Cutaneous adverse eruptions.
Cutaneous irAEs are one of the most prevalent irAEs caused by anti-PD-1/PD-L1 agents. In the case reports studied, both anti-PD-1 agents (nivolumab and pembrolizumab) and anti-PD-L1 agents (atezolizumab, durvalumab, avelumab), presented cutaneous irAEs in 30-40% of the patients. However, the vast majority of these cutaneous irAEs caused by immune checkpoint inhibitors are self-limiting and present an acceptable skin toxicity profile 4. These cutaneous irAEs can be classified into six main categories: bullous eruptions, pruritus, pigmentary disorders, inflammatory dermatoses, severe cutaneous adverse reactions (SCARs), or life-threatening drug reactions 5(Figure 2).
Based on the histological and clinical severity and percentage of skin/body surface area involvement, the cutaneous adverse events are mainly classified into the following grades:
Grade 1: asymptomatic with macules/papules covering majorly <10% of the body/skin surface area
Grade 2: macules/papules covering 10% to 30% of the body/skin surface area can be symptomatic as well as asymptomatic.
Grade 3: about >30% of the body/skin surface area is covered. The appearance of macules/papules with or without symptoms.
Grade 4: it is the most severe cutaneous response and can be life-threatening such as Stevens-Johnson syndrome, TEN, and bullous dermatitis involving about >30% of skin/body surface area. Intensive care should be taken for the proper management.
Other notable dermatologic irAEs include pruritus and vitiligo, with high-grade pruritus occurring in less than 2% of patients. 8% of patients developed vitiligo, primarily those with melanoma6. The incidence of all-grade rash due to anti-PD-1 therapy is 14-17% and the severe rash is less than 2% as shown in the figure (Figure3). The most common cutaneous irAEs associated with immune checkpoint mAb therapy is skin rash, including lichenoid (lichenoid dermatitis and bullous disorders including bullous pemphigoid), which poses a greater risk due to their severity and potentially life-threatening consequences. The pathophysiological mechanisms involving cutaneous toxicities of immune checkpoint inhibitors are mainly unknown, but the majority are T-cell mediated. The development of these cutaneous irAEs involves blockade of a common antigen, which is co-expressed on both tumor cells and dermo-epidermal junction, and/or other parts of the skin. They likely target the antigens in the dermis/epidermis of the skin by reactivating CD4+/CD8+ T cells and producing the inflammatory response after cross-reaction with normal skin7.
Inflammatory Skin Reactions