Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis) : Causes, Symptoms & Treatment

Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis) : Causes, Symptoms, Diagnosis, Treatment & Prevention


  • Hypersensitivity pneumonitis (HP) (extrinsic allergic alveolitis) is a pulmonary disease that occurs due to inhalational exposure to a variety of antigens leading to an inflammatory response of the alveoli and small airways.
  • Systemic manifestations such as fever and fatigue can accompany respiratory symptoms. Although sensitization to an inhaled antigen as manifested by specific circulating IgG antibodies is necessary for the development of HP, sensitization alone is not sufficient as a defining characteristic, because many sensitized
    individuals do not develop HP.
  • The incidence and prevalence of HP are variable, depending on geography, occupation, avocation, and
    environment of the cohort being studied. As yet unexplained is the decreased risk of developing HP in smokers.

Causes (Offending Antigens)

HP can be caused by any of a large list of potential offending inhaled antigens. The various antigens and environmental conditions described to be associated with HP give rise to an expansive list of monikers given to specific forms of HP.

  • Antigens derived from fungal, bacterial, mycobacterial, bird-derived, and chemical sources have all been implicated in causing HP.
  • Potential offending antigens include thermophilic actinomycetes or Aspergillus species.


The pathophysiology of HP has not been characterized in depth on an immunologic level, although it has been established that Hypersensitivity pneumonitis is an immune-mediated condition that occurs in response to inhaled antigens that are small enough to deposit in distal airways and alveoli.

  • From a lymphocyte perspective, HP has been categorized as a condition with a TH1 inflammatory pattern.
  • However, emerging evidence suggests that TH17 lymphocyte subsets may be involved in the pathogenesis of the disease as well.
  • Although the presence of precipitating IgG antibodies against specific antigens in HP suggests a prominent role for adaptive immunity in the pathophysiology of HP, innate immune mechanisms may also make an important contribution.
    This is highlighted by the observation that Toll-like receptors and downstream signaling proteins such as MyD88 are activated in HP.
  • Although no clear genetic basis for HP has been established, in specific cohorts, polymorphisms in genes involved in antigen processing and presentation, including TAP1 and major histocompatibility complex type II, have been observed.

Clinical Symptoms

Given the heterogeneity among patients, variability in offending antigens, and differences in the intensity and duration of exposure to antigen, the presentation of Hypersensitivity pneumonitis is accordingly variable.
Although these categories are not fully satisfactory in capturing this variability, Hypersensitivity pneumonitis has been traditionally categorized as having acute, subacute, and chronic forms.

  • Acute HP usually manifests itself 4–8 h following exposure to the inciting antigen, often intense in nature. Systemic symptoms, including fevers, chills, and malaise, are prominent and are accompanied by dyspnea. Symptoms resolve within hours to days if no further exposure to the offending antigen occurs.
  • In subacute HP resulting from ongoing antigen exposure, the onset of respiratory and systemic symptoms is typically more gradual over the course of weeks. A similar presentation may occur as a culmination of intermittent episodes of acute HP. Although respiratory impairment may be quite severe, antigen avoidance generally results in resolution of the symptoms, although with a slower time course, on the order of weeks to months, than that seen with acute HP.
  • Chronic HP can present with an even more gradual onset of symptoms than subacute HP, with progressive dyspnea, cough, fatigue, weight loss, and clubbing of the digits. The insidious onset of symptoms and frequent lack of an anteceding episode of acute HP make diagnosing chronic HP a challenge. Unlike with the other
    forms of HP, there can be an irreversible component to the respiratory impairment that is not responsive to removal of the responsible antigen from the patient’s environment.

The disease progression to hypoxemic respiratory failure can mirror that seen in idiopathic pulmonary fibrosis (IPF). Fibrotic lung disease is a potential feature of chronic HP due to exposure to bird antigens, whereas an emphysematous phenotype may be seen in farmer’s lung.


Although there is no set of universally accepted criteria for arriving at a diagnosis of Hypersensitivity pneumonitis, diagnosis depends foremost on establishing a history of exposure to an offending antigen that correlates with respiratory and systemic symptoms.
A careful occupational and home exposure history should be taken and may be supplemented if necessary by a clinician visit to the work or home environment.
Specific inquiries will be influenced by geography and the occupation of the patient.
When HP is suspected by history, the additional workup is aimed at establishing an immunologic and physiologic response to inhalational antigen exposure with chest imaging, pulmonary function testing, serologic studies, bronchoscopy, and, on occasion, lung biopsy.
Clinical Prediction Rule : Although not meant as a set of validated diagnostic criteria, a clinical prediction rule for predicting the presence of HP has been published by the HP Study Group. They identified six statistically significant predictors for HP, the strongest of which was exposure to an antigen known to cause HP. Other predictive criteria were the presence of serum precipitins, recurrent symptoms, symptoms occurring 4–8 h after antigen exposure, crackles on inspiration, and weight loss.

Differential Diagnosis

Differentiating HP from other conditions that cause a similar constellation of respiratory and systemic symptoms requires an increased index of suspicion based on obtaining a history of possible exposure to an offending antigen.
Presentations of acute or subacute HP can be mistaken for respiratory infection.


The mainstay of treatment for Hypersensitivity pneumonitis is antigen avoidance.
A careful exposure history must be obtained to attempt to identify the potential offending antigen and to identify the location where a patient is exposed. Once a potential antigen and location are identified, efforts should be made to modify the environment to minimize patient exposure. This may be accomplished with measures such
as removal of birds, removal of molds, and improved ventilation.
Because acute HP is generally a self-limited disease after a discrete exposure to an offending antigen, pharmacologic therapy is generally not necessary.
However, in so-called subacute and chronic forms of the disease, there is a role for glucocorticoid therapy. In patients with particularly severe symptoms as a result of subacute HP, antigen avoidance may be insufficient after establishing the diagnosis.

  • Although glucocorticoids do not change the long-term outcome in these patients, they can accelerate the resolution of symptoms.
  • While there is significant variability in the approach to glucocorticoid therapy by individual clinicians, prednisone therapy can be initiated at 0.5–1 mg/kg of ideal body weight per day (not to exceed 60 mg/d or alternative glucocorticoid equivalent) over a duration of 1–2 weeks, followed by a taper over the next 2–6 weeks.

In chronic HP, a similar trial of corticosteroids may be used, although a variable component of fibrotic disease may be irreversible.


The mainstay of treatment for HP is antigen avoidance.
Personal protective equipment including respirators and ventilated helmets can be used but may not provide adequate protection for sensitized individuals. In some cases, fully avoiding specific environments may be necessary, although such a recommendation must be balanced against the effects to an individual’s lifestyle or occupation.
It is not uncommon for patients with HP due to exposure to household birds to be unwilling to remove them from the home.

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