Most cases of infectious mononucleosis resolve in one to three weeks, although malaise and fatigue occasionally persist for several weeks to months. Complications of infectious mononucleosis can affect nearly every organ system. Tonsillar enlargement can be extreme, causing respiratory embarrassment. Splenic rupture is rare but must be considered when abdominal pain develops, particularly during the second and third weeks of illness. Patients with splenic rupture usually have left upper quadrant pain and tenderness, often accompanied by signs of peritoneal irritation and laboratory evidence of a falling hematocrit.
Prompt splenectomy is required if a diagnosis of splenic rupture is confirmed.
Neurologic complications occur in fewer than one percent of patients with infectious mononucleosis and include encephalitis, aseptic meningitis, transverse myelitis, Guillain-Barr syndrome, optic neuritis, and peripheral neuropathies. Despite the severity of the neurologic complications, most patients with such complications recover completely. Autoimmune hemolytic anemia mediated by cold agglutinins directed against i antigens may occur, usually during the second or third week of illness. Aplastic anemia, thrombocytopenia with bleeding, and severe granulocytopenia with superinfection are very rare but have potentially fatal complications. EBV has been detected in bone marrow specimens by in situ hybridization.