Evaluation of weight loss in infants over six months of age, children, and adolescents

INTRODUCTION — This topic will discuss the approach to weight loss in the older infant and adolescent. Weight loss in young infants is discussed separately. (See "Evaluation of weight loss in infants six months of age and younger".)

BACKGROUND — There are many causes of weight loss throughout childhood. Dehydration, infection (especially viral gastroenteritis), malnutrition, and child neglect are common causes in older infants and young children. Depression, eating disorders, inflammatory bowel disease, malignancy, and malabsorption (eg, lactose intolerance, celiac disease) are more frequent in school-age children and adolescents. Weight loss and slow weight gain can have serious long term consequences extending into adulthood [1]. Assessments of the degree and acuity of the weight loss along with specific historical and physical findings should guide the evaluation of these patients.

TERMINOLOGY — Weight loss may be classified as intentional or unintentional:

●Acute or progressive unintentional weight loss often indicates a serious medical illness that requires evaluation and treatment.

●Intentional weight loss in overweight or obese individuals is benign in most instances but must be followed closely in the pediatric patient to ensure the patient has appropriate growth. The frequency of intentional loss in association with altered body image or other psychiatric illness (eg, anorexia nervosa) increases with advancing age, peaking in adolescence and early adulthood.

PATHOPHYSIOLOGY — The major components of body weight consist of water, protein, carbohydrates, and fats. Weight loss occurs when the intake of one or several of these components becomes less than the output.

Causes include:

●Decreased calorie intake either voluntary (eg, eating disorder) or due to intercurrent illness with normal or increased metabolic expenditure

●Normal calorie intake with increased metabolic utilization (eg, hyperthyroidism, excessive exercise)

●Normal or increased calorie intake in the setting of malabsorption or excessive loss of nutrients (eg, inflammatory bowel disease, diabetes mellitus, celiac disease, or self-induced losses [purging by vomiting, diuretics, or laxative use])

●Acute fluid losses that exceed intake during acute illnesses, such as gastroenteritis

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for weight loss in the older infant, child, and adolescent is wide and may require an extensive work-up (table 1). In many cases, a diagnosis is not revealed during initial care, but the evaluation may begin and specialist referrals can be made as needed.

Life threatening conditions

Diabetes mellitus — Patients with new onset diabetes mellitus may present with significant weight loss in the setting of polyuria and polydipsia over days to weeks. Laboratory studies show hyperglycemia and glycosuria. Weight loss is a result of hypovolemia (due to a hyperglycemia-induced osmotic diuresis) and increased catabolism. Insulin deficiency impairs glucose utilization in skeletal muscle and increases fat and muscle breakdown. Initially appetite is increased, but over time, children may become anorexic, contributing to weight loss. Patients may also present with significant illness due to diabetic ketoacidosis. (See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents", section on 'Classic new onset'.)

Adrenal insufficiency — Patients with adrenal insufficiency may present with excessive fluid losses and hemodynamic instability due to a deficiency of corticosteroid production, which leads to altered fluid and salt balance. Primary adrenal insufficiency (Addison disease) occurs when the adrenal gland itself is dysfunctional while secondary or tertiary (central) adrenal insufficiency occurs when there is a lack of adrenocorticotropic hormone (ACTH) from the pituitary or corticotropin-releasing hormone (CRH) from the hypothalamus, respectively, that leads to inadequate adrenal function (eg, hypopituitarism, diencephalic syndrome). (See "Clinical manifestations and diagnosis of adrenal insufficiency in children", section on 'Determine primary versus central adrenal insufficiency'.)

Patients suffering from adrenal insufficiency present with vomiting, anorexia, dehydration, and weight loss, which can lead to cardiovascular collapse. Physical findings may include hyperpigmentation, especially on the extensor surfaces, and weakness. Hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis are classic laboratory findings in the initial assessment. Stabilization involves management of airway, breathing and circulation with a focus on volume resuscitation and corticosteroid replacement. Whenever possible, measurement of serum cortisol should precede corticosteroid administration. (See "Causes of primary adrenal insufficiency in children" and "Causes of central adrenal insufficiency in children", section on 'Overview of clinical manifestations' and "Treatment of adrenal insufficiency in children".)

Eating disorders — Patients with anorexia nervosa typically present with a refusal to maintain body weight at or above a minimally normal weight for age and height defined as either 85 percent of that expected for age and height or a body mass index (BMI) ≤17.5 (calculator 1 and calculator 2). Additional features include an intense fear of gaining weight or becoming fat despite being underweight, distorted perception of body weight and shape, and, in postmenarchal females, amenorrhea (table 2). Bulimia nervosa is characterized by recurrent episodes of binge eating and inappropriate compensatory behavior to prevent weight gain, occurring on average at least two times per week for three months. Other clinical features options of anorexia nervosa and bulimia nervosa are discussed separately. In severe eating disorders, patients may develop profound bradycardia or electrolytes abnormalities that are life threatening. (See "Anorexia nervosa in adults and adolescents: Medical complications and their management", section on 'Diagnosis of anorexia nervosa' and "Eating disorders: Overview of epidemiology, clinical features, and diagnosis".)

Dehydration — Severe dehydration from acute gastroenteritis or other illnesses with significant fluid losses can lead to weight loss and hemodynamic compromise. Children with acute gastroenteritis typically present with acute onset of diarrhea, vomiting, fever, anorexia, and abdominal cramps. Blood or mucous in the stool or rice water stool suggest bacterial enteritis or cholera, respectively. Findings of significant dehydration (eg, prolonged capillary refill, dry mucous membranes, lethargy) are commonly found on physical examination. (See "Clinical assessment of hypovolemia (dehydration) in children", section on 'Clinical assessment'.)

Repletion of fluid losses and management of gastroenteritis are discussed in more detail separately. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings" and "Diagnostic approach to diarrhea in children in resource-abundant settings", section on 'Algorithmic approach to the patient'.)

Common conditions

Viral gastroenteritis — Mild to moderate weight loss commonly accompanies viral gastroenteritis. Clinical manifestations include nonbloody watery diarrhea, nonbilious vomiting, variable fever, abdominal pain, and anorexia. The diagnosis of acute viral gastroenteritis is made clinically. Testing for specific viruses usually is not necessary in immunocompetent hosts with routine gastroenteritis. However, it may be indicated during outbreaks of gastroenteritis, to make decisions about specific therapy, and for cohorting and isolation of hospitalized patients. Most previously healthy patients recover uneventfully but severe dehydration may rarely occur. (See 'Dehydration' above and "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis", section on 'Clinical presentation'.)

Depression — Chronic weight loss may be a neurovegetative sign of depression, especially in adolescents. Other findings may include decreased appetite, change in sleep, and lack of energy (table 3). Problems with school work, drug use, and risky sexual behaviors are additional comorbidities. Recognition of depression can be difficult due to nonspecific complaints and symptoms. In addition to neurovegetative signs described above, depressed school-age children may also present with irritability, generalized body pains, sleep disturbances, headaches, and poor oral intake with associated weight loss. Additional features suggesting depression in older children or adolescents include chronic disease (eg, diabetes mellitus or cancer), a family history of depression in siblings or a parent, and situational stressors. Diagnosis should be based upon a formal clinical interview with the patient that is supplemented by information from parents and, in the primary care setting, from teachers. All patients with signs of depression warrant screening for suicidal ideation. (See "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Diagnosing depressive disorders' and "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Assessment'.)

Inflammatory bowel disease — Ulcerative colitis (UC) and Crohn's disease (CD) make up the disorders of inflammatory bowel disease. UC affects the colon, whereas CD can involve any component of the gastrointestinal (GI) tract from the oral cavity to the anus. The peak incidence of IBD occurs in patients between the ages of 15 and 25 years. Approximately 25 to 30 percent of patients with CD and 20 percent of patients with UC present before the age of 20 years. Adolescents and children with IBD may present with oral lesions (eg, mucogingivitis or deep ulcerations), abdominal pain, weight loss, tenesmus, perianal fistulas or skin tags, diarrhea, and hematochezia. Growth failure and delayed puberty are present in about 30 percent of children and is due to a combination of anorexia and increased energy needs related to inflammation. (See "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents" and "Clinical presentation and diagnosis of inflammatory bowel disease in children".)

Acute infections — Patients with underlying acute infections, such as urinary tract infection, pneumonia, or bacterial pharyngitis, can present with weight loss due to decreased ability or desire to feed in conjunction with increased metabolic needs. Fever is frequently present along with other clinical findings that provide clues to the source of infection (eg, cough and respiratory distress [pneumonia], suprapubic or costovertebral angle tenderness [urinary tract infection], sore throat with tonsillar exudate or swelling [streptococcal pharyngitis, peritonsillar abscess]) [2].

Celiac disease — Celiac disease is a multifactorial autoimmune disorder that occurs in genetically susceptible individuals. It is triggered by a well-identified environmental factor (gluten and related prolamins). The disease primarily affects the small intestine, where it progressively leads to flattening of the small intestinal mucosa. Three cereals contain gluten and are toxic for patients with celiac disease: wheat, rye, and barley. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Pathogenesis and risk factors'.)

The typical form of celiac disease presents with GI symptoms that characteristically appear at age 9 to 24 months. Infants and young children typically present with chronic diarrhea, anorexia, abdominal distension, abdominal pain, poor weight gain or weight loss, and vomiting after the introduction of gluten-containing foods. Severe malnutrition can occur if the diagnosis is delayed. Behavioral changes are common and include irritability and an introverted attitude. Rarely, severely affected infants present with a celiac crisis, which is characterized by explosive watery diarrhea, marked abdominal distension, dehydration, hypotension, and lethargy, often with profound electrolyte abnormalities, including severe hypokalemia. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children".)

Child neglect — Child neglect is the most prevalent form of child abuse, accounting for more than one-half of cases reported to child protection services. It is defined by the National Center of Child Abuse and Neglect as failure to provide for a child's basic physical, emotional, educational, or medical needs.

The manifestations of child neglect include starvation or dehydration due to inadequate provision of food and water; poor hygiene of a child's body; severe, untreated dental caries; failure to provide routine health care including immunizations, and physical abuse [3,4]. Many but not all children will have physical signs of abuse including fractures and bruises. Often children also suffer from ongoing emotional abuse in conjunction with physical abuse or neglect. (See "Child neglect: Evaluation and management".)

Malnutrition and failure to thrive — Inadequate access to food affects a large number of children, especially in the developing world. Severe protein-energy malnutrition is associated with one of two classical syndromes, marasmus (wasting syndrome) and kwashiorkor, or with manifestations of both. Each type of protein-energy malnutrition may be classified as acute or chronic, depending upon the duration of nutritional deprivation [5]. Children with acute malnutrition appear wasted, whereas children with chronic malnutrition have stunted linear growth. A detailed social history can often reveal poverty and economic stressors as potential contributors to weight loss from lack of resources. Patients may present with weight loss or poor weight gain because of decreased intake due to the inability to acquire adequate amounts of nutrition and chronic conditions that are due to poor food availability [6]. Often, patients have no reliable housing, schooling, and other social support issues that need to be addressed. (See "Malnutrition in children in resource-limited settings: Clinical assessment", section on 'Clinical assessment'.)

Failure to thrive (FTT) is a sign that describes a particular problem, rather than a diagnosis. The term FTT is used to describe instances of growth failure, or more specifically, failure to gain weight appropriately, especially in children three years of age and younger. In more severe cases, linear growth and head circumference also may be affected. A wide variety of medical problems and psychosocial stressors can contribute to FTT (table 4). However, the underlying cause is always related to inadequate nutrition. Several definitions of failure to thrive exist. All definitions identify children with failure to thrive as having low weight in relation to age or length or insufficient weight gain over time. (See "Poor weight gain in children younger than two years in resource-abundant settings: Etiology and evaluation" and "Poor weight gain in children younger than two years in resource-abundant settings: Etiology and evaluation", section on 'Definitions'.)

Lactose intolerance — Lactose malabsorption may occur as a primary condition or may complicate other conditions, such as inflammatory bowel disease (especially Crohn's disease), celiac disease, and giardiasis (table 5). Characteristics symptoms after the ingestion of lactose include abdominal pain, bloating, flatulence, diarrhea, and, particularly in adolescents, vomiting. The abdominal pain may be crampy in nature and is often localized to the periumbilical area or lower quadrant. Borborygmi may be audible on physical examination and to the patient. The stools are usually bulky, frothy, and watery. Undiagnosed patients who continue with lactose intake may have significant weight loss. Lactose malabsorption should be confirmed by a test of absorption (eg, lactose absorption test) or malabsorption (lactose breath hydrogen test). (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management", section on 'Clinical features' and "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management", section on 'Diagnostic evaluation'.)

Drug use — Anorexia with weight loss may accompany use of methylphenidate and other amphetamines for the treatment of attention deficit disorder with hyperactivity. Administering the medicine at or after a meal, encouraging the ingestion of nutrient dense foods, and offering foods that the child likes for lunch (the meal most likely to be affected) may overcome decreased appetite. If stimulant therapy is associated with growth failure that crosses two major percentiles (ie, the 5^th, 10^th, 25^th, 50^th, 75^th, 90^th, and 95^th), then a drug holiday may be beneficial as long as marked impairment in psychological functioning does not occur. (See "Attention deficit hyperactivity disorder in children and adolescents: Treatment with medications", section on 'Managing stimulant adverse effects'.)

Other conditions — A variety of less common but important conditions may present or be associated with weight loss as follows:

●Malignancy – Patients with continued, unintentional weight loss in the setting of anemia, pallor, bruising, body pains, unexplained fevers, or fatigue may have an underlying malignancy. Although childhood cancers are rare events, they are the fourth leading cause of death in individuals between 1 and 19 years of age in the United States after unintentional injury, homicide, and suicide. Common sites include blood and bone marrow, brain, bone, lymph nodes, nervous system, kidneys, and soft tissues. A thorough physical examination may reveal additional worrisome findings, such as lymphadenopathy or hepatosplenomegaly that constitute need for further evaluation. (See "Overview of common presenting signs and symptoms of childhood cancer".)

●Tuberculosis – Though a rare cause of unexplained weight loss in children and adolescents in resource-rich countries, tuberculosis should be considered in patients presenting with weight loss and chronic cough or respiratory symptoms with fevers lasting more than three weeks. A thorough exposure history should evaluate for any international travel, close adult contacts born in endemic areas, contact with incarcerated individuals, or any history of having been homeless. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'United States' and "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

●Human immunodeficiency virus – Clinical manifestations of human immunodeficiency virus (HIV) infection in children and adolescents are varied and nonspecific. Patients may present with recurrent unexplained infections leading to gradual weight loss. Furthermore, loss of lean body mass or wasting is a well-recognized AIDS-defining condition for children and adolescents. HIV infection, opportunistic infections, and increased metabolic demands all can lead to loss of weight and lean body mass. In children, wasting can severely impact normal growth and development and is associated with a high risk for HIV disease progression and short-term mortality. (See "Pediatric HIV infection: Classification, clinical manifestations, and outcome", section on 'Clinical manifestations' and "Pediatric HIV infection: Classification, clinical manifestations, and outcome", section on 'Wasting syndrome'.)

In children and adolescents with possible or established HIV infection, a thorough social and sexual history should explore risk factors, including history of blood transfusions, homelessness, having an HIV-infected parent, sexual contacts, intravenous drug use, and incarceration. (See "Epidemiology of pediatric HIV infection" and "The adolescent with HIV infection".)

●Primary immunodeficiency – Children with primary immunodeficiency often have poor weight gain or even weight loss. This is particularly true in the presence of oral ulcers, candidiasis, or chronic diarrhea. Almost three-fourths of the primary immunodeficiencies are caused by an antibody (B cell) deficiency or a combined antibody plus cellular (T cell) abnormality (figure 1). Isolated T cell defects, as well as phagocytic cell, complement, and other innate immune defects, are much less common. Thus, B cell (antibody) or combined B and T cell diseases should be considered initially, unless clinical features suggest otherwise. Recurrent infections comprise the most common clinical findings. The type and pattern of recurring infections depend on which components of the immune system are affected (table 6). Infection severity also varies, ranging from mild respiratory infections to overwhelming systemic infections. (See "Approach to the child with recurrent infections", section on 'Clinical features suggestive of a primary immunodeficiency'.)

●Other chronic infections – Several chronic infections may cause weight loss in association with prolonged fever and nonspecific and variable clinical findings, such as lymphadenopathy, hepatitis, and myalgias including brucellosis, leptospirosis, tularemia, and Epstein-Barr virus. Specific diagnosis typically requires a careful history, physical examination, and targeting serologic testing. (See "Fever of unknown origin in children: Etiology" and "Fever of unknown origin in children: Evaluation", section on 'Overview of evaluation'.)

●Giardiasis and other intestinal parasites – Weight loss is a prominent symptom of both acute and chronic giardiasis. Acute disease is notable for nausea, vomiting, diarrhea, abdominal cramps, malaise, and flatulence. Chronic disease is marked by waxing and waning findings that include steatorrhea, malaise, fatigue, abdominal pain, flatulence, and burping. Patients with chronic giardiasis can lose up to 10 to 20 percent of their body weight. Stool microscopy is the initial diagnostic test of choice. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

Children with a large burden of intestinal parasites other than Giardia may have weight loss and failure to thrive due to poor absorption of nutrients. (See "Tapeworm infections" and "Ascariasis".)

●Superior mesenteric artery syndrome – Superior mesenteric artery (SMA) syndrome is characterized by compression of the third portion of the duodenum due to narrowing of the space between the superior mesenteric artery and aorta. In children, SMA syndrome is associated with spinal surgery and is also more common in intellectually disabled patients who commonly present with intolerance of gastrostomy tube feedings [7]. Patients typically present with postprandial epigastric abdominal pain and early satiety, while those with more advanced obstruction may have severe nausea, bilious emesis and weight loss [8]. Physical examination findings are often nonspecific but may include abdominal distension, a succussion splash, and high-pitched bowel sounds. Laboratory examination can be normal or, in patients with severe vomiting, significant electrolyte abnormalities may be present. Upper gastrointestinal fluoroscopy with small bowel follow through is diagnostic. (See "Superior mesenteric artery syndrome".)

●Cystic fibrosis – Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a complex chloride channel and regulatory protein found in all exocrine tissues. Deranged transport of chloride and/or other CFTR-affected ions, such as sodium and bicarbonate, leads to thick, viscous secretions in the lungs, pancreas, liver, intestine, and reproductive tract, and to increased salt content in sweat gland secretions. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Overview of clinical features'.)

Although screening for CF is performed in many resource-rich countries and most children otherwise present with signs or symptoms as infants, rarely older children and adolescents with intermediate derangements in CFTR may come to attention because of weight loss in association with frequent pneumonias, chronic cough, sinus disease, or pancreatic insufficiency. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Overview of clinical features'.)

●Cyclic vomiting – Cyclic vomiting syndrome (CVS) is an idiopathic disorder characterized by three or more recurrent discrete episodes of vomiting with varying intervals of completely normal health between episodes. Patients have no organic cause to their recurrent vomiting. The specific pattern of vomiting episodes is variable among patients but, importantly, is stereotypical for an individual patient. In general, CVS episodes tend to begin in the early morning hours (2:00 to 7:00 AM) and may involve a prodromal period of pallor, anorexia, nausea, abdominal pain, and/or lethargy (table 7). In children, the attacks last an average of 24 to 48 hours. (See "Cyclic vomiting syndrome", section on 'Clinical manifestations'.)

Supportive criteria for the diagnosis of CVS include a history or family history of migraine headaches, the self-limited nature of the attacks, associated symptoms of nausea, abdominal pain, headache, motion sickness, photophobia, and lethargy, and associated signs of fever, pallor, diarrhea, dehydration, excess salivation, and social withdrawal. In children, nausea and possibly lethargy are considered to be key diagnostic features. (See "Cyclic vomiting syndrome", section on 'Clinical manifestations'.)

●Pancreatitis – Chronic pancreatitis should be considered in the differential diagnosis of children with growth failure, particularly those with a weight deficit and malnutrition. Abdominal pain is the cardinal feature of chronic pancreatitis. However, the pain pattern varies among patients and tends to fluctuate during the course of the disease. The pain typically is epigastric, often radiates to the back, is often associated with nausea and vomiting, and may be relieved by sitting upright or leaning forward. The pain often is worse 15 to 30 minutes after eating, especially if fatty food is consumed. Early in the course of chronic pancreatitis, the pain may occur in discrete attacks; as the condition progresses, the pain tends to become more continuous. Findings of malabsorption (steatorrhea) and glucose intolerance (glycosuria, frank diabetes mellitus) may also be present. The examination is often normal, but may include epigastric or upper abdominal tenderness. An epigastric mass may be palpated if the patient has developed a pseudocyst. (See "Clinical manifestations and diagnosis of chronic and acute recurrent pancreatitis in children", section on 'Clinical manifestations'.)

The diagnosis of chronic pancreatitis is relatively straightforward and can be suspected clinically in patients who present with acute pancreatitis followed by recurring attacks of pain. Diagnosis is more challenging in those with few or mild symptoms. In such patients, the diagnosis depends upon the strength of clinical features, combined with functional and morphologic evaluation of the pancreas, as described separately. (See "Clinical manifestations and diagnosis of chronic and acute recurrent pancreatitis in children".)

●Liver disease – Hepatic insufficiency with jaundice, anorexia, weakness, and malabsorption of fat may lead to weight loss in children. Right upper quadrant abdominal pain, hepatosplenomegaly, ascites, and encephalopathy are frequently present. Viral and drug-induced hepatitis, immune dysregulation, and rarely, Wilson disease comprise potential etiologies. (See "Acute liver failure in children: Etiology and evaluation", section on 'Clinical presentation' and "Acute liver failure in children: Etiology and evaluation", section on 'Causes of pediatric acute liver failure'.)

●Rheumatologic disease – Untreated collagen vascular diseases (eg, systemic lupus erythematosus, juvenile idiopathic arthritis) increase metabolic requirements and may present with weight loss. Associated findings include fever, characteristic rash (butterfly malar or evanescent macular papular rash), arthralgia or arthritis, elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), leukocytosis, and anemia.

●Hyperthyroidism – Hyperthyroidism in children and adolescents has unique effects on growth and development. Children will often have delayed growth plate closure with a subsequent increase in growth rate. This leads children to cross growth percentiles upwards for height in the setting of a significant weight loss. Other clinical features include lid lag and stare, diffuse goiter, tachycardia, increased gastrointestinal motility, proximal muscle weakness, tremor, hyper-reflexia, sleep disturbance, and distractibility. Diagnosis is made by measurement of serum thyroid function tests.

●Hypercalcemia – Hypervitaminosis D, hyperparathyroidism, myositis ossificans in patients with dermatomyositis, adverse effects of medications (eg, thiazide diuretics or lithium) and, rarely malignancy are potential causes of hypercalcemia in children [9]. Serum calcium levels >12 mg/dL (3 mmol/L) are associated with anorexia, abdominal pain, constipation, and arginine vasopressin resistance (AVP-R, previously called nephrogenic diabetes insipidus) manifested by polyuria and polydipsia. Patients may present with weight loss caused by dehydration. (See "Clinical manifestations of hypercalcemia".)

●Lead poisoning – Marked elevation in blood lead above 60 mcg/dL (2.9 micromol/L) may cause lead colic, which is marked by weight loss in association with sporadic vomiting, anorexia, abdominal pain, and constipation in a child with environmental exposure to lead. Measurement of a venous blood lead level is diagnostic. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Gastrointestinal'.)

●Sarcoidosis – Symptomatic sarcoidosis is rare in older children and adolescents. Presenting symptoms include pulmonary findings (cough, dyspnea, chest pain) and systemic symptoms of fever, anorexia, fatigue, and weight loss. Sarcoidosis has a myriad of extrapulmonary manifestations (table 8). Diagnosis is supported by compatible clinical findings and radiographic features, exclusion of other diseases with similar presentation (eg, tuberculosis, lymphoma), and histopathology showing noncaseating granulomas in the lung (picture 1). (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Typical presentations'.)

EVALUATION — The goal of the evaluation of the child or adolescent with weight loss is to identify any signs and symptoms of underlying disease and then to explore potential psychosocial factors that may be involved. A careful, thorough history and physical examination, in conjunction with the judicious use of laboratory tests will often reveal the cause. Laboratory investigation is unlikely to reveal an organic cause in the absence of suggestive evidence from the initial history or physical examination.

History — The clinician should begin by determining the severity and acuity of weight loss:

●Acute weight loss – Rapid weight loss is more indicative of a life-threatening process and needs prompt evaluation and treatment. Acute weight loss (usually less than one to two weeks in duration) is often caused by inadequate fluid and caloric intake, increased losses, or increased metabolic needs associated with an intercurrent illness.

Key historical features suggest specific etiologies as follows (see 'Life threatening conditions' above):

•Polyuria and polydipsia (diabetes mellitus)

•Vomiting and weakness (adrenal insufficiency)

•Distorted body image with intentional weight loss (eating disorders)

•Significant fluid losses with lethargy and inadequate oral intake (dehydration)

●Chronic weight loss – Patients who have been experiencing weight loss over a longer period of time (usually greater than three weeks or via a slow progression) may have increased metabolic needs from underlying chronic disease, malabsorption, or other psychosocial stressors as contributing factors.

The clinician should ask about any known medical conditions or changes in overall health. Changes in stool quality and quantity, the presence of blood in the stool, or changes to the diet may indicate malabsorption or inflammation (eg, celiac disease or inflammatory bowel disease). Unexplained fevers, malaise, or joint swelling should prompt the provider to consider rheumatologic or oncologic etiologies. Change in appetite, sleep, or school failure may indicate signs of depression.

A family history should be completed specifically assessing for any relatives with malabsorption, gastrointestinal disease, malignancy, or eating disorders.

●Diet history – A complete diet history should be completed for all patients with particular attention to amount of daily intake, types of foods, recent changes (eg, fad dieting, change to vegetarianism/veganism, decreased appetite), dietary supplements, or pica. A food intake diary can be helpful in cases where the exact intake may be over or under-estimated. The provider should note if weight loss began or progressed after introduction of specific foods (ie, gluten, dairy, or fats).

●Social history – Key elements of the social history include:

•History of frequent unintentional injuries, missed medical appointments, involvement of social services, or siblings with failure to thrive suggesting childhood neglect

•Frequent feelings of sadness, guilt, worthlessness or frequent thoughts of death or suicidal ideation as signs of depression

•Recreational drug use, especially alcohol, cocaine, and amphetamines

•History of cigarette smoking

•Amenorrhea, intense fear of gaining weight, or disturbed body image indicating an eating disorder

Physical examination — In addition to a complete physical examination, measurements of weight and, as appropriate, height should be documented on a standard growth chart and compared with any previous available measurements to assess for rate of loss and changes in weight percentile.

Patients with signs of shock warrant prompt reversal of findings including support of airway and breathing, rapid vascular access, and rapid administration of isotonic intravenous fluids (algorithm 1). (See "Shock in children in resource-abundant settings: Initial management".)

Physical findings that suggest potential etiologies include:

●Body habitus – Weight for age and height defined as either 85 percent of that expected for age and height or a body mass index (BMI) ≤17.5 suggests an eating disorder (calculator 1 and calculator 2).

●General appearance – Patients with celiac disease, child neglect, malnutrition, or eating disorders often appear wasted. Depressed patients often have a flat or sad affect. Pallor is frequently found in children with malignancy, especially leukemias, or rheumatologic disease (eg, systemic lupus erythematosus, SLE).

●Fever – Fever may be present in patients with infection, inflammatory bowel disease, rheumatologic disease, or malignancy.

●Heart rate – Tachycardia is common in patients with diabetic ketoacidosis, dehydration, hyperthyroidism, pancreatitis, and acute infections. Bradycardia is frequently found in patients with eating disorders.

●Compensated shock or hypotension – Tachycardia with prolonged capillary refill time or hypotension may occur in patients with diabetic ketoacidosis, adrenal insufficiency, dehydration, or serious acute infections.

●Tachypnea – Patients with diabetic ketoacidosis commonly display Kussmaul breathing, which is characterized more by deep than by rapid respirations. Findings of rales or wheezes suggest pneumonia in association with cystic fibrosis, human immunodeficiency virus infection, or tuberculosis.

●Sinusitis – Sinus tenderness and discharge with sinusitis frequently occurs in children with cystic fibrosis.

●Oral findings – Mucositis and oral ulcers may be seen in patients with inflammatory bowel disease. Hard palate lesions suggest rheumatologic disease. Patients with diabetic ketoacidosis have a fruity odor to their breath. Patients with frequent vomiting (eating disorder or cyclic vomiting) may have loss of enamel on the inside portion of the teeth.

●Goiter – Enlargement of thyroid gland is commonly seen in children with hyperthyroidism.

●Generalized lymphadenopathy – Cervical, axillary, and inguinal lymphadenopathy accompanies tuberculosis, human immunodeficiency virus infection, sarcoidosis, and malignancies.

●Abdominal tenderness – Diffuse tenderness suggests viral gastroenteritis, giardiasis, and inflammatory bowel disease. Epigastric tenderness and distension is frequently found in patients with pancreatitis or superior mesenteric artery syndrome.

●Hepatosplenomegaly – Enlargement of the liver and/or spleen may be found in patients with liver disease or malignancy.

●Rectal findings – Perianal skin tags and guaiac positive stool are potentially indicative of inflammatory bowel disease.

●Joint findings – Joint effusions or pain with range of motion suggests rheumatologic disease or septic arthritis.

●Skin findings – Hyperpigmentation often accompanies adrenal insufficiency. Erythema nodosum may occur in patients with inflammatory bowel disease or sarcoidosis. Children with malignancy (especially leukemia) or child neglect may have bruising in areas that are not prone to trauma. Malar rash or evanescent salmon patches occur in patients with SLE and juvenile idiopathic arthritis, respectively.

●Neurologic findings – Diffuse weakness frequently occurs in patients with adrenal insufficiency and liver disease. Proximal weakness with hyperreflexia suggests hyperthyroidism.

Ancillary studies — There is no routine laboratory or radiographic evaluation for weight loss, and many patients with chronic weight loss require no testing in the emergency department. Further testing should be prompted by specific findings in the history and physical examination. (See 'Physical examination' above.)

Studies that may be warranted to initiate evaluation include the following:

●Complete blood count

●Erythrocyte sedimentation rate

●C- reactive protein

●Serum electrolytes

●Serum calcium and phosphorus

●Blood urea nitrogen and serum creatinine

●Rapid blood or serum glucose

●Serum total protein and albumen

●Serum lipase

●Serum aspartate and alanine aminotransferase

●Serum lactate dehydrogenase

●Serum uric acid

●Serum cortisol

●Ferritin

●Serum iron and iron-binding capacity

●Rapid human immunodeficiency virus testing

●Thyroid stimulating hormone and thyroxine levels

●Serologic studies for celiac disease (ie, antiendomysial antibodies, tissue transglutaminase (algorithm 2))

●Serologic studies for rheumatic disease (eg, antinuclear antibodies)

●Stool guaiac

●Stool for fat

●Bacterial cultures of stool

●Stool for ova and parasites

●Urine dipstick for glucose and ketones

●Urine toxicology screen (amphetamines, cocaine)

●Electrocardiogram

●Chest radiograph (AP and lateral)

APPROACH — The table summarizes the causes of weight loss in children and adolescents, highlighting the most common and the most life threatening causes (table 1). The approach to the evaluation of weight loss in older children and adolescent is summarized in the algorithms (algorithm 3A-B).

Acute weight loss — Assessments of the degree and acuity of the weight loss along with specific historical and physical findings should guide the evaluation of these patients. Children and adolescents with acute weight loss who are ill, have signs of significant dehydration, or shock warrant rapid support of airway, breathing, and circulation (algorithm 4). Further features that suggest specific etiologies include (algorithm 3A):

●Glycosuria and ketonuria – Diabetic ketoacidosis (diabetes mellitus)

●Hypoglycemia, hyperkalemia, and hyperpigmentation – Adrenal insufficiency

●Vomiting without diarrhea with history of stereotypical episodes – Cyclic vomiting

●Short duration of fever with vomiting and diarrhea – Acute gastroenteritis

●Polyuria, polydipsia, constipation, and normal glucose – Hypercalcemia

Chronic weight loss — Features that help differentiate among the various causes of chronic weight loss in children and adolescents include (algorithm 3B):

●Prolonged fever – Fever longer than one to two weeks of duration suggests chronic infection (eg, tuberculosis, human immunodeficiency virus), rheumatic disease (eg, systemic lupus erythematosus), inflammatory bowel disease, or malignancy.

●Abdominal pain without fever – Potential diagnoses include recreational drug use, liver disease, lead poisoning, inflammatory bowel disease, giardiasis, celiac disease, lactose intolerance, superior mesenteric artery syndrome, and pancreatitis.

●Neither fever nor abdominal pain – Chronic weight loss in patients who have no history of fever or abdominal pain may be caused by cystic fibrosis, diabetes mellitus, adrenal insufficiency, hyperthyroidism, malnutrition, child abuse and neglect, eating disorder, depression, or drug use.

SUMMARY AND RECOMMENDATIONS

●Differential diagnosis – The causes of weight loss in older infants, children, and adolescents are listed in the table (table 1). (See 'Differential diagnosis' above.)

Infants, children and adolescents with acute weight loss who are ill, have signs of significant dehydration, or shock warrant rapid support of airway, breathing, and circulation (algorithm 4). (See 'Acute weight loss' above.)

●Evaluation and approach – Assessments of the degree and acuity of the weight loss along with specific historical and physical findings help to identify specific etiologies and the diagnostic approach as shown in the algorithms (algorithm 3A-B). (See 'Evaluation' above and 'Approach' above.)