Infectious mononucleosis and infectious lymophocytosis. Differential diagnosis in patients with enlarged lymph nodes.

Question 1

ETIOLOGY OF INFECTIOUS MONONUCLEOSIS

Answer 1

Epstein-Barr virus (EBV), also called human herpesvirus 4 (HHV-4)

Question 2

EPIDEMIOLOGY OF INFECTIOUS MONONUCLEOSIS

Answer 2

15–24 years of age

Only reservoir are humans

ONcogenic potential

Question 3

TRANSMISSION OF INFECTIOUS MONONUCLEOSIS

Answer 3

highly contagious and spreads via bodily secretions, especially saliva. Therefore, it is also called kissing disease.

Question 4

PATHOGENESIS OF INFECTIOUS MONONUCLEOSIS //

Answer 4

EBV infects B lymphocytes in mucosal epithelium (e.g., oropharynx, cervix) → infected B lymphocytes induce a humoral (B-cell) as well as a cellular (T-cell) immune response
→ an increased concentration of atypical lymphocytes in the bloodstream, which are CD8+ cytotoxic T cells that fight infected B lymphocytes

affected B-
lymphocytes and can even lead to immortality of these cells

This lymphoproliferation
can become very severe in immunosuppressive states or
even lead to malignant transformation of cells

Question 5

INCUBATION PERIOD OF INFECTIOUS MONONUCLEOSIS

Answer 5

6 weeks

Question 6

CLINICAL FEATURES OF INFECTIOUS MONONUCLEOSIS

Answer 6

last for 2–4 weeks.

Young children are often asymptomatic.

Splenomegaly,Possibly hepatomegaly and jaundice

fever,

Pharyngitis and/or tonsillitis (reddened, enlarged tonsils covered in pus),

palatal petechiae

Bilateral cervical lymphadenopathy (especially posterior) that may become generalized and can, in severe cases, lead to airway obstruction

Abdominal pain

Maculopapular rash (similar to measles): The rash is caused by the infection itself in about 5% of cases but is MOST COMMONLY ASSOCIATED WITH THE ADMINISTRATION OF AMINOPENICILLIN (e.g., ampicillin, amoxicillin)

In MOST CASES, A MACULOPAPULAR RASH OCCURS DUE TO EMPIRIC ADMINISTRATION OF AMINOPENICILLINS, and not due to EBV infection.

Question 7

COMPLICATION OF EBV?

Answer 7

splenomegaly can lead to a potentially life-threatening splenic rupture!

b cell lymphoma

hodgkin lymphoma

central and west africa = infected EBV lymphocytes and plasmodia can cause burrkitt lymphoma

HIV infection in stage B - EBV infection - oral hairy leukoplakia

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Nervous system
Guillain-Barré syndrome
Meningoencephalitis
primary cmv lymphoma

Hematological system
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH): a life-threatening hematologic disorder involving pancytopenia and severe inflammation due to increased activity of cytotoxic T cells and macrophages 

Autoimmune hemolytic anemia, thrombocytopenia

ASSOCIATED MALIGNANCIES
Burkitt lymphoma (BL), a non-Hodgkin lymphoma
Associated with EBV infection
Occurs mainly in Africa
Typically affects the jaw and facial bones

Nasopharyngeal carcinoma (common in Asian adult population)

Post-transplant lymphoproliferative disorder: EBV reactivation in patients with severe immunosuppression
Commonly progresses to B-cell lymphoma: poor prognosis

Question 8

DIAGNOSIS OF INFECTIOUS MONONUCLEOSIS?

Answer 8

Monospot test
latex agglutination test
Detects heterophile antibodies produced in response to EBV infection using RBCs from sheep or horses
=
Patient’s serum is mixed with a solution of sheep/horse RBC in vitro
Positive test: cross-reaction between heterophile antibodies and sheep/horse RBCs → agglutination

Peripheral smear: lymphocytosis with > 10% atypical lymphocytes (in some cases, up to 90%)

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Serology: indicated if IM is suspected but monospot testing is negative
Anti-viral capsid antigen igm antibodies (anti-VCA)

Anti-VCA IgM: appears early and vanishes ∼ 3 months after infection )negative for past infection)

Anti-VCA IgG: appears after 2–4 weeks and persists for life

Anti-EBV nuclear antigen-antibody (anti-EBNA-1) IgG

Question 9

DD OF IM

Answer 9

mononucleosis like syndrome :

Streptococcal pharyngitis, tonsillitis
Acute HIV infection
CMV infection (CMV mononucleosis)

Question 10

TREATMENT OF IM?

Answer 10

Avoid physical activity because of the risk of splenic rupture.

Fluids

Analgesics/antipyretics

Steroids are not recommended for routine use but may be considered in complicated cases.

Question 11

EPIDEMIOLOGY OF CMV ?

Answer 11

seroprevalence increases with age - esp over 80 years

only persists in humans

Question 12

what are the characteristics of CMV ?

Answer 12

human herpes 5

Question 13

what is the TRANSMISSION OF CMV ?

Answer 13

blood transfusion 
sexual transfusion 
transplacental 
perinatal 
body fluids - resp droplets , saliva , urine 
transplant transmitted

Question 14

what is the PATHOGENESIS OF CMV ?

Answer 14

CMV binds to integrins - transmembrane receptor protein which stabalses cellular adhesion

they activate integrins
and the activate - apoptotic pathway
and infected cells enlarge and show characteristics of cytomegalic changes

after primary infection resolves

CMV remains in latency in mononuclear cells such as myeloid cells / lymphocytes or salivary hands -reactivation occur if patient becomes immunocompromised

Question 15

INCUBATION OF CMV

what are the CLINICAL FEATURES OF CMV ?

Answer 15

incubation 2-6 weeks

90 percent asymptomatic

less than 10percent
CMV mononucleosis
fever , malaise , arthralgia , myalgia , headache
less common - sore throat , cervical lymphadenopathy , hepatomegaly , splenomegaly

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immunocompromised

cmv mononucleosis

cmv pneumonia - interstitial pneumonitis

cmv retinitis - floaters , photopsia , visual defects
fundoscopy - pizza - pie appearance - opacities around retinal vessels resembling cotton wool spots

cmv esophagitis or CMV colitis
most commonly in patient with HIV

Cmv encephalitis

Question 16

dd of cmv ?

Answer 16

EBV

Question 17

DIAGNOSIS OF CMV ?

Answer 17

cbc
relative lymphocytosis - more than 10 percent atypical lymphocytes
sometomes pancytopnea (some degree of bone marrow suppression)

tissue biopsy - large atypical lymphocytes with intranucelar inclusions that have owl eye appearance

monospot test

serological test - to see if the disease is active
four fold increase in IGg levels confers this
igm and Igg - acute
persistent - only igg
reactivated - higher igg titre and positive igm

PCR - cmv dna
indirect immunofluorescence

Question 18

TREATMNET FOR CMV ?

Answer 18

immunocompetent patients - no therapy is needed

immunosuppressed patients -
cmv retintisis and cmv colitis - valgancyclovir
CMV pneumonia - ganciclovir
CMV encephalitis - ganciclovir and foscarnet

Question 19

complication of cmv ?

Answer 19

intrauterine CMV 0 chorioretinitis , hepatosplenomegaly , deafness , microcephaly

symptoms prevent though week o month after birth

mentioned treatment for cmv are teratogenic, therefore during an acute infection
during pregnancy only “off-
label” treatment with
hyperimmunoglobulins
is indicated

Question 20

what is the EPIDEMIOLOGY OF HERPES SIMPLEX 1 AND 2 ?

Answer 20

humans are the only reservoir

hsv1 - usually acquired in childhood

Question 21

what is the TRANSMISSION OF HERPES SIMPLEX VIRUS ?

Answer 21

hsv1 - direct contact such as kissing , droplet or smear infection
90 percent is latency infected with the virus
usually acquired in childhood

HSV2 - sexual contact
or perinatal transmission during childbirth

virus enters the body through mucosa through dermal lesions

Question 22

what is the PATHOGENESIS OF HERPES SIMPLEX ?

Answer 22

virus enters the body through mucosa through dermal lesions

it invades speeds and replicates in the nerve cell

after the primary infection the virus remains dormant in the ganglion
HSV1 - trigeminal
HSV2 - sacral

reactivation is triggered through immunodeficiency or trauma

dissemination can occur - making the infection spread to unusual sites such as GI , eyes

Question 23

what is the INCUBATION PERIOD OF HERPES SIMPLEX ?

Answer 23

incubation period for an initial herpes infection is 4 days (range, 2 to 12)

hsv2 - 2-7 days

Question 24

what re the CLINICAL FEATURES OF HERPES SIMPLEX ?

Answer 24

primary infection is usually asymptomatic - If symptomatic, the infection is often sudden and severe - ., fever, malaise, myalgias, and headaches

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labial herpes 
Prodromal symptoms (∼ 24 hours) :pain tingling and burning 

recurring erythematous vesicles turn to painful ulceration also kwown as cold sores - affecting oral mucosa and lip borders

dd- herpes zoster 0 shingles

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genital herpes
mostly asymptomatic
genital redness , swelling , pruritus , pain
unusual vaginal discharge
painful lymphadenopathy in groin
punched out lesions later which turn into ulcerations

• lesions can be single or disseminated , red bumps or white vesicles

recurrence is very common

Question 25

DIAGNOSIS OF HERPES ?

Answer 25

high micro on tzanck smear
- from ulcer base scrapping
- detect multinucleated giant cells
cowdry a inclusions - intranuclear inclusions in eosinophils
unable to differentiate between HSV1 and 2

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viral culture
culture taken from fresh vesicle either from skin or genitals

====

PCR detects the HSV dna

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direct fluorescent antibody test

Question 26

what is the TREATMENT OF HERPES ?

Answer 26

recurrence cannot be prevented.

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Agents
First-line: oral acyclovir
In case of acyclovir-resistant HSV-1: foscarnet

Valacyclovir
Oral application

Penciclovir
Topical application
Effective against HSV-1, HSV-2, VZV, and EBV

Famciclovir
Oral application - hsv1

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Barrier creams to avoid lip adhesion in cases of lesions on the lips
Pain relief (oral or IV)
Antipyretics
Antibiotics

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Patients with severe orofacial infections may have difficulties drinking and eating, particularly children. In these cases, the administration of IV fluids

children with herpetic gingivostomatitis hospitalized because of lacking fluid intake

Question 27

PROPHYLAXIS OF HERPES ?

Answer 27

indicated in the case of frequent or severe relapses; in patients with prodromal symptoms

Long-term suppressive therapy with (val)acyclovir

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Use of condoms, gloves
Consider isolation of hospitalized patients with shedding lesions