Background

Anetoderma (anetos, Greek for slack) is a benign condition with focal loss of dermal elastic tissue, resulting in localized areas of flaccid or herniated saclike skin. The condition has been reported under various names, including macular atrophy, anetoderma maculosa, and atrophia maculosa cutis. Primary lesions consist of localized areas of flaccid skin, which can be macular, papular, or depressed.

Historically, idiopathic lesions were classified based on a clinically inflammatory (Jadassohn-Pellizzari) or noninflammatory (Schweninger-Buzzi) onset. However, both types of lesions may be found in the same individual, and they are histologically similar. Currently, anetoderma is classified as either primary anetoderma, which is an idiopathic occurrence of atrophic lesions in areas of skin that appear normal prior to the onset of atrophy, or secondary anetoderma, which is preceded by an inflammatory, autoimmune, infectious, or neoplastic process. Both types may be associated with systemic diseases. A familial form that manifests as primary anetoderma has also been described.^[1]

Pathophysiology

The exact cause of anetoderma is unknown. Possible explanations for the loss of elastic tissue include defective elastin synthesis, uncontrolled production of elastolytic enzymes, loss of elastolytic enzyme inhibitors, elastophagocytosis, or degeneration of elastic fibers secondary to local ischemia induced by microthromboses in dermal vessels.^[2]Some investigators have proposed a possible common epitope between elastic fibers and phospholipids as an explanation for an autoimmune-mediated process.^[2]

Elastolytic enzymes such as matrix metalloproteinases (MMPs) may be directly responsible for elastin degradation in anetoderma. Alternatively, they may act indirectly by modulating other inflammatory events, such as proteolytic activation of latent cytokines, which, in turn, may regulate the activity of other undiscovered elastolytic enzymes. Known elastolytic enzyme inhibitors include serine proteinase inhibitors (serpins) and tissue inhibitors of metalloproteinase (TIMPs).

An imbalance in levels of MMPs and TIMPs altering the rate of elastin turnover has been suggested as one explanation of the pathophysiology of anetoderma. Specifically, MMP-2 and MMP-9 have been suggested as possible culprits at the origin of elastic fiber destruction in anetoderma.^[3]

Furthermore, a 2016 study involving nine patients with idiopathic anetoderma found that the dermal expression of fibulin-4 (which binds tropoelastin and is involved in various aspects of elastic fiber development) was significantly decreased in anetoderma when compared with healthy controls. These findings suggest that in addition to elastolytic overactivity, altered reassembly of elastic fibers may also play a significant role in the pathogenesis anetoderma.^[4]

Frequency

The exact incidence of anetoderma is unknown, but secondary anetoderma is probably more common than the primary form. Familial anetoderma is uncommon, with only 12 families reported in the literature.^{[5, 6, 7, 8]}Inheritance may be autosomal dominant, autosomal recessive, or undefined.

Sex

Primary anetoderma occurs slightly more frequently in women than in men.

Age

Primary anetoderma usually presents between the second and fourth decades of life, although patients of all ages have been reported to develop anetoderma.^{[9, 10, 11]}

Prognosis

Once developed, the lesions do not change over time.

Clinical Presentation

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