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Management of Immune-Related Cutaneous Adverse Reactions to PD-1 and PD-L1 Inhibitors for the Inpatient Dermatologist


Purpose of Review

Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors are immunotherapeutic agents associated with a range of auto-inflammatory cutaneous toxicities. This paper reviews the clinical approach to the diagnosis and management of immune-related cutaneous adverse events (irCAEs) to PD-1 and PD-L1 inhibitors, with emphasis on disease processes practitioners may encounter in hospitalized patients.

Recent Findings

A systematic approach for suspected irCAEs has been well-detailed in recent clinical guidelines. However, the breadth of irCAE manifestations and treatment options continues to be actively delineated in the literature.


The characterization and management of irCAEs is an ever-evolving realm of oncodermatology. The dermatologist’s role is to limit morbidity and mortality, maximize quality of life, and prevent discontinuation of immunotherapy. Non-steroidal immunomodulatory agents are being increasingly utilized for moderate to severe cutaneous reactions and present an opportunity for further research into safe and effective therapies.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1

    Blank C, Gajewski TF, Mackensen A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother. 2005;54(4):307–14.

    CAS  PubMed  Google Scholar 

  2. 2

    Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99(19):12293–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–2465. Multicenter phase 1 clinical trail following patients on PD-1 and PD-L1 inhibitors prospectively. Demonstrated 9% of patients experienced grade 3 or grade 4 immune-related adverse events.

  5. 5.

    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current diagnosis and Management of Immune Related Adverse Events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol. 2017;8:49.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    • Costa R, Carneiro BA, Agulnik M, et al. Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Oncotarget. 2017;8(5):8910–8920. Systematic review and meta-analysis of PD-1 therapy compared with non-immunotherapeutic interventions demonstrating comparably lower toxicity profile associated with PD-1 inhibitors. The most common toxicities included pruritus, vitiligo, and thyroid dysfunction.

  9. 9.

    Belum VR, Benhuri B, Postow MA, Hellmann MD, Lesokhin AM, Segal NH, et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer. 2016;60:12–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Sibaud V, Meyer N, Lamant L, Vigarios E, Mazieres J, Delord JP. Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Curr Opin Oncol. 2016;28(4):254–63.

    CAS  PubMed  Google Scholar 

  11. 11.

    •• Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;36(17):1714-1768. Systematic review and expert consensus on guidelines to manage immune-related adverse events of checkpoint inhibitor therapy.

  12. 12.

    Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group. J Immunother Cancer. 2017;5(1):95.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, et al. Management of Immunotherapy-Related Toxicities, version 1.2019. J Natl Compr Cancer Netw. 2019;17(3):255–89.

    CAS  Google Scholar 

  14. 14.

    Haanen J, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv264-iv266.

  15. 15.

    •• Phillips GS, Wu J, Hellmann MD, et al. Treatment Outcomes of Immune-Related Cutaneous Adverse Events. J Clin Oncol. 2019;37(30):2746–2758. Retrospective analysis of immune-related adverse events noted in oncodermatology clinics reporting variable efficacy of topical steroids, systemic steroids, and immunomodulatory agents for specific cutaneous reactions.

  16. 16.

    Sibaud V. Dermatologic reactions to immune checkpoint inhibitors : skin toxicities and immunotherapy. Am J Clin Dermatol. 2018;19(3):345–61.

    PubMed  Google Scholar 

  17. 17.

    Freeman-Keller M, Kim Y, Cronin H, Richards A, Gibney G, Weber JS. Nivolumab in resected and Unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res. 2016;22(4):886–94.

    CAS  PubMed  Google Scholar 

  18. 18.

    Hwang SJ, Carlos G, Wakade D, et al. Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: a single-institution cohort. J Am Acad Dermatol. 2016;74(3):455–61 e451.

    PubMed  Google Scholar 

  19. 19.

    Curry JL, Tetzlaff MT, Nagarajan P, Drucker C, Diab A, Hymes SR, et al. Diverse types of dermatologic toxicities from immune checkpoint blockade therapy. J Cutan Pathol. 2017;44(2):158–76.

    PubMed  Google Scholar 

  20. 20.

    Shi VJ, Rodic N, Gettinger S, Leventhal JS, Neckman JP, Girardi M, et al. Clinical and histologic features of Lichenoid Mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy. JAMA Dermatol. 2016;152(10):1128–36.

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Sibaud V, Eid C, Belum VR, Combemale P, Barres B, Lamant L, et al. Oral lichenoid reactions associated with anti-PD-1/PD-L1 therapies: clinicopathological findings. J Eur Acad Dermatol Venereol. 2017;31(10):e464–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ameri AH, Foreman RK, Vedak P. Chen S. Demehri S. Hypertrophic Lichen Planus with Histological Features of Squamous Cell Carcinoma Associated with Immune Checkpoint Blockade Therapy. Oncologist: Miller DM; 2020.

  23. 23.

    Cogen AL, Parekh V, Gangadhar T, Lipoff JB. Lichen planopilaris associated with pembrolizumab in a patient with metastatic melanoma. JAAD Case Rep. 2018;4(2):132–4.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Coscarart A, Martel J, Lee MP, Wang AR. Pembrolizumab-induced pseudoepitheliomatous eruption consistent with hypertrophic lichen planus. J Cutan Pathol. 2020;47(3):275–9.

    PubMed  Google Scholar 

  25. 25.

    Donaldson M, Owen JL, Chae YK, Choi JN. Management of Persistent Pruritus and Lichenoid Reaction Secondary to Nivolumab with narrowband ultraviolet B phototherapy. Front Oncol. 2018;8:405.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Edwards C, Fearfield L. Nivolumab-induced lichenoid dermatitis occurring in a patient with metastatic melanoma successfully treated with alitretinoin. Clin Exp Dermatol. 2018;43(5):609–10.

    CAS  PubMed  Google Scholar 

  27. 27.

    Fixsen E, Patel J, Selim MA, Kheterpal M. Resolution of Pembrolizumab-associated steroid-refractory Lichenoid dermatitis with cyclosporine. Oncologist. 2019;24(3):e103–5.

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Lindner AK, Schachtner G, Tulchiner G, Staudacher N, Steinkohl F, Nguyen VA, et al. Immune-related lichenoid mucocutaneous erosions during anti-PD-1 immunotherapy in metastatic renal cell carcinoma - a case report. Urol Case Rep. 2019;23:1–2.

    PubMed  Google Scholar 

  29. 29.

    Randhawa M, Archer C, Gaughran G, Miller A, Morey A, Dua D, et al. Combined immune therapy grade IV dermatitis in metastatic melanoma. Asia Pac J Clin Oncol. 2019;15(4):262–5.

    PubMed  Google Scholar 

  30. 30.

    Wakade DV, Carlos G, Hwang SJ, Chou S, Hui R, Fernandez-Penas P. PD-1 inhibitors induced bullous lichen planus-like reactions: a rare presentation and report of three cases. Melanoma Res. 2016;26(4):421–4.

    PubMed  Google Scholar 

  31. 31.

    Cho M, Nonomura Y, Kaku Y, Dainichi T, Otsuka A, Kabashima K. Generalized lichen Nitidus following anti-PD-1 antibody treatment. JAMA Dermatol. 2018;154(3):367–9.

    PubMed  Google Scholar 

  32. 32.

    Schaberg KB, Novoa RA, Wakelee HA, Kim J, Cheung C, Srinivas S, et al. Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy. J Cutan Pathol. 2016;43(4):339–46.

    PubMed  Google Scholar 

  33. 33.

    Tetzlaff MT, Nagarajan P, Chon S, Huen A, Diab A, Omar P, et al. Lichenoid dermatologic toxicity from immune checkpoint blockade therapy: a detailed examination of the Clinicopathologic features. Am J Dermatopathol. 2017;39(2):121–9.

    PubMed  Google Scholar 

  34. 34.

    Phillips GS, Freites-Martinez A, Wu J, Chan D, Fabbrocini G, Hellmann MD, et al. Clinical characterization of immunotherapy-related pruritus among patients seen in 2 Oncodermatology clinics. JAMA Dermatol. 2019;155(2):249–51.

    PubMed  Google Scholar 

  35. 35.

    Santini D, Vincenzi B, Guida FM, Imperatori M, Schiavon G, Venditti O, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13(10):1020–4.

    CAS  PubMed  Google Scholar 

  36. 36.

    Ito J, Fujimoto D, Nakamura A, Nagano T, Uehara K, Imai Y, et al. Aprepitant for refractory nivolumab-induced pruritus. Lung Cancer. 2017;109:58–61.

    PubMed  Google Scholar 

  37. 37.

    Kwatra SG, Stander S, Kang H. PD-1 blockade-induced pruritus treated with a mu-opioid receptor antagonist. N Engl J Med. 2018;379(16):1578–9.

    PubMed  Google Scholar 

  38. 38.

    Balak DMW, Hajdarbegovic E. More on mu-opioid receptor antagonists in PD-1 blockade-induced pruritus. N Engl J Med. 2019;380(6):601.

    PubMed  Google Scholar 

  39. 39.

    Hendricks AJ, Yosipovitch G, Shi VY. Dupilumab use in dermatologic conditions beyond atopic dermatitis - a systematic review. J Dermatolog Treat. 2019:1–10.

  40. 40.

    Maurer M, Rosen K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368(10):924–35.

    CAS  PubMed  Google Scholar 

  41. 41.

    Coleman E, Ko C, Dai F, Tomayko MM, Kluger H, Leventhal JS. Inflammatory eruptions associated with immune checkpoint inhibitor therapy: a single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. J Am Acad Dermatol. 2019;80(4):990–7.

    CAS  PubMed  Google Scholar 

  42. 42.

    De Bock M, Hulstaert E, Kruse V, Brochez L. Psoriasis vulgaris exacerbation during treatment with a PD-1 checkpoint inhibitor: case report and literature review. Case Rep Dermatol. 2018;10(2):190–7.

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    • Bonigen J, Raynaud-Donzel C, Hureaux J, et al. Anti-PD1-induced psoriasis: a study of 21 patients. J Eur Acad Dermatol Venereol. 2017;31(5):e254-e257. Multicenter study and review of psoriasis caused by anti-PD-1 therapy, delineating clinical findings and therapeutic options.

  44. 44.

    Politi A, Angelos D, Mauri D, Zarkavelis G, Pentheroudakis G. A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review. SAGE Open Med Case Rep. 2020;8:2050313X19897707.

  45. 45.

    Voudouri D, Nikolaou V, Laschos K, Charpidou A, Soupos N, Triantafyllopoulou I, et al. Anti-PD1/PDL1 induced psoriasis. Curr Probl Cancer. 2017;41(6):407–12.

    PubMed  Google Scholar 

  46. 46.

    Kaunitz GJ, Loss M, Rizvi H, Ravi S, Cuda JD, Bleich KB, et al. Cutaneous eruptions in patients receiving immune checkpoint blockade: Clinicopathologic analysis of the Nonlichenoid histologic pattern. Am J Surg Pathol. 2017;41(10):1381–9.

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Fattore D, Annunziata MC, Panariello L, Marasca C, Fabbrocini G. Successful treatment of psoriasis induced by immune checkpoint inhibitors with apremilast. Eur J Cancer. 2019;110:107–9.

    CAS  PubMed  Google Scholar 

  48. 48.

    Johnson D, Patel AB, Uemura MI, Trinh VA, Jackson N, Zobniw CM, et al. IL17A blockade successfully treated Psoriasiform dermatologic toxicity from immunotherapy. Cancer Immunol Res. 2019;7(6):860–5.

    CAS  PubMed  Google Scholar 

  49. 49.

    Monsour EP, Pothen J, Balaraman R. A novel approach to the treatment of Pembrolizumab-induced psoriasis exacerbation: a case report. Cureus. 2019;11(10):e5824.

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Kim YE, Kim TM, Jo SJ. Histologically-diagnosed psoriasiform dermatitis induced by nivolumab successfully controlled by etanercept: a case report. J Dermatol. 2019;46(12):e464–6.

    PubMed  Google Scholar 

  51. 51.

    Rios A, Cen P, Dinh B, Mays SR, Patel AB. Dramatic response of nivolumab-associated psoriasiform dermatitis to etoposide. Eur J Cancer. 2019;107:97–9.

    PubMed  Google Scholar 

  52. 52.

    Ito M, Hoashi T, Endo Y, Kimura G, Kondo Y, Ishii N, et al. Atypical pemphigus developed in a patient with urothelial carcinoma treated with nivolumab. J Dermatol. 2019;46(3):e90–2.

    PubMed  Google Scholar 

  53. 53.

    Schmidgen MI, Butsch F, Schadmand-Fischer S, Steinbrink K, Grabbe S, Weidenthaler-Barth B, et al. Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic melanoma. J Dtsch Dermatol Ges. 2017;15(7):742–5.

    PubMed  Google Scholar 

  54. 54.

    Krammer S, Krammer C, Salzer S, Bagci IS, French LE, Hartmann D. Recurrence of Pemphigus Vulgaris Under Nivolumab Therapy. Front Med (Lausanne). 2019;6:262.

  55. 55.

    Singer S, Nelson CA, Lian CG, Dewan AK, LeBoeuf NR. Nonbullous pemphigoid secondary to PD-1 inhibition. JAAD Case Rep. 2019;5(10):898–903.

    PubMed  PubMed Central  Google Scholar 

  56. 56.

    Haug V, Behle V, Benoit S, Kneitz H, Schilling B, Goebeler M, et al. Pembrolizumab-associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma. Br J Dermatol. 2018;179(4):993–4.

    CAS  PubMed  Google Scholar 

  57. 57.

    Zumelzu C, Alexandre M, Le Roux C, et al. Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature. Front Med (Lausanne). 2018;5:268.

  58. 58.

    Chen WS, Tetzlaff MT, Diwan H, Jahan-Tigh R, Diab A, Nelson K, et al. Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: a spectrum of immune reactions from paraneoplastic pemphigus-like to Grover-like lesions. J Cutan Pathol. 2018;45(10):764–73.

    PubMed  Google Scholar 

  59. 59.

    Siegel J, Totonchy M, Damsky W, Berk-Krauss J, Castiglione F Jr, Sznol M, et al. Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: a retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. J Am Acad Dermatol. 2018;79(6):1081–8.

    CAS  PubMed  Google Scholar 

  60. 60.

    •• Lopez AT, Khanna T, Antonov N, Audrey-Bayan C, Geskin L. A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors. Int J Dermatol. 2018;57(6):664–669. Comprehensive literature review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors demonstrating preceding pruritus, variable time to onset, and need for discontinuation of immunotherapy in most cases.

  61. 61.

    Damsky W, Kole L, Tomayko MM. Development of bullous pemphigoid during nivolumab therapy. JAAD Case Rep. 2016;2(6):442–4.

    PubMed  PubMed Central  Google Scholar 

  62. 62.

    Sadik CD, Langan EA, Gratz V, Zillikens D, Terheyden P. Checkpoint inhibition may trigger the rare variant of anti-LAD-1 IgG-positive, anti-BP180 NC16A IgG-negative bullous Pemphigoid. Front Immunol. 2019;10:1934.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Ridpath AV, Rzepka PV, Shearer SM, Scrape SR, Olencki TE, Kaffenberger BH. Novel use of combination therapeutic plasma exchange and rituximab in the treatment of nivolumab-induced bullous pemphigoid. Int J Dermatol. 2018;57(11):1372–4.

    PubMed  Google Scholar 

  64. 64.

    Sowerby L, Dewan AK, Granter S, Gandhi L, LeBoeuf NR. Rituximab treatment of Nivolumab-induced bullous Pemphigoid. JAMA Dermatol. 2017;153(6):603–5.

    PubMed  Google Scholar 

  65. 65.

    Bezinelli LM, Eduardo FP, Migliorati CA, Ferreira MH, Taranto P, Sales DB, et al. A severe, refractory case of mucous membrane Pemphigoid after treatment with Pembrolizumab: brief communication. J Immunother. 2019;42(9):359–62.

    CAS  PubMed  Google Scholar 

  66. 66.

    Yu KK, Crew AB, Messingham KA, Fairley JA, Woodley DT. Omalizumab therapy for bullous pemphigoid. J Am Acad Dermatol. 2014;71(3):468–74.

    CAS  Google Scholar 

  67. 67.

    Rofe O, Bar-Sela G, Keidar Z, Sezin T, Sadik CD, Bergman R. Severe bullous pemphigoid associated with pembrolizumab therapy for metastatic melanoma with complete regression. Clin Exp Dermatol. 2017;42(3):309–12.

    CAS  PubMed  Google Scholar 

  68. 68.

    Hwang SJ, Carlos G, Chou S, Wakade D, Carlino MS, Fernandez-Penas P. Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies. Melanoma Res. 2016;26(4):413–6.

    CAS  PubMed  Google Scholar 

  69. 69.

    Cai ZR, Lecours J, Adam JP, et al. Toxic epidermal necrolysis associated with pembrolizumab. J Oncol Pharm Pract. 2019;1078155219890659.

  70. 70.

    Maloney NJ, Ravi V, Cheng K, Bach DQ, Worswick S. Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review. Int J Dermatol. 2020;59:e183–8.

    PubMed  Google Scholar 

  71. 71.

    Logan IT, Zaman S, Hussein L, Perrett CM. Combination therapy of Ipilimumab and Nivolumab-associated toxic epidermal Necrolysis (TEN) in a patient with metastatic melanoma: a case report and literature review. J Immunother. 2020;43(3):89–92.

    PubMed  Google Scholar 

  72. 72.

    Dasanu CA. Late-onset Stevens-Johnson syndrome due to nivolumab use for hepatocellular carcinoma. J Oncol Pharm Pract. 2019;25(8):2052–5.

    CAS  PubMed  Google Scholar 

  73. 73.

    Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115(2):149–53.

    CAS  PubMed  Google Scholar 

  74. 74.

    Saw S, Lee HY, Ng QS. Pembrolizumab-induced Stevens-Johnson syndrome in non-melanoma patients. Eur J Cancer. 2017;81:237–9.

    CAS  PubMed  Google Scholar 

  75. 75.

    Griffin LL, Cove-Smith L, Alachkar H, Radford JA, Brooke R, Linton KM. Toxic epidermal necrolysis (TEN) associated with the use of nivolumab (PD-1 inhibitor) for lymphoma. JAAD Case Rep. 2018;4(3):229–31.

    PubMed  PubMed Central  Google Scholar 

  76. 76.

    Basu P. Tong Y. Schneider JA. Nivolumab-induced toxic epidermal necrolysis with retiform purpura. Br J Dermatol: Hinds BR; 2020.

  77. 77.

    Vivar KL, Mancl K, Seminario-Vidal L. Stevens-Johnson syndrome/toxic epidermal necrolysis associated with zonisamide. Clin Case Rep. 2018;6(2):258–61.

    PubMed  Google Scholar 

  78. 78.

    Kumar R, Bhandari S. Pembrolizumab induced toxic epidermal necrolysis. Curr Probl Cancer. 2020;44(2):100478.

    PubMed  Google Scholar 

  79. 79.

    Lu J, Thuraisingam T, Chergui M, Nguyen K. Nivolumab-associated DRESS syndrome: a case report. JAAD Case Rep. 2019;5(3):216–8.

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Mirza S, Hill E, Ludlow SP, Nanjappa S. Checkpoint inhibitor-associated drug reaction with eosinophilia and systemic symptom syndrome. Melanoma Res. 2017;27(3):271–3.

    CAS  PubMed  Google Scholar 

  81. 81.

    Voskens CJ, Goldinger SM, Loquai C, Robert C, Kaehler KC, Berking C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS One. 2013;8(1):e53745.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Maximova N, Maestro A, Zanon D, Marcuzzi A. Rapid recovery of postnivolumab vemurafenib-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome after tocilizumab and infliximab administration. J Immunother Cancer. 2020;8(1).

  83. 83.

    Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part II. Management and therapeutics. J Am Acad Dermatol. 2013;68(5):709 e701–709; quiz 718-720.

  84. 84.

    Page B, Borradori L, Beltraminelli H, Yawalkar N, Hunger RE. Acute generalized exanthematous pustulosis associated with ipilimumab and nivolumab. J Eur Acad Dermatol Venereol. 2018;32(7):e256–7.

    CAS  PubMed  Google Scholar 

  85. 85.

    Matsubara T, Uchi H, Haratake N, Takamori S, Toyozawa R, Miura N, et al. Acute generalized Exanthematous Pustulosis caused by the combination of Pembrolizumab plus chemotherapy in a patient with squamous-cell carcinoma. Clin Lung Cancer. 2020;21(2):e54–6.

    PubMed  Google Scholar 

  86. 86.

    Wang CY, Khoo C, McCormack CJ, Xu W, Pan Y. Acute localised exanthematous pustulosis secondary to pembrolizumab. Australas J Dermatol. 2017;58(4):322–3.

    PubMed  Google Scholar 

  87. 87.

    Coleman EL, Olamiju B, Leventhal JS. The life-threatening eruptions of immune checkpoint inhibitor therapy. Clin Dermatol. 2020;38(1):94–104.

    PubMed  Google Scholar 

  88. 88.

    Jove M, Vilarino N, Nadal E. Impact of baseline steroids on efficacy of programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in patients with advanced non-small cell lung cancer. Transl Lung Cancer Res. 2019;8(Suppl 4):S364–8.

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    • Horvat TZ, Adel NG, Dang TO, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with Ipilimumab at memorial Sloan Kettering Cancer center. J Clin Oncol. 2015;33(28):3193-3198. Retrospective review demonstrating no effect of systemic steroids on overall survival and time to treatment failure in patients with melanoma with an immune-related adverse event to ipilimumab.

  90. 90.

    Kim ST, Tayar J, Trinh VA, Suarez-Almazor M, Garcia S, Hwu P, et al. Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series. Ann Rheum Dis. 2017;76(12):2061–4.

    PubMed  Google Scholar 

  91. 91.

    Burdett N, Hsu K, Xiong L, et al. Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune-related adverse events after immune checkpoint inhibitor therapy. Asia Pac J Clin Oncol. 2020;16(2):e139–45.

    PubMed  Google Scholar 

  92. 92.

    Dutertre M, de Menthon M, Noel N, Albiges L, Lambotte O. Cold agglutinin disease as a new immune-related adverse event associated with anti-PD-L1s and its treatment with rituximab. Eur J Cancer. 2019;110:21–3.

    CAS  PubMed  Google Scholar 

  93. 93.

    •• Cornejo CM, Haun P, English J, 3rd, Rosenbach M. Immune checkpoint inhibitors and the development of granulomatous reactions. J Am Acad Dermatol. 2019;81(5):1165–1175. Comprehensive literature review of granulomatous reactions to PD-1 and PD-L1 inhibitors, delineating clinical presentation, management strategies, and correlation with response to immunotherapy.

  94. 94.

    Elosua-Gonzalez M, Pampin-Franco A, Mazzucchelli-Esteban R, et al. A case of de novo palmoplantar psoriasis with psoriatic arthritis and autoimmune hypothyroidism after receiving nivolumab therapy. Dermatol Online J. 2017;23(8).

  95. 95.

    Yatim A, Bohelay G, Grootenboer-Mignot S, et al. Paraneoplastic Pemphigus Revealed by Anti-programmed Death-1 Pembrolizumab Therapy for Cutaneous Squamous Cell Carcinoma Complicating Hidradenitis Suppurativa. Front Med (Lausanne). 2019;6:249.

  96. 96.

    Castillo B, Gibbs J, Brohl AS, Seminario-Vidal L. Checkpoint inhibitor-associated cutaneous small vessel vasculitis. JAAD Case Rep. 2018;4(7):675–7.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Kosche C, Stout M, Sosman J, Lukas RV, Choi JN. Dermatomyositis in a patient undergoing nivolumab therapy for metastatic melanoma: a case report and review of the literature. Melanoma Res. 2020;30(3):313–6.

    PubMed  Google Scholar 

  98. 98.

    Barbosa NS, Wetter DA, Wieland CN, Shenoy NK, Markovic SN, Thanarajasingam U. Scleroderma induced by Pembrolizumab: a case series. Mayo Clin Proc. 2017;92(7):1158–63.

    PubMed  Google Scholar 

  99. 99.

    Kosche C, Owen JL, Choi JN. Widespread subacute cutaneous lupus erythematosus in a patient receiving checkpoint inhibitor immunotherapy with ipilimumab and nivolumab. Dermatol Online J. 2019;25(10).

  100. 100.

    Andres-Lencina JJ, Burillo-Martinez S, Aragon-Miguel R, et al. Eosinophilic fasciitis and lichen sclerosus in a patient treated with nivolumab. Australas J Dermatol. 2018;59(4):e302–4.

    PubMed  Google Scholar 

  101. 101.

    Tetzlaff MT, Jazaeri AA, Torres-Cabala CA, Korivi BR, Landon GA, Nagarajan P, et al. Erythema nodosum-like panniculitis mimicking disease recurrence: a novel toxicity from immune checkpoint blockade therapy-report of 2 patients. J Cutan Pathol. 2017;44(12):1080–6.

    PubMed  Google Scholar 

  102. 102.

    Zhao CY, Consuegra G, Chou S, Fernandez-Penas P. Intracorneal pustular drug eruption, a novel cutaneous adverse event in anti-programmed cell death-1 patients that highlights the effect of anti-programmed cell death-1 in neutrophils. Melanoma Res. 2017;27(6):641–4.

    PubMed  Google Scholar 

  103. 103.

    Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group. J Immunother Cancer. 2017;5(1):95.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Kato Y, Otsuka A, Miyachi Y, Kabashima K. Exacerbation of psoriasis vulgaris during nivolumab for oral mucosal melanoma. J Eur Acad Dermatol Venereol. 2016;30(10):e89–91.

    CAS  PubMed  Google Scholar 

  105. 105.

    Grimaux X, Delva R, Jadaud E, Croue A. Nivolumab-induced bullous pemphigoid after radiotherapy and abscopal effect. Australas J Dermatol. 2019;60(3):e235–6.

    PubMed  Google Scholar 

  106. 106.

    Morris LM, Lewis HA, Cornelius LA, Chen DY, Rosman IS. Neutrophil-predominant bullous pemphigoid induced by checkpoint inhibitors: a case series. J Cutan Pathol. 2020;47:742–6.

    PubMed  Google Scholar 

  107. 107.

    Matsui Y, Makino T, Ishii N, Hashimoto T, Shimizu T. Detection of IgG antibodies to BP180 NC16a and C-terminal domains and LAD-1 in nivolumab-associated bullous pemphigoid. Eur J Dermatol. 2019;29(5):554–5.

    PubMed  Google Scholar 

  108. 108.

    Shibata A, Yoshikawa T, Makita S, Nakagawa S, Ueda Y, Akiyama M. A case of recurrent Stevens-Johnson syndrome caused by nivolumab therapy. Eur J Dermatol. 2019.

  109. 109.

    Kumar R, Bhandari S. Pembrolizumab induced toxic epidermal necrolysis. Curr Probl Cancer. 2019;100478.

  110. 110.

    Nayar N, Briscoe K, Fernandez PP. Toxic epidermal Necrolysis-like reaction with severe satellite cell necrosis associated with Nivolumab in a patient with Ipilimumab refractory metastatic melanoma. J Immunother. 2016;39(3):149–52.

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Correspondence to Jennifer Choi.

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Chadha, S., Para, A.J. & Choi, J. Management of Immune-Related Cutaneous Adverse Reactions to PD-1 and PD-L1 Inhibitors for the Inpatient Dermatologist. Curr Derm Rep 9, 231–243 (2020).

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  • Immune-related adverse event
  • Immune-related cutaneous adverse event
  • Immune checkpoint inhibitor
  • PD-1 inhibitor
  • PD-L1 inhibitor
  • Oncodermatology