Dermatologic Reactions to Immune Checkpoint Inhibitors

Skin Toxicities and Immunotherapy

Vincent Sibaud


Am J Clin Dermatol. 2018;19(3):345-361. 

In This Article

Other Cutaneous Toxicities


The occurrence of sarcoidosis with anti-PD-1/PD-L1 or with ipilimumab treatment is not uncommon. An exacerbation of a preexisting sarcoidosis is also possible.[42,84] The most commonly involved sites are the lungs (e.g., pulmonary micronodular and ground-glass infiltrates, mediastinal and hilar lymphadenopathy),[85–87] and it can sometimes be mistaken for cancer progression. Other organs can be involved, such as eyes, bones, kidney, spleen, the nervous system, joints with Löfgren's syndrome, and the skin.[28,84–91]

Immune checkpoint-related cutaneous sarcoidosis mainly manifests in the form of subcutaneous embedded erythematous nodules,[84,87,92] with non-caseating epithelioid granuloma. Other forms have been reported: papules or coalescing plaques of varying degrees,[86–88] annular lesions,[85] exclusive facial involvement,[91] and a specific localization at previous scar sites[87,90] or tattoosarcoidosis.[88] They most often occur in association with pulmonary involvement, although they are sometimes isolated.[85,91]

Systemic corticosteroids generally allow for regression of the lesions, and the immunotherapy can most often be resumed. The isolated cutaneous lesions can also be treated with topical corticosteroids[89] or synthetic anti-malarial drugs.[91]

Some authors consider immunotherapy-induced sarcoidosis to be a paradoxical reaction.[87,91,92] Indeed, an upregulation of PD-1 by the T CD4+ lymphocytes of patients with sarcoidosis has recently been shown.[93]

Sweet's Syndrome

Several cases have been noted with ipilimumab[94–96] and more recently with nivolumab treatment.[19] Localized acral variants (''neutrophilic dermatosis of the hands'') can also occur.[94] These lesions respond rapidly to oral corticosteroids. Two cases of pyoderma gangrenosum have also been reported with ipilimumab.[52,97]

Acneiform Rash and Papulopustular Rosacea

An acneiform rash (or papulopustular folliculitis), mainly on the torso, can sometimes be seen with anti-CTLA-4,[54,98] anti-PD-1 or anti-PD-L1 monoclonal antibodies.[11,23,99,100] A preexisting rosacea can be also exacerbated by immunotherapy, mainly in the form of facial papulopustular rosacea.[21,98,101]

Infrequent Toxicities

A wide range of other dermatologic reactions has been sporadically described with immune checkpoint inhibitors. They are listed in Table 2.