ORIGINAL ARTICLE Atrophic and hypertrophic photoaging: Clinical, histologic, and molecular features of 2 distinct phenotypes of photoaged skin Dana L. Sachs, MD, a James Varani, PhD, b Heather Chubb, MS, a Suzanne E. G. Fligiel, MD, b Yilei Cui, PhD, a Ken Calderone, BS, a Yolanda Helfrich, MD, a Gary J. Fisher, PhD, a and John J. Voorhees, MD a Ann Arbor, Michigan Background: Exposure to the sun causes premature skin aging, known as photoaging. Clinical features of photoaging vary widely among individuals. In one form, skin appears thin with telangiectasia, and in another form, skin appears thickened with coarse wrinkles. Etiologic, clinical, and therapeutic distinctions among different forms of photoaging remain largely unknown. Objective: To characterize the clinical, histologic, and molecular features of hypertrophic and atrophic photoaging. Methods: In total, 53 individuals were clinically classified as having primarily atrophic or hypertrophic photoaging or neither (controls). Participants’ demographic and sun exposureerelated lifestyle data were captured by questionnaire. Fifteen clinical features of participants were qualitatively or quantitively scored. Facial biopsies were analyzed for gene expression and histologic characteristics. Results: Actinic and seborrheic keratosis, telangiectasia, and prior incidence of skin cancers were statistically significantly greater and photoaging scale severity, coarse wrinkles, thickness, and sallowness were significantly reduced in atrophic versus hypertrophic groups. Histology also revealed significantly less elastotic material in atrophic photoaging. Gene expression of matrix metalloproteinases and collagens did not differ between the 2 forms of photoaging. Limitations: The study was not designed to identify other possible subtypes of photoaging. Conclusion: Systematic, categorical, and quantitative clinical and histologic assessments distinguish atrophic and hypertrophic photoaging. ( J Am Acad Dermatol https://doi.org/10.1016/j.jaad.2019.03.081.) Key words: aging; elastosis; photoaging; skin cancer; telangiectasia; wrinkles. E xtrinsic skin aging, also known as photoaging, is skin aging due to external factors, the major one being ultraviolet (UV) irradiation from the sun. 1-4 Other extrinsic factors, such as tobacco smoke and ionizing radiation, likely contribute to this clinical phenotype. 5-8 Extrinsic skin aging is best observed on sun-exposed sites, such as the face, lateral neck, and extensor forearms. Photoaging is clinically characterized by uneven skin color man- ifested as erythema, telangiectasia, dyspigmentation, lentigines, and sometimes sallowness, a yellowish hue of the skin. Wrinkles might be pronounced in some cases and might be fine, coarse, or both. The extrinsic aging phenotype is associated with many cosmetic concerns, skin fragility, easy bruising, and skin barrier disruption. Extrinsic influences that lead From the Department of Dermatology a and Department of Pathology, b University of Michigan, Ann Arbor. Funding sources: Supported by funds from the Department of Dermatology, University of Michigan. Conflicts of interest: None disclosed. Accepted for publication March 8, 2019. Reprints not available from the authors. Correspondence to: Dana L. Sachs, MD, Department of Dermatology, University of Michigan, 1910 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109. E-mail: dsachs@ med.umich.edu. Published online June 20, 2019. 0190-9622/$36.00 Ó 2019 Published by Elsevier on behalf of the American Academy of Dermatology, Inc. https://doi.org/10.1016/j.jaad.2019.03.081 1