Causes of pernicious anemia
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Causes of Pernicious Anemia
Autoimmune Gastritis and Intrinsic Factor Deficiency
Pernicious anemia (PA) is primarily caused by an autoimmune response that leads to chronic atrophic gastritis (CAG). This condition results in the destruction of the stomach's parietal cells, which are responsible for producing intrinsic factor (IF), a glycoprotein essential for vitamin B12 absorption 134. The lack of intrinsic factor prevents the proper absorption of vitamin B12 from the terminal ileum, leading to cobalamin deficiency (CD) 69.
Genetic Susceptibility
Genetic factors also play a significant role in the development of pernicious anemia. Genome-wide association studies have identified several genetic loci associated with an increased risk of PA, including PTPN22, PNPT1, HLA-DQB1, IL2RA, and AIRE genes 28. These genetic markers suggest a hereditary predisposition to the autoimmune processes that lead to the destruction of parietal cells and intrinsic factor deficiency.
Association with Other Autoimmune Disorders
Pernicious anemia is frequently associated with other autoimmune disorders, such as type 1 diabetes, vitiligo, and autoimmune thyroid diseases 248. This association underscores the autoimmune nature of PA, where the body's immune system mistakenly attacks its own tissues, including the gastric mucosa and intrinsic factor.
Helicobacter pylori Infection
Long-standing infection with Helicobacter pylori has been implicated in the pathogenesis of pernicious anemia. The infection can lead to chronic inflammation and atrophy of the gastric mucosa, eventually triggering an autoimmune response that results in the destruction of parietal cells and intrinsic factor deficiency 4.
Diagnostic Challenges
Diagnosing pernicious anemia can be challenging due to its diverse clinical presentations and the limitations of current diagnostic tools. Patients may present with non-specific symptoms or even normal cobalamin levels, complicating the diagnosis 379. The presence of intrinsic factor and parietal cell antibodies can serve as useful markers for PA, but their sensitivity and specificity vary 410.
Conclusion
Pernicious anemia is a multifaceted disorder primarily caused by autoimmune gastritis leading to intrinsic factor deficiency and subsequent vitamin B12 deficiency. Genetic susceptibility and associations with other autoimmune disorders further complicate its pathogenesis. Despite advances in understanding the disease, diagnostic challenges remain, necessitating a high index of suspicion and comprehensive diagnostic approaches to manage and treat PA effectively.
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