Infectious mononucleosis and infectious lymophocytosis. Differential diagnosis in patients with enlarged lymph nodes. Flashcards
ETIOLOGY OF INFECTIOUS MONONUCLEOSIS
Epstein-Barr virus (EBV), also called human herpesvirus 4 (HHV-4)
EPIDEMIOLOGY OF INFECTIOUS MONONUCLEOSIS
15–24 years of age
Only reservoir are humans
ONcogenic potential
TRANSMISSION OF INFECTIOUS MONONUCLEOSIS
highly contagious and spreads via bodily secretions, especially saliva. Therefore, it is also called kissing disease.
PATHOGENESIS OF INFECTIOUS MONONUCLEOSIS //
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
INCUBATION PERIOD OF INFECTIOUS MONONUCLEOSIS
6 weeks
CLINICAL FEATURES OF INFECTIOUS MONONUCLEOSIS
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.
COMPLICATION OF EBV?
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
DIAGNOSIS OF INFECTIOUS MONONUCLEOSIS?
Monospot test
latex agglutination test
Detects heterophile antibodies produced in response to EBV infection using RBCs from sheep or horses
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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
DD OF IM
mononucleosis like syndrome :
Streptococcal pharyngitis, tonsillitis
Acute HIV infection
CMV infection (CMV mononucleosis)
TREATMENT OF IM?
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.
EPIDEMIOLOGY OF CMV ?
seroprevalence increases with age - esp over 80 years
only persists in humans
what are the characteristics of CMV ?
human herpes 5
what is the TRANSMISSION OF CMV ?
blood transfusion sexual transfusion transplacental perinatal body fluids - resp droplets , saliva , urine transplant transmitted
what is the PATHOGENESIS OF CMV ?
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
INCUBATION OF CMV
what are the CLINICAL FEATURES OF CMV ?
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
dd of cmv ?
EBV
DIAGNOSIS OF CMV ?
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
TREATMNET FOR CMV ?
immunocompetent patients - no therapy is needed
immunosuppressed patients -
cmv retintisis and cmv colitis - valgancyclovir
CMV pneumonia - ganciclovir
CMV encephalitis - ganciclovir and foscarnet
complication of cmv ?
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
what is the EPIDEMIOLOGY OF HERPES SIMPLEX 1 AND 2 ?
humans are the only reservoir
hsv1 - usually acquired in childhood
what is the TRANSMISSION OF HERPES SIMPLEX VIRUS ?
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
what is the PATHOGENESIS OF HERPES SIMPLEX ?
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
what is the INCUBATION PERIOD OF HERPES SIMPLEX ?
incubation period for an initial herpes infection is 4 days (range, 2 to 12)
hsv2 - 2-7 days
what re the CLINICAL FEATURES OF HERPES SIMPLEX ?
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
DIAGNOSIS OF HERPES ?
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
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PCR detects the HSV dna
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direct fluorescent antibody test
what is the TREATMENT OF HERPES ?
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
========= 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
PROPHYLAXIS OF HERPES ?
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
