Stop Drug-Induced Lupus

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.

The Agents

New Warnings

Formoterol fumarate (Foradil) and tiotropium bromide (Spiriva). The FDA has issued a warning regarding the proper use of these two inhalation powders, the former through the Aerolizer device, the latter through the HandiHaler device. These two devices are used to deliver powder contained in capsules. The FDA and the National Poison Control Center have received numerous reports of patients swallowing the capsules rather than administering them in their inhalation devices. The following information is provided for the correct use of these products for in-hospital use or for discharge prescriptions:

The capsules should not be swallowed;
The contents of the Foradil/Spiriva capsules are to be inhaled into the lungs using the respective inhalation devices. The capsule should be removed from the blister pack prior to use and the capsule placed in the inhalation device prior to inhalation;
Instruct patients on the proper use of each device, whether it is a new prescription, or whether the patient has been on it for a while. This will ensure proper medication use; and
If a patient is prescribed formoterol or tiotropium and does not experience breathing improvement, ascertain how the patient is taking the medication in order to determine if they are swallowing the capsule rather than inhaling its contents.

The FDA and the company’s manufacturers continue to monitor this problem.—MK

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: