Wound care and infection prevention are essential when there is denuded skin. Gentle cleansing is a daily priority, as well as maintaining moist occlusion of affected areas. Limited disease may be managed with super potent topical corticosteroids; yet patients with bullous disease that is symptomatic, limits daily routine, or covers >30% of body surface area require systemic therapy. Systemic corticosteroids may provide immediate effect but should be limited when possible with preference for steroid-sparing agents for long-term maintenance therapy. Steroid-sparing agents include dupilumab, omalizumab, dapsone, methotrexate, and rituximab.25,36-40 Doxycycline and niacinamide may be used in mild presentations, but careful consideration should be taken with ICI-induced bullous pemphigoid given the association of systemic antibiotic use with dysregulation of the gut microbiome, which has been shown to potentially restrict the intended immune response of ICIs.41
Lichenoid Eruption
Lichenoid eruptions are associated with anti-PD-1/PD-L1 therapy and occur in 6% to 25% of patients.6,13,42 The clinical presentation is variable, with classic pruritic erythematous to violaceous flat-topped papules and plaques with Wickham striae seen frequently on the trunk and extremities (Figure 3). However, bullous, erosive, hypertrophic, inverse, papulosquamous, transient acantholytic dermatosis-like, and oral variants have been described. Lichenoid eruptions may also mimic eczematous or maculopapular reactions; however, their onset is typically later in the treatment course, with a mean time to onset of 4 months; and histopathologic features are distinguishing.5,43,44
Mild-moderate lichenoid eruptions can be treated with topical therapies including moderate-strength corticosteroids, calcineurin inhibitors, or vitamin D analogs. Systemic corticosteroids can be considered for moderate-severe disease with transition to steroid-sparing agents such as acitretin, narrowband UVB phototherapy, doxycycline, and cyclosporine.5,25,42,45 Classic lichen planus has been treated with dupilumab46-48 as well as biologic inhibitors of interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-alpha)49,50; thus efficacy of
these therapies for ICI-induced lichenoid eruptions are feasible and may be considered for refractory disease. Nonetheless, the benefits of biologic therapy are theoretical, and effects on a patient’s malignancy must be considered, so shared decision-making with the oncologic team is essential.
Psoriasiform Eruption
ICI-associated psoriasiform eruptions are most common in patients with a history of psoriasis, and these patients tend to flare soon after initiation of immunotherapy. De novo disease represents a minority of reported cases and occurs later in the treatment course. Plaque psoriasis is typical, although guttate, pustular, inverse, and scalp-limited varieties have been described, along with psoriatic arthritis.5,25,51,52
Topical therapies including moderate-strength corticosteroids, calcineurin inhibitors, and vitamin D analogs are foundational for psoriasiform eruptions and are typically sufficient in mild-moderate disease. Moderate-severe or recalcitrant disease can be treated with classic psoriasis therapeutics such as apremilast, acitretin, and narrowband UVB phototherapy.5,53 Systemic steroids may be used in devastating disease, although it is generally avoided given the propensity for rebound flaring when discontinued. Oral immunosuppressives used in classic disease, such as methotrexate and cyclosporine, are generally discouraged given their contraindication in cancer patients. Similarly, biologics including inhibitors of TNF-alpha, IL-17, interleukin-12/23 (IL-12/23), interleukin-23 (IL-23), which are routinely used in classic psoriasis, are approached with hesitancy given the historical belief that they may propagate malignancy. Ongoing research suggests that these proinflammatory pathways may facilitate progression and metastasis in certain malignancies, so their inhibition may provide theoretical anti-cancer benefit in these cases while also treating the psoriasiform eruption.54,55
CONCLUSION
Widespread application of ICIs is improving cancer outcomes; however, cirAEs are common and necessitate rapid and appropriate recognition, diagnosis, and management in order to limit the severity and duration of toxicity that leads to the interruption of therapy and more severe complications and ultimately to promote an optimized quality of life. All clinicians interfacing with cancer patients should be able to recognize these common cutaneous reactions to expedite consultation or proper treatment, as suggested by the multidisciplinary physician-developed algorithm. Moderate-severe or recalcitrant cutaneous reactions are best managed cooperatively with a dermatologist and the oncologic team so that therapeutic interventions have enhanced effects, time away from intended anti-cancer treatment is minimized, and patient experience is improved.
