What are the symptoms of pernicious anemia?

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Symptoms of Pernicious Anemia

Pernicious anemia presents with a combination of hematological, gastrointestinal, and neurological symptoms due to vitamin B12 deficiency caused by intrinsic factor deficiency.

Common Clinical Manifestations

Hematological Symptoms

  • Fatigue and weakness due to reduced oxygen-carrying capacity 1, 2
  • Pallor (pale appearance) of skin and mucous membranes 1, 3
  • Shortness of breath and exercise dyspnea, particularly with exertion 1, 3
  • Tachycardia and systolic flow murmurs as compensatory mechanisms 1, 4

Gastrointestinal Symptoms

  • Glossitis (smooth, red, and sometimes painful tongue) 1, 5
  • Angular stomatitis (cracking or inflammation at the corners of the mouth) 1, 2
  • Anorexia and weight loss 4, 5
  • Diarrhea in some cases 3, 5

Neurological Symptoms

  • Paresthesias (tingling and numbness), particularly in extremities 2, 6
  • Ataxia (loss of coordination) and gait disturbances 3, 6
  • Decreased position and vibration sense 6
  • Muscle weakness, particularly in lower extremities 3, 6
  • Hyperreflexia 6
  • In severe cases, subacute combined degeneration of the spinal cord 7, 6

Neuropsychiatric Symptoms

  • Depression and mood changes 3, 6
  • Memory impairment and cognitive dysfunction 4, 6
  • Psychotic episodes in some cases 3, 6
  • Alterations to vision and smell 6

Other Clinical Findings

  • Koilonychia (spoon-shaped nails) 1
  • Blue sclerae (bluish discoloration of the whites of the eyes) 1
  • Pagophagia (craving for ice) 1
  • Restless legs syndrome 1
  • Urinary incontinence in advanced cases 6

Laboratory Findings

  • Macrocytic anemia with elevated mean corpuscular volume (MCV) >100 fL 3, 6
  • Hypersegmented neutrophils on peripheral blood smear 3
  • Low vitamin B12 (cobalamin) levels 4, 3
  • Elevated methylmalonic acid (MMA) and homocysteine levels 7, 3
  • Positive intrinsic factor antibodies and/or parietal cell antibodies 4, 5

Important Considerations

  • Neurological symptoms may occur without significant anemia in approximately one-third of cases 7, 6
  • Early diagnosis is crucial as some neurological complications may become irreversible despite treatment 2, 6
  • Pernicious anemia is frequently associated with other autoimmune disorders, particularly autoimmune thyroid disease (40%) and diabetes mellitus (10%) 5
  • The disease is often insidious in onset and progression, with patients becoming acclimatized to symptoms 2
  • Pernicious anemia represents 20%-50% of vitamin B12 deficiency causes in adults 4

Warning Signs Requiring Urgent Attention

  • Severe neurological deficits suggesting subacute combined degeneration of the spinal cord 7, 6
  • Profound anemia with hemoglobin levels <7 g/dL 3
  • Signs of heart failure due to severe anemia 1
  • Psychotic symptoms or significant cognitive impairment 3, 6

Early recognition and treatment with vitamin B12 replacement can prevent irreversible neurological damage and effectively manage hematological abnormalities 7, 6.

References

Guideline

Physical Examination Findings of Anemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Pernicious anemia: Pathophysiology and diagnostic difficulties.

Journal of evidence-based medicine, 2021

Research

Optimal management of pernicious anemia.

Journal of blood medicine, 2012

Research

Primary Neurologic Symptoms: Have You Considered Pernicious Anemia?

The Journal of emergency medicine, 2023

Guideline

Dietary Management of Megaloblastic Anemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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