Hypersensitivity Pneumonitis: Symptoms, Types, Causes and Treatment

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a complex lung disease triggered by an abnormal immune response to environmental antigens. These antigens are typically inhaled organic or, less commonly, inorganic particles found in settings ranging from farms to homes and modern workplaces. Despite being relatively rare, HP poses significant diagnostic and management challenges due to its variable symptoms, diverse causes, and potential to progress to chronic, irreversible lung damage. This article provides a comprehensive, evidence-based overview of HP—exploring its symptoms, classification, causes, and available treatments.

Symptoms of Hypersensitivity Pneumonitis

Recognizing HP can be difficult, as its symptoms often resemble those of other lung diseases. However, understanding its typical presentations is key to timely diagnosis and management.

Symptom	Description	Frequency/Pattern	Sources
Dyspnea	Shortness of breath, often progressive	Common, acute or chronic	1 2 4 5
Cough	Typically dry, may be persistent	Common, all stages	1 2 4 5
Fever	Low-grade, may accompany acute exposures	Acute or subacute forms	3 4
Fatigue	General tiredness, malaise	Especially in acute phases	3 5
Weight loss	Unintentional, over weeks to months	More in chronic HP	3 5
Crackles	Inspiratory lung sounds on auscultation	More in chronic HP	5
Digital clubbing	Bulbous enlargement of fingers/toes	Advanced chronic HP	5
Cyanosis	Bluish discoloration of skin/lips	Severe, chronic HP	5

Table 1: Key Symptoms of Hypersensitivity Pneumonitis

Acute Versus Chronic Symptom Profiles

HP symptoms vary depending on the stage and duration of antigen exposure:

• Acute HP: Typically presents hours after intense exposure. Patients may experience fever, chills, malaise, cough, and shortness of breath. Symptoms resemble a flu-like illness and usually resolve within days if exposure ceases 3 4.
• Subacute HP: Develops after repeated, lower-level exposures. Presents as insidious onset of cough and dyspnea, often without fever. Fatigue and malaise may persist 3 4 12.
• Chronic HP: Due to prolonged, low-grade exposure. Symptoms progress slowly over months or years. Chronic cough, progressive dyspnea, weight loss, digital clubbing, and sometimes cyanosis are observed. Crackles are common on lung exam 4 5 7.

Symptom Triggers and Patterns

• Symptom onset is often related to environmental exposures—for example, handling birds, cleaning moldy areas, or exposure to certain workplace chemicals 1 11.
• Symptoms may improve on weekends or vacations, only to worsen upon return to the exposure source—a key diagnostic clue 13.
• In chronic HP, symptoms may become persistent and less obviously linked to exposure, complicating diagnosis 5 12.

Physical and Radiological Findings

• Physical exam may reveal inspiratory crackles, especially in chronic cases 5.
• Radiological findings include ground-glass opacities in acute/subacute HP, and reticulation, honeycombing, and traction bronchiectasis in chronic/fibrotic HP 4 5 8.

Types of Hypersensitivity Pneumonitis

HP is not a single disease but a spectrum, classified by clinical course, radiological findings, and, increasingly, by underlying pathology.

Type	Hallmark Features	Course/Prognosis	Sources
Acute HP	Sudden onset; flu-like symptoms; ground-glass CT	Good with exposure removal	2 4 8 18
Subacute HP	Insidious onset; cough, dyspnea; nodular CT	Variable	2 4 8 12
Chronic Non-fibrotic	Persistent symptoms; minimal fibrosis	May stabilize if treated	6 9 18
Chronic Fibrotic	Progressive dyspnea; fibrosis/honeycombing on CT	Poor; risk of lung failure	6 7 9 18

Table 2: Main Types of Hypersensitivity Pneumonitis

Clinical Classification: Acute, Subacute, and Chronic

Traditionally, HP has been categorized into:

• Acute HP: Rapid onset within hours of significant antigen exposure. Symptoms are intense but resolve with antigen avoidance 2 4 8.
• Subacute HP: Occurs with repeated, moderate exposures; symptoms less dramatic but more prolonged 2 4 8.
• Chronic HP: Develops after months or years of low-level exposure. Characterized by persistent cough, exertional dyspnea, and often progressive lung function decline 4 5 9.

Note: The distinction between “subacute” and “chronic” is increasingly blurred, and many experts now emphasize a two-group model: non-fibrotic (acute/subacute) and fibrotic (chronic with fibrosis) HP 6 9 18.

Radiological and Pathological Phenotypes

• Non-fibrotic HP: CT shows ground-glass opacities, centrilobular nodules, and air trapping. Histology reveals lymphocytic alveolitis, sometimes with poorly formed granulomas 1 8 18.
• Fibrotic HP: CT demonstrates reticulation, traction bronchiectasis, and honeycombing. There may be overlap with other interstitial lung diseases (ILDs) such as idiopathic pulmonary fibrosis 5 6 8 9.

Clinical Implications of Classification

• Non-fibrotic HP often responds well to exposure avoidance and short-term corticosteroids, with good prognosis 2 4 18.
• Fibrotic HP may progress despite treatment and is associated with higher mortality, especially in older individuals 5 7 9 18.

Causes of Hypersensitivity Pneumonitis

HP arises from an immune reaction to inhaled antigens, predominantly organic particles. Understanding the causes is crucial for both prevention and management.

Cause Category	Typical Examples	Settings/Exposure	Sources
Bird antigens	Pigeon, parakeet, chicken proteins	Pet birds, poultry farms	1 11 12
Mold/fungi	Aspergillus, Penicillium, household molds	Damp homes, hay, compost	1 11 13
Bacteria	Thermophilic actinomycetes, Mycobacteria	Farmer's lung, hot tubs	1 11 13
Plant proteins	Grains, mushrooms, coffee beans	Agriculture, food processing	1 10 13
Chemicals/metals	Isocyanates, metalworking fluids, cobalt	Factories, manufacturing	2 10 13
Unknown agents	Unidentified environmental exposures	Variable, often chronic cases	5 11

Table 3: Common Causes and Exposures in Hypersensitivity Pneumonitis

Most Frequent Offending Antigens

• Bird proteins: The leading cause in many settings. “Bird fancier’s lung” occurs in people who keep or work with birds 1 11 12.
• Molds and fungi: Exposure to moldy hay (farmer’s lung), compost, or water-damaged buildings is a common trigger 1 11 13.
• Bacterial antigens: Thermophilic actinomycetes in hay, or Mycobacterium avium complex in hot tubs (“hot tub lung”) 1 11 13.

Occupational and Environmental Exposures

• Farming: Hay, grain, and silage workers are at high risk due to exposure to spores and actinomycetes 1 11 13.
• Pet owners and breeders: Especially those with birds 1 11 12.
• Industrial exposures: Metalworking fluids, isocyanates (in plastics and paints), and other chemicals can trigger HP 2 10 13.
• Home environments: Moldy bathrooms, poorly ventilated homes, or water-damaged buildings can lead to HP 1 11 13.

Unidentified Exposures

• In up to 25% of HP cases, no specific antigen is identified, especially in chronic forms. These cases have a worse prognosis and may be more likely to progress 5 11.

Host and Environmental Risk Factors

• Not everyone exposed to these antigens develops HP; genetic predisposition, smoking status, and other environmental cofactors play roles 12 17 18.
• The “two-hit hypothesis” suggests that both exposure and an underlying susceptibility are required for disease 8 17.

Treatment of Hypersensitivity Pneumonitis

Effective management of HP hinges on early identification and removal of the offending antigen. Pharmacologic therapy is often necessary, especially in chronic or progressive cases.

Treatment Approach	Main Details	Indication/Stage	Sources
Antigen Avoidance	Remove/limit exposure to trigger	All cases; cornerstone	1 4 10 12
Corticosteroids	Prednisone, oral; short course in acute HP	Acute/subacute; some chronic	1 3 8 12
Immunosuppressants	Azathioprine, mycophenolate mofetil	Chronic/fibrotic HP	15 16 19
Antifibrotic Agents	Nintedanib, pirfenidone (investigational)	Progressive/fibrotic HP	9 18 17
Lung Transplantation	For end-stage, progressive disease	Advanced fibrotic HP	8 9 18

Table 4: Major Treatment Strategies in Hypersensitivity Pneumonitis

Antigen Avoidance

• Primary intervention for all HP patients.
• Removal from exposure can halt and, in early cases, reverse disease progression 1 4 10 12.
• For some, this may mean significant occupational or lifestyle changes, which can be challenging 13.

Pharmacologic Therapy

Corticosteroids

• Oral corticosteroids (prednisone) are commonly used to reduce inflammation, particularly in acute or subacute HP.
• They may hasten symptom resolution, but long-term efficacy, especially in chronic HP, remains unproven 3 8 12.
• Tapering and discontinuation are recommended as soon as possible to minimize side effects 12.

Immunosuppressive Agents

• Azathioprine and mycophenolate mofetil are increasingly used in chronic/fibrotic HP, particularly when corticosteroids are insufficient or cause side effects 15 16 19.
• These agents may help stabilize lung function and reduce adverse events compared to corticosteroids alone 15 16.
• Not all patients respond; bronchoalveolar lavage lymphocytosis may predict better response to azathioprine 19.

Antifibrotic Therapies

• Nintedanib and pirfenidone, used in idiopathic pulmonary fibrosis, are under investigation for fibrotic HP 9 17 18.
• May slow disease progression in patients with progressive fibrosis.

Lung Transplantation

• Reserved for patients with advanced, refractory fibrotic HP or respiratory failure 8 9 18.
• Outcomes are generally better than for idiopathic pulmonary fibrosis, but risks remain 9.

Supportive Care and Monitoring

• Supplemental oxygen, pulmonary rehabilitation, and treatment of comorbidities are important in advanced cases 8 12.
• Regular follow-up with pulmonary function tests and imaging is essential to monitor disease course and treatment response 6 12.

Multidisciplinary Approach

• Diagnosis and management require collaboration among pulmonologists, radiologists, occupational/environmental health specialists, and sometimes pathologists 6 10 12.

Conclusion

Hypersensitivity pneumonitis is a multifaceted syndrome with a wide variation in causes, symptoms, and outcomes. Timely recognition, accurate identification of the offending antigen, and appropriate management are critical to improving patient outcomes. As our understanding of HP evolves, so too do strategies for diagnosis and treatment.

Key Points:

• HP is triggered by immune reactions to inhaled antigens, most commonly bird proteins, molds, and certain workplace chemicals 1 11 13.
• Symptoms differ between acute (flu-like, rapid onset) and chronic (persistent cough, dyspnea, weight loss) forms 3 4 5.
• Chronic/fibrotic HP is associated with a worse prognosis, especially when the antigen is unidentified or exposure cannot be avoided 5 7 9.
• Mainstay of treatment is antigen avoidance; corticosteroids and immunosuppressants are often used in chronic or severe cases 1 8 15 16.
• Antifibrotic therapies and lung transplantation may be necessary in advanced or progressive disease 9 18.
• Multidisciplinary care and regular monitoring are essential for optimizing outcomes 6 10 12.

By increasing awareness and understanding of HP, both patients and healthcare providers can work towards earlier diagnosis, effective management, and, ultimately, better quality of life for those affected.