Chart 3.

Studies involving systemic retinoids in prevention and treatment of actinic keratoses, in chronological order

Author (year)	Study design Nº patients	Drug and treatment duration	Results
Moriarty (1982)18	Cross-over, open, randomized, controlled; 50 immunocompetent patients	Etretinate 5mg 3x/day versus placebo, 2months, after, the groups were swapped for 2 more months (placebo x etretinate)	84% of the etretinate group had complete or partial response compared to 5% in the placebo group
Shuttleworth (1988) 37	Cases series 6 transplanted patients	Etretinate 1mg/kg/day, 6months	"Almost" complete resolution of neoplastic and pre-neo-plastic lesions in 4 patients, partial response in 1 patient
Kelly (1991)26	Cases series 4 transplanted patients	Etretinate 50mg/day, 8-13months	AKs were not counted but they became less severe after treatment
Bavinck (1995)27	Double-blind, randomized, controlled 44 transplanted patients	Acitretin 30mg/ day versus placebo, 6 months	13.4% of patients in the acitretin group saw decreases in the number of AKs, while in the placebo group, 28.2% of the patients saw increases
Majewski (1994)32	Cases series 4 immunocompetent patients	Isotretinoin 0.4-0.5mg/kg/day + calci-triol 0.5-1µg, 12months, approximately	Patient 1- complete clearance; Patients 2 and 3- AK regression about 50 to 80%; Patient 4 - regression of 40% of AKs in number and size
Yuan (1995)33	Cases series 15 transplanted patients	Acitretin 10-50mg/day, 6-12 months	The number of skin cancers decreased in 4 of the 6 patients. All warts and AKs had improvement in all patients (without counting)
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 improvement in AKs 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% regression of AKs while 2 in the tretinoin group obtained improvement, after six months
Hughes (1998)30	Cases series 15 immunocompetent patients	Etretinate,18 month follow-up 1st month - 1.5mg/kg/day 2nd and 3rd months - 0.75mg/kg/day	Only 12 patients with AKs completed the study, with an average reduction in the number of AKs before and after treatment of 12.73 to 5.82
McKenna (1999)38	Cases series, 16 transplanted patients	Acitretin 0.3mg/kg/day, 5 years	There was significant improvement in warts and AKs, but they were not counted
George (2002)35	Cross-over, open, randomized controlled 23 immunocompetent patients	Group 1: Acitretin 25mg/day (variable) + placebo, 12months Group 2: Placebo + Acitretin 25mg/day (variable), 12months	In the acitretin group, complete clearance or reduction in number of AKs occurred in all patients, except one. In the placebo group, there was an increase of 50% in the number of AKs in 3 patients and 6 remained with no significant change
McNamara (2002)36	Cases series 5 transplanted patients	Acitretin 10 or 25mg/day, 10-24 months	AKs seemed to be in varying degrees of resolution with treatment but they were not counted
De Sevaux (2003)28	Open, randomized controlled 26 transplanted patients	Acitretin Group 1: 0.4mg/kg/ day, 12 months Group 2: 0.4mg/kg/ day, 3 months + 0.2mg/kg/ day, 9 months	Significant reduction in number of AKs in both groups after 2 months, but no difference between the groups at any particular point
Smit (2004)45	Cases series 33 transplanted patients	Acitretin: up to 0.4mg/kg/ day, 3months (biopsy of AKs)	Reduction of 44% in epidermal thickness due to stratum corneum, no difference in expression of p53 and Ki67 and an increase in the expression of K13 and K19 after treatment with acitretin