Epstein–Barr virus is cause of boy’s complicated secondary CAD
Treatment was complicated by the unusual combination of CAD, HLH
A young boy in Portugal developed cold agglutinin disease (CAD) and an inflammatory condition called hemophagocytic lymphohistiocytosis (HLH) secondary to an infection with the Epstein-Barr virus, which can cause infectious mononucleosis, or mono.
The boy recovered fully after being treated with corticosteroids, a type of anti-inflammatory and immunosuppressive medication, and acyclovir, an antiviral medication. While corticosteroids are not a mainstay CAD treatment, they are the main therapy for HLH.
His case, which was complicated by the unusual combination of CAD and HLH, was published in Cureus in “Cold Agglutinin Syndrome and Hemophagocytic Lymphohistiocytosis: An Unusual Combination Caused by Epstein–Barr Virus Infection.”
CAD is an autoimmune condition caused by self-reactive antibodies called cold agglutinins, which bind to red blood cells at low temperatures, marking them for destruction. When this is triggered by an underlying illness, such as an infection, it’s called secondary CAD.
CAD is rare in adults and even more rare in children, as is hemophagocytic lymphohistiocytosis, a life-threatening condition marked by excessive inflammation. HLH is caused mostly by infections, such as from the Epstein-Barr virus, which spreads primarily through saliva and can be caught by children by objects being shared that might’ve been drooled on. Children are often infected with Epstein-Barr, but can manifest no symptoms. Complications can occur, however.
CAD secondary to Epstein-Barr infection
“There are only a few published cases in medical literature of [CAD] and HLH as complications of a primary [Epstein-Barr virus] infection,” wrote four researchers in Portugal who described the unusual case of a 12-year-old boy who developed both CAD and HLH secondary to an infection with Epstein–Barr.
The boy went to the hospital after having a fever, sore throat, vomiting, and diarrhea for four days. He also had jaundice, a yellowing of the skin and whites of the eyes, abdominal pain, and a rash. A physical examination revealed an enlarged liver.
A blood test revealed a high red blood cell sedimentation rate, which describes red blood cells in a lab tube sinking at a rate that’s faster than normal and suggests that red blood cell clumps are forming. This can happen with cold agglutinins and inflammation. The boy’s blood also had high levels of markers of inflammation, red blood cell destruction (hemolysis), and liver damage.
Cold agglutinins and acute infection with the Epstein-Barr virus were discovered in subsequent analyses.
An abdominal ultrasound showed an enlarged liver and spleen, and signs of cholestasis, or a slowed flow of bile from the liver to the gallbladder and intestines. Bile is a digestive fluid.
The boy was diagnosed with Epstein-Barr virus infection associated with liver inflammation, cholestasis, and cold agglutinin-mediated hemolysis and was started on ursodeoxycholic acid, a medication used for cholestasis.
His fever remained by his third day in the hospital, however, and his jaundice, and liver and spleen enlargement worsened. Blood testing revealed lower than normal hemoglobin, the protein that carries oxygen in red blood cells, and other abnormalities that fulfilled several HLH criteria.
The findings pointed to a diagnosis of CAD and HLH triggered by Epstein-Barr virus infection. The boy was started on dexamethasone and the antiviral acyclovir.
Within three days, his fever went away and his hemoglobin levels along with hemolysis and inflammatory markers returned to normal. The boy was discharged on the ninth day and switched to prednisolone, another corticosteroid, which was tapered over three weeks.
After eight weeks, a physical exam and blood test were unremarkable. He showed no signs of chronic Epstein-Barr virus infection at five months.
“Although rare, cold agglutinin syndrome [secondary CAD] and HLH can complicate infectious mononucleosis and should be considered in a patient with clinical deterioration,” the researchers wrote. “Corticosteroids are the mainstay treatment of HLH and may be beneficial in infection-associated [CAD].”
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