Avoidant Restrictive Food Intake Disorder

Etiology

Despite increasing attention, ARFID's etiology and neurobiology remain poorly understood in the academic literature. The causes of ARFID are complex, encompassing genetic predispositions, environmental influences, neurobiological mechanisms, and psychosocial factors akin to other eating disorder etiologies.[4] ARFID shares several eating disorder characteristics (eg, anorexia nervosa), including restrictive eating, low body weight, and nutritional deficiencies.[5] Evidence also suggests a possible shared etiology between anorexia nervosa and ARFID, as patients with ARFID may be diagnosed with anorexia nervosa later.[6]

A recent sizeable Swedish twin study has indicated a significant heritable component to ARFID, suggesting that genetic factors play an essential role in the development of the disorder. In this study, twins aged 6 to 12 years showed that the predisposition to ARFID was primarily due to additive genetic factors, with inherited factors contributing approximately 79% and unshared environmental factors accounting for an estimated 21%, indicating a robust hereditary influence.[7] These findings encourage further genetic research into the disorder. Early childhood experiences, sensory sensitivities, and anxiety disorders may also contribute to the development of ARFID.[8] Neurobiological models propose that ARFID exhibits abnormalities in appetite regulation, sensory perception, and heightened fear system activation, which contribute to the emergence of comorbid anxiety disorders and the perpetuation of restrictive eating behaviors. Notably, ARFID encompasses a heterogeneous population influenced by biological and environmental factors in the development and persistence of their eating patterns.[9][8]

Epidemiology

Previous studies employing comparable diagnostic criteria have reported an ARFID prevalence in the general child population ranging from 0.35% to 3.2% and globally in adult populations from 0.3% to 3.1%.[10][11][12][13][14][15] Some studies have shown males with ARFID have a higher prevalence than females, especially in pediatric populations.[16][17] However, DSM-V indicates a more balanced sex distribution of ARFID compared to other eating disorders (eg, anorexia nervosa and bulimia nervosa), which predominantly affect females. Furthermore, according to some studies, a larger proportion of ARFID cases are represented by males than in other eating disorders. These findings highlight the necessity for gender-sensitive approaches in both diagnosis and treatment.[16]

Moreover, ARFID commonly occurs with other comorbid conditions, particularly neurodevelopmental disorders, including autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD).[5][16][18] Learning disabilities, obsessive-compulsive disorders (OCD), and anxiety disorders also occur with ARFID more frequently than other eating disorders.[5][17][19] This association suggests that the underlying mechanism of ARFID may be related to broader neurodevelopmental and psychological processes. The worldwide prevalence of ARFID is unclear due to ambiguity in diagnostic definitions and operationalization; however, ARFID poses a significant clinical challenge due to the condition's diverse and often subtle presentations.[20]

Pathophysiology

ARFID is associated with alterations in brain regions involved in reward, motivation, and the sensory processing of food.[8] For instance, the insula, an area that helps regulate internal body states and process sensory information, is critical in the pathophysiology of ARFID.[21] When exposed to food stimuli, individuals with ARFID may have atypical activation patterns in the insula, leading to aversive responses to certain textures, tastes, or food smells. In addition, a recent study proposed that the pathophysiology of ARFID may be associated with the following 3 neurobiological hypotheses:

1. Individuals with sensory sensitivity may have an intensified perception of tastes, particularly bitter and sweet, which might classify them as "supertasters" due to a biological predisposition. 
2. A lack of interest in food observed in some with ARFID could be linked to reduced brain activity in appetite-regulating areas (eg, hypothalamus and insula), which affect hunger sensations and satiety. 
3. For patients with ARFID  stemming from fear of aversive consequences (eg, choking), an exaggerated fear response may be present, possibly triggered by overactive fear-related brain circuitry involving the amygdala and prefrontal cortex.[8]

Research regarding ARFID is still emerging; the role of serotonin in sensory processing and anxiety suggests a potential mechanism through which neurotransmitter dysregulation could influence the disorder. Moreover, sensory processing issues, which are not exclusive to ARFID but are also present in other conditions (eg, autism), may be associated with abnormal serotonin function, further supporting the need to investigate serotonin's role in ARFID.[22]

History and Physical

Clinical History

ARFID is clinically diagnosed and comprises the patient's medical, nutritional, and psychological assessment. Evaluation for ARFID primarily entails gathering a thorough history, including the onset, duration, and extent of restrictive eating behaviors, any precipitating factors (eg, traumatic feeding experiences), and associated gastrointestinal complaints. The DSM-V outlines the following 4 criteria for diagnosing ARFID:

• Criterion A: An eating or feeding disturbance linked to significant weight loss, nutritional deficiency, reliance on enteral feeding or supplements, or a notable change in psychosocial functioning is present. The possible causes for this disruption outlined in the DSM-V-TR include low appetite, sensory issues with food, and fear-related avoidance of eating.[23]
• Criterion B: The interference with eating is not due to religious or cultural factors or lack of food availability.
• Criterion C: The disturbance is not attributable to other eating disorders like anorexia nervosa or bulimia nervosa, as evidenced by the absence of body image concerns.
• Criterion D: Other psychiatric or medical conditions are excluded as an etiology for the disturbance.[1][2][23][24]

Adding to the diagnostic complexity, ARFID can manifest differently in individuals, with an array of symptoms across the 3 major drivers of the disorder.[3] Individuals with ARFID may display a persistent disinterest in eating or food, potentially leading to significant weight loss or an inability to meet nutritional needs adequately. While some patients with ARFID may have low body weight, the disorder can affect individuals of any weight.[6] Individuals with ARFID frequently have a reduced appetite or adopt behaviors restricting food intake, including eating small bites, prolonged meal times, or excessive chewing.[5] In female patients, clinicians should also obtain a menstrual history, which may identify primary amenorrhea in premenarchal females and secondary amenorrhea in postmenarchal females secondary to malnutrition and significant weight loss.[24] Furthermore, ascertaining the presence of mental health comorbidities or underlying medical conditions is imperative. Psychiatric comorbidities are frequently observed in those with ARFID, particularly anxiety disorders, including generalized anxiety disorder.[6][24][25] ARFID is also commonly associated with neurodevelopment disorders (eg, autism spectrum disorder and ADHD).[26][27] Additionally, various conditions may also present with appetite loss or weight reduction, including tumors or endocrine disorders (eg, type 1 diabetes, hyperthyroidism, or Addison disease), infections, gastrointestinal ailments (eg, Crohn disease, ulcerative colitis, or celiac disease), and swallowing difficulties (eg, achalasia or tonsillar hypertrophy). Therefore, differential diagnoses should be considered during the evaluation process.[24] 

As part of a dietary history, a patient's eating habits should be documented, including past and current eating patterns, the types and amounts of food and drinks consumed, typical eating locations, preferred cooking methods, food brands, and meal sources (eg, specific restaurants or homemade meals). Additionally, clinicians should identify individual dietary preferences and aversions regarding textures, flavors, aromas, and food appearances.[28] Weight loss, failure to achieve expected growth, or reliance on nutritional supplements should also be noted. Dietary preferences characteristically revolve around aversions to specific food tastes, textures, colors, or smells rather than concerns about body shape or weight.[29] Symptoms may include abdominal pain, nausea, or other gastrointestinal discomfort associated with eating, as well as intense fears of choking, nausea, vomiting, allergic reactions, or illness.[5][3][30] Symptom onset may be sudden following a traumatic food-related incident, often accompanied by an anxiety disorder.[5] Mealtimes often become stressful for families, and patients may avoid social gatherings involving food. Caregivers may notice a consistent pattern where the individual exhibits selectivity in their food preferences, often opting for a narrow variety of foods.[5] Despite their nutritional impact, these behaviors are not driven by an expressed desire to lose weight but rather by the distressing experience associated with eating. 

Physical Examination

In addition to assessing an individual's anxiety or phobic responses to eating, a full review of systems and a thorough physical examination are essential. Reviewing growth curves, including weight, height, and body mass index (BMI), is crucial in determining the patient's condition. Objective findings on physical examination may reveal signs consistent with malnutrition, including cachexia, muscle wasting, or micronutrient deficiencies (eg, pallor from anemia, petechiae, or vitamin C deficiency ecchymosis). In contrast to anorexia nervosa, ARFID does not involve body image disturbances. However, patients may suffer from significant nutritional deficiencies and experience physical effects, including fatigue, lack of concentration, and growth delay in children and adolescents due to inadequate food intake. Consequently, patients with ARFID may also develop anemia, bradycardia, or muscle-wasting conditions. Sexual maturity should also be assessed to determine the puberty stage and identify growth abnormalities.[24] Vital sign abnormalities may include bradycardia, hypotension, and orthostatic changes. In pediatric patients, body mass index (BMI) measurements and growth parameters should be carefully assessed against standard growth charts to identify deviations from expected growth trajectories. A gastrointestinal examination may reveal signs of delayed gastric emptying or constipation secondary to low dietary fiber intake.[1]

Evaluation

Diagnostic Studies

While laboratory tests are not diagnostic for ARFID, they are necessary to assess the nutritional status and identify deficiencies or metabolic disturbances. A complete blood count, a comprehensive metabolic panel with liver function tests, thyroid function, and vitamin and mineral levels are frequently performed, particularly in cases where malnutrition is suspected.[28] In addition, various laboratory tests to exclude differential diagnoses may be considered, including erythrocyte sedimentation rate, luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, urinalysis, and Celiac disease screening with tissue transglutaminase antibodies and total IgA.[24] These studies help to evaluate the hydration status, check for inflammatory conditions or malignancies, and assess hormone levels and nutritional deficiencies that may result from malnutrition. Radiographic imaging is not typically necessary unless specific gastrointestinal symptoms (eg, chronic constipation or suspicion of gastrointestinal obstruction) warrant further investigation through diagnostic imaging studies. Other tests, such as bone density scans, may be considered to assess the impact of chronic malnutrition on bone health, especially in longstanding cases. 

Psychological Evaluation

In the last decade, assessments have emerged for screening, evaluating, and tracking treatment outcomes for ARFID.[23] Psychological evaluation for ARFID includes structured office-based interviews and self-reporting measures. Office-based screens that may be utilized for ARFID evaluation include the Eating disorder assessment for DSM-5 (EDA-5), structured clinical interview for DSM-5 (SCID-5), eating disorder examination (EDE) ARFID module, and pica, ARFID, and rumination disorder interview (PARDI assess ARFID). Each of these screening methods has positive and negative features.

Self-reporting screens, including the food phobia scale (FNS), nine-item ARFID screen (NIAS), pica, ARFID, and rumination disorder – ARFID questionnaire (PARDI-AR-Q), and the eating disorder examination questionnaire (EDE-Q) may also be utilized in the evaluation of ARFID. These self-reporting screens measure different aspects of ARFID psychopathology. While these measures offer valuable insights, they have limitations and require validation with office-based screening. Combining structured clinical interviews with self-reports provides a more thorough assessment, aiding diagnosis and treatment monitoring.

Additional Evaluation

Further evaluation or consultation services may be indicated following clinical assessment with growth trajectories and laboratory evaluation.[28] Consultation with a dietitian for nutritional assessment is recommended in patients with ARFID. In cases where comorbid psychological conditions are suspected, a mental health evaluation is also essential. Patients who exhibit slow eating may need to evaluate their chewing and swallowing abilities; patients with growth concerns may be referred to an endocrinologist, while those with gastrointestinal symptoms may require a referral to a gastroenterologist.[28]

Treatment / Management

Due to the recent emergence of the ARFID diagnosis, limited evidence supporting treatment strategies for this condition exists, and consensus guidelines have yet to be established. Cognitive behavioral therapy, family-based therapy, and pharmacotherapy are the most common treatment modalities suggested in the existing literature.[31] To date, no studies have evaluated the effectiveness of ARFID-specific treatment through randomized, fully powered, controlled trials.[23] The treatment goals for individuals diagnosed with ARFID should consist of the following key components:(B3)

• Attain medical stability, addressing immediate health concerns and stabilizing comorbid medical conditions.
• Determine the most appropriate level of care, whether outpatient or inpatient, based on individual needs and severity of symptoms.
• Provide adequate nutrition and monitor progress regularly to restore weight to a healthy range and ensure proper growth.
• Enhance nutritional health by expanding the variety and quantity of foods consumed and addressing any nutrient deficiencies.
• Address and manage any fears or discomforts related to eating, which may involve exposure therapy or other behavioral interventions.
• Promote the enjoyment of eating by identifying enjoyable foods and developing a positive relationship with food.[24]

Pharmacological Management

Pharmacotherapy is not the primary approach for treating ARFID but may be applicable in certain cases.[32] For instance, mirtazapine has been cited due to its appetite-stimulating and anxiolytic properties. Medications, including cyproheptadine, selective serotonin reuptake inhibitors (SSRIs), or atypical antipsychotics (eg, olanzapine), are often used to address associated symptoms rather than ARFID itself. Cyproheptadine, in particular, is an effective off-label option for ARFID as this medication enhances appetite; consideration as a potential treatment for malnourished adults and children, including those diagnosed with ARFID, is warranted.[28][31] (B3)

Olanzapine has also been used off-label to help reduce anxiety, cognitive rigidity, and food-related beliefs that can contribute to ARFID symptoms; in some patients, weight gain may be promoted.[33][34] A case study reported that the addition of low-dose olanzapine to ARFID treatment helped reduce anxiety and depression in a patient.[35] Another case series found that using olanzapine, along with the antidepressant fluoxetine, helped 2 adolescent twins with ARFID reach their target weights within 3 to 6 months of starting treatment.[34] However, the supportive evidence for ARFID treatment with olanzapine is still limited, with no randomized controlled trials demonstrating efficacy. Therefore, olanzapine remains an off-label, experimental treatment.(B2)

Inpatient Management

In cases of ARFID, hospitalization may be necessary to address poor nutritional intake or dangerously low weight and to restore healthy eating behaviors.[36] Studies primarily focused on adolescent or mixed-age groups have examined the hospital course of ARFID. Some findings suggest that adolescents and young adults with ARFID present with similar body mass index (BMI) or percent target weight upon admission compared to patients with anorexia nervosa.[37] However, discrepancies among study findings have been noted.[38][30] Length of hospital stay varies across studies, with some reporting longer stays for ARFID patients and others finding no significant difference. Furthermore, weight gain rates during hospitalization also vary, with some studies indicating slower weight gain in ARFID compared to anorexia nervosa patients, though weight outcomes at discharge appear comparable. Longer-term follow-up studies suggest that adolescents with ARFID may have higher recovery rates compared to those with anorexia nervosa, although further research is needed to confirm these findings.(B3)

The American Psychiatric Association recommends hospitalization be considered in patients with ARFID if the following clinical factors are present:

• BMI <75% of the median for age and gender
• Dehydration symptoms
• Abnormal electrolyte levels (eg, hypokalemia, hyponatremia, or hypophosphatemia)
• ECG irregularities, including prolonged QTc interval or significant bradycardia
• Physiological instability signs, such as:
• daytime bradycardia (<50 bpm) or nighttime bradycardia(<45 bpm)
• Hypotension (<90/45 mm Hg)
• Hypothermia (<96 °F (35.6 °C)
• Significant orthostatic pulse changes (increase in heart rate by >30 bpm for adults older than 19 or >40 bpm for adolescents younger than 19, or a sustained blood pressure decrease of >20 mm Hg systolic or >10 mm Hg diastolic) [39][40]
• Stunted growth and developmental progress
• Unsuccessful outpatient treatment attempts
• Food refusal
• Immediate malnutrition-related medical complications like fainting, seizures, cardiac failure, or pancreatitis.
• Presence of a concurrent psychiatric or medical condition complicating or hindering effective outpatient care, such as severe depression, suicidal ideation, obsessive-compulsive disorder, psychosis, or type 1 diabetes.[41][42][43][44]
(A1)

Nutritional Management

Nutritional rehabilitation, which focuses on establishing regular eating patterns and reintroducing a broader range of foods, is the cornerstone of ARFID management. Nutritional management often requires the expertise of dietitians specializing in eating disorders. Close monitoring of growth and development, particularly in pediatric populations, is crucial. The primary management of ARFID focuses on gradually improving nutritional adequacy, balanced eating habits, and weight gain with the help of a registered dietitian nutritionist (RDN) and the patient's family.[28] Together, they work to increase the patient's overall food intake, introduce new foods gradually, and help the patient make significant progress toward better nutritional health.

In severe cases, hospitalization may be necessary to address nutritional deficiencies and ensure safety. To avoid adverse effects on taste, hunger, mood, and energy, ensuring the timely replenishment of essential nutrients (eg, vitamin B12, vitamin C, iron, zinc, and folate) is vital. Nasogastric tube feedings may also be necessary to counteract malnutrition in severe cases where patients consume minimal food and drink. As the patient's overall intake improves, whether in a hospital or outpatient setting, the foods and beverages they previously enjoyed will gradually be reintroduced into their diet, with the ultimate goal of resuming their typical diet over time. Consequently, the nutritional treatment for ARFID aims to enhance the overall nutritional status, eating habits, and social functioning regarding food.[28]

Psychological Management

Psychotherapeutic interventions form a significant part of the treatment landscape for ARFID. Cognitive-behavioral therapy tailored for ARFID, family-based therapy, and exposure therapies have shown efficacy. These therapies aim to reduce meal-related anxiety, modify disruptive eating patterns, and address distorted beliefs about food. These 3 psychological therapies primarily revolve around the following evidence-based approaches for ARFID:

1. Family-based treatment for ARFID: This approach targets specific aspects of ARFID based on the subtype, typically focusing on consistent and necessary eating habits and gradual weight gain. Therapists aim to enhance parents' confidence in modifying feeding strategies to decrease restrictive eating patterns.[24][28]
2. Cognitive behavior therapy for ARFID: This therapy addresses nutritional deficiency, increases exposure to new foods, and reduces negative feelings and expectations about food and eating.[24][28]
3. Supportive parenting for anxious childhood emotions for ARFID: A specific mental health treatment designed for children with anxiety disorders and OCD. With this approach, clinicians concentrate exclusively on working with caregivers to address caregiver accommodation to modify caregivers' behaviors and reactions to their child's symptoms.[28] 

Psychological management often involves a combination of outpatient therapy sessions, intensive outpatient programs, and even partial hospitalization, depending on the severity of the condition. National and international guidelines advocate for a personalized approach to care, considering each patient's unique needs with ARFID. Collaborative care models are considered best practices, where an interprofessional team of healthcare professionals works together. Engaging a team of healthcare professionals with diverse specializations is recommended, including a primary care clinician, a mental health specialist, a dietician, a gastroenterologist, an occupational therapist, and a speech therapist, based on the patient's specific requirements.[31](B3)

Differential Diagnosis

Several diagnoses may present with distinct clinical features that mimic ARFID and warrant specific clinical evaluations. Therefore, a careful and thorough assessment is necessary to distinguish ARFID from other medical, psychological, or psychiatric conditions. The differential diagnoses for ARFID that should also be considered include:

• Anorexia nervosa
• Bulimia nervosa
• Gastroesophageal reflux disease 
• Eosinophilic esophagitis
• Inflammatory bowel disease
• Food allergies
• Celiac disease
• Chronic idiopathic constipation
• Pica
• Rumination disorder
• Autism spectrum disorders (where food selectivity is common)
• Anxiety disorders
• Major depressive disorder (with changes in appetite or weight)
• Social phobia (may affect eating in public settings)
• OCD
• Post-traumatic stress disorder, following a traumatic event related to eating or food
• ADHD, when associated with impulsivity affecting eating behaviors
• Neurodevelopmental disorders with sensory sensitivities affecting feeding
• Structural anomalies of the oropharynx or gastrointestinal tract affecting intake
• Endocrine disorders like Addison disease or hypothyroidism affect appetite

Prognosis

Evidence regarding the different dimensions of ARFID is lacking. Moreover, the existing data are insufficient to determine the course of the illness and prognosis for patients diagnosed with ARFID.[45] The prognosis for ARFID can vary depending on several factors, including age of onset, duration of illness, and comorbidities. Early diagnosis and intervention are critical for successful treatment, but unfortunately, access to mental health services and treatment options is currently limited. In addition, chronic cases can lead to severe nutritional deficits and psychosocial impairments. A thorough biopsychosocial approach is necessary for effective treatment. Increasing awareness and targeted interventions will lead to better outcomes and improved access to care.[46][47][48] Ongoing research is crucial to understand long-term outcomes better.

Complications

The medical complications arising from ARFID can closely mirror those of anorexia nervosa, mainly due to malnutrition and nutritional deficiencies. The condition can lead to various medical, psychological, and social complications. Complications of ARFID can be extensive, affecting various body systems due to persistent nutritional deficits.[24][49][50][51][50]

Cardiopulmonary Complications

Medical complications specific to the cardiopulmonary system include:

• Bradycardia
• Hypotension
• Cardiac arrhythmias
• Refeeding syndrome
• Reduced cardiac mass
• Mitral valve prolapse
• Orthostatic hypotension
• Pericardial effusion
• Cardiomyopathy
• Heart failure
• Pulmonary edema associated with refeeding syndrome

Renal Complications

Complications affecting the renal system include:

• Acute kidney injury
• Electrolyte imbalances (eg, hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia, and hypophosphatemia)
• Chronic kidney disease
• Proteinuria
• Renal calculi

Gastrointestinal Complications

Medical complications specific to the gastrointestinal system include:

• Constipation
• Gastroparesis
• Gastroesophageal reflux disease
• Dysphagia
• Bloating and gas
• Irritable bowel syndrome
• Functional dyspepsia
• Peptic ulcers
• Abnormal liver function

Endocrinological and Reproductive Complications

The following reproductive and hormonal complications may also develop:

• Growth hormone dysregulation
• Hypothalamic amenorrhea
• Thyroid function abnormalities (eg, euthyroid sick syndrome, hypothyroidism, low metabolic rate)
• Adrenal insufficiency
• Delayed puberty
• Bone metabolism disturbances (eg, decreased bone mineral density and increased fracture risk)
• Hypoglycemia
• Leptin and ghrelin imbalance
• Pancreatic function impairment
• Low libido
• Infertility
• Pregnancy complications
• Erectile dysfunction

Musculoskeletal Complications

Complications affecting muscle and skeletal systems include:

• Decreased muscle mass
• Osteopenia and osteoporosis
• Growth retardation
• Rickets
• Muscle weakness
• Delayed recovery from injury

Dermatological Complications

The following skin disorders may also develop:

• Dry, flaky skin
• Bruising
• Hair thinning or loss
• Eczema or dermatitis
• Pallor
• Acrodermatitis
• Edema

Hematological Complications

Complications affecting the hematologic system include:

• Anemia (eg, iron, vitamin B12, or folate deficiencies)
• Leukopenia
• Thrombocytopenia
• Coagulation disorders

Immunological Complications

Complications affecting the immunologic system include:

• Increased infection susceptibility
• Impaired wound healing
• Reduce efficacy of vaccinations (due to weakened immune system)
• Chronic inflammation
• Atrophy of lymphoidtTissues

Neuropsychological Complications

Several neurologic and psychologic conditions may develop due to ARFID, including:

• Cognitive Impairments (including memory, attention, and executive function)
• Neuropathy
• Seizures
• Developmental delays
• Mood disorders
• Concentration and learning difficulties
• Headaches
• Reduced brain volume
• Sleep disturbances
• Syncope
• Eating disorders
• Personality changes (eg, irritability and emotional lability)
• Social isolation
• Impaired social development and decreased overall quality of life
• Strained family relationships and increased stress