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Lung-nontumor

Infections

Adenovirus pneumonia


Reviewers: Elliot Weisenberg, M.D. (see Reviewers page)
Revised: 23 December 2011, last major update August 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

Definition
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● Lung disease caused by infection with adenovirus, a non-enveloped, lytic, double stranded DNA virus

Epidemiology
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● At least 51 serotypes of adenovirus have been associated with clinical syndromes; not well understood why specific sterotypes are associated with specific syndromes, but differences in mode of transmission and virus tropism are likely to play a role
● Seven species are known (groups A-G); respiratory disease is caused by groups C, E and some members of group B
● Infection is ubiquitous; most individuals have had several infections during childhood

Sites
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● In addition to lung, also occurs in the upper respiratory tract (tonsils, adenoids), liver, GI tract, CNS, heart, kidneys, urinary bladder, ear, eyes

Clinical features
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● Half of infections are subclinical
● Represent 5-10% of febrile illness in infants and young children
● Transmission is through respiratory droplets, fomites, or fecal-oral
● In children, causes 5% of upper respiratory tract infections and 10% of cases of pneumonia; adult infection is less common
● Can persist as a latent infection for years after primary disease; tonsils and adenoids are likely reservoirs
● Outbreaks among military recruits have caused epidemics of serious disease at military training centers
● Certain subgroups are associated with severe pneumonia, especially young children
● Virulent strains have led to fatalities in previously healthy young adults (Clin Infect Dis 2003;37:e142)
● Serious disease has occurred in immunocompromised hosts, especially patients with solid organ and hematopoietic stem cell transplants, although infection may be associated only with asymptomatic shedding
● Adenovirus infections are only rare causes of significant disease in AIDS patients
● When symptomatic, upper respiratory tract infection causes fever, sore throat, cough, hoarseness, rhinorrhea
● Disease may mimic tonsillitis with group A streptococcal infection, due to exudative pharyngitis and enlarged cervical lymph nodes
● Otitis media may occur children under age 1 year
● Upper respiratory tract infection may progress to involve lower respiratory tract with cough and shortness of breath; often with systemic symptoms of fever, headache, myalgias; abdominal pain may occur
● May cause a pertussis-like syndrome
● Chest X-ray: bilateral, patchy, ground-glass opacities consistent with viral pneumonia
● In hematopoietic stem cell transplants, the GI tract is more commonly affected than lungs; cold agglutinins are present in 20% of patients with adenovirus pneumonia
● In solid organ transplants, usually the transplanted organ affected is by adenovirus
● In lung transplant patients, disease usually occurs in early post-transplant period and is associated with graft failure, bronchiolitis obliterans, and often death
● Disease in transplant patients may be due to primary infection or reactivation
● Diagnosis: rountine tissue culture, PCR, serology, or antigen-specific assays; in tissue samples, use immunostains

Prognostic factors
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● In transplant patients, increasing viral load by PCR and greater immunosuppression increases the risk of serious disease
● Other risk factors are young patient age, graft vs. host disease, unrelated stem cell donor, T-cell depletion of graft, cord stem cell transplant, low T-cell counts post transplant, total body irradiation, use of anti-lymphocyte antibodies

Treatment
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● Only supportive care is known to be effective
● Some studies have shown benefit of ribavirin therapy, but this is not universal
● Immunotherapy is being investigated
● Appropriate hand hygiene can reduce transmission
● In the United States, military recruits formerly received vaccinations against some strains of adenovirus; production of this vaccine stopped, however, efforts to resume production are ongoing

Micro description
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● Epithelial cells contain smudged nuclei with brick-like, intranuclear inclusions; start as small, eosinophilic inclusions, then briefly appear as basophilic inclusions with a thin halo; then enlarge to obscure the nuclear membrane to take on the typical smudgy appearance
● Two patterns of disease are commonly encountered that may occur concurrently: diffuse alveolar damage like pattern with interstitial edema, mononuclear cell infiltrates and exudative fluid accumulation in alveoli with hyaline membranes; second pattern is necrosis of bronchi, bronchioles, and alveoli with neutrophilic and histiocytic infiltrates, with interstitial fibrosis and obliterative bronchiolitis as potential sequelae

Micro images
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Interstitial inflammation (no inclusions identifiable)

   
Various images


Adenovirus inclusions in lung from an infant chimpanzee

Positive stains
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● Adenovirus immunohistochemistry

EM description
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● 60-90 nm, icosahedral particles in crystalline array

Differential diagnosis
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● The diagnosis can be made by rountine tissue culture, PCR, serology, or antigen-specific assays
● In tissue samples, immunohistochemistry can confirm the diagnosis

Additional references
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Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases, 7th ed., 2010

End of Lung-nontumor > Infections > Adenovirus pneumonia


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