Elevated Cobalamin Levels
Elevated cobalamin levels are defined as serum levels above 950 pg/ml (701 pmol/L) and can be caused by excess intake or administration (e.g. with cobalamin therapy), liberation from an internal reservoir, and commonly from a qualitative or quantitative increase in transcobalamin (transporter of cobalamin) from excess production or a lack of clearance, as well as a lack of affinity for transcobalamin to cobalamin. Elevated cobalamin is seen in several pathologic states, including chronic myelogenous leukemia, promyelocytic leukemia, polycythemia vera, and hypereosinophilic syndrome. Of these conditions, the greatest elevation of cobalamin is seen in hypereosinophilic syndrome. The increased cobalamin level is caused by increased production of haptocorrin by granulocytes and their precursors. Haptocorrin can be a useful tool in differentiating primary and secondary eosinophilia, as it is not associated with secondary eosinophilia, as seen with parasitic infections. In hypereosinophilic syndrome, elevated cobalamin levels in combination with elevated tryptase levels can identify a subset of patients with a myeloproliferative variant of the disease with tissue fibrosis and poor prognosis. These patients harbor the FIP1L1-PDGFRA mutation, which confers responsiveness to imatinib. In addition to myeloproliferative disorders, acute hepatitis, cirrhosis, hepatocellular carcinoma, and metastatic liver disease can show an increase in circulating cobalamin, caused by cobalamin release during hepatic cytolysis and/or decreased cobalamin clearance by the affected liver. Many of the disease processes that have elevated cobalamin levels can also have skin findings. For example, hypereosinophilic syndrome can manifest as eczema, erythroderma, lichenification, recurrent urticaria, angioedema, and less commonly in difficult-to-treat mucosal ulcers. Additionally, elevated cobalamin levels from cobalamin therapy can result in cutaneous manifestations and are discussed later.
Am J Clin Dermatol. 2015;16(1):27-33. © 2015 Adis Springer International Publishing AG