Glandular Fever

Original Author: Dr Thomas Stubington and Dr Bindy Sahota
Last Updated: 13th August 2018
Revisions: 15

Glandular fever is a colloquial term used to describe infectious mononucleosis (IM). IM is caused by Epstein-Barr virus and presents as a sore throat with associated fever and lymphadenopathy. [1] IM-like disease can also be caused by other viruses such as Cytomegalovirus (CMV). The final diagnosis is usually made on serology but there are certain features that increase clinical suspicion (see below.)

In this article, we shall look at the pathophysiology, diagnosis and management of glandular fever


Epidemiology

The most common age group for presentation with acute symptoms is teenagers and young adults, typically quoted as a range of 18-22. [1] [2] Most adults are antibody positive by the age of 30 (90%) but in most people seroconversion happens without producing any symptoms. [3] [2]

There are two peaks in primary infection: the first is age 1-6 and the second is 18-22, where individuals not previously exposed to the virus are suddenly exposed to it through mixing at either school or university. Even during this second peak only 50% seroconvert with overt clinical symptoms. [3]


Risk Factors

The most common transmission route is exchange of saliva by kissing and the incubation period is around six weeks. The virus is also spread by blood transfusion, and stem cell and solid organ transplant, although this is a rare route of transmission. [2]


Clinical Features


From history


Glandular fever may present with predominantly head and neck complaints, more general systemic upset, or a combination of the two:

  • Sore throat – Often described by the patient as the worst they’ve ever had
  • Snoring and even sleep apnoea due to significant tonsillar enlargement
  • Swollen neck

 

  • Feverish
  • Headaches
  • Nausea & vomiting
  • Generally tired all the time, despite adequate sleep
  • Generalised aches and pains in the muscles and joints (myalgia and arthralgia)

The odynophagia typically lasts 7-10 days but generalized malaise, aches and myalgia and cervical lymphadenopathy may well persist for several weeks. [2]

From examination


  • Enlarged inflamed tonsils, often meeting in the middle and referred to as “kissing tonsils” (both because they “kiss” in the midline and because of the route of spread)
  • Significant cervical lymphadenopathy (both anterior and posterior cervical chains)
  • Abdominal tenderness & splenomegaly (in as many as 50%)
  • Hepatomegaly (in as many as 25%) [3]
  • Palatal petechiae

Differential Diagnosis

  • Tonsilitis – Bacterial tonsillitis is generally shorter-lived and tends to have fewer of the systemic symptoms (myalgia, malaise etc.)
  • Quinsy – Tends to be unilateral with swelling predominantly superior to the tonsil. Look for hot potato voice, drooling and difficulty swallowing even saliva (see separate article)

Investigations


Routine Blood Tests


FBC – Typically a raised white cell count with a lymphocyte predominance

LFTs – Around 75% will develop elevation of liver enzymes. This is most noticeable in the 2nd or 3rd week and should resolve by week 5 [3] [2]

Specific Testing


The monospot test is the primary technique for identifying infection with Epstein-Barr virus. However it relies on the generation of non-specific heterophile IgM autoantibodies, which are not produced immediately following viral infection of B lymphocytes and may take a week to appear. Indeed, some studies report as many as 50% of children with EBV infection may not be positive for heterophile antibodies and, because of it’s non-specificity, it may also be positive in a number of other conditions. [3] [2]

More specific ELISA based immunoassays are available and anti-Viral Capsid Antigen IgG is usually detectable by the time of clinical symptoms and persists. [3] [2]


Management


Antivirals


There is minimal clinical evidence to support the use of antivirals in the treatment of glandular fever. They are not commonly prescribed in immunocompetent patients. [2] [3]

Steroids


The subject of steroid therapy is controversial and the consensus view is that steroid therapy should be reserved for patients with respiratory compromise [2] [4].  A Cochrane review concluded that the main evidence is for reduction in duration of sore throat, and even here the evidence is described as insufficient. [5]

Antibiotics


Bacterial superinfection is present in as many as 30% and so penicillin-based antibiotics (usually benzylpenecillin/penicillin V) are often prescribed. [3]


Complications


Post-viral fatigue


Epstein-Barr virus is one of a number of viruses shown to be linked to the development of post-infective fatigue syndromes. Different studies use different classifications, but it is generally taken to be persistence of disabling fatigue, musculoskeletal pain or mood disturbances (depression/ anxiety) 6 months after initial infection [6] [7]. These symptoms may persist for a year, although there is some debate as to whether this may actually be due to chronic infection or re-activation of the virus. [8]

Malignancy


Epstein-Barr virus has shown to be associated with the development of a number of different lymphomas (Burkitts, Hodgkins, T Cell) as well as nasopharyngeal carcinoma. [3]

Guillain-Barre Syndrome


There is an association between Guillain-Barré syndrome and Epstein-Barr Virus described in the literature. [9]

Encephalitis


Encephalitis can occur, resulting in fever, seizures, unusual behavior or gait disturbance. It is sometimes preceded by symptoms of glandular fever, but may also occur without preceding symptoms. [10]

Splenic Rupture


Splenic rupture is a risk in infectious mononucleosis. This complication usually occurs within 14 days, but can occur up to 8 weeks after presentation. [11] In some instances there is a history of preceding trauma that results in spenic rupture, but recent studies suggest that as many as 86% may be spontaneous. [11]

Current recommendations suggest avoiding contact sports for 4-6 weeks post treatment; evidence suggests that the highest risk is in the 2nd and 3rd week of illness. [12]


References

(1) E. Johannsen and K. Kaye, “Epstein-Barr Virus (Infectious mononucleosis, Epstein Barr Virus associated malignant diseases and other diseases),” in Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (Eighth Edition), Elsevier, 2015, pp. 1754-1771.
(2) S. Dunmire, K. Hogquist and H. Balfour, “Infectious Mononucleosis,” in Epstein Barr Virus Volume 1, Current Topics in Microbiology, Springer International, 2015, pp. 211-240.
(3) M. Papesch and R. Watkins, “Epstein-Barr Virus Infectious mononucleosis,” Clinical Otolaryngology, vol. 26, pp. 3-8, 2001.
(4) S. Thompson, T. Doerr and A. Hengerer, “Infectious Mononucleosis and Corticosteroids,” Archives otolaryngology head and neck surgery, vol. 131, no. 10, pp. 900-904, 2005.
(5) E. Rezk, Y. Nofal, A. Hamzeh, M. Aboujaib, M. AlKheder and M. Al Hammad, “Steroids for symptom control in infectious mononucleosis,” The Cochrane Library, 2015.
(6) I. Hickie, T. Davenport, D. wakefield, U. Vollmer-Conna, B. Cameron, S. Vernon, W. Reeves and A. Lloyd, “Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study,” BMJ, vol. 333, no. 575, 2006.
(7) P. White, J. Thomas, J. Amess, S. Grover, H. Kangro and A. Clare, “The existence of a fatigue syndrome after glandular fever,” Psychological Medicine, vol. 25, pp. 907-916, 1995.
(8) P. Kraugsbjerg, “Chronic active mononucleaosis,” Scandinavian journal of infectious disease, vol. 29, pp. 517-518, 1997.
(9) B. Jacobs, P. Rothbarth, F. van der Meche, P. Herbrink, P. I. M. Schmitz, M. A. de Klerk and P. A. van Doorn, “The spectrum of antecedent infections in Guillain-Barré syndrome,” Neurology, vol. 51, no. 4, pp. 1110-1115, 1998.
(10) A. Doja, A. Bitnun, E. l. F. Jones, S. Richardson, R. Tellier, M. Petric, H. Heurter and D. MacGregor, “Pediatric Epstein-Barr Virus—Associated Encephalitis: 10-Year Review,” Journal of Child Neurology, vol. 21, no. 5, pp. 384-391, 2006.
(11) A. Bartlett and R. Williams, “Splenic rupture in infectious mononucleosis: A systematic review of published case reports,” Injury, vol. 47, no. 3, pp. 531-538, 2016.
(12) R. Howman-Giles, D. Gilday and S. Vengopal, “Splenic Trauma non-operative management and long term follow up by scintiscan,” Journal of Pediartric Surgery, vol. 13, no. 2, pp. 121-125, 1978.

 

Authors:

1st draft: Dr Thomas Stubington

Senior Review: Dr Raguwindar Sahota (Senior ENT registrar)

Student Reviewer: Luke Austen

 

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