Oral Isotretinoin Versus Topical Tretinoin for Actinic Keratosis

Inclusion Criteria:

1. Signature of the Free and Clarified Consent Term before any procedure of the study;
2. Men and women, aged 50-75 years, in good health;
3. Women in menopause for 1 year or more;
4. Phototypes I-IV by Fitzpatrick classification;
5. Glogau photodamage classification scale from moderate to severe
6. At least 10 and maximum 60 visible and/or palpable actinic keratosis, in the face and forearms, in a standardized distribution;
7. Absence of topical treatment in the face and forearms, except sunscreens, with:

   * tretinoin in the last 6 months;
   * alphahydroxyacids, polyhydroxyacids, betahydroxyacids and ascorbic acid in the last 3 months;
   * drugs or procedures that may change the natural evolution of actinic keratosis, such as imiquimod 5% cream, diclofenac 3% in hyauronic acid gel, photodynamic therapy, 5-FU, in the last 6 months;
8. Absence of previous treatment in the face and forearms with chemical peels and microdermabrasion, in the last 6 months;
9. Absence of previous treatment with oral retinoids in the last 6 months;
10. Absence of anti-cancer chemotherapy in the last 3 months;
11. Absence of hypersensitivity to parabens (present in the majority of drugs as a preserving agent);
12. Absence of infectious or inflammatory diseases in the face and forearms;
13. Absence of immunossupression;
14. Absence of photodermatosis;
15. Agreement in avoiding sun exposure during the research;
16. Agreement in not performing any other kind of treatment that could change the natural history of actinic keratosis; and
17. Agreement with the study conditions, ability to understand and follow strictly the given orientations, availability to attend the periodical evaluations.

For the isotretinoin group (ISO):

1. Absence of history of isotretinoin hypersensitivity;
2. Avoid alcohol intake and;
3. Absence of previous and actual history of rheumatologic diseases.

For the tretinoin group (AR):

1\. Absence of history of tretinoin hypersensitivity;

Exclusion Criteria:

For all patients:

1. Men and women who dón't agree with the terms of the research or without ability to understand and/or follow strictly the conditions of the study, without availability to understand and attend the periodical evaluations or who decline to sign the Free and Clarified Consent Term;
2. Patients with less than 10 and more than 60 actinic keratosis in the face and forearms;
3. Fertile, pregnant or lactating women;
4. Fitzpatrick phototypes V e VI ;
5. Topical treatment in the face and forearms, except sunscreens, with:

   * tretinoin in the last 6 months;
   * alphahydroxyacids, polyhydroxyacids, betahydroxyacids and ascorbic acid in the last 3 months;
   * drugs or procedures that may change the natural evolution of actinic keratosis, such as imiquimod 5% cream, diclofenac 3% in hyauronic acid gel, photodynamic therapy, 5-FU, in the last 6 months;
6. Previous treatment in the face and forearms with chemical peels and microdermabrasion, in the last 6 months;

8\. Previous treatment with oral retinoids in the last 6 months

For the isotretinoin group (ISO):

1. Presence of significative hepatic laboratory alterations (elevated liver enzymes twice ashigh as the upper normal limit;
2. Diabetic patients, with fast glucose values superior to 110mg/dl;
3. Significant lipid profile alterations (triglycerides \> 300 mg/dl; total cholesterol\> 250 mg/dl);
4. Low count of white blood cells (leukocytes \< 3000/mm3);
5. History of hypersensitivity to isotretinoin and parabens;
6. Alcohol intake;
7. Previous or actual history of rheumatologic diseases;
8. Anticancer chemotherapy in the last 3 months;
9. Previous history of hypervitaminosis A;
10. Previous history of bone or muscular diseases;
11. Patients who are in use or may use the following drugs (risk of drug interaction):

    * tetracyclines and derivatives - in the last 7 days;
    * vitamin A - in the last 30 days;
    * carbamazepine - in the last 7 days.