eMedicine Specialties > Dermatology > Diseases of the Dermis

Anetoderma

Author: Anne Laumann, MB, ChB, MRCP(UK), FAAD, Associate Professor, Department of Dermatology, Feinberg School of Medicine, Northwestern University
Coauthor(s): Julia Sanger Minocha, MD, Resident Physician, Department of Medicine, Feinberg School of Medicine, Northwestern University; Stephen C Ho, MD, Boulder Dermatology Clinic
Contributor Information and Disclosures

Updated: Jun 22, 2009

Introduction

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 and dermatitis atrophicans maculosa.

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 patient, 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 dermatosis in the same location. Both types may be associated with systemic diseases.

Pathophysiology

The exact cause of anetoderma is unknown. Possible explanations for elastolysis include defective elastin synthesis, uncontrolled production of elastolytic enzymes or loss of their inhibitors, elastophagocytosis, or degeneration of elastic fibers secondary to local ischemia induced by microthrombosis in dermal vessels.¹  Some investigators have proposed a possible common epitope between elastic fibers and phospholipids as an explanation for an autoimmune-mediated process.¹

Elastolytic activity has been shown in matrix metalloproteinases (MMPs),² cathepsins, and elastases. Inflammatory cells (macrophages and neutrophils) are the most important producers of these enzymes. Many different proinflammatory stimuli can cause them to produce elastolytic enzymes. These stimuli include, but are not limited to, the deposition of autoimmune complexes, infections, hypoxia/reoxygenation, and physiochemical injuries.

The elastolytic enzymes may be directly responsible for elastin degradation. 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 of the elastolytic enzymes and their inhibitors may change the rate of elastin turnover in affected areas, resulting in the apparent lesions.

Frequency

United States

The exact incidence of anetoderma is not known, but secondary anetoderma is probably more common than the primary form. Familial anetoderma is uncommon, with only 7 families reported in the literature.^3,4,5 Inheritance may be autosomal dominant, autosomal recessive, or undefined in pattern.

International

Secondary anetoderma seems to be more frequent in Central Europe than in North America, paralleling the incidence of chronic atrophic acrodermatitis. This suggests that Borrelia species may be involved.

Mortality/Morbidity

Primary anetoderma is usually asymptomatic and not associated with mortality.

Sex

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

Age

Most patients with primary anetoderma present between the second and fourth decade of life, although much younger^6,7 and older ages of onset have been reported.

Clinical

History

• The initial primary lesions may be noticed as crops of small asymptomatic erythematous macules, plaques, nodules, or urticarial wheals that enlarge over weeks to reach several centimeters in diameter.
• Lesions appear on the upper arms, the trunk, the thighs, and less commonly on the neck, face, and rarely on distal extremities.
• Comorbid lesions may already exist.
• End-stage lesions do not change over time, and new lesions may continue to develop over years.

Physical

• Patients have multiple, small, circumscribed, skin-colored, grey-white or blue, wrinkled macules or patches that may bulge slightly like pouches and herniate into the skin upon palpation (see Media Files 1-2).

• On pressure, a normal ring of surrounding skin is felt.
• The scalp, the palms, the soles, and the mucous membranes are usually spared.
• A few to hundreds of lesions may form. These may coalesce and become indistinguishable from acquired cutis laxa.
• Anetoderma is one of several elastolytic disorders that also include cutis laxa, mid dermal elastolysis, and granulomatous slack skin. Anetoderma is clinically recognized by the phenomenon of well-demarcated saclike bulging when pandermal elastolysis is present. If the elastolysis is only partial, the bulging may not be appreciated.
  • Acquired cutis laxa differs from anetoderma by its generally widespread nature of sagging or lax skin.
  • Mid-dermal elastolysis is characterized by selective loss of elastic fibers in the mid dermis. This results in widespread fine wrinkling with or without perifollicular papules.
  • Granulomatous slack skin is a rare variant of cutaneous T-cell lymphoma manifesting as erythematous pendulous folds of lax skin. It is histologically characterized by granulomas with phagocytosis of elastic fibers.⁸

Causes

• Primary or idiopathic anetoderma originates from previously healthy skin with unknown pathogenesis. Various autoimmune, ocular, bony, cardiac, and other abnormalities have been reported with anetoderma, including the familial forms. Whether these findings are coincidental or related in pathogenesis is unknown. Thus, a thorough history and a complete physical examination are essential.
• The association of lupus erythematosus, and other autoimmune disorders, and primary anetoderma is frequently cited in the literature. In these patients, findings of antinuclear antibodies, antiphospholipid antibodies, hypocomplementemia, and/or a positive lupus band test are frequent. However, the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus are typically not met. 
• Studies have suggested a strong association between primary anetoderma and antiphospholipid antibodies, with or without antiphospholipid antibody syndrome.⁹   In several cases of antiphospholipid antibody syndrome, primary anetoderma appeared many years earlier than the classic signs of the autoimmune syndrome.  This observation has provoked investigators to recommend a search for clinical and laboratory signs of autoimmune disorders including antiphospholipid antibody syndrome in every patient presenting with primary anetoderma.^9,10
• Reported associations with primary anetoderma include the following:
  • Autoimmune -Lupus erythematosus, antiphospholipid antibody syndrome, Addison disease, hypothyroidism, Sjögren syndrome¹¹
  • Eye - Cataract, keratoconus, blue sclerae, optic atrophy¹²
  • Bone - Calcifications, kyphoscoliosis, brachydactyly, congenital cervical fusions, spina bifida, osteopetrosis, metaphyseal dysplasia
  • Blegvad-Haxthausen syndrome - Anetoderma, blue sclerae, osteogenesis imperfecta
  • Cardiovascular -Mitral valve prolapse, aortic insufficiency, Wolff-Parkinson-White conduction disturbance, myocardial infarction
  • Miscellaneous - Diverticulum of the mid esophagus, emphysema, protrusion of the teeth,¹³ pyramidal syndrome, myotonic dystrophy, focal sclerosing glomerulopathy, and decreased serum level of alpha1-antitrypsin
• Secondary anetoderma is associated with various conditions. Examples that have been cited multiple times in the literature include the following (listed alphabetically):
  • Acne
  • Acrodermatitis chronica atrophicans
  • Amyloidosis
  • Antiphospholipid antibody syndrome
  • B-cell lymphoma¹⁴ (1 case with concomitant Sjögren syndrome¹⁵ )
  • Benign cutaneous lymphoid hyperplasia
  • Cutaneous lymphoma
  • Dermatofibroma
  • Hansen disease
  • Hereditary¹⁶
  • Insect bites
  • Lupus erythematosus
  • Lupus profundus
  • Lymphocytoma
  • Perifolliculitis
  • Pilomatrixoma¹⁷
  • Sarcoidosis
  • Syphilis¹⁸
  • Tuberculosis
  • Urticaria pigmentosa
  • Varicella
• Secondary anetoderma associations that have been reported very rarely in the literature include the following (listed alphabetically):
  • Angular cheilitis¹⁹
  • Congenital melanocytic nevi with hamartomatous features²⁰
  • Cutaneous plasmacytoma²¹
  • Dermatofibrosarcoma protuberans²²
  • Discoid lupus
  • Granuloma annulare²³
  • Hepatitis B vaccination²⁴
  • HIV disease²⁵
  • Juvenile xanthogranuloma
  • Langerhans cell histiocytosis
  • Lyme disease²⁶
  • Molluscum contagiosum²⁷
  • Mycosis fungoides²⁸
  • Myxofibrosarcoma²⁹
  • Neuroblastomalike schwannoma³⁰
  • Penicillamine use³¹
  • Pityriasis versicolor
  • Prurigo nodularis³²
  • Recurrent deep vein thrombosis
  • Sjögren syndrome¹⁵
  • Takayasu arteritis⁷
  • Under electrodes in growth restricted preterm infants³³
  • Xanthoma
• Some secondary anetodermal lesions only vaguely resemble idiopathic anetoderma clinically, despite all lesions showing a loss of dermal elastic fibers. Examples of such secondary lesions include those associated with angular cheilitis, HIV disease, pilomatrixoma, and prurigo nodularis.
• Many secondary anetodermal lesions are parainflammatory or appear at the same location following a primary skin process. Nonetheless, some lesions occur at sites of previously uninvolved skin. This subset of secondary anetoderma includes lesions associated with syphilis, HIV disease, lupus, hepatitis B vaccination, neonatal prematurity, Addison disease, and hypothyroidism.

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