🔑 Neurological signs of B12 deficiency can occur even without anaemia. ⚠️ There is a 1–2% increased risk of thyroid disease or gastric cancer. 🧪 Pernicious anaemia is best confirmed with an anti-intrinsic factor antibody test. Anti-parietal cell antibody is less reliable.

📖 About

Autoimmune cause of vitamin B12 deficiency → haematological + neurological features.
Associated with other autoimmune diseases and ↑ risk of gastric carcinoma.

🧬 Aetiology

Autoimmune destruction of gastric parietal cells → loss of intrinsic factor & HCl.
Loss of IF → impaired B12 absorption in terminal ileum.
Occasionally, steroids can reverse the autoimmune gastritis.

⚙️ Physiology

Normal diet: ~20 μg/day B12 (requirement 1–2 μg/day).
B12 binds intrinsic factor in stomach → absorbed in terminal ileum.
Transported via transcobalamin II in portal blood.
Liver stores last 2–4 years.
Essential for homocysteine → methionine conversion (DNA synthesis + myelin integrity).

👩‍⚕️ Clinical Features

Mean age ≈ 60 yrs; more common in fair-skinned, blue-eyed individuals.
May have pallor, mild splenomegaly.
Autoimmune associations: vitiligo, Addison’s, thyroid disease.
Glossitis = “beefy red painful tongue.”

🧠 Neurological Signs

Optic atrophy, retinal haemorrhages 👁️
Cognitive decline / dementia 🧑‍🦳
Peripheral neuropathy → paraesthesia, sensory loss, absent ankle jerks.
Dorsal column dysfunction → loss of vibration + proprioception.
Corticospinal tract → brisk reflexes, extensor plantars.
Untreated → irreversible spinal cord lesions (subacute combined degeneration).

🔎 Investigations

FBC: Macrocytic anaemia (MCV >110 fL), anisopoikilocytosis, hypersegmented neutrophils, ↓ WCC/platelets.
Serum B12: Low (normal 160–960 ng/L).
Folate: Often low; check ferritin too.
IF antibodies: Highly specific, ~50% sensitive.
Anti-parietal cell antibodies: supportive but non-specific.
↑ Methylmalonic acid & homocysteine = functional deficiency markers.
Endoscopy: atrophic gastritis, achlorhydria.
Bone marrow (rarely): megaloblastic erythropoiesis.

🩺 Differentials

Post-gastrectomy (loss of IF).
Atrophic gastritis (non-autoimmune).
Terminal ileal disease (Crohn’s, resection).
Poor diet (strict veganism).

💊 Management

Avoid transfusion unless life-threatening (risk of overload).
B12 replacement: Hydroxocobalamin 1 mg IM twice weekly × 3 weeks → then lifelong 1 mg IM every 3 months.
Folate 5 mg OD if co-deficient (never give folate alone → can worsen neuro signs).
Expect:
- Reticulocytosis day 4–7 📈
- Temporary fall in Hb before recovery
- Hypokalaemia risk from rapid erythropoiesis
Monitor for associated autoimmune disorders & gastric carcinoma risk.

📚 OSCE/Exam Pearls – Always ask about neurological symptoms in macrocytic anaemia. – “Glossitis + peripheral neuropathy + macrocytosis” → think Pernicious Anaemia. – Never give folate alone if B12 deficiency is suspected. – Screen for thyroid & adrenal disease in long-term follow-up.

Cases — Pernicious Anaemia

Case 1 — Classic presentation 🌡️: A 62-year-old woman presents with fatigue, pallor, and glossitis. Bloods: Hb 7.8 g/dL, MCV 110 fL. B12 markedly low, folate normal. Antibodies: intrinsic factor Ab positive. Diagnosis: pernicious anaemia. Managed with lifelong intramuscular B12 replacement.
Case 2 — Neurological features 🧠: A 54-year-old man presents with paraesthesia in hands and feet, unsteady gait, and memory problems. Exam: reduced vibration sense, positive Romberg’s sign. Bloods: macrocytic anaemia, low B12. MRI spine: posterior column changes. Diagnosis: subacute combined degeneration of the cord due to pernicious anaemia. Managed with urgent B12 replacement to prevent permanent neurological damage.
Case 3 — Associated autoimmune disease 🧬: A 45-year-old woman with autoimmune thyroiditis is found to have macrocytic anaemia on routine bloods. B12 low, intrinsic factor antibody positive, anti-parietal cell antibody positive. Diagnosis: pernicious anaemia in the context of autoimmune polyendocrinopathy. Managed with lifelong B12 injections and thyroid disease monitoring.

Teaching Point 🩺: Pernicious anaemia is an autoimmune gastritis causing intrinsic factor deficiency → impaired B12 absorption. Presents with macrocytic anaemia, glossitis, and neurological symptoms. Strongly associated with other autoimmune conditions. Treated with lifelong parenteral B12 replacement.

The content on this website is provided for educational and informational purposes only to support exam preparation (e.g., MLA, MRCP, USMLE) and learning. This is NOT medical advice, diagnosis, treatment, or professional guidance. It does not replace consultation with a qualified healthcare professional, official guidelines (e.g., NICE, GMC, BNF), or supervised clinical practice. Always verify information with current, authoritative sources. Makindo and its contributors accept no liability for any reliance on this content, including errors, omissions, or any resulting harm, loss, or consequences. By using this site, you agree to these terms.

Pernicious anaemia