Cold type autoimmune hemolytic anemia- a rare manifestation of infectious mononucleosis; serum ferritin as an important biomarker

Abstract

BackgroundInfectious mononucleosis is one of the main manifestations of Epstein – Barr virus, which is characterized by fever, tonsillar-pharyngitis, lymphadenopathy and atypical lymphocytes. Although 60% of patients with IMN develop cold type antibodies, clinically significant hemolytic anemia with a high ferritin level is very rare and validity of serum ferritin as an important biomarker has not been used frequently.Case presentation18-year-old girl presented with fever, malaise and sore throat with asymptomatic anemia, generalized lymphadenopathy, splenomegaly and mild hepatitis. Investigations revealed that she had cold type autoimmune hemolysis, significantly elevated serum ferritin, elevated serum lactate dehydrogenase level with serological evidence of recent Epstein Barr infection. She was managed conservatively and her hemoglobin and serum ferritin levels normalized without any intervention following two weeks of the acute infection.ConclusionCold type autoimmune hemolytic anemia is a rare manifestation of infectious mononucleosis and serum ferritin is used very rarely as an important biomarker. Management of cold type anemia is mainly supportive and elevated serum ferritin indicates severe viral disease.

Acute Cytomegalovirus Illness in an Immunocompetent Adult Causing Intravascular Hemolysis and Suspected Hemophagocytic Lymphohistiocytosis

“…His calculated HScore put him at a moderate probability of having reactive HLH. Because EBV-induced infectious mononucleosis and hemolytic anemia elevate ferritin levels [29], an acute CMV monolike illness with hemolytic anemia may do the same. Our patient's CD25 level was not in a range typically observed in HLH cases.…”

A Case of Severe Systemic Viral Infection Associated With Intravenous Immunoglobulin G–Resistant Kawasaki Disease and Multiple False-Positive Serologic Tests: How Multiple Diseases in One Child Can Have One Simple Explanation

“…Although the pathogenesis of EBV-induced AIHA is poorly understood, proposed mechanisms include the initial formation of IgM antibodies to EBV during the B-cell proliferation and polyclonal expansion phase that later contributes to molecular mimicry. 11 IgM antibodies cross-react with RBC antigens forming antigen-antibody complexes that activate the complement pathway, specifically C3b attaching to the RBC membrane. 11,12 In cold temperatures, IgM antibody also attaches to the RBC membrane to cause intravascular hemolysis, while in warm temperatures, the IgM antibody dissociates from RBC membrane and C3b remains, eventually causing extravascular hemolysis via the reticuloendothelial system.…”

“…11 IgM antibodies cross-react with RBC antigens forming antigen-antibody complexes that activate the complement pathway, specifically C3b attaching to the RBC membrane. 11,12 In cold temperatures, IgM antibody also attaches to the RBC membrane to cause intravascular hemolysis, while in warm temperatures, the IgM antibody dissociates from RBC membrane and C3b remains, eventually causing extravascular hemolysis via the reticuloendothelial system. 11,12 The elevated levels of circulating IgG, IgA, and IgM prior to IVIG treatment in this patient, showing the substantial lymphocyte proliferation from EBV infection, support this theory that overwhelming polyclonal expansion may cause AIHA as well as multiple false-positive serum markers of infection and autoimmune antibodies.…”

“…11,12 In cold temperatures, IgM antibody also attaches to the RBC membrane to cause intravascular hemolysis, while in warm temperatures, the IgM antibody dissociates from RBC membrane and C3b remains, eventually causing extravascular hemolysis via the reticuloendothelial system. 11,12 The elevated levels of circulating IgG, IgA, and IgM prior to IVIG treatment in this patient, showing the substantial lymphocyte proliferation from EBV infection, support this theory that overwhelming polyclonal expansion may cause AIHA as well as multiple false-positive serum markers of infection and autoimmune antibodies. This differs from the antigen mimicry of the herpes virus family because CMV IgG and IgM were negative while pathogens outside of the herpes virus family were falsely positive.…”

Epidemiological and Liver Biomarkers Profile of Epstein-Barr Virus Infection and Its Coinfection with Cytomegalovirus in Patients with Hematological Diseases

“…High levels of serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) in infected individuals may indicate EBV-induced liver injury [8,9]. A study case reported high serum levels of ferritin and lactate dehydrogenase (LDH) in an 18 years old girl carrier of EBV-related infectious mononucleosis [10]. The girl was also a carrier of autoimmune hemolytic anemia, which could be caused by the EBV infection.…”