In a toddler with poor appetite, failure to thrive, no diarrhea and a positive urine reducing substances test, what is the differential diagnosis and recommended work‑up and initial management?

Positive Urine Reducing Substances in a Toddler with Poor Appetite and Slow Growth

Key Clinical Interpretation

A positive urine reducing substances test (1+) in a toddler with poor appetite and failure to thrive—but without diarrhea—is a non-specific finding that does NOT indicate clinically significant carbohydrate malabsorption requiring dietary modification. 1 The absence of diarrhea makes true glucose malabsorption extremely unlikely, as clinically significant carbohydrate malabsorption would manifest with dramatic increases in stool output. 1

Primary Differential Diagnosis

Food Protein-Induced Enterocolitis Syndrome (FPIES)

• Chronic FPIES is the leading consideration in toddlers presenting with poor appetite, failure to thrive, and intermittent symptoms even without overt diarrhea. 1
• Stool examination may show occult blood, neutrophils, eosinophils, and/or reducing substances. 1
• Common trigger foods include cow's milk, soy, rice, oat, and certain vegetables. 1
• Diagnostic criterion: resolution within days after food elimination and recurrence upon re-introduction. 1

Gastroesophageal Reflux Disease (GERD)

• GERD with feeding aversion must be evaluated in toddlers with unexplained failure to thrive. 1
• Severe feeding difficulties and gastroesophageal reflux are common causes of poor growth in this age group. 2

Behavioral Feeding Issues

• Oral aversion and sensory integration difficulties leading to inadequate caloric intake are important contributors to poor weight gain. 2, 1

Recommended Initial Work-Up

Growth Assessment

• Plot weight, length/height, and weight-for-height on age-appropriate growth curves (adjusted for gestational age if premature). 1, 3
• Document growth trajectory to confirm failure to thrive. 3

Laboratory Evaluation

• Complete blood count with differential to screen for anemia and eosinophilia (supporting allergic or inflammatory processes). 1, 3
• Serum albumin and pre-albumin to assess protein-energy status. 1
• Serum electrolytes to identify metabolic disturbances. 1, 3
• Thyroid function tests to evaluate for hypothyroidism. 3
• Tissue transglutaminase IgA antibodies when celiac disease is a consideration. 1

Tests NOT Recommended

• Do NOT use stool pH or reducing substances alone to diagnose lactose intolerance; clinical worsening after lactose re-introduction is required for diagnosis. 1
• Do NOT restrict lactose solely based on a positive reducing substances test, as the incidence of clinically evident glucose malabsorption is only about 1%. 1
• Routine endoscopy is not indicated unless there is rectal bleeding, severe symptoms, or lack of response to empiric management. 1

Initial Management Strategy

Nutritional Goals

• Aim for energy intake of approximately 120 kcal/kg/day initially to promote catch-up growth. 1

Empiric Food Elimination Trial (When FPIES Suspected)

• Conduct a 2-week elimination of the most likely trigger (commonly cow's milk) while maintaining adequate nutrition. 1
• Document improvements in appetite, weight gain, and stool pattern during elimination. 1
• If symptoms resolve, perform a supervised oral food challenge to confirm diagnosis. 1
• Positive re-challenge criteria: vomiting 1-4 hours after ingestion plus ≥2 of the following: lethargy, pallor, diarrhea 5-10 hours later, hypotension, hypothermia, or rise in neutrophil count. 1

Critical Pitfall to Avoid

• Avoid unnecessary dietary restrictions based solely on the positive reducing substances test, as this is a non-specific finding. 1, 4

When to Escalate Care

• Refer to pediatric gastroenterology if failure to thrive persists despite adequate caloric intake and appropriate empiric elimination trials. 1, 3
• Arrange supervised oral food challenge with an allergy specialist for suspected FPIES to achieve definitive diagnosis. 1
• Obtain occupational therapy evaluation and consider video swallow study for children with feeding dysfunction or suspected aspiration. 1
• Consider specialized referrals (endocrinology, genetics, neurology) when initial evaluation does not identify a cause or when specific abnormalities are detected. 3