What are the oral or injectable treatment options for individuals with more than 50 actinic keratoses?

Oral and Injectable Treatment Options for Extensive Actinic Keratosis

For patients with more than 50 actinic keratoses, systemic retinoids (acitretin) are the most appropriate oral treatment option, particularly in high-risk patients such as organ transplant recipients. 1

Systemic Treatment Options

Oral Retinoids

• Acitretin is the most commonly used oral treatment for extensive actinic keratosis:
  • Starting dose: 10-25 mg daily 1
  • Most appropriate for patients with extensive AKs (>50 lesions)
  • 56% of dermatologists recommend systemic retinoids for extensive AK 1
  • Higher recommendation rate (74-81%) when patients also have multiple squamous cell carcinomas 1

Other Systemic Options

• Capecitabine (oral cytotoxic agent):

  • Can reduce monthly incidence of AKs to 45% of pretreatment levels 1
  • Significant side effects: 33% of patients discontinue after 1 year 1
  • Generally reserved for immunosuppressed patients with extensive disease

• Celecoxib (COX-2 inhibitor):

  • Limited evidence for AK treatment specifically
  • May reduce BCCs and SCCs but does not appear to significantly affect AK count 1

Treatment Algorithm for Extensive AK

1. First-line approach: Field-directed topical therapies

   • 5-Fluorouracil (5-FU) - strongly recommended 1, 2
   • Imiquimod - strongly recommended 1, 2
   • Photodynamic therapy (PDT) - conditionally recommended 1, 2

2. When to consider systemic therapy:

   • When topical treatments have failed
   • For patients with >50 lesions
   • For immunosuppressed patients (especially organ transplant recipients)
   • When multiple SCCs are also present

3. Systemic treatment selection:

   • Acitretin (first choice): 10-25 mg daily
   • Capecitabine (second choice): Consider in organ transplant recipients with frequent SCCs and extensive AKs

Important Clinical Considerations

• Monitoring: Regular follow-up is essential due to:

  • Potential rebound effect when systemic therapy is stopped 1
  • Side effect management
  • Need to assess treatment response

• Duration of therapy:

  • Acitretin may need to be continued long-term in high-risk patients
  • Evidence suggests residual histological dysplasia may lead to relapse when treatment is discontinued 1

• Combination approaches:

  • Consider combining systemic therapy with field-directed treatments
  • Photodynamic therapy can be used in conjunction with systemic therapy for enhanced efficacy

• Pitfalls to avoid:

  • Abrupt discontinuation of systemic retinoids may lead to rebound flares
  • Failure to monitor for systemic side effects of retinoids (lipid abnormalities, hepatotoxicity)
  • Not addressing UV protection as part of the treatment plan 1, 2

Special Populations

• Organ transplant recipients:

  • Higher priority for systemic therapy due to increased risk of progression to SCC
  • Low-dose acitretin is recommended in European best practice guidelines for renal transplant patients with multiple dysplastic skin lesions 1
  • Consider immunosuppression reduction if possible (multidisciplinary approach) 1

• Patients with history of multiple SCCs:

  • More aggressive approach warranted
  • Higher doses of acitretin may be considered
  • Closer monitoring for malignant transformation

Remember that while topical treatments remain first-line for most patients with AK, those with extensive disease (>50 lesions) often require systemic approaches to effectively manage their condition and prevent progression to invasive squamous cell carcinoma.