Pernicious anemia: Pathophysiology and diagnostic difficulties

Pernicious anemia (PA) is the most common cause of vitamin B12 (cobalamin) deficiency anemia in the world. It is an autoimmune disease, comprising of salient features of autoimmune chronic atrophic gastritis (CAG) and cobalamin deficiency (CD). Although the anemia was first described as pernicious, it may well be controlled with vitamin B12 replacement. The onset and progression of PA is often insidious. Alternatively, patients may have no anemic symptoms since they become acclimatized to the subtle nature of the disease. Oftentimes, there is a possibility that the underlying disease may be missed unless a full blood count (FBC) is investigated, leading to hindrance in the treatment journey. Diagnostic challenges remain tangible for many practicing clinicians, since there is lack of reliable cobalamin assays to diagnose CD as well as clinical mimics, which simulate many other hematological conditions, such as myelodysplastic syndrome, acute leukemia, sideroblastic anemias, bone marrow failure states, thrombotic microangiopathy, and thromboembolism. Moreover, prompt recognition of the symptoms of CD is also vital, because some neurologic sequalae may become irreversible despite replenishing cobalamin. Herein, we discuss a literature review on the pathophysiology, challenging clinical presentations and diagnostic difficulties of PA. Since the cobalamin replacement therapy for PA is straightforward, it will not be discussed in this review.