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STRUCTURAL DISORDERS OF THE DERMIS, COLLAGEN , AND ELASTIC TISSUES

Dermal atrophy: introduction

Dermal atrophy may:

Selected specific examples are discussed here.

Lichen sclerosus

Etiology and pathogenesis

Lichen sclerosus (previously termed lichen sclerosus et atrophicus) is an inflammatory dermatosis that especially affects genital skin (Ch.20) but also occurs at extragenital sites; the two forms may occur together or in isolation. It has a female predominance, especially in genital skin. At extragenital sites, it usually presents due to color change or textural abnormality, and is therefore discussed as an atrophic disorder, although the histology of early lesions actually resembles that of lichen planus (Ch.8).

    The etiology is uncertain and may be multifactorial. There are well-documented associations with a variety of autoimmune conditions, especially thyroid disease, vitiligo, alopecia areata, and diabetes. Other associations include lichen planus, sclerodermas, atopic dermatitis, primary biliary cirrhosis, pernicious anemia, and lupus erythematosus. Even in patients with no evidence of any of these disorders, there may be positive autoantibodies, such as antigastric parietal cell, antithyroid microsomal, or low-titer antinuclear antibodies.

Figure 22.6 Wrinkling and sagging skin of the upper arm, an age-related phenomenon.

Figure 22.7 Facial wrinkling involves age changes, solar damage, and in this case a component from cigarette smoking. Smoking activates neutrophil polymorphs, which may release elastase, hence damaging the facial skin

    Familial cases have been described, including sibling involvement in young children and twins. However, there are also studies suggesting a microbial cause, the strongest (but not definite) evidence implicating Borrelia or other spirochetes. There are also local factors in the skin that may be involved, as a Koebner reaction is not uncommon in active lichen sclerosus (Fig. 22.8).

Clinical features

Lichen sclerosus may occur at any age. Most studies indicate a strong female preponderance, although the frequent involvement of genitalia in either sex, and the relatively high frequency of asymptomatic lesions, may mean that published studies are not truly representative of the overall prevalence and sex ratio.

    The histologic features in the early stages include a lichenoid pattern of lymphocytic infiltrate, basal cell vacuolation, colloid bodies, and upper dermal edema. As lesions progress, the infiltrate lessens but the epidermis is thinned (atrophic) and the upper dermal collagen becomes amorphous and hyalinized, giving the lesions a white color (Figs 22.9 – 22.13). Follicles have keratin plugs initially but gradually shrink.

Figure 22.8 Lichen sclerosus demonstrating the Koebner phenomenon; this is the small spot pattern, forming a linear band of lesions along the site of a bra strap. The patient had herself appreciated this localization and was avoiding new lesions by wearing looser clothing. The Koebner phenomenon may also occur in vitiligo, which can look rather similar but does not have any textural change and does not usually produce this pattern of small spots.

Figure 22.9 Lichen sclerosus is typically fairly symmetric, as shown in this case. The wrists are a relatively common site (see also Fig. 22.11).

    There are three main clinical patterns, based on the body sites affected, which have many shared features but some site-specific aspects. These are as follows.

All the genital forms are discussed in Chapter 20; this section will concentrate on the overtly atrophic extragenital variant.

    In extragenital lichen sclerosus, lesions occur particularly on the upper trunk and abdomen (often at the waistline or under bra straps, which may represent a Koebner reaction). Initially, there are often multiple adjacent small plaques that merge together. In some patients, the pattern may persist as a collection of tiny areas (guttate pattern). The striking feature is the white atrophic appearance of affected skin. There is often a mild halo of inflammation around newer lesions, and such lesions may be quite itchy, although many cases are asymptomatic. At extragenital sites in particular, the plaques are typically studded with prominent follicular keratoses or pits representing follicular openings, particularly in relatively recently affected areas.

Fig. 22.10  (a) Lichen sclerosus. Follicular prominence or keratotic plugs are a typical feature, especially in early lesions. This is helpful to distinguish lichen sclerosus from morphea (b) and vitiligo (c). In morphea, the skin isfirm and sclerotic, but atrophy of skin appendages is a common early feature, imparting a shiny appearance (b). In vitiligo, the skin has normal texture and appendages (c). The morphea and vitiligo illustrated are unusual, as they were both present in the same patient.

Figure 22.11 Lichen sclerosus at the wrists. The atrophic component is particularly apparent in this case, with easily visible veins. This patient also had cutis laxa (shown in Fig. 22.22).

Figure 22.12 The small-spot pattern of lichen sclerosus causes particular diagnostic difficulty, often being confused with disorders such as pityriasis versicolor, although it lacks thefine scaling of the latter.

Differential diagnosis (extragenital lesions)

This includes the following.

Treatment

There is no consistently useful treatment for the color changes and skin atrophy of lichen sclerosus, other than camouflage measures. Treatment is aimed at improving the symptoms and the inflammatory component that indicates progressive disease. Although many patients do not have symptomatic lesions, some suffer intense itch, and in such cases use of a potent topical steroid may be required. A small number of patients with severe and unremitting symptoms may require systemic immunosuppressive therapy. Treatment of genital lichen sclerosus is detailed in Chapter 20.

Figure 22.13 The abnormal collagen in the upper dermis in lichen sclerosus means that capillaries are poorly supported, and purpura due to leakage of blood from easily disrupted small vessels is a common feature (a). This causes particular concern in genital lesions (see Chapter 20). Occasionally, the purpuric component of lichen sclerosus may be the main clinical feature (b). This is most likely in lesions with significant itch and scratch, or (as in this case in the inframammary region) in flexural lesions where the skin is subject to shearing stress.s

Figure 22.14 Eroded areas due to bullous lesions in lichen sclerosus, a rare pattern. See also Fig. 16.13.

Ehlers–Danlos syndrome (cutis hyperelastica)

Etiology and pathogenesis

This is a group of inherited disorders characterized by hyperextensible skin, together with varying degrees of hyperextensibility of joints and abnormality of blood vessels. Although also termed cutis hyperelastica, this is a misnomer: the defect in Ehlers–Danlos syndrome is actually one of deficient collagen. The different clinical patterns reflect the different mechanisms involved. Collagen is composed of a  chains that coil together in groups of three to form fibrils, which in turn coalign to form fibers. The Ehlers–Danlos defects may affect the a  chains themselves, or the subsequent cross-linking, giving rise to different phenotypes.

Figure 22.15 Ehlers–Danlos syndrome, showing typical thin, atrophic scars on the leg with a purplish-brown color due to repeated bruising. See also Fig.19.53.

Clinical

This group of disorders has been reclassified over the years. The current classification is as follows.

Differential diagnosis

The main dermatologic differential is from simple bruising or stretching of scars over joints, which occurs due to skin tension and movement. Occasionally, platelet defects, artefactual disease, and so-called easy bruising syndrome may be in the differential. The joint laxity needs to be distinguished from ‘normal' laxity and from Marfan syndrome.

Treatment

There is no useful treatment other than prevention of undue trauma and symptomatic treatment of complications.

Anetoderma

Etiology and pathogenesis

Anetoderma is a localized area of lax skin, often with herniation of the underlying tissues, although lesions may be depressed (Figs 22.16 – 22.18). It may occur as solitary or multiple lesions, and may be in one of the following groups.

Figure 22.16 Anetoderma in the axilla, demonstrating that the skin is atrophic and out-pouching in this area of relatively lax skin.

Figure 22.17 Anetoderma. There is an elevated lesion due to the subcutaneous tissues bulging through an area of atrophic dermis. These lesions are typically soft.

Clinical

Lesions of anetoderma are not obviously atrophic, as they protrude from the skin rather than being depressed or thinned. They represent soft
areas of herniation that can be compressed inward with a blunt probe (Fig.22.18). Preceding inflammation or urticarial lesions occur in some patterns.

Differential diagnosis

The main issue is the differential diagnosis of the cause, rather than that there is anetoderma, although this will not be recognized if the skin protuberance is not palpated and compressed. The wrinkling of mid-dermal elastolysis may appear similar, but this is not associated with a herniation effect.

Treatment

Ongoing infective or inflammatory causes should be excluded. Occasionally, surgical treatment may be appropriate for individual troublesome lesions.

Other causes of dermal atrophy

Striae and scars

Striae (stretch marks) are primarily due to changes in dermal collagen, but the shearing of the dermis that occurs causes the overlying epidermis to be thinned, especially when there is already damage to the epidermis (e.g. in cases due to overuse of topical steroids, Figs 22.19 – 22.21).

    Scars may also become stretched if they are at areas of tension; even if supported by subcutaneous sutures, these will not give full tissue strength. Such stretch is generally a slower process, so epidermal growth usually means that the epidermis is relatively well maintained. Note that scars may also become thickened (see later). A similar stretching process of the dermis may occur over rapidly enlarging subcutaneous nodules such as epidermoid cysts.

Cutis laxa

This is a defect of elastic tissue that may occur as dominant, recessive, X-linked recessive, and acquired forms. The acquired forms may be apparently idiopathic, but some cases are paraneoplastic and some occur following inflammation of the skin. Similar changes can occur due to long-term penicillamine therapy. The striking clinical feature is laxity, with wrinkling and sagging of the skin (Fig.22.22), producing a prematurely aged facies. As well as the skin defect, there may be internal features such as hernias, emphysema, and gastrointestinal diverticula. Clinically similar but localized wrinkled skin can occur over plexiform neuromas in neurofibromatosis. There is no specific treatment, but surgery to sagging areas of skin may improve the appearance.

Figure 22.18 Anetoderma, demonstrating that the soft subcutaneous tissue can easily be compressed through the dermal defect. Neurofibromas may also have a similar morphology, with a dumbbell-shaped soft nodule traversing the dermis, and capable of some degree of compressibility.

Figure 22.19 Topical steroids may cause striae if overused. Caution is required in thin flexural skin, such as around the axillae, where there may also be significant stretching tension on the skin, and in obese patients. The atrophy was so severe that the skin tore, forming an ulcer.

Figure 22.20 Striae distensae typically occur when the skin is stretched rapidly, for example by weight gain or during pregnancy. They often appear quite red initially, but older striae lose their redness and appear white or silvery withfine wrinkling.

Figure 22.21 Multiple horizontal striae of this type are common in adolescents, usually boys, due to rapid vertical growth. They have been confused with child abuse. Although patients with these are often referred for exclusion of endocrine disorders such as Cushing syndrome, they are generally thin andfit rather than overweight and cushingoid.

Figure 22.22 Cutis laxa on the neck, causing the characteristic wrinkled appearance. This patient was unusual in also having lichen sclerosus (shown in Fig. 22.11)

Figure 22.23 Blepharochalasis: laxity of the skin of the upper eyelid.

Blepharochalasis

This disorder is rather like a localized form of cutis laxa confined to the upper eyelids, although it is sporadic in nature. It causes drooping of the upper eyelid, in some cases sufficiently obvious that a surgical correction is required (Fig. 22.23).

Focal dermal hypoplasia

A streaky pattern of skin atrophy, and sometimes fatty herniations, occurs in this rare genodermatosis. It is discussed in more detail in Chapter 19.

Atrophodermas

These are a group of rather varied disorders in which there is a depression in the skin surface. Recognized patterns include the following.

Dermal thickening: introduction

Numerous conditions lead to thickening of the dermis, including edema, cellular and other infiltrates, altered mucin content of the ground substance, and changes in collagen or elastic tissue (Table 22.2). However, most of these are covered in other chapters; the emphasis in this section will be on the collagen and elastic tissues.

Figure 22.24 Atrophoderma of Pasini and Pierini, showing the typical distribution of brownish lesions on the lower part of the back.

Figure 22.25 Atrophoderma of Pasini and Pierini. The lesions are sharply demarcated with a palpable border due to the depression of the atrophic lesional skin.

Table 22.2 SOME CAUSES OF DERMAL THICKENINGa

Appearance	Cause	Examples
Discrete lesions with scaling or other surface change	Cellular infiltrate	Numerous inflammatory dermatoses, for example psoriasis, early discoid lupus
Smooth localized swelling	Fluid Cellular infiltrate Other infiltrate Altered connective tissue	Urticaria, localized edema essner lymphocytic infiltrate Some xanthomas, nodular mucinosis, discrete areas of calcinosis Keloid scar, dermatofibroma, localizedfibromas
Papular or cobblestoned appearance	Altered connective tissue Cellular infiltrate Other infiltrates	Granuloma annulare, pretibial myxedema, scleromyxedema, solar elastosis, connective tissue nevi, pseudoxanthoma elasticum Sarcoidosis, some psoriasis or eczema (especially lichenified) Some xanthomas, lichen amyloidosis
Smooth plaque lesions	Sclerotic disorders (see Ch.13)	Scleroderma, morphea, diabetic stiff skin
Peau d'orange appearance	Cellular infiltrate Fluid Altered connective tissue	Neoplastic infiltration Early pretibial myxedema, scleredema, some connective tissue nevi Some dependent edema,

aNote that there is overlap between the clinical appearances, so some conditions may have more than one morphology; also, some may have more than one type of process occurring (e.g. connective tissue change and cellular infiltrate in granuloma annulare or dermatofibroma). (From Lawrence CM, Cox NH. Physical Signs in Dermatology, 2nd edn. London: Mosby, 2002.)

Figure 22.26 Atrophoderma vermiculatum: a typical honeycomb atrophy pattern on the cheek of a child. (From Lawrence CM, Cox NH. Physical Signs in Dermatology, 2nd edn. London: Mosby, 2002.)

Figure 22.27 Keloids tend to occur on the upper torso, as shown in (a) and (b). Spontaneous lesions on the anterior chest presumably reflect skin tension, as they typically run across the chest (a). Occasionally, keloids in this site contain coiled-up hairs, which may possibly cause some initial inflammation. Why some scars become keloidal and others do not (b) is a mystery. People with black skin have a higher risk of keloid scarring (c).

Figure 22.28 Extensive keloid scarring on the back, in this case due to severe acne. Acne in patients with a keloid tendency may warrant aggressive therapy.

Scars and keloids

Scars are an inevitable consequence of any injury into the dermis. They may cause either thickening or thinning of the skin; the latter is discussed earlier. Cosmetic aspects of scar placement and scar treatment are not addressed here.

    Persistently itchy scars, in which infection or trapped hairs are not the cause, can be treated with topical or intralesional steroids. Laser treatments are also possible for erythematous scars.

    Keloids are a persistent, proliferative type of scar tissue (Figs 22.27 – 22.30). They may arise after surgical procedures, the risk being greatest on the neck and upper trunk or upper arm in young adults and especially in African-Caribbean people (see also Ch.21). Inflamed lesions such as acne, tuberculosis inoculation sites, and ingrowing hairs may also cause keloids; some are apparently spontaneous. Hypertrophic scars appear similar but are confined to wound sites, do not proliferate laterally, and tend to gradually flatten with time.

    Keloids are difficult to treat. Therapy is usually with topical or intralesional steroids. Silastic gel in various formulations may be helpful in some cases, and laser treatments (especially to early keloids with a vascular component) can be useful. Cryotherapy may reduce some of the bulk of a keloid scar. Surgical excision has the risk of further keloid, but may be successful if the wound is subsequently treated with steroid, silastic gel sheets, pressure bandaging, or radiotherapy. UVA1 may be proved useful; various intralesional cytotoxics and interferon have also been tried, with variable benefit.

Figure 22.29 Postoperative keloid scarring. The interesting paradox in this patient is that her keloid scars arose following operations for recurrent dislocations of the patella, suggesting a degree of collagen defect.

Figure 22.30 The earlobe is a common site for keloids, usually related to the trauma of ear piercing, but occasionally occurring after contact dermatitis or infection. (See also Fig. 5.8.)

Figure 22.31 Plantarfibromatosis (a) is uncommon but requires histologic confirmation, as malignant sarcomas as well as benign lesions such as schwannoma (b) may appear similar. Although the markedfirmness of plantarfibromatosis is a useful clue, even intrinsically soft lesions deeply situated on the sole can appear quite hard.

Fibromatoses, pachydermoperiostosis, and other collagen proliferations

Scleroderma (hard skin) is a feature of several skin disorders. This is discussed with a differential diagnosis in the context of collagen vascular disease, the commonest cause of a diffuse sclerodermatous process (Ch.13). Note that some cases may have a thickened dermis but are depressed below the normal skin surface contour (therefore appearing atrophic) due to deeper tethering.

    Fibromatoses are uncommon. They may affect fibrous tissue at different levels in the skin, although some are confined to the dermis or to the deeper fascia (see later). They may present a diagnostic challenge, as deep, diffuse types may be difficult to distinguish with certainty from soft tissue sarcomas or other lesions (Fig.22.31), and are also difficult to remove surgically without risk of interfering with function.

    Pachydermoperiostosis describes a thickening of tissues including the skin and deeper structures, including periosteum, as implied from its name. Finger clubbing is a type of pachydermoperiostosis that occurs in conjunction with internal malignancy, especially bronchial carcinoma. A more extreme version occurs as an autosomal dominant condition, which is particularly prominent in males. There is marked coarsening of facial features, with greasy skin and palmoplantar hyperhidrosis (Fig. 22.32).

    Periungual fibromas may occur as sporadic (usually solitary) lesions, at least some of which appear to be traumatic in origin. Multiple periungual fibromas are a feature of tuberous sclerosis (Ch.19 and Fig. 22.33).

    Connective tissue nevi usually present in early childhood as yellowish white plaques with a cobblestoned surface (Fig.22.34). They may occur in tuberous sclerosis (collagen) and in Buschke–Ollendorff syndrome (elastic, Fig.22.35). Localized collagenous overgrowth also occurs in Proteus syndrome (Ch.19) and other congenital disorders (Fig. 22.36).

    Hypertrophic and lichenified dermatoses . Some patients with itchy dermatoses, particularly on the lower leg, develop smooth rounded nodules with dermal thickening. Lesions may be discrete or may produce a semiconfluent cobblestoned pattern. It is not specific to any one underlying disorder, and occurs, for example, in long-term dermatitis, psoriasis, or even lichen planus (Fig.22.37). Prolonged use of topical steroids has been blamed by some, but rubbing the area is a more likely explanation; this pattern does seem to be related to chronicity.

Pseudoxanthoma elasticum

Etiology and pathogenesis

Pseudoxanthoma elasticum (PXE) is a recessively inherited disorder, most individuals having a mutation in the gene MRP6 . Some apparent dominantly inherited cases have also been reported. Additionally, a localized, non-heritable, periumbilical perforating variant of PXE occurs in obese black women. In all types, the abnormality is an accumulation of calcium and other minerals on elastic fibers, which appear fragmented and clumped on routine microscopy.

Clinical

Skin and blood vessels are affected. The characteristic cutaneous lesions are grouped yellowish papules that predominantly affect the neck and axillae but also other flexural areas (Fig.22.38). There is also some sagging of the skin, giving rise to the description of a plucked chicken appearance. Internal organs may be affected, with papules on various mucosal surfaces; the elastic deficiency also affects the Bruch membrane in the eye, which develops ragged brown linear tears that resemble vessels and are known as angioid streaks.

    The importance of the condition is the involvement of blood vessels internally, mid-sized arteries being predominantly affected. This is most commonly apparent as gastrointestinal bleeding, especially in pregnancy. Bleeding from the uterus or urogenital tract may occur, and retinal hemorrhage is a frequent complication. Hypertension, angina, peripheral vascular disease, and cerebrovascular bleeds are all potential causes of serious morbidity or death.

Figure 22.32 Pachydermoperiostosis. Deep, furrow-like folds of skin on the forehead (a) and scalp (b), with clubbing of thefingers (c) in primary pachydermoperiostosis. The skin changes, known as cutis verticis gyrata, may occur withoutfinger clubbing as a separate entity, and lesser changes of this type may occur in acromegaly.

Differential diagnosis

This might include the following.

Figure 22.33 Periungualfibromas may be solitary or multiple, the latter being a feature of tuberous sclerosis.

Figure 22.34 Connective tissue nevus on the neck. These may occur in isolation or associated with tuberous sclerosis or Buschke–Ollendorff syndrome (see Fig. 22.35).

Figure 22.35 Buschke–Ollendorff syndrome, in which elastomas are associated with bony changes known as osteopoikilosis.

Treatment

There is no specific prophylactic treatment, but cardiovascular risk factors should be minimized and ophthalmic review is required.

Figure 22.36 A congenital overgrowth of collagen, producing a soft, rubbery mass on the hand. This is probably the palmar equivalent of a disorder that occurs on the foot, known as plantar cerebriform hyperplasia.

Figure 22.37 Cobblestoned pattern of skin thickening that can occur in itchy dermatoses. This typically affects the lower leg. It may be just a variant of lichenification

Figure 22.38 Pseudoxanthoma elasticum (PXE), showing typical ‘plucked chicken’ grouped yellowish papules and prominent skin folds on the neck, axilla, etc. Lesions are usually most apparent on the neck or in the axillary region; the latter may be confused with Fox–Fordyce disease (Ch. 23), but this is confined to the axilla and does not have the soft slackness of the skin that is a feature of PXE.

Figure 22.39 Elastosis perforans serpiginosa, demonstrating the annular morphology of the grouped lesions.

Other disorders of elastic tissue

Some additional disorders of elastic tissue are grouped together for convenience.

Elastosis perforans serpiginosa

This is a perforating dermatosis in which abnormal elastic fibers are extruded through the skin surface. Patients are usually older children or young adults. It is common in patients with trisomy 21 (Down syndrome), and also occurs due to prolonged high-dose penicillamine therapy (e.g. in Wilson disease) and in conjunction with other defects of connective tissue such as Marfan syndrome, Ehlers–Danlos syndrome, and PXE.

    The lesions are grouped papules, often with an annular or a serpiginous pattern, which typically occur on the neck and arms (Fig.22.39). They usually appear umbilicated or centrally crusted due to the elimination of altered elastic tissue through the skin. Histologic examination is useful to demonstrate elastic tissue within the epidermis, and there are characteristic ‘lumpy bumpy' elastic fibers in cases due to penicillamine. Treatment is usually with strong topical or intralesional steroids, but the response is often poor.

Other types of elastosis and related disorders

In addition to PXE and cutis laxa, discussed earlier, other elastotic and elastolytic disorders include the following.

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.