Pernicious anemia
Pernicious anemia is autoimmune atrophic gastritis that destroys gastric parietal cells and abolishes intrinsic factor production, causing vitamin B12 malabsorption, megaloblastic macrocytic anemia, and a potentially irreversible myelopathy and neuropathy. Diagnosis rests on a low or borderline B12 with an elevated methylmalonic acid, confirmed by anti-intrinsic factor antibody, and treatment is lifelong vitamin B12 replacement.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Definition: autoimmune atrophic gastritis in which autoantibodies destroy gastric parietal cells, abolishing intrinsic factor production and causing vitamin B12 (cobalamin) malabsorption.
- Epidemiology
Most common cause of cobalamin deficiency: dietary B12 deficiency is uncommon because hepatic stores last years, so malabsorption, and pernicious anemia specifically, dominates the workup.
- Risk factors
Personal or family history of autoimmune disease: autoimmune thyroiditis, type 1 diabetes, vitiligo, and celiac disease cluster with pernicious anemia and should prompt case-finding.
- Pathophysiology
Autoimmune targeting of parietal cells: T-cell- and antibody-mediated injury destroys the acid- and intrinsic-factor-producing parietal cells of the gastric body and fundus, producing body-predominant atrophic gastritis.
- Clinical features
Anemia and hematologic symptoms: progressive fatigue, weakness, and pallor from a slowly developing macrocytic anemia, sometimes with "lemon-yellow" skin from combined pallor and mild jaundice.
- Differential diagnosis
Folate (vitamin B9) deficiency: identical megaloblastic, macrocytic anemia with hypersegmented neutrophils and elevated homocysteine, but methylmalonic acid is normal and there is no neurologic…
- Diagnosis
Establish cobalamin deficiency first, then confirm pernicious anemia as the cause: a serum vitamin B12 level below 200 ng/L strongly suggests deficiency, and a borderline-low level of 200 to 400 ng/L…
- Management
Confirm the vitamin B12 level and check folate before treating, because giving folic acid to a patient with unrecognized B12 deficiency corrects the anemia and masks the diagnosis while subacute combined degeneration continues to progress.
- Complications
Irreversible neurologic injury: subacute combined degeneration present for a prolonged period may not fully reverse with treatment, making early recognition critical.
- Prognosis
Hematologic recovery is excellent with treatment: reticulocytosis begins within days, and the anemia typically resolves over several weeks once cobalamin is adequately replaced.
- Prevention
No primary prevention for the autoimmune process itself; prevention targets deficiency-related complications through early detection and lifelong replacement once diagnosed.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Autoimmune hemolytic anemias
Autoimmune hemolytic anemia is antibody-mediated red cell destruction confirmed by a positive direct antiglobulin (Coombs) test, split into warm IgG disease with splenic clearance and spherocytes and cold agglutinin IgM disease with complement-mediated agglutination worse in the cold. Warm disease is treated with glucocorticoids first and cold agglutinin disease with cold avoidance and rituximab, and roughly half have an identifiable secondary cause that must be sought and treated.
- Celiac disease
Celiac disease is an immune-mediated small-intestinal enteropathy triggered by dietary gluten in genetically predisposed individuals, presenting with malabsorptive diarrhea, iron-deficiency anemia, or dermatitis herpetiformis. Diagnosis requires IgA tissue transglutaminase serology with a total IgA level while the patient still eats gluten, confirmed by duodenal biopsy showing villous atrophy, and the only treatment is a strict lifelong gluten-free diet.
- Type 1 diabetes mellitus
Type 1 diabetes mellitus is an insulin-deficient state from autoimmune (type 1A) or idiopathic (type 1B) destruction of pancreatic beta cells, presenting with hyperglycemia that can range from mild to life-threatening diabetic ketoacidosis. Diagnosis combines standard glycemic criteria with autoantibody testing (GAD65, IA-2), and lifelong insulin therapy, generally as a basal-bolus regimen, is required from diagnosis, with self-monitoring or continuous glucose monitoring to guide dosing.
- Vitiligo
Vitiligo is a common acquired autoimmune condition in which destruction of melanocytes produces well-demarcated, completely depigmented macules and patches without scale, most often on the extensor surfaces, hands, face, and periorificial skin. Diagnosis is clinical, supported by Wood's lamp examination showing bright, sharply delineated fluorescence, and first-line treatment is a topical high-potency corticosteroid or a topical calcineurin inhibitor such as tacrolimus, with phototherapy for widespread disease.