These abnormalities include the presence of enlarged oval shaped red blood cells (macroovalocytes) and hypersegmented neutrophils (defined as a neutrophil with six or more lobes). Hypersegmented neutrophils may be seen in the absence of macroovalocytes as hypersegmentation of neutrophils is an early sign of megaloblastic anemia and may precede the appearance of macroovalocytes; they may also be seen in other anemias (e.g., iron deficiency anemia) and thus are suggestive of megaloblastic anemia but not specific for it. An increased red cell distribution width (anisocytosis) also suggests megaloblastosis and is commonly seen in Vitamin B12 deficiency and folic acid deficiency. This type of anemia is caused by impaired DNA synthesis and repair, often from deficient thymidine production. Thiamine responsive megaloblastic anemia syndrome also causes megaloblastic anemia.The red blood cells grow larger because they cannot produce DNA quickly enough to divide at the right time as they grow and thus grow too large before division. Additional causes of megaloblastic anemia include medications that interfere with DNA synthesis or with the absorption or metabolism of Vitamin B12 or folate such as methotrexate, sulfasalazine, metformin, anticonvulsant medications (e.g., valproic acid or phenytoin), certain antibiotics (e.g., trimethoprim/sulfamethoxazole), antiretroviral medications, cholestyramine, triamterene,  and nitrous oxide.
Erythema marginatum is a type of erythema (redness of the skin or mucous membranes) involving pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.An association with bradykinin has been proposed in the case of hereditary angioedema. Presentation
The rings are barely raised and are non-itchy. The face is generally spared. Associated conditions
It occurs in less than 5% of patients with rheumatic fever, but is considered a major Jones criterion when it does occur. The four other major criteria include carditis, polyarthritis, Sydenhams chorea, and subcutaneous nodules. In this case, it is often associated with Group A streptococcal infection, otherwise known as Streptococcus pyogenes infection, which can be detected with an ASO titer.It is an early feature of rheumatic fever and not pathognomonic of it. It may be associated with mild myocarditis (inflammation of heart muscle). It is also seen in conditions like allergic drug reactions, sepsis and glomerulonephritis.It often occurs as a harbinger of attacks in hereditary angioedema. In this case it may occur several hours or up to a day before an attack. Diagnosis
Types
Some sources distinguish between the following:
"Erythema marginatum rheumaticum"
"Erythema marginatum perstans"

Treatment
Erythema marginatum can be treated with hydrocortisone and adrenocorticotropc hormone (ACTH). References


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