What is the likely cause and recommended work‑up for a 2‑year history of a fissured, painful tongue that worsens with spicy foods and is only temporarily relieved by vitamin B12 supplementation?

Fissured Tongue with Recurrent Pain: Diagnostic Work-Up and Management

This presentation strongly suggests underlying vitamin B12 deficiency that is inadequately treated, requiring comprehensive diagnostic evaluation including serum B12, methylmalonic acid (MMA), complete blood count with MCV, and assessment for malabsorption causes rather than intermittent supplementation. 1, 2

Clinical Presentation Analysis

The 2-year history of fissured tongue with pain triggered by spicy foods that temporarily responds to vitamin B12 but recurs is characteristic of atrophic glossitis secondary to B12 deficiency. 2 This pattern of temporary relief followed by recurrence indicates:

• Functional B12 deficiency where serum levels may appear "normal" but cellular B12 remains inadequate 1
• Underlying malabsorption that prevents sustained correction with oral supplementation alone 3
• Glossodynia (painful tongue sensation) that worsens with irritating foods like spices, citrus, and hot beverages 4, 2

The fissured tongue itself may be a chronic anatomic variant, but the pain and sensitivity to spicy foods point specifically to nutritional deficiency-related glossitis rather than benign fissured tongue syndrome. 5, 2, 6

Recommended Diagnostic Work-Up

First-Line Laboratory Testing

Measure serum total vitamin B12 as the initial test (cost ~£2, rapid turnaround), interpreting as follows: 1

• <180 pg/mL (<133 pmol/L): Confirmed deficiency—initiate treatment immediately 1
• 180-350 pg/mL (133-258 pmol/L): Indeterminate range—proceed to MMA testing 1
• >350 pg/mL (>258 pmol/L): Deficiency unlikely, but consider MMA if high clinical suspicion persists 1

Order methylmalonic acid (MMA) when B12 falls in the indeterminate range (180-350 pg/mL) to confirm functional deficiency, as standard serum B12 misses up to 50% of cases with true cellular deficiency. 1 MMA >271 nmol/L confirms functional B12 deficiency with 98.4% sensitivity. 1

Complete blood count with differential to assess for: 1, 2

• Macrocytosis (MCV >98 fL), often the earliest laboratory sign appearing before anemia develops 1
• Megaloblastic anemia with hypersegmented neutrophils 1
• Note that one-third of B12-deficient patients present with neurological/oral symptoms without anemia 7

Serum folate and ferritin to exclude concurrent deficiencies that can cause similar glossitis. 1, 5, 2

Etiologic Investigation for Malabsorption

Since symptoms recur despite B12 supplementation, investigate underlying causes: 3, 2

Intrinsic factor antibodies to diagnose pernicious anemia, which requires lifelong intramuscular B12 therapy. 1, 2 Patients with confirmed intrinsic factor antibodies need lifelong treatment, typically via IM injections. 1

Gastrin level if pernicious anemia suspected—markedly elevated levels (>1000 pg/mL) indicate atrophic gastritis. 1

Medication review for drugs impairing B12 absorption: 1, 3

• Metformin use >4 months (3-fold increased deficiency risk) 1
• Proton pump inhibitors or H2 blockers >12 months 1
• Colchicine, anticonvulsants, sulfasalazine, methotrexate 1

Dietary assessment for inadequate intake (strict vegetarian/vegan diet, malnutrition, alcohol use disorder). 3

History of gastrointestinal surgery (gastric bypass, ileal resection >20 cm) or inflammatory bowel disease affecting terminal ileum. 4, 1

Treatment Algorithm

For Confirmed B12 Deficiency (<180 pg/mL or elevated MMA)

Without neurological involvement: 8

• Hydroxocobalamin 1000 mcg intramuscularly three times weekly for 2 weeks 8
• Then maintenance 1000 mcg IM every 2-3 months for life 8

With any neurological symptoms (paresthesias, cognitive difficulties, memory problems): 8

• Hydroxocobalamin 1000 mcg IM on alternate days until no further improvement 8
• Then 1000 mcg IM every 2 months for life 8
• Urgent specialist referral to neurology and hematology 8

Oral supplementation (1000-2000 mcg daily) may be considered for dietary deficiency without malabsorption, but parenteral administration remains the reference standard for malabsorption-related deficiency. 1, 8

Symptomatic Management During Treatment

Avoid painful stimuli while glossitis heals: 4

• Spicy, hot, raw, or crusty foods 4
• Citrus fruits and tomatoes 4
• Hot drinks 4
• Alcohol and smoking 4

Maintain oral hygiene with soft toothbrush and alcohol-free mouthwash. 4

Lubricate lips with lip balm (avoid chronic petrolatum use which promotes dehydration). 4

Critical Pitfalls to Avoid

Never administer folic acid before treating B12 deficiency—this may mask anemia while allowing irreversible neurological damage to progress. 1, 7, 8

Do not rely solely on serum B12 to rule out deficiency, especially in patients >60 years, where metabolic deficiency is common despite "normal" serum levels. 1 Up to 50% of patients with normal serum B12 have elevated MMA indicating functional deficiency. 1

Do not delay treatment while awaiting confirmatory tests if B12 <180 pg/mL and clinical features are present—initiate therapy immediately. 1

Do not use intermittent oral supplementation for malabsorption-related deficiency—this leads to the recurrent pattern described. Patients with malabsorption require lifelong parenteral therapy or high-dose daily oral supplementation (1000-2000 mcg). 1, 8

Monitoring and Follow-Up

Recheck B12 levels after 3-6 months of treatment to confirm normalization. 1

Annual B12 screening is recommended for high-risk populations: 1

• Age >75 years (18.1% prevalence of metabolic deficiency) 1
• Metformin use >4 months 1
• PPI/H2 blocker use >12 months 1
• Inflammatory bowel disease with ileal involvement 4, 1
• Post-bariatric surgery 1

Target homocysteine <10 μmol/L for optimal cardiovascular outcomes if measured. 1