What is the diagnosis and treatment for a patient, likely a child or adult from a disadvantaged background, presenting with Bitot spots, a sign of vitamin A deficiency?

Bitot Spots: Diagnosis and Management

Definition and Clinical Presentation

Bitot spots are grey/white, foamy triangular or round-shaped lesions on the conjunctiva that represent a pathognomonic sign of vitamin A deficiency and require immediate high-dose vitamin A supplementation to prevent progression to irreversible blindness. 1

• The lesions typically have a base at the temporal limbus with the apex pointing toward the lateral canthus 2
• They appear as superficial keratin buildup on the conjunctival surface 3
• Bitot spots represent an intermediate stage in the progression of xerophthalmia, occurring after night blindness but before keratomalacia 1

Pathophysiology

• Vitamin A deficiency impairs normal conjunctival epithelial differentiation, preventing the formation of mucin-5AC-positive goblet cells 3
• This leads to keratinization of the conjunctival epithelium with accumulation of keratinization-related proteins 3
• The deficiency also causes increased susceptibility to respiratory and gastrointestinal infections due to impaired intestinal immune and barrier function 1

Diagnostic Approach

Clinical Diagnosis

• Bitot spots are diagnosed clinically by slit lamp examination revealing the characteristic foamy, white-grey conjunctival lesions 4
• Always assess for other signs of vitamin A deficiency including night blindness, conjunctival xerosis, and corneal involvement (xerophthalmia, keratomalacia, corneal ulceration) 1

Laboratory Confirmation

• Measure serum retinol levels, though treatment should not be delayed waiting for results 1
• Normal serum retinol: >0.70 μmol/L (>20 μg/dL) 1
• Critical caveat: Serum retinol decreases with inflammation, so adjust for inflammatory markers (CRP, AGP) when interpreting results 1
• In patients with liver disease, chronic alcohol use, or malabsorption, serum levels may appear normal despite depleted liver stores 1

Differential Diagnosis Consideration

• Recent case series demonstrate that Bitot-like spots can occur with normal vitamin A levels in children with aniridia, WAGR syndrome, Axenfeld-Rieger syndrome, and chronic use of benzalkonium chloride-containing eye drops 2, 5
• However, in resource-limited settings or patients from disadvantaged backgrounds, always treat as vitamin A deficiency first 1

Treatment Protocol

Immediate High-Dose Vitamin A Supplementation

For any patient presenting with Bitot spots, administer the full treatment schedule of oral vitamin A immediately: 1

Adults and Children ≥12 Months:

• Day 1: 200,000 IU oral vitamin A 1, 6
• Day 2: 200,000 IU oral vitamin A 1, 6
• 1-4 weeks later: 200,000 IU oral vitamin A 1, 6

Infants <12 Months:

• Day 1: 100,000 IU oral vitamin A (half dose) 1, 6
• Day 2: 100,000 IU oral vitamin A 1, 6
• 1-4 weeks later: 100,000 IU oral vitamin A 1, 6

Evidence for Treatment Efficacy

• A randomized controlled trial demonstrated that both 100,000 IU and 200,000 IU doses effectively heal Bitot spots, but the 200,000 IU dose provides 82% greater protection against relapse at 6 months 7
• This justifies the current WHO recommendation for 200,000 IU dosing despite higher rates of transient mild side effects 7
• Most responsive lesions heal within 7 weeks, with baseline serum retinol being the strongest predictor of treatment response 7

Ongoing Supplementation After Acute Treatment

After completing the 3-dose treatment schedule, continue preventive supplementation: 1

• Children 12 months to 5 years: 200,000 IU every 3 months 1, 8
• Infants <12 months: 100,000 IU every 3 months (total 400,000 IU in first year) 1, 8
• Lactating mothers: 200,000 IU within 2 months postpartum to ensure adequate vitamin A in breast milk 1, 8

Documentation

• Record all vitamin A doses on the patient's growth chart or medical record 1, 8
• Recheck vitamin A levels at 3 months after treatment in adults 9, 8

Management of Underlying Conditions

Nutritional Assessment

• Evaluate for severe malnutrition (weight-for-height Z-score <-3) which requires enrollment in therapeutic feeding programs 1, 6
• Screen for concurrent micronutrient deficiencies including iron, folate, and vitamin C 1

High-Risk Populations Requiring Screening

Actively screen for vitamin A deficiency in: 1, 9

• Patients with chronic liver disease (prevalence increases with disease severity) 1, 9
• Chronic alcohol consumers (depleted liver stores despite potentially normal serum levels) 1, 9
• Malabsorption syndromes: short bowel syndrome, cystic fibrosis, celiac disease, chronic diarrhea 1, 9
• Post-bariatric surgery patients 9
• Chronic kidney disease (requires regular monitoring as levels fluctuate) 1, 9

Monitoring and Follow-Up

Clinical Response

• Examine weekly for the first 7 weeks, then biweekly until lesions heal on two consecutive examinations 7
• Monitor for progression to keratomalacia (corneal softening with inflammation) or xerophthalmia (corneal maceration), which can lead to secondary infection and blindness 1

Treatment Failure

• If Bitot spots persist despite adequate vitamin A supplementation, consider surgical excision with amniotic membrane transplantation 3
• This may be particularly relevant in adults where age-related factors may reduce supplementation efficacy 3
• Investigate for underlying causes including aniridia, chronic dry eye, or medication-related factors (benzalkonium chloride exposure) 2, 5

Toxicity Concerns

Vitamin A toxicity is not a concern with the standard treatment protocol: 1, 6

• Acute toxicity requires >300,000 IU in adults or >60,000 IU in children within hours to days 1, 6
• The 200,000 IU dosing schedule is well below toxic thresholds 1, 6
• Chronic toxicity requires approximately 30,000 μg/day (100,000 IU/day) over prolonged periods 8

Critical Pitfalls to Avoid

• Never delay treatment waiting for laboratory confirmation - Bitot spots are a clinical diagnosis requiring immediate intervention 1
• Do not reduce the 200,000 IU dose to minimize side effects - the higher dose provides essential protection against relapse 7
• Do not assume normal serum retinol excludes deficiency in liver disease or chronic alcohol use - liver stores may be depleted despite normal serum levels 1
• Always complete the full 3-dose treatment schedule - single-dose therapy has unacceptably high relapse rates 7
• Screen for and treat concurrent infections - vitamin A deficiency increases susceptibility to respiratory and gastrointestinal infections that worsen outcomes 1