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Pernicious Anemia (PA)

Pernicious Anemia (PA): Causes, Symptoms, and Management

Pernicious anemia (PA) is an autoimmune disorder causing vitamin B12 deficiency due to impaired absorption. It arises from autoantibodies targeting intrinsic factor (IF), a stomach protein essential for B12 uptake, or gastric mucosal cells. Below is a synthesis of its key aspects, supported by current evidence.

Causes and Pathogenesis

1. Autoimmune Mechanism:
   • Intrinsic factor deficiency: Autoantibodies destroy IF or gastric parietal cells, blocking B12 absorption136.
   • Genetic predisposition: Linked to HLA-DQ2/DQ8 haplotypes, increasing autoimmune risk36.
2. Congenital Forms:
   • Juvenile PA: Rare, diagnosed in infancy due to inherited IF deficiency or gastric atrophy26.

Symptoms

Symptoms develop gradually due to stored B12 reserves but worsen without treatment:

Early Signs	Advanced/Neurological
Fatigue, weakness	Numbness/tingling in hands/feet
Shortness of breath	Balance issues, ataxia
Pale/yellow skin	Memory loss, confusion, depression
Swollen tongue, diarrhea	Hallucinations, paranoia
Loss of appetite	Permanent nerve damage if untreated123

Diagnosis

1. Blood Tests:
   • Low serum B12 (<200 pg/mL) and elevated methylmalonic acid (MMA).
   • Anemia markers: Macrocytic anemia (high MCV), low reticulocytes16.
2. Autoantibody Testing:
   • Anti-intrinsic factor antibodies (confirmatory for PA)13.
3. Gastrointestinal Evaluation:
   • Endoscopy: Gastric atrophy or polyps (linked to gastric cancer risk)36.

Treatment

1. Vitamin B12 Supplementation:
   • Initial phase: Intramuscular hydroxocobalamin (1 mg every 2–3 days for 2 weeks)178.
   • Maintenance: Monthly injections or oral high-dose B12 (1,000–2,000 mcg/day) if absorption improves168.
2. Monitoring:
   • B12/MMA levels: Adjust dosing to prevent relapse.
   • Neurological exams: Early intervention prevents irreversible damage36.
3. Associated Risks:
   • Gastric cancer screening: Endoscopy every 2–5 years36.

Prognosis

• With treatment: Full recovery of anemia; neurological deficits may improve if addressed early16.
• Untreated: Permanent nerve damage, increased cancer risk, and mortality36.

Conclusion
Pernicious anemia is a treatable autoimmune disorder requiring lifelong B12 supplementation. Early diagnosis and adherence to therapy prevent complications like neurological decline and gastric malignancy.

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References

1. WebMD: Pernicious Anemia
2. NORD: Pernicious Anemia
3. Penn Medicine: Pernicious Anemia
4. Cleveland Clinic: Pernicious Anemia
5. Phyathai Hospital: Pernicious Anemia
6. StatPearls: Pernicious Anemia
7. Siloam Hospitals: Pernicious Anemia
8. NHS: B12 Deficiency Treatment