Extrinsic allergic alveolotis (EAA), also known as hypersensitivity pneumonitis, results from the inhalation of an antigen in previously sensitized patients.
Presentation
Extrinsic allergic alveolitis presents with a variety of systemic and respiratory symptoms irrespective of the inciting antigen. The symptoms tend to occur about 4 to 12 hours after exposure to the offending agent [8].
Common symptoms are listed below:
- Fever
- Myalgia
- Sweating
- Headache
- Joint pain
- Flu like symptoms
Respiratory symptoms:
On the basis of the severity and the pattern of clinical symptoms, the disease is classified as:
- Acute progressive disease: The symptoms are very severe and progress after each exposure.
- Acute intermittent non-progressive disease: The symptoms are less severe and there are periods of remission.
- Chronic progressive disease: There are no acute episodes.
- Sub-clinical disease: Antibody response is present but the person is symptom-free.
Workup
The diagnosis of extrinsic allergic alveolitis is largely based on patient history which may give information about his/her occupation, hobbies and living environment.
In addition to this certain laboratory and radiological investigations help in confirming the diagnosis.
- Blood tests: Blood tests are used to detect antigen-specific IgG, leukocytosis, hypergammaglobulinaemia and rheumatoid factor [9].
- Chest radiograph: This is done to look for pulmonary infiltrates.
- CT scan: Findings on CT scan may include ground glass shadows and air trapping [10].
- Lung function: Lung function is evaluated to find out any restriction of lung volume, hypoxemia or airway obstruction.
- Lung biopsy: Diffuse interstitial inflammation, granulomas and fibrosis are probed for [11].
Treatment
The management of the disease consists of either complete cessation of exposure to the allergen or limiting the exposure by using respiratory protection masks and ensuring proper ventilation of the working environment. In patients with severe disease, changing of occupation or living environment may be required.
Medical therapy in hypersensitivity pneumonitis includes oral steroids. In acute progressive disease, 40 to 60mg oral prednisolone is administered daily. The dose may be tapered according to the condition of the patient.
The patients with chronic disease who do not respond to medical treatment may develop complications like pulmonary fibrosis. This may lead to cor pulmonale and death. The treatment of choice in such patients is lung transplantation.
Prognosis
The prognosis of patients with allergic alveolitis depends upon the severity of symptoms as well as avoidance of exposure to the predisposing antigens.
With limited exposure and adequate medical treatment, the symptoms can be effectively controlled and the quality of life of the patient is unaffected.
Rarely, complications like irreversible fibrosis and cor pulmonale can occur which may lead to death of the patient.
Etiology
The condition is caused by inhalation of a multitude of inciting agents including husks, wood, grain, dried urine of rodents, baggase, animal danders, bacteria, fungal spores and certain chemicals. These inhaled particles act as antigens and cause an immunological reaction in the alveoli of the susceptible individuals. The susceptibility is determined by the genetic differences among individuals.
The pigeon breeders with extrinsic allergic alveolitis have got increased expression of certain human leukocyte antigens; namely HLA-DRB1*1305, HLA-DRQB1*0501 and TNF-alpha(308) promoter. These cause high production of TNF-alpha (a pro-inflammatory cytokine).
Depending upon the causative antigen, extrinsic allergic alveolitis has been divided into many different types:
- Bird fancier’s lung: It is caused by avian proteins [1].
- Bagassosis: Bagassosis results due to thermophilic actinomycetes.
- Farmer’s lung: Aspergillus species, micropolyspora feani and thermophilic actinomycetes are responsible for Farmer’s lungs.
- Cheese-washer’s lung: Penicillum casei is the causal agent of Cheese-washer’s lung [2].
- Chemical worker’s lung: Chemicals such a toluene diisocyanate, trimellitic anhydride cause chemical worker’s lung.
- Coffee worker’s lung: Prolonged exposure to coffee beans proteins results in coffee worker’s lung.
- Detergent worker’s disease: Enzymes of bacillus subtilis cause detergent worker’s disease.
- Hot tub lung: Mycobacterium avium complex (mist from hot tubs).
- Humidifier’s lung: Micropolyspora faeni is responsible for humidifier’s lung.
- Malt worker’s lung: Malt worker’s lung is caused by aspergillus clavatus.
- Wood worker’s lung: Penicillum chrysogenum is the causal agent of wood worker’s lung.
- Animal handler’s lung: Handling of laboratory animals can result in animal handler’s lung.
- Rat handler’s lung: Rat serum proteins are responsible for rat handler’s lung.
Epidemiology
Extrinsic allergic alveolitis is a common condition affecting people who work in environments with high levels of organic dusts, molds or fungus.
There is no age, gender or ethnic predilection for this disease. It is more common in farmers and bird fanciers because they are more exposed to the causative antigens.
Even among the exposed, 10 to 40% of the individuals do not develop the symptoms of hypersensitivity pneumonitis. According to some studies, high attack rates have been documented in sporadic outbreaks only.
The annual incidence rate of the disease among farmers has been found to be 8 to 540 cases per 100,000 persons and 6000 to 21,000 cases per 100,000 persons among pigeon breeders. Prevalence of the disease varies by region, farming particles as well as climate. Reported prevalence among farmers has been 0.4 to 7%. In bird breeders, the prevalence is estimated to be 20 to 20,000 cases per 100,000 individuals at risk.
Pathophysiology
As the name indicates, this disease is an allergic reaction to continued exposure to certain antigens of external origin which leads to an exaggerated immune response.
The symptoms appear after 4 to 12 hours of exposure to the offending particle. The immune response appears to involve a combination of type III and type IV hypersensitivity reactions and is characterized by interstitial and alveolar inflammation as well as granuloma formation [3].
The immunopathogenesis of the disease consists of binding of the antigen to the IgG antibody to form immune complexes which get deposited in the alveoli and lung parenchyma and evoke an inflammatory reaction [4].
There are high titers of antigen specific IgG in the serum and bronchoalveolar lavage fluids of these patients. However, the presence of granulomas and lymphocytic infiltrates in the lungs suggests the role of delayed type hypersensitivity reaction as well. In acute disease, CD-4 lymphocytes are predominant while in case of chronic disease, CD-8 lymphocytes predominate [5]. There are also variable numbers of plasma cells in the bronchoalveolar lavage fluid [6].
The inflammatory response is characterized by a variety of pro-inflammatory and regulatory cytokines. Tumor necrosis factor alpha, interleukin-1 and interleukin-8 are the pro-inflammatory cytokines produced by alveolar macrophages. These are responsible for the symptoms like fever and neutrophilia [7].
The regulatory cytokines such as interlekin-12, interleukin-18 and interleukin-10 play a role in reducing the inflammation and granuloma formation.
The interplay of these pro-inflammatory and regulatory cytokines determines the clinical outcome of antigen exposure which in turn is determined by the genetic makeup of the individual.
Prevention
There are no guidelines for prevention of extrinsic allergic alveolitis.
Summary
Extrinsic allergic alveolotis (EAA), also known as hypersensitivity pneumonitis, is a group of respiratory disorders characterized by inflammation of the alveoli due to inhalation of certain substances like animal and vegetable dusts.
It may also be caused by exposure to fungi or bacteria in humidifiers, air-conditioning or heating systems. Certain chemicals like isocyanates and acid anhydrides may also lead to hypersensitivity pneumonitis. The subjects are exposed to the inciting agents mostly in their occupational environments.
The inhaled particles evoke a hypersensitivity response in the susceptible hosts over a period of months to years, causing a variety of respiratory as well as systemic symptoms like fever, myalgia, headache, cough, breathlessness and so on.
The condition is diagnosed on the basis of history of exposure to the antigen and the working environment of the patient.
Treatment of this disease mainly consists of avoiding the causative allergens and the use of anti-inflammatory drugs like corticosteroids. Depending upon the severity of the condition the patient may also need to switch his or her occupation.
Patient Information
Extrinsic allergic alveolitis is a common disease of the respiratory system. It is caused by inhalation of certain animal and vegetable dusts like husk, wood, grain, dust from bird feathers, bacteria and molds. These particles evoke an allergic response in the individuals with this disease.
Patients may be symptom free or they may present with cough, fever, breathlessness, headache, sweating etc.
The disease can be controlled by avoiding exposure to the causative agents and by taking medications to relieve the symptoms. It is not a life threatening illness but in rare cases it may progress to irreversible changes in the lungs.
References
- Radermecker M, Salmon J, Reginster A. [Pigeon breeder's disease: allergic extrinsic alveolitis of pigeon breeders]. Acta clinica Belgica. 1971;26(4):207-217.
- Galland C, Reynaud C, De Haller R, Polla BS, Leuenberger P. Cheese-washer's disease. A current stable form of extrinsic allergic alveolitis in a rural setting. Revue des maladies respiratoires. 1991;8(4):381-386.
- Mohr L. Hypersensitivity pneumonitis. Curr Opin Pulm Med. September 2004;10(5):401-411.
- Baena-Cagnani C, Baena-Cagnani CE. Immunopathological mechanisms involved in extrinsic allergic alveolitis. Allergologia et immunopathologia. Mar-Apr 1980;8(2):117-124.
- Desrues B, Delaval P, Genetet N, et al. T lymphocyte subsets in alveolar lavage and peripheral blood in sarcoidosis and extrinsic allergic alveoliti]. Pathologie-biologie. Dec 1987;35(10):1301-1308.
- Kaminskaia GO, Abdullaev R, Filippov VP. Biochemical characteristics of fluid and cells of bronchoalveolar washings in patients with extrinsic allergic alveolitis. Problemy tuberkuleza. 2002(8):26-30.
- Bousquet J, Gayraud JP, Michel FB. Physiopathology of extrinsic allergic alveolitis. Le Poumon et le coeur. 1978;34(2):157-169.
- Khomenko AG, Duma ZV, Ozerova LV, et al. The clinical characteristics of extrinsic allergic alveolitis in woodworkers. Vrachebnoe delo. Aug 1991(8):91-95.
- McSharry C, Banham SW, Lynch PP, Boyd G. Antibody measurement in extrinsic allergic alveolitis. European journal of respiratory diseases. May 1984;65(4):259-265.
- Ban CJ, Dai HP, Zhang S, Zhang L, Ye Q, Zhu M. [Chest high resolution CT features of extrinsic allergic alveolitis and its diagnostic value]. Zhonghua yi xue za zhi. Apr 27 2010;90(16):1105-1108.
- Diao XL, Jin ML, Dai HP, Li X, Wei P, Zhang YG. [Pathologic diagnosis and clinical analysis of chronic extrinsic allergic alveolitis]. Zhonghua bing li xue za zhi Chinese journal of pathology. Nov 2011;40(11):732-735.