Table 2.

Reports dealing with red flags/screening and their major finding

Domains	Reference	Highlighted
Red flags/screening	Lantzouni E, 2021 [8]	Weight loss, functional hypothalamic amenorrhea, unexplained growth or pubertal delay, restrictive or abnormal eating behaviors, overexercising, or recurrent vomiting are red flags for AN. The reduction in energy intake, excessive exercise, stress, and loss of fat mass can all lead to hypothalamic hypogonadotropic hypogonadism. This can cause primary or secondary amenorrhea. Secondary amenorrhea occurs in 66-84% of patients with AN.
Red flags/screening	Neale J, 2020 [9]	History including questions about compensatory behaviors. Key signs on examination: pallor, lanugo hair, dehydration, poor dentition, parotid gland enlargement. Cardiovascular instability: the most common clinical finding, indicators of risk: bradycardia, hypotension, postural hypotension and hypothermia.
Red flags/screening	Sattler FA, 2020 [10]	Investigations on ten samples focusing on body image disturbance, of individuals aged 10.5–18 years from Austria, Canada, Germany, and Spain published between 1993 and 2017. 75% of samples reported overall higher perceptive body image disturbance in AN patients, compared to healthy controls; 85.71% of the studies of female children and adolescents with AN or bulimia nervosa exhibited greater body dissatisfaction, higher affective or cognitive body image disturbance than controls; 40% clinical samples (age range 13–18 years) reported behavioral disturbance throughout, while two (40%) samples (age range 13–18 years) in half of the measures.
Red flags/screening	Rizk M, 2020 [11]	Large variation in the amount of physical activity approximately one year prior to the onset of AN was detected. Patients who had been very active as children, engaged in more pathological physical activity during their illness than those who were average active as children.
Red flags/screening	Franceschini A, 2021 [12]	Males are younger and with a higher body weight at ED onset than females. Adolescent males with eating disorders are involved more in over-activity than females, and usually report lower weight and shape concerns.
Red flags/screening	Casper RC, 2022 [13]	Nearly 90% of patients with acute AN, restricting type, reported either an increased urge for movement and/or physical restlessness, despite experiencing fatigue and feeling tired.
Red flags/screening	Mellowspring A, 2023 [14]	97% of people hospitalized for an eating disorder have a concomitant health condition: mood disorders, anxiety disorders, such as obsessive- compulsive disorder, post-traumatic stress disorder, and substance use disorder.
Red flags/screening Genetic neurological pathways	Bhattacharya A, 2020 [15]	Some neuropsychiatric disorders tend to be more associated with AN, such as oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety disorders, obsessive compulsiveness, depressive symptoms, and suicidal ideation. Prior to puberty, the impact of genetics on developing an ED is 50% in males and 0% in females; at puberty it increases to 50% in females with puberty. As the insula helps to integrate and regulate autonomic, affective, and sensory systems, researchers proposed a theory of insular dysfunction playing an etiologic role in AN.
Red flags/screening	Villa FM, 2023 [16]	Many children with ADHD additionally present a comorbid eating disorder. The drive for thinness, is common among female adolescent patients with AN and among patients with ADHD and one hypothesis indicates the role of genetic risk factors, namely a melanocortin-4- receptor deficiency as common base responsible of the compresence of both diseases
Red flags/screening	Dufresne L, 2020 [17]	Differences between ED groups and normative groups for the four-personality trait domains studied (Negative Affectivity vs. Emotional Stability, Detachment vs. Extraversion, Antagonism vs. Agreeableness, and Disinhibition vs. Conscientiousness). Negative Affectivity (g = 0.78; k = 25; 95% confidence interval [CI] = 0.59–0.96; p < .001) and Detachment (g = 0.69; k = 14; 95% CI = 0.59–1.08; p < .001) were significantly higher in ED adolescents. The Disinhibition domain was significantly lower in ED adolescents (g = − 0.53; k = 19; 95% CI = − 0.72 to − 0.34; p < .001). No significant differences were found for Antagonism (g = 0.18; k = 5; 95% CI = − 0.21 to 0.58; p = .107).
Red flags/screening Environment neurological patways	McAdams CJ, 2022 [18]	Self-esteem and socializing problems are associated with ED symptoms during adolescence. Social stressors often concur with ED symptom onset. Common stressors are bullying about shape/weight/appearance. In Fijian adolescents, social pressures from a changing society correlate to body size concerns and ED. Adolescents with AN presented reduced activation in the superior temporal sulcus. Adolescents who recovered from AN had no whole-brain differences, and less activation in the precuneus one year later. Study in adolescents with AN showed reduced processing in the social condition in the medial prefrontal cortex and less activation in this region at baseline was associated with worse outcomes a year later. In adolescents with AN, dorsolateral prefrontal cortex activation at baseline was related to increased amygdala.
Red flags/screening	Nagata JM, 2020 [19]	Sexual minorities and gender minorities are at higher risk of developing eating disorder behaviors and body dissatisfaction compared to heterosexual individuals.
Red flags/screening	Beckmann EA, 2023 [20]	There is a correlation with ED and chronic functional abdominal pain. Chronic functional abdominal pain is a risk factor for the development of a restrictive eating disorder.
Red flags/screening	Quadflieg N, 2021 [21]	Recurrent abdominal pain in childhood (age 7–9 years) as a risk factor for fasting at age 16, for weight control. Three abdominal pain episodes a year in childhood were found to be predictive of future fasting.
Red flags/screening Genetic neurological patways	Grammatikopoulou MG, 2023 [22]	Children and adolescents with autoimmune or autoinflammatory diseases are at greater risk (HR: 37%) of developing AN. Specific brain-reactive autoantibodies in juvenile SLE correlate with neuropsychiatric disorders. Twin studies indicated heritability. Brain scans of affected persons and genome-wide association studies pointed to the fact that AN is primarily observed in families with perfectionist, obsessive, and competitive traits.
Red flags/screening Genetic	Breton E, 2022 [23]	Children and adolescents with an autoimmune or autoinflammatory disease, or a family history of such diseases, are at higher risk of ED; likewise, individuals with a diagnosis of ED are at higher risk of autoimmune or autoinflammatory diseases. Findings support an overlap between gene pathways related to obesity and AN as for a genetic correlation between AN and traits related to energy metabolism. AN has identified single-nucleotide polymorphisms in EBF transcription factor 1 which influences leptin signaling and the development of the immune system and which are both likely altered in AN
Red flags/screening Genetics	Sirufo MM, 2022 [24]	AN and autoimmune diseases have common immunopathological pathways.
Red flags/screening Genetic	Barakat S, 2023 [25]	Autoimmune reactions are a risk factor for the development of AN. In adolescents with SLE, steroid-induced alterations in body weight and shape might act as triggers for body image dissatisfaction and consequently for AN. Corticosteroids use is also associated with psychiatric events: anxiety, agitation, psychosis, insomnia, catatonia, depression, mood and cognitive changes, euphoria, depersonalization, delirium, dementia, and hypomania. These can drive the development of AN in adolescents with juvenile lupus.
Red flags/screening	Salatto A, 2023 [26]	Children with eating disorders should be identified early given the increasing number of affected individuals in pediatric age. They identified possible red flags that an eating disorder is arising in the pediatric population. The likelihood of developing comorbidities appears to be the same for atypical AN as in subjects with “typical” AN.
Red flags/screening	Charrat JP, 2023 [27]	The systematic review underscores the prominence of prepubescent low BMI and body dissatisfaction as conceivable predictors of AN onset. Associations have been found between AN onset and childhood traumatic factors, anxiety, BMI, drive for thinness, early childhood temperament and psychopathology, obsessive compulsive disorders, depression. Similarly, environmental factors need to be further tested including: family discord and parental mood disorders.
Red flags/screening Environment	Herpertz-Dahlmann B, 2021 [28]	Children had a significantly shorter duration of illness and a higher body mass index percentile at admission than adolescents in case of regular pediatric health check-up for 12–15 year old in Germany since 1998. The effects of appearance-focused gaming vs. ED-neutral gaming were assessed in young girls: those exposed to appearance- focused gaming had higher body dissatisfaction.
Red flags/screening	Monda M, 2021 [29]	Clinical signs of systemic disease and nutritional deficiency may be precociously detected in the oral cavity due to the rapid turnover of epithelial cells in the mucous membranes (3–7 days) compared to the skin (up to 28 days). 94% of subjects with ED have oral manifestations such as dental erosion, carious disease, periodontal diseases (spontaneous gingival bleeding, ulceration, dental mobility and increased periodontal infections) induced by vitamin C deficiency.
Red flags/screening	Treasure J, 2020 [30]	No difference in physical parameters on presentation, except for the lower white blood cell count in the “typical” AN group, have been found.