Drug-induced pneumonitis (DIP) is an adverse drug reaction causing inflammation of the lung tissue. This condition is a form of drug-induced interstitial lung disease (DI-ILD), which involves damage to the interstitium, the delicate space surrounding the air sacs. DIP is an inflammatory response, making it distinctly different from infectious pneumonia caused by bacteria or viruses. Doctors confirm DIP only after ruling out all other potential causes, such as infections, heart failure, or the patient’s underlying disease progression.
Understanding Drug Induced Pneumonitis
Pneumonitis is a general term for inflammation within the lungs, and in DIP, this inflammation is triggered by a medication. Injury mechanisms involve direct cell toxicity or an immune-mediated hypersensitivity reaction. Some drugs directly damage alveolar epithelial or capillary endothelial cells, while others initiate a dysregulated immune response that mistakenly attacks the lung tissue.
The inflammation primarily affects the lung interstitium. This injury can manifest in various ways, including non-specific interstitial pneumonia, organizing pneumonia, or hypersensitivity pneumonitis. The onset of the condition is highly variable, ranging from an acute reaction that develops within days to a chronic reaction that may take months or even years to appear.
Acute DIP often presents as a sudden and severe inflammatory process, sometimes mimicking acute respiratory distress syndrome, but it may resolve quickly once the offending drug is stopped. In contrast, chronic DIP involves a more insidious, gradual onset that can lead to permanent scarring, or fibrosis, within the lung tissue if the drug exposure continues. The unpredictability of the reaction means that the same drug can cause different injury patterns in different patients, highlighting the role of individual biological variability.
Identifying Causal Medications
A wide variety of prescription and non-prescription medications have been implicated in causing drug-induced pneumonitis. The reaction is often idiosyncratic, meaning it is unpredictable and not necessarily related to the dosage. However, for some cytotoxic agents, a high cumulative dose may increase the risk of toxicity.
Chemotherapy agents are a major category associated with DIP due to their cytotoxic nature, which directly injures lung cells. Examples include methotrexate and bleomycin, a cancer drug known for its potential to cause pulmonary fibrosis. Other antineoplastic drugs, such as cyclophosphamide and busulfan, have also been linked to lung injury.
Cardiac medications, particularly amiodarone, are also culprits, with toxicity often associated with high-dose and long-term use. Amiodarone’s pulmonary toxicity can manifest in several patterns of lung injury. Certain antibiotics, notably nitrofurantoin and sulfa medicines, can also trigger a hypersensitivity-type pneumonitis involving an exaggerated immune response.
Newer classes of biologic agents, particularly immune checkpoint inhibitors (ICIs) like nivolumab and pembrolizumab, are increasingly recognized as causes of DIP. These immunotherapies, used primarily to treat cancer, work by activating the immune system. This activation can sometimes lead to inflammation in healthy organs like the lungs. The onset of lung toxicity with ICIs typically occurs within two to three months after treatment initiation.
Recognizing Symptoms and Clinical Presentation
The symptoms of drug-induced pneumonitis are highly non-specific, meaning they resemble those of many other common respiratory illnesses, such as the flu or infectious pneumonia. This lack of specific symptoms makes diagnosis challenging and often requires a high index of suspicion from the healthcare provider. The clinical presentation varies depending on whether the condition is acute or chronic.
Acute DIP tends to have a rapid onset, developing over hours or a few days, and is often accompanied by systemic symptoms. Patients frequently experience a sudden onset of shortness of breath, a dry cough, and a fever, sometimes along with chills and general achiness. This rapid progression can sometimes lead to acute respiratory failure, requiring immediate medical intervention.
In contrast, chronic DIP has a more insidious presentation, with symptoms developing gradually over weeks or months of drug exposure. The primary complaints are typically a persistent, dry cough and gradually worsening dyspnea, or shortness of breath, which limits exercise capacity. Patients may also experience generalized fatigue, exhaustion, and unexplained weight loss.
A detailed medical history is necessary for clinical evaluation when these symptoms arise. Clinicians must review all current and recent medications, looking for a temporal relationship between drug use and the onset of respiratory symptoms. Improvement after temporarily stopping a suspected drug is a strong indicator that the medication is the underlying cause.
Diagnosis and Management
Diagnosing drug-induced pneumonitis relies on a combination of clinical suspicion, imaging studies, and the exclusion of other diseases. The first step in the diagnostic workup typically involves chest imaging, including a chest X-ray and a high-resolution computed tomography (HRCT) scan. The HRCT scan is particularly useful as it can reveal patterns of lung injury, such as ground-glass opacities, which are common in DIP.
Laboratory tests mainly rule out infectious causes, which can present with similar symptoms. Blood tests may check for markers of inflammation, such as C-reactive protein (CRP) or lactate dehydrogenase (LDH), and sometimes for an elevated count of eosinophils, which can suggest a hypersensitivity reaction. Pulmonary function tests measure lung function, often showing restrictive changes indicating stiffening of the lung tissue.
More invasive procedures, such as bronchoalveolar lavage (BAL) or a lung biopsy, are sometimes performed to confirm the diagnosis. BAL involves analyzing collected fluid and cells, which can show an increased number of inflammatory cells. A lung biopsy, while rarely required, provides tissue samples that allow pathologists to identify specific patterns of drug-induced lung damage.
The most effective management strategy is the immediate and permanent discontinuation of the suspected causative drug. Stopping the exposure should lead to an easing of symptoms. For patients with severe or progressive disease, systemic corticosteroids, such as prednisone, are often prescribed to quickly reduce lung inflammation.
Supportive care, including oxygen therapy, may be necessary if the patient is experiencing breathing difficulty or low blood oxygen. The prognosis is generally favorable for acute episodes, which often show improvement within 48 to 72 hours after the drug is stopped. However, chronic forms of DIP that progress to pulmonary fibrosis may result in permanent lung damage even after the medication is discontinued.