The average age at the time of diagnosis is 3 to
5 years. Common presenting symptoms are initially nonspecific, such as
fever, nausea, vomiting, and abdominal pain. The three main phenotypes can
be distinguished. As mentioned earlier, about half of patients experience a
fulminant mononucleosis resulting in liver failure and death. About a
quarter of all patients develop a malignant non-Hodgkin lymphoma (often
B-cell lymphoma of the Burkitt type) later in life, which may well respond
to the initial treatment but seems to have a high relapse rate and
ultimately often results in death. The ileocecal area and the central
nervous system are the most common primary sites of these lymphomas. About
30% present with dysgammaglobulinemia (variants ranging from
agammaglobulinemia over hypogammaglobulinemia [hypo-IgG1 and IgG3]
to polyclonal hypergammaglobulinemia [hyper-IgA, hyper-IgM] have been
described). Other manifestations may include aplastic anemia, vasculitis,
and pulmonary lymphomatoid granulomatosis leading to arterial wall
destruction and aneurysm formation. Seventy percent of the boys where a
follow-up exists (87% of patients) died before the age of 10 years, and
only two lived to 40 years. The clinical management includes regular
treatment with immunoglobulins containing antibodies against EBV. In
patients with hypogammaglobulinemia, immunoglobulins are indicated to
prevent recurrent infections. Allogenic bone marrow transplant is a newer
and successful treatment option; however, it remains to be seen whether the
long-term outcome changes for these patients.