Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review

To the Editor,

Pityriasis lichenoides (PL) is a rare cutaneous disorder characterized by erythematous and often pruritic papules. ¹ Iatrogenic PL eruption has been documented following biologic treatment. ² Evaluating the safety of biologics for inflammatory disease is imperative to mitigate adverse effects and support treatment adherence. This systematic review investigates the onset of PL in patients receiving biologic therapies for immune-mediated diseases.

Following registration on PROSPERO (ID-CRD42023480398), searches on MEDLINE and EMBASE were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using the keywords and variations: “pityriasis lichenoides” and “biologics.” A total of 13 studies (publication date: 2009-2022) with 14 participants were included (Figure S1; Supplemental Files 1 and 2: https://data.mendeley.com/datasets/k2wxs45mth/1).

The mean age of participants was 47.8 years (range: 15-74 years), comprising of 7 females (50%) and 7 males (50%). PL incidence was reported in patients receiving tumor necrosis factor α inhibitors (TNF-α) in 71.4% of cases (adalimumab, n = 5; infliximab, n = 3; etanercept, n = 2), and in patients receiving programmed cell death protein 1 (PD-1) inhibitors in 28.6% of cases (pembrolizumab, n = 3; atezolizumab, n = 1). Chronic (pityriasis lichenoides chronica) and acute [pityriasis lichenoides et varioliformis acuta (PLEVA)] PL incidence occurred in 64.3% (n = 9) and 35.7% (n = 5) cases, respectively. Clinical presentation of PL included the arms, back, buttocks, face, feet, legs, neck, trunk, and extremities.

The mean latency period of PL following biologic therapy initiation was 2.6 months (range: 0.25-12 months). Mean latency period in patients receiving TNF-α and PD-1 therapy was 3.1 months (adalimumab = 4.8; etanercept = 1.8; infliximab = 2.3) and 1.1 months (atezolizumab = 1.5; pembrolizumab = 0.9), respectively. Resolution of PL was reported in 85.7% of cases and categorized as complete (CR) or partial (PR) resolution. CR was documented in 66.7% (n = 8) of cases following cessation of biologics (n = 3), treatment with methotrexate (n = 4), and narrowband ultraviolet B therapy (n = 1). PR was reported in 33.3% (n = 4) of cases following cessation of biologics (n = 2), prednisolone (n = 1), and antibiotic therapy (n = 1; Supplemental Table S1: https://data.mendeley.com/datasets/k2wxs45mth/1).

TNF-α was the most common pathway preceding PL in this review (n = 10). TNF-α therapy has been implicated in psoriasis and other lichenoid disorders. ² It is postulated that immune dysregulation, specifically TNF blockade leading to upregulation of type 1 interferons through plasmacytoid dendritic cells, produces the histologic and clinical PL reaction. ³ This may also explain increased plasmacytoid dendritic cells in PLEVA events. ⁴ PD-1 therapy preceded PL in 4 cases and has been implicated in cutaneous immune-related adverse reactions including psoriasiform and lichenoid dermatitides, through evoking a cytotoxic T-cell response against malignant cells. ⁵ This suppression of autoimmunity and subsequent cytotoxic T-cell response can act on native cellular systems, ⁵ potentially explaining adverse PL eruption.

Study limitations in this review included lack of standardized follow-up and observational nature of the studies, subsequently hindering confirmed causality between biologic therapy and PL eruption. Furthermore, small sample sizes affected generalizability of results. Larger-scale studies are warranted to confirm the findings of this review.

Supplemental Material

sj-docx-1-cms-10.1177_12034754241265714 – Supplemental material for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review

Supplemental material, sj-docx-1-cms-10.1177_12034754241265714 for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review by Hibo Rijal, Naïla Bouadi and Sonja Molin in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-docx-2-cms-10.1177_12034754241265714 – Supplemental material for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review

Supplemental material, sj-docx-2-cms-10.1177_12034754241265714 for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review by Hibo Rijal, Naïla Bouadi and Sonja Molin in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-docx-3-cms-10.1177_12034754241265714 – Supplemental material for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review

Supplemental material, sj-docx-3-cms-10.1177_12034754241265714 for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review by Hibo Rijal, Naïla Bouadi and Sonja Molin in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-png-1-cms-10.1177_12034754241265714 – Supplemental material for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review

Supplemental material, sj-png-1-cms-10.1177_12034754241265714 for Onset of Pityriasis Lichenoides in Patients Treated With Biologic Therapy: A Systematic Review by Hibo Rijal, Naïla Bouadi and Sonja Molin in Journal of Cutaneous Medicine and Surgery