Viral Infections in Heme Disorders Flashcards
viral infections - general principles
viruses…
*are obligate intracellular organisms
*utilize host cell machinery to replicate
*often exhibit tropism for specific cell type(s)
*may establish latency/chronic infection as part of the natural history of infection w/ potential for reactivation
*are often difficult to diagnose
*are challenging to treat because therapeutic windows are typically narrow and available antiviral therapies are limited in number
infectious mononucleosis syndrome - clinical features
*malaise/fatigue
*fever
*sore throat w/ or w/o exudative pharyngitis
*hepatosplenomegaly
*absolute mononuclear cell predominance with the presence of “atypical” lymphocytes
*anemia and/or thrombocytopenia
*transaminitis with ALT>AST; total bili may also be increased
ddx of infectious mononucleosis syndrome
*EBV
*CMV
*HIV
*toxoplasmosis
*HHV-6
*group A strep
*viral hepatitis
*lymphoma or other lymphoproliferative disorders
*drugs
viral ddx of (pan)cytopenias in immunoCOMPETENT host
*parvovirus B19
*EBV
*CMV
*HIV
*HBV/HCV
parvovirus B19 - overview
*single strand DNA virus which exclusively infects humans
*transmission via respiratory route
*exposure to virus is common & generally occurs early in life
*infection targets ERYTHROID PROGENITORS which leads to cessation of RBC production:
-transient in the normal host
-prolonged and severe in pts with baseline increased erythropoiesis (ex. sickle cell) or host immunocompromise
parvovirus B19 - clinical manifestations
*erythema infectiousum (Fifth disease):
-healthy children
-febrile prodrome, then “slapped cheek” facial rash
*polyarthropathy syndrome:
-healthy adults
-symmetric arthritis that may mimic RA
*transient aplastic crisis (TAC)
*pure red cell aplasia/chronic anemia
*hydrops fetalis (pregnant women)
parvovirus B19 - diagnosis
*IgM antibody in normal hosts or those with TAC
*parvovirus B19 virus DNA in immunocompromised hosts
*giant pronormoblasts (see image) on exam of bone marrow
parvovirus B19 - management
*RBC transfusions as indicated
*intravenous immunoglobulin (IVIG) for ICHs
*no specific antiviral Rx available
Epstein-Barr Virus (EBV) - overview
*DNA virus in the family Herpesviridae
*worldwide in occurrence with peaks of infection in early childhood and late adolescence
*90% of adults are seropositive
*spread by contact with oral secretions
*primary infection involves epithelial cells of oropharynx & salivary glands -> B lymphocytes (which become “immortal”) -> lifetime latent infection with potential for reactivation
Epstein-Barr Virus (EBV) - associations with malignancy
*Burkitt lymphoma
*anaplastic nasopharyngeal carcinoma (southern China)
*Hodgkin disease
*non-hodgkin lymphoma
Epstein-Barr Virus (EBV) - diagnostic tools
*heterophile antibody (monospot test):
-Ab that agglutinates sheep, horse, or cow RBCs
-does not interact with EBV proteins
-about 80% sensitivity
-note: this is the FIRST test you would order
*specific EBV serologies:
-Abs to viral capsid antigen (VCA IgG and IgM)
-Abs to early antigens (EA-D and EA-R)
-Abs to Epstein-Barr nuclear antigen (EBNA)
-used for patients with suspected EBV who are heterophile neg or for pts with atypical infections
*PCR for EBV DNA in blood or tissue
Epstein-Barr Virus (EBV) - management
*supportive/symptomatic
*avoidance of strenuous activity
*glucocorticoids (in some cases):
-impending airway obstruction
-AIHA or severe thrombocytopenia
-CNS or cardiac complications
*no antiviral therapy
cytomegalovirus (CMV) - overview
*double-stranded DNA virus in family Herpesviridae with potential for both lytic (productive) & latent infection
*worldwide distribution with most infection occurring perinatally & in early childhood
*transmission can occur by multiple routes (secretions, blood, breast milk, sexually) but often requires intimate or prolonged exposure
*infection may target multiple cells (WBCs, endothelium, epithelium, fibroblasts), often resulting in enlarged cells w/ intranuclear & cytoplasmic inclusions
cytomegalovirus (CMV) - clinical features (in immunocompetent host)
*asymptomatic infection
*congenital infection (usually associated with primary infection in mom; petechiae, HSM, jaundice)
*perinatal infection (often asymptomatic)
*CMV mononucleosis syndrome
cytomegalovirus (CMV) - diagnosis
*clinical diagnosis not reliable
*serodiagnostic testing in serum? cell culture? PCR?
*HISTOPATHOLOGY of tissue:
-demonstration of virocytes (cytomegalic cells with inclusions -> “owl eyes”)
-immunohistochemical staining w/ monoclonal antibody
