Advanced Search
Main Menu

Infectious Mononucleosis
Author: Daryl Lum, M.D.
Last Revised: Fri, 18-Aug-2006
Article Size: 14 KB

PDF Version



Infectious Mononucleosis

Daryl Lum, M.D.

A 32-year-old male with no significant past medical history presented with acute onset of left upper quadrant pain after eating dinner. The pain was sharp and without radiation. There was some worsening with inspiration; however, there was no chest pain or dyspnea. He denied nausea, vomiting, or diarrhea. The patient denied any fevers, chills, or sweats. There were no complaints of dysuria or hematuria. Approximately 2 weeks earlier, the patient reported a 3-day history of malaise, fevers, and headaches, which had resolved completely. The patient presented to an emergency room and vital signs revealed a temperature of 37.0°C, blood pressure 118/65 mm Hg and a pulse of 72 beats per minute. Physical examination was remarkable only for mild left upper quadrant tenderness without rebound or guarding. Laboratory tests revealed a white blood cell count of 9.1, hemoglobin level of 15.3, and platelet count of 271. Urinalysis revealed a specific gravity of 1.020, with negative blood, nitrites, and leukocyte esterase. The patient underwent an abdominal series, the results of which he was told were normal, although there was distention of the stomach and a question of a sharp turn in the splenic flexure. The patient's symptoms improved and he was discharged from the emergency room with a possible diagnosis of abdominal pain caused by gas trapped by the sharp turn in the splenic flexure.

Over the next 48 hours, the patient had continued, intermittent episodes of left upper quadrant pain. He presented to another physician who noted splenomegaly on examination. Review of the patient's laboratory results from the emergency room visit 3 days earlier revealed 28% atypical lymphocytes on the complete blood cell count. The final reading of the abdominal series showed possible distention of the stomach with possible splenomegaly. A computed tomographic (CT) scan was performed which showed splenomegaly, measuring 13.5 cm craniodaually. A tiny attention lesion along the superior aspect of the spleen as well as a small amount of perisplenic fluid was noted. In addition, a moderate amount of high-density fluid was noted in the cul-de-sac. The impression was of splenomegaly with rupture causing moderate hemorrhage in the cul-de-sac. At this time the patient was afebrile with normal blood pressure and pulse. Laboratory tests revealed a white blood cell count of 11.3, with 26% atypical lymphocytes, hemoglobin level of 15.7, and platelet count of 267. The patient also was noted to have a transaminitis with an aspartate aminotransferase of 191 (normal 1759), alanine aminotransferase of 287 (normal 11-66), and an elevated alkaline phosphatase of 187 (normal 38-126). Given the splenic rupture, a splenectomy was considered; however, the decision was made to follow the patient's clinical examination and hemoglobin levels serially. He developed pharyngitis and cervical adenopathy, but the abdominal pain gradually improved and hemoglobin levels remained stable. Laboratory tests conducted on admission subsequently revealed a positive infectious monoscreen. The patient underwent a repeat CT scan that showed no worsening of the splenic rupture and was discharged home after 4 days.

Infectious Mononucleosis

Epstein-Barr virus (EBV) infection in infants and children is usually asymptomatic, but frequently results in infectious mononucleosis in adolescents and adults. The highest incidence is seen in individuals aged 10 to 19 years with 6 to 8 cases per 1000 persons per year.1 There is typically a 4 to 7 week incubation period, followed by a 3 to 5 day prodrome of fever, malaise, and myalgias, which are often attributed to a routine viral infection. The triad of fever, pharyngitis, and lymphadenopathy is seen in greater than 50% of patients,2 but some patients may present with only one component of this triad. Patients with infectious mononucleosis may also present with splenomegaly, hepatomegaly, or palatal petechiae. Hoagland's criteria for the diagnosis of infectious mononucleosis consists of greater than 50% lymphocytosis with greater than 10% atypical lymphocytes in the presence of fever, pharyngitis, and adenopathy, plus confirmation by a positive serologic test. Serologic diagnosis of infectious mononucleosis is often made by detecting heterophile antibodies; however, there is a high false negative rate in the first week of illness and in patients younger than 12 years.1 In individuals with a high suspicion for infectious mononucleosis and a negative heterophile antibody test, VCA-IgM and VCA-IgG tests are used to make the diagnosis.

The atypical lymphocytes seen in infectious mononucleosis represent T cells responding to EBV-infected B cells. It is believed that 2 weeks after the onset of illness, splenomegaly results from infiltration of normal and atypical lymphocytes into the capsule and trabecula of the spleen. Splenomegaly is often not apparent on physical examination and may be obscured by abdominal musculature in young athletes. One study demonstrated that 100% of patients with infectious mononucleosis were found to have splenomegaly on ultrasound.3

Treatment of infectious mononucleosis generally consists of supportive care. Although patients have fatigue, there is no indication for bed rest and one study demonstrated that bed rest actually slowed recovery.1 Studies investigating medical therapy for infectious mononucleosis have also not shown any benefits. Acyclovir reduces viral shedding and inhibits EBV replication, but does not affect the clinical course of the disease. Corticosteroids can help with some of the symptoms, but should be reserved for patients with severe complications of infectious mononucleosis such as impending airway obstruction or hemolytic anemia.

One of the common questions raised regarding infec-tious mononucleosis is how soon an athlete can return to normal activity, given the increased risk of splenic rupture. Although there have been no formal studies, many authorities recommend avoiding strenuous activity for at least 3 to 4 weeks. Because splenomegaly is often not apparent on clinical exam-ination, some have recommended performing an ultrasound prior to returning to contact sports. An algorithm developed by Auwaerter4 suggests that for patients participating in contact sports, one should assess for splenomegaly at 4 weeks by physical exam-ination. If no palpable splenomegaly is present, an ultrasound should be performed, and if the spleen is normal, the patient may return to contact sports. If splenomegaly is apparent on ultrasound, one should wait for 1 to 2 weeks and then repeat the ultrasound. For patients with splenomegaly present at 4 weeks, one should wait 2 weeks and reassess. Once the palpable splenomegaly has resolved, one should perform an ultrasound and proceed as above. Because waiting only 2 weeks to repeat an ultrasound is a very short interval, this algorithm could be modified to waiting 4 weeks or perhaps longer to repeat an ultra-sound after finding splenomegaly.

Splenic Rupture

Splenic rupture is an extremely rare complication of infectious mononucleosis and occurs in approximately 0.1% to 0.5% of cases. Although the exact mechanism is not completely understood, it is believed that splenic fragility is increased due to lymphocytic infiltration of the spleen and weakening of its supporting structures. Because of the risk of splenic rupture, athletes with mononucleosis are advised to avoid contact sports. One review of 55 cases of splenic rupture showed that the majority of cases occurred during the first 3 weeks of illness. Surprisingly, greater than 50% of these cases were not related to trauma.5 Although examination of the spleen in infectious mononucleosis is important to assess for splenomegaly, repeated examination should be avoided as there have been 2 case reports of splenic rupture attributed to repeated physical examination.6

Spontaneous splenic rupture is extremely rare but is the most common cause of fatality in infectious mononucleosis. The majority of cases are in men younger than 25 years, and spontaneous splenic rupture most commonly presents as abdominal pain. Intraperitoneal blood can cause diaphragmatic irritation resulting in pain referred to the left shoulder (Kehr's sign); however, patients can also present with right shoulder pain. Other symptoms of splenic rupture include hypotension, tachycardia, dizziness, or syncope. Diagnosis is usually made by ultrasound or CT scan, but some characteristic signs of splenic rupture (e.g. distention of the stomach with displace-ment to the right, serration of the greater curvature, an extrinsic pressure defect from the enlarged spleen noted in the fundus, or downward displacement of the splenic flexure) can be seen on plain radiographs of the abdomen.7

In order to make a diagnosis of spontaneous splenic rupture in infectious mononucleosis, the following criteria should be met: (1) no history of recent trauma, (2) hematologic and serologic evidence of infectious mononucleosis, (3) recent clinical symptoms of infectious mononucleosis, and (4) histologic examination of the spleen should show changes consistent with infectious mononucleosis.8 There have been some recommendations to modify Rutkow's criteria so that the diagnosis of spontaneous splenic rupture can be made from either histologic or radiographic splenic changes in the presence of clinical and serologic evidence.6

In the past, splenectomy was universally recommended for the treatment of splenic rupture, particularly in cases where hypotension, ongoing transfusion requirements, or peritoneal irritation were present. In selected patients with spontaneous splenic rupture, non-operative management may be safe and effective. An examination of 19 patients with spontaneous splenic rupture who were managed non-operatively found that stable hemoglobin levels were best associated with a favorable outcome.9 Patients who undergo splenectomy should receive the pneumococcal vaccine and should also be considered for meningococcus and Haemophilus influenzae Type b immunization.


Infectious mononucleosis can be complicated by splenic rupture and is often spontaneous and not caused by trauma. In this case, the atypical lymphocytes were not noted on the patient's initial presentation to the emergency room; had they been, the possibility of infectious mononucleosis would likely have been raised. In a patient with clinical symptoms of mononucleosis, one must consider splenic rupture if the patient presents with left upper quadrant or any type of abdominal pain regardless of a history of trauma. In this case, the patient's initial abdominal series in the emergency room showed distention of the stomach and the sharp turn noted in the splenic flexure were likely due to splenomegaly and splenic rupture. This patient did not have any of the typical symptoms of infectious mononucleosis upon initial presentation to the emergency room; however, the atypical lymphocytosis and transaminitis are commonly seen in patients with the disease.

Although splenectomy has been universally recommended in cases of splenic rupture in the past, recent data suggests that, in patients with stable hemoglobin levels, conservative management is a safe alternative to surgery. Fortunately, the patient is this case did not suffer a drop in hemoglobin after being discharged from the emergency room and ultimately did not require surgery. Following discharge from the hospital, the patient resumed normal activities and has had no recurrence of abdominal pain. A repeat ultrasound performed approximately 2 months after the initial hospitalization showed that the splenomegaly had resolved completely.


  1. Ebell MH. Epstein-Barr virus infectious mononucleosis. Am Fam Physician. 2004 Oct 1;70(7):1279-87.

  2. Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000 Aug 17;343(7):481-92.

  3. Dommerby H, Strangerup SE, Strangerup M, Hancke S. Hepatosplenomegaly in infectious mononucleosis, assessed by ultrasonic scanning. J Laryngol Otol. 1986 May;100(5):573-9.

  4. Auwaerter PG. Infectious mononucleosis: return to play. Clin Sports Med. 2004 Jul;23(3):485-97,xi.

  5. Burroughs KE. Athletes resuming activity after infectious mononucleosis. Arch Fam Med. 2000 Nov-Dec;9(10):1122-3.

  6. Farley DR, Zietlow SP, Bannon MP, Farnell MB. Spontaneous rupture of the spleen due to infectious mononucleosis. Mayo Clin Proc. 1992 Sep;67(9):846-53.

  7. Sokolowski JW Jr, Kent DC. Spontaneous rupture of spleen in infectious mononucleosis. Value of roentgenography. N Y State J Med. 1968 May 1;68(9):1172-4.

  8. Rutkow IM. Rupture of the spleen in infectious mononucleosis: a critical review. Arch Surg. 1978 Jun;113(6):718-20.

  9. Asgari MM, Begos DG. Spontaneous splenic rupture in infectious mononucleosis: a review. Yale J Biol Med. 1997 Mar-Apr;70(2):175 - 82

Originally submitted on February 18, 2005

Infectious Mononucleosis
© copyright 2015 Stephen Ng & UCLA Department of Medicine
© 2004-2009, Department of Medicine, UCLA
All rights reserved. We make no representations whatsoever about any other website that may be accessed through this site. When you access a non-DOM website, please understand that it is independent from our organization, and that we have no control over the content of that website
For patient related questions
For medical school admission info
For questions about this website