JAMA study reports drug-induced lupus erythematosus in users of proton pump inhibitors

Proton pump inhibitors (PPIs) are medications that exhibit their action by reducing the amount of stomach acid made by glands present in the linings of the stomach. PPIs role has been suggested in the occurrence of drug-induced lupus erythematosus for both drug-induced cutaneous lupus erythematosus (DI-CLE) and drug-induced systemic lupus erythematosus (DI-SLE) but remains poorly characterized.

Considering the above, Pauline Bataille, Hôpital Tenon, Paris, France, and colleagues aimed to examine the pharmacovigilance signal of PPI-associated DILE using different indicator tools for disproportionate reporting. They also strived to better characterize the spectrum of PPI-associated DILE by focusing on the DILE type as well as therapeutic management.

To achieve their objectives, the researchers performed a disproportionality study. They used data from VigiBase, the global pharmacovigilance database of WHO. Case-non-case studies was conducted for all PPIs and each molecule to test potential pharmacovigilance signals in reporting odds rations (RORs) and computing the information. For cases published after r January 1, 2002 sensitivity analyses was performed. The researchers took into account immunological, clinical, and therapeutic management of potential PPI-associated DILE from the French pharmacovigilance database. By using both the DILE types and therapeutic management, the authors aimed to better characterize the spectrum of PPI-associated DILE.

Based on the study, the authors reported the following:

· 559 cases were reported in the VigiBase between January 1985 and December 2019, 21,104, 625 of which were DILE associated with a PPI. The median age at DILE onset was 59 years and 78.2% were female patients.

· In about half of these cases (49.1%, n = 307), a PPI was the only suspected drug, with omeprazole shown as the most frequent PPI (30.4%, n = 190).

· Pharmacovigilance signals were noted for lansoprazole (IC 0.72; ROR, 1.97), esomeprazole (IC 0.67; ROR, 1.84), and omeprazole (IC 0.70; ROR, 1.87).

·791,922 cases were reported in the French pharmacovigilance database, of which 60 were DILE associated with a PPI and 49 were included. 65.3% were female patients.

· In the database, esomeprazole was the most frequently involved PPI (46.9%, n = 23).

· An isolated DI-CLE was seen in 79.6% patients, including discoid DI-CLE (5.1%, n = 2), subacute DI-CLE (48.7%, n = 19), unspecified DI-CLE (43.6%, n = 17), and tumidus DI-CLE (2.6%, n = 1).

· Additionally, 7 patients (14.3%) reported DI-SLE with cutaneous involvement, with most specified cases being of the subacute type (42.9%, n = 3).

· PPI was stopped in 71.5% of patients (n = 35/41) and remission occurred in 51.4% (n = 18/35) without specific treatment.

The authors concluded, ""This descriptive case series highlights that PPIs may be associated with not only isolated DI-CLE, but also DI-SLE with or without cutaneous involvement."

Reference:

Bataille P, Lebrun-Vignes B, Tubach F, et al. Proton Pump Inhibitors Associated With Drug-Induced Lupus Erythematosus. JAMA Dermatol. Published online August 17, 2022. doi:10.1001/jamadermatol.2022.2421