Cold agglutinin disease in an infant: remission after intravenous immunoglobulin

Abstract

Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA), usually caused by autoantibodies that react optimally at low temperatures. Although rituximab has been shown to be effective against adult CAD, no established treatment is available for pediatric AIHA due to its rarity in infancy and childhood. We report an infantile case of CAD that responded to intravenous immunoglobulin (IVIG) treatment. A 2-month-old previously healthy Japanese female presented with jaundice and poor feeding 3 days after receiving the first doses of Haemophilus influenzae type b conjugate vaccine and pneumococcal conjugate vaccine. No exposure to cold temperature could be identified. There was no family history of anemia, spherocytosis, or splenectomy. Physical examination revealed scleral icterus and generalized pallor, but no acrocyanosis or hepatosplenomegaly. Her laboratory data showed a hemoglobin (Hb) level of 3.8 g/dL, mean corpuscular volume of 87.3 fl, reticulocyte count of 3.4%, total bilirubin (TB) of 10.4 mg/dL, direct bilirubin of 0.8 mg/dL, lactate dehydrogenase (LDH) of 606 U/l, haptoglobin of 3 mg/dL, and no hemoglobinuria. A direct antiglobulin test (DAT) with polyspecific anti-IgG and anti-C3 was positive at 4°C and room temperature but negative at 37°C. Peripheral blood smears revealed no spherocytes. Bone marrow smears showed erythroid hyperplasia. Based on clinical signs and laboratory evaluations, we diagnosed her with cold AIHA. Further investigation concluded that monospecific DAT was positive for IgG and negative for C3. Her cold agglutinin titer was 1:16. The autoantibody was specific for the I antigen. The Donath-Landsteiner antibody test was negative, ruling out paroxysmal cold hemoglobinuria. Infectious agents were excluded with serology tests. These laboratory findings led to a diagnosis of low-titer CAD.