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`Kaken Exhibit 2013
`Acrux V. Kaken
`
`IPR2017-00190
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`Kaken Exhibit 2013
`Acrux v. Kaken
`IPR2017-00190
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`

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`Page 2 of 13
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`THE UNIVERSITY OF TEXAS AT AUSTIN
`THE GENERAL LIBRARIES
`
`This Item is Due on the Latest Date Stamped
`
`RETURNED
`
`JUN U 1 2005
`
`JAN 1 6 2007
`
`AR
`
`:1:
`
`,f?T:’.3
`
`LE 1' ‘Cf
`1‘
`"1
`JAN 1 7 2013
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`Page 3 of 13
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`

`

`FITZPATR|CK’S
`
`DERMATOLOGY
`IN GENERAL
`MEDICINE
`
`FIFTH EDITION
`
`Page 4 of 13
`
`

`

`IRWIN M. FREEDBERG, MD
`George Miller MacKee Professor and Chairman
`The Ronald 0. Perelman Department of Dermatology
`New York University Medical Center
`New York. New York
`
`ARTHUR Z. EISEN, MD
`Winfred A. and Emma R. Showman Professor of Medicine
`Chairman, Division of Dermatology
`Washington University School of Medicine
`Dermatologist-in-Cl'tief
`Bames Hospital
`St. Louis. Missouri
`
`KLAUS WOLFF, MD, DSc(H0n)
`Professor and Chairman. Department of Dennatology
`University of Vienna Medical School
`Head. Division of General Dermatology
`Vienna General Hospital
`Vienna. Austria
`
`K. FRANK AUSTEN, MD
`Theodore Bevier Bayles Professor of Medicine
`Harvard Medical School
`
`Brigham and Women’s Hospital
`Boston, Massachusetts
`
`LOWELL A. GOLDSMITH, MD
`Dean
`University of Rochester School of Medicine and Dentistry
`Rochester. New York
`
`STEPHEN I. KATZ, MD, PhD
`Chief. Dermatology Branch. National Cancer institute
`Director. National Institute of Arthritis and Musculoskelelul and Skin Diseases
`
`National Institutes of Health
`Bethesda. Maryland
`
`THOMAS B. FITZPATRICK, MD, PhD, DSc(H0n)
`
`Edward C. Wigglesworth Professor of Demiattology. Emeritus
`Chainnan Emeritus. Department of Dennatology
`Harvard Medical School
`Chief Emeritus. Dermatology Service
`Massachusetts General Hospital
`Boston. Massachusetts
`
`Page 5 of 13
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`;
`
`l
`
`2
`
`I
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`I
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`»
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`-
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`Page 5 of 13
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`

`

`FITZPATRICK’S
`
`DERMATOLOGY
`IN GENERAL
`MEDICINE
`
`FIFTH EDITION
`
`EDITORS
`
`IRWIN M. FREEDBERG, MD
`
`ARTHUR 2. EISEN, MD
`
`KLAUS WOLFF, Mo, DSc(Hon)
`
`K. FRANK AUSTEN, MD
`LOWELL A. GOLDSMITH,’ MD
`STEPHEN I. KATZ, MD, PhD
`
`THOMAS B. FITZPATRICK, MD, PhD, DSc(Hon)
`
`VOLUME 1
`
`M C G R A W - H I L L
`._._H___
`Health Professions Division
`Lisbon
`San Francisco Auckland
`Bogota’ Caracas
`New York Stlouis
`London Madrid Mexico Milan Montreal New Delhi
`Paris
`San Juan
`Singapore
`Sydney
`Tokyo
`Toronto
`
`/
`
`3
`/
`
`I
`
`Page 6 of 13
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`Page 6 of 13
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`

`

`McGraw-Hill
`A Division of TI1eMcGraw-Hill (jrrmpauirzs
`
`2:?
`
`Note: Dr. Stephen Katz's work as editor and author was performed outside the scope
`of his employment as a U.S. government employee. This work represents his personal
`and professional views and not necessarily those of the U.S. government.
`
`FITZPATRICK’S DERMATOLOGY IN GENERAL MEDICINE
`
`Fifth Edition
`
`Copyright © I999. 1993. 1987, I979. 197] by The McGraw-Hit!
`Companies. Inc. All rights reserved. Printed in the United States of America.
`Except as permitted under the United States Copyright Act of 1976, no part-
`of this publication may be reproduced or distributed in any form or by any
`means. or stored in a database or retrieval system. without prior written per-
`mission of the publisher.
`
`1234567890 QPKQPK 998
`
`Set Volume: ISBN 0-01912938-2
`Volume 1: ISBN 0-07-02l942-7
`Volume 11: ISBN 0-07-021943-5
`
`This book was set in Times Roman by York Graphic Services. Inc. The
`editors were Martin Wonsiewicz. Mariapaz Ramos Englis, and Lucinda Bauer;
`the production supervisor was Richard Ruzycka. The index was prepared by
`Irving Condé Tullar. Text and cover were designed by Marsha Cohen/Parallelo-
`gram. Quebecor PrintinglKingspor1 was printer and binder.
`
`Library of Congress Cataloging-in-Publication Data
`Fil1paln'ck's Dennalology in general medicine.—5tJ1 ed. /editors.
`Irwin M. Freedberg .
`.
`. [et ai.]
`p.
`cm.
`Rev. ed. of: Dermatology in general medicine. 4th ed. cl993.
`Includes bibliographical references and index.
`ISBN 0-07-9l2938—2 (set).—lSBN 0-07'-UZI943-S (v. 2).—[SBN
`O-O7-02I942-7 tv. 1)
`I. Dermatology. 2. Skin—Diseases. 3. Cutaneous manifestations
`of general diseases.
`I. Freedberg. Irwin M.
`[I. Fitzpatrick.
`Thomas B. (Thomas Bernard). date.
`[DNLM:
`l.' Skin Diseases. 2. Skin Manifestations. WR IOUFSS9
`I999]
`RL'Il.D46
`6l6.S—dc2l
`DNLMIDLC
`
`I999
`
`for Library of Congress
`
`Page 7 of 13
`
`Page 7 of 13
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`

`

`CHAPTER 18
`
`Antonella Tosti
`
`Bianca Maria Piraccini
`
`Biology of Nails
`
`The nail apparatus consists of a horny “dead“ product, the nail plate.
`and four specialized epithelia: the proximal nail fold. the nail ma-
`trix. the nail bed, and the hyponychium (Fig. 18-1). The nail ap-
`paratus develops during the ninth embryonic week from the epi~
`dermis of the dorsal tip of the digit as a rectangular area. the nail
`field. which is delineated by a continuous groove.‘ The proximal
`border of the nail field extends downward and proximally into the
`dermis to fonn the nail matrix primordium. By the 15th week, the
`nail matrix is completely developed and starts to produce the nail
`plate, which will continue to growth until death.
`The nail apparatus lies immediately above the periostium of the
`distal phalanx (Fig. 18-2). The intimate anatomic relationship be-
`tween the nail and the bone is responsible for the common occur-
`rence of bone alterations in nail disorders and vice versa. The shape
`of the distal phalangeal bone also determines the shape and the
`transverse curvature of the nail.
`
`Fingernails usually present a longitudinal major axis and toenails
`a transverse major axis. The size of the nails varies in the different
`digits, the largest nail being that of the first toe, which covers about
`50 percent of the dorsum of the digit.
`The nails have numerous functions. Fingernails not only con-
`tribute to the aesthetic appearance of the hands but are very im-
`portant in protecting the distal phalanges and enhancing tactile dis-
`crimination and the capacity to pick up small objects. They are also
`widely utilized for scratching and grooming and are an efficient
`
`FIGURE 15-l
`
`Diagramrnatit: drawing of a normal nail. PNF, proximal nail fold; NM.
`nail matrix; NB, nail bed; NP, nail plate; HYP. hyponychium; CU. cu-
`ticle; L, lunula region.
`
`FIGURE 18-2
`
`.in.mumt
`X-ray of the distal phalanx showing the t'lt'.:tS1'
`between the nail and the underlying distal plt.tl.invt.
`
`rt-I.it..mstt.p
`
`natural weapon. Toenails protect the distal toes and contribute lu
`pedal biomechanics.
`
`NAIL PLATE
`
`is L'Ul1|I1l|.It!tI\l}
`The nail plate is a fully keratinized structure that
`produced throughout life. It results from tnaturatinn and kct;tttttt-
`zation of the nail matrix epithelium and is firmly nttaclicd tn the
`nail bed, which partially contributes to its fontttitiun.
`l'rn\tttt.i|l_\
`and laterally, the nail plate is surrounded by the nail lnlds. ulttcli
`cover its proximal third and lateral margitts. At the tip oi the digit.
`the nail plate separates from the underlying tissues at
`the hypo-
`nychium.
`ll-l-.1 I.
`The nail plate is rectangular in shape and trunsparcnt tl-‘lg.
`It is curved in both the longitudinal and transverse ttxcs. cspcctttll}
`in the toes. The nail p1ate‘s surface is normally smooth but
`itc-
`quently shows mild longitudinal ridges that increase with aging. The
`pattern of these ridges can be utilized for forensic idctttilictttiott.
`The inner surface of the nail plate shows longitudinal ridpcs that
`correspond to the rete ridges of the nail bed. The nail plate appears
`homogeneously pink in color except for its free edge which is \\l'lllL'
`The pink color of the nail plate is due to tire blood \'csst.‘l\ he-
`neath it.
`the
`The proximal parts of the fingernails. especially those oi
`thumbs, show a whitish, opaque. half moonwshapcd area. the lunulti.
`which is the visible portion of the nail matrix. In this area the l‘I;IIl
`plate’s attachment to the underlying epithcliutn is luustt.
`lr'.Ill'v
`More than 90 percent of fingemttils show at thin. distal.
`verse white band. the onychocomeal band. which nturks the must
`distal portion of firm attachment of the nail plate to the nail l"N.‘tl.
`-
`
`Page 8 of 13
`
`239
`
`Page 8 of 13
`
`

`

`SECTION FOUR
`Biology 8: Function of Epidermis & Appentlages
`
`FIGURE 18-4
`
`FM
`
`NE
`
`OC
`
`OD
`
`240
`
`FIGURE 183
`
`
`
`Frontal picture of a normal nail. L, lunula; NB, nail bed; OC, onycho-
`corneal band; OD, onychodermal band; FM, free margin.
`
`This area represents an important anatomic barrier against environ-
`mental hazards; its disruption produces nail plate detachment with
`onycholysis. The onychocomeal band is separated from the nail
`plate‘s white free edge by a 1-
`to 1.5-mm pink band called the
`()l1_\'t'flrJ(f£-’.l‘Hml band.
`In transverse sections. the nail plate consists of three portions:
`the dorsal nail plate. the intermediate nail plate, and the ventral nail
`plate.‘ The dorsal and the intermediate portions of the nail plate are
`produced by the nail matrix, whereas its ventral portion is produced
`by the nail bed. Above the lunula.
`the nail plate is thinner and
`consists only of the dorsal and intermediate portions. There is a
`natural line of cleavage between the dorsal and intennediate nail
`plate.
`The nail plate progressively thickens from its emergence to its
`distal margin, the mean toenail thickness at the distal margin being
`1.65 i 0.43 mm in men and 1.38 i 0.20 mm in women. Finger-
`nails are thinner, their mean thickness being 0.6 mm in men and
`0.5 mm in women. There is an increase in nail thickness with age.
`particuiarly in the first two decades. Nail thickness depends on the
`length of the nail matrix and nail bed} Thinning of the nails is
`usually a sign of nail matrix disorders, whereas nail thickening is
`most commonly a consequence of nail bed disorders.
`
`PROXIMAL NAIL FOLD
`
`Thelproximlal nail fold is a skin fold consisting of dt)r'sal and vggniml
`P0|’il0I_1S (Fig. 18-4). The dorsal portion is anatomically similar to
`the skin of the dorsum of the digit but thinner and devoid of pilo-
`
`Page 9 of 13
`
`
`
`st-t tion sliovwnt; the dorsal and the ventral portions it the
`Histoloiiit
`proximal nail told. The rutitlo prowrlos arllu-sion lit-rm-r-:1 the vt.-ntral
`nail fold and the nail plate.
`
`sebaceous units. The ventral portion. which cannot be seen from
`the exterior and continues pro.~tim'.1lly with the gerniinative matrix.
`covers approximately one-fourth of the nail plate. it adheres closely
`to the nail p|atc's surface and keratinizes with a granular layer. The
`limit between the proximal nail fold and the nail matrix can be
`histologically established at the site of disappearance of the granular
`layer.
`fold forms the cuticle.
`The horny layer of the proximal nail
`which is Firmly attached to the superficial nail plate and prevents
`the separation of the plate front the nail fold. The integrity of the
`cuticle is essential for maintaining the homeostasis of this region.
`The dermis of the proximal nail fold contains numerous capil-
`laries that run parallel to the surface of the skin. as may easily be
`observed in vivo by capillary microscopy. This permits the obser-
`vation of both the arterial and venous limbs of the capillaries. which
`are arranged in parallel rows and appear as fine regular loops with
`a small space between the afferent and efferent limbs. The mor-
`phology of prmtirnal nail
`l'old's capillaries is typically altered in
`connective tissue disct1scs.5
`
`NAIL MATRIX
`
`The nail matrix is a specialized epithelial structure that lies above
`the midportion of the distal phalanx. After elevation of the proximal
`nail fold. the matrix appears as a distally com-‘ex crescent. with its
`lateral horns extending proximally and laterally.
`ln longitudinal sections. the matrix has a wedge-shaped app€-'if-
`ance: it consists of a proximal tdorsal) and a distal [ventral] porlifltl
`(Fig. I8-5}. Nail matrix keratinocytes divide in the basal cell layer
`and keratinize in the absence of a granular zone. Comifted onyL‘h0-
`cytcs are composed mainly of keratin filaments. high—sulfur Ittalrii
`proteins. and the marginal band. which consists of precipitated P1“
`teins on the cytoplasniic side of the cell membrane." The site of
`keratiriization tkeratogenous 7.onc_) of nail matrix onychocylcs C39
`be clearly distinguished in histologic sections as an eosinophilit‘
`area where cells show fragmentation of their nuclei and condensa-
`
`Page 9 of 13
`
`

`

`
`
`Histologic section of the proximal nail malrix. (Courtesy of C. Misciali,
`MD.)
`
`tion of their cytoplasm.’ In this area, nuclear fragments are de-
`stroyed by DNases and RNases. In some conditions. nuclear frag-
`ments may persist within the intermediate nail plate, producing leu-
`ltonychial spots. These, however.
`frequently disappear before
`reaching the nail's free edge. due to persistence of active enzymes
`that lyse DNA and RNA within the horny nail plate.
`The maturation and differentiation of nail matrix keratinocytes
`do not follow a vertical axis. as in the epidermis, but occur along
`a diagonal axis that is distally oriented. For this reason, keratini-
`ration of the proximal nail matrix cells produces the dorsal nail
`plate and keratinization of the distal nail matrix cells produces the
`intermediate nail plate.
`In some fingers, the distal matrix is not completely covered by
`the proximal nail fold but is visible through the nail plate as a white
`half rnoon—shaped area. the lunula. The white color of the lunula
`results from the following two main anatomic factors: (I) the ker-
`atugenous zone of the distal matrix contains nuclear fragments that
`cause light diffraction and (2) the capillaries of the nail matrix are
`less visible than those of the nail bed because the relative thickness
`
`of the nail matrix epithelium.-’
`
`FIGURE 18-6
`
`CHAPTER 18
`
`
`
`Biology of Nails 24] p
`
`phenomenon and stratified growth in a semilunar area. which "3-
`sembles the architecture of the nail matrix (Fig. 18-6).
`
`Melanocytes
`
`Nail matrix melanocytes are usually quiescent and therefore not
`detectable in pathologic sections. However. they possess the key
`enzymes necessary for melanin production and may become acti-
`vated by a large number of physiologic and pathologic conditions. '3
`l’~la1l matrix melanocyte activation produces diffuse or banded nail
`pigmentation and is more common in blacks and Asians than in
`Caucasians.
`
`Using the dopa stain, dendritic melanocytes are especially seen
`in the distal nail matrix. where they are frequently arranged in small
`clusters among the suprabasal layers of the nail matrix epithelium
`(Fig. l8-7). The suprabasal location of nail matrix mellnocytes rnly
`be a consequence of the distribution of the adhesion rnoleculcs in
`the nail epithelium. where o:3,81 integrin. which possibly regulates
`melanocyte-lteratinocyte adhesion. has a basal and supnibasal ex-
`pression.” Nail matrix melanocytes of Caucasians do not contain
`mature melanosornes. which are normally found in the nails of
`Asians and blacks.”
`
`Langerhans Cells
`
`Langerhans cells are more numerous in the proximal than in the
`distal nail matrix. As in normal epidennis. Langerhans cells are
`predominantly found in the suprabasal layers. They may. however.
`occasionally be seen within the basal layer of the nail matrix epi-
`thelium.
`
`Merkel Cells
`
`The presence of Merkel cells has been demonstrated in the nail
`matrix. Their density is possibly influenced by age. mi these cells
`are more numerous in fetal than in adult nails."
`
` .
`
`'
`'
`-
`.
`larization
`ex mination of spontaneous migration phenomenon. pn
`'
`E|eti:t'm'i1‘ Ilnltcirll-.i'Ci‘rjtl)F:isitit;i1n of basal cells Bar 2 turn (X3600). (From Pimrdo or .11.“ with
`'
`'
`an In! ta 5
`P€"”'l55l°”‘l
`
`—-
`
`Nail Matrix Keratinocytes
`
`The nail matrix cells are able to synthetize both
`“soft" or sltin—type and “hard" or hair-type kera-
`tins.3 According to Kitahara and Ogawaf’ the dorsal
`nail matrix keratinocytes in bovine hoof in vivo
`produce soft keratins while the ventral nail matrix
`lreratinocytes produce hard keratins. Results from
`in vitro studies. however. indicate that all cells are
`able to change their course of differentiation and
`express multiple keratins.°-‘°
`When cultured in a chemically defined medium.
`flail matrix cells are considerably larger than ePl'
`tlcnnal keratinocytes and show low nucleuslcyto—
`Plasm and high euchromatin heterochromatin ra—
`tios. The growth rate of cultured nail matrix cells
`is higher than that of epidermal keratinocytes."
`When cultured in serum containing medium,
`the
`nail matrix cells show a spontaneous migration
`
`Page 10 of 13
`
`Page 10 of 13
`
`

`

`SECTION FOUR
`Biology 8: Function of Epidermis 8: Appendages
`
`l.3ASl-EMENT MEMBRANE ZONE
`
`242
`
`FIGURE 18-7
`__.
`
`____
`
`.-—
`
`
`
`Dopa stain showing dendritic melanocytes within the suprabasal layers
`of the nail matrix.
`
`NAIL BED
`
`The nail bed extends from the distal margin of the lunula to the
`onychoderrnal band and is completely visible through the nail plate.
`The nail bed epithelium is so adherent to the nail plate that it re-
`mains attached to the undersurface of the nail when the nail
`is
`avulsed.
`The nail bed epithelium is thin and consists of two to five cell
`layers. Its rete ridges, which are longitudinally oriented, interdigitate
`with the underlying dermal ridges in the fashion of a “tongue and
`groove” joint.
`Nail bed keratinization produces a thin, horny layer that fonns
`the ventral nail plate. The nail bed’s contribution to nail plate for-
`mation corresponds to about one—fifth of the terminal nail thickness
`and mass.” In pathologic sections, the ventral nail plate is easily
`distinguishable because of its light eosinophilic appearance.
`Nail bed keratinization is not associated with the formation of a
`
`granular layer. A granular layer may, however, appear when the
`nail bed becomes exposed after nail avulsion.‘
`Although the distribution of melanocytes in the nail bed has not
`been extensively studied, our preliminary data indicate that sparse
`melanocytes are present in the nail bed epithelium.
`
`HYPONYCHIUM’
`
`The hyponychium marks the anatomic area between the nail bed
`and the distal groove, where the nail plate detaches from the dorsal
`digit. Its anatomic structure is similar to that of plantar and V0131-
`skin and keratinization occurs through the formation of a granular
`layer. The horny layer of the hyponychium partially accumulates
`under the nail pla1e’s free margin.
`The hyponychium is normally covered by the distal nail plate,
`but it may become visible in nail biters.
`
`Page 11 of 13
`
`The antigenic structure of the basement membrane none of the inn
`is identical to that of the epidermis. aihd there are no differences in
`the antigenic composition of the basement membrane zone among
`the different portions of the nail apparatus.” This similarly may
`explain the involvement of the nails in conditions characterized by
`mutations of genes encoding basement membrane components as
`well as in autoimmune skin diseases involving the antigens of the
`basement membrane zone.”
`
`THE ISERMIS
`
`The nail apparatus is devoid of subcutaneous tissue. and its dermis
`does not contain pilosebaceous units. The arrangement of the rete
`ridges varies in the different ponions of the nail apparatus. The
`dermis beneath the proximal nail matrix consists of condensed con-
`nective tissue that forms a tendon-like structure connecting the ma-
`trix to the periosteum of the proximal phalanx (posterior ligament).
`A small amount of subclennal fat tissue is present close to the peri-
`ostium of the base of the phalanx.” The close connection between
`the lateral horns and the periosteum is possibly responsible for the
`nail plate‘s lateral convexity. The rete ridges of the dermis under-
`neath the nail matrix are characteristically long and rootlike. The
`dermis under the distal matrix consists of a loose network of con-
`nective tissue containing numerous blood vessels and rare glcmus
`bodies.
`The dermis of the nail bed has a unique arrangement, with lon-
`gitudinal grooves and ridges that run from the luuula to the hypo
`nychium.' The longitudinal orientation of the capillary vessels
`within the nail bed grooves explains the linear pattern of nail bed
`hemorrhages (“splinter" hemorrhages). The nail bed dermis contains
`an abundant connective tissue network with bundles radiating to the
`phalangeal periostium. It also contains numerous glomus bodies.
`
`stoop AND NERVE SUPPLY
`
`The nail apparatus has an abundant blood supply provided by the
`lateral digital arteries. These run along the sides of the digits and
`produce both branches that supply the matrix and the proximal nail
`fold and arches that supply the matrix and the nail bed. Therefore.
`the matrix has two different sources of blood supply.
`The nail bed is richly supplied by encapsulated neurovascular
`structures containing one to four aneriovenous anastomoses and
`nerve endings. These glomus bodies are possibly involved in I116
`regulation of the blood supply to the digits in cold weather.
`The cutaneous sensory nerves. which originate from the dorsal
`branches of the paired digital nerves. run parallel to the digital VES-
`sels.
`
`CHEMICAL PROPERTIES
`
`The nail plate, like hair, consists mainly of low-sulfur filamentous
`P1'0l€lDS (keratins) embedded in an amorphous matrix comp0S°d °l
`high-Sulfur proteins rich in cystine. Other nail constituents incllldi
`water, lipids, and trace e1emem5_
`
`Page 11 of 13
`
`

`

`Nail lteratins consist of 80 to 90 percent hard "hair-type" lceratins
`and ll) to 20 P6703“ 501‘! “$ki“'lYP'3" keratins. Hard lteratins have
`been ldfimlficd 315 the acidic Ha I
`to 4 keratins and basic Hb 1
`to
`4 keratins. Soft keratins have been identified as epithelial kc;-arms
`5. 6. 14. 15. and 17 keratin Pairs-2” Keratin filaments have a trans-
`versal orientation that is parallel to the nail surface. This explains
`why the nail plate is more susceptible to transverse than to longi_
`tudinal fractures.
`In normal conditions, the water content of the nail plate is 18
`percent. most of it being in the intermediate nail plate.“ This may,
`however, significantly vary due to the high porosity of the nail
`plate, which can be rapidly hydrated and dehydrated. Dehydration
`is faster when the nails are kept long. When the water content falls
`below l8 percent. the nail becomes brittle; when it increases above
`30 percent, it becomes opaque and sof .32
`The nail contains less than 5 percent lipids. mainly cholesterol,
`and traces of several inorganic elements. the most prominent being
`iron, zinc. and calcium. These. however. do not contribute to the
`na.il's hardness.
`
`PHYSICAL PROPERTIES
`
`The nail plate is hard. strong. and flexible. The hardness and
`strength of the nail plate are due to its high content of hard keratins
`and eystine-rich high—sulfur proteins. while its flexibility depends
`on its water content and increases with nail plate hydration.” The
`double curvature of the nail plate along its longitudinal and trans-
`verse axes enhances its resistance to mechanical stress.“ The
`strength of fingernails is similar to that of wool and human hair,
`with a maximum elastic stress varying from 420 to 880 kgicm3.25
`The physical properties of the nail also depend on the arrange-
`ment and adhesion of onychocytes in the different portions of the
`nail plate as well as on the orientation of the keratin filaments
`within the nail plate onychocytes.“
`At an ultrastructural
`level,
`the comeocytes of the dorsal nail
`plate are flat, with their shorter diameter perpendicular to the nail
`plate‘s surface. On average, these cells are 34 ,t.trn in length. 64 ,um
`in width. and 2.2 ,t.tm in height?“ Cell adhesion is strong, and this
`portion of the nail is responsible for the hardness and sharpness of
`the nail plate. The onychocytes of the intermediate nail plate show
`multiple interdigitations of their cell membranes. On average, these
`cells are 40 um in length. 53 ,u.m in width, and 5.5 tum in height.
`Cell adhesion is provided by desmosomes and complex interdigi-
`rations. This part of the nail plate is responsible for the nail’s pli-
`ability and elasticity. The ventral nail plate is thin and consists of
`soft keratins. It provides adhesion to the underlying nail bed.
`
`NAIL GROWTH
`
`The nail plate grows continuously during life. Fingernails grow
`faster than toenails. mean growth being 3 mm per month for fin-
`gernails and 1 mm per month for toenails. Complete replacement
`of a fingernail therefore requires about 100 to I80 days (6 months)-
`When the nail plate is extracted. it takes about 40 days before the
`new fingernail first emerges from the proximal nail fold. After a
`
`Page 12 of 13
`
`CHAPTER 1 8
`
`Biology of Nails
`
`34 ;
`
`further I20 days, it will reach the fingertip}: The total rrgciicnuioo
`time for a toenail is ii! to 18 months. As a consequence of the nail‘-t
`slow growth rate, diseases of the nail matrix. become evident only
`after a considerable delay and require at long time to disappear utter
`treatment. The rate of nail growth varies among different mdmd-
`uals and among the different digits of the same individual
`It dc-
`pends on the turnover rate of the nail matrix cells and is iiiflucnccd
`
`by several physiologic and pathologic conditions. The nail gnwtili
`rate is slow at birth, slightly increases during childhood and usually
`reaches its maximum between the second and the ll'I|f(l decade.-. nl
`
`it decreases sliarply-'7 (‘ontIitinm
`life. Then, after the age of 50.
`that have been associated with a slow growth rate include \_\xlCl'||lt.'
`illness, malnutrition, peripheral vascular or iicurologic tllscuscs. uiitl
`treatment with antimitotic drugs. Nails affected by onyclioiiuco-ox
`frequently exhibit a slow growth rate. and an am-at til" nail gnmtli
`is a typical feature of the yellow-nail syndrome.
`Conditions that have been associated with an accelerated rule oi"
`
`itlltl treat-
`nail growth include pregnancy. linger trauma. psoritisis.
`ment with oral retinoids and itraconazole.” Accelerated nail grmttli
`may cause longitudinal ridging of the nail plate (nail lvcadiiigl ll‘l}:
`13-8). Due to their slow growth rate. the nails iii-.i_v provide mini-
`mation on pathologic conditions that have occurred up to ~.c\er.tl
`months before the time of observation. Since drugs and toxic oth-
`stances are stored within the nail. nail clippings can be utililcd In
`detect previous exposure to drugs or cltemicals. The nail til the hit:
`toe is the best site for such investigation becattse ol
`its me and
`slow growth rate. In some metabolic diseases. nail plate .iii.tl_t-sis
`can be utilized for diagnostic and therapeutic purposes.’ Nail .lip-
`pings may also be utilized for genetic analysis and dctcrriiirmion
`of blood groups. DNA can. in fact. be easily extracted from lin-
`gemail clippings an utilized for enzymatic amplilication and ge-
`notypic or individual identification.”
`
`FIGURE 18-8
`
`Nail plate ridging (beading) after treatment with lll.lt nn.i;m|t-.
`
`Page 12 of 13
`
`

`

`244
`
`SECTION FOUR
`Biology 8: Function of Epitiermis 8: Appendages
`
`9°99‘
`
`REFERENCES
`in Health and
`in The Nail
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`1.
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`Sonnex TS et al: The nature and significance of the transverse white
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`Dawber RPR: The ultrastructure and growth of human nails. Arch
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`Johnson M et al: Determination of nail thickness and length. Br J
`Dennaml l30:l95, i994
`Tosti A et al: The nail in systemic diseases and drug-induced changes.
`in Dr'sease.r of the Nails and Their Management. 2d ed. edited by
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`Tosti A et al: Characterization of nail matrix melanocytes using anti-
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`Cameli N et al: Expression of integrins in human nail matrix. Br
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`Johnson M et :1]: Nail is produced by the normal nail bed: A contm.
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`I996
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`Young RW ct al; Strength of Ftngcmails. J hl|'t'.i‘! Dermarul-14:35
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`Achtcn G ct al: Nails in light and electron microscopy. Semin Der.
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`Bean WB: Nail growth: 30 years of observation. Arch lnrem Med
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`Page 13 of 13
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