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:

Systemic symptoms:

• Fever
• Myalgia
• Sweating
• Headache
• Joint pain
• Flu like symptoms

Respiratory symptoms:

• Cough
• Wheeze
• Breathlessness
• Chest tightness

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.

• Fever

  In view of the increasing popularity of these devices, humidifier lung and humidifier fever should be considered in the differential diagnosis of patients with unexplained pulmonary or flu-like illnesses with fever. [ncbi.nlm.nih.gov]

  […] exposure; in the acute form, respiratory symptoms and fever start several hours after exposure to the dust; in the chronic form, there is eventual diffuse pulmonary fibrosis after exposure over several years. [medical-dictionary.thefreedictionary.com]

  This disease is also called hypersensitivity pneumonitis or humidifier fever. [onlinelibrary.wiley.com]

  fever Onset after exposure Gradual after 4-8h Immediate or Gradual after 3-8h late Physical findings Bibasil. crackles Expirat. wheezes None Chest X-ray Infiltrates/norm. [slideplayer.com]

• Weight Loss

  Chronic hypersensitivity pneumonitis is characterized by long-term progressive dyspnea, weight loss, cough, and fatigue. [amboss.com]

  loss exertional dyspnoea type 1 resp failure cor pulmonale steroid and antigen avoidance [brainscape.com]

  Patients can also present subacutely with recurrent pneumonia or chronically with exertional dyspnea, productive cough, and weight loss. [emedicine.medscape.com]

• Fatigue

  The subacute form is characterized by the insidious onset of productive cough, dyspnea, and fatigue over weeks to months. Chronic hypersensitivity pneumonitis is characterized by long-term progressive dyspnea, weight loss, cough, and fatigue. [amboss.com]

  Symptoms appear relatively suddenly and include: Fever Chills Fatigue Breathlessness Chest tightness Cough If the person is removed from the antigen exposure, the symptoms usually resolve over 24 to 48 hours. Recovery is often complete. [ucsfhealth.org]

  A 39-year-old man was hospitalized with a history of fatigue, dyspnoea and low grade fever which seemed to be related to his working environment. [ncbi.nlm.nih.gov]

  Jauhoastmasta sementti-ihottumaan.Työterveyslaitos, Helsinki 1997 6 EAA, symptoms flu-like illness cough high fever, chills dyspnea, chest tightness malaise, myalgia 4-8 hours after exposure chronic disease: dyspnea in strain, sputum production, fatigue [slideplayer.com]

  Jauhoastmasta sementti-ihottumaan.Työterveyslaitos, Helsinki 1997 6 EAA, symptoms flu-like illness cough high fever, chills dyspnea, chest tightness malaise, myalgia4-8 hours after exposure chronic disease dyspnea in strain, sputum production, fatigue [powershow.com]

• Chills

  Symptoms appear relatively suddenly and include: Fever Chills Fatigue Breathlessness Chest tightness Cough If the person is removed from the antigen exposure, the symptoms usually resolve over 24 to 48 hours. Recovery is often complete. [ucsfhealth.org]

  […] people exposed to birds Age Usually in adults Gender No predilection for any particular gender Ethnicity No predilection for any particular ethnic group Site Lung without predilection for specific side or lung segment Presentation Cough Dyspnea Fever Chills [basicmedicalkey.com]

  Three to six hours after seven of the eight challenges the patients showed two or more of the following symptoms and signs: chills, fever, dry cough, dyspnoea, and inspiratory crepitant râles. [onlinelibrary.wiley.com]

  People may develop fever, cough, chills, and shortness of breath within 4 to 8 hours of re-exposure to substances to which they are sensitized. [msdmanuals.com]

• Malaise

  A 13-year-old boy suffering from celiac disease (CD) developed shortness of breath at exercise and episodes of malaise, fever and acute dyspnea following contact with pigeons. [ncbi.nlm.nih.gov]

  […] birds Age Usually in adults Gender No predilection for any particular gender Ethnicity No predilection for any particular ethnic group Site Lung without predilection for specific side or lung segment Presentation Cough Dyspnea Fever Chills Wheezing Malaise [basicmedicalkey.com]

  - delayed hypersensitivity reaction which maybe immune complex ( III ) or cell mediated ( IV ) - eg: farmer's lung (Micropolyspora faeni), bird fancier's lung, maltworker's lung, humidifier fever - typically fever, malaise, cough and shortness of breath [mrcpart1revision.blogspot.com]

  Headache, bibasilar crackles, inspiratory crackles, and malaise develop within 4-6 hours after exposure and may clear within 24 hours after removing the offending substance. [visualdx.com]

  Hot tub lung Humidifier lung Diagnostic Criteria Clinical May present as acute, subacute or chronic disease Acute Usually follows 2-9 hours after a heavy exposure Patient must be presensitized (frequently unknowingly) Flu-like symptoms Fever, chills, malaise [surgpathcriteria.stanford.edu]

• Cough

  References:[4][6] Pathology Granulomatous inflammation with lymphocytes and polynuclear giant cells References:[3][4] Differential diagnoses See differential diagnosis of acute cough. See differential diagnosis of chronic cough. [amboss.com]

  A case of hot tub lung in a 48-year-old woman with dyspnea and dry cough. Organizing pneumonia in hot tub lung is shown. Two fibroblast plugs (arrowheads) are present within airspaces. [emedicine.medscape.com]

  Patients with chronic HP often describe chronic symptoms, such as shortness of breath or cough, that have gotten worse. [ucsfhealth.org]

  A 65-yr-old female developed cough, fever and dyspnoea following repeated exposure to a home ultrasonic humidifier. High-resolution computed tomography showed ground-glass opacity in both lung fields. [ncbi.nlm.nih.gov]

  The chronic disease usually has a higher morbidity; in most instances, the signs are weight loss, poor production, and persistent coughing. [merckvetmanual.com]

• Dyspnea

  A case of hot tub lung in a 48-year-old woman with dyspnea and dry cough. Organizing pneumonia in hot tub lung is shown. Two fibroblast plugs (arrowheads) are present within airspaces. [emedicine.medscape.com]

  The subacute form is characterized by the insidious onset of productive cough, dyspnea, and fatigue over weeks to months. Chronic hypersensitivity pneumonitis is characterized by long-term progressive dyspnea, weight loss, cough, and fatigue. [amboss.com]

  Jauhoastmasta sementti-ihottumaan.Työterveyslaitos, Helsinki 1997 6 EAA, symptoms flu-like illness cough high fever, chills dyspnea, chest tightness malaise, myalgia 4-8 hours after exposure chronic disease: dyspnea in strain, sputum production, fatigue [slideplayer.com]

  Jauhoastmasta sementti-ihottumaan.Työterveyslaitos, Helsinki 1997 6 EAA, symptoms flu-like illness cough high fever, chills dyspnea, chest tightness malaise, myalgia4-8 hours after exposure chronic disease dyspnea in strain, sputum production, fatigue [powershow.com]

  A 13-year-old boy suffering from celiac disease (CD) developed shortness of breath at exercise and episodes of malaise, fever and acute dyspnea following contact with pigeons. [ncbi.nlm.nih.gov]

• Dry Cough

  A case of hot tub lung in a 48-year-old woman with dyspnea and dry cough. Organizing pneumonia in hot tub lung is shown. Two fibroblast plugs (arrowheads) are present within airspaces. [emedicine.medscape.com]

  A 34 year old sawmill maintenance engineer developed a dry cough that was associated with widespread wheezes and crackles in his lungs. His symptoms worsened, with work related lethargy, fever, and breathlessness, and the loss of a stone in weight. [ncbi.nlm.nih.gov]

  cough SOB dyspnoea crackles coarse end inspiratory upper zones weight loss exertional dyspnoea type 1 resp failure cor pulmonale steroid and antigen avoidance [brainscape.com]

  Three to six hours after seven of the eight challenges the patients showed two or more of the following symptoms and signs: chills, fever, dry cough, dyspnoea, and inspiratory crepitant râles. [onlinelibrary.wiley.com]

  Clinically, an acute reaction occurs 4-6 hours post exposure and manifests as fever, rigors, dry cough, dyspnoea and myalgia. Auscultation of the lungs might reveal crackles but no wheeze. [mrcpandme.blogspot.com]

• Rales

  Your provider may hear abnormal lung sounds called crackles (rales) when listening to your chest with a stethoscope. Lung changes due to chronic hypersensitivity pneumonitis may be seen on a chest x-ray. [nlm.nih.gov]

  […] fine crackles upon auscultation Symptoms subside after 12 hours to several days (in the absence of additional exposure) Chronic (months after continuous exposure) Insidious onset of fatigue, productive cough, progressive dyspnea, cyanosis Bilateral rales [amboss.com]

  Crepitant rales can be elicited in some patients. Pulmonary function tests generally reveal a restrictive defect in early disease and a restrictive, obstructive, or mixed defect in late disease. [emedicine.medscape.com]

• Productive Cough

  The subacute form is characterized by the insidious onset of productive cough, dyspnea, and fatigue over weeks to months. Chronic hypersensitivity pneumonitis is characterized by long-term progressive dyspnea, weight loss, cough, and fatigue. [amboss.com]

  It can present as an acute illness with flu-like symptoms, subacute with repeated episodes of pneumonia, or chronic with dyspnea and productive cough. [ebi.ac.uk]

  Most affected patients present acutely with flulike illness with cough. Patients can also present subacutely with recurrent pneumonia or chronically with exertional dyspnea, productive cough, and weight loss. [emedicine.medscape.com]

  Abstract We report a case of subacute extrinsic allergic alveolitis due to occupational exposure to Penicillium spores in a 43-years old female working in a salami factory that developed a dry cough that gradually evolved to productive cough, shortness [content.sciendo.com]

• Cyanosis

  […] without wheezing Diffuse fine crackles upon auscultation Symptoms subside after 12 hours to several days (in the absence of additional exposure) Chronic (months after continuous exposure) Insidious onset of fatigue, productive cough, progressive dyspnea, cyanosis [amboss.com]

  These may involve more severe symptoms including fever, crackling sounds during breathing (rales), breathing difficulty, bluish appearance of the skin (cyanosis), and possibly, expectoration of blood 3. [rarediseases.org]

  EAA, symptoms flu-like illness cough high fever, chills dyspnea, chest tightness malaise, myalgia 4-8 hours after exposure chronic disease: dyspnea in strain, sputum production, fatigue, anorexia, weight loss 7 EAA, clinical findings Status dyspnea, cyanosis [slideplayer.com]

  6 EAA, symptoms flu-like illness cough high fever, chills dyspnea, chest tightness malaise, myalgia4-8 hours after exposure chronic disease dyspnea in strain, sputum production, fatigue, anorexia, weight loss 7 EAA, clinical findings Status dyspnea, cyanosis [powershow.com]

  People with more advanced ILD may have: Abnormal enlargement of the base of the fingernails (clubbing) Blue color of the lips, skin, or fingernails due to low blood oxygen levels (cyanosis) Symptoms of the other diseases such as arthritis or trouble swallowing [medlineplus.gov]

• Tachycardia

  She had a low-grade fever together with evidence of sinus tachycardia, tachypnoea and bibasilar fine crackles. A chest radiograph revealed an increase in lung density predominantly on the left lower fields. [erj.ersjournals.com]

• Chest Pain

  Extrinsic allergic alveolitis manifests acutely with sudden-onset chest pain, cough, dyspnea, and fever following exposure to antigens. [visualdx.com]

• Lethargy

  His symptoms worsened, with work related lethargy, fever, and breathlessness, and the loss of a stone in weight. At that time, while still at work, he had a neutrophil leucocytosis and increased concentration of gamma globulins. [ncbi.nlm.nih.gov]

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].

• Pulmonary Infiltrate

  A 22-year-old woman was admitted with symptoms of dyspnea and fever with pulmonary infiltrates noted on her chest X-ray study. [ncbi.nlm.nih.gov]

  Asthma with Pulmonary Infiltrates and EosinophiliaIt has been recognized for many years that some patients suffered from recurrent illnesses characterized by changing pulmonary infiltrates and marked eosinophilia, at times associated with asthma. [nejm.org]

  Página 54 - Ward HN: Pulmonary infiltrates associated with leukoagglutinin transfusion reactions. Ann Intern Med 73:689-694. 1970. 234. Thompson JSA. [books.google.es]

  DIFFERENTIAL DIAGNOSIS Clinical Diagnosis Histologic Pattern Duration of Illness Radiological findings HRCT Prognosis Acute respiratory distress syndrome Diffuse alveolar damage Acute 1 – 2 weeks • Diffuse pulmonary infiltrate • Ground-glass opacities [slideshare.net]

• Lung Function Testing Abnormal

  They had abnormal lung function tests, abnormal chest radiographs and symptoms of lung disease such as breathlessness, cough, wheeze, fatigue and fever. [bc-legal.co.uk]

• HLA-DR2

  An over-representation of human leucocyte antigen (HLA)-DR2 (15) was detected, particularly among patients with farmer's lung. An increased selected T-cell receptor V gene usage may follow specific interactions between T-cells and antigens. [ncbi.nlm.nih.gov]

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.

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.

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.

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.

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.

There are no guidelines for prevention of extrinsic allergic alveolitis.

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.

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.

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3. Mohr L. Hypersensitivity pneumonitis. Curr Opin Pulm Med. September 2004;10(5):401-411.
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5. 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.
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