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

Abstract

A previously healthy 17-month-old male presented with 7 days of persistent fever, erythematous rash of the lower extremities and trunk, and swelling of the lower extremity. Initially thought to be a viral syndrome, he was admitted to the hospital for further workup when symptoms did not resolve. On presentation, physical examination was significant for periorbital swelling, conjunctivitis, cracked lips, bilateral cervical lymphadenopathy, edematous hands and feet, lower extremity desquamation, and splenomegaly. The patient exhibited decreased activity and appetite. Significant laboratory findings included C-reactive protein 141 mg/dL and hemoglobin 5.6 g/dL, a drop from 8 g/dL taken 6 days ago. He had an elevated white blood cell count of 17 700/mm and 2% bands, liver enzymes within normal limits, and normal renal function. Workup for infection included a lumbar puncture with unremarkable results. Parvovirus immunoglobulin (Ig) M and IgG and human immunodeficiency virus (HIV) Ag/Ab screen were positive. Epstein-Barr virus (EBV) viral capsid antigen IgG and IgM were positive indicating acute EBV infection. Cytomegalovirus (CMV) IgG and IgM were negative. Investigations of the acute drop in hemoglobin revealed a normocytic anemia. Iron studies were unremarkable and hemoglobin electrophoresis was normal. Type and screen showed O-negative blood type and positive anti-E antibodies for cold autoantibodies. Direct antiglobulin test was positive for anti-IgG, anti-C3b, and anti-C3d; haptoglobin decreased at <8.1 mg/dL; uric acid elevated at 8.8 mg/dL; and lactate dehydrogenase elevated at 1142 U/L, all consistent with autoimmune hemolytic anemia (AIHA). Bone marrow biopsy did not reveal any other etiology of anemia. Abdominal ultrasound showed mild splenomegaly. Immunoglobulin quantification demonstrated an overproduction of immunoglobulins with significantly elevated circulating IgG 2660 mg/dL, IgA 161 mg/dL, and IgM 1680 mg/L, suggesting a possible autoimmune etiology when combined with positive anti-nuclear antibody (ANA) titers (1:1280) and positive cardiolipin IgG and IgM antibodies.