Chapter 67. Anetoderma and Other Atrophic Disorders of the Skin

Epidemiology

The lesions in anetoderma usually occur in young adults between the ages of 15 and 30 years and more frequently in women than men. Anetoderma is rare, but the incidence is unknown. Several hundred cases have been reported.1–4

Pathogenesis

The pathogenesis of anetoderma is unknown. The key defect is damage to the dermal elastic fibers. Anetoderma may be considered to be unusual scars, because scars also have decreased elastic tissue. The loss of dermal elastin could be the result of an impaired turnover of elastin caused by either increased destruction or decreased synthesis of elastic fibers.

Clinical Findings

All types of anetoderma are characterized by a circumscribed loss of normal skin elasticity. The characteristic lesions are flaccid circumscribed areas of slack skin with the impression of loss of dermal substance forming depressions, wrinkling, or sac-like protrusions (Fig. 67-1). These atrophic, skin-colored, or blue–white lesions are 5–30 mm in diameter. The number varies from a few to hundreds. The skin surface can be wrinkled, thinned, and often depigmented, and a central depression may be seen. Coalescence of smaller lesions can give rise to larger herniations. The examining finger sinks without resistance into a distinct pit with sharp borders as if into a hernia ring (buttonhole sign). The protrusion reappears as soon as the pressure from the finger is removed.4

The most common sites for these asymptomatic lesions are the chest, back, neck, and upper extremities. They usually develop in young adults, and new lesions often continue to form for many years as the older lesions fail to resolve.

Primary anetoderma occurs when there is no underlying associated skin disease (i.e., it arises on clinically normal skin). It is historically subdivided into two types: (1) those with preceding inflammatory lesions, mainly erythema (the Jadassohn–Pellizzari type), and (2) those without preceding inflammatory lesions (the Schweninger–Buzzi type). This classification is only of historical interest, because the two types of lesions can coexist in the same patient; the prognosis and the histopathology are also the same.4

True secondary anetoderma implies that the characteristic atrophic lesion has appeared in the exact same site as a previous specific pathology; the most common causes are probably acne and varicella. Numerous and heterogeneous dermatoses have been associated with secondary anetoderma, namely syphilis, Lyme disease, molluscum contagiosum, pilomatricomas, juvenile xanthogranuloma, xanthomas, granuloma annulare, leprosy, discoid lupus, sarcoidosis, and lichen planus, to mention only a few. Anetoderma has also been described in premature infants and, in some cases, it may have been related to the use of cutaneous monitoring leads or adhesives.5 Both types may be associated with an underlying disease, mainly antiphospholipid syndrome6 and human immunodeficiency virus. Although most cases are sporadic, rare cases of familial anetoderma have been recently described and are usually not associated with preexisting lesions.7

Pathology

In routinely stained sections, the collagen fibers within the dermis of affected skin appear normal. Perivascular lymphocytes are often present in all types of anetoderma and do not correlate with clinical inflammatory findings.8

The predominant defect as revealed by elastic tissue stains is a focal partial or complete loss of elastic tissue in the papillary and/or midreticular dermis. There are usually some residual abnormal, irregular, and fragmented elastic fibers (Fig. 67-2).9 Presumably, the weakening of the elastic network leads to flaccidity and herniation. Direct immunofluorescence sometimes shows linear or granular deposits of immunoglobulins and complement along the dermal–epidermal junction or around the dermal blood vessels in affected skin.10 Electron microscopy demonstrates that the elastic fibers are fragmented and irregular in appearance and occasionally can be engulfed by macrophages.

Differential Diagnosis

Anetoderma must be differentiated from other disorders of elastic tissue as well as atrophies of the connective tissue (Box 67-1).

Keloids form nodules that are much firmer on palpation. A history of trauma is often elicited, and the pathology is very distinct.

Glucocorticoid-induced atrophy occurs most commonly over the triceps or buttocks at sites where injections are usually given. Clinically, the lesions resemble atrophoderma. History is obviously most helpful in making the diagnosis. On histopathology, polarization may show the steroid crystals in the dermis.

Nevus lipomatosus superficialis of Hoffman and Zurhelle presents as a clustered group of soft, skin-colored to yellow nodules usually on the lower trunk and buttocks and present since birth. Histology shows ectopic mature lipocytes located in the dermis.

Papular elastorrhexis is an acquired disorder characterized by white, firm nonfollicular papules measuring 1–3 mm, evenly scattered on the chest, abdomen, and back. It usually appears in adolescence or early adulthood. The pathology demonstrates focal degeneration of elastic fibers and normal collagen. There are no associated extracutaneous abnormalities. This is believed by some authors to be a variant of connective tissue nevi11 or an abortive form of the Buschke–Ollendorff syndrome,12 whereas others think that these represent papular acne scars.13 They are differentiated from anetoderma by being firm noncompressible lesions.

Middermal elastolysis (MDE) usually consists of larger areas with diffuse wrinkling without herniation and with elastolysis limited to the middermis (See below).

Treatment

There is no regularly effective treatment. In secondary anetoderma, appropriate treatment of the inflammatory underlying condition might prevent new lesions. In patients with limited lesions that are cosmetically objectionable, surgical excision may be useful. Various therapeutic modalities have been tried but with no improvement of existing atrophic lesions, including intralesional injections of triamcinolone and systemic administration of aspirin, dapsone, phenytoin, penicillin G (benzylpenicillin), and vitamin E. Some authors have reported improvement with hydroxychloroquine.

Middermal Elastolysis

MDE is a rare acquired disorder of elastic tissue. It is characterized by patches and plaques of diffuse, fine, wrinkled skin, most often located on the trunk, neck, and arms. In 1977, Shelley and Wood reported the first case of “wrinkles due to idiopathic loss of middermal elastic tissue.”14 Since then, fewer than 100 cases have been reported. The vast majority of patients are Caucasian women between the ages of 30 and 50 years.15,16

Pathogenesis

The pathogenesis of this acquired elastic tissue degeneration is still unknown. Ultraviolet (UV) exposure has been postulated to be a major contributing factor in the degeneration of elastic fibers,17 including narrowband UVB.18 Other possible mechanisms include defects in the synthesis of elastic fibers, autoimmunity against elastic fibers, and damage to elastic fibers through the release of elastase by inflammatory cells or fibroblasts. More recent data suggest that inflammatory processes and an altered balance between matrix metalloproteinase and tissue inhibitor of metalloproteinases are possibly involved in the pathogenesis of MDE.19

Clinical Features

MDE is characterized by asymptomatic, well-demarcated, or diffuse areas of fine wrinkling (Fig. 67-3A). Rarely, erythematous patches, telangiectasias, or a reticular variant can be seen. Discrete perifollicular papules can be seen in some cases, leaving the hair follicle itself as an indented center. Lesions are typically found on the trunk, neck, and upper extremities. They are chronic and give the skin a prematurely aged appearance. There is usually no history of a preceding inflammatory dermatosis, but some patients report mild-to-moderate erythema. There is no associated systemic involvement.

Histopathology

The pathology shows a normal epidermis and, occasionally, a mild perivascular infiltrate in the dermis. The characteristic histology is seen on elastic tissue stains and reveals a selective band-like loss of elastic fibers in the middermis (see Fig. 67-3B). There is preservation of normal elastic tissue in the superficial papillary dermis above, in the reticular dermis below, and along adjacent hair follicles. Electron microscopy studies have shown phagocytosis of normal as well as degenerated elastic fiber tissue by macrophages.20

Differential Diagnosis

MDE must be differentiated from the other common disorders of elastic tissue.

Solar elastosis differs by its onset in an older age group, location in only sun-exposed areas, yellowish color, and coarser wrinkling, as well as by hyperplasia and abnormalities of elastic fibers and basophilic degeneration of the collagen in the papillary dermis.

Anetoderma is characterized clinically by smaller soft macules and papules instead of diffuse wrinkling, and histologically by elastolysis that can occur in any layer of the dermis.

Perifollicular elastolysis differs by a selective and almost complete loss of elastic fibers surrounding hair follicles compared with preservation of elastic fibers around follicles in MDE. Elastase-producing Staphylococcus epidermidis was found in the hair follicles and is the presumed etiology of this condition.21

Postinflammatory elastolysis and cutis laxa were originally described in young girls of African descent. An inflammatory phase, consisting of indurated plaques or urticaria, malaise, and fever, preceded the diffuse wrinkling, atrophy, and severe disfigurement. Insect bites may be the trigger for the initial inflammatory lesions.22

There is no known effective treatment for MDE. Sunscreens, colchicine, and topical retinoic acid have been tried without good success.15,16

Striae

(See Chapters 108 and 151)

Striae are very common and usually develop between the ages of 5 and 50 years.

They occur about twice as frequently in women as in men. They commonly develop during puberty, with an overall incidence of 25%–35%,23,24 or during pregnancy, with an incidence of 77%.25

The factors leading to the development of striae have not been fully elucidated. Striae distensae are the results of breaks in the connective tissue, resulting in dermal atrophy. Many factors, including hormones (particularly corticosteroids), mechanical stress, and genetic predisposition, appear to play a role.

During puberty, striae appear in areas where there is a rapid increase in size. In girls, the most common sites are the breasts, thighs, hips, and buttocks, whereas in boys, they are seen on the shoulders, lumbosacral region, and thighs. Other less common sites include the abdomen, upper arms, neck, and axillae.

Striae distensae are a common finding on the abdomen, and less so on the breasts and thighs, of pregnant women, especially during the last trimester. They are more common in younger primigravidas than in older pregnant women and are associated with larger weight gain and with babies of higher birth weight. Striae gravidarum can be associated with a higher risk of lacerations during vaginal delivery.26

Clinical Findings

Striae are usually multiple, symmetric, well-defined linear atrophic lesions that follow the lines of cleavage. Initially, striae appear as red-to-violaceous elevated lines (striae rubra) (see Fig. 107-3). Over time, the color gradually fades, and the lesions become atrophic, with the skin surface exhibiting a fine, white, wrinkled appearance (striae alba).24 The striae can measure several centimeters in length and a few millimeters to a few centimeters in width. The striae associated with systemic corticosteroid therapy and Cushing syndrome can be larger and more widely distributed.

Histopathology

Histologic findings show a decrease in dermal thickness and in collagen in the upper dermis. The collagen bundles are thinned and lie parallel to the epidermis, but they are also arranged transversely to the direction of the striae. Alterations in elastic fibers are variable, but dermal elastin can be fragmented, and specific elastin staining can demonstrate a marked reduction in visible elastin content compared with adjacent normal dermis.27 There is absence of both hair follicles and other appendages.

Differential Diagnosis

The diagnosis of striae distensae is usually simple, but the differential diagnosis does include linear focal elastosis (elastotic striae) that was first described by Burket et al in 1989.28 Linear focal elastosis is characterized by rows of yellow palpable striae-like bands on the lower back. Unlike striae, the lesions are raised and yellow rather than depressed and white. Elderly men are most commonly affected, although cases in teenagers have been described. Linear focal elastosis is probably not an uncommon condition. Histologically, there is a focal increase in the number of elongated or fragmented elastic fibers and a thickened dermis. It is postulated that linear focal elastosis may represent an excessive regenerative process of elastic fibers and could be thought of as a keloidal repair of striae distensae.29

Treatment

Striae distensae have no medical consequences, but they are frequently distressing to those affected. As stretch marks tend to regress spontaneously to some degree over time, the usefulness of treatments that have been tried without case controls is difficult to assess. Topical treatments that have shown some improvement of early stage striae are: tretinoin 0.1% cream,30 a combination of 0.05% tretinoin/20% glycolic acid, or 10% l-ascorbic acid/20% glycolic acid.31 Several lasers have been used in treating striae: the 585-nm pulsed-dye laser has been demonstrated to be of some efficacy in improving the appearance of striae rubra but has no effect on stria alba32; improvement in the leukoderma of the striae alba was noted with 308-nm excimer laser but maintenance treatment is required to sustain the cosmetic benefit.33 The long-term future of treatment strategies is encouraging with the advance in laser technologies.

Idiopathic Atrophoderma of Pasini and Pierini

Epidemiology and Pathogenesis

Idiopathic atrophoderma of Pasini and Pierini is a form of dermal atrophy that presents as one or several sharply demarcated depressed patches with no outpouching, usually on the back of adolescents or young adults.34 Whether atrophoderma is a nonsclerotic, primarily atrophic variant of morphea or a separate distinct entity is still debated.35–39 Its relationship to morphea is favored by its striking clinical and histologic similarities to the atrophy seen at sites of regressing plaques of morphea. Antibodies to Borrelia burgdorferi have been reported.37 Typical lesions of morphea, lichen sclerosus, and atrophoderma have been observed to occur simultaneously in the same patient but in different areas, supporting the view that these conditions are related. In a series of 139 patients, 17% had white induration in the central portions of their atrophic lesions, and 22% had superficial plaques of morphea coexisting in areas outside of their atrophic foci.35 However, to some, the different course and outcome of atrophoderma of Pierini and Pasini as compared with morphea justifies preservation of a distinct name.

This disorder is more frequently encountered in women than in men, with a ratio of 6:1. It usually starts insidiously in young individuals in the second or third decades of life. A congenital case was recently reported.40 The lesions usually occur on the trunk, especially on the back and lumbosacral region, followed in frequency by the chest, arms, and abdomen.37 The distribution is often symmetric and bilateral.

The lesions are single or multiple and usually round or ovoid, ranging in size from a few centimeters to patches covering large areas of the trunk (Fig. 67-4). They are usually asymptomatic and lack inflammation. When lesions coalesce, they can form large, irregular, brown patches but can be hypopigmented.41 The surface of the skin is normal in appearance, and there is no skin induration or sclerosis.

The borders or edges of these lesions are sharply defined, and they are usually described as abrupt, “cliff drop” borders ranging from 1 to 8 mm in depth, although they can have a gradual slant.34 These depressed patches are characteristic and give the impression of inverted plateaus, or, if multiple lesions are present, they can have the appearance of Swiss cheese. They are even more apparent when present on the back because the dermis is thicker in this area. The skin surrounding the patches is normal in appearance, and there is no erythema or lilac ring as in morphea.

Course

The course of this benign disease is progressive, and lesions can continue to appear for decades before reaching a standstill. Transformation to generalized morphea has not been observed.

Histopathology

The histologic picture is generally not diagnostic. The epidermis is usually normal or slightly atrophic. Collagen bundles in the mid- and reticular dermis show varying degrees of homogenization and clumping. Dermal thickness is eventually reduced when compared with adjacent normal skin.38 Some irregular clumping and loss of elastic fibers were described in earlier case reports,34 but in most series, no abnormality was seen with elastic tissue stains35,37; therefore, this is not of diagnostic value. The appendages are usually preserved. If sclerodermatous changes appear in preexisting patches, the histology reveals varying degrees of collagen sclerosis resembling morphea.

Differential Diagnosis

The differential diagnosis is to be made with active lesions of morphea that usually present as indurated, often hyperpigmented plaques with a characteristic peripheral lilac rim.

Therapy

No treatment has been proved effective. Dramatic response to oral hydroxychloroquine was recently reported in one patient.42

Follicular Atrophoderma

Follicular atrophoderma refers to dimple-like depressions at the follicular orifices. It can occur as an isolated defect of limited extent, in association with a variety of disorders in which hair follicles are plugged with keratin, or with rare genodermatoses.43,44

Distinctive ice-pick depressions around hair follicles can be seen most commonly on the back of the hands or feet and on the cheeks. These pitted scars can present at birth or early in life. A family history may be present. Follicular atrophoderma occurs in the conditions described in the following sections.

Atrophoderma Vermiculatum

Atrophoderma vermiculatum is a term that applies when the lesions are found exclusively on the cheeks. It is a condition that can either occur sporadically, be inherited as an autosomal dominant disorder, be part of a group of related diseases including keratosis pilaris atrophicans, or be associated with various syndromes.

Multiple inflammatory symmetric papules on the cheeks, presumably centered around hair follicles, may precede the atrophic lesions. These papules then go on to develop pitted, atrophic, and depressed scars in a reticulated or honeycomb pattern (Fig. 67-5). These lesions can extend to the forehead and preauricular regions. This condition usually has its onset in childhood or, less often, around puberty. Men and women seem to be affected equally.45 It usually has a slow progressive course.

Keratosis Pilaris Atrophicans

Keratosis pilaris atrophicans46 can include atrophoderma vermiculatum but also a group of closely related disorders that includes keratosis follicularis spinulosa decalvans and ulerythema ophryogenes. These conditions are characterized by keratotic follicular papules, variable degrees of inflammation, and secondary atrophic scarring. Keratosis follicularis spinulosa decalvans begins in infancy with keratotic follicular papules over the malar area and progresses to involve the eyebrows, scalp, and extremities, with scarring alopecia. This condition is inherited in an X-linked recessive fashion in some patients. Ulerythema ophryogenes (or keratosis pilaris atrophicans faciei) differs from atrophoderma vermiculatum by affecting primarily the lateral portion of the eyebrows (ophryogenes) with erythema, follicular papules, and alopecia (Fig. 67-6).

The underlying pathologic defect in these disorders appears to be abnormal follicular hyperkeratinization of the upper third of the hair shaft leading to obstruction of the growing hair and production of chronic inflammation. The end result of this process is scarring below that level. Histopathology is usually not very helpful and shows dilated follicles, sometimes associated with plugging, inflammation, and sclerosis of dermal collagen.

Associated Syndromes

The various syndromes that include atrophoderma vermiculatum are the Rombo syndrome (milia, telangiectasias, basal cell carcinomas, hypotrichosis, acral cyanosis, and, rarely, trichoepitheliomas), Nicolau–Balus syndrome (syringomas and milia), Tuzun syndrome (scrotal tongue), and finally the Braun–Falco–Marghescu syndrome (palmoplantar hyperkeratosis and keratosis pilaris).

Therapy

These disorders are mainly a cosmetic but vexing problem. Various topical treatments, including emollients, corticosteroids, tretinoin, and keratolytics, have shown no consistent benefit. Systemic isotretinoin has been shown to stop progression and to induce remission in some cases.46 Dermabrasion as well as carbon dioxide and 585-nm pulsed-dye lasers are other options to improve the appearance of the atrophic scars.47

Bazex–Dupré–Christol Syndrome (OMIM #301845)

Bazex–Dupré–Christol syndrome is characterized by follicular atrophoderma, milia, multiple basal cell carcinomas, hypotrichosis, and localized hypohidrosis.48–50 The follicular atrophoderma described as multiple ice-pick marks or patulous follicles can be found most commonly on the dorsa of the hands. It is inherited in an X-linked dominant fashion, and the gene has been linked to Xq24–q27.48 Subsequently reported findings include facial hyperpigmentation, hair shaft dystrophy, and multiple genital trichoepitheliomas.

Conradi–HüNermann–Happle Syndrome (X-Linked Dominant Chondrodysplasia Punctata, CDPX2, OMIM #302960)

Conradi–Hünermann syndrome is an X-linked dominant disorder that occurs only in girls because it is usually lethal in hemizygous males. The underlying molecular defect consists of mutations in the emopamil-binding protein gene at Xp11.23-p11.22.50 The clinical manifestations include an ichthyosiform scaling erythroderma patterned along the lines of Blaschko that usually resolves during the first year of life and is replaced by bands of follicular atrophoderma.43 Hyperpigmentation, cataracts, scarring alopecia, saddle-nose deformity, asymmetric limb reduction defects, and stippled calcifications of the epiphyses can be seen. Ichthyosis with keratotic follicular plugs containing dystrophic calcification in newborns are distinctive histopathologic features.51

Many systemic conditions [scleroderma (see Chapter 157), lupus erythematosus (see Chapter 155), dermatomyositis (see Chapter 156)], and genodermatoses (poikiloderma congenitale, dyskeratosis congenita, Cockayne syndrome, Hallermann–Streiff syndrome) have skin atrophy as an associated finding and are described in other chapters.