<p>BACKGROUND: There are few studies on the natural history of acne lesions including the antecedents of atrophic scars.</p> <p>STUDY DESIGN: Prospective study of relationship between primary (papules, pustules, comedones) and secondary lesions (atrophic scars, macular erythema, and hyperpigmentation) over 6 months. Subjects (n=32) had moderate facial acne including 10 or more atrophic acne scars and were their own control via randomized split-face design. Lesions were mapped 2x/week for 2 months and every 2 weeks thereafter until month 6 to track pathogenic progression.</p> <p>RESULTS: Clinical assessment showed acne scars continuously forming throughout the 6-month study period. While the majority (66.2%) of these scars did not resolve by study endpoint, the remainder were transient. The likelihood of a scar developing from a primary acne lesion was 5.7%, and almost all scars arose from erythematous macules or hyperpigmentation (83%) and some (16%) developed directly from papules and pustules. Duration of papules was a key factor in the risk of scarring. The majority (81.7%) of the scars remaining at 6 months were still present at 2-year follow-up.</p> <p>CONCLUSIONS: Atrophic acne scars continuously form, some resolve, and evolve primarily from inflammatory and post-inflammatory lesions. Clinicians should closely monitor patients with macular erythema for scarring.</p> <p><em>J Drugs Dermatol. 2017;16(6):566-572.</em></p>.