Published: 2 March 2017

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Drug-induced Lupus

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Prescriber Update 38(1): 11-12
March 2017

The Centre for Adverse Reactions Monitoring (CARM) recently received a report of probable drug-induced lupus (DIL) in a patient taking mesalazine¹. Anti-histone antibodies were detected¹. The dose of mesalazine was gradually reduced and subsequently stopped, with improvement of symptoms¹.

What is Drug-induced Lupus?

DIL is a rare, mild to moderately severe, lupus-like syndrome². It occurs due to continuous exposure to a specific medicine and resolves after the triggering medicine is stopped².

Drug-mediated disruption of immune tolerance is believed to be involved in the development of DIL, but the pathogenesis is not fully understood³.

DIL is a separate diagnosis to drug-induced flares of pre-existing or latent systemic lupus erythematosus (SLE)². However, it can be difficult to distinguish idiopathic SLE from DIL in a patient taking a medicine associated with DIL.

Differences Between Drug-induced Lupus and Systemic Lupus Erythematosus

Patients with DIL usually experience mild or few lupus-like symptoms initially. These symptoms include fever, malaise, weight loss, arthritis, arthralgia and myalgia³. Symptoms generally worsen the longer the patient is maintained on the suspect medicine³. Some symptoms such as malar or discoid rash, photosensitivity, oral ulcers, hair loss and renal or neurological disorders are common in SLE, but are uncommon in DIL³.

The latent period between starting the medicine and first symptoms appearing ranges from one month to more than 10 years².

Certain types of antinuclear antibodies, such as anti-histone antibodies, can help to confirm a diagnosis of DIL³. Although these autoantibodies are also common in SLE, patients with SLE usually have additional autoantibodies such as antibodies against double stranded DNA³. Therefore, when a diagnosis of SLE or DIL cannot be clearly distinguished on clinical grounds, the presence of double stranded DNA antibodies should be considered as evidence against a diagnosis of DIL³.

Medicines Associated with Drug-induced Lupus

Medicines associated with DIL are classified as high, moderate, low or very low risk³. There are up to 58 medicines that have been reported to induce autoimmunity and, less frequently, lupus-like disease³. Examples of medicines reported in association with DIL are summarised in Table 1.

Medicines that are associated with DIL should be avoided in patients with SLE³.

Table 1: Examples of medicines reported in association with DIL (this is not an exhaustive list)^2,3

Medicine	Risk
Procainamide*	High
Hydralazine	High
Quinidine*	Moderate
Isoniazid	Low
Minocycline	Low
Methyldopa	Low
Chlorpromazine	Low
TNFα inhibitors (eg, adalimumab)	Low/very low
Mesalazine	Very low

*These medicines are no longer available in New Zealand

Management

The suspect medicine should be stopped². Symptoms generally improve within one to two weeks of stopping the medicine³. Autoantibodies eventually normalise but can take as long as one to two years to disappear³.

No specific treatment is usually required². However, the use of non-steroidal anti-inflammatory drugs (NSAIDs) and oral corticosteroids (eg, prednisone) may be useful if severe manifestations such as pericarditis with tamponade, debilitating polyarthritis or glomerulonephritis develop³.

New Zealand Cases

Procainamide is the most common medicine reported to CARM in association with DIL reactions. However, procainamide is no longer available and the last report received for this medicine was in 1978. Other medicines reported include adalimumab (13 reports), infliximab (five reports), mesalazine and methyldopa (three reports each).

Please continue to report any adverse reactions to CARM. Reports can be submitted on paper or electronically (https://nzphvc.otago.ac.nz/).

References

1. CARM case ID 115326. URL: www.medsafe.govt.nz/Projects/B1/adrsearch.asp
2. DermNet New Zealand. 2016. Drug-induced lupus erythematosus. URL: www.dermnetnz.org/topics/drug-induced-lupus-erythematosus/ (accessed 13 July 2016).
3. Rubin RL. 2015. Drug-induced lupus. Expert Opinion on Drug Safety 14(3): 361-78.