Disorders Of  Elastic Tissue
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Disorders Of Elastic Tissue

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the most important dermal elastoses

the most important dermal elastoses

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Disorders Of  Elastic Tissue Disorders Of Elastic Tissue Presentation Transcript

  • Elastic Tissue disorders BY M.YOUSRY ABDEL-MAWLA
  • ELASTIC 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)
  • Cutaneous 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.
  • Elastin 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
  • Histopathologic 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
  •  
  • Elastic 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.
  •  
    • 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
    • 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).
  • 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.)
    • Inherited disorders of connective tissuec omprise a clinically and genetically diverse group of conditions affecting pri-marily the skin, joints, and, often, the car-diovascular system.
    • The severity of the skin phenotype depends on the type of mutation and the role of the affected pro-tein on dermal structure and function
    • Some inherited connective tissue disorders are characterized by hyperextensible skin and joints
    • whereas others show cutaneous laxity.
    • Some disorders have specific cutaneous changes that reflect the alternations in the dermis, such as the striae in Marfan syndrome and the cutaneous papules of pseudoxanthoma elasticum.
  • The Ehlers-Danlos syndromes (EDSs)
    • A heterogeneous group of disorders characterized by hypermobile joints,hyperextensible skin, and fragile tissues that are extremely susceptible to trauma.
    • As many as 1 in 5000 individuals may be affected by some form of the disease.
    • The seven sub-types of EDS have been categorized based on clinical manifestations and corresponding molecular pathogenetic findings in collagen types I, III, and V, or processing enzyme
  • Pathogenic Mechanisms
    • Pathogenic alterations of fibrillar collagens in EDs result from deficient collagen processing enzymes, insufficiency, or mutations in collagen alpha chain
    • The classical type of EDS is characterized by an alteration in type V fibrillary collagen
    • and is inherited in an autosomal dominant
    • (AD) fashion.
    • Mutations in COL5A1 and COL5A2
    • A few patients have shown mutations in COL1A1 , a gene more commonly mutated in osteogenesis imperfecta
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  • MARFAN SYNDROME
    • ■ Incidence: 1 in 5000 to 10,000 (Online
    • ■ Autosomal dominant inheritance with mutations in fibrillin 1 ( FBN1 ; gene for fibrillin 1 chromosome15q21.1)
    • ■ Cutaneous features include striae distensae (two-thirds of patients), inguinal or incisional hernias, and, rarely, elastosis perforans serpiginosa.
    • ■ Extracutaneous manifestations include
    • hyperextensible joints, upward lens displacement,
    • skeletal abnormalities, and cardiac aberrations, such as aortic aneurysm and rupture.
  • FBN1
    • FBN1 is a major constitutive element of ECM microfibrils throughout the body. It is abundant in tissues affected in Marfan syndrome—the ascending aorta, suspensory ligament of the lens, periosteum, and the skin.
    • Fibrillin plays a major role in the normal functioning of microfibrils, which are critical structural components of many tissues.
    • The fibrillin molecule is spanned by cysteine-rich repeats interspersed with latent transforming growth factor-β (TGF-β)–binding protein-like and EGF-like motifs
  • HOMOCYSTINURIA
    • Incidence: 1 in 65,000 to 344,000
    • (Online Mendelian Inheritance in Man#236200).
    • ■ Autosomal recessive inheritance, mutations in cystathionine β-synthase, chromosome 21q22.3
    • ■ Cutaneous features include malar flush, fair and thin skin and hair, and livedo reticularis
    • ■ Extracutaneous manifestations include
    • downward lens displacement, osteoporosis, mental retardation, thromboembolism,and severe hyperhomocysteinemia.
  • METABOLIC DEFECTS
    • Patients with homocystinuria have primary hepatic deficiency of cystathionine β synthase ( CBS ), a pyridoxine-dependent enzyme in the methionine transsulfuration pathway, resulting in high plasma levels of the toxic amino acid L-homocysteine. Elevated homocystine levels inhibit cross-linking of collagen.
    • A minority of patients have an acquired (dietary) deficiency of cobalamin or heritable disorders that prevent conversion of dietary cobalamine to its biologically active forms;
    • Some have defects that cause decreased
    • availability of 5-methyltetra-hydrofolate which is also required in the metabolism of methionine
  • PSEUDOXANTHOMA ELASTICUM
    • ■ 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.
    • Pseudoxanthoma elasticum.
    • Papules on the neck. There is a distinct yellowish hue. Loose, thickened skin with a pebbled appearance on the neck.
    • Pseudoxanthoma elasticum, elastic tissue stain. The elastic fibers show marked degeneration.
    • They are swollen, tortuous, and irregularly clumped.
  •  
  •  
  • CONGENITAL CUTIS 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.
  • CONGENITAL CUTIS 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)
    • 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.
  •  
  •  
  • Elastosis perforans serpiginosa
  • ELASTOSIS PERFORANS SERPIGINOSA( EPS )
    • 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.