Glandular fever (EBV)

Epstein-Barr Virus (EBV) is the virus that causes glandular fever (infectious mononucleosis or IM)
a frequent infection, particularly in young adults, mainly due to spread via saliva such as kissing or sharing drinks
- Incidence ages 10 to 19 years: 6-8 per 1,000/year
- Incidence ages >30 years: <1 case per 1,000/year
- Incidence ages <10 years: <1 case per 1,000/year
- Mononucleosis is rare under age 1 year old (due to passive maternal Immunity)
- Mononucleosis in age 1-5 year olds may occur more in developing countries and unsanitary conditions
- Peak Incidence (highest Incidence ages 15 to 24 years old)
- commonly occurs in congested, confined space – College Students, Military recruits
EBV is transmitted via
- intimate contact with body secretions, primarily oropharyngeal secretions.
  - EBV infects the B cells in the oropharyngeal epithelium.
- may also be shed from the uterine cervix, implicating the role of genital transmission in some cases.
- On rare occasion, EBV is spread via blood transfusion.
A rapid and efficient T-cell response results in control of the primary EBV infection and lifelong suppression of EBV.
Ineffective T-cell response (such as in those on immunosuppressants for Mx of transplants) may result in excessive and uncontrolled B-cell proliferation, resulting in B-lymphocyte malignancies
Life long infection: Adults (by age 35 years) who have been previously infected and are carriers: 90-95% worldwide

clinical features of acute EBV infection

incubation Range: 4-8 weeks (may be as short as 2 weeks)
most patients are asymptomatic (50% of 5yr olds and 90% of adults show serologic evidence of past infection)
when infection occurs during adolescence, it causes infectious mononucleosis pharyngitis picture in ~50%
when infection occurs in the elderly, it mainly causes a viral hepatitis picture

Adolescent infectious mononucleosis

fever (in >97% of cases) Persists for 7-10 days
pharyngitis – (>97%) often pustular with bilateral large inflamed “kissing” tonsils which may compromise airway, and later, palatial petechiae (these also can occur in Strept tonsillitis)
generalised lymphadenopathy – (>97%) in particular, the finding of posterior cervical LN’s helps differentiate it from bacterial tonsillitis which generally only causes anterior cervical lymphadenitis, but adenitis is uncommon in the elderly who mainly present with an anicteric viral hepatitis.
malaise/fatigue
- may be profound initially
- usually settles after a variable period but often takes 3 months
- May cause Chronic fatigue syndrome
- reporting of prominent fatigue:
  - 41% during acute illness
  - 71% at 1 month
  - 43% at 2 months
  - 9% at 6 months
Splenomegaly (50 to 75%) may be present but usually returns to normal by 3 weeks
- rarely may result in splenic rupture (1-2% of symptomatic cases) – thus contact sports should be avoided if splenomegaly is present
Hepatomegaly and abnormal LFTs are common
- jaundice occurs in < 10% of young adults and in ~30% of the elderly with acute EBV
early, transient, faint macular rash is common but easily missed
Periorbital edema (33%)
widespread macular rash may occur, but particularly likely if the patient has received amoxycillin

Investigations

leukocytosis, rather than leukopenia, often with atypical lymphocytes > 20% +/- thrombocytopenia
Monospot IM screen may be negative in the first week or two and overall has a sensitivity of 85% (in children over age 2yrs) and specificity of 100%
- those with negative Monospot but suggestive clinical picture may need weekly Monospot tests for up to 6 weeks.
EBV Anti VCA-IgM
EBV Anti VCA-IgG
EBV Early Antigen (EA) Antibody EIA
EBV Nuclear Antigen Antibody (EBNA) EIA

Clinical Status	IgM VCA (<36)*	IgG VCA (<18)*	Anti-EA (<9)*	Anti-EBNA (<18)*
Susceptible	Negative	Negative	Negative	Negative
Acute Primary Infection	Positive	Positive	Positive	Neg/Wk Pos
Recent Primary Infection	Neg/Wk Pos	Positive	Positive	Positive
Past Infection	Negative	Positive	Negative	Positive
Reactivation in Immunosuppressed or Immunocompromised Individuals	Negative	Positive	Positive	Positive
Burkitts’ Lymphoma	Negative	Positive	Positive	Positive
Nasopharyngeal Carcinoma	Negative	Positive	Positive	Positive

ESR is usually raised (but is not so in Strep tonsillitis!)

Complications of Epstein–Barr Virus–Associated Mononucleosis

Rash, including nonallergic rash to amoxicillin and other antibiotics
Airway obstruction
Splenomegaly and splenic rupture
Splenic infarct
Autoimmune hemolytic anemia
Thrombocytopenia
Aplastic anemia
Hepatitis and cholestasis
fatal hepatic necrosis is a rare complication, and is more likely in males
Meningoencephalitis or Guillain–Barré syndrome
Hemophagocytic syndrome
Malignancy (Hodgkin lymphoma; Burkitt lymphoma in Africa; nasopharygeal carcinoma in Asia; CNS lymphoma in AIDS; lymphoproliferative disease in transplant patients)

ED Mx of presumed acute EBV pharyngitis/tonsillitis

FBE, IM screen +/- LFTs are generally performed
if significant dysphagia or potential airway risk, admit for iv fluids and iv dexamethasone
patients with splenomegaly should be warned to avoid contact sports
if clearly EBV and not Strept tonsillitis, avoid antibiotics, and particularly amoxycillin as likely to develop a florid rash
encouraged to rest as much as possible and to refrain from active physical activity for 3 weeks
seek specialist advice if immunocompromised or rare complication

long term sequelae

neoplasia risk:
- endemic Burkitt lymphoma in children in malarial countries such as Africa
- Hodgkin’s lymphoma – 3x risk; 40% of HL cases in Western countries are EBV genome-positive
- Non-Hodgkin’s lymphoma
- hairy leukoplakia
- leiomyomas and leiomyosarcomas in immunocompromised children
- nasopharyngeal carcinoma appears to be always caused by EBV, high prevalence in southern China and other parts SE Asia
- Most instances of post-transplant lymphoproliferative disorder (PTLD) are associated with EBV.
- B-cell lymphomas (post-transplant lymphoma PTL) risk if on immunosuppressants for Mx of transplants
multiple sclerosis (MS) risk 20 fold in those with high titres of EBV antibodies and a specific HLA-DR15 or HLA-A genotype
there is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome

Treatment Options