Hydralazine is a medication primarily used as a vasodilator to treat high blood pressure and, often combined with other drugs, to manage heart failure. It works by relaxing the muscles in the blood vessel walls, which lowers blood pressure and makes it easier for the heart to pump blood. Although effective, hydralazine is associated with an uncommon side effect: the development of a lupus-like syndrome. This autoimmune reaction, first reported in 1953, can occur after prolonged use.
The Specific Condition: Drug-Induced Lupus
The condition caused by hydralazine is specifically known as Drug-Induced Lupus Erythematosus (DILE). Unlike Systemic Lupus Erythematosus (SLE), DILE is an immune reaction directly triggered by continuous medication exposure. This syndrome is typically milder and rarely affects major internal organs such as the kidneys or the brain.
The underlying mechanism involves the body processing the medication, leading to reactive byproducts. These byproducts interfere with immune cell function and bind to proteins, confusing the immune system. This results in an autoimmune response where the body attacks its own healthy tissues, causing lupus-like symptoms. A distinct feature of DILE is the presence of specific antibodies directed against histone proteins, found in up to 95% of cases.
Recognizing the Symptoms
Symptoms usually develop after months to years of continuous therapy. The most common clinical manifestations are musculoskeletal, with up to 90% of patients experiencing joint pain (arthralgia) and muscle aches (myalgia). Patients also commonly experience a low-grade fever, general malaise, and fatigue.
Inflammation of the linings around the heart or lungs, known as serositis, is also a reported symptom, specifically pleuritis or pericarditis. Importantly, the characteristic “butterfly rash” associated with SLE is rare or absent in hydralazine-induced lupus. While generally milder than SLE, symptoms are persistent and can sometimes require hospitalization.
Understanding the Risk and Contributing Factors
DILE is an uncommon side effect, though hydralazine is one of the most frequently implicated drugs. The risk of developing this syndrome is closely tied to the daily dosage and treatment duration. Historically, the risk significantly increases at daily doses greater than 200 mg, although cases have occurred at doses as low as 50 mg.
A primary patient-specific variable increasing susceptibility is a genetic trait known as “slow acetylator” status. This means the liver metabolizes hydralazine more slowly, leading to a buildup of the drug’s reactive byproducts. The incidence is also higher in women and older patients. For patients with the slow acetylator phenotype, the risk can be as high as 10%.
Treatment and Reversibility
The management of hydralazine-induced lupus is straightforward. The primary and most effective treatment is the immediate discontinuation of the medication under physician guidance. Symptoms of DILE are generally reversible because the underlying trigger is removed.
The prognosis is favorable, with most patients experiencing a resolution of clinical symptoms within weeks to months after stopping the drug. If joint pain or inflammation is severe, a short course of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids may be used to manage discomfort. This complete resolution contrasts with the lifelong management required for systemic lupus, reinforcing the temporary nature of the drug-induced form.