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Elastic Tissue disordersElastic Tissue disorders

BYBY

M.YOUSRY ABDEL-MAWLAM.YOUSRY ABDEL-MAWLA

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ELASTIC TISSUEELASTIC TISSUE

• Elastic fibers are the principal components of connective tissue that impart resilience and elasticity to the skin.

• Mature elastic fibers in the reticular dermis are composed of microfibrils (15% by weight, containing fibrillins and microfibrilassociated glycoproteins) that surround a core of amorphous elastin (85% by weight, a single polypeptide chain of 800 amino acids);

• The immature fibers seen in children have a higher percentage of microfibrils (50% by weight)

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Cutaneous elastinCutaneous elastin

• Cutaneous elastin and microfibrillar glycoproteins are synthesized primarily by fibroblasts.

• Elastin is initially secreted as tropoelastin, which is crosslinked with and stabilized by desmosine to form elastin. A critical enzyme in this process is lysyl oxidase, a copper-dependent enzyme that deaminates lysine to form crosslinks in both elastic and collagen fibers.

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Elastin MetabolismElastin Metabolism

• Elastin is metabolized by proteolytic enzymes, including serine-type elastases, which are secreted by neutrophils, macrophages, human fibroblasts, and other types of cells.

• Elastic fibers are also degraded by matrix metalloproteinases (MMPs), of which there are at least 23 different enzymes secreted by a variety of types of cells.

• The MMPs stromelysin, macrophage•metalloproteinase (MMP-12), the gelatinases

(MMP- 2 and MMP-9), and matrilisin (MMP-7) are the most active against elastic fibers

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Histopathologic OrientationHistopathologic Orientation

• Elastic fibers of the papillary dermis are oriented parallel (elaunin fibers) or perpendicular (oxytalan) to the dermal-epidermal junction and are thin and few in number.

• Oxytalan fibers lack the elastin core., elaunin fibers contain a small amount of elastin

• Mature elastic fibers are found predominantly in the reticular dermis

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Elastic Tissue disordersElastic Tissue disorders

• Several disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described

• They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis, acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favre´-Racouchot syndrome.

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Focal dermal elastosis.

A, Antecubital fossa showing multiple 1- to 3-mm diameter discrete and coalescing yellow papules.

B, Thickened elastic fibers in the mid to deep reticular dermis

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• Elastofibroma. • A, Linear arrangement of globular, aggregated elastic

fibers (arrow). (Hematoxylin-eosin stain; original magnification 320.)

• B, Elongated serrated elastic fibers

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Favre´-Racouchot syndrome• Dilated follicular infundibula with small infundibular cysts

filled with lamellar keratin and lined b squamous epithelium. Foci of solar elastosis are present in

the superficial dermis. (Hematoxylin-eosin stain)

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Papular elastorrhexis

• A, Back showing a 4-mm-diameter, well demarcated white papule.

• B, Fragmentation of elastic fibers throughout the dermis. (Elastic stain, original magnification 310).

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Anetoderma

• A, Flank showing multiple discrete saclike bulging papules of the Schweninger-Buzzi type.

• C, Zone of elastolysis involving the papillary and reticular dermis. (Elastic stain; original magnification.)

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PSEUDOXANTHOMAELASTICUM

■ Incidence: 1 in 25,000 to 100,000

■ Autosomal recessive inheritance, occasional pseudo-dominant.■ Mutations in multidrug resistance associated protein (MRP6),

encoded by (ABCC6) on chromosome 16q13.1.■ Cutaneous features include yellow, flat,papules in the neck,

flexures, and periumbilical areas. Less frequent skin,lesions include acneiform lesions, elastosis perforans serpiginosa, reticulate pigmentation, and granulomatous nodules.

■ Extracutaneous manifestations include angioid streaks, visual impairment, peau d’orange retinal hyperpigmentation, cardiovascular disease, and bleeding.

■ Histopathology shows swollen, clumped, fragmented elastic fibers and calcium deposits in the mid and deep reticular dermis. Alterations easily visualized with calcium (i.e., von Kossa) and elastic (i.e., Verhoeff-van Gieson or orcein) stains.

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• Pseudoxanthoma elasticum.

Papules on the neck. There is a distinct yellowish hue. Loose, thickened skin with a pebbled appearance on the neck.

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Pseudoxanthoma elasticum, elastic tissue stain. The elastic fibers show marked degeneration.

They are swollen, tortuous, and irregularly clumped.

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CONGENITALCUTIS LAXA

Inheritance may be autosomal dominant

autosomal recessive or X- linked recessive (also known as occipital horn syndrome).

• Mutations in elastin (ELN) or fibulin-5 (FBLN5) in autosomal dominant;

• In fibulin- 5 (FBLN5, EVEC, DANCE) or fibulin-4 (FBLN4) in autosomal recessive;

• A copper transport adenosine triphosphatase

(ATP7A) in the X-linked type.

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CONGENITALCUTIS LAXA

• Cutaneous features include pendulous, inelastic skin, with an aged facies.

• ■ Extracutaneous manifestations may include pulmonary emphysema, aortic aneurysm, pulmonary artery and valve stenosis, hernias, gastrointestinal diverticula, joint laxity, low serum ceruloplasmin, and bilateral exostoses of the occiput (or occipital horn syndrome).

■ Histopathology shows sparse and fragmented elastic fibers, better visualized with stains (i.e., Verhoeff-van Gieson or orcein)

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• Cutis laxa due to fibulin-4 mutation. The facial skin hangs in loose folds giving the appearance of premature aging. The prominent periorbital vessels.

• The tracheostomy was placed for diaphragmatic and respiratory difficulty.

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Elastosis perforans serpiginosa

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ELASTOSIS PERFORANS SERPIGINOSA(EPSEPS))

• Characterized by hyperkeratotic papules and plaques, transepidermal elimination of abnormal elastic fibers, and focal dermal elastosis

• it has been postulated that focal irritation (biochemical or mechanical) in the dermis may induce formation of epidermal and follicular channels to extrude the irritating agent.

• In many cases, the trigger for elastogenesis is unknown.

• D-Penicillamine therapy for Wilson disease, cystinuria, and rheumatoid arthritis have been associated with one

subtype of EPS.