The chronic inflammatory disease lupus, usually traced to environmental and genetic causes, also can be drug-induced (DILE). It occurs in patients differently than systemic lupus erythematosus (SLE).
DILE tends to strike:
- Older patients (ages 50-70);
- Men more than women; and
- Whites more than blacks.
It was first described in 1945 as a side effect of sulfadiazine. Between 15,000 and 20,000 cases of drug-induced lupus erythematosus (DILE) occur yearly. Symptoms usually appear within three to six months of taking an offending drug.1 However, it also can occur within two years of receiving a triggering drug.2,3 The reaction usually resolves within days or months after removal of the offending medication. Care must be taken to correctly diagnose DILE and differentiate it from the systemic autoimmune disease SLE.
DILE arises mainly from the production of autoantibodies in reaction to certain drugs.4 Patients may also have a genetic predisposition, particularly for agents that are metabolically acetylated (e.g., hydralazine, procainamide). DILE is likely to appear more rapidly in patients who are slow acetylators. These patients include those with the HLA-DR4 or HLA-DR0301 genes, the complement C4 null allele, and females.
DILE symptoms include anorexia, arthralgia, fever, lymphadenopathy, malaise, myalgia, rash, serositis, and weight loss.5 The rash usually presents as polycyclic, with scaling and erythema in sun-exposed areas. Serologic findings include a positive antinuclear antibody (ANA) in 75% or more of patients and anti-histone antibodies. Levels of C3/C4 are usually normal. Antibodies to anti-double stranded DNA (anti-ds DNA) are rare, in contrast to SLE where C3/C4 levels usually decrease and anti-ds DNA is usually (50%-70%) positive. An elevated erythrocyte sedimentation rate (ESR 80%) may also be present. The absence of renal or central nervous system involvement is more suggestive of DILE. Renal effects occur in 5% to 10% of hydralazine-induced DILE cases, and renal deaths have been reported in rare cases.
Many agents can cause DILE. A large number of these agents rarely are used in present-day medicine. The more commonly used agents/classes include:
- Procainamide; and
Other agents that may possibly cause DILE include:
- Anti-tumor necrosis factor agents (adalimumab, etanercept, infliximab);
- Non-steroidal anti-inflammatory agents;
- Statins; and
Diagnosis is made by confirming the patient has:
- One or more clinical symptoms;
- A positive ANA;
- No SLE history prior to using the suspected agent;
- Not taken the drug anytime from three weeks to two years before the symptoms appeared; and
- Clinical resolution occurs rapidly upon “suspected drug” discontinuation.
A complete blood count should be obtained to evaluate for anemia (rare in DILE, common in SLE). Liver function tests, blood urea nitrogen, creatinine, and urinalysis can be performed to evaluate for other complications.
DILE usually resolves following drug discontinuation, but severe cases may require low doses of systemic corticosteroids. TH
Michele B Kaufman, PharmD, BSc, is a registered pharmacist based in New York City.
- Vasoo S. Drug-induced lupus: an update. Lupus 2006;15:757-761.
- Kauffman CL. Lupus erythematosus, drug-induced. eMedicine 2007. Available at www.emedicine.com/derm/TOPIC107.htm. Accessed April 8, 2008.
- MedlinePlus. www.nlm.nih.gov/medlineplus/ print/ency/article/000446.htm. Accessed April 8, 2008.
- Schur PH, Rose BD. Drug-induced lupus 2008; Patients UpToDate Version 16.1. Available www.uptodate.com/patients/content/topic.do;jsessionid=1934E0AFFCBBB588269DBFEE5F96BDF4.1002?topicKey=~kU3CGByPyaH&selectedTitle=2~103&source=search_result. Accessed April 8, 2008.
- Borchers A, Keen CL, Gershwin ME. Drug-induced lupus. Ann NY Acad Sci. 2007;1108:166-182.