Mononucleosis


Article Author:
Michael Mohseni
Michael Boniface


Article Editor:
William Gossman


Editors In Chief:
Lauren Camaione


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
7/11/2019 11:33:58 PM

Introduction

Mononucleosis classically presents with fever, lymphadenopathy, and tonsillar pharyngitis. The term “infectious mononucleosis” was first used in the 1920s to describe a group of students with a similar pharyngeal illness and blood laboratory findings of lymphocytosis and atypical mononuclear cells. It was only later that Epstein-Barr virus (EBV) was established as the cause of mononucleosis after an exposed healthcare worker developed a positive heterophile test.[1][2]

Etiology

The cause of mononucleosis is the Epstein-Barr virus (EBV). EBV is a type of herpesvirus spread by contact, typically with salivary secretions. The duration of oral shedding is not entirely clear, but high levels of shedding can continue for a median of 6 months after illness onset. Transmission is generally person-to-person, but EBV is not considered a highly contagious disease. [3]

Epidemiology

It is estimated that up to 95% of adults in the world are eventually seropositive to EBV. Therefore, EBV is widely disseminated in all population groups. The traditional age group where peak incidence is noted, however, is in 15 to 24-year olds. Classically, the symptomatic infection is in adolescents, which is why laypersons may refer to the infection as the “kissing disease.” Mononucleosis is uncommon in adults:  approximately 2% of all pharyngeal disease in adults is attributable to this disease. Adults are generally not susceptible to clinical illness because of previous exposure. In the United States, clinically evident infection occurs at rates estimated at 30 times higher in whites than in blacks. One explanation for this disparity is that if acquired at a young (childhood) age, EBV is often subclinical. This would suggest earlier EBV exposures in blacks, and a higher frequency of asymptomatic infection as young children. [1][4]

Pathophysiology

When EBV is introduced into the oropharynx, the virus begins the replication process. There is a predilection for infection of the B-cells of lymphoid tissue. Subsequently, the infection spreads through the lymphatic system. The body reacts by developing antibodies against the virus. In 90% or more of cases, heterophile antibodies are produced in response to the infection with EBV. EBV is a lifelong infection with periodic reactivation.  In poor immune response systems, there is a small risk of EBV-induced malignancy, such as Hodgkin lymphoma.[5][6]

History and Physical

Fever, sore throat, fatigue, and tender lymph nodes are classic findings on history-taking in infected individuals with mononucleosis. The classical triad is fever, pharyngitis, and lymphadenopathy. Additional complaints include a headache, general malaise, and poor oral intake.  Unfortunately for some, fatigue can be persistent for months in select individuals. Lymphadenopathy is more common in the posterior cervical region. The pharyngitis is often heralded with tonsillar exudates. Petechial lesions on the palate occur infrequently. Also, splenomegaly is a key finding on physical in up to half of patients with active clinical mononucleosis. Identification is important in patients prone to future injury, e.g., active sports participants. Skin examination in some patients may infrequently reveal a nonspecific, generalized maculopapular rash. This is separate from the antibiotic-induced rash discussed below.

Evaluation

As always, initial evaluation should include airway assessment to determine that the airway is patent and there is no impending occlusion or compromise. In rare instances, abscess or edema can impede proper maintenance of the airway. Also, determination of hemodynamic stability is important to rule out concomitant splenic injury or rupture in the acute illness of mononucleosis. Laboratory evaluation most commonly will reveal lymphocytosis, with a lymphocyte differential often greater than 50%. Atypical lymphocytosis of greater than 10% can be seen on blood smear. A general leukocytosis and occasionally thrombocytopenia may also be appreciated. Imaging is generally not needed in the evaluation of mononucleosis. The monospot (or heterophile antibody) test for mononucleosis is the diagnostic test of choice and is nearly 100% specific for the disease. The sensitivity of this test is closer to 85%.  If the patient is early in the illness, the test may be falsely negative, and it should be repeated later during the course of the disease. If the diagnosis is unclear, the patient should also undergo evaluation for streptococcal infection by rapid antigen testing or throat culture.[7][8][9]

Treatment / Management

Treatment is generally supportive for mononucleosis. Antipyretics and anti-inflammatory medications help to treat fever, sore throat, and the general fatigue seen in this illness. Hydration, rest, and good nutritional intake should also be encouraged. Corticosteroids are not generally recommended in the routine treatment of mononucleosis because of concerns with immunosuppression; however, in cases of airway obstruction, corticosteroids (and possible otolaryngology consultation) are indicated along with appropriate airway management. In instances where antibiotics have been inappropriately administered in patients with mononucleosis, a generalized maculopapular rash may develop. Classically, this is after administration of amoxicillin but can be seen with other antibiotics as well. All athletes should avoid sports during the early course of the illness (approximately three weeks) because of the splenic enlargement was seen in approximately 50% of patients with mononucleosis and the associated risk of splenic rupture.[10][11]

Differential Diagnosis

Many other viral and some rickettsial illnesses have characteristics similar to EBV. The differential includes cytomegalovirus, human immunodeficiency virus (HIV), human herpesvirus type 6, hepatitis B, and tick-borne illnesses such as Lyme disease. Primary HIV may present with mucocutaneous ulcerations; furthermore, skin rash is frequently seen in primary HIV and is far less common in mononucleosis.

Prognosis

The majority of patients with EBV infection recover without sequelae and develop lifelong immunity to controlling the dormant virus. The acute phase of the illness resolves by the second week, but malaise symptoms may persist for months. In rare situations, malignancies have been linked with EBV infection, but additional study is needed to prove causation. Resumption of normal activity should be guided by the risk of splenic injury as well as other limitations that may be imposed by the fatigue that accompanies the illness.

Complications

  • Upper airway obstruction from massive lymphadenopathy
  • Splenic rupture
  • Autoimmune hemolytic anemia
  • Pancytopenia
  • Hemolytic uremic syndrome

Pearls and Other Issues

The diagnostic test of choice for mononucleosis is the heterophile antibody (monospot) test. This can be occasionally falsely negative in early disease and require repeat testing later in the course of the illness.

The most important entity to exclude from the differential diagnosis is primary HIV infection.

Splenic rupture is a rare complication in mononucleosis but can be potentially life-threatening if not diagnosed in a timely fashion.  Consider it on the differential in the patient with classic mononucleosis, abdominal pain, and anemia. Airway obstruction is another rarely seen adverse outcome that requires immediate treatment and management. 

Enhancing Healthcare Team Outcomes

Once a patient has been diagnosed with infectious mononucleosis, the nurse and primary care provider should educate the patient on potential complications and the course of the illness. The patient should be told to avoid all physical activity for at least 4-6 weeks to minimize the risk of splenic rupture. The patient should be told about the signs and symptoms of splenic rupture and when to return to the hospital. All patients should be told about the need to follow up until the symptoms subside and permission to return to physical activity. [12][13](Level V)

Outcomes

The majority of individuals who develop mononucleosis have an excellent outcome. The disorder is self limited and recovery is common in 2-4 weeks. The rare patient may develop a splenic rupture but even these cases are now managed conservatively as long as the patient remains hemodynamically stable.[14][15] (Level V)


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Mononucleosis - Questions

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A 17-year-old presents with swollen glands in the oral cavity, a low-grade fever, and general malaise. Two days later the patient complains of severe abdominal pain and anorexia. What is the most appropriate test for the suspected diagnosis?



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A 17-year-old is seen in the emergency department with a sore throat and a cough for 3 days. He denies smoking and says he has general malaise and arthralgia. Examination reveals a mild cervical adenopathy. Blood work is normal, but the smear reveals the presence of Downey cells. What is the most likely diagnosis?



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A 17-year old male reports general malaise, cough, and a low-grade fever. He says he has no appetite and has had a sore throat for a few days. Examination reveals palpable adenopathy in the neck and a palpable spleen in the left upper quadrant. He denies the use of any medications and does not smoke. What is the most likely cause of his symptoms?



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A 14-year-old boy with a low-grade fever and a cough is seen in the ER. The physician sends blood work for measurement of heterophile antibodies because he suspects which of the following?



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A 17-year-old female presents with a severe sore throat. She has been sick with fever for 4 days. The patient's voice is muffled and she prefers not to speak secondary to pain. She has not been able to eat solids for 2 days and has refused to drink for 1 day. Vital signs show a temperature of 39.8 C, heart rate 140 beats/min, respiratory rate 20, and blood pressure 110/70 mmHg. The exam shows the tonsils to be four-plus enlarged with airway obstruction and grey-white exudates. There also is cervical lymphadenopathy and splenomegaly. A CBC shows atypical lymphocytes. What is the most appropriate management?



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Which of the following conditions would suggest infectious mononucleosis in a child who has tonsillitis?



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A 4 year old boy has a 3-day history of mild headache and decreased activity. This is followed by fever to 103 degrees F (39.4 C), mild cough, and sore throat. On physical exam the child has anterior and posterior cervical lymphadenopathy and splenomegaly. The white blood cell count is 5000/mm3 with a normal differential. The alanine aminotransferase level is increased at 280 U/L. Of the following, which is the most appropriate diagnostic study to perform?



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A patient is diagnosed with infectious mononucleosis and splenomegaly. How long should contact sports be avoided?



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Which of the following infectious agents does NOT cause heterophile negative infectious mononucleosis?



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A patient with a sore throat, fatigue, and fever on exam has an exudative pharyngitis and cervical adenopathy. After a few days of treatment with amoxicillin, a macular erythematous rash occurs. What is the most likely cause?



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Which of the following diagnostic tests is the gold standard for diagnosing infectious mononucleosis?



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Which of the following findings is not characteristic of infectious mononucleosis?



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The primary causative organism of mononucleosis is implicated in all except which of the following diseases?



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A young female was recently diagnosed with infectious mononucleosis. What should be advised?



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Heterophile antibodies may not be positive in which of the following patients infected with Epstein Barr virus?



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Which of the following serology tests excludes acute Epstein Barr virus (EBV) infection?



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Which of the following medications can be used in cases where Epstein Barr virus infections cause severe airway compromise?



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A basketball player is diagnosed with infectious mononucleosis. How long does he have to rest before going back to his game?



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How is infectious mononucleosis generally transmitted?

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In a patient with infectious mononucleosis with a secondary bacterial pharyngitis, which antibiotic must be avoided?



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A 15-year-old male presents with a 2-week history of fevers to 38.7 degrees Celsius, sore throat, lethargy, and weight loss. Exam shows inguinal and cervical tender lymphadenopathy, tonsilar enlargement and exudates, splenomegaly, and >10 percent atypical lymphocytes on CBC. Select the appropriate next step.



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A 16-year-old male is treated for fatigue and severe exudative pharyngitis with amoxicillin and develops a rash. What is the most likely infectious organism?



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What is the most likely cause of mononucleosis?



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Which activity is recommended for a child recovering from mononucleosis?



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An adolescent presents to you with sore throat, fever, lymphadenopathy, and splenomegaly. He also complains of headache but has been previously well. Which should be done?



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A 17-year old boy with a low-grade fever, malaise, and a cough is seen. He has been feeling unwell for 4 days. Physical exam reveals fever, redden pharynx, a non-conspicuous rash on the chest and mild periorbital edema. The abdominal exam reveals dullness to percussion over Traube's space. The clinician sends blood work for measurement of heterophile antibodies because she suspects what disorder?



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A 17-year old male presents to the emergency department with complaints of general malaise, cough, and a low-grade fever for the past 3 days. He says he has no appetite and has had a sore throat for a few days. Examination reveals palpable masses in the neck and the left upper quadrant of the abdomen. He denies the use of any medications and does not smoke. If this were an elderly patient with the same disorder, what would be the most common clinical feature?



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A seventeen-year-old boy has been diagnosed with mononucleosis. What important safety information should the discharge instructions include? Select all that apply.



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Mononucleosis - References

References

Smatti MK,Al-Sadeq DW,Ali NH,Pintus G,Abou-Saleh H,Nasrallah GK, Epstein-Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update. Frontiers in oncology. 2018     [PubMed]
Stemberger M,Jung C,Bogner JR, [Mononucleosis: a disease with three different etiologies]. MMW Fortschritte der Medizin. 2018 May     [PubMed]
Correia S,Bridges R,Wegner F,Venturini C,Palser A,Middeldorp JM,Cohen JI,Lorenzetti MA,Bassano I,White RE,Kellam P,Breuer J,Farrell PJ, Sequence variation of Epstein-Barr virus: viral types, geography, codon usage and diseases. Journal of virology. 2018 Aug 15     [PubMed]
Downham C,Visser E,Vickers M,Counsell C, Season of infectious mononucleosis as a risk factor for multiple sclerosis: A UK primary care case-control study. Multiple sclerosis and related disorders. 2017 Oct     [PubMed]
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Koester TM,Meece JK,Fritsche TR,Frost HM, Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases. Clinical medicine     [PubMed]
Kolesnik Y,Zharkova T,Rzhevskaya O,Kvaratskheliya T,Sorokina O, [CLINICAL AND IMMUNOLOGICAL CRITERIA FOR THE ADVERSE COURSE OF INFECTIOUS MONONUCLEOSIS IN CHILDREN]. Georgian medical news. 2018 May     [PubMed]
Li Y,George A,Arnaout S,Wang JP,Abraham GM, Splenic Infarction: An Under-recognized Complication of Infectious Mononucleosis? Open forum infectious diseases. 2018 Mar     [PubMed]
Vogler K,Schmidt LS, [Clinical manifestations of Epstein-Barr virus infection in children and adolescents]. Ugeskrift for laeger. 2018 May 14     [PubMed]
Dunmire SK,Verghese PS,Balfour HH Jr, Primary Epstein-Barr virus infection. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2018 May     [PubMed]
Olympia RP, School Nurses on the Front Lines of Medicine: A Student With Fever and Sore Throat. NASN school nurse (Print). 2016 May     [PubMed]
Grimes RM,Hardwicke RL,Grimes DE,DeGarmo DS, When to consider acute HIV infection in the differential diagnosis. The Nurse practitioner. 2016 Jan 16     [PubMed]
Aslan N,Watkin LB,Gil A,Mishra R,Clark FG,Welsh RM,Ghersi D,Luzuriaga K,Selin LK, Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires. mBio. 2017 Dec 5     [PubMed]
De Paor M,O'Brien K,Fahey T,Smith SM, Antiviral agents for infectious mononucleosis (glandular fever). The Cochrane database of systematic reviews. 2016 Dec 8     [PubMed]

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