Managing Skin Reactions and Rash from Checkpoint Inhibitor Therapy

Skin reactions are among the most common side effects of checkpoint inhibitors, affecting 30-40% of patients. While usually not serious, they can significantly impact quality of life. Most skin reactions are manageable with appropriate treatment, allowing continued immunotherapy.

**Types of Skin Reactions**

Maculopapular Rash (Most Common):
- Red, flat or slightly raised spots
- Often itchy
- Affects 20-30% of patients
- Usually appears within 6 weeks of starting treatment
- Resembles allergic reaction or viral rash

Pruritus (Itching):
- Affects up to 35% of patients
- Can occur with or without visible rash
- May be localized or generalized
- Often worse at night
- Can be severe and disabling

Vitiligo (Loss of Pigmentation):
- White patches on skin
- Occurs in 5-10% of melanoma patients
- Usually permanent
- Sign of immune activation
- Associated with better treatment response

Other Reactions:
- Psoriasis-like eruptions
- Lichenoid reactions
- Stevens-Johnson syndrome (rare but serious)
- Bullous pemphigoid (blistering)
- Exfoliative dermatitis

**Severity Grading**

Grade 1 (Mild):
- Rash covering <10% of body
- No significant symptoms
- No impact on daily activities
- Mild itching

Grade 2 (Moderate):
- Rash covering 10-30% of body
- Moderate symptoms
- Interfering with daily activities
- Significant itching

Grade 3 (Severe):
- Rash covering >30% of body
- Severe symptoms
- Limiting self-care
- Unbearable itching
- Secondary infection

Grade 4 (Life-Threatening):
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Severe blistering or sloughing

**Treatment by Severity**

Grade 1 (Mild):

Continue Immunotherapy

Topical Treatments:
- Moisturizers liberally and frequently
- Topical corticosteroids (moderate potency):
* Triamcinolone 0.1% cream for body
* Hydrocortisone 1% for face
* Apply twice daily to affected areas

For Itching:
- Oral antihistamines:
* Hydroxyzine 25-50 mg every 6 hours
* Cetirizine 10 mg daily
* Diphenhydramine 25-50 mg at bedtime
- Colloidal oatmeal baths
- Cool compresses

Monitoring:
- Weekly assessment
- Watch for spread or worsening
- Document extent with photos

Grade 2 (Moderate):

Hold Immunotherapy Temporarily

Systemic Treatment:
- Oral prednisone 0.5-1 mg/kg daily (30-60 mg)
- Continue topical steroids
- Antihistamines around the clock
- Resume immunotherapy when improved to Grade 1

Dermatology Consultation:
- Confirm diagnosis
- Rule out other causes
- Skin biopsy if diagnosis unclear
- Recommend treatment plan

Monitoring:
- Daily assessment initially
- Photos to track progress
- Watch for infection

Grade 3-4 (Severe):

Discontinue Immunotherapy (Temporarily or Permanently)

Immediate Treatment:
- High-dose prednisone 1-2 mg/kg daily
- Hospitalization if Grade 4
- Intensive skin care
- Wound care if blistering
- IV immunosuppression if steroid-refractory

Additional Therapy:
- Mycophenolate mofetil if not responding to steroids
- IVIG for severe cases
- Antibiotics if secondary infection
- Pain management

**Managing Severe Itching**

Pharmacologic Approaches:

First-Line:
- Hydroxyzine 25-50 mg every 6 hours
- Doxepin 10-25 mg at bedtime (strong antipruritic)
- Gabapentin 300-900 mg at bedtime for neuropathic itch

Second-Line:
- Aprepitant (Emend) 80 mg daily x 3 days
- Dupilumab (Dupixent) for severe cases
- Low-dose naltrexone 4.5 mg daily

Topical:
- Menthol 1-3% lotion
- Pramoxine 1% cream
- Calamine lotion
- Capsaicin cream (for localized itch)

Non-Pharmacologic Strategies:

Skincare:
- Lukewarm showers (not hot)
- Gentle, fragrance-free cleansers
- Pat dry, don't rub
- Moisturize within 3 minutes of bathing
- Use thick creams or ointments (Aquaphor, CeraVe)

Environmental:
- Keep bedroom cool (65-68°F)
- Use humidifier in dry climates
- Soft, breathable cotton clothing
- Avoid tight or irritating fabrics
- Keep nails short to prevent scratching injury

Behavioral:
- Distraction techniques
- Relaxation exercises
- Cool compresses instead of scratching
- Gentle pressure instead of scratching
- Scratching alternative surfaces

**Managing Vitiligo**

Understanding Vitiligo:
- White patches from melanocyte destruction
- Common in melanoma patients (good prognostic sign)
- Usually permanent
- May appear during or after treatment
- Often affects face, hands, and arms

Cosmetic Management:
- Self-tanning products
- Makeup (Dermablend, Covermark)
- Sunscreen essential (SPF 50+)
- Embrace as badge of successful treatment

Psychological Support:
- Support groups
- Counseling if distressing
- Remember: associated with better cancer outcomes
- Many patients view it as positive sign

**Sun Protection**

Critical During Immunotherapy:
- Checkpoint inhibitors increase photosensitivity
- Vitiligo areas especially vulnerable
- Sun exposure can trigger flares

Recommendations:
- Broad-spectrum sunscreen SPF 50+
- Reapply every 2 hours outdoors
- Wear protective clothing (UPF 50+)
- Wide-brimmed hat
- Seek shade 10 AM - 4 PM
- UV-protective sunglasses

**When to Seek Immediate Care**

Go to ER if:
- Sudden widespread blistering
- Mucous membrane involvement (mouth, eyes, genitals)
- Fever with rash
- Facial swelling
- Difficulty breathing or swallowing
- Skin sloughing or peeling

Contact Doctor Same-Day if:
- Rapidly spreading rash
- Signs of infection (pus, increasing pain, warmth)
- Unable to sleep due to itching
- Rash interfering with eating or daily activities

**Resuming Immunotherapy**

Generally Safe if:
- Grade 1-2 reactions fully resolved
- No signs of infection
- Off systemic steroids or on low dose
- Patient willing to continue

Exercise Caution if:
- Grade 3 reaction
- Required high-dose steroids
- Blistering or mucosal involvement
- May rechallenge with close monitoring

Permanent Discontinuation:
- Grade 4 reactions
- Stevens-Johnson syndrome or TEN
- Severe bullous disorders
- Life-threatening reactions

**Prevention Strategies**

Before Starting Treatment:
- Establish baseline skin exam
- Photograph existing lesions
- Sun protection education
- Moisturizer routine

During Treatment:
- Daily inspection for new rashes
- Liberal moisturizer use
- Avoid harsh soaps and irritants
- Sun protection always
- Report changes promptly

**Questions to Ask Your Doctor**

- What type of skin reaction do I have?
- Can I continue immunotherapy?
- What treatments can help my symptoms?
- Should I see a dermatologist?
- How can I prevent worsening?
- Will this be permanent?

**Patient Success Story**

"I developed an itchy rash on my chest and arms after my third OPDIVO treatment. It was unbearable at night. My oncologist prescribed hydroxyzine, strong moisturizers, and triamcinolone cream. Within a week, the itching was 50% better. I continued OPDIVO without interruption. After 3 weeks, my rash resolved completely. I learned to moisturize religiously and keep my skin well-hydrated - that made all the difference."

Our team can provide dermatology referrals and skincare product recommendations for managing immunotherapy skin reactions.