Lichenoid Drug Eruptions Associated With the Use of Biologic Therapy: A Systematic Review

Recently, with the development of biologic medications, there have been reports of lichenoid drug eruptions (LDEs) after initiation of biologic therapy. ¹ LDEs can usually be managed by discontinuing the offending agent, but this is not always an option for the patient and LDEs are challenging to distinguish from LP due to morphological and histological resemblances. ² This systematic review summarizes reports of lichenoid lesions following biologic therapy.

This review was conducted according to the PRISMA statement. MEDLINE and Embase databases were searched on September 30, 2020 (Supplemental File 1) with manual checking of references. There were 49 included articles with 67 patients (mean age: 50.7 years) (Supplemental File 2). The most implicated biologics were tumor necrosis factor alpha (TNF-α) inhibitors (77.6%, n = 52/67), IL (interleukin)−1 inhibitors (9.0%, n = 6/67), and Il-17A inhibitors (4.5%, n = 3/67), with 38.8% (n = 26/67) of patients receiving other concomitant medications. Time between biologic administration and lichenoid eruption was median 3.0 months (IQR: 0.9-8). The mean Naranjo adverse drug reaction probability scale was 4.6 (range: 2-9), suggesting possible to probable drug reaction (Supplemental File 3).

Across 56 treatment attempts (Supplemental File 4), biologics were discontinued in 71.4% (n = 40/56), with complete lesion resolution rates of 81.3% (n = 13/16) with concomitant corticosteroids, 90.0% (n = 9/10) with discontinuation alone, and 77.5% (n = 31/40) overall. In 16 treatment attempts without discontinuation, complete resolution rates were 70.0% (n = 7/10) with corticosteroids and 62.5% (n = 10/16) overall. Among 6 biologic rechallenge attempts, 5 resulted in recurrence of lesions while Adalimumab rechallenge led to no reaction. There were 4 same-class switches between TNF-α inhibitors and 1 switch between IL-17 inhibitors, with recurrence after switching from Adalimumab to Infliximab. Biologic class switch from Adalimumab to Tocilizumab and twice from Infliximab to Secukinumab led to no recurrence in lesions (Supplemental File 5).

LDEs are thought to be a T-helper (Th)1 cell/type 1 innate lymphoid cell (ILC1)-interferon (IFN)-γ mediated immune response that stimulates CD8 +and NK cell cytotoxicity, resulting in basal keratinocyte apoptosis. ³ Inhibition of TNF-α can create an imbalance between TNF-α and IFN-α levels, leading to an amplified Th1 response and lichenoid reaction. The relationship between other biologics and LDEs are less understood but have been attributed to 4 key mechanisms: cytokine imbalances, changes in cutaneous immune responses, migration of innate and adaptive immune cells, and dysregulation of regulatory T-cells. ¹ Corticosteroids are currently considered first line therapy for all forms of LP and has been reported to decrease the production of IFN-α, suggesting their effectiveness in managing LDE. ^4,5 No recurrence was noted in three biologic class switches in this review, potentially highlighting an option for patients who require biologic therapy for management of their disease.

Limitations of this review include purely observational data, small sample sizes, and patients receiving concomitant medications. Despite these limitations, our review summarized lichenoid lesions following biologic therapy to raise awareness of this adverse event, especially after TNF-α inhibitor therapy, and described past management strategies to inform future guidelines. Further exploration of this topic is required by larger studies before the causality, pathophysiology, and management for lichenoid reactions after biologic use can be concluded.