Disease state
Drug-Induced Lupus due to Anti-Tumor Necrosis Factor α Agents

https://doi.org/10.1016/j.semarthrit.2007.08.003Get rights and content

Purpose

To evaluate the reported cases of drug-induced lupus erythematosus (DILE) due to anti-tumor necrosis factor (TNF) α therapy and to compare “classic” DILE with DILE secondary to anti-TNFα therapy. We also add 3 case reports related to 3 different anti-TNFα drugs to the literature.

Methods

We searched the Medline database for cases published in English and evaluated 53 cases in 27 papers purported to be TNFα-induced DILE. We compared the clinical and laboratory features of cases that fulfilled our criteria for TNFα DILE to those of DILE due to non-TNFα drugs as found in standard texts. We also report the clinical and laboratory findings of our 3 patients with drug-induced lupus related to anti-TNFα drugs, 1 each in patients treated with adalimumab, etanercept, and infliximab.

Results

Of the 53 purported cases of DILE due to anti-TNFα therapy, we excluded 17 with cutaneous manifestations alone and 3 with overlap syndromes and mixed connective tissue disease. In the 33 cases that met our criteria for systemic DILE, 21 cases were due to infliximab, 10 cases were due to etanercept, and only 2 cases were related to adalimumab. TNFα-blocker-induced DILE cases had a higher prevalence of antibodies to double-stranded DNA, rash, and hypocomplementemia than DILE due to other drugs. Fever is common in both types of DILE. Renal disease, which is rare in classic DILE, has been reported in cases of TNFα DILE.

Conclusions

TNFα DILE has significant clinical and laboratory manifestations which distinguish it from DILE due to drugs other than anti-TNF agents and may be difficult to diagnose in patients treated for autoimmune diseases. It is appropriate to consider whether all patients who are begun on anti-TNF therapy should have pretreatment serologic evaluation for systemic lupus erythematosus.

Section snippets

Methods

We performed a PubMed search with the following keywords: “drug-induced lupus and anti-TNFα,” “drug-induced lupus and biologics,” “drug-induced lupus and infliximab,” “drug-induced lupus and etanercept,” and “drug-induced lupus and adalimumab.” We also searched the Medline database with the headings “tumor-necrosis factor blockade/adverse effects,” “systemic lupus erythematosus/chemically induced,” and “antirheumatic agents/chemically induced.” We evaluated all series, reviews, and case reports

Patient 1

A 22-year-old woman was diagnosed with RA on the basis of symmetric polyarthritis, a positive rheumatoid factor (RF), and antibodies to cyclic citrullinated peptide (CCP). She had low titer (1:80) antinuclear antibodies (ANA) but no rash or other clinical evidence of systemic lupus erythematosus (SLE). She was initially treated with nonsteroidal anti-inflammatory drugs and low-dose prednisone. She began adalimumab 4 months after the onset of arthritis. Her joint symptoms responded promptly to

Discussion

The patients that we describe in the present report had findings similar to those in previous reports of DILE from anti-TNFα therapy. The first patient with RA had a low positive ANA before beginning adalimumab therapy. On adalimumab, she developed fever, rash, antibodies to dsDNA, and proteinuria, all of which resolved after discontinuation of anti-TNFα therapy. We believe this is the third well-described case of DILE due to adalimumab reported in the literature. Our second patient's case was

Acknowledgments

The authors acknowledge Drs. Edward V. Lally and Harald A. Hall for their thoughtful review of the manuscript and contribution of case material. We also appreciate the secretarial assistance provided by Kathy Poland and Marsha Potenza.

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    The authors have no conflicts of interest to disclose.

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