What causes 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 . The lack of intrinsic factor prevents the proper absorption of vitamin B12 from the terminal ileum, leading to cobalamin deficiency (CD) .
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 . These genetic markers suggest a hereditary predisposition to the autoimmune processes that lead to PA.
Autoimmune Disorders and Coexisting Conditions
Patients with pernicious anemia often have a higher incidence of other autoimmune disorders, such as type 1 diabetes, vitiligo, and autoimmune thyroid diseases . This association underscores the autoimmune nature of PA and suggests that the immune system's dysregulation plays a crucial role in its pathogenesis.
Helicobacter pylori Infection
Long-standing infection with Helicobacter pylori has been implicated in the development of autoimmune gastritis, which can eventually lead to pernicious anemia. The infection may trigger an autoimmune response that results in the gradual destruction of the gastric mucosa, culminating in intrinsic factor deficiency and vitamin B12 malabsorption.
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 normal or high serum cobalamin levels, normocytic or microcytic anemia, or even non-anemic macrocytosis, complicating the diagnostic process . Additionally, the presence of intrinsic factor and parietal cell antibodies, although useful, may not always be detected, further complicating diagnosis .
Conclusion
Pernicious anemia is a multifaceted disorder primarily caused by autoimmune gastritis leading to intrinsic factor deficiency and subsequent vitamin B12 malabsorption. Genetic predisposition and coexisting autoimmune conditions further contribute to its development. Despite advances in understanding its pathogenesis, diagnosing PA remains challenging due to its varied clinical manifestations and the limitations of current diagnostic assays. Early recognition and treatment are crucial to prevent potentially irreversible complications.
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