Chart 4.

Studies on the use of topical retinoids (tretinoin, adapalene and isotretinoin) in prevention and treatment of actinic keratoses, in chronological order.

Author (year)	Study design Nº patients	Drug and treatment duration	Results
Bollag (1970)29	Case series 60 immunocompetent patients	Tretinoin 0.1% and 0.3% cream, 2x/day, in AKs and lx/day, occlusive in BCCs, 3 to 8 weeks	44 patients showed total or more than 50% of regression of the AKs. Tretinoin 0,3% showed higher rates of regression, as well as the face, compared to the upper limbs
Purcell (1986)46	Double-blind, non-randomized, controlled; 24 immuno-competent patients (8 drop out)	Tretinoin 0.05% ointment x placebo, 12months	There was no statistically significant difference between the groups in relation to the number of AKs
Kligman (1991)39	Double-blind, controlled 1265 immunocompetent patients (multicentered)	Tretinoin 0.05% x tretinoin 0.1% x placebo ointment, up to 15 months	The most effective treatment for reducing AKs was 0.1% tretinoin, applied twice daily (P.001). An excellent response was observed in 73% of tretinoin-treated patients compared with only 40% of placebo
Misiewicz (1991)40	Double-blind, randomized, controlled, 25 immunocom-petent patients	Ro 14-9706 x tretinoin 0.05% ointment, 16 weeks	Decrease of 37.8% in AK numbers with Ro 14-9706, while with tretinoin, the decrease was 30.3%. There was no difference between the two drugs, although Ro 14-9706 was better tolerated
Euvrard (1992)31	Double-blind, randomized, controlled, 22 transplanted patients	Tretinoin 0.05% ointment x placebo, 3 months	Reduction of 45% versus 23% of AKs in the tretinoin 0.05% group versus placebo, respectively
Alizerai (1994)41	Double-blind, randomized, placebo-controlled 100 immunocompetent patients	Isotretinoin 0.1% ointment, 2x/day x placebo, 24 weeks	66% of the patients with isotretinoin versus 45% of the patients with placebo had a partial or complete response, whereas 34% of patients with isotretinoin versus 55% of patients with placebo had no response or worsening on the face
Rook (1995)25	Open, non-randomized, controlled 11 transplanted patients	Group 1= 7 patients (tretinoin 0.025% to 0.05% according to tolerance) + (etretinate 10mg/day or alternate days), 6 months according to AK improvement, Group 2= 4 patients (tretinoin 0.025 to 0.05%, according to tolerance)	Both groups obtained a decrease in the number of AKs and an improvement in the number of Langerhans cells. Four patients in the combined group obtained almost 50% of regression of AKs, while 2 in the tretinoin group obtained improvement, after six months
Moglia (1997)42	Case series 18 immunocompetent patients	Retinoid fenretinide 2x/day, 3months	Complete and partial regression was observed in 56% and 44% of patients, respectively
Euvrard (1998)34	Randomized, controlled 40 transplanted patients	Adapalene 0.1% x adapalene 0.3%, 6 months	Reduction of 32% versus 21% in AKs number with concentrations of 0.3% and 0.1% respectively
Campanelli (2002)43	Case series 61 immunocompetent patients	Retinaldehyde 0.05%, 6-142 months	37% of the patients aged over 60 and 10% between 41-60 years developed AKs during the treatment. Retinaldehyde alone does not appear to have prophylactic effects on the development of AKs
Smit (2002)44	Open, non-randomized, controlled, 13 immunocom-petent patients	Group 1: Tretinoin 0,02%	There were no significant differences in clinical, histological and immunohistochemical parameters between the four different therapies during a 6-week treatment period.
		Group 2: calcipotriol
		Group 3: both
		Group 4: emollient
		All 2x/day, 6 weeks