The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have each developed guidelines for the definition and management of toxicities related to immune checkpoint inhibitors (ICIs). Both guidelines are based on the Common Terminology Criteria for Adverse Events (CTCAE) but include considerations for ICI-specific eruptions and cutaneous symptoms. In many areas, these guidelines are overlapping and similar; however, they differ in certain respects, such as the categories of dermatologic eruptions included. NCCN includes maculopapular rash, pruritus, bullous dermatitis, Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN), lichen planus / lichenoid diseases, psoriasis / psoriasiform diseases, oral mucosa inflammation, dry mouth (sicca syndrome), and oral dysesthesia. ASCO includes only 3 categories: rash or inflammatory dermatitis, bullous dermatitis, and severe cutaneous adverse reaction (SCAR).

ASCO assigns a grade from 1 through 4 depending on severity, and NCCN assigns a severity score of mild, moderate, or severe. Cutaneous immune-related adverse events (irAEs) are graded as follows:

Rash / Inflammatory Dermatitis ("Maculopapular")
Look For: Macules and papules coalescing into patches and plaques that frequently affect the upper trunk, spread centripetally, and may be associated with pruritus.

Grade 1 (G1), or "mild": Rash covers less than 10% body surface area (BSA) and may or may not be symptomatic (eg, pruritus, burning, tightness, tenderness).

• Management: Continue ICI therapy; counsel patients to avoid skin irritants. Treat with topical emollients and/or low- or mid-potency topical corticosteroids, and consider antihistamines for pruritus.

Grade 2 (G2), or "moderate": Rash covers 10%-30% BSA with or without associated symptoms (eg, pruritus, burning, tightness, tenderness); rash limits instrumental activities of daily living (iADLs). ASCO guidelines suggest that rashes covering more than 30% BSA with mild symptoms or asymptomatic can be included in G2.

• Management: Consider holding ICI therapy (ASCO) or continue ICI (NCCN); treat with topical emollients and mid- or high-potency topical corticosteroids, and consider oral antihistamines for pruritus. If unresponsive to topical therapies within 1-2 weeks, consider prednisone at dosing 0.5-1 mg/kg/day, tapering over 4 weeks. Monitor weekly for improvement. If there has been no improvement after 4 weeks, then upgrade toxicity to G3.
• If ICI was held, consider resuming ICI until improved to G1, and only topical therapies are indicated.

Grade 3 (G3), or "severe": Rash covers more than 30% BSA with moderate or severe symptoms and limits self-care iADLs. Of note, NCCN also includes rashes of more than 30% BSA with mild symptoms / asymptomatic, whereas ASCO places these patients in G2.

• Management: Hold ICI therapy; treat with topical emollients and high-potency topical corticosteroids. Start prednisone at 1 mg/kg/day or intravenous (IV) methylprednisolone 0.5-1 mg/kg/day (increase up to 2 mg/kg/day if no improvement), tapering over at least 4 weeks and until symptoms improve to G1, then taper over 4-6 weeks. Consider inpatient care.
• Once downgraded to G1 and prednisone (or equivalent) tapered to less than 10 mg/day, consider resuming ICI with close monitoring and dermatology follow-up.

Grade 4 (G4), or "life threatening" (ASCO only): Rash with severe consequences requiring hospitalization and/or urgent interventions.

• Management: Immediately hold ICI, admit patient to oncology with dermatology consultation, and start IV methylprednisolone (or equivalent) dosed at 1-2 mg/kg with slow taper once toxicity resolves. Monitor closely for progression to SCAR (see SCAR heading below).
• Consider an alternative antineoplastic rather than resuming ICI if the rash does not downgrade to G1 or lower. If ICI is the only option for the patient, consider resuming once the reaction reaches G1 level with close dermatology follow-up.

For Lichen Planus and Lichenoid Diseases (NCCN only):
Look for: Violaceous scaly papules and plaques, typically on the trunk or extremities, that may also present with erosions and Wickham's striae on the oral and vulvar mucosa.

"Mild": < 10% BSA

• Management: Continue ICI and treat with high-potency topical steroids or tacrolimus 0.1% ointment. Select topical formulations appropriate to the location of eruption (eg, gel or paste for mucosa, foam or solution for scalp).

"Moderate": 10%-30% BSA, or not responsive to high-potency topical corticosteroids

• Management: Hold ICI and treat with high-potency topical steroids or tacrolimus 0.1% ointment. Consider oral antihistamines for pruritus. Consider treating with prednisone 0.5-1 mg/kg/day until the reaction improves to the "mild" category, then taper over 3 weeks. Trial narrowband ultraviolet B (NB-UVB) if available. If not responsive, increase classification to the "severe" category.
• Consider resuming ICI after the reaction improves to the "mild" category and only topical therapies are indicated.

"Severe": > 30% BSA

• Management: Hold ICI and treat with high-potency topical steroids or tacrolimus 0.1% ointment. Treat with prednisone / IV methylprednisolone at 0.5-1 mg/kg/day until symptoms improve to G1, then taper over 3 weeks. Consider steroid-sparing immunosuppressants such as acitretin (if no childbearing potential), dupilumab, methotrexate, or hydroxychloroquine. Consider resuming ICI after the reaction improves to the "mild" category, and only topical therapies are indicated.

For Psoriasis and Psoriasiform Diseases (NCCN only):
Look for: Pink guttate papules or plaques with silvery scale, typically most prominent on the extensor surfaces, scalp, umbilicus, and postauricular areas, that may also present with palmoplantar or inverse psoriasis features.

"Mild": < 10% BSA

• Management: Continue ICI and treat with high-potency topical steroids. Transition to nonsteroidal alternatives, including topical calcineurin inhibitors (eg, tacrolimus 0.1% ointment) and calcipotriene 0.005%, for long-term management of intertriginous or facial involvement.

"Moderate": 10%-30% BSA, or not responsive to high-potency topical corticosteroids

• Management: Hold ICI and treat with high-potency topical steroids. Use nonsteroidal alternatives, including topical calcineurin inhibitors and calcipotriene 0.005%, for long-term management of intertriginous or facial involvement. Trial NB-UVB if available. Consider apremilast, acitretin (if no childbearing potential), or biologics (anti-TNF, IL-23, or IL-17 inhibitors). If not responsive, escalate therapy to that mentioned in the "severe" category below.
• Consider resuming ICI with close monitoring and dermatology follow-up once symptoms are controlled and BSA is less than 30%, especially if on psoriasis-targeted biologic therapy.

"Severe": > 30% BSA

• Management: Hold ICI and treat with high-potency topical steroids. Use nonsteroidal alternatives, including topical calcineurin inhibitors and calcipotriene 0.005%, for long-term management of intertriginous or facial involvement. Trial NB-UVB if available. Consider apremilast, acitretin (if no childbearing potential), biologics (anti-TNF, IL-23, or IL-17 inhibitors), cyclosporine, and methotrexate.
• Consider resuming ICI with close monitoring and dermatology follow-up once symptoms are controlled and BSA is less than 30%, especially if on psoriasis-targeted biologic therapy.

For Bullous Dermatoses:
Look for: Tense or flaccid bullae that may be preceded and/or associated with pruritus.

G1, or "mild": Blisters cover less than 10% BSA; asymptomatic with no associated erythema (if symptomatic with bullae or erosions on the mucosal surface, upgrade to at least G2).

• Management: Cessation of ICI not necessary but can consider holding; treat with local wound care and high-potency topical steroids.

G2, or "moderate": Painful blisters cover 10%-30% BSA and affect quality of life (QOL) / limit iADLs, requiring intervention (but not meeting the criteria for a higher grade).

• Management: Hold ICI therapy; practice local wound care (plain petrolatum and bandages over open erosions). Start high-potency topical corticosteroids and reassess every 3 days for progression (if no improvement after 3 days, consider dermatology consult or inpatient care with dermatology access). Have a low threshold to treat with prednisone or IV methylprednisolone at 0.5-1 mg/kg/day until improved to G1, then taper over 4-6 weeks. If bullous pemphigoid is diagnosed by biopsy or serology, consider dupilumab (600 mg subcutaneously [SQ] once, then 300 mg SQ every 2 weeks) or rituximab (1000 mg IV once every 2 weeks divided into 2 doses, then 500 mg at months 12 and 18, as needed).
• Consider resuming ICI with close monitoring and dermatology follow-up once G1 has been reached.

G3, or "severe": Skin sloughing over more than 30% BSA with associated pain that limits self-care iADLs.

• Management: Discontinue ICI therapy; NCCN suggests to admit to hospital with urgent dermatology consultation, whereas ASCO encourages consideration of admission. Start IV methylprednisolone at 1-2 mg/kg, converting to oral steroids when appropriate, with taper over at least 4 weeks. If bullous pemphigoid is diagnosed by biopsy or serology, consider steroid-sparing options, including dupilumab or rituximab (1000 mg once every 2 weeks divided into 2 doses, then 500 mg at months 12 and 18, as needed). Consider IV immunoglobulin (IVIG) (2 g/kg over 2-5 days with a monthly cycle until clear as an adjunct to rituximab).
• ASCO suggests consideration of ICI resumption with close monitoring and dermatology follow-up once G1 has been reached.

G4, or "life threatening": Blisters cover > 30% BSA with associated fluid or electrolyte abnormalities.

• Management: Discontinue ICI therapy permanently; admit to hospital immediately with dermatology consultation to intensive care unit (ICU) or burn unit. Start IV methylprednisolone at 1-2 mg/kg, then convert to oral steroids when appropriate, with taper over at least 4 weeks. If bullous pemphigoid is diagnosed by biopsy or serology, consider steroid-sparing options, including dupilumab or rituximab (1000 mg once every 2 weeks divided into 2 doses, then 500 mg at months 12 and 18, as needed). Consider IVIG (2 g/kg over 2-5 days with a monthly cycle until clear as an adjunct to rituximab).
• The culprit ICI should not be resumed in patients with G4 bullous cutaneous toxicities.

For Severe Cutaneous Adverse Reaction (SCAR):
According to ASCO, SCAR includes Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) / drug-induced hypersensitivity syndrome (DIHS).

Look for: Clinical presentation depends on the type of drug eruption. For example, SJS and TEN are characterized by rapidly progressing, dusky, coalescing patches, skin detachment, and mucosal involvement. Various extracutaneous symptoms may be seen in SCARs such as DRESS / DIHS, including fever, lymphadenopathy, hematologic abnormalities, and other organ dysfunction.

G1 and G2: Not applicable; if limited BSA with bullae or erosions, concern should remain for the reaction progressing to G3 or G4.

G3: Skin sloughing over less than 10% BSA with mucosal involvement and associated signs of erythema, purpura, epidermal detachment, and mucous membrane detachment.

• Management: Perform complete medication list review for other potential culprits. Hold ICI therapy. Admit to burn unit and/or consult wound services. Practice supportive care with fluids / electrolyte balance, and focus on infection prevention. Treat with topical emollients (petrolatum or dimethicone) and high-potency topical corticosteroids. Start IV methylprednisolone 0.5-1 mg/kg, converting to oral steroids when appropriate, with taper over at least 4 weeks. For mucous membrane involvement of SJS / TEN, consult ophthalmology, otolaryngology, urology, and/or gynecology, as appropriate, to prevent sequelae from scarring.
• Seek an alternative antineoplastic rather than resuming ICI. If ICI is the only option for the patient, consider carefully resuming in a controlled environment under supervision of oncology, dermatology, and critical care services. True SJS / TEN reaction to ICI should always lead to permanent drug discontinuation.

G4: Skin erythema and blistering or sloughing over 10% BSA or more with associated signs of erythema, purpura, epidermal detachment, and mucous membrane detachment, along with systemic symptoms and concerning blood work abnormalities (eg, liver function test elevations in the setting of DRESS / DIHS).

• Management: Perform complete medication list review for other potential culprits. Permanently discontinue ICI therapy, and admit to burn unit or ICU with dermatology and wound care consulted. Start IV methylprednisolone 1-2 mg/kg, tapering over 4-6 weeks only when toxicity resolves to normal. IVIG (2 g/kg over 3-5 days with a monthly cycle until clear) may be considered in severe cases and those unresponsive to steroids. Other immunosuppressive therapies such as etanercept and cyclosporine can be considered; however, benefit must be weighed against the risk of infection. For mucous membrane involvement of SJS / TEN, consult ophthalmology, otolaryngology, urology, and/or gynecology, as appropriate, to prevent sequelae from scarring. Per ASCO, consider pain or palliative care consultation in patients with DRESS / DIHS manifestations.
• The culprit ICI should not be resumed in patients with G4 SCAR.

For Pruritus (NCCN only):
Look for: Intense itching sensation that presents with or without associated rash. Pruritus may overlap with other cutaneous adverse reactions (eg, maculopapular, bullous, lichenoid) secondary to ICIs.

G1, or "mild": Mild or localized itch

• Management: Continue ICI. Treat with oral antihistamines and whole-body emollients without fragrance. Start mid-potency topical corticosteroids for localized pruritus, and consider over-the-counter topical anesthetics or anti-itch cream (eg, diphenhydramine, pramoxine, camphor, menthol).

G2, or "moderate": Intense or widespread itch with intermittent skin changes from scratching (eg, edema, papulation, excoriations, lichenification, oozing / crusts); limits iADLs

• Management: Hold immunotherapy. Treat with oral antihistamines and whole-body emollients without fragrance. Consider gabapentinoids (gabapentin, pregabalin), NB-UVB, dupilumab, or omalizumab. Treat with mid-potency topical corticosteroids if pruritus is local or with prednisone / IV methylprednisolone 0.5-1 mg/kg/day if widespread until improved to G1, then taper over 4-6 weeks.
• Consider resuming ICI when improved to G1, and only topical therapies indicated.

G3, or "severe": Intense or widespread, constant itch limiting self-care iADLs or sleep

• Management: Hold immunotherapy; treat with oral antihistamines and whole-body emollients without fragrance. Treat with prednisone / IV methylprednisolone 0.5-1 mg/kg/day until improved to G1, then taper over 4-6 weeks. Consider gabapentinoids such as gabapentin or pregabalin. If no response in 1 month, consider dupilumab, omalizumab, or NB-UVB.
• Consider resuming ICI when improved to G1, and only topical therapies indicated.