Lung - nontumor
Other interstitial pneumonitis / fibrosis
Acute interstitial pneumonia

Author: Akira Yoshikawa, Junya Fukuoka, M.D., Ph.D. (see Authors page)
Editor: Andrey Bychkov, M.D., Ph.D.

Revised: 17 October 2017, last major update October 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed search: Acute interstitial pneumonia [title]

Cite this page: Yoshikawa, A., Fukuoka, J. Acute interstitial pneumonia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumoracuteinterstitialp.html. Accessed December 14th, 2017.
Definition / general
  • In 1935, Hamman and Rich first reported autopsy cases of initially healthy individuals who developed a rapidly progressive and fatal type of interstitial lung disease, which differed from other interstitial pneumonia clinically and pathologically (Trans Am Clin Climatol Assoc 1935;51:154)
  • Katzenstein et al. coined the term "acute interstitial pneumonia (AIP)" (Am J Surg Pathol 1986;10:256)
  • In the multidisciplinary classification of idiopathic interstitial pneumonias by American Thoracic Society / European Respiratory Society, acute interstitial pneumonia is categorized as "acute / subacute interstitial pneumonia" (Am J Respir Crit Care Med 2013;188:733)
Essential features
  • Rare and aggressive type of idiopathic interstitial pneumonia with diffuse alveolar damage (DAD), characterized by diffuse inflammation with hyaline membrane and fibroblastic proliferation
  • Acute interstitial pneumonia shares common features with acute respiratory distress syndrome (ARDS) clinically and morphologically
Terminology
  • Also called Hamman-Rich syndrome and idiopathic diffuse alveolar damage
ICD-10 coding
Epidemiology
  • Extremely rare (no conclusive epidemiological data available)
  • Mean age 50 years but can occur at any age (7 - 83 years) (Eur Respir J 2000;15:412)
  • No sex predilection
Sites
  • Bilateral lung, usually in all five lobes of the lung
Pathophysiology
  • Both endothelial and epithelial injury result in decreased integrity of the alveolar capillary membrane
  • Imbalance of proinflammatory and anti-inflammatory mediators
  • Neutrophils increase in alveoli and interstitium and release metabolites leading to lung injury
  • Alveolar epithelial cells may go through epithelial - mesenchymal transition to become myofibroblasts, resulting in interstitial organization and fibrosis (BMC Pulm Med 2014;14:67)
Etiology
  • No definite cause; no risk factors have been identified
Clinical features
  • Influenza-like illness, followed by progressive shortness of breath (Am J Surg Pathol 1986;10:256)
  • Vast majority of patients are previously healthy and lack history of lung disease
  • Many clinical characteristics of acute interstitial pneumonia are similar to acute respiratory distress syndrome (Chest 2003;124:554)
    • Acute interstitial pneumonia can progress to respiratory failure as profound as severe acute respiratory distress syndrome (PaO2/FIO2 ≤ 100 mm Hg) and almost all patients need mechanical ventilation and hospital care
    • Respiratory failure usually appears 1 - 3 weeks from the onset, later than acute respiratory distress syndrome (16.8 days vs. 2.2 days)
    • Multiple organ failure is less common in acute interstitial pneumonia
Diagnosis
Laboratory
  • Hypoxia
  • Increased serum ferritin, D dimer and C reactive protein
  • KL-6 may increase slightly
Radiology description
  • Heterogeneous bilateral ground glass opacity due to pulmonary edema
  • Chest radiograph
    • Ground glass opacity
    • Consolidation with air bronchogram
  • Chest CT
Radiology images

Images hosted on other servers:

Chest radiograph

Exudative phase on CT

Organizing phase on CT


Comparison on CT and histology

Prognostic factors
  • Most patients die within 2 months unless appropriate treatment is provided (Eur Respir J 2000;15:412)
  • High dose steroid therapy drastically improves the prognosis with long term survival of more than 80% (Chest 2006;129:753, Chest 2003;124:554)
  • Survivors may suffer recurrences or develop chronic lung injury
Case reports
Treatment
  • Oxygen therapy for respiratory failure
    • Mechanical ventilation with positive end expiratory pressure
  • High dose steroid pulse (Chest 2006;129:753)
  • Direct hemoperfusion using polymyxin B immobilized fiber column was recently found to effectively improve the prognosis of acute interstitial pneumonia patients (Ther Adv Respir Dis 2017;11:261)
Gross description
  • Dark blue lungs with hemorrhagic dots on pleural surface
  • Heavy and firm due to edema and fibrosis
  • Dilatation of alveolar ducts
Gross images

Images hosted on other servers:

Gross images of diffuse alveolar damage

Microscopic (histologic) description
  • Acute interstitial pneumonia shows diffuse alveolar damage, which is almost completely identical to acute respiratory distress syndrome / diffuse alveolar damage morphologically (Eur Respir J 2000;15:412)
  • Proliferative / organizing (subacute) phase of diffuse alveolar damage is most common in acute interstitial pneumonia but also exudative (acute) phase and fibrotic (chronic) phase can be seen
  • Exudative phase
    • Hyaline membranes in alveolar duct or sacs; scattered or not apparent, unlike in acute respiratory distress syndrome
    • Interstitial and intra-alveolar edema
    • Collapsed alveoli
    • Denudation and necrosis of type I pneumocytes
    • Hemorrhage, usually mild
  • Proliferative / organizing phase (Am J Surg Pathol 1986;10:256, Eur Respir J 2003;21:187)
    • Organizing pneumonia with / without remnants of hyaline membrane
    • Interstitial and intra-alveolar proliferation of fibroblasts / myofibroblasts
    • Lymphocytic infiltration; usually more prominent than in acute respiratory distress syndrome
    • Proliferation of type II pneumocytes with occasional cellular atypia
    • Endothelial injury and fibrinous thromboembolism in arterioles / arteries
  • Fibrosis phase
    • Diffuse collagenous fibrosis
    • Microscopic honeycomb-like change
    • Traction bronchiolectasis
    • Squamous metaplasia
    • Organized thrombus
    • Thickening of pleura with dilatation of lymphatic / blood vessels
Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Akira Yoshikawa:
Patient was an 88 year old man who was an ex smoker (59 pack years).
He was previously healthy but hospitalized for acute onset (8 days) of shortness of breath.
Negative history of lung disease, collagen vascular disease or exposure to causative antigens
for hypersensitivity pneumonitis. Biopsy is from S9.

Low power

Architectural destruction

Fibroblastic proliferation


Type II pneumocyte hyperplasia

Lymphocytic infiltration

Epithelial denudation

Dense fibrosis with smooth muscle hyperplasia



Images hosted on other servers:

Organizing phase

Organizing phase - fibroblastic proliferation

Exudative phase and organizing phase


Organizing phase - proliferation of fibroblasts and type II pneumocytes

Cytology description
Cytology images

Images hosted on other servers:

Atypical epithelial cells in BAL fluid

Positive stains
  • Elastica van Gieson (fiber staining) is helpful to evaluate architectural destruction of alveoli
Electron microscopy description
  • Proliferation of type II pneumocyte with cytoplasmic projection into alveolar septa, abnormally large lamellar bodies or denudation from basement membrane (Am J Surg Pathol 1986;10:256)
Differential diagnosis
Board review question #1
Which of the following findings is not required for the diagnosis of acute interstitial pneumonia?

  1. Absence of exposure to causative factors of respiratory failure
  2. Absence of prior history of lung disease
  3. Bilateral shadows on chest radiograph
  4. Diffuse alveolar damage on histology
  5. PaO2/FIO2 ≤ 300 mm Hg
Board review answer #1
E. PaO2/FIO2 ≤ 300 mm Hg is one of the diagnostic criteria of acute respiratory distress syndrome. Acute interstitial pneumonia can also cause the similar severe respiratory failure, however it is not a diagnostic requirement for acute interstitial pneumonia.