Actinic Keratosis

• Fred F. Ferri, M.D.
• Heather Ferri, D.O.

 Basic Information

Definition

Actinic keratoses (AKs) are common skin lesions usually presenting as multiple erythematous or yellow-brown, dry, scaly lesions in the middle aged or elderly.

Synonyms

1. Solar keratosis

2. Senile keratosis

3. AK

ICD-10CM CODES
L57.0	Actinic keratosis

Epidemiology & Demographics

Incidence

In regions of the northern hemisphere, 11%-25% of adults have a minimum of one AK. In regions closer to the equator, 40%-60% of adults have a minimum of one AK.

Peak Incidence

The risk of squamous cell carcinoma in patients with AK is 6%-10%. Risk factors associated with increased risk of invasive squamous cell carcinoma arising from actinic keratosis include lesion location (lip, ear, extremities), lesion characteristics (ulceration, induration, hyperkeratotic, proliferative, inflamed, bleeding, large surface area and depth), pigmentation (any rapid changes in presentation, presence of multiple lesions, evidence of greater ultraviolet [UV]-induced skin damage), presence of concomitant illness (lymphoma, leukemia), and use of concomitant medications (immunosuppressive agents, medications that increase sun sensitivity).¹

Prevalence

1. •

   In the United States, 58.08 million per year.

2. •

   Highest prevalence in those with fair complexions with high sun exposure.

3. •

   Approximately 60% of predisposed individuals older than 40 years will have one AK.

4. •

   Caucasians’ risk increases with age: at age 20-29 prevalence is <10%; at age 80-89, prevalence is approximately 75%.

Predominant Sex and Age

Males > females, age 65-74. Occurs most in those with fair complexions who burn rather than tan following sun exposure.

Genetics

There is increased frequency of non-melanoma skin cancers connected to squamous cell cancers with the genetic conditions xeroderma pigmentosum, oculocutaneous albinism, epidermodysplasia verruciformis, dystrophic epidermolysis bullosa, Ferguson-Smith syndrome, and Muir-Torre syndrome.

Risk Factors

1. •

   Immunosuppression, exposure to UV light, ionizing radiation, arsenic, human papillomavirus, cigarette smoke, chronic ulcers, thermal burns, chronic discoid lupus erythematosus, and nonhealing wounds.

2. •

   Lichen planus, lichen sclerosis, linear and classic porokeratosis, and disseminated superficial actinic porokeratosis.

3. •

   Age, gender, skin color, and mutations in p53 tumor suppressor gene.

Physical Findings & Clinical Presentation

1. •

   Typical lesions occur on sun-damaged skin, usually on the face and neck and the dorsal aspects of hands and forearms (Fig. E1).

   

2. •

   Advanced lesions are characterized by a hard, spiky scale and usually measure 1 cm in diameter or less. Early lesions manifest with redness and minimal scale. With progression, scales become thicker and yellow and may resemble a small squamous cell carcinoma. On examinations, lesions are rough and gritty.

3. •

   The surrounding skin frequently shows additional features of sun damage, including atrophy, pigment changes, and telangiectasia.

4. •

   Classifications

   1. 1.

      Hypertrophic AK with a cutaneous horn: Biopsy is necessary to distinguish the cutaneous horn from squamous cell carcinoma, seborrheic keratosis, verruca, and trichilemmoma and basal cell carcinoma. Hypertrophic AK has appearance of thick, scaling skin elevations.

   2. 2.

      Lichenoid AK: Most commonly found on the torso and upper extremities. Must be distinguished from BCC due to pink and pearly characteristics.

   3. 3.

      Proliferative AK: Often reappear after treatment and are characterized by a diameter >1 cm. Often occurs in same differential as Bowen’s disease or SCC.

   4. 4.

      Spreading pigmented AK: Must be biopsied to distinguish from lentigo maligna–type melanoma in situ as well as solar lentigo.

   5. 5.

      Actinic cheilitis: Characterized by red and sometimes abrasive lesions around the border of the lips and skin.

Etiology

1. •

   Sun exposure, ionizing radiation.

2. •

   Arsenic, polycyclic hydrocarbon exposure.

Diagnosis

Differential Diagnosis

1. •

   Heavily pigmented variants may be clinically mistaken for lentigo maligna.

2. •

   Basal cell or squamous cell carcinoma.

3. •

   Seborrheic keratosis.

4. •

   Eczema.

5. •

   Bowen disease (intraepithelial carcinoma).

6. •

   Wart.

7. •

   Lichenoid keratosis.

8. •

   Cutaneous lupus.

Workup

1. •

   History, physical, and lesion biopsy. Include risk assessment and family or personal history of skin cancers or previous skin lesions.

Laboratory Tests

1. •

   Skin biopsy in recurrent lesions or when diagnosis is unclear to rule out squamous cell or basal cell carcinoma.

2. •

   Microscopy reveals atypical keratinocytes in the lower epidermis basal layers. They are enlarged and often lack normal polarity. The thickness of the epidermis can be compromised with a distribution of atrophic to hyperplastic. Abnormal keratinocytes can cause parakeratosis of the overlying stratum corneum. Visible signs of an alternating orthohyperkeratosis can overlie the spared epithelium, causing the signature “flag sign.” Additionally, there is a distinct margin between normal epidermis and the region of AK at lateral edges. Histologic subtypes are hypertrophic, acantholytic, lichenoid, and bowenoid, which are characterized by a thick stratum corneum, lack of intracellular cohesion, presence of lymphocytic infiltrate in papillary dermis, and either lack of association of adnexal epithelium or full epithelial thickness with pleomorphic keratinocytes, respectively.

Treatment

Nonpharmacologic Therapy

1. •

   Cryotherapy with liquid nitrogen: treatment of choice for most isolated, superficial AKs.

2. •

   Carbon dioxide laser.

3. •

   Dermabrasion.

4. •

   Chemical peel.

5. •

   Curettage.

6. •

   Excision.

7. •

   Photodynamic therapy with 5-aminolevulinic acid and blue light (16 minutes) or methyl aminolevulinate and red light (7-10 minutes).

Acute General Rx

1. •

   Topical 5-fluorouracil (5-FU) bid for 4-6 weeks. Table E1 summarizes guidelines for duration of 5-FU therapy according to site.

   TABLEE1 Guidelines for Duration of 5-Fluorouracil Therapy According to SiteFrom Habif TP: Clinical dermatology, ed 6, Philadelphia, 2016, Elsevier.

   Site	Early Signs of Inflammation (days)	Duration of Treatment (weeks)
   Face, lips	3-5	2-4
   Scalp	4-7	3-5
   Neck	4-7	2-4
   Arms, hands, legs	10-14	4-8
   Back	10-14	4-6
   Chest	10-14	4-6

2. •

   Topical diclofenac sodium 3% gel bid for 60-90 days.

3. •

   Topical imiquimod 5% cream bid for 3-4 months.

4. •

   Oral retinoids.

5. •

   Topical ingenol mebutate 0.05% gel applied for 2 days with exception of face—or 0.015% for 3 days. Combination medication therapy or nonpharmacologic therapy with pharmacologic therapy is common (especially in refractory AK).

6. •

   A 10% nanoemulsion gel formulation of the porphyrin-based photosensitizers aminolevulinic acid (Ameluz) is available for use in combination with a narrow-band red light photodynamic therapy (PDT) lamp (BF-RhodoLED) for mild to moderate severity AK on face and scalp.

7. •

   Table E2 describes preparations for treatment of actinic keratosis.

Referral

1. •

   To a dermatologist for biopsy of suspicious lesions, then follow up minimum annually or semiannually.

Pearls & Considerations

Comments

1. •

   AKs are of particular importance because they are a sensitive indicator of exposure to UV light and strongly predict the likelihood of developing cutaneous squamous cell carcinoma.

2. •

   The cumulative probability of development of invasive squamous cell carcinoma in patients with 10 or more AKs has been estimated at 14% in a 5-year period.

3. •

   It is estimated that up to 10% of AKs tend to progress to invasive carcinoma. Factors associated with increased risk of invasive squamous cell carcinoma include presence of multiple lesions, large surface area and depth, hyperkeratotic proliferative lesions, location on lip, ear, and extremities and concomitant illness (leukemia, lymphoma), and use of immunosuppressive agents and agents that increase sun sensitivity.

Prevention

1. •

   Avoidance of sun exposure or tanning booths.

2. •

   Use of sunscreens.

3. •

   Routine self-skin examinations.

4. •

   Pharmaceutical prevention:

   • 1.

     Mild to moderate reduction of AK formation has been documented with the use of topical tretinoin, isotretinoin, and arotinoid methylsulfonyl.

   • 2.

     Nicotinamide as preventive rx has been documented to have a possible 30% relative reduction in AK.

   • 3.

     Decreased AK development has been documented with the use of high-SPF sunscreens.

   • 4.

     Decreased AK development has been seen in patients with xeroderma pigmentosum who used DNA repair enzymes.

   • 5.

     Decreased AK formation has been documented in high-risk patients (specifically those with xeroderma pigmentosum, nevoid basal cell carcinoma syndrome, and organ transplantation recipients) with the use of oral retinoids.

     Suggested Reading

     • E. Uhlenhake: Optimal treatment of actinic keratosis. Clin Interv Aging. 8:29–35 January 2013 Dove Medical Press Ltd 23345970