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Anti-TNF-α-induced lupus syndrome

Two case reports and review of current literature

Anti-TNF-α-induziertes Lupussyndrom

Übersicht über die aktuelle Literatur und 2 Kasuistiken

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Abstract

Anti-tumor necrosis factor‑α (TNF-α)-induced lupus (ATIL) represents a diagnostic and treatment challenge. Most cases are caused by infliximab and in some cases by etanercept and adalimumab. Symptoms can range from cutaneous manifestations to more rare and serious conditions. Diagnosis requires a temporal relationship between symptoms and positive autoantibody determination. Arthritis and cutaneous symptoms are the most common manifestations accompanied by positive antinuclear antibody (ANA) and anti-double strand DNA (dsDNA) determinations. The etiology of ATILS remains to be definitively established. Several mechanisms have been proposed for anti-TNF-α-induced lupus, including apoptosis, immunosuppression and humoral autoimmunity. Treatment includes discontinuation of anti-TNF‑α agents and in some cases corticosteroids and immunosuppressors. Questions to be answered: (1) Are soluble TNF receptor fusion proteins such as etanercept and anti-TNF chimeric antibodies equally likely to cause ATIL? (2) Can patients with ATIL switch from one anti-TNF‑α antagonist to another? (3) Can the concurrent use of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) like methotrexate or hydroxychloroquine reduce the probability of ATIL?

Zusammenfassung

Durch Antitumornekrosefaktor α-Antagonisten (Anti-TNF-α) induzierter Lupus (ATIL) stellt eine diagnostische und therapeutische Herausforderung dar. Die meisten Fälle werden durch Infliximab verursacht, und in einigen Fällen durch Etanercept und Adalimumab. Die Symptome reichen von kutanen Manifestationen bis hin zu selteneren und schweren Veränderungen. Für die Diagnose ist ein zeitlicher Zusammenhang zwischen den Symptomen und einer positiven Testung auf Autoantikörper erforderlich. Arthritis und kutane Symptome sind die häufigsten Manifestationen, die von positiven Untersuchungen auf antinukleäre Antikörper (ANA) und Antidoppelstrang-DNA(dsDNA)-Antikörper begleitet werden. Die Ätiologie des ATIL-Syndroms (ATILS) muss noch abschließend geklärt werden. Bisher wurden verschiedene Mechanismen für ATIL unterbreitet, einschließlich Apoptose, Immunsuppression und humoraler Autoimmunität. Zur Behandlung gehören das Absetzen von Anti-TNF-α-Antagonisten und in einigen Fällen Kortikosteroide und Immunsuppressiva. Noch zu beantwortende Fragen sind: (1) Sind lösliche TNF-Rezeptor-Fusionsproteine wie Etanercept und chimäre Anti-TNF-Antikörper gleichermaßen wahrscheinliche Auslöser für ATIL? (2) Können Patienten mit ATIL von einem Anti-TNF-α-Antagonisten zu einem anderen wechseln? (3) Kann die gleichzeitige Anwendung von einem csDMARD („conventional synthetic disease-modifying antirheumatic drug“) wie Methotrexat oder Hydroxychloroquin die Wahrscheinlichkeit für ATIL vermindern?

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Acknowledgements

The authors acknowledge the assistance of study participants, radiographers, study nurses and laboratory staff who participated in the study.

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Authors and Affiliations

  1. Rheumatology Department, Complejo Asistencial Universitario de León, Calle Altos de nava, s/n, 24001, León, Spain

    Cristiana Sieiro Santos MD & Carolina Álvarez Castro MD, PhD

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  1. Cristiana Sieiro Santos MD
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  2. Carolina Álvarez Castro MD, PhD
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  3. Clara Moriano Morales MD
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  4. Elvira Díez Álvarez MD
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Corresponding author

Correspondence to Cristiana Sieiro Santos MD.

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Conflict of interest

C. Sieiro Santos, C. Álvarez Castro, C. Moriano Morales and E. Diez Alvarez declare that they have no competing interests.

This study was approved by the Medical Ethical Committee of Complejo Asistencial Universitario de León.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Sieiro Santos, C., Álvarez Castro, C., Moriano Morales, C. et al. Anti-TNF-α-induced lupus syndrome. Z Rheumatol 80, 481–486 (2021). https://doi.org/10.1007/s00393-021-00983-8

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