65-year-old male patient with Pembrolizumab-induced Lichen planus
Metastatic non-small cell lung cancer (NSCLC), stage IV M1C (UICC):
Spleen, kidney, and bone metastases
Initial diagnosis: April 24
04/2024: Initial diagnosis of metastatic NSCLC
04/2024: Cerebral radiation therapy
05/2024: Initiation of combined immunochemotherapy with 6 cycles of pemetrexed, carboplatin, and 200 mg pembrolizumab
Since August 2024: 200 mg pembrolizumab qw3, NSCLC in partial response
Since December 2024, the patient has reported severe pruritus (VAS 8/10) along with the appearance of multiple erythematous papules. Treatment with topical and oral steroids, including 20 mg of prednisolone prescribed by the oncologist and general practitioner, was initiated but proved ineffective.
In February 2025, the patient presented to the dermatology department. At that time, oral prednisolone was gradually tapered, and a skin biopsy confirmed the diagnosis of lichen planus. Following this, treatment with acitretin 20 mg (administered as 0-0-2 from February 28 to May 9, 2025) and UVB 311 nm phototherapy (from March 3 to April 14, 2025) was initiated. However, this resulted in only partial improvement, and the condition worsened after discontinuation of the light therapy.
Given the severity of the condition (CTCAE Grade 3 lichen planus) and the insufficient response to UVB 311, steroid and acitretin therapy, methotrexate treatment was started after a multidisciplinary discussion in out ToxBoard. Subcutaneous methotrexate at a dose of 15 mg once weekly was initiated on May 14, 2025. Folic acid supplementation was also started, and topical steroid therapy was continued.
Treatment with pembrolizumab was continued.
Despite the clinically significant therapeutic successes, treatment with PD-1 inhibitors such as pembrolizumab is associated with a number of immune-mediated side effects that can affect almost any organ system. The skin is particularly frequently affected. Dermatological side effects range from mild manifestations such as pruritus and maculopapular exanthema to autoimmune phenomena such as vitiligo, psoriasis-like changes to severe immune-mediated diseases (1). According to the European S1 guidelines, first-line treatments for lichen planus include the administration of topical or systemic corticosteroids, as well as therapy with acitretin. Second-line options comprise broadband or narrowband UVB phototherapy, a combination of UVB with acitretin, or the topical application of calcineurin inhibitors (2). In cases refractory to these measures, third-line therapies may be considered. These include methotrexate (15–20 mg per week for 4 to 15 weeks), azathioprine (administered orally at 50 mg twice daily or 1–2 mg/kg/day for a duration of 3 to 7 months), cyclophosphamide (50–100 mg/day for 3 to 6 months) as well as extracorporeal photopheresis (2). The literature suggests that methotrexate demonstrates high efficacy and a favorable safety profile, particularly in cases of extensive cutaneous lichen planus, making it a viable alternative to corticosteroids (3). The patient should be clearly informed about the potential risk of worsening the underlying oncological disease with methotrexate therapy. Therefore, a strict and well-considered indication is essential in such cases. An increasing number of reports in the literature have identified extracorporeal photopheresis (ECP) as a promising treatment option for steroid-refractory immune-related adverse events, including lichen planus. This is particularly relevant given the immunopathogenic nature of lichen planus, which involves T-cell mediated inflammation. In cases where conventional immunosuppressive therapies fail, ECP offers an immunomodulatory approach that may help restore immune tolerance without the broad immunosuppression associated with systemic steroids. Therefore, ECP should be considered a viable therapeutic option in the management of steroid-refractory lichen planus (4, 5).
Immune response lichen planus often responds poorly to acitretin. In patients with non-small cell lung cancer, phototherapy with 311nm UVB has been shown to provide good relief, but it is indicated with caution in skin tumors. Patients should be advised of the slow onset of action of methotrexate therapy and treated symptomatically for pruritus. ECP is recommended in cases of severe pruritus (VAS 8/10), otherwise sufficient improvement should not be achieved.
1. Sibaud V. Dermatologic Reactions to Immune Checkpoint Inhibitors : Skin Toxicities and Immunotherapy. Am J Clin Dermatol. 2018;19(3):345-61.
2. Ioannides D, Vakirlis E, Kemeny L, Marinovic B, Massone C, Murphy R, et al. European S1 guidelines on the management of lichen planus: a cooperation of the European Dermatology Forum with the European Academy of Dermatology and Venereology. J Eur Acad Dermatol Venereol. 2020;34(7):1403-14.
3. Khurana A, Sharath S, Sardana K. Efficacy And Safety Of Low-Dose Methotrexate In Generalized And Recalcitrant Lichen Planus: A Retrospective Study At A Tertiary Care Center. Dermatol Pract Concept. 2024;14(4).
4. Ruf T, Rahimi F, Anz D, Tufman A, Salzer S, Zierold S, et al. Extracorporeal Photopheresis as a Treatment Option for Immune-Related Adverse Events: Two Case Reports and a Prospective Study. J Immunother. 2024;47(6):227-31.
5. Birckel E, Lipsker D, Cribier B. [Efficacy of photopheresis in the treatment of erosive lichen planus: A retrospective study]. Ann Dermatol Venereol. 2020;147(2):86-92.
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