AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

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, elastophagocytosis, or loss of elastolytic enzyme inhibitors.

Elastolytic activity has been shown in matrix metalloproteinases (MMPs),¹ 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, 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.^{2, 3, 4} 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^{5, 6} and older ages of onset have been reported.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

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.⁷

Causes

• Primary or idiopathic anetoderma originates from previously healthy skin with unknown pathogenesis. Various 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.
• Reported associations with primary anetoderma include the following:
• • Eye - Cataract, keratoconus, blue sclerae, optic atrophy⁸
  • 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,⁹ 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
  • Amyloidosis
  • Antiphospholipid antibody syndrome
  • Acrodermatitis chronica atrophicans
  • B-cell lymphoma¹⁰ (1 case with concomitant Sjögren syndrome¹¹)
  • Benign cutaneous lymphoid hyperplasia
  • Cutaneous lymphoma
  • Dermatofibroma
  • Hansen disease
  • Hereditary¹²
  • Insect bites
  • Lupus erythematosus
  • Lupus profundus
  • Lymphocytoma
  • Perifolliculitis
  • Pilomatrixoma¹³
  • Sarcoidosis
  • Syphilis¹⁴
  • Tuberculosis
  • Urticaria pigmentosa
  • Varicella
• Secondary anetoderma associations that have been reported very rarely in the literature include the following (listed alphabetically):
• • Addison disease
  • Angular cheilitis¹⁵
  • Congenital melanocytic nevi with hamartomatous features¹⁶
  • Cutaneous plasmacytoma¹⁷
  • Dermatofibrosarcoma protuberans¹⁸
  • Discoid lupus
  • Granuloma annulare¹⁹
  • Hepatitis B vaccination²⁰
  • HIV disease²¹
  • Hypothyroidism
  • Juvenile xanthogranuloma
  • Langerhans cell histiocytosis
  • Molluscum contagiosum²²
  • Myxofibrosarcoma²³
  • Penicillamine use²⁴
  • Pityriasis versicolor
  • Prurigo nodularis²⁵
  • Recurrent deep vein thrombosis
  • Sjögren syndrome¹¹
  • Takayasu arteritis⁶
  • Under electrodes in growth restricted preterm infants²⁶
  • 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.
• The association of lupus erythematosus and secondary anetoderma is frequently cited in the literature. In these patients, findings of antinuclear antibodies, antiphospholipid antibodies, hypocomplementemia, and/or a positive lupus band test result are frequent. However, the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus are typically not met. Among those with systemic lupus erythematosus and anetoderma, antiphospholipid antibodies are a common finding.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Atrophic scars
Insect bites and urticaria (may resemble early inflammatory anetoderma)
Neurofibromas
Nevus lipomatosus
Perifollicular atrophoderma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• No laboratory findings are specific for anetoderma. The following laboratory tests may be considered if clinically indicated because of other clinical findings:
• • ACE level
  • Antinuclear antibody (ANA) test, complement (C3, C4)
  • Antiphospholipid antibody test; testing for other autoantibodies (anti-Ro, anti-La, antimitochondria, antithyroglobulin, anti–smooth muscle)
  • CBC count
  • Lyme disease titers
  • Purified protein derivative (PPD)
  • Rapid plasma reagin (RPR)/Venereal Disease Research Laboratory (VDRL) test
  • Sedimentation rate

Histologic Findings

A perivascular and periadnexal lymphohistiocytic infiltrate is seen in the papillary dermis, upper reticular dermis, or both. A marked loss of elastic fibers is observed, although fine microfibrils may remain. The collagen fibers appear normal. Desmosine, a cross-linking compound found only in elastin, is reduced in lesional skin. Early lesions may show a pronounced monocytic infiltrate of predominantly T helper lymphocytes, but occasionally, the predominant cell types are histiocytes, neutrophils, or eosinophils. Scattered macrophages showing elastophagocytosis may be present.

Direct immunofluorescence is usually not helpful, but findings similar to those of lupus erythematosus may be found,²⁷ with granular deposits of immunoglobulin G (IgG), immunoglobulin M (IgM), and/or complement (C3) along the dermoepidermal junction and blood vessels. Sometimes, fibrillar immunoglobulin and complement deposits are present in the papillary dermis. This probably corresponds to deposition on elastic tissue, although indirect immunofluorescence studies have failed to demonstrate elastic fiber autoantibodies.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

No effective treatment for anetoderma is known. Past treatments have included intralesional steroids, penicillin G, aspirin, phenytoin, dapsone, vitamin E, and niacin, with inconsistent results. Anecdotal reports describe topical epsilon-aminocaproic acid (an antifibrinolytic)²⁸ and oral colchicine²⁹ being used to prevent the formation of new inflammatory lesions.

Surgical Care

Surgical excision is an option if lesions are small and few in numbers.

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

For primary anetoderma, patients should be periodically reevaluated for associated conditions that did not manifest initially. The evaluation includes a complete physical examination and appropriate screening laboratory tests.

Prognosis

Once developed, the lesions do not change over time.

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

Failure to do a thorough history and a complete physical examination to look for underlying problems is a pitfall.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Multiple lesions of anetoderma.
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Media type:  Photo

Media file 2:  Close-up view of a single lesion of anetoderma.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

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16. Cockayne SE, Gawkrodger DJ. Hamartomatous congenital melanocytic nevi showing secondary anetoderma-like changes. J Am Acad Dermatol. Nov 1998;39(5 Pt 2):843-5. [Medline].
17. Jubert C, Cosnes A, Wechsler J, Andre P, Revuz J, Bagot M. Anetoderma may reveal cutaneous plasmacytoma and benign cutaneous lymphoid hyperplasia. Arch Dermatol. Mar 1995;131(3):365-6. [Medline].
18. Sheehan DJ, Madkan V, Strickling WA, Peterson CM. Atrophic dermatofibrosarcoma protuberans: a case report and reappraisal of the literature. Cutis. Oct 2004;74(4):237-42. [Medline].
19. Ozkan S, Fetil E, Izler F, Pabucçuoglu U, Yalçin N, Günes AT. Anetoderma secondary to generalized granuloma annulare. J Am Acad Dermatol. Feb 2000;42(2 Pt 2):335-8. [Medline].
20. Daoud MS, Dicken CH. Anetoderma after hepatitis B immunization in two siblings. J Am Acad Dermatol. May 1997;36(5 Pt 1):779-80. [Medline].
21. Ruiz-Rodriguez R, Longaker M, Berger TG. Anetoderma and human immunodeficiency virus infection. Arch Dermatol. May 1992;128(5):661-2. [Medline].
22. Shalders K, Ilchyshyn A, Walzman M. Secondary anetoderma following molluscum contagiosum infection. Acta Derm Venereol. 2003;83(6):461-2. [Medline].
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24. Johnson WC. Wilson's disease and penicillamine-induced anetoderma. Arch Dermatol. 1977;113:976.
25. Hirschel-Scholz S, Salomon D, Merot Y, Saurat JH. Anetodermic prurigo nodularis (with Pautrier's neuroma) responsive to arotinoid acid. J Am Acad Dermatol. Aug 1991;25(2 Pt 2):437-42. [Medline].
26. Prizant TL, Lucky AW, Frieden IJ, Burton PS, Suarez SM. Spontaneous atrophic patches in extremely premature infants. Anetoderma of prematurity. Arch Dermatol. Jun 1996;132(6):671-4. [Medline].
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33. Kim JM, Su WP. Mid dermal elastolysis with wrinkling. Report of two cases and review of the literature. J Am Acad Dermatol. Feb 1992;26(2 Pt 1):169-73. [Medline].
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Article Last Updated: Sep 19, 2006