Pleurisy (pleuritis) is inflammation of the pleura, the two thin layers of tissue separating the lungs from the chest wall. While infections, particularly viruses, are the most common cause, various therapeutic agents can also induce this inflammation as an adverse reaction. Drug-induced pleurisy occurs when a prescribed medication triggers an inflammatory response in the pleural lining. Understanding the associated drugs and their effects is necessary for accurate diagnosis and management.
Recognizing Drug-Induced Pleurisy
The symptoms of drug-induced pleurisy are consistent with pleurisy from any other cause, primarily involving sharp, localized chest pain. This discomfort intensifies with movements that expand the lungs, such as deep breathing, coughing, or sneezing. Patients may also experience shortness of breath, often due to taking shallow breaths to avoid the pain.
Distinguishing drug-induced pleurisy from an infectious cause is challenging, making a complete medication history a primary diagnostic tool. Symptoms may appear acutely or develop gradually over months of therapy. They often resolve once the offending medication is identified and discontinued. Imaging, such as a chest X-ray, may reveal an accumulation of fluid in the pleural space, known as a pleural effusion.
Medications Implicated in Pleurisy
Many classes of medications have been linked to the development of pleurisy and associated pleural effusions.
Anti-Arrhythmics and Cardiovascular Drugs
Several anti-arrhythmic agents, notably Amiodarone, cause pleural disease, often as part of broader pulmonary toxicity. The risk associated with Amiodarone increases with higher cumulative doses over time. Another group includes drugs that induce a syndrome resembling systemic lupus erythematosus (SLE), known as drug-induced lupus. Classic examples are Procainamide (for heart rhythm disorders) and Hydralazine (for blood pressure). These drugs stimulate an autoimmune-like response that targets the pleural tissue.
Chemotherapy and Autoimmune Agents
Certain chemotherapy agents are implicated due to their toxicity. Procarbazine, for instance, can cause pleural involvement. Methotrexate, an antimetabolite used for cancer and autoimmune diseases, has also been documented to cause pleural disease.
Other Drug Classes
Antibiotics, such as Nitrofurantoin (used for urinary tract infections), have been linked to pulmonary and pleural side effects, especially with chronic use. Drugs acting on the central nervous system, including the anticonvulsant Phenytoin and the muscle relaxant Dantrolene, have also been reported to cause pleural effusions. Immunomodulatory agents, such as TNF-alpha inhibitors and Interleukin-2, can trigger pleural inflammation as part of an immune-mediated reaction. The dopamine agonist Bromocriptine is known to cause chronic pleural thickening and fibrosis that can persist after discontinuation.
How Medications Trigger Inflammation
Medications induce pleural inflammation through two primary pathways: direct toxicity and immunologic hypersensitivity reactions.
Direct Toxicity
In direct toxicity, the drug or one of its metabolic byproducts directly damages the cells of the pleural lining. This irritation leads to an inflammatory cascade and subsequent leakage of fluid into the pleural space.
Immunologic Reactions
The second pathway involves the immune system mistakenly attacking the pleura. The medication acts as an antigen or modifies the body’s proteins, causing the immune system to launch an inflammatory response. This hypersensitivity reaction can manifest with systemic signs, such as antinuclear antibodies in the blood, and may include the accumulation of eosinophils in the pleural fluid.
In drug-induced lupus, the medication interferes with immune system regulation, leading to autoantibodies that target the body’s own tissues, including the pleura. The resulting inflammation is sterile, meaning it is caused by the immune system’s overreaction rather than a direct infection. For certain drugs, like Methysergide, the inflammation can lead to dense fibrosis and thickening of the pleura, a permanent structural change.
Management and Recovery
The definitive step in managing drug-induced pleurisy is the complete discontinuation of the suspected medication under supervision. Since the presentation is non-specific, a physician will order imaging, such as a chest X-ray, and potentially analyze accumulated pleural fluid to rule out infectious or malignant causes. The close temporal relationship between starting the drug and the onset of symptoms supports the diagnosis.
Supportive treatment focuses on managing the chest pain associated with the inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are the standard first-line treatment for pain control. Indomethacin is often the preferred NSAID due to its effectiveness in reducing pleuritic pain.
In most instances, inflammation and symptoms begin to resolve gradually after the offending drug is withdrawn. If symptoms are severe or persistent, a short course of corticosteroids may be administered to suppress the immune-mediated inflammation. The prognosis for full recovery is favorable once the drug is stopped, though agents causing fibrosis may leave residual pleural thickening.