Skin Toxicities

Grading Toxicity

MACULOPAPULAR RASH (aka morbilliform rash)

Definition: A disorder characterized by the presence of macules (flat) and papules (elevated); frequently affecting the upper trunk, spreading centripetally and associated with pruritus

Macules/papules covering <10% BSA with or without symptoms (e.g., pruritus, burning, tightness)

Macules/papules covering 10-30% BSA with or without symptoms (e.g., pruritus, burning, tightness); limiting instrumental ADLs

Macules/papules covering >30% BSA with or without associated symptoms; limiting self-care ADLs; skin sloughing covering <10% BSA

Papules/pustules covering any % BSA with or without symptoms and associated with superinfection requiring IV antibiotics; skin sloughing covering 10-30% BSA

PRURITUS

Definition: A disorder characterized by an intense itching sensation

Mild or localized; topical intervention indicated

Intense or widespread; intermittent; skin changes from scratching (e.g., edema, papulation, excoriations, lichenification, oozing/crusts); limiting instrumental ADLs

Intense or widespread; constant; limiting self-care ADL or sleep

Management

Overall Strategy:

Assess for other etiology of rash: ask patient about new medications, herbals, supplements, alternative/complementary therapies, lotions, etc.

Advise gentle skin care:
- Avoid soap. Instead, use non-soap cleansers that are fragrance- and dye-free (use mild soap on the axillae, genitalia, and feet)
- Daily applications of non-steroidal moisturizers or emollients containing humectants (urea, glycerin)
- Apply moisturizers and emollients in the direction of hair growth to minimize development of folliculitis
Advise sun-protective measures
Assess patient & family understanding of prevention strategies and rationale
- Identify barriers to adherence

Immunotherapy to continue
Oral antihistamines will be used in some patients
Topical corticosteroids will be used in some patients (0.5 mg/kg)
Advise vigilant skin care
- Increase to twice daily applications of non-steroidal moisturizers or emollients applied to moist skin
- Moisturizers with ceramides and lipids are advised; however, if cost is an issue, petroleum jelly is also effective
- Soothing methods
  - Cool cloth applications
  - Topicals with cooling agents such as menthol or camphor
  - Refrigerating products prior to application
- Avoid hot water; bathe or shower with tepid water
- Keep fingernails short
- Cool temperature for sleep
Advise strict sun protection
Monitor vigilantly. Instruct patient & family to call clinic with any sign of worsening rash/symptoms. Anticipate office visit for evaluation
Assess patient & family understanding of skin care recommendations and rationale
- Identify barriers to adherence

Ipilimumab will be withheld for any Grade 2 event
Oral corticosteroids (0.5 mg/kg–1.0 mg/kg) and oral antihistamines/oral anti-pruritics to be used
Consider dermatology consult
Patient education:
- Proper administration of oral corticosteroids
  - Take with food
  - Take early in day
  - Concomitant medications may be prescribed
    - H2 blocker
    - Antibiotic prophylaxis
Advise vigilant skin care
- Gentle skin care
- Tepid baths; oatmeal baths
Advise strict sun protection
Assess patient & family understanding of toxicity and rationale for treatment hold
- Identify barriers to adherence

Nivolumab to be withheld for Grade 3 rash or confirmed SJN or TEN
Ipilimumab to be discontinued for any Grade 3/4 event, and nivolumab for Grade 4 rash or confirmed SJS or TEN
Pembrolizumab or nivolumab to be discontinued for any Grade 3/4 event that recurs, persists ≥12 weeks, or for inability to reduce steroid dose to ≤10 mg prednisone or equivalent within 12 weeks
Anticipate hospitalization and initiation of IV corticosteroids (1.5–2.0 mg/kg)
Anticipate dermatology consult +/- biopsy
Provide anticipatory guidance:
- Rationale for hospitalization and treatment discontinuation
- Rationale for prolonged steroid taper
- Side effects of high-dose steroids
- Risk of opportunistic infection and need for antibiotic prophylaxis
- Effects on blood sugars, muscle atrophy, etc.
Assess patient & family understanding of toxicity and rationale for treatment discontinuation
- Identify barriers to adherence, specifically compliance with steroids when transitioned to oral corticosteroids

RED FLAGS:

Extensive rash (>50% BSA), or rapidly progressive
Oral involvement
Concern for suprainfection