Biologic-Induced Lichen Planus

Lichen planus (LP) is a chronic inflammatory immune-mediated disorder of the skin and mucous membranes, also affecting hair and nails, and is typically triggered by viral infections as well as pharmacological agents. With the increased use of biologics, lichen planus has gained recognition as a drug-induced adverse event. Recently, a literature review was published in the Journal of Inflammation Research exploring how modern biologic therapies can trigger lichen planus. This is considered a paradox as biologics are designed to suppress inflammation. Lichen planus has a hyper-inflammatory effect driven by a cytotoxic immune response that induces the cellular death of skin stem cells at the lowest layer of the epidermis.

The authors analyzed 145 publications describing 157 cases of lichen planus or lichenoid eruptions associated with biologic agents, aiming to uncover correlations and a more well-rounded understanding of the possible immune mechanisms driving these reactions. Drug-induced lichen planus presents in a wide range of forms: classic cutaneous LP, oral LP, lichen planus pemphigoides, nail LP, and lichen planopilaris (from most to least commonly referred to in the literature, respectively). The biologic classes most frequently implicated were immune checkpoint inhibitors (anti-PD-1/PD-L1), tumor necrosis factor-alpha (TNF-α) inhibitors, and inhibitors of IL-17 and IL-23.

Several overlapping immune pathways may explain how LP develops in a state of immunosuppression. “They appear to result from disruptions to immune homeostasis that ultimately favor cytotoxic T cell-mediated injury at the dermoepidermal junction… [these include] cytokine imbalance, immune pathway redirection, unmasking of antigens and epitope spreading, dysregulation of keratinocyte apoptosis pathways, and potential genetic or host susceptibility factors.” Most cases improved after discontinuation of the biologic and standard lichen planus therapies (which include steroid-sparing agents), but the unpredictable onset and variety of presentations highlight the need for clinician awareness. Authors also emphasize that the findings compiled in the review are largely observational, primarily based on case reports. Furthermore, future research focusing on identifying biomarkers, as well as genetic and cytokine profiles, that predict susceptibility may lead to a safer use of biologics in patients with autoimmune predispositions.

Citation

Podolsky, A. S., & Lipner, S. R. (2025). Mechanisms Underlying Lichen Planus in Association with Biologic Therapy. Journal of inflammation research, 18, 14961–14970. https://doi.org/10.2147/JIR.S554375