Hamman-Rich syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

Acute interstitial pneumonitis is a rare, and fulminant disease leading to acute respiratory failure and, or death. Acute interstitial pneumonitis is an entity of a group of Idiopathic interstitial lung diseases first described by two pathologists Hamman and Rich. The etiology is unknown (idiopathic). Acute interstitial pneumonitis occurs typically previously healthy individuals in the age group of 50 to 55years with out pre eexisting lung disease. It affects men and women equally. Acute interstitial pneumonitis shows the histopathologic appearance of diffuse alveolar damage. On gross examination, lungs appear firm, heavy and have a dark red or beefy appearance and show irregular areas of consolidation and fibrosis. On microscopic examination, acute interstitial pneumonitis shows bilateral, temporal uniformity of the diffuse alveolar damage, hyaline membrane deposition and extensive fibroblastic and myofibroblastic proliferation. Acute interstitial pneumonitis may be considered as an idiopathic cause of ARDS. Acute interstitial pneumonitis must be differentiated from other diseases that present with respiratory failure and show diffuse alveolar damage on histopathological examination. These include ARDS, acute eosinophilic pneumonitis, Infections, hypersensitivity pneumonitis, connective tissue diseases, and drug-induced lung toxicity. Patients with acute interstitial pneumonitis usually present with flu-like viral illness or upper respiratory tract infection, which progresses very rapidly to acute respiratory failure. Common symptoms include fatigue, headache, myalgia, cough, fever, and dyspnea. The acute onset of symptoms is characteristic of acute interstitial pneumonitis. Physical examination shows tachypnea, tachycardia, crackles, wheezing and signs of hypoxemia. Chest radiograph of patients with Acute interstitial pneumonitis shows bilateral airspace opacifications. Most of the patients with acute interstitial pneumonitis on HRCT will show bilateral ground-glass attenuation, traction bronchiectasis, airspace consolidation, architectural distortion. Bronchioalveolar lavage and surgical lung biopsy can be helpful in diagnosing other diseases that causing diffuse alveolar damage that present same as acute interstitial pneumonitis There is no effective treatment for acute interstitial pneumonitis, Management in general includes supportive therapy and administration of glucocorticosteroids and Immunosuppressive agents. Lung transplantation may be considered as an alternative treatment for patients with acute interstitial pneumonitis if the conventional therapy fails. Prognosis is very poor.

In 1935, Hamman and rich first described cases with rapidly progressing pulmonary fibrosis of unknown etiology. After that, the eponym, Hamman-Rich syndrome have been used to describe idiopathic pulmonary fibrosis. In 1975, Liebow came up with classification to distinguish between pulmonary fibrosis and idiopathic interstitial lung diseases. In 1986, Katzenstein coined the term acute interstitial pneumonitis. Further studies helped to differentiate acute interstitial pneumonitis from pulmonary fibrosis.

According to American Thoracic Society/European Respiratory Society (ATS/ERS) 2002 consensus, Acute interstitial pneumonitis is an entity of a group of Idiopathic interstitial lung diseases. The classification is based on clinical, radiological and histopathologic findings. The classification has been updated by ATS/ERS International multidisciplinary panel recently based on the literature review on idiopathic interstitial lung diseases published between 2000-2011.

Acute interstitial pneumonitis shows the histopathologic appearance of diffuse alveolar damage. On gross examination, lungs appear firm, heavy and have a dark red or beefy appearance and show irregular areas of consolidation and fibrosis. On microscopic examination, acute interstitial pneumonitis shows bilateral, temporal uniformity of the diffuse alveolar damage, hyaline membrane deposition and extensive fibroblastic and myofibroblastic proliferation.

There is no specific etiology (idiopathic), that is responsible for developing acute interstitial pneumonitis.

Acute interstitial pneumonitis must be differentiated from other diseases that present with respiratory failure and diffuse infiltrates on chest radiographs. Some of the differentials include ARDS, acute eosinophilic pneumonitis, Infections, hypersensitivity pneumonitis, connective tissue diseases, and drug-induced lung toxicity.

• The world wide incidence of acute interstitial pneumonitis is approximately 97 cases per 100,000 individuals. The prevalence of acute interstitial pneumonitis is not known.

• Acute interstitial pneumonitis occurs typically previously healthy individuals in the age group of 50 to 55years with out pre-existing lung disease.

• Acute interstitial pneumonitis affects men and women equally.

• In general there is no racial predilection to acute interstitial pneumonitis.

• There are no established risk factors associated with acute interstitial pneumonitis.

If left untreated, patients with acute interstitial pneumonitis have high fatality rate and die because of severe respiratory failure. Most of the survivors after initial hospitalization may develop recurrent disease or chronic lung fibrosis. Acute interstitial pneumonitis usually has a very poor prognosis.

• Abrupt onset of respiratory symptoms resulting in acute respiratory failure
• Chest radiographs show bilateral lung infiltrates
• The absence of an identifiable etiology
• Absence of predisposing condition
• Organising diffuse alveolar damage seen on histopathological examination

• Patients with acute interstitial pneumonitis usually present with flu-like viral illness or upper respiratory tract infection, which progresses very rapidly to acute respiratory failure. Common symptoms include fatigue, headache, myalgia, cough, fever, and dyspnea. The acute onset of symptoms is characteristic of acute interstitial pneumonitis.

• Patients with acute interstitial pneumonitis usually appear ill. Physical examination shows tachypnea, tachycardia, crackles, wheezing and signs of hypoxemia.

• There are no diagnostic laboratory findings associated with acute interstitial pneumonitis. However, routine laboratory tests may help in identifying alternative diagnoses rather than making a diagnosis of acute interstitial pneumonitis, include abnormal arterial blood gases, physiologic lung testing, complete blood count, and sputum examination, and microbiologic tests.

• Chest radiograph of patients with Acute interstitial pneumonitis shows bilateral airspace opacifications.
• Most of the patients with acute interstitial pneumonitis on HRCT will show bilateral ground-glass attenuation, traction bronchiectasis, airspace consolidation, architectural distortion. This pattern of abnormality is typically found in acute interstitial pneumonitis but it is not diagnostic.

• Bronchioalveolar lavage and surgical lung biopsy can be helpful in diagnosing other diseases that causing diffuse alveolar damage that present same as acute interstitial pneumonitis.

• There is no effective treatment for acute interstitial pneumonitis, Management in general includes supportive therapy and administration of glucocorticosteroids and Immunosuppressive agents

• Lung transplantation may be considered as an alternative treatment for patients with acute interstitial pneumonitis if the conventional therapy fails.

• There are no sufficient guidelines for the primary prevention of acute interstitial pneumonitis. However, preventing general triggering agents that leads to fibrotic changes in lungs including smoking cessation and vaccination against influenza may be helpful in preventing pulmonary fibrosis and other idiopathic fibrotic lung conditions

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

In 1935, Hamman and rich first described cases with rapidly progressing pulmonary fibrosis of unknown etiology. After that, the eponym, Hamman-Rich syndrome have been used to describe idiopathic pulmonary fibrosis. In 1975, Liebow came up with classification to distinguish between pulmonary fibrosis and idiopathic interstitial lung diseases. In 1986, Katzenstein used the term acute interstitial pneumonitis. Further studies helped to differentiate acute interstitial pneumonitis from pulmonary fibrosis.

The historical perspective of the acute interstitial pneumonitis is as follows:

• In 1935, the two pathologists Hamman and Rich have reported four cases of very rapidly progressing pulmonary fibrosis with identical histologic appearances.^[1]
• After this, the eponym, Hamman-Rich syndrome used to describe the cases of progressive pulmonary fibrosis of no identifiable etiology.
• After that Hamman-Rich syndrome used synonymously with idiopathic pulmonary fibrosis.
• In 1975, to avoid confusion between idiopathic pulmonary fibrosis and idiopathic interstitial lung diseases, Liebow proposed a classification.
  • Classification includes five distinct entities:
    • Usual interstitial pneumonia
    • Desquamative interstitial pneumonia
    • Bronchiolitis obliterans with interstitial pneumonia
    • Lymphoid interstitial pneumonia
    • Giant cell interstitial pneumonia.
  • He described more rapidly progressing pulmonary fibrotic diseases including Hamman-Rich syndrome under usual interstitial pneumonia.
• In 1986, eight cases of acute respiratory failure of unknown etiology, showing organizing diffuse alveolar damage on histopathological specimens were reported by Katzenstein.^[2]
  • They likened the disease to the acute interstitial fibrosis first reported by Hamman and Rich in 1935.
  • Then he proposed the term acute interstitial pneumonitis to differentiate from the acute respiratory distress syndrome, which has same pathology of organizing diffuse alveolar damage.
• Olson et al reviewed three of Hamman and Rich’s original cases. They confirmed the histopathologic lesion in those cases is diffuse alveolar damage. Those studies helped in establishing both acute interstitial pneumonitis and Hamman-Rich syndrome have same clinical and pathogical presentations and helped to distinguish pulmonary fibrosis from acute interstitial pneumonitis.
• In 2000, the American Thoracic Society and the European Respiratory Society international consensus published a statement stating acute interstitial pneumonitis is distinct from pulmonary fibrosis.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

According to American Thoracic Society/European Respiratory Society (ATS/ERS) 2002 consensus, Acute interstitial pneumonitis is an entity of a group of Idiopathic interstitial lung diseases. The classification is based on clinical, radiological and histopathologic findings. The classification has been updated by ATS/ERS International multidisciplinary panel recently based on the literature review on idiopathic interstitial lung diseases published between 2000-2011.

• According to American Thoracic Society/European Respiratory Society (ATS/ERS) 2002 consensus, Acute interstitial pneumonitis is a variant of a group of Idiopathic interstitial lung diseases.^[1][2]
• This classification divides Idiopathic interstitial pneumonias into 7 clinicopathological entities.
  • Idiopathic pulmonary fibrosis (IPF)
  • Nonspecific interstitial pneumonia (NSIP)
  • Respiratory bronchiolitis-associated interstitial lung disease
  • Respiratory bronchiolitis-associated lung disease/desquamative interstitial pneumonia
  • Cryptogenic organizing pneumonia
  • Acute interstitial pneumonia
  • Lymphocytic interstitial pneumonia (LIP)
• American Thoracic Society/European Respiratory Society (ATS/ERS) panel classification of Idiopathic interstitial lung diseases has been updated recently,including changes to previously described clinical entities, describing new clinical entities, and describing new histologic patterns using literature review between 2000-2011.^[3]
• Revised classification of American thoracic society/European respiratory society international multidisciplinary panel of Idiopathic interstitial pneumonias:
  • Major idiopathic interstitial pneumonias
    • Idiopathic pulmonary fibrosis
    • Idiopathic nonspecific interstitial pneumonia
    • Respiratory bronchiolitis–interstitial lung disease
    • Desquamative interstitial pneumonia
    • Cryptogenic organizing pneumonia
    • Acute interstitial pneumonia
  • Rare idiopathic interstitial pneumonias
    • Idiopathic lymphoid interstitial pneumonia
    • Idiopathic pleuroparenchymal fibroelastosis
  • Unclassifiable idiopathic interstitial pneumonia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

Acute interstitial pneumonitis shows the histopathologic appearance of diffuse alveolar damage. On gross examination, lungs appear firm, heavy and have a dark red or beefy appearance and show irregular areas of consolidation and fibrosis. On microscopic examination, acute interstitial pneumonitis shows bilateral, temporal uniformity of the diffuse alveolar damage, hyaline membrane deposition and extensive fibroblastic and myofibroblastic proliferation.

• The mechanism of initial injury to the pulmonary epithelium in acute interstitial pneumonitis is not known.
• Based on the findings of lung biopsy, the uniformity and extent of the injury, it is assumed that a single insult triggers the pathologic process.
• On microscopy, appearance of hyaline membrane remenats and organizing alveolar exudate may suggest that acute interstitial pnemonia progresses from the exudative stage of diffuse alveolar damage.
• Diffuse alveolar damage occurs in 3 stages.^[1][2]
  • Acute, exudative
  • Proliferative, organizing
  • Fibrotic
• The rapid and abrupt onset of a widespread injury pattern may be suggested as an initiating factor involving pulmonary endothelium. This is followed by damage to alveolar epithelium and cell death, that leads to release of mediating factors such as tumor necrosis factor alpha, interleukins and monocyte chemoattractant factor.
• Followed by the influx of neutrophils into the alveolar spaces and alveolar walls leads to further cellular damage, by the release of toxic oxygen free radicals and proteases.
• Neutrophils and other inflammatory cells can contribute to the progression of the epithelial cell injury and airspace exudation.
• The extent of epithelial injury and basement membrane damage may modulate the nature and extent of the subsequent fibroblastic response in acute interstitial pneumonitis.
• Following the acute phase, a stage of organization occurs.
  • The hyaline membranes are resorbed into the alveolar septa and overgrown by proliferating type II pneumocytes.
• In fibrotic phase, proliferation of fibroblasts and differentiation into myofibroblasts leads to the production of collagen, causes widening of the alveolar septa, and organization of the alveolar exudate.
• Collapse of alveolar wall and apposition, associated with reepithelization of the fibrotic exudate within the alveolar space may contribute to the severity and extent of the fibrotic process.

• Patients with acute interstitial pneumonitis, gross appearance of lungs is identical to the patients with ARDS.^[3]
• The gross appearance of lungs correlates with the stage of the diffuse alveolar damage.
  • In the early phase, the lungs are firm, boggy, and have a dark red or beefy appearance.
  • In later phases, the lungs are extremely heavy due to edema and show irregular areas of dense consolidation and fibrosis.
  • As the fibrosis progresses, cobblestoning of the pleural surface may occur.
  • Formation of peripheral cysts and honeycombing may suggest the possibility of underlying chronic fibrotic lung disease.

• On microscopic histopathological analysis, Acute interstitial pneumonitis will show following features:^[4][5]
  • Diffuse alveolar damage
  • Hyaline membrane formation
  • Interstitial fibrosis:
    • It is diffuse, bilateral, uniform temporally with extensive fibroblastic and myofibroblastic proliferation and relatively less collagen deposition.
    • The uniformity of the fibroblastic/myofibroblastic proliferation and prominent activity distinguish AIP from the other types of idiopathic interstitial pneumonia.
  • Type II pneumocyte hyperplasia with cytologic atypia and bronchiolar squamous metaplasia is present.
  • Thickening and distortion of alveolar septa caused by spindle cell proliferation.
  • Intraluminal polypoid plugs formation
  • Organizing thrombi in small and medium-sized arteries
  • Biopsies taken in the later course of the disease show:
    • Enlarged and remodeled airspaces that resemble honeycomb change of UIP (usual interstitial fibrosis), but extensive fibroblastic/ myofibroblastic proliferation and collagen deposition is still present within the walls of the alveoli.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

There is no specific etiology (idiopathic), that is responsible for developing acute interstitial pneumonitis.

• Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no known life-threatening causes of acute interstitial pneumonitis.

• There is no specific etiology (idiopathic), that is responsible for developing acute interstitial pneumonitis.
• Acute interstitial pneumonitis can be considered as an idiopathic cause of ARDS.^[1]
• On histopathological examination acute interstitial pneumonitis shows diffuse alveolar damage, therefore, the known causes of diffuse alveolar damage should be ruled out.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

Acute interstitial pneumonitis must be differentiated from other diseases that present with respiratory failure and diffuse infiltrates on chest radiographs. Some of the differntials include ARDS, acute eosinophilic pneumonitis, Infections, hypersensitivity pneumonitis, connective tissue diseases, and drug-induced lung toxicity.

• Acute interstitial pneumonitis present with acute onset of respiratory symptoms resulting in severe hypoxia and respiratory failure.
• Any acute lung disease presenting with respiratory failure and show diffuse infiltrates on radiograph should be included in the differential diagnosis of acute interstitial pneumonitis.^[1]
  • Acute respiratory distress syndrome
  • Acute eosinophilic pneumonia
  • Acute hypersensitivity pneumonitis
  • Acute cryptogenic organizing pneumonia
  • Congestive heart failure
  • Acute exacerbation of Idiopathic pulmonary fibrosis
  • Diffuse alveolar hemorrhage:
    • Vasculitis-induced:
      • Antiphospholipid antibody syndrome
      • Behcet’s syndrome
      • Goodpasture’s syndrome
      • Microscopic polyangiitis
      • Wegener’s granulomatosis
    • Bland hemorrhage
      • coagulopathy
      • idiopathic pulmonary hemosiderosis
      • Mitral stenosis
  • Drug toxicity
  • Infection
  • Radiation therapy
  • Noninfectious pulmonary complications of hematopoietic stem-cell or solid-organ transplantation
  • Inhalation/toxic exposure

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

The world wide incidence of acute interstitial pneumonitis is approximately 97 cases per 100,000 individuals. The prevalence of acute interstitial pneumonitis is not known. Acute interstitial pneumonitis affects men and women equally. Acute interstitial pneumonitis occur typically previously healthy individuals in the age group of 50 to 55years.

• The world wide incidence of acute interstitial pneumonitis is approximately 97 cases per 100,000 individuals.^[1][2]

• The prevalence of acute interstitial pneumonitis is not known.

• Case fatality rate is high approximately 27%-78%.^[1][3]
• The mean time from symptom onset to death was approximately 20 days – 6 months.

• Acute interstitial pneumonitis occur typically previously healthy individuals in the age group of 50 to 55years.^[1]

• In general there is no racial predilection to acute interstitial pneumonitis.

• Acute interstitial pneumonitis affects men and women equally.

• There is insufficient evidence to support the regional distribution of acute interstitial pneumonitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

There are no established risk factors associated with acute interstitial pneumonitis.

There is insufficient evidence to prove risk factors for the acute interstitial pneumonitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

If left untreated, patients with acute interstitial pneumonitis have high fatality rate and die because of severe respiratory failure. Most of the survivors after initial hospitalization may develop recurrent disease or chronic lung fibrosis. Acute interstitial pneumonitis usually has a very poor prognosis.

• Acute interstitial pneumonitis has an acute and severe onset, progresses very rapidly and have a high mortality rate. If left untreated, patients die because of respiratory failure. Survivors after initial hospitalization may develop recurrent disease or chronic lung fibrosis.^[1]

• Common complications of acute interstitial pneumonitis include:^[2]
  • Respiratory failure and its complications
    • Pulmonary emboli
    • Barotrauma
    • Pneumonia
    • Gastrointestinal hemorrhage
    • Renal failure
  • Progressive pulmonary fibrosis

• Prognosis of acute interstitial pneumonitis is poor.^[3][4]
• Most patients die because of acute respiratory failure or its complications.
• Mortality rate is very high, more than half of the patients die within 2 months. Patients who survive the initial hospitalization die within six months of presentation of disease.
• Recurrence of the disease and progression to chronic interstitial lung disease can occur among survivors.

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