Prospective Study of Pathogenesis of Atrophic Acne Scars and Role of Macular Erythema

June 2017 | Volume 16 | Issue 6 | Original Article | 566 | Copyright © June 2017

Jerry Tan MD FRCPC,a Valérie Bourdès MD MPH,b Robert Bissonnette MD,c Laurent Petit B. Eng,b Philippe Reynier PhD,b Amir Khammari PhD,d and Brigitte Dreno MD PhDd

aWindsor Clinical Research Inc. and Western University, Windsor, Ontario, Canada bGalderma R&D, Evaluation Department, Sophia Antipolis, France cInnovaderm Research, Montreal, Canada dCHU Nantes, CIC, Inserm U1232, Nantes, France


BACKGROUND: There are few studies on the natural history of acne lesions including the antecedents of atrophic scars.

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.

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.

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.

J Drugs Dermatol. 2017;16(6):566-572.


Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit, affecting approximately 80% of young adults and adolescents.1-3 It is a polymorphic disease in which several types of lesions are usually present concurrently: primary lesions reflecting active acne (including comedones and inflammatory types) and secondary lesions which originate from active acne lesions (including scars, macular erythema, and post-inflammatory hyperpigmentation [PIH]). In addition to the diverse presentation of active acne lesions, acne scars are also highly variable, and sometimes do not correlate with acne severity (eg, scarring can occur even with mild acne). The most frequently occurring scars involve loss of tissue (atrophic scars) in diverse shapes, sizes, and degrees. Excess tissue can also occur as an acne scar, and can be categorized as hypertrophic scars and keloids (often determined by location and racial factors).4 Atrophic acne scarring is very common, with reports indicating some degree of scarring in up to >87% of patients with mild to moderate acne.5, 6 Clinically relevant atrophic scarring (mild or greater) is most frequent on the face (55% of subjects), followed by the back (24%) and chest (14%).6 Nevertheless, relatively little is known about acne scar pathophysiology, epidemiology, and natural history. A recent study of prevalence and risk factors of acne scarring found that acne severity, time between acne onset and effective treatment, and acne relapse were the most significant risk factors associated with scarring.7 In addition, patients suffering from severe inflammatory acne were 3.4 to 6.8 times more likely to develop scars compared to those with less severe acne.7 Finally, acne scars can have an important psychological impact on sufferers, contributing to self-consciousness, anxiety, depression, and in severe cases suicide.8,9 Given the paucity of literature on the evolution of acne lesions, the objective of this study was to evaluate the relationship between primary and secondary acne lesions, with a focus on the genesis of atrophic acne scars.



Subjects were male and female aged 18 to 35 years with moderate facial acne vulgaris, defined as 20 to 40 inflammatory lesions (papules and pustules, excluding the nose), no more than 1 acne nodule, and a minimum of 10 atrophic acne scars (>1.5 mm in diameter) on each side of the face, with a relatively equivalent distribution on each side. The study was performed in accordance with Good Clinical Practice and was approved