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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
HUMAN T-LYMPHOTROPIC VIRUS TYPE I INFECTION
The torso of a patient with HTLV-I associated ATLL
demonstrates multiple skin lesions consistent with
Viral Infections: Viral Infections Requiring Ancillary Tests
tumor involvement. (Courtesy D. Fisher, DFCI.)
TERMINOLOGY
Abbreviations
Human T-lymphotropic virus type I (HTLV-I)
Manifestations
Adult T-cell leukemia lymphoma (ATLL)
HTLV-I-associated myelopathy/tropical spastic
paraparesis
ETIOLOGY/PATHOGENESIS
Infectious Agents
4 subtypes of HTLV-I
A (cosmopolitan)
B (Central African group)
C (Melanesian)
D (new Central African group)
Virus tropism is for CD4(+) T cells (similar to HIV)
CLINICAL ISSUES
A peripheral blood smear from a patient with ATLL shows
a classic cloverleaf or flower cell , which is highly
suggestive of the disease. (Courtesy E. Morgan, MD.)
Presentation
ATLL
HTLV-I myelopathy/tropical spastic paraparesis
Neurological manifestations
Encephalomyelitis, myelopathy, polymyositis,
inclusion body myositis
Peripheral neuropathy, autonomic neuropathy,
amyotrophic lateral sclerosis-like disease
Uveitis
Treatment
Malignancies
Chemotherapy, bone marrow transplantation
Antiviral approaches
Valproic acid with zidovudine
Prognosis
Opportunistic infections (e.g. strongyloidiasis) in
infected individuals usually lead to morbidity and
mortality
MICROBIOLOGY
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Epidemiology
10-20 million people infected worldwide
Prevalence in affected populations ranges from 1-30%
Japan: 10% of population, reasons unknown
Indigenous Australian population: 25%
Taiwan, parts of China, Iran, Pacific islands,
Caribbean: ~ 1%
10:1 ratio of HIV to HTLV-I in USA general
population
Intravenous drug users
30-50% of black population in specific geographic
sites in United states
2:1 ratio of HIV to HTLV-I
Transmission similar to human immunodeficiency
virus
Virus
Enveloped, positive-sense RNA retrovirus (80-100 nm)
8.5 kb with 9 proteins/polyproteins producing 16
functional products
Important viral oncoprotein is Tax (transcription
factor)
MICROSCOPIC PATHOLOGY
Histologic Features
ATLL
Diffuse infiltration of lymph nodes and other organs
(early lesions may show paracortical expansion)
Variable morphology, typically medium to large cells
with coarse chromatin and prominent nucleoli
HUMAN T-LYMPHOTROPIC VIRUS TYPE I INFECTION
Etiology
Virus tropism is for CD4(+) T cells (similar to HIV)
Clinical Issues
10-20 million people infected worldwide
Prevalence in affected populations ranges from 1-30%
Transmission similar to human immunodeficiency
virus
Adult T-cell leukemia/lymphoma
HTLV-I myelopathy/tropical spastic paraparesis
Key Facts
Microscopic Pathology
Lymphomatous involvement (ATLL)
Cutaneous involvement (ATLL)
Viral Infections: Viral Infections Requiring Ancillary Tests
Medium to large pleomorphic cells with prominent
nucleoli
Pautrier-like microabscesses (similar to mycosis
fungoides)
Large to medium-sized cells with glassy basophilic
cytoplasm, multilobed nuclei, coarse chromatin, and
prominent nucleoli
EBV(+), CD30(+), Reed-Sternberg-like cells may be
present in background
Eosinophilia may be present
Cutaneous
Pautrier-like microabscesses (similar to mycosis
fungoides)
Dermal and epidermotropic infiltrates that are
perivascular &/or extending as nodules into fat
Cytologic Features
Cloverleaf or flower-shaped nuclei in peripheral blood
ANCILLARY TESTS
Immunohistochemistry
ATLL cells are positive for CD2, CD3, CD4, CD5,
CD25, TCR-, FOXP3
ATLL cells are negative for CD7, CD8, CD10, CXCL13,
TCL1, ALK1
DIFFERENTIAL DIAGNOSIS
Other T-Cell Neoplasm/Condition
Mycosis fungoides/Sezary syndrome
Cerebriform cells in peripheral blood
May be impossible to distinguish on histological
basis
Anaplastic large cell lymphoma
Strong, uniform expression of CD30, bizarre
(horseshoe, embryoid) forms
Anaplastic variant of ATLL may show these
features
Perforin(+), granzyme-B(+), ALK1(+ variable)
Angioimmunoblastic T-cell lymphoma
Expanded follicular dendritic cell network, increased
vascularity
CD10(+), PD1(+), CXCL13(+)
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Epidemiological exposure to HTLV-I from endemic
country is helpful
Pathologic Interpretation Pearls
Cloverleaf- or flower-shaped nuclei in peripheral blood
is highly suggestive of ATLL
SELECTED REFERENCES
1. Hatanpaa KJ et al: Neuropathology of viral infections.
Handb Clin Neurol. 123:193-214, 2014
2. Qayyum S et al: Adult T-cell leukemia/lymphoma. Arch
Pathol Lab Med. 138(2):282-6, 2014
MICROSCOPIC FEATURES
(Left) Low-power view of a skin biopsy with ATLL demonstrates an infiltrate of tumor cells in the dermis and epidermis . (Center) High
magnification of the epidermis of a patient with ATLL in the skin shows a Pautrier abscess filled with tumor cells
the dermis of a patient with ATLL in the skin shows malignant tumor cells
. (Courtesy E. Morgan, MD.)
. (Right) High magnification of
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HUMAN IMMUNODEFICIENCY VIRUS INFECTION
Florid follicular hyperplasia with prominent follicles
is shown in a lymph node from a patient
Viral Infections: Viral Infections Requiring Ancillary Tests
with multifocal lymphadenopathy consistent with HIV
infection, confirmed by antibody testing.
TERMINOLOGY
Abbreviations
Human immunodeficiency virus (HIV)
Manifestations
Acquired immunodeficiency syndrome (AIDS)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Human immunodeficiency virus (HIV)-1 or -2
HIV-1 most common worldwide (B type)
HIV-2 more limited geography with less severe
disease in AIDS
CLINICAL ISSUES
Presentation
Primary HIV infection
50% of patients report fever, lethargy, fatigue, rash,
myalgias, and headache
Rash (uncommon)
Maculopapular rash, roseola, mucosal ulcerations
affecting face, neck, trunk (< 1 cm)
Mononucleosis-like illness (common)
Fever, pharyngitis, arthralgias, myalgias, and
lymphadenopathy without tonsillar involvement
Meningoencephalitis (rare)
Photophobia, neck stiffness, headaches, and
disordered consciousness with depression and
mood changes
Latent phase
Patient remains asymptomatic with variable viral
load and CD4 count
I
May present with persistent lymphadenopathy, HIV
encephalitis, or HIV-associated nephropathy
Acquired immunodeficiency syndrome
2
Medium magnification of a reactive follicle is shown in a
lymph node from a patient with HIV infection. Patients
with unexplained lymphadenopathy who demonstrate
this pattern need HIV testing.
Uncontrolled viral load, low CD4 count
Opportunistic infections
Laboratory Tests
HIV serological antibodies for primary diagnosis
Traditionally confirmed by Western blot
PCR for diagnosis (qualitative) or viral load
(quantitative) predicts long-term prognosis
CD4 count to stage immune system
Treatment
Highly active antiretroviral therapy (HAART) tailored
to virus genotype and viral load
Prognosis
With HAART therapy, excellent long-term prognosis
Accelerated aging occurs (HIV effect vs. HAART effect)
MICROBIOLOGY
Virus Characteristics
Icosahedral enveloped, encapsulated single-strand
RNA retrovirus
9,700 bp, 3 orf, produces polyproteins
Contains reverse transcriptase (DNA from RNA)
Contains tat/rev transcription factor (cross-activates
other viruses, e.g. HHV-8)
Culture
Phytohemagglutinin-stimulated peripheral blood
mononuclear cells from seronegative donors
MICROSCOPIC PATHOLOGY
Histologic Features
Persistent lymphadenopathy
Florid lymphoid hyperplasia of lymph nodes with
prominent germinal centers
HIV encephalitis
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HUMAN IMMUNODEFICIENCY VIRUS INFECTION
Clinical Issues
Primary HIV infection: 50% of patients report fever,
lethargy, fatigue, rash, myalgias, and headache
Latent phase: May present with persistent
lymphadenopathy
Acquired immunodeficiency syndrome:
Opportunistic infections
PCR for diagnosis (qualitative) or viral load
(quantitative) predicts long-term prognosis
Microscopic Pathology
Persistent lymphadenopathy: Florid lymphoid
hyperplasia of lymph nodes with prominent germinal
centers
HIV encephalitis: Microglial nodules in/around
vessels with giant cells, focal necrosis
Microglial nodules in/around vessels with giant
cells, focal necrosis
Giant cells are infected activated microglia, which
are positive for p24 antigen
HIV-associated nephropathy
Focal segmental glomerulosclerosis with segmental
and global collapse of capillaries, hypertrophy and
hyperplasia of podocytes, and tubulointerstitial
disease
Opportunistic infections
Wide range of organisms and patterns from no
inflammation to severe inflammatory responses
> 150 known infections/complications of HIV
infection
Tuberculosis
Mycobacterium avium complex
Cryptococcus
Polyomavirus (progressive multifocal
leukoencephalopathy)
Kaposi sarcoma
Pneumocystis jirovecii
Diffuse large B-cell lymphoma/EBV-related
lymphomas
Candidiasis
Herpes simplex
Herpes zoster
Toxoplasmosis
Cytomegalovirus
Cryptosporidiosis
Salmonella sepsis
Immune reconstitution syndrome
Unchecked replication and spread of an
opportunistic infection
Initiation of HAART therapy reconstitutes
immune response
Widespread immunological attack on infectious
agent leads to severe disease
Key Facts
HIV-associated nephropathy: Focal segmental
glomerulosclerosis with segmental and global
collapse of capillaries, hypertrophy and hyperplasia
of podocytes, and tubulointerstitial disease
Opportunistic infections: Wide range of organisms
and patterns from no inflammation to severe
inflammatory responses
Immune reconstitution syndrome: Unchecked
replication and spread of an opportunistic infection
at initiation of HAART therapy
Ancillary Tests
Immunohistochemistry: Antigen p24 staining can
confirm encephalitis
ANCILLARY TESTS
Immunohistochemistry
Antigen p24 staining can confirm encephalitis
DIFFERENTIAL DIAGNOSIS
Primary Infection
Syphilis (rash)
EBV mononucleosis, CMV mononucleosis-like disease
(mono)
Enteroviral meningitis (meningitis)
Latent-Phase Lymphadenopathy
Lymphoma/leukemia
Cat scratch disease
HIV-Associated Nephropathy
Pattern on histology is very similar to idiopathic
collapsing glomerulopathy and can be seen in
parvovirus B19 infection and treatment with
pamidronate
AIDS
Iatrogenic immunosuppression
Congenital immunodeficiencies
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Lack of universal testing requires due diligence when
histology suggests diagnosis
SELECTED REFERENCES
1. Berger JR: Progressive multifocal leukoencephalopathy.
2. Grill MF et al: Central nervous system HIV-1 infection.
Viral Infections: Viral Infections Requiring Ancillary Tests
Handb Clin Neurol. 123:357-76, 2014
Handb Clin Neurol. 123:487-505, 2014
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HUMAN IMMUNODEFICIENCY VIRUS INFECTION
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Microscopic Features
(Left) A section of brain
tissue from a patient with HIV
encephalitis demonstrates
erivascular inflammation
and microglial nodule
formation. (Right) A section of
brain tissue from a patient with
HIV encephalitis demonstrates
erivascular giant cells ,
which are the hallmark of the
disease.
Viral Infections: Viral Infections Requiring Ancillary Tests
(Left) An
immunohistochemical stain
for HIV p24 antigen shows the
iant cells of HIV encephalitis
to be diffusely positive for
the protein. (Right) A single
acid-fast bacilli within a
iant cell is shown from a case
of tuberculosis. Tuberculosis
affects both HIV-positive and
HIV-negative patients but has
higher mortality in the former.
(Left) A small bowel
biopsy demonstrates
cryptosporidiosis, which
causes watery diarrhea in
untreated HIV patients. Note
the lack of inflammation
and subtle intracytoplasmic
surface coccidian parasites .
(Right) A large cryptococcoma
caused by Cryptococcus
neoformans, which presented
as a large abdominal mass in
an undiagnosed HIV patient, is
shown with sheets of fungi
spaced by the mucoid capsule
and no inflammation. The
atient died within days of
surgery.
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HUMAN IMMUNODEFICIENCY VIRUS INFECTION
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Microscopic Features
(Left) Candida infections
(most commonly Candida
albicans
HIV-infected patients before
they have low CD4 counts or
other signs of clinical AIDS.
The appearance is typical
of other Candida infections,
although inflammation
may be limited. (Right)
Kaposi sarcoma caused
by human herpesvirus-8
(Kaposi sarcoma-associated
herpesvirus) demonstrates
typical slit-like spaces
filled with blood. The KSHV
virus is cross-activated by
the HIV tat/rev transcription
complex.
) can occur in
Viral Infections: Viral Infections Requiring Ancillary Tests
(Left) Cytomegalovirus is
a common reactivating
infection in patients with
untreated HIV, which
can affect any organ. As
seen here, there is no
inflammatory reaction
associated with the viral
inclusion . (Right)
Mycobacterial infections in
HIV patients may include
tuberculosis, the MAC
complex, or several other
rare pathogens including M.
ordonae and M. kansasii.
Unlike TB, organism burden
may be very high,
as seen here in non-TB
mycobacterial disease.
(Left) Diffuse large B-cell
lymphoma associated with
Epstein-Bar virus infection is
a common fatal complication
of untreated HIV infection,
although it may also occur
in patients on therapy.
Features are identical to
DLBCL occurring in other
hosts, except that EBV in
situ hybridization is more
often positive. (Right) A
Toxoplasma cyst
in the small bowel of an HIV
atient with clinical diarrhea,
mucosal distortion
no inflammation.
is seen
, and
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INFLUENZA VIRUS AND OTHER RESPIRATORY VIRUS INFECTIONS
Autopsy lung section from a fatal case of H1N1
influenza shows severe acute and organizing lung injury,
Viral Infections: Viral Infections Requiring Ancillary Tests
a nonspecific pattern requiring clinical, laboratory, or IHC
correlation for definitive diagnosis.
INFLUENZA VIRUS
Terminology
Synonyms: "The flu"
Etiology/Pathogenesis
Viral infections transmitted person to person via
respiratory droplets
Incubation period: 1-4 days
Infectious period: 1 day before until 5 days after onset
of symptoms
Hemagglutinin (HA) binds sialic acids on cell surface
causing viral uptake into host cells
Neuraminidase (NA) enzymatically removes sialic
acids, promoting viral release from infected cells
Antigenic drift: Production of new viral strains by
mutations in HA and NA genes
Antigenic shift: Development of new combinations of
HA and NA genes due to reassortment of viral genome
subunits; can result in pandemics
Microbiology
Orthomyxoviridae family: Derived from
"ortho" (straight) and "myxo" (mucus)
Influenza A: Infects humans, birds, and pigs
18 HA and 11 NA serotypes
Influenza B: Primarily infects humans
1 HA and 1 NA serotype
2 lineages (Victoria-like and Yamagata-like)
Influenza C: Infects humans and pigs
Hemagglutinin-esterase fusion (HEF) antigen
Viral features
Enveloped, single-strand RNA viruses
Spherical (100-200 nm diameter), with helical
nucleocapsid
14,000 nucleotide segmented genome (10 proteins)
Culture
I
Grows in several cell lines (e.g., Vero and MDCK)
Detectable by immunofluorescence after 4-8 days
2
Chest radiograph of a 61-year-old man with chronic
lymphocytic leukemia and an acute influenza infection
shows bilateral asymmetric patchy airspace and interstitial
opacities. (From DI2: Chest.)
Epidemiology
Seasonal influenza A and B
Worldwide: 3-5 million hospitalizations and
250,000-500,000 deaths per year
USA: 5-20% infected, 226,000 hospitalizations, and
21,600 deaths per year
Pandemic influenza A
H3N8 Russian influenza (1889): 1 million deaths
worldwide
H1N1 Spanish influenza (1918): 50 million deaths
worldwide (675,000 USA)
H3N2 Asian influenza (1957): 2 million deaths
worldwide (69,800 USA)
H3N2 Hong Kong influenza (1968): 1 million deaths
worldwide (33,800 USA)
H1N1 Swine flu (2009): 284,000 deaths worldwide
Avian influenza (H5)
Exposure to birds in Asia, with high mortality
No person-to-person transmission
Site
Upper and lower respiratory tract
Presentation
Abrupt onset of fever, myalgia, headache, malaise,
nonproductive cough, sore throat, and rhinitis
Laboratory Tests
Best samples: Nasopharyngeal or nasal swab, nasal
aspirate or wash (collect with 4 days of onset of
illness)
Rapid antigen assays ( 15 minutes ); 50-70%
sensitive and > 90% specific; no subtype information
Viral culture (3-10 days); essential for strain
determination and surveillance
Immunofluorescence, direct (DFA) or indirect (IFA)
fluorescent antibody staining (1-4 hours)
RT-PCR (1-6 hours)
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INFLUENZA VIRUS AND OTHER RESPIRATORY VIRUS INFECTIONS
Viral Infections: Viral Infections Requiring Ancillary Tests
Natural History
Self-limited infection that resolves after 3-7 days
(cough and malaise can last for > 2 weeks)
Complications include viral pneumonia or secondary
bacterial pneumonia, encephalopathy, transverse
myelitis, myositis, myocarditis, and pericarditis
Treatment
Primary prevention
Influenza vaccine: Recommended annually for all
persons > 6 months old
Contains HA antigen of 2 influenza A strains (i.e.,
H1N1 and H3N2) and 1 or 2 influenza B strains
(Victoria and Yamagata)
Updated yearly to match antigenically circulating
strains according to WHO predictions
Traditionally produced by egg-based methods;
cell-based and recombinant vaccines approved by
FDA in 2012 and 2013
Upon presentation with symptoms
Largely supportive care
M2 inhibitors: Amantadine, rimantadine
No longer used due to widespread resistance
Neuraminidase inhibitors: Oseltamivir, zanamivir
New antivirals targeting M2, neuraminidase,
hemagglutinin, RNA-dependent RNA polymerase,
and nucleoprotein are under development
Prognosis
Uncommonly fatal in immunocompetent (H1N1,
avian flu, influenza B in pediatric patients with
myocarditis)
Highest risk at age > 65, children, pregnant women,
and those with underlying health conditions (morbid
obesity, diabetes, underlying respiratory illness)
Imagining Findings
CXR: Normal in uncomplicated disease; diffuse
infiltrates, mottled densities, and consolidations in
severe disease
Macroscopic Findings
Fatal cases: Heavy, congested, edematous lungs;
mucosal surfaces of trachea and bronchi hyperemic
and swollen
Microscopic Findings
Seasonal influenza A and B: Diffuse, superficial,
necrotizing tracheobronchitis
Pandemic influenza A (H1N1): Inflammation of large
airways and diffuse alveolar damage and hemorrhage
No viral inclusions detectable by light microscopy
Ancillary Tests
Immunohistochemistry
Seasonal influenza A and B: Respiratory epithelial
cells in distal trachea and bronchi
Pandemic influenza A (H1N1): Upper and lower
airways
RT-PCR (fresh or formalin-fixed tissue) more sensitive
for prolonged illness or with extensive necrosis
Differential Diagnosis
Other infectious causes of tracheobronchitis and
pneumonia
Adenovirus, respiratory syncytial virus, rhinovirus,
parainfluenza viruses, coronaviruses, human
metapneumoviruses, Mycoplasma pneumoniae,
Legionella spp., etc.
Detection of specific pathogen by culture, direct
fluorescent antibody and rapid antigen assays,
serology, PCR, histochemical stains, or IHC
OTHER RESPIRATORY VIRUSES
Etiology/Pathogenesis
Viral infections transmitted person to person via
respiratory droplets
Human parainfluenza viruses (HPIVs)
Hemagglutinin-neuroaminidase-mediated
attachment and cell uptake
Incubation period: 1-7 days
Rhinovirus optimally replicates between 33-35 C
(intranasal temperature)
Virus binds ICAM-1/CD54 receptors on respiratory
epithelial cells
Incubation period 2-3 days
Microbiology
Human parainfluenza viruses
Paramyxoviridae family: Derived from
"para" (beyond) and "myxo" (mucus)
Viral features
Enveloped, single-strand RNA viruses
150-250 nm with helical capsid
15,000 nucleotide genome (6 proteins)
5 types (HPIV-1, HPIV-2, HPIV-3, HPIV-4a,
HPIV-4b)
Culture
Grows in primary monkey kidney (PMK) and LLCMK2 cells
Detection by hemadsorption with guinea pig
erythrocytes within 3-10 days
Rhinoviruses: Derived from "rhino" (nose)
Picornaviridae family: Derived from "pico" (small)
and "RNA"
Viral features
Nonenveloped, single-strand RNA viruses
Spherical, 30 nm with icosahedral capsid
7,200-8,500 nucleotide genomes (1 ORF)
3 species (A, B, C); > 100 different serotypes
Culture
Grows in human fetal embryonic lung fibroblast
cell lines, HeLa cells, and human embryonic
kidney cell lines
Detection of cytopathic effects after 2-6 days at
33-35 C
Epidemiology
Human parainfluenza viruses
Common in infants/children (antibodies by age 5)
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INFLUENZA VIRUS AND OTHER RESPIRATORY VIRUS INFECTIONS
41,000 hospital admissions per year in USA (2nd
highest after RSV); HPIV-1 and HPIV-2 peak in fall;
HPIV-3 peak in spring/summer
Rhinoviruses
30-50% of common cold (~ 20-33 million cases per
year in USA); most common in fall and spring
Site
Upper and lower respiratory tract
Presentation
Human parainfluenza viruses: Fever, rhinorrhea,
cough, croup/laryngotracheobronchitis (HPIV-1
and HPIV-2); bronchitis, bronchiolitis, pneumonia
(HPIV-3)
Rhinoviruses: Sneezing, coughing, rhinorrhea,
pharyngitis, nasal congestion, watery eyes, mild
headache, mild body aches
Laboratory Tests
Viral Infections: Viral Infections Requiring Ancillary Tests
Typically unnecessary for diagnosis
RT-PCR, direct viral antigen tests, viral culture,
serology (IgM or rise in IgG)
Natural History
Typically self-limited, resolves within 7-10 days
Treatment
Primary prevention
No FDA-approved vaccines available
Good hygiene with handwashing; avoidance of sick
individuals
Upon presentation with symptoms
No specific antiviral treatments available
Primarily symptomatic/supportive treatment; rest
and rehydration
Hospitalization for respiratory distress, stridor, or
severe dehydration
Prognosis
Mortality rare in immunocompetent
Imaging Findings
CXR: For evaluation of croup (classic steeple sign),
epiglottitis, or pneumonia
Macroscopic Findings
Human parainfluenza viruses: Heavy, congested,
hemorrhagic, and edematous lungs
Rhinoviruses: No prominent gross findings
Microscopic Findings
Human parainfluenza viruses: From mild
tracheobronchitis to interstitial pneumonitis with
mononuclear cell infiltrates, diffuse alveolar damage,
multinucleated giant cells with cytoplasmic inclusions
Rhinoviruses: Minimal damage to nasal epithelium,
mild inflammatory infiltrate (lymphocytes and
eosinophils), neutrophils abundant in nasal lavage
fluids
Ancillary Tests
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Immunohistochemistry
Human parainfluenza viruses: HPIV antigens
detectable in alveolar lining cells and giant cells
Rhinoviruses: Antigens detectable in nasal
epithelium
Electron microscopy
Human parainfluenza viruses: 150-300 nm
enveloped virions with helical nucleocapsid
Rhinoviruses: 30 nm nonenveloped virions with
icosahedral nucleocapsid
Differential Diagnosis
Other infectious causes of tracheobronchitis,
pneumonia, and giant cell pneumonia
Measles, influenza, adenoviruses, coxsackie
viruses, respiratory syncytial virus, human
metapneumovirus, varicella-zoster virus, herpes
simplex virus, henipaviruses, Chlamydia pneumoniae,
Mycoplasma pneumoniae, etc.
Detection of specific pathogen by culture, direct
fluorescent antibody and rapid antigen assays,
serology, PCR, histochemical stains, or IHC
Allergic rhinitis
Associated with specific allergens; may be seasonal
or perennial; improves with steroids and allergen
avoidance
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Sick-contact exposure, travel, immunization,
seasonality, and immunocompetency histories
essential
KEY POINTS
Etiology
Viral infections transmitted by respiratory droplets
Clinical Issues
Millions infected yearly with seasonal variations
Severity of symptoms ranges from sneezing and
rhinorrhea (rhinoviruses) to pneumonia and death
(pandemic influenza)
Annual vaccines recommended for influenza;
antivirals can decrease symptoms
Often diagnosed clinically, treated supportively/
symptomatically
Microscopic Pathology
Range from mild mucosal inflammatory infiltrate
(rhinoviruses) to diffuse alveolar damage (pandemic
influenza)
RT-PCR, viral culture, serology, IHC, and rapid
antibody/antigen tests useful when specific diagnosis
is needed
SELECTED REFERENCES
1. Szewczyk B et al: Introduction to molecular biology of
influenza a viruses. Acta Biochim Pol. 61(3):397-401, 2014
2. Kennedy JL et al: Pathogenesis of rhinovirus infection.
Curr Opin Virol. 2(3):287-93, 2012
3. Schomacker H et al: Pathogenesis of acute respiratory
illness caused by human parainfluenza viruses. Curr Opin
Virol. 2(3):294-9, 2012
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INFLUENZA VIRUS AND OTHER RESPIRATORY VIRUS INFECTIONS
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Gross, Radiologic, and Microscopic Features
Viral Infections: Viral Infections Requiring Ancillary Tests
(Left) Lungs from a fatal
case of H1N1 influenza
are large (3x upper limit
of normal weight) and
diffusely hemorrhagic.
(Right) Section from a fatal
case of H1N1 influenza
shows acute and organizing
lung injury consistent with
a diffuse alveolar damage
attern of injury with
intraalveolar hemorrhage
and hemosiderosis.
(Left) Section from a fatal
case of H1N1 influenza
exhibits a diffuse alveolar
damage pattern with hyaline
membrane formation
and increased collagen
within the alveolar walls.
(Right) Hyaline membrane
formation and increased
collagen within alveolar
walls are typical findings of
fatal pandemic influenza
infection.
(Left) Cavitating abscess
formation of at least
several weeks duration
is present in this section
of lung from a fatal case
of H1N1 influenza with
bronchopneumonia. (Right)
Lateral neck radiograph
of a young child with
croup (likely caused by
arainfluenza infection)
shows marked subglottic
airway narrowing
overdistension of the
hypopharynx , and a
normal-appearing epiglottis.
(From DI: Pediatrics.)
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