Snapshot A 21-year-old female presents with pain in her fingers and toes and has noticed that they turn purple. Other complaints include a continuous, nonproductive cough with low grade fever. She believes that her symptoms are due to the winter temperature, as her symptoms improve when she is indoors. On physical exam, there is a bluish discoloration of the ears, nose-tip, and fingers. Pulmonary auscultation is notable for rales. Introduction Immunohemolytic anemia at low temperatures IgM antibodies directed against red blood cells low temperatures increases antibody avidity to its antigen can lead to complement fixation extrinsic hemolytic anemia Cold agglutinin antibody production can be secondary to: Mycoplasma pneumoniae mononucleosis (EBV and CMV) HIV B-cell neoplasms Waldenstrom macroglobulinemia idiopathic Presentation Symptoms anemia pallor, dyspnea acrocyanosis and levido reticularis can appear when exposed to cold temperatures acrocyanosis purplish discoloration of the tip of the nose, ears, fingers, and toes can improve when warm insignificant reactive hyperemia differentiates it from Raynaud phenomenom studies Direct Coombs test positive for anti-C3 negative for anti-IgG Elevated cold agglutinin titers Low C3 and C4 levels secondary to consumption Red blood cell aggregation on peripheral blood smear Treatment Dependent on disease severity avoiding the cold rituximab in those with severe hemolysis may be given with fludarabine other options can be used as well glucocorticoids, cyclophosphamide, cyclosporine, IVIg