II. Epidemiology
- Most common premalignant skin lesion
- Responsible for 60% of Squamous Cell Carcinoma involving the skin
-
Prevalence: White skin (increases with age)
- Age 20-29: 10%
- Age 80-89: 75%
III. Pathophysiology
- Superficial keratotic tumor
- Previously considered distinct premalignant changes
- Now thought to be very early Squamous Cell Carcinomas
IV. Risk Factors
- Fair-skinned, blue-eyed persons
- Living in sunny climate
- Cummulative extensive Sun Exposure
- Older persons
V. Symptoms
- Typically asymptomatic
- May be pruritic or burning
VI. Signs
- Characteristics: Rough Scaly patches
- Distribution: Sun exposed areas
- Face and neck
- Left more common (Car driver's window side)
- Dorsal hands
- Forearms
- Face and neck
VII. Diagnosis
- Diagnosis by "feel": Rough
- Palpated more easily than seen
- Biopsy is rarely indicated
VIII. Management: Procedures
-
Cryotherapy with Liquid Nitrogen
- Debride hyperkeratotic lesions first
- Freeze, slowly thaw and then refreeze
- Efficacy increases with duration of freeze time
- Freeze 5 seconds: 39% cure rate
- Freeze 20 seconds: 83% cure rate
- Curettage
- Infiltrate area with Local Anesthetic
- Consider for hyperkeratotic lesions
- Adjuncts
- Trichloroacetic acid (TCA) before curettage
- Electrosurgery post-curettage to destroy residual tissue
- Photodynamic therapy
- Photosensitizer applied to skin followed by exposure to specific light source
- Protocols
- Aminolevulinic Acid (Levulan Kerastick): Exposure to blue light after 14 hours
- Methyl aminolevulinate (Metvixia): Exposure to red light after 3 hours
IX. Management: Topical Treatments with Keratolytics
- Indicated when numerous lesions (e.g. >15 lesions present)
- Topical 5-Flourouracil (5-FU)
- Preparations
- Fluorouracil cream 5% (Efudex) - preferred, most effective at lowest cost
- Fluorouracil cream 1% (Fluoroplex)
- Fluorouracil microspore cream 0.5% (Carac)
- Adverse effects
- Healing may require 2 months
- Photosensitivity (protect from direct sun)
- Dryness, erythema, irritation, crusting, pealing and even disfigurement on the face
- Irritation more common with 5% cream; 0.5% appears better tolerated (but less effective)
- Apply Skin Lubricants frequently (consider petrolatum at night)
- May apply cool compresses to soothe skin
- Technique
- Use twice daily to twice weekly for 2-4 weeks until marked inflammation and lesion crusts over
- Consider 0.5% cream for one week prior to Cryotherapy
- Wait 30 min before applying Sunscreen or makeup
- If excessive response occurs, stop for 2-3 days and then restart for total of 2-4 cummulative weeks
- Efficacy
- 5-Fluorouracil 5% cream more effective, less re-treatement than Imiquimod, ingenol and Phototherapy
- 5-FU 5% cream is also among the most cost effective options (<$100 per course)
- However lower concentrations (e.g. Carac) having more limited efficacy, at 10 times the cost
- Jansen (2019) N Engl J Med 380:935-46 [PubMed]
- 5-Fluorouracil 5% cream more effective, less re-treatement than Imiquimod, ingenol and Phototherapy
- Preparations
- Topical Diclofenac 3% gel in 2.5% hyaluronic acid (Solaraze)
- Technique: Apply twice daily for 90 days
- Efficacy
- Complete resolution in 50% of cases
- Less effective than Imiquimod (Aldara), 5-Fluorouracil (5-FU) or ingenol (Picato), yet >$600 per course
- Adverse Effects
- Reference
-
Imiquimod 5% Cream (Aldara)
- Applied 3-4 times weekly at bedtime and wash off in AM; use for up to 16 weeks
- Efficacy
- Complete response in up to 57% of patients
- Partial response (75% reduction) in up to 72% of patients
- Adverse effects
- Cosmetic outcomes not studied
- Severe erythema (80%)
- Severe erosions (40%)
- Alternative preparation
- Zyclara (2.5 to 3.75% cream) used for 2 weeks on and 2 weeks off cycles (at 10 times the cost of Aldara)
- References
- Ingenol mebutate (Picato gel)
- Technique: Total course is 2-3 days
- Adverse effects
- Skin irritation (erythema, flaking or crusting)
- Efficacy
- Similar to Imiquimod and 5-Fluorouracil, but very expensive ($1000)
- Tirbanibulin (Klisyri) 1% Ointment
- Released in 2021
- Only 5 day course, but with no evidence of benefit over 5-FU in efficacy or tolerability and at 10 times the cost (>$1000)
- (2021) Presc Lett 28(7): 41
-
Chemical Peels for face (applied by dermatology)
- Similar efficacy to Fluorouracil
- Preparations
- Jessner's Solution (Resorcinol, Lactic Acid, Salicylic acid)
- Trichloroacetic acid 35% (Tri-Chlor)
- References
X. Management: Adjunctive measures
-
Niacinamide
- Indicated if Actinic Keratosis patient with 2 or more Nonmelanoma Skin Cancers
- Decreases risk of new Actinic Keratosis lesions and Nonmelanoma Skin Cancers
- Dose: 500 mg orally twice daily ($5/month)
XI. Prevention
- See Sun Exposure (lists general preventive measures)
- See Sunscreen
XII. Course
- Spontaneous resolution in 25-50% of lesions over 12 months
- Progression to squamous cell cancer: 6-10% over 10 years
- Actinic Keratoses are a marker of invasive SCSS
- Malignant transformation rate may be as high as 20% per year
- Malignant transformation of Actinic Keratoses are responsible for 60% of CSCC cases
- Higher risk of Squamous Cell Carcinoma progression in thick tumors (especially on scalp), Immunosuppression
XIII. References
- (2019) Presc Lett 26(5)
- Habif (2004) Dermatology p. 736-43
- Mcintyre (2007) Am Fam Physician 76(5):667-71 [PubMed]
- Stulberg (2004) Am Fam Physician 70:1481-8 [PubMed]