN levels, which reflects a level of dehydration and decreased glomerular filtration rate (GFR), is present. Electrolyte imbalances are secondary to vomiting, and potassium is most often affected. Other abnormalities include disturbances of calcium, magnesium, and phosphorus.

Prognosis

• As described in Mortality/Morbidity, outcome depends on various prognostic factors, including age at onset, weight loss at presentation, duration of symptoms, duration of inpatient care, and state of family relationships.
• Metacognition plays a role in predicting adverse outcomes or suicide, as does alexithymia.⁴¹
• The mortality rate in anorexia nervosa is 10-20%. Overall, 50% of patients recover completely. Another 20% remain emaciated, 25% are thin, and 5-10% remain overweight or die of starvation.¹⁰
• Joint family therapy is not as effective as separated family therapy when levels of maternal criticism are raised.²³

Patient Education

• For excellent patient education resources, visit eMedicine's Eating Disorders Center and Women's Health Center. Also, see eMedicine's patient education articles Anorexia Nervosa and Amenorrhea.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

Medical/Legal Pitfalls

• Maintain safety is important; therefore, hospitalization should not be shunned because anorexia nervosa is a complex chronic disorder associated with high comorbidity and significant mortality and complications.⁴² It is difficult to treat due to the shame, denial, and lack of insight concomitant with the disorder.
• Restoring normal eating patterns is crucial because otherwise the restoration of health cannot occur.⁴³

Special Concerns

A history of previous attempts, physical pain, drug use, and laxative use may correlate with a higher likelihood of suicide attempts.^{14, 44, 15}

FURTHER READING

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

The SCOFF questionnaire is a screening tool for eating disorders. One point is awarded for every positive reply. A score greater than 2 indicates likely anorexia nervosa or bulimia. The questionnaire is as follows:⁴⁵

• Do you make yourself Sick because you feel uncomfortably full?
• Do you worry you have lost Control over how much you eat?
• Have you lost more than One stone in a 3-month period?
• Do you believe yourself to be Fat when others say you are too thin?
• Would you say that Food dominates your life?

ACKNOWLEDGMENTS

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Jennifer DA Liburd, MD to the development and writing of this article.

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• MISCELLANEOUS
• Further Reading
• Acknowledgments
• References

1. Slupik RI. Managing adolescents with eating disorders. Int J Fertil Womens Med. May-Jun 1999;44(3):125-30. [Medline].
2. Fetissov SO, Harro J, Jaanisk M, et al. Autoantibodies against neuropeptides are associated with psychological traits in eating disorders. Proc Natl Acad Sci U S A. Oct 11 2005;102(41):14865-70. [Medline].
3. APA. Diagnostic and Statistical Manual of Mental Disorders. 4^th ed. Washington, DC: APA; 1994.
4. Feldman MB, Meyer IH. Childhood abuse and eating disorders in gay and bisexual men. Int J Eat Disord. Jul 2007;40(5):418-23. [Medline].
5. National Institute of Mental Health. National Comorbidity Survey (NCS) and National Comorbidity Survey Replication (NCS-R). Collaborative Psychiatric Epidemiology Surveys. Available at http://www.icpsr.umich.edu/CPES/. Accessed October 30, 2007.
6. Button E, Aldridge S. Season of birth and eating disorders: patterns across diagnoses in a specialized eating disorders service. Int J Eat Disord. Jul 2007;40(5):468-71. [Medline].
7. Grice DE, Halmi KA, Fichter MM, et al. Evidence for a susceptibility gene for anorexia nervosa on chromosome 1. Am J Hum Genet. Mar 2002;70(3):787-92. [Medline].
8. Mehler PS, Gray MC, Schulte M. Medical complications of anorexia nervosa. J Womens Health. Oct 1997;6(5):533-41. [Medline].
9. Rooney B, McClelland L, Crisp AH, Sedgwick PM. The incidence and prevalence of anorexia nervosa in three suburban health districts in south west London, U.K. Int J Eat Disord. Dec 1995;18(4):299-307. [Medline].
10. Speranza M, Loas G, Wallier J, Corcos M. Predictive value of alexithymia in patients with eating disorders: A 3-year prospective study. J Psychosom Res. Oct 2007;63(4):365-71. [Medline].
11. Bryant-Waugh R, Knibbs J, Fosson A, Kaminski Z, Lask B. Long term follow up of patients with early onset anorexia nervosa. Arch Dis Child. Jan 1988;63(1):5-9. [Medline].
12. Jordan J, Joyce PR, Carter FA, et al. Specific and nonspecific comorbidity in anorexia nervosa. Int J Eat Disord. Jan 2008;41(1):47-56. [Medline].
13. Lesinskiene S, Barkus A, Ranceva N, Dembinskas A. A meta-analysis of heart rate and QT interval alteration in anorexia nervosa. World J Biol Psychiatry. Apr 5 2007;1-6. [Medline].
14. Franko DL, Keel PK, Dorer DJ, Blais MA, Delinsky SS, Eddy KT. What predicts suicide attempts in women with eating disorders?. Psychol Med. Jul 2004;34(5):843-53. [Medline].
15. Holm-Denoma JM, Witte TK, Gordon KH, et al. Deaths by suicide among individuals with anorexia as arbiters between competing explanations of the anorexia-suicide link. J Affect Disord. Apr 2008;107(1-3):231-6. [Medline].
16. Lilenfeld LR, Kaye WH, Greeno CG, et al. A controlled family study of anorexia nervosa and bulimia nervosa: psychiatric disorders in first-degree relatives and effects of proband comorbidity. Arch Gen Psychiatry. Jul 1998;55(7):603-10. [Medline].
17. Kreipe RE, Birndorf SA. Eating disorders in adolescents and young adults. Med Clin North Am. Jul 2000;84(4):1027-49, viii-ix. [Medline].
18. Puxley F, Midtsund M, Iosif A, Lask B. PANDAS anorexia nervosa--endangered, extinct or nonexistent?. Int J Eat Disord. Jan 2008;41(1):15-21. [Medline].
19. Roberts CM, Martin-Clavijo A, Winston AP, Dharmagunawardena B, Gach JE. Malnutrition and a rash: think zinc. Clin Exp Dermatol. Nov 2007;32(6):654-7. [Medline].
20. Nicholls D, Viner R. Eating disorders and weight problems. BMJ. Apr 23 2005;330(7497):950-3. [Medline].
21. Kyriacou O, Treasure J, Schmidt U. Expressed emotion in eating disorders assessed via self-report: an examination of factors associated with expressed emotion in carers of people with anorexia nervosa in comparison to control families. Int J Eat Disord. Jan 2008;41(1):37-46. [Medline].
22. Morris J, Twaddle S. Anorexia nervosa. BMJ. Apr 28 2007;334(7599):894-8. [Medline].
23. Eisler I, Simic M, Russell GF, Dare C. A randomised controlled treatment trial of two forms of family therapy in adolescent anorexia nervosa: a five-year follow-up. J Child Psychol Psychiatry. Jun 2007;48(6):552-60. [Medline].
24. Rosenblum J, Forman S. Evidence-based treatment of eating disorders. Curr Opin Pediatr. Aug 2002;14(4):379-83. [Medline].
25. Rigaud D, Brondel L, Poupard AT, Talonneau I, Brun JM. A randomized trial on the efficacy of a 2-month tube feeding regimen in anorexia nervosa: A 1-year follow-up study. Clin Nutr. Aug 2007;26(4):421-9. [Medline].
26. Becker AE, Grinspoon SK, Klibanski A, Herzog DB. Eating disorders. N Engl J Med. Apr 8 1999;340(14):1092-8. [Medline].
27. Krantz MJ, Mehler PS. Resting tachycardia, a warning sign in anorexia nervosa: case report. BMC Cardiovasc Disord. Jul 16 2004;4:10. [Medline].
28. Jagielska G, Tomaszewicz-Libudzic EC, Brzozowska A. Pellagra: a rare complication of anorexia nervosa. Eur Child Adolesc Psychiatry. Oct 2007;16(7):417-20. [Medline].
29. Thien V, Thomas A, Markin D, Birmingham CL. Pilot study of a graded exercise program for the treatment of anorexia nervosa. Int J Eat Disord. Jul 2000;28(1):101-6. [Medline].
30. Gordon CM, Grace E, Emans SJ, et al. Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa. J Bone Miner Res. Jan 1999;14(1):136-45. [Medline].
31. Ramoz N, Versini A, Gorwood P. Eating disorders: an overview of treatment responses and the potential impact of vulnerability genes and endophenotypes. Expert Opin Pharmacother. Sep 2007;8(13):2029-44. [Medline].
32. Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment. Am J Psychiatry. Jan 2006;163(1):41-7. [Medline]. [Full Text].
33. Szmukler GI, Young GP, Miller G, Lichtenstein M, Binns DS. A controlled trial of cisapride in anorexia nervosa. Int J Eat Disord. May 1995;17(4):347-57. [Medline].
34. Bergh C, Brodin U, Lindberg G, Sodersten P. Randomized controlled trial of a treatment for anorexia and bulimia nervosa. Proc Natl Acad Sci U S A. Jul 9 2002;99(14):9486-91. [Medline].
35. McIntosh VV, Jordan J, Carter FA, et al. Three psychotherapies for anorexia nervosa: a randomized, controlled trial. Am J Psychiatry. Apr 2005;162(4):741-7. [Medline].
36. Geist R, Heinmaa M, Stephens D, et al. Comparison of family therapy and family group psychoeducation in adolescents with anorexia nervosa. Can J Psychiatry. Mar 2000;45(2):173-8. [Medline].
37. Robin AL, Siegel PT, Moye A. Family versus individual therapy for anorexia: impact on family conflict. Int J Eat Disord. May 1995;17(4):313-22. [Medline].
38. Matzkin V, Slobodianik N, Pallaro A, Bello M, Geissler C. Risk factors for cardiovascular disease in patients with anorexia nervosa. Int J Psychiatr Nurs Res. Sep 2007;13(1):1531-45. [Medline].
39. Facchini M, Sala L, Malfatto G, Bragato R, Redaelli G, Invitti C. Low-K+ dependent QT prolongation and risk for ventricular arrhythmia in anorexia nervosa. Int J Cardiol. Jan 13 2006;106(2):170-6. [Medline].
40. Golden NH. Eating disorders in adolescence: what is the role of hormone replacement therapy?. Curr Opin Obstet Gynecol. Oct 2007;19(5):434-9. [Medline].
41. Woolrich RA, Cooper MJ, Turner HM. Metacognition in patients with anorexia nervosa, dieting and non-dieting women: a preliminary study. Eur Eat Disord Rev. Sep 22 2007;[Medline].
42. Gowers SG. Management of eating disorders in children and adolescents. Arch Dis Child. Apr 2008;93(4):331-4. [Medline].
43. Muscari M. Effective management of adolescents with anorexia and bulimia. J Psychosoc Nurs Ment Health Serv. Feb 2002;40(2):22-31. [Medline].
44. Witte TK, Merrill KA, Stellrecht NE, Bernert RA, Hollar DL, Schatschneider C. "Impulsive" youth suicide attempters are not necessarily all that impulsive. J Affect Disord. Sep 3 2007;[Medline].
45. Morgan JF, Reid F, Lacey JH. The SCOFF questionnaire: assessment of a new screening tool for eating disorders. BMJ. Dec 4 1999;319(7223):1467-8. [Medline].
46. Steiner H, Lock J. Anorexia nervosa and bulimia nervosa in children and adolescents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. Apr 1998;37(4):352-9. [Medline].
47. Steinhausen HC. Outcome of anorexia nervosa in the younger patient. J Child Psychol Psychiatry. Mar 1997;38(3):271-6. [Medline].
48. Tan JO, Hope T, Stewart A, Fitzpatrick R. Control and compulsory treatment in anorexia nervosa: the views of patients and parents. Int J Law Psychiatry. Nov-Dec 2003;26(6):627-45. [Medline].
49. Tchanturia K, Davies H, Campbell IC. Cognitive remediation therapy for patients with anorexia nervosa: preliminary findings. Ann Gen Psychiatry. 2007;6:14. [Medline].
50. Wade TD, Gillespie N, Martin NG. A comparison of early family life events amongst monozygotic twin women with lifetime anorexia nervosa, bulimia nervosa, or major depression. Int J Eat Disord. Sep 14 2007;40(8):679-686. [Medline].
51. Ward L, Tricco A, Phuong P, Cranney A, Barrowman N, Gaboury I. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007;(4):CD005324. [Medline].
52. Wildes JE, Marcus MD, Gaskill JA, Ringham R. Depressive and manic-hypomanic spectrum psychopathology in patients with anorexia nervosa. Compr Psychiatry. Sep-Oct 2007;48(5):413-8. [Medline].

Article Last Updated: Mar 31, 2008