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