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Actinic Keratosis Treatment Information for Professionals



Cryosurgery


Liquid nitrogen (-195.8C), the most common cryogen, is applied using a spray device or a cotton tip applicator. The atypical cells are destroyed when the skin temperature is lowered to -50C.

Advantages

  • highly effective treatment
  • a minimum of treatments (once or twice)

Disadvantages

  • application causes discomfort and/ or pain to the patients
  • side-effects such as blistering, erythema, edema, hypo- or hyperpigmentation
  • risk of scarring
  • infection may occur due to delayed wound-healing
  • no standardization concerning duration and depth of freezing
  • only appropriate for a few lesions or multiple scattered lesions

Curettage
Actinic keratoses can be scraped away with a curette. Afterwards, electrosurgery may be used to stop bleeding or to apply more damage to the area of the atypical cells. Aluminum chloride and ferric chloride are also used as hemostatics.

Advantages

  • efficacious treatment

Disadvantages

  • local anesthetic required
  • scar formation possible if the skin is too rigorously burned
  • infection, hypo- and hyperpigmentation rarely occur
  • less practicable with multiple or confluent lesions

Topical 5-fluorouracil


5-fluorouracil is a cytostatic agent which inhibits several enzymes in tumor cells, through interaction with RNA. It is applied locally in a thin layer and the lesion is subsequently covered with a plastic film. The treatment is repeated daily until the lesion erodes (usually a treatment length of 2 to 4 weeks is necessary).

Advantages

  • efficacious treatment
  • good cosmetic results
  • treatment of large areas possible
  • non-visible lesions can be treated

Disadvantages

  • long treatment period (2 to 4 weeks)
  • erythema, inflammation, erosions, and pain during entire treatment period
  • usually low patient compliance
  • cure rates depend on patient compliance

Photodynamic therapy (PDT)


Dermatological indications for PDT

  • superficial non-pigmented epithelial tumors such as

    • actinic keratosis
    • Bowen`s disease
    • superficial basal cell carcinoma
    • superficial squamous cell carcinoma
    • keratoacanthoma

  • experimental: inflammatory dermatosis (eg. psoriasis vulgaris, acne)
  • experimental: HPV-associated dermatoses (eg. warts, epidermodysplasia verruciformis)

The technique
PDT is based on the coaction of a photosensitizer, often a porphyrin-derivative, with visible light and oxygen. The photosensitizer specifically accumulates in rapid growing cells (e.g. tumor cells) and is activated by irradiation with visible light. The tumor destruction is caused by the formation of cytotoxic efficient reactive oxygen species, in particular singlet oxygen.

There are several photosenitizer presently in use (porphyrins, porphines, phthalocyanines, etc.) but most of them are not ideal for dermatological indications since they have to be administered systemically and cause general photosensitivity in patients. The most frequent used substance for PDT in dermatology is 5-ALA (d-aminolevulinic acid) and its derivatives. 5-Ala works as a prodrug that is metabolized intracellularly into protoporphyrin IX (PpIX) - the actual photosensitizer. PpIX will, when activated by light, generate singlet oxygen which will cause death of the tumor cells. Besides PDT the photosensitizer can also be activated by Wood light leading to fluorescence of the targeted lesion. In this way tumor lesions can be detected by photo diagnosis (PD).

The use
The standardized procedure for the treatment of AK involves the application of 20% ALA or its ester in a solution or cream. emulsion. 5-ALA then penetrates the skin and is metabolized into PpIX. ALA-uptake is higher by dysplastic cells and PpIX is synthesized more specifically in abnormal cells leading to a higher concentration of PpIX in abnormal than in healthy cells. After an application time of several hours the lesion will be exposed to light of a certain wavelength and intensity. In clinical trials the complete response rate of lesions was more than 90 % after one to two treatments. Furthermore, the cosmetic outcome was rated excellent or good in more than 90 % of patients. Consequentially 5-ALA PDT is at least as effective as standard treatments but with superior cosmesis.

For Irradiation of the leasion there are now several non-coherent light sources in use which differ mainly by their emission spectrum (red light, blue light, green light) and the irradiation area.

Advantages

  • high efficacy
  • excellent cosmetic results
  • fast healing (approximately 2 weeks)
  • treatment of large areas possible and multiple lesions in one session
  • single/ twice treatment
  • non-operative method
  • topical administration without generalized cutaneous photosensitivity
  • standardized therapy

Disadvantages

  • a typical "PDT-response" such of local symptoms such as stinging, burning, itching, erythema and/or edema
  • pain during irradiation may require anesthesia
  • two-step process(application of photosensitizer and irradiation)

Other treatments



  • Dermabrasion
  • Chemical or cryosurgical peel
  • Laser
  • Salicylic acid
  • Tretinoin or other topical retinoids
  • Alpha hydroxy acids
  • Topical masoprocol
  • Excisional surgery
  • Interferon
  • Oral retinoids (in combination with 5-FU)
  • Topical tubercidin
  • Experimental: Imiquimod



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