DIAGNOSIS

Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are distinct nosologic/diagnostic classes in the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5). DSM-5 defines AN according to three criteria, the first one being an excessive restriction of food intake as compared to nutrient requirements, which results in a significantly low body weight for the patient's age, sex, and health status. The second criterion includes intense fear of weight gain or becoming obese, even when underweight. The last criterion includes a disordered perception of weight or body image, overrated influence of the latter on self-evaluation, or lack of recognition of the dangers entailed by low body weight.

BN has 3 key characteristics according to DSM-5 -recurrent episodes of binge eating, inappropriate recurrent compensatory behaviors to prevent weight gain, and self-evaluation unduly influenced by weight and body shape. Binge eating episodes and compensatory behaviors occur once weekly on average (instead of twice weekly as in DSM-IV) for at least 3 months. Binge eating is defined as the intake, during a short period of time (within 2 hours), of an amount of food that is definitely larger than most people would eat during a similar period of time and under the same circumstances, with a sense of lack of control over eating. BED is characterized by recurrent episodes of binge eating not associated with inappropriate compensatory behaviors. Other emerging clinical conditions are also reviewed ^1,2,3,4.

EPIDEMIOLOGY AND ETIOPATHOGENESIS

Interest in these conditions has significantly rekindled in recent years, perhaps because of the perception that they are increasingly common emerging disorders. EDs are more common in women and in adolescents; without treatment, they develop a chronic, disabling clinical course. Currently, a combined prevalence of 13% was estimated for all EDs. BED represents the most prevalent ED in the adult population. AN is the most common psychiatric illness in younger women, and the third most common chronic condition after obesity and asthma among adolescents.

Although the etiopathogenesis of EDs remains unclear as of today, a plurifactorial origin is presumed with the involvement of genetic, psychologic, biologic, sociofamiliar, and cultural factors, amongst others. Common to all EDs is a history of excessive concern over weight, obsession with a thin body, sociofamiliar distress, dieting, and childhood sexual abuse ^5,6,7,8.

THE THERAPEUTIC TEAM

EDs are highly variable in presentation and severity, which leads to different management considerations and individualized therapy. Therefore, a multidisciplinary, highly specialized approach is key. A treating team includes: psychiatrists, psychologists, family doctors, nutrition physicians (or endocrinologists), dieticians, nurses, and occupational therapists, with each professional unquestionably contributing their unique skills.

ED units and teams are usually coordinated by a psychiatrist, who is responsible for overall management supervision. Family doctors, provided they are trained, will play a role in relapse prevention, as well as in primary prevention programs and in reaching a diagnosis as soon as possible.

Patients should be placed under the supervision and management of a nutrition physician, responsible for assessing their nutritional status and potentially accompanying somatic complications. A dietician is the right person to provide nutritional education (NE), although highly trained, experienced nurses in this topic may also play this role ^{9,10,11,12,13}.

CLINICAL AND NUTRITIONAL ASSESSMENT

History taking should focus on diagnosing a specific ED, on assessing nutritional status and presence of organicity or comorbidity symptoms, and on reaching a differential diagnosis with other conditions. Patients are commonly unaware of their disease and may hide symptoms suggesting their illness. Anamnesis should explore eating behavior, potential food restriction, duration, quantity and quality of ingested food, and presence of binge eating, purging behavior, and other compensatory mechanisms, making it advisable to corroborate a patient's story with information collected from their relatives and friends.

Physical examination findings will depend on ED type and may include depleted body compartments, deficiency signs, and evidence of hemodynamic adaptation to prolonged fasting or purging habits. Weight, height, and body mass index (BMI) should be collected, as well as their deviation from ideal weight and course over time. Anthropometric data must be adjusted for children and adolescents using percentile curves for age, sex, and height.

Initial laboratory tests should not differ from usual practice. Save for complications, results will be within normal values. An electrocardiogram (ECG) should be routinely performed. A nutritional and body composition assessment is advisable according to available recources. Energy expenditure at rest may be estimated using predictive equations such as the Harris-Benedict formula, but indirect calorimetry is more appropriate ^{14,15,16,17,18}.

ASSOCIATED COMPLICATIONS

EDs are associated with multiple medical complications related to severity, duration, and predominant eating pattern - restrictive, compulsive and/or purgative.

Patients presenting with malnutrition develop atrophy in multiple vital organs and systems, which varies according weight loss extent and disease chronicity. They may exhibit fatigability, reduced functional capacity, chest pain, palpitations, hypotension, orthostatism, and increased risk for heart failure. Among hormonal disorders, persistent hypogonadism is most clinically significant because of its deleterious effects on bone mineral density. From a metabolic perspective, hypoglycemia and high cholesterol levels may develop in over 50% of patients. Slow gastric emptying is common, as are constipation and changes in liver enzyme profile. Regarding the kidneys, patients with malnutrition have reduced glomerular filtration and impaired urine concentration. In the lungs, respiratory muscle and diaphragmatic weakness result in diminished functional capacity and increased risk for spontaneous pneumothorax and pneumomediastinum. In the blood a number of cytopenias may develop, with anemia and leukopenia being most common. Patients may exhibit cognitive impairment and neuropsychological dysfunction primarily involving attention, memory, and executive functions, and to a lesser extent visual processing and verbal aptitude. Micronutrient deficiency may lead to neuropathy.

Obesity, found in up to 30% of patients with BED, entails a higher risk for metabolic conditions such as type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, and other secondary disorders (hiatal hernia, cholelithiasis, steatosis, respiratory failure, sleep apnea, heart failure, venous insufficiency, intracranial hypertension, and musculoskeletal conditions), as well as a higher incidence of selected tumors.

Compensatory purging may result in local complications (tooth decay, gingivitis, periodontal disease, temporomandibular joint disorders, sialadenosis, laringopharyngeal reflux, bronchoaspiration, gastroesophageal reflux, esophagitis, Mallory-Weiss syndrome, Boerhaave syndrome, cathartic colon, rectal prolapse, hemorrhoids, and Russell's sign) and systemic issues (water-electrolyte and acid-base balance disorders, and neurological, cardiac or renal manifestations) ^{19,20,21,22,23,24,25}.

GENERAL MANAGEMENT MEASURES

The goals of treatment for patients with EDs must be individualized, realistic, and adapted to the patient's context and clinical status:

The treatment of patients with ED may comprise different levels of care, and must always be multidisciplinar, its primary pillars encompassing psychotherapy, medical management, and nutritional support.

The psychologic therapy recommended for BED and BN is the cognitive-behavioral approach. Medical aspects include management of ED-associated comorbidities, of malnutrition-derived complications (both malnutrition and obesity), and of compensatory behaviors.

The nutritional plan should include not only individualized dietary counseling to ensure an appropriate nutritional status but also education, providing patients with the information needed to modify eating habits in the long term, and stop purging and binge eating behaviors. Such plan has peculiarities according to ED type and clinical status. In low-weight individuals, as is often the case with AN and occasionally BN patients, recovery of normal weight and nutritional status should be encouraged, taking special care with the development of refeeding syndrome in severely malnourished individuals. Artificial nutrition (ArN) may be necessary, particularly oral supplementation. In patients with overweight, as may be the case in BED and BN individuals, healthy lifestyle modifications are to be encouraged. "Anti-obesity" drugs may be useful in BED, but their use is controversial and should be contraindicated in patients with BN because of their potential for misuse or abuse.

Bariatric surgery (BS) may be used for selected patients with ED, but is contraindicated for BN. Inclusion criteria are the same as for the obese population eligible for BS in the absence of ED. Weight loss in the short-to-mid run in patients with ED undergoing BS is identical to that of patients without ED. An adequate nutritional education program is essential, as is psychological support for patients with ED and morbid obesity both before and after surgery.

Drug therapy is not indispensable but may prove useful. The largest body of evidence involves the indication of fluoxetine for BN, this being considered the best drug available in terms of acceptability, tolerance, and symptom reduction ^14,26,27,28.

NUTRITIONAL EDUCATION

NE should be part of the treatment for ED, and should be action-oriented and practice-centered. Its primary goal is to facilitate the voluntary adoption of eating behaviors to foster good health and well-being. It should take into account not only the disorder diagnosed but also the patient's eating pattern and nutritional understanding.

As regards AN, NE pursues to improve attitude and behavior in relation to food, improve eating patterns, clarify myths, and favor nutritional status recovery with all these changes. For BN, the first step should be the adoption of a reasonable meal schedule focusing on timetables, and at any rate avoiding lengthy periods of fasting. In a later stage food quality will be addressed, always using small, gradual changes and prioritizing the incorporation of healthier foods in order to address, in a final stage, the quantitative aspects involved in the achievement of the desired nutritional balance. For BED, appropriate food selection is emphasized, prioritizing those foods with less energy density that induce greater satiety, as well as control and serve size. Long-term behavior changes will be promoted for obese patients in order to maintain a reasonable weight by selecting healthier foods, acquiring new eating habits, and adopting a healthier regimen of physical activity.

Often NE should be extended to family members, which improves the effectiveness of educational interventions and the adherence of the whole household to the new behavioral models proposed ^{29,30,31,32,33}.

INDICATIONS FOR ARTIFICIAL NUTRITION

ArN encompasses those nutrition modalities (oral, enteral, parenteral) that aim at meeting body needs when such thing is not feasible or is done insufficiently with commonly ingested foods. ArN reduces morbidity and mortality for malnourished patients. It should be indicated following a step-wise schedule, starting with simpler measures such as oral nutritional supplementation (ONS) to later proceed to more complex modalities such as enteral nutrition (EN) and-exceptionally-parenteral nutrition (PN).

Few studies are available on the use of ONS for EDs. However, in clinical practice ONS represents a key tool for the recovery of many patients with AN, particularly when used for short periods of time, always under medical supervision.

For inpatients with ED and low weight ONS allows faster weight gain, and on occasion reduced treatment duration and hospital stay. They are also needed for pregnant women with ED and presence or risk of malnutrition. In the outpatient setting ONS may be indicated after EN withdrawal to sustain nutritional recovery and avoid or attenuate further weight loss on hospital discharge. It is also useful for malnourished outpatients as an alternative to hospitalization, provided there is no vital risk. ONS should be supported by psychotherapy and complete nutritional measures, and its duration must be previously discussed and agreed with the patient. EN through a nasogastric tube is almost exclusively used for inpatients where severity or lack of cooperation mandate its use. Exceptionally, PN may be required when no enteral route is available or EN is contraindicated by a concurrent disease ^{34,35,36,37,38,39}.

OUTPATIENT TREATMENT AND FOLLOW-UP

Outpatient care is the commonest, longest level of treatment for ED, always using a multidisciplinary approach. It requires clinical stability, absence of self-harm risk, and adequate capacity for family, academic, and career life. All patients should receive a structured nutritional assessment. A clinical assessment should be performed at baseline for all EDs, and later at varying intervals according to illness severity. It should cover aspects such as purging behavior (vomiting, laxative or diuretic use), orodental health, vital signs, growth and development in children and adolescents, ovarian cycle in younger females or hypogonadism symptoms in males, physical exam, and laboratory tests.

Medical treatment should accompany psychotherapy to restore nutrient and electrolyte deficiencies. There is no definite consensus among guidelines regarding daily kcal intake, but there is one regarding a weight gain target of 0.5 kg/week for severe malnutrition. Obesity-related issues should be considered in BED (in this case not avoiding caloric restriction and considering bariatric surgery for selected patients).

With a still low level of evidence, telemedicine has shown some promising results in EDs. Some special situations, as concurrent type 1 diabetes mellitus, pregnancy or breastfeeding, require specific, individualized measures ^{40,41,42,43,44,45,46,47,48,49,50}.

NUTRITIONAL SUPPORT FOR INPATIENTS

No evidence-based criteria establish which patients with ED will require hospitalization, hence medical and psychiatric signs and symptoms, as well as the course of the condition, should be considered as admission criteria. Overall, admission to hospital will be indicated in the presence of acute medical complications, acute psychiatric conditions, or self-harm attempts. Loss of control in the patient's familiar and social environment, and outpatient management failure may also represent admission criteria.

Hospitalization for ED may be voluntary or involuntary, but always using a multidisciplinary approach. Usually during hospitalization patients will receive oral nutrition, and ArN will only rarely be used.

Hospital discharge criteria include: sustained stable medical status, resolution of both medical and psychological acute complications, and significant control of behavioral changes to ensure adherence and that targets will be accomplished after discharge.

In contrast to AN, admissions for BN tend to be short-lived, and their goal is to provide contention and to break the vicious cycle the patient is in ^{51,52,53,54,55}.

NUTRITIONAL TREATMENT AT THE DAY HOSPITAL

Day hospital for ED (EDDH) emerged as a potentially useful alternative for the management of patients with ED, midway between traditional ambulatory care (consultations, individual and group therapy) and full hospitalization. Here patients receive medical treatment, nutritional support (accompanied/monitored meals), nutritional education, individual or group psychiatric and psychological care, occupational therapy, and social support, always following a multidisciplinary, intensive approach.

Some EDDH models are oriented towards short-term therapies (weeks) to achieve symptom control and weight stabilization; others aim at integral treatment by addressing psychodynamic aspects, interpersonal and psychosocial skills, and symptom insight, with gradual nutritional status recovery (over several months).

Usually, EDDH admission criteria include: diagnosis with ED, failed ambulatory care, transition to outpatient management after hospitalization, absence of high-risk weight or severe complications making (medical or psychiatric) full hospitalization advisable, motivation, and commitment. EDDHs should follow a well-defined, consensus protocol including a structured program, and admission requirements are usually negotiated within a therapeutic contract.

Discharge from EDDH usually requires reaching and sustaining the established weight target, correcting inappropriate eating behaviors, addressing irrational thinking, and ensuring adequate sociofamiliar support for outpatient follow-up. Should set goals in the EDDH program fail to be appropriately met, or complications arise, the patient should be transferred to a different treatment modality that better suits his or her needs ^56,57.

ASSESSMENT OF RESULTS

Evidence is sparse when it comes to assess both clinical and cost-effectiveness outcomes for the various treatments of ED. Most recommendations provided by guidelines are based on expert consensus statements.

Complete cure rates remain at 50-60%; chronification occurs in 20-30% of AN or BN cases, whereas 70% of BED cases reach full remission. Patients with ED are at higher risk for morbidity and mortality. Mortality rates are 10-12-fold higher than in the general population, and increase over the course of disease.

Social and family costs are high, and quality of life is severely affected. Further large-scale studies are necessary to assess the impact of ED and related comorbidities on the financial, familiar, and quality of life settings ^40,58,59.