Actinic Keratoses

See Also

Epidemiology

Most common premalignant skin lesion
1. Responsible for 60% of Squamous Cell Carcinoma involving the skin
Prevalence: White skin (increases with age)
1. Age 20-29: 10%
2. Age 80-89: 75%

Pathophysiology

Superficial keratotic tumor
Previously considered distinct premalignant changes
Now thought to be very early Squamous Cell Carcinomas
1. Ortonne (2002) Br J Dermatol 146:20-3 [PubMed]

Risk Factors

Fair-skinned, blue-eyed persons
Living in sunny climate
Cummulative extensive Sun Exposure
Older persons

Symptoms

Typically asymptomatic
May be pruritic or burning

Signs

Characteristics: Rough Scaly patches
1. Discrete, circumscribed
2. Verrucous or keratotic
3. White scale or rough patch
4. Red-brown, pink or skin-colored Macule or Papule
5. Often recurs after patient "picks off" scale
6. Vary in size from millimeters to centimeters (typically 2-6 mm in size)
Distribution: Sun exposed areas
1. Face and neck
  1. Left more common (Car driver's window side)
2. Dorsal hands
3. Forearms

Diagnosis

Diagnosis by "feel": Rough
1. Palpated more easily than seen
Biopsy is rarely indicated

Management
Procedures

Cryotherapy with Liquid Nitrogen
1. Debride hyperkeratotic lesions first
2. Freeze, slowly thaw and then refreeze
3. Efficacy increases with duration of freeze time
  1. Freeze 5 seconds: 39% cure rate
  2. Freeze 20 seconds: 83% cure rate
Curettage
1. Infiltrate area with Local Anesthetic
2. Consider for hyperkeratotic lesions
3. Adjuncts
  1. Trichloroacetic acid (TCA) before curettage
  2. Electrosurgery post-curettage to destroy residual tissue
Photodynamic therapy
1. Photosensitizer applied to skin followed by exposure to specific light source
2. Protocols
  1. Aminolevulinic Acid (Levulan Kerastick): Exposure to blue light after 14 hours
  2. Methyl aminolevulinate (Metvixia): Exposure to red light after 3 hours

Management
Topical Treatments with Keratolytics

Indicated when numerous lesions (e.g. >15 lesions present)
Topical 5-Flourouracil (5-FU)
1. Preparations
  1. Fluorouracil cream 5% (Efudex) - preferred, most effective at lowest cost
  2. Fluorouracil cream 1% (Fluoroplex)
  3. Fluorouracil microspore cream 0.5% (Carac)
2. Adverse effects
  1. Healing may require 2 months
  2. Photosensitivity (protect from direct sun)
  3. Dryness, erythema, irritation, crusting, pealing and even disfigurement on the face
    1. Irritation more common with 5% cream; 0.5% appears better tolerated (but less effective)
    2. Apply Skin Lubricants frequently (consider petrolatum at night)
    3. May apply cool compresses to soothe skin
3. Technique
  1. Use twice daily to twice weekly for 2-4 weeks until marked inflammation and lesion crusts over
  2. Consider 0.5% cream for one week prior to Cryotherapy
  3. Wait 30 min before applying Sunscreen or makeup
  4. If excessive response occurs, stop for 2-3 days and then restart for total of 2-4 cummulative weeks
4. Efficacy
  1. 5-Fluorouracil 5% cream more effective, less re-treatement than Imiquimod, ingenol and Phototherapy
    1. 5-FU 5% cream is also among the most cost effective options (<$100 per course)
    2. However lower concentrations (e.g. Carac) having more limited efficacy, at 10 times the cost
    3. Jansen (2019) N Engl J Med 380:935-46 [PubMed]
Topical Diclofenac 3% gel in 2.5% hyaluronic acid (Solaraze)
1. Technique: Apply twice daily for 90 days
2. Efficacy
  1. Complete resolution in 50% of cases
  2. Less effective than Imiquimod (Aldara), 5-Fluorouracil (5-FU) or ingenol (Picato), yet >$600 per course
3. Adverse Effects
  1. Skin inflammation (Local irritation, dryness and Pruritus
    1. Less irritating than Imiquimod (Aldara), 5-Fluorouracil (5-FU) or ingenol (Picato)
4. Reference
  1. Rivers (1997) Arch Dermatol 133:1239-42 [PubMed]
Imiquimod 5% Cream (Aldara)
1. Applied 3-4 times weekly at bedtime and wash off in AM; use for up to 16 weeks
2. Efficacy
  1. Complete response in up to 57% of patients
  2. Partial response (75% reduction) in up to 72% of patients
3. Adverse effects
  1. Cosmetic outcomes not studied
  2. Severe erythema (80%)
  3. Severe erosions (40%)
4. Alternative preparation
  1. Zyclara (2.5 to 3.75% cream) used for 2 weeks on and 2 weeks off cycles (at 10 times the cost of Aldara)
5. References
  1. Stockfleth (2002) Arch Dermatol 138:1498-502 [PubMed]
Ingenol mebutate (Picato gel)
1. Technique: Total course is 2-3 days
  1. Picato 0.05%: Apply to torso or extremities for 2 days
  2. Picato 0.015%: Apply to face or scalp for 3 days
2. Adverse effects
  1. Skin irritation (erythema, flaking or crusting)
3. Efficacy
  1. Similar to Imiquimod and 5-Fluorouracil, but very expensive ($1000)
Tirbanibulin (Klisyri) 1% Ointment
1. Released in 2021
2. Only 5 day course, but with no evidence of benefit over 5-FU in efficacy or tolerability and at 10 times the cost (>$1000)
3. (2021) Presc Lett 28(7): 41
Chemical Peels for face (applied by dermatology)
1. Similar efficacy to Fluorouracil
2. Preparations
  1. Jessner's Solution (Resorcinol, Lactic Acid, Salicylic acid)
  2. Trichloroacetic acid 35% (Tri-Chlor)
3. References
  1. Lawrence (1995) Arch Dermatol 131:176-81 [PubMed]

Management
Adjunctive measures

Niacinamide
1. Indicated if Actinic Keratosis patient with 2 or more Nonmelanoma Skin Cancers
2. Decreases risk of new Actinic Keratosis lesions and Nonmelanoma Skin Cancers
3. Dose: 500 mg orally twice daily ($5/month)

Prevention

See Sun Exposure (lists general preventive measures)
See Sunscreen

Course

Spontaneous resolution in 25-50% of lesions over 12 months
Progression to squamous cell cancer: 6-10% over 10 years
1. Actinic Keratoses are a marker of invasive SCSS
2. Malignant transformation rate may be as high as 20% per year
3. 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

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]