Atypical Anorexia Nervosa

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Anorexia Nervosa/Atypical Anorexia Nervosa Lindsay Moskowitz, MD,a,c and Eric Weiselberg, MDb,c

Anorexia nervosa has the highest mortality rate among all psychiatric illnesses, as it can result in significant psychopathology along with life-threatening medical complications. Atypical anorexia nervosa is a new variant described in the latest DSM edition, which has much in common with anorexia nervosa and also can result in significant morbidity and mortality. The evolution of the criteria for these illnesses is reviewed, and the two are compared and contrasted in this article. Important labs to monitor for in those with these

illnesses, along with an emphasis on the monitoring of vital signs and weight, are reviewed here. The necessity for close psychiatric monitoring of safety concerns, including suicidal thoughts, is also stressed. The etiology and the treatment of these illnesses are reviewed from a biopsychosocial approach; and lastly, the prognosis of these illnesses is discussed.

Anorexia Nervosa and Atypical AN—A DSM Perspective/Diagnostic Criteria

or a denial of the seriousness of the low weight, and (5) amenorrhea (lack of 3 menstrual cycles in a row).5 These criteria led to much debate about what an “ideal” weight was, how one infers a “refusal” to maintain a “normal” weight, and how to determine an “intense fear” of maintaining weight. Expression of eating disorder (ED) symptoms often depends on the chronicity of the symptoms and the developmental capacities of the individual; thus, the DSM-IV criteria often did not capture EDs in children and adolescents who frequently do not express the fear of gaining weight or concern with body image or do not have the same chronicity as in adults.6–8 This often led to a delay in treatment until full-blown symptoms were present in these patients, making a successful recovery less likely. In reexamining the DSM-IV criteria, the cognitive requirements of AN have been debated. Given that many patients will not admit to a fear of weight gain for various reasons (i.e., denial, shame, and lack of insight), the DSM-5 now recognizes persistent behavior that interferes with weight gain as an alternative to endorsing this fear of weight gain.8,9 This change is supported by the fact that a majority of individuals with EDs do not disclose their symptoms, and there is a small body of literature that failed to find any difference in outcome between those individuals with AN who denied their ED symptoms and those who admitted them.10 Furthermore, many with EDs appear to be high functioning and can be quite convincing in their denial; thus, behavior is a more reliable indicator than self-reporting.

Anorexia Nervosa

norexia nervosa (AN) is a diagnostic term that literally means neurotic loss of appetite. Sir William Gull first reported a case of AN in the Lancet in 1888.1 The diagnostic criteria for AN have evolved considerably over time. For example, in the DSM III, the weight loss criterion was more stringent in that a 25% weight loss was required. There was, however, no amenorrhea criterion at that time. The criteria also used to specify that the weight loss was not due to another medical illness.2 It was not until the DSM III-R that the amenorrhea criterion was added, and in DSM-IV the weight criterion was changed to a 15% weight loss.3,4 The AN criteria that most clinicians are likely familiar with are those found in the DSM-IV-TR: (1) a refusal to maintain a normal weight, (2) a suggested weight cutoff of below 85% ideal body weight (IBW), (3) possession of an intense fear of gaining weight, (4) a disturbance in body image

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From the aDepartment of Psychiatry, Northwell Health, New Hyde Park, NYbDivision of Adolescent Medicine, Cohen Children's Medical Center, Northwell Health, New Hyde Park, NYcHofstra-Northwell School of Medicine, Hempstead, NY. Curr Probl Pediatr Adolesc Health Care 2017;47:70-84 1538-5442/$ - see front matter & 2017 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.cppeds.2017.02.003

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TABLE 1. Summary of DSM-IV-TR to DSM-5 changes for anorexia nervosa

Criterion

DSM-IV-TR

DSM-5

Weight Fear Body image Amenorrhea

85% below IBW Intense fear of gaining weight Distorted image or denial of seriousness of low weight Exists as criterion

No cutoff number/must be significantly below weight Or persistent behavior interfering with weight gain Distorted image or lack of recognition of low weight No longer exists as criterion

The weight criterion has also proved problematic in DSM-5, compared to the DSM-IV-TR, are summardiagnosing AN. While the DSM-IV weight criterion was ized in Table 1. never meant to be interpreted literally, in practice, most clinicians and insurance companies adhered to the guideAtypical Anorexia Nervosa line.8,11 The suggested 85% IBW cutoff was problematic Studies showed that eating disorder not otherwise for two reasons. First, it did not define how the IBW specified (EDNOS), as described in the DSM-IV,4 was would be determined, as some use a pre-morbid weight, a mid-point on a growth chart, body mass index (BMI), or the most prevalent ED and that many who ended up in adult weight calculations for height. Second, the cutoff did this category were children and adolescents.11 With most not account for those who were overweight pre-morbidly, patients being lumped into this heterogeneous category, it and although they may have lost a considerable amount of told clinicians very little about the actual diagnosis and weight, they were still above the 85% threshold. made treatment problematic.8,11 This category included One of the most debated DSM-IV criteria for AN was extremes of presentations, such as those a few pounds amenorrhea, as it was often not met in subthreshold cases. away from meeting the 85% IBW cutoff for AN, and It also did not take into account those with a more recent others with binge-eating disorder who were morbidly onset of the AN or adolescents with irregular menses. obese. Often those in this category were denied coverage Furthermore, amenorrhea has never been clearly associfor treatment by insurers and were not accepted into ated with a critical percentage of body fat, as some women treatment programs targeted towards AN. The DSM-5 with a lower percentage of body fat or who are considattempts to better define those in the EDNOS group, now 12 erably underweight continue to have normal menses. re-labeling it as other specified feeding or eating disorders (OSFED).9 The changes made to the AN diagnosis above Additionally, this criterion is inapplicable to prepubescent girls, postmenopausal females, women who never had also serve to remove some of those previously classified regular periods or were on oral as EDNOS and diagnose them contraceptive pills, and men; furwith AN. Besides removing ameA new diagnosis of atypical thermore, it is not specific to AN norrhea as a criterion for AN, the (e.g., those who are amenorrheic DSM-5 also changed the 85% anorexia nervosa has been secondary to the female athlete introduced, which in the past IBW requirement to “restriction triad, polycystic ovarian synof energy intake related to requiremay have been considered drome, and medications).13,14 ments, leading to a significant low “subthreshold AN”. This term body weight in the context of age, Patients with all other symptoms sex, developmental trajectory and of AN but who still menstruate describes those patients who can have significant health com- have all of the features of AN, physical health.”9 This change plications with malnutrition allows the provider to take into such as restricting, over-exer- account growth expectations, alone.15 One study found that cising, binging/purging, and the non-amenorrhea group exhibweight history and age. In so doing, one study of 309 patients ited the same level of ED symphaving a significant fear of with ED showed that 26.2% had toms in terms of treatment being overweight, and like response, psychopathology, bone been diagnosed with AN under those with AN, lose a large the DSM-IV criteria; however per density, etc.16 Moreover, amenoramount of weight, but they are the DSM-5 criteria, the rate rose to rhea is not reliably reported by not considered significantly patients.8,13,14 32.3%.17 The changes in the diagnosis Within the OSFED category, underweight. of AN that were made in the a new diagnosis of atypical

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TABLE 2. Contributing factors to eating disorders

Biological

Psychological

Social

Susceptibility loci (i.e., chromosomes 1, 2, and 13)

Traits (i.e., perfectionism, obsessionality, inflexibility, neuroticism, and harm avoidance) Low self-esteem Autonomy issues Maturity fears Comorbid psychiatric disorders (i.e., depression, anxiety, and personality disorders

Cultural influences

Neurotransmitter abnormalities (i.e., OPRD1 and HTR1D) Hormone abnormalities (i.e., cortisol and leptin) Family studies (i.e., higher rates in offspring) Twin studies (i.e., higher rates in mono vs. dizygotic twins)

anorexia nervosa has been introduced, which in the past may have been considered “subthreshold AN”. This term describes those patients who have all of the features of AN, such as restricting, over-exercising, binging/purging, and having a significant fear of being overweight, and like those with AN, lose a large amount of weight, but they are not considered significantly underweight.9 This can occur because these patients start out as overweight or obese. However, based on their trajectory of weight loss and restrictive behaviors, they are actually in a state of malnourishment. These patients would have previously been classified under EDNOS. Citing the study of the 309 ED patients, 30% now met the DSM-5 criteria for atypical AN, signifying this to be a very prevalent, significant disease among adolescents with EDs.17 Given that atypical AN is a new term, the literature to date on this diagnosis is limited. In the past, the term “atypical AN” was often used to describe those patients with autism-related sensory issues with eating or those with eating struggles accompanied by other medical illness. These would now go under the new DSM-5 diagnosis of avoidant restrictive food intake disorder (ARFID).9,18,19 Atypical AN was also previously used to describe those who did not endorse fear of gaining weight or a distorted body image.20 While the term “atypical” literally means aberrant or deviant, atypical AN should not be misinterpreted as being any less serious than AN. As discussed further in this review, these patients can have just as severe medical and psychiatric complications as patients with AN.

Etiology While the etiology of EDs is largely unknown, it is thought that a combination of biological, psychological, and social factors contribute to the illness (Table 2). We know EDs tend to cluster in families.21 Though based on small sample sizes, we also know from twin studies that the concordance for monozygotic twins having AN

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Family influences Peer influences Dieting Stressors (i.e., college, moving bullied, abuse, and death)

is greater than for dizygotic twins.22 Genes are thought to contribute anywhere from more than 50% up to 74% of the risk to developing AN.23 Studies also show there is an increased risk of offspring having an ED if the mother has an ED while pregnant, although it is difficult at times to tease apart the role of genetics versus the environment.24 Although the role of genetics is still largely unknown, there have been some studies exploring multiple possibilities. One study looking at ANrestricting subtype, found a susceptibility locus located on chromosome 1.25 In looking for drive for thinness and obsessionality, there have been associations with chromosomes 1, 2, and 13.26 When separating out for vomiting behavior, the signal on chromosome 10p (susceptibility locus using a linkage analysis) was found to be stronger.27 The anorexia nervosa genetics initiative (ANGI) study will look at approximately 13,000 patients, including those with AN and controls, from the US, Denmark, Sweden, and Australia. It is the most rigorous study to date attempting to look at the genetics of AN, which will likely help elucidate its etiology (https://clinicaltrials.gov/ct2/show/NCT01916538). In terms of biology, it is known that certain neurotransmitter abnormalities can be found. For example, recovered patients still show decreased 5HT2a activity in the cingulate and other areas.28 Delta opioid receptor (OPRD1) and serotonin 1D (5HTR1D) abnormalities are also associated with the AN-restricting cohort.29 Abnormalities in dopamine are also thought to play a role, accounting for hyperactive motor behavior and abnormalities in reward and behavioral inhibition.30 In terms of biological factors, given that atypical AN often occurs in those who are obese/overweight but then lose a large amount of weight, being overweight/ obese is a de facto precursor to atypical AN. For that matter, there are many shared risk factors between obesity and EDs, and obesity may in fact be a significant risk factor for all EDs.31 In terms of psychological factors, it is thought that those predisposed to AN have various traits such as

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alexithymia, i.e., dysfunction in recognizing emotions minimal western cultural influence, although often in oneself.32 It is thought that those with AN have different reasons for the food refusal and weight loss, lower levels of emotional awareness compared to those such as religious devotion, are cited.44 Family dysfunction has also been associated with AN, as patients with BN.33 Limited coping skills, poor distress tolertypically perceive families as triggers to EDs.45 In the ance, perfectionism, obsessionality, inflexibility, neuroticism, negative emotionality, harm avoidance, past, it was thought that overbearing or enmeshed compulsivity, social inhibition, emotional restraint, mothers in particular contributed to EDs, although the and decreased self-esteem are also common traits American Academy of Eating Disorders now takes a amongst those with AN.34 However, those with AN firm stance against any model for EDs in which families are seen as the primary cause of AN or BN.46 AN may or atypical AN who also engage in binging and often be precipitated by stressful life transitions, such as purging display more impulsivity and sensation seekgoing to college, moving, losing a parent, etc., or often ing.35 Those with AN classically tend to have problems by being bullied or teased. Sexual abuse has been with identify formation, autonomy issues, and maturity associated with EDs as well, mostly with BN, and in fears.36 The restricting subtype of AN is associated particular with those who develop post-traumatic stress with personality disorders such as obsessive compuldisorder.47,48 sive personality disorder (OCPD) or avoidant personality disorder. Borderline personality disorder (BPD) is also common, especially among those with bingepurge subtype.37,38 Self-injurious behavior and suicide Demographics/Prevalence attempts are commonly associated with AN as well.37 In general, the incidence of AN in society is relatively AN has a strong association with anxiety. In terms of low, with one study citing it as 8/100,000, with average axis I comorbidities, an anxiety disorder is present in prevalence rates being 0.3 for young females, and 0.3– over two thirds of those with AN and obsessive 1% for BN.49,50 The lifetime prevalence of AN is compulsive disorder (OCD) is present in more than between 0.5% and 2%.51 However, since EDNOS has 40%.38 Depressive disorders are also extremely comaccounted for the majority of ED diagnoses, in the past, mon in those with AN.39 the overall prevalence rate is felt In examining social factors to be 3%.50 One multi-site study contributing to EDs, dieting is a risk factor for all EDs. Often In examining social factors con- looking at the ED population in times adolescents with AN and tributing to EDs, dieting is a risk 14 adolescent medicine clinics showed that 33.9% of patients atypical AN see parents modelfactor for all EDs. met criteria for atypical AN and ing dieting behaviors at home, 53.6% for AN.52 whereas other times the parents are obese and may have been diagnosed with medical issues such as cancer, diabetes, or heart problems, triggering the Medical Complications adolescent to diet. Dieting is an established risk factor for development of an ED, although with that being The major cause for the medical complications in AN said, only a small percent of those who diet will end up is the imbalance between energy intake and requirewith an ED.31,40,41 One study showed that adolescents ments, leading to a hypometabolic state. Therefore, in an effort to maintain homeostasis in the malnourished who diet to a severe degree have an 18-fold risk of state, the body down regulates, causing many of the developing an ED.42 Society has long been blamed for triggering AN, given its ideals equating beauty with signs and symptoms observed in AN. Little has been reported as yet on the medical complications of thinness. While AN used to be found largely in atypical AN. One study of 118 individuals, 59 meeting Caucasian women and westernized societies, we know it is now found in all races and ethnicities. The internaDSM-IV criteria for AN, and another 59 with “subthreshold” AN, showed no difference in physical tional Fiji study is perhaps the best known study for parameters on presentation except for lower white showing that exposure to western media can lead to an increased desire of women to reshape their bodies and to blood cell counts in the AN group.53 It is the 43 greater rates of ED attitudes and behaviors. However, experience of the authors as well, that individuals with AN and atypical AN share similar degrees of caloric AN can be found in non-industrialized societies with a

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medical parameters and the motivation of the patient; however, bradycardia at less than 40 beats/minute almost Cardiac Bradycardia Low energy, fatigue always warrants a higher level of care. Other cardiac Orthostatic hypotension Syncope findings can include a prolonged QT interval on the Arrhythmia, prolonged Dizziness, palpitations, electrocardiogram, which may be secondary to hypokaQT and syncope Pericardial effusion Typically none and lemia if purging is present. A small pericardial effusion is chest pain not uncommon and resolves with improved nutrition. Myocardial atrophy Edema and congestive Severe malnutrition can lead to myocardial atrophy with heart failure decreased contractility and cardiac output. Care therefore Electrolyte Hypokalemia (purging, Muscle pain, imbalance laxatives) arrhythmias must be taken in avoiding fluid overload by overHyponatremia (excessive Seizures aggressive hydration, which may lead to edema and water drinking) congestive heart failure. Endocrine Hypogonadotropic Amenorrhea (primary hypogonadism or secondary) Electrolyte imbalances may occur for patients with Osteopenia/osteoporosis Fractures AN who engage in purging behaviors. A hypokalemic Sick euthyroid syndrome hypochloremic metabolic alkalosis may be present in Gastroenterological Gastric dysmotility Constipation, reflux Delayed gastric Bloating, abdominal the AN-purging subtype as in BN, with the hypokaleemptying pain mia putting the patient at risk for cardiac dysrhythmias Hematologic Bone marrow suppression Usually none, bruising, and death. Hyponatremia may be found in some pallor patients who drink large amounts of water prior to a Integumentary Acrocyanosis Cold hands and feet Lanugo Increase fine body hair weigh-in in order to falsify their low body weight. Hair loss Other patients may engage in excessive water drinking Russell signs Calluses from purging to help curb hunger or as part of their inappropriate Hypercarotenemia Yellow skin HEENT Parotid enlargement From purging “healthy” lifestyle. Dental enamel loss Caries A common presentation that often may initially lead Refeeding Hypophosphatemia Seizure, delirium, the patient to medical care is amenorrhea. The malnusyndrome death trition, in an effort to conserve energy, leads to central hypothalamic suppression, causing hypogonadotropic restriction and malnutrition, and therefore have similar hypogonadism, with decreased levels of luteinizing medical courses. For the purpose of this article, the hormone, follicle stimulating hormone and estradiol. medical complications of AN and atypical AN will Furthermore, the absence of estrogen production leads therefore be discussed as one, and these are summarto the most chronic medical concern present in AN, that ized in Table 3. being osteopenia and osteoporosis. As adolescence is One of the most significant medical complications, the time of peak bone mass acquisition, the development which often leads to hospitalization is vital sign instaof amenorrhea and the deficiency in bone mass can lead bility, including bradycardia and to early premature fracture risk. orthostatic hypotension, caused Treatment is weight gain with by the underlying malnutrition A common presentation that resumption of menses; however, and increased vagal tone.54 if bone loss has occurred, the often may initially lead the Published recommendations for patient to medical care is ame- patient may still not reach full hospitalization include severe bone mass potential even with bradycardia at less than norrhea. The malnutrition, in an recovery.56 Other neuropeptides, 50 beats/minute during the day, effort to conserve energy, leads such as IGF-1, ghrelin and leptin, or hypotension at less than may also be involved in the to central hypothalamic sup80/50 mmHg.55 As patients may pression, causing hypogonado- devolvement of amenorrhea and present with chronic malnutrition, bone loss, and is an avenue of tropic hypogonadism, with a trial of outpatient care may be active research.57 Also secondecreased levels of luteinizing dary to the hypothalamic state attempted, while carefully monitoring for vital sign stability is the development of a euthyhormone, follicle stimulating and taking into account the roid sick syndrome, with hormone and estradiol. degree of malnutrition, other increased conversion of T4 to TABLE 3. Medical complications of anorexia nervosa

System

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Finding

Symptom

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with severe malnutrition, in starvation states, or with reverse T3 instead of T3; in spite of the low T3, TSH evidence of declining phosphorus levels in the first typically remains normal or slightly low, reflecting the 57 weeks of treatment.62 central suppression. Gastrointestinal complaints of dyspepsia, abdominal pain and constipation are very common among those Psychiatric Comorbidities/ with AN, secondary to dysmotility and delayed gastric Complications emptying. Abdominal complaints may at times be interpreted as a refusal to cooperate; however, the As a general rule, AN is typically present with other symptoms generally are quite psychiatric disorders, with one study examining adolesreal, leading to interference with cent females finding cormobidity nutritional recovery. Slow steady rates as high as 73.3%.63 These As a general rule, AN is typically refeeding along with reassurance comorbid disorders should always present with other psychiatric be screened for as they can further that the discomfort will resolve disorders, with one study with improvement in nutritional complicate treatment.64 Two of status can ease the anxiety in examining adolescent females the most common psychiatric both patient and parents.58 Bone comorbidites present with AN finding cormobidity rates as are depression and anxiety disormarrow suppression can lead to high as 73.3%. ders. One study showed mood mild anemia, leukopenia or thrombocytopenia, typically in disorders were the most common at around 60.4%.63 Anxiety disorders are also highly the more severely malnourished patients; however, the finding of multiple cell line suppression warrants further prevalent, with one study finding that those with AN and hematologic investigation.59 BN had lifetime anxiety disorder rates from 64% to 83%.38,64 Social phobia is thought to be the most common A dangerous complication, especially during the early recovery phase, is development of the refeeding synof the comorbid anxiety disorders, with rates of comordrome. When going from a starvation/anabolic state to a bidity in AN from 20% to 55%.38,64 One study showed catabolic state with the reintroduction of food, energy that the anxiety disorder predated the AN in 75% of production is increased in the form of cellular adenocases.64 Obsessive compulsive disorder (OCD) is also sine-50 -triphosphate (ATP). The nutritional load, espehighly comorbid with AN, at a range from 16.8% in one study, to around 30% in another, up to 41% in yet another cially in the form of carbohydrates, leads to a surge in study.38,64,65 However, it is important to make sure that insulin that causes an intracellular shift of ions, including phosphorus, magnesium and calcium, required for the obsessions and compulsions are not only in the eating cellular processes, leading to the potential for the and weight realm before making a second diagnosis of development of hypophosphatemia.60 Refeeding synOCD. One study showed that the comorbidity of AN and BN with anxiety disorders was not statistically different.65 drome can lead to delirium, stupor, seizures, coma and death, and therefore any signs of a refeeding hypophosSubstance use disorders have been found to be less phatemia need to be managed urgently. Prevention has commonly comorbid with AN, at around 7.9%, although been the rule, with the generally accepted approach on they were 18 times more likely to occur in the AN-bingean inpatient unit of feeding slowly, beginning at 1000– eating sybtype.63 1400 calories per day, and increasing by 100–200 It should be noted that depression and anxiety calories per day. There are reports of a quicker approach symptoms can often exist secondarily to the ED and in refeeding by using a low carbohydrate load along it may be difficult to tease apart primary depressive and with prophylactic phosphorus supplementation, though anxiety disorders from depressive and anxiety symp61 this has not become standard practice. As refeeding toms due to malnutrition, as there is much overlap in symptoms. For example, low energy, psychomotor syndrome is an uncommon condition, especially given the careful prevention strategies, there are no evidenceagitation, irritability, poor concentration and low mood can be impaired in depression, anxiety, and/or AN.9 based protocols for treatment, and treatment has therefore been as per provider’s experience. However, it has Suicidal ideation is common in depression and anxiety become standard that oral phosphorus supplementation and unfortunately, along with high rates of self-injury, should be begun early, especially in those at greatest risk both can be found at high rates in AN.66 In terms of for a refeeding hypophosphatemia, i.e., AN patients psychiatric complications associated with AN and

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these patients report an intense fear of gaining weight atypical AN, it is prudent to be mindful of safety issues and often deny or do not recognize the seriousness of in terms of suicidal ideation and self-injurious behavthe weight loss. They also consistently demonstrate ior. One meta-analysis showed that 27% of deaths in persistent behaviors that interfere with weight gain.9 AN are a result of suicide.67 Personality disorders are also highly comorbid with Many think that atypical AN is less serious than AN. AN. One study found 27% of a sample with AN had a Indeed, its name and the fact that it is part of the comorbid personality disorder.68 AN is highly comorbid “Other” ED category often misleads one into thinking this is the case. One of the most striking and concernwith those classified as cluster C personality disorders, ing similarities is that, although such as obsessive compulsive they appear of normal weight or personality disorder (OCPD). overweight to others, patients One study found rates of OCPD One of the most striking and at 22% for the restricting subconcerning similarities is that, with atypical AN can have just severe or even more severe type.38 AN is also highly comoralthough they appear of normal as medical complications than bid with borderline personality disorder (BPD), which is classi- weight or overweight to others, those with AN, and can require patients with atypical AN can medical admission for severe fied as a cluster B personality disorder.68 Approximately 25– have just as severe or even more bradycardia or electrolyte distur39% of patients with AN-binge/ severe medical complications bances. Their current weight can be deceiving, as those with atyppurge subtype, have BPD, than those with AN ical AN have often lost large whereas prevalence is thought amounts of weight very rapidly, to be somewhat lower, at around not allowing their bodies the opportunity to compen22%, in the AN-restricting group.38,68 When BPD is sate. While amenorrhea is no longer a criterion for AN, comorbid with AN it can complicate treatment, as it is often patients with atypical AN will have amenorrhea associated with substance use, self-injury, high relapse as well. rates, and premature dropout, and in general when personality disorders are comorbid with AN, recovery is significantly slower.68 Limited literature exists on the prevalence of psychiDifferences Between Anorexia atric comorbidities with atypical AN, although in clinical Nervosa and Atypical Anorexia practice, as supported by one study, depression and Nervosa anxiety are highly comorbid, along with OCD, substance use, and personality disorders.69 One study showed that a In comparing and contrasting AN with atypical AN, the similarities are more striking than the differences. combined group of AN and atypical AN had rates of In terms of differences between the two, there is suicidal behavior at 60% and self-harm around 49%.69 Future studies should be done to compare and contrast essentially one main difference, the patient’s weight. Patients with AN are often significantly emaciated, the prevalence of all of these disorders with atypical AN which may raise concerns with parents, teachers, etc. versus AN. Those with atypical AN can be of normal weight, overweight, obese or slightly underweight. Although there is essentially no available literature Similarities Between Anorexia comparing the two diagnoses, in looking at the DSM-5 Nervosa and Atypical Anorexia criteria, and in the authors' experience, one difference Nervosa that stands out is the distorted body image element. When patients with atypical AN see themselves as There are many similarities between AN and atypical being overweight or obese, these perceptions are often AN, and the criteria is almost the same, as discussed in true based on BMI standards. It is therefore unclear the the next section. Those with atypical AN have lost a extent to which these patients actually have a distorted large amount of weight by engaging in ED behaviors, body image. Thus, further research on their perceptions including restricting and often over-exercising, and is needed because these patients may see themselves as may binge/purge, vomit or abuse diet pills, laxatives or more overweight than they actually are. One area of diuretics as in the AN-binge/purge subtype. Further,

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complicating treatment is that society often views patients with atypical AN as being overweight. In some cases, those with atypical AN were initially told by others, including physicians, to lose weight, which may have triggered or perpetuated the ED. In general, patients with EDs are resistant to treatment, especially if weight gain is expected. Those with atypical AN are no different, although compared to those with AN, they often feel less entitled to help because they often view themselves as being not as sick as those with AN. Often it is not a matter of them not wanting treatment, but feeling they do not deserve it. Further research is needed to see if those with atypical AN are even more resistant to gaining weight than those with AN. Often, those with atypical AN have had traumatic experiences, such as significant social struggles, including bullying, when they were overweight, and seem even more fearful of gaining further weight as a result. Further research also should examine whether those with atypical AN have more denial compared to those with AN, in that they do not see their weight loss as serious, since they may have struggled with or been encouraged to lose weight. Many physical and psychiatric complications can occur in those who are overweight or obese. The issue in many of these cases is not that the patient would not have benefited from some weight loss; rather it is the eating disorder behaviors they engaged in to lose the weight, the rapidity of the weight loss, and the severity of their thoughts about their weight, shape, and body that makes it an ED and leads to significant dangers.

Making the Diagnosis of Anorexia Nervosa versus Atypical Anorexia Nervosa Despite the different diagnostic criteria for AN and atypical AN found in the DSM-5, distinguishing between the two can prove challenging. For AN, the below 85% IBW cutoff was eliminated as a criterion9 which allows clinicians to exercise their discretion in determining what is a significantly low weight. While there are suggested BMI guidelines included in the severity specifiers for mild, moderate, severe and extreme AN,9 these BMI guidelines mostly apply to adults, not to adolescents, and even less so to children. Thus, there are no clear weight guidelines now to distinguish between AN and atypical AN, and there is

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no specified amount of weight one must lose to qualify for a diagnosis of atypical AN. Age, sex, culture, and personal norms can all contribute to a clinician’s judgment of a patient’s weight and whether that patient receives a diagnosis of AN or atypical AN. What is deemed a healthy weight can vary such that two individuals can be the same height and weight, yet one can be considered healthy and the other unhealthy. Furthermore, certain institutions and insurance companies have their own weight cutoffs to distinguish between the two diagnoses. One study found that whether a patient receives a diagnosis of AN or EDNOS varied within a 15-lb weight range for females and a 25-lb weight range for males, depending on which site the patient was at.11 Utilizing numbers to judge whether a patient is at a healthy weight needs to be examined. According to the Centers for Disease Control and Prevention (CDC) guidelines, BMI percentiles between the 5th and 84th percentiles are considered to be within normal limits for children, although many within that range can have various EDs as well. As previously discussed, atypical AN and AN have many more similarities than differences. Part of the rationale for changing the threshold criteria for AN was that the subthreshold cases did not differ in terms of psychological comorbidities, medical complications, or prognosis.11 Studies examining the previous EDNOS diagnosis showed that the most common reason to be diagnosed with a subthreshold AN within EDNOS was that the person met all criteria for AN except the weight cutoff.16,70 A study examining an increase in the previous AN threshold criteria from 85% to 90% IBW found that the change would significantly minimize those who received an EDNOS or subthreshold AN diagnosis.71 These studies highlight a gray area in terms of differentiating between atypical AN and AN, and the overlap between the two.

Evaluation/Assessment/Monitoring— Medical and Psychiatric In terms of medical assessment, all patients with AN and atypical AN need a thorough baseline medical evaluation to check for medical stability. The examination should include patient's height, post-void undressed weight, BMI, BMI percentile and orthostatic vital signs (blood pressure and pulse rates), along with temperature and respiratory rates. A full physical

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disturbances on the heart.62 The presence of an examination should include all organ systems, looking for signs of ED behavior (calluses or parotid enlargearrhythmia may warrant hospitalization and cardiac ment from purging) and to rule out other causes for consultation. If there is severe malnutrition, an echomalnutrition. Included in the difcardiogram can be obtained, ferential diagnosis are gastroinwhich may show small pericarIncluded in the differential testinal disorders, such as dial effusions.62 If amenorrhea diagnosis are gastrointestinal has been present for at least 6– inflammatory bowel disease and celiac disease, endocrinologic disorders, such as inflammatory 12 months, a, bone density scan diseases, such as hyperthyroidbowel disease and celiac dis- can be considered to assess for ism or Addison’s disease, and the presence of osteoporosis/ ease, endocrinologic diseases, other chronic illness that may osteopenia.62 If any focal neusuch as hyperthyroidism or lead to weight loss, such as an rological signs or acute changes underlying malignancy.72 These Addison’s disease, and other in mental status are noted, a medical conditions should all be chronic illness that may lead to magnetic resonance imaging test (MRI) of the brain should ruled out for those with atypical AN as well. A pre-morbid his- weight loss, such as an under- be obtained. While there are lying malignancy. changes that take place in the tory of obesity, might suggest brain with severe starvation other concerns, such as Prader (e.g., loss of gray and white matter, enlargement of Willi, hypothyroidism, polycystic ovarian syndrome, ventricles, etc.), an MRI of the brain is not routinely and metabolic syndrome.73 obtained to look for these findings. If there is concern a To assess for stability and to aid in the differential patient might have an aspiration pneumonia from diagnosis, laboratory screening should include a compurging, a chest X-ray should be obtained. If conplete blood count, a comprehensive complete metacerned about gastrointestinal symptoms, further evalbolic panel to asses for dehydration, hypokalemia, uation, including ultrasound or endoscopy, may be hyponatremia, hypophosphatemia, and transaminitis, warranted. In general, all of the above testing is which may be found with malnutrition.62 Markers of performed when signs and symptoms indicate it is nutritional status such as albumin, prealbumin, and necessary to evaluate for findings separate from those transferrin can also be useful to check, although they caused by malnutrition or when the results of addiare seldom needed in clinical practice. Testing amylase tional testing will have a direct effect on the treatment may also suggest purging if elevated. A thyroid approach that needs to be used. function panel should be obtained, as central hypoIn terms of psychiatric assessment, a full history of thyroidism and the euthyroid sick syndrome are often present illness and a detailed past psychiatric, family, found, which typically correct with refeeding and social, and developmental history, along with an abuse should not be treated by adding thyroid hormone.62 and legal history, should be obtained. Psychiatric A urinalysis should be obtained to evaluate the patients comorbidities should appropriately be assessed for as for dehydration or water loading.62 A stool guaiac above. Special attention should be paid to assessing might be useful if inflammatory bowel disease is safety issues, including suicidality and self-injurious suspected, or for those patients who are suspected of behavior. While most deaths from AN are thought to abusing laxatives or enemas. Urine drug screens and be due to cardiac complications, approximately one in alcohol levels are obtained in some cases.74 Testing for five are thought to be from suicide.75 A thorough amenorrhea includes luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, and pregmental status examination should be performed. Signs 62 nancy testing. The laboratory findings that are most of psychosis, such as auditory and visual hallucinations and paranoia, as well as cognioften seen in patients with AN tive status, including attention are summarized in Table 4. Special attention should be paid and concentration, should be An electrocardiogram is perto assessing safety issues, assessed, as often refeeding formed as needed to rule out bradycardia, arrhythmias, proincluding suicidality and self- syndrome can present with delirium.76 The presence of longed QT interval or to check injurious behavior. for the effects of electrolyte psychosis can also be a marker

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TABLE 4. Laboratory findings in anorexia nervosa

Test

Finding

Cause

Chemistries Sodium Potassium Chloride Serum CO2 Amylase SGOT/SGPT Cholesterol

Low Low Low High High High High

Excessive water drinking Purging Purging Purging Purging Malnutrition Low T3, low binding globulin

Hematologic Hemoglobin Hemoglobin White blood cell Platelet count Erythrocyte sedimentation rate

Normal/low High Normal/low Normal/low Low

Bone marrow suppression Dehydration Bone marrow suppression margination Bone marrow suppression Low fibrinogen

Endocrinologic Luteinizing hormone, follicle stimulating hormone Estradiol Testosterone Total triiodothyronine Thyroid stimulating hormone thyroxine Prolactin

Low Low Low Low Normal/low Low

Central suppression Central suppression Central suppression Sick euthyroid syndrome Central suppression Central suppression

Refeeding syndrome Phosphorous Magnesium Calcium

Low Low Low

Energy depletion Energy depletion Energy depletion

of another medical or psychiatric disorder contributing to the malnutrition/starvation.

studies have shown that patients typically gain approximately 2 pounds per week in a DTP setting;78 and in inpatient settings, often 3 lb/week can occur, after calories have been adjusted during the first week or two.79 Treatment—Biological Determining target goal weights may be challenging for both those with AN and atypical AN. It has been The primary treatment for both AN and atypical AN is shown that vital sign stability is achieved at 80% of for the patient to consume sufficient caloric intake and IBW and resumption of menses at 90% IBW.80,81 correct the underlying malnutrition. Though cliché, food However, again, the term IBW can be misleading as is the best medicine to treat an ED. Not only will the there is no accepted definition. nutritional rehabilitation correct For children and pre-adolesthe medical complications, but it Though cliché, food is the best cents, the goal is to return to can also help correct the psychomedicine to treat an ED. the individual’s growth curve, to logical aspects, as typically ED allow for proper growth and thoughts, and to some extent pubertal development. For adolescents who have depression and anxiety, will improve with refeeding. reached pubertal maturity, BMI percentile can be used Despite the fact that patients with atypical AN are often to calculate what weight would be needed to achieve a overweight, nutritional recovery with weight gain is BMI at the 50th percentile. For those with atypical AN, every bit as important a treatment goal, just as it is for who may already be over the 50th percentile of BMI, a those with AN. Those with atypical AN are in a relative mid-point between the 50th percentile of BMI and state of emaciation and, as discussed above, can have maximum weight may be desired. Throughout recovery, severe medical complications from losing weight inaphowever, interim goal weights may need to be estabpropriately. In general, in weekly outpatient treatment, a lished and recalculated according to nutritional intake, weight gain of 1 lb/week is expected;77 day treatment medical stability, and resumption of menses. programs (DTP) can allow for more rapid weight gain, as

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When refeeding a patient with AN or atypical AN, often a low number of calories (e.g., 1000–1400 kcals daily) is initially required in order to minimize the risk of refeeding syndrome, with increases of no more than 400 kcals every 3–4 days.79 Early on, due to the hypometabolism, patients will gain weight on a low number of calories and then plateau as metabolism improves. Rapid weight gain, however, may signal an impending refeeding syndrome and needs to be assessed. It should be noted that in order to gain the weight back, patients can often require a large number of calories for weight gain. In order to aid in weight gain, and especially if there is bradycardia or hypotension, disruption of exercise and physical activity is necessary until a stable weight is achieved.82,83 It is unclear yet if adding back exercise earlier on might be useful for patients with atypical AN given that they were previously overweight and exercise can potentially lead to improvement in depressive and anxiety symptoms. While some patients with atypical AN might need to lose weight in the future, this is not recommended until the ED has resolved and the patient is able to lose weight in a healthy manner. Psychiatric medications have been shown to have a limited role in the treatment of AN, while research on their use for atypical AN is limited. For AN, studies have shown that in the acute, malnourished state, selective serotonin reuptake inhibitors (SSRIs) do not appear to be helpful for weight gain purposes or for treating depressive or anxiety symptoms.84 For adults with BN, fluoxetine has been approved and strong evidence exists that it helps decrease binging and purging, and can improve depressive symptoms.85 Some evidence also exists that fluoxetine is helpful for adolescents with BN.82 Therefore, it is possible that SSRIs may be more effective in atypical AN given that these patients are at a higher weight, like those patients with BN; however, given that these patients are in a relative malnourished state, SSRIs may still be ineffective. As no evidence-based treatment exists for treating atypical AN, use of medications should generally be limited. In clinical practice, though, those with atypical AN, some of whom may have also engaged in binging/purging and/or are significantly depressed or anxious, and in particular for those with suicidal ideation, the benefits of trying SSRIs may outweigh the risks. SSRIs should only be initiated if the patient has minimal or no gastrointestinal symptoms (due to the risks of SSRIs worsening them) and if informed consent is given for the limited use of these medications.

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Atypical antipsychotics have been utilized for treatment-resistant patients with severe AN. Case reports and open label studies examining the use of atypical antipsychotics (mainly olanzapine) in treatment of AN for adolescents show some potential benefits.86–88 To date, however, meta-analyses do not show the effectiveness of their use.89 Further, their use should be cautioned against in atypical AN due to the potential for large weight gain and the risk of metabolic side effects. Given that patients with EDs are already at risk from a cardiac standpoint, appropriate screening and monitoring (electrocardiograms, lipid panels, fasting glucose, HbA1C) should be performed if atypical antipsychotics are initiated, and informed consent should be obtained.

Treatment—Psychological As mentioned above, refeeding is the first step in treatment, and is necessary to help with depressive and anxiety symptoms and is a vital precursor to more effective therapy. While limited evidence exists that therapies other than a family-based treatment (FBT) approach helps treat patients with AN, refeeding patients is often done alongside other psychotherapy approaches. Cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), interpersonal therapy (IPT), cognitive remediation therapy (CRT), and acceptance commitment therapy (ACT) are all therapies that have been studied in AN and produced varying results.19 FBT has the strongest evidentiary support for helping those with AN gain weight at follow-up compared to individual therapy.90 It typically works well for those less than 18 years old who have been sick for less than 3 years.90 Limited evidence currently exists examining which treatments work best for atypical AN. It is known that therapy is more effective for BN compared to AN, largely thought to be due to the weight difference. Perhaps, given that patients with atypical AN present at a higher weight, therapy might be more effective compared to that for AN.19 However, given the acute and severe nature of the weight loss in those with atypical AN, the cognitive capacity of these patients might be comparable to a patient with AN, consequently limiting the effectiveness of therapy. Thus, further studies are needed to examine the cognitive capacity and effectiveness of different therapies for those with atypical AN.

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Given that those with atypical AN are expected to gain weight, it seems natural that FBT would be a useful starting point to help these patients. The FBT manual for BN utilizes more of a collaborative approach with the patient’s family, given that BN is typically more ego-dystonic and patients are often more motivated for treatment.91 Thus, future adaptations of FBT for atypical AN should be examined. In clinical practice, an FBT approach for atypical AN modeled after the AN approach, rather than the BN approach, might be more appropriate because strict parental control is needed for successful weight gain. Given that some patients with atypical AN have used binging/purging behaviors and often possess cluster B traits and engage in self-injurious behavior, DBT might also be a useful approach.19 Enhanced cognitive behavioral therapy for EDs (CBT-E) is the gold standard for BN, and interpersonal therapy (IPT) is the only therapy that rivals it.92 Evidence exists that both help with binge-eating disorder (BED) as well, and may be useful in those with atypical AN.19 However, CBT-E is known to be less effective for the acute phase of AN when the brain is starved, which raises questions as to how effective CBT-E is for atypical AN.19 CBT-E showed effectiveness in two studies (one in adults and one in adolescents) in patients with AN who were underweight over a prolonged follow-up period.92,93 Therefore, one can hypothesize that CBT-E may be effective for atypical AN given that common mechanisms are involved.19

appointments and ensuring insurance coverage and compliance. In situations where parents do not take these illnesses seriously and they are non-compliant with treatment, social services may need to be involved due to concern for neglect.

Prognosis

Despite advances in psychiatry, the prognosis for AN remains guarded. It is thought that, on average, less than half recover, one third have a varied course, and 20% remain chronically ill.94 A 21-year follow-up study of 84 patients who were hospitalized for AN showed that 51% had recovered, while 10% still met full diagnostic criteria for AN and 16% had passed away from complications of the AN.95 While specific studies do not yet exist examining the prognosis of atypical AN, it can be surmised to be similar to that of AN. In terms of what is currently known about the prognosis for atypical AN, one study showed it had the longest episode duration at 11.2 months versus 8 months for AN. Though this study had a small sample size, it showed one year remission rates were very similar for atypical AN (71%) compared to that of AN (75%). Of 14 patients with atypical AN, none had progressed to AN, although one patient did progress to purging disorder (2%).96 As stated earlier, AN has the highest mortality rate among psychiatric disorders, secondary to underlying medical complications or suicide, with a rate of 0.56 per year (5.6 % per decade).67 It should be noted, however, that almost all of the Treatment—Social AN has the highest mortality follow-up studies performed Social treatment for both AN rate among psychiatric disor- over the years in patients with and atypical AN involves buildders, secondary to underlying AN have mostly included adult ing up the lives of these patients patients, many of whom required medical complications or sui- psychiatric outside of the ED. Adolescents hospitalization. with AN and atypical AN benefit cide, with a rate of 0.56 per There is evidence that the proggreatly from self-esteem building nosis in adolescent patients with year (5.6 % per decade). activities, including finding areas AN, especially those who do not of success, whether it be through require inpatient care, is not nearly as bleak as the new hobbies, excelling in an area in school, obtaining a general overview in the literature suggests.97 job, feeling more independent, making new friends, etc. Given the complexity of AN and atypical AN, as well as Conclusion the high acuity associated with these illnesses, multidisciplinary treatment is a must. This requires multiple Since the first case report of anorexia nervosa follow-up appointments with various specialties, includappeared in the literature over 125 years ago, much ing adolescent medicine, pediatrics, psychiatry, psycholhas been learned about eating disorders. Presently, ogy, nutrition, dentists, etc. Involvement of intensive case eleven distinct eating disorders are categorized in the managers can be crucial to coordinating all of these DSM-5, from the classic anorexia nervosa, to

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rumination disorder and night-eating syndrome. Research regarding causation, course, complications, and treatments fill the literature. Indeed, entire programs and careers focus solely on the care of those with eating disorders. However, in spite of this effort, the prevalence of eating disorders continues to be significant, affecting newer populations and communities. Recovery remains slow, and, for many, unattainable. Treatment options and knowledge regarding pharmacologic agents continue to expand, yet no single approach has proven to be entirely curative. And mortality rates continue to be the highest among all psychiatric disorders. However, investigations into the nature of brain functioning, neuropeptides and genetic markers add promise. By further classifying eating disorders with ever more specific diagnostic criteria, future research can move closer to full prevention and cure.

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