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Synonym: hypersensitivity pneumonitis
In extrinsic allergic alveolitis there is diffuse, granulomatous inflammation of the lung parenchyma and airways in people who have been sensitised by repeated inhalation of organic antigens in dusts (eg, from dairy or grain products, animal dander and protein and water reservoir vapourisers).[1, 2]
There are acute, subacute and chronic forms. Acute and subacute forms cause a pneumonitis which can be recurrent. Chronic disease can cause fibrosis, emphysema and permanent lung damage.
The pathogenesis is thought to involve both cell-mediated and immune complex-mediated hypersensitivity reactions.There may also be a genetic predisposition. It has been suggested that a possible viral trigger may initiate a flare.
Implicated antigens include avian antigens, mammalian proteins, fungi and fungal spores, bacterial antigens and small-molecular-weight chemicals. However, the provoking antigen can sometimes be difficult to identify with certainty.
It can be associated with many occupations and hobbies. Examples are:
- Farmer's lung - one of the most common forms. Due to exposure to mouldy hay. The major antigen is Saccharopolyspora rectivirgula.
- Bird-fancier's lung - one of the most common forms. Due to exposure to avian proteins - eg, pigeons, parakeets.
- Cheese-worker's lung - exposure to cheese mould, Penicillium casei.
- Malt worker's lung - exposure to Aspergillus clavatus in mouldy malt.
- Hot tub lung - exposure to Mycobacterium avium in poorly-maintained hot tubs.
- Chemical worker's lung - trimellitic anhydride, diisocyanate and methylene diisocyanate act as the antigens during the manufacture of plastics, polyurethane foam and rubber.
- Mushroom worker's lung - exposure to thermophilic actinomycetes in mushroom compost.
- The annual incidence of interstitial lung diseases has been estimated as 30:100,000 with hypersensitivity pneumonitis accounting for fewer than 2% of these cases.
- There is a lack of consistent epidemiological data but most studies show prevalence of farmer's lung in exposed farmers to be estimated at between 0.5% and 3%.
- It is usually a disease of adults but bird fancier's lung can occasionally present in children.
- Pre-existing lung disease.
- Specific occupations (including farmers, cattle workers, ventilation system workers, vets, people working with grain and flour, those whose job involves working with chemicals).
- Bird keeping and other hobbies.
- Regular use of hot tubs.
- Symptoms usually start 4-8 hours after exposure to the sensitising antigen and resolve quickly, usually within days.
- There is a flu-like illness with fever, chest tightness, dry cough and dyspnoea. Associated symptoms include malaise, chills, headache, generalised aches and pains, anorexia and tiredness.
- Symptoms are directly related to level of exposure and low-level acute exposure may produce mild symptoms that last for just a few hours.
- Signs include fever, tachypnoea and bibasal fine inspiratory crackles. Wheeze is rare.
- In very severe cases, patients may develop life-threatening respiratory failure with cyanosis, respiratory distress at rest and high fever.
Subacute or intermittent form
- Symptoms tend to be less severe and more gradual in onset with a productive cough, dyspnoea, fatigue, anorexia and weight loss.
- There may be a history of repeated acute attacks.
- It can present as recurrent pneumonia.
- Signs are similar to above.
- Severe episodes can be life-threatening.
- After the exposure is removed it can take weeks or months for symptoms to resolve.
- In the chronic form there are often no systemic symptoms except weight loss and gradual diminution of exercise tolerance due to dyspnoea.
- If the source of the antigen is removed, there may only be partial improvement of symptoms.
- Cyanosis and clubbing may develop.
- Tachypnoea, obvious respiratory distress and inspiratory crackles over the lower lung fields may be present.
- Eventually there may be chronic hypoxaemia and pulmonary hypertension with right heart failure.
- There may also be acute exacerbations in those with chronic disease.[9, 10]
- Infection (bacterial, fungal, viral including tuberculosis).
- Connective tissue disorders causing interstitial lung disease.
- Pulmonary fibrosis (including idiopathic).
- Drug-induced interstitial lung disease.
- Good history-taking is essential to aid diagnosis. A high index of suspicion is needed.
- Sensitisation can occur after a period of exposure to the antigen, varying from weeks to years.
- Be alert to occupation, pets, hobbies and environmental factors in those who present with chronic cough and respiratory symptoms or acute symptoms with no obvious infectious trigger.
- Also remember that water damage to the patient's home or school may precipitate symptoms as well as the use of a hot tub, sauna or swimming pool.
- Blood tests: inflammatory markers may be raised but are nonspecific. There may be serum antibodies detectable in some patients but there are no detectable antibodies in many. The presence of antibodies is nonspecific, as they may also occur in those who have been exposed but have no disease.Despite the pitfalls of false positives and false negatives, analysis of antigen-specific IgG antibodies can be useful as supportive evidence for diagnosis. The antibody titre level may also be helpful.
- CXR: in the acute form this may be normal in some or show diffuse micronodular interstitial shadowing. In the subacute form, there may be micronodular or reticular opacities in the mid/upper lung fields. In the chronic form, there may be features of fibrosis with loss of lung volume.
- CT scanning: high-resolution CT is a good way to evaluate the stage of disease and usually shows typical changes.
- Lung function testing: this can help to determine the degree of respiratory impairment. Spirometry shows a restrictive defect in acute and subacute forms but there may be a mixed restrictive/obstructive picture in the chronic form. Oxygen saturation may be reduced with further desaturation on exercise. There may also be reduced capacity of the lungs to diffuse carbon monoxide.
- Inhalation challenge test (provocation testing): temperature, circulating neutrophil and lymphocytes, lung function and exercise tests are performed after inhaling the suspected allergen. This can produce symptoms and may aid diagnosis. However, its use is controversial because it may provoke clinically significant disease.
- Bronchoalveolar lavage: analysis of the lymphocyte count and CD4/CD8 cell ratio in bronchoalveolar lavage fluid may aid diagnosis. There is usually a lymphocytosis and the CD4/CD8 ratio is reduced to less than 1.
- Transbronchial or open lung biopsy: this may show characteristic histopathological features.
Possible diagnostic criteriaThe diagnosis of extrinsic allergic alveolitis often relies on histopathology. The following criteria have been identified in one study and shown to be good diagnostic predictors, the authors suggesting that this removes the need for invasive testing (eg, biopsy or bronchoalveolar lavage):
- Exposure to a known offending antigen.
- Positive precipitating antibodies to the offending antigen.
- Recurrent episodes of symptoms.
- Inspiratory crackles on physical examination.
- Symptoms occurring 4-8 hours after exposure.
- Weight loss.
- In acute severe cases with significant respiratory distress and/or the presence of cyanosis, consider immediate referral to hospital for further assessment.
- Supplemental oxygen should be given to treat hypoxaemia.
- In less severe acute cases, or in the chronic form, avoidance of exposure to the allergen, along with investigations to confirm or refute the diagnosis should be carried out, usually in conjunction with a respiratory specialist.
- Once the diagnosis is made it is important to avoid allergen exposure. This may require a change of job. Before such a drastic step, consultation with a respiratory consultant or specialist in occupational medicine may be prudent.
- In the acute form, simply avoiding further exposure will usually result in recovery without medication.
- Corticosteroids may be indicated for the treatment of severe acute and subacute forms and for chronic forms that are severe or progressive.However, steroids don't seem to alter the long-term outcome. Exposure to the offending antigen still needs to be avoided as well.
- In advanced chronic disease, pulmonary fibrosis can still progress and death can occur despite aggressive corticosteroid therapy.
- Treatment in chronic or residual disease is supportive.
These can include:
- Spontaneous pneumothorax.
- Pulmonary fibrosis.
- Respiratory insufficiency or failure.
- Cor pulmonale.
- Early recognition and control of exposure is key to outcome.
- In acute and subacute forms, most patients recover lung function completely when exposure to the antigen stops. However, this may take several years for subacute forms.
- Bird fancier's lung has a worse prognosis than farmer's lung.
- The chronic form may be progressive and irreversible and result in debilitating fibrotic lung disease with high mortality rates.
- Health and Safety measures at work, including wearing appropriate protective equipment and having adequate air filters and ventilation.
- Avoiding pastimes which provoke the illness.
- Adequate maintenance of hot tubs/indoor swimming pools, humidifiers, heating, ventilation and air-conditioning equipment.
Further reading and references
Morell F, Roger A, Reyes L, et al; Bird fancier's lung: a series of 86 patients. Medicine (Baltimore). 2008 Mar87(2):110-30.
Franzen D, Bloch KE; Something in the air. Lancet. 2011 Sep 10378(9795):1048.
Ito T, Sugino K, Satoh D, et al; Bird fancier's lung which developed in a pigeon breeder presenting organizing pneumonia. Intern Med. 201049(23):2605-8. Epub 2010 Dec 1.
Ismail T, McSharry C, Boyd G; Extrinsic allergic alveolitis. Respirology. 2006 May11(3):262-8.
Girard M, Israel-Assayag E, Cormier Y; Pathogenesis of hypersensitivity pneumonitis. Curr Opin Allergy Clin Immunol. 2004 Apr4(2):93-8.
Woda BA; Hypersensitivity pneumonitis: an immunopathology review. Arch Pathol Lab Med. 2008 Feb132(2):204-5.
Selman M; Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med. 2004 Sep25(3):531-47, vi.
Lacasse Y, Cormier Y; Hypersensitivity pneumonitis. Orphanet J Rare Dis. 2006 Jul 31:25.
Hypersensitivity pneumonitis; Haz-Map
Stauffer Ettlin M, Pache JC, Renevey F, et al; Bird breeder's disease: a rare diagnosis in young children. Eur J Pediatr. 2006 Jan165(1):55-61. Epub 2005 Nov 4.
Lacasse Y, Selman M, Costabel U, et al; Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003 Oct 15168(8):952-8. Epub 2003 Jul 3.
Miyazaki Y, Tateishi T, Akashi T, et al; Clinical predictors and histologic appearance of acute exacerbations in chronic hypersensitivity pneumonitis. Chest. 2008 Dec134(6):1265-70. Epub 2008 Aug 8.
Olson AL, Huie TJ, Groshong SD, et al; Acute exacerbations of fibrotic hypersensitivity pneumonitis: a case series. Chest. 2008 Oct134(4):844-50.
Mohr LC; Hypersensitivity pneumonitis. Curr Opin Pulm Med. 2004 Sep10(5):401-11.
McSharry C, Dye GM, Ismail T, et al; Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis. BMC Pulm Med. 2006 Jun 266:16.
Silva CI, Churg A, Muller NL; Hypersensitivity pneumonitis: spectrum of high-resolution CT and pathologic findings. AJR Am J Roentgenol. 2007 Feb188(2):334-44.
Baur X, Fischer A, Budnik LT; Spotlight on the diagnosis of extrinsic allergic alveolitis (hypersensitivity pneumonitis). J Occup Med Toxicol. 2015 Apr 2010:15. doi: 10.1186/s12995-015-0057-6. eCollection 2015.
Chan AL, Juarez MM, Leslie KO, et al; Bird fancier's lung: a state-of-the-art review. Clin Rev Allergy Immunol. 2012 Aug43(1-2):69-83. doi: 10.1007/s12016-011-8282-y.
Solaymani-Dodaran M, West J, Smith C, et al; Extrinsic allergic alveolitis: incidence and mortality in the general population. QJM. 2007 Apr100(4):233-7. Epub 2007 Feb 16.
Has anyone been diagnosed with pleuroparnchymal fibroelastosis (PPFE). Pulmonologist and radiologist think I might have it. Not much written on it - fairly new to the medical community, I believe....CherylH
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