New drugs implicated in risk of lupus

3 minute read

A commonly prescribed anti-histamine and an anti-emetic have just been listed among those drugs that increase the risk of developing lupus erythematosus.

A commonly prescribed anti-histamine and an anti-emetic have just been listed among those drugs that increase the risk of developing lupus erythematosus.

According to the case-controlled study just published in JAMA Dermatology, taking the antihistamine, fexofenadine hydrochloride  increased the risk of developing subacute cutaneous lupus erythematosus (CLA) five times over that of people not taking the medication. And the likelihood of developing systemic lupus erythematosus was increased more than 2.5 times.

The other drugs newly implicated in increasing the risk of lupus were metoclopramide hydrochloride, levothyroxine sodium and metronidazole.

Drug-induced lupus erythematosus is not a new concept. Apparently up to 30% of cases of subacute cutaneous lupus erythematosus are thought to be caused by drugs and up to 15% of SLE cases are believed to be drug-induced. However what has been less clear is which particular drugs are most to blame, in fact more than 100 drugs have been suspected at some stage.

“To our knowledge, no study has examined the association between drug use and a subsequent diagnosis of systemic lupus erythematosus or cutaneous lupus erythematosus based on a systematic screening process of the drugs in a large-scale setting,” the study authors said.

To investigate this the researchers identified and analysed all the incident cases of these two lupus diseases on the Danish National Patient Register over almost 20 years. They then compared these cases (3148 patients) with matched controls from the general population (31,480 people).

Interestingly the profile of the incident cases of both cutaneous lupus and systemic lupus on the patient register reflects current understanding of the disease – mainly that it predominantly affects women (CLE:79% women and SLE:83%) and usually starts in middle age – the median age at diagnosis was 50.5 years for CLE and 45 years for SLE.

They then worked backwards to find which drugs had been taken prior to the diagnosis. In particular they were looking at which drugs had been taken ‘long-term’ which they defined as a period of exposure in the time between three months and 12 months prior to diagnosis.

The researchers were careful to eliminate ‘protopathic bias’, meaning they were careful not to mistakenly implicate drugs that might have been prescribed to treat the symptoms of the yet-to-be diagnosed disease, for example NSAIDs. They also said that the association they found between both tumour necrosis factor(TNF) inhibitors and terbinafine with lupus, was already well-known, and therefore not particularly newsworthy.

But having eliminated these obviously linked treatments from the equation, the significantly increased risk associated with the four common and quite different agents was worth noting.

“The potentially new, significant associations that we found were metoclopramide hydrochloride and levothyroxine sodium for SLE and metronidazole hydrochloride and fexofenadine hydrochloride for both CLE and SLE,” they said.

The one caveat they suggested related to thyroxine. The study authors took note of the fact that hypothyroidism had been reported in as many as 4% of patients with SLE, so the link might be more related to the disease than the drug.

Nonetheless the researchers were keen that clinicians keep these latest findings in mind when patients present with recent onset lupus symptoms.

“The list of drugs reported to induce [drug-induced lupus erythematosus] is constantly changing as new drugs arise. Therefore, it is important that physicians are updated on the changing drug list and remain aware of potential new drug associations.”

Ref: doi:10.1001/jamadermatol.2020.2786

This article was first published on the Healthed newsletter 10.9.20

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