Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in many rheumatologic diseases, including SLE. Despite their common use and over-the-counter status, they are a potential cause of adverse reactions and should be prescribed with caution.

Aseptic meningitis refers to the clinical picture of meningeal inflammation (stiff neck, headache, fever, photophobia, Kernig and Brudzinski signs) and pleocytosis of the cerebrospinal fluid (CSF), but without an infectious agent identified in the CSF. It is, therefore, a diagnosis of exclusion, and most cases will require empiric antibiotic coverage while cultures and viral studies are pending. With the development of sensitive viral assays, many cases that previously would have been classified as aseptic meningitis are probably now being diagnosed as viral meningitis. Enteroviral infections (coxsackievirus, echovirus, polio) are a common cause of viral meningitis in children. Mumps and California virus are also possible. Localized infections, such as an epidural abscess, cranial osteomyelitis, and sinusitis, can cause meningeal inflammation, mimicking aseptic meningitis. And other infectious agents, such as mycobacteria, malaria and other parasites, fungi, spirochetes, and Rickettsiae, can cause meningitis and may not be identified with the usual CSF testing.

There are a number of recognized causes of aseptic meningitis, including drug reactions, autoimmune diseases, meningeal involvement with tumors, Borrelia burgdorferi infection (Lyme disease), and the acute retroviral syndrome. Ibuprofen is the most common medication responsible for drug-induced aseptic meningitis, and the risk appears to be greater among patients with SLE or other autoimmune diseases. Other NSAIDs have been implicated, as well as trimethoprim with or without sulfamethoxazole, cephalosporins and other antibiotics, intravenous immunoglobulin (IVIG), and other agents. Not surprisingly, a number of intrathecal medications and contrast agents have also been responsible. NSAID-induced aseptic meningitis can occur after only one dose, and typically occurs shortly after ingestion
of ibuprofen, but it can be delayed until after 2 years of regular use. Some patients have suffered multiple episodes until the relationship was recognized. In most cases, patients can be successfully treated with another NSAID, but there are some reports of patients who developed aseptic meningitis with multiple different NSAIDs.