CECIL
`TEXTBOOK
`
`20TH EDITION
`
`OF
`
`MEDICINE
`
`Edited by
`
`J. CLAUDE BENNETT, M.D.
`President, University of Alabama at Birmingham
`Birmingham, Alabama;
`Formerly Spencer Professor of Medicine
`and Chairman, Department of Medicine
`University of Alabama School of Medicine
`Birmingham, Alabama
`
`FRED PLUM, M.D.
`Anne Parrish ’l'it7.el| Professor of Neurology and Neuroscience
`Chairman, Department Of Neurology and Neuroscience
`Cornell University Medical College;
`NeurologisL—in—Chief
`The New York Hospital—COrncll Medical Center
`New York, New York
`
`W.B. SAUNDERS COMPANY
`A Division ufHczrwm‘t Brace & Company
`
`PHILADELPHIA -
`
`LONDON -
`
`TORONTO - MONTREAL
`
`-
`
`SYDNEY
`
`-
`
`TOKYO
`
`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2046 - 1/6
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2046 - 1/6
`
`

`
`W. B. SAUNDERS COMPANY
`A Division of Harcourt Brace & Company
`The Curtis Center
`Independence Square West
`Philadelphia, PA 19106
`
`Library of Congress Cataloging-in-Publication Data
`
`Cecil textbook of medicine / edited by J. Claude Bennett, Fred Plum.—20th ed.
`
`p.
`
`cm.
`
`Includes bibliographical references and index.
`
`ISBN o—721s—35s1—x (single v.).—|SBN 0~7216—3574—1 (V. 1).—lSBN O—7216—3575—X (V. 2).-
`ISBN 0-7216-3573-3 (set)
`
`I. Cecil, Russell L. (Russell La Fayette), 18814965.
`Internal medicine.
`1.
`Ill. Plum, Fred,
`IV. Title: Textbook of medicine.
`[DNLM: 1.
`Medicine. WB 100 03888 1996]
`RC46.C423
`1996
`616—dc20
`
`ll. Bennett, J. Claude.
`
`DNLM/DLC
`
`94-43773
`
`CECIL TEXTBOOK OF MEDICINE
`
`Volume I
`ISBN 0~72l6~3574~l
`ISBN 0—72l6—3575—X Volume 2
`ISBN 0—72I6—3573—3
`Set (Vols 1 & 2)
`ISBN 0—72l6—3561—X Single volume
`
`Copyright © I996, I991, I988, I985, I982, I979, I975, I971, I963, I959, 1955 by W. B. Saunders Corn-
`pany.
`
`Copyright I951, I947. I943, I940. I937, I933, I930, 1927 by W.B. Saunders Company.
`
`Copyright renewed I991 by Paul Beeson.
`
`Copyright renewed 1979 by Russell L. Cecil and Robert F. Loeb.
`
`Copyright renewed I987. I975, I971, I965, I961, I958, 1955 by W. B. Saunders Company.
`
`'
`
`All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any
`means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval
`system, without permission in writing from the publisher.
`
`Printed in the United States of America.
`
`Last digit is the print number:
`
`9
`
`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2046 - 2/6
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2046 - 2/6
`
`

`
`Ointinents (Continuerl)
`sulfur, scabies treated with, 2195
`vehicles used in, 2194t, 2194-2195
`Okelbo disease, 1809-1810
`Olfactory bulb agenesis, 1306
`Olfactory sense. See Srmalt.
`~ Oligodcndroglioma. 2127-2128, 2l28t, 2132
`classification of, 21261
`MR1 scan of, 2127-2128, 2128t
`Oligonucleotides, antisense, 1073-1074. 1074
`trip1eX—forming, 1073-1074, 1074
`Oligospermia, 1337
`Oliguria. glomerulonephritis causing, 575
`heart failure causing, 220
`hyponatrernic. 514. 5l4t
`Olive oil, 1142, 1143
`Ollicr’s disease, 1390
`Omphalocele, 1581
`Omsk hemorrhagic fever, 1798t, 1801-1802, 1806t
`Onchocerciasis, l942t. 1942-1943
`Oncogene(s), 1011-1012, 1071-1077
`ab], 1011-1012, 10361. 1058
`alkylation resistance due to, 1059
`br:]—2, 1011-1012, 1036t, 1058
`fos, 1059
`HER, 1011-1012, 1036t
`leukemia and, 9261, 926-927, 936, 938, 1011-1012
`myc, 1036t
`mt‘, 1011-1012, 1059, 1076
`therapy related to, 1071-1077, 1074
`Oncotaxis, 1031
`Oneotie pressure, pulmonaly cdctna and, 476, 477
`volume regulation role of, 525
`Oncovin (Vineristine), Hodg1<in’s disease and, 952t.
`953
`non-Hodgkin’s lymphoma and, 945t
`Onion bulb appearance, 2153, 2154t
`Onuf’s nucleus, 2010
`Onycliogryphosis, 22161
`Onycholysis. 22l6t
`psoriatic arthritis with, 147]
`Onychomycosis, 2214. 22l6t
`O’nyong—nyong virus. 1805t. 1809
`Oocysts, eryptosporidial, 1910-1911, 19]], 1912
`malarial, 1893, 1893
`Oocytes, 1293, 1293
`number of, 1293, 1293
`ovulation and, 1293
`Ophthalmopalhy. See also Eye; Wsion.
`AIDS/HIV with, 1868-1870. l869t
`Graves’ disease causing, 1233, 2180
`rheumatoid arthritis with, 1464, 2178
`Ophthalmoplcgia, 2019
`degenerative disorders with, 205lt
`migraine with, 2032
`Opioids, 51, 19751
`accumulation of, 102
`administration of, l03t, 103-104, 104t
`adverse reactions to, 52-53, 103-105, l04t
`agonist, 51
`antagonist, 51
`definition of, 51
`diarrhea treated with, 695
`drug abuse with, 51-53, 561, 5041. 508. 1975t
`endogenous peptide, 1186, 1186-1187, 1187t
`distribution of, 1186-1187, 1187t, 1199
`families of, 1186, I186
`receptors for, 1187, 1199
`structure of, 1186, 1186
`equianalgcsic dose of, 102, 1041
`neurologic effects of, 1975t
`overdose with, 52, 504t, 508, 19751
`patient—con1ro1 led, 103
`pharmacology of, 52
`septic shock role of, 499
`starting dose for, 104t
`withdrawal of, 53, 508
`Opisthorchiasis, 1931-1932, l932t
`Opisthotonos, 1637
`Opsoclonus-myoclonus, 2020
`paraneoplastic, 1018, 1028
`Optic chiasm, 2017
`Optic disk, 2177-2178
`drusen in, 2177
`edema of, 2016, 20161, 2177t. 2177-2178
`pallor of, 2178
`Optic nerve, 2l74t
`atrophy of. l708t, 1709, 2178
`disorders allecting, 2l74t
`drusen of, 2177
`
`Optic nerve ((7nntirt1tetl)
`glaucoma effect on, 2174t, 2175
`papilledema and, 20161, 2016-2017, 2017. 2177
`syphilis effect on, 17081, 1709
`tumors of, 2l77t
`Optic neuritis, 20161, 2016-2017, 2017, 2111
`multiple sclerosis and, 2111
`retrobulbar. 2016, 2177
`Optic neuropathy, anterior ischemic, 2177-2178
`diabetic, 1273, 2181-2182
`Leber’s, 2167, 2178
`neoplasia with, 1028. 1030
`Optic radiations, 2017
`blood supply to, 2061)
`damage to, 1985, 1987t
`Optic tract, 2015, 2017, 2017
`Oral cavity. See Mouth.
`Oral contraceptives, cancer prevention using, 1010
`hepatotoxicity of, 773, 7731, 775
`Oral glucose—lowering agents, 1267-1268, l268t
`Orbit, Graves’ disease effect on, 2180
`mucormyeosis affecting, 1833
`neoplasia of, 2180
`Wegener’s granulomatosis affecting, 1495t, 1496.
`l496t
`Orchitis, 1335
`mumps causing, 1336, 1769
`viral, 1335
`Organ donation, See also 'I‘mn.vplzmtati0n.
`heart as, 361-362, 362t
`Organ of Zuckcrkandl, chromaffin cells of, 1254
`pheochromocytoma affecting, 1254
`Organophosphates, 510t
`poisoning due to, 504t, 509-510, 5l0t
`Orgasm, 1308
`headache with, 2033
`male, 1320
`Oriental cholangiohepatitis, 812
`Ornithine, en‘/,.yme defect and, 146t
`urinary. 11021
`Ornithine transcarbamoylase, I I I 0
`deficiency of, 1110t, 1110-1111
`Ornithosis, 58t
`occupational exposure to, 58t
`Oropharynx, candidiasis of, 1828
`enterovirus affecting, 1787t, 1789-1791
`flora of, anaerobic, 1639, [639
`aspiration pneumonia due to, 1579, 1582
`ulceration of, histoplasmosis causing, 1817
`Oroya fever, 1682
`Orthomyxovirus. I739
`Orthopnea, 217
`Osborn wave, 503, 503
`Oscillopsia, 2027
`Osler maneuver, 260
`Osler’s nodes, endocarditis with, 1599, 16001
`lupus erythematosus with, 1478
`Osler—Weber-Rendu disease, 720-721
`Osmolality, 532-538
`ADH and, 533, 533-534, 536
`diabetic hypcrosmolar syndrome and, 1270
`lluid transfer role of, 532-534, 533
`hypertonic disorders of, 537t, 537-538
`hypothalamic osmostat and, 1222. I222
`hypotonic disorders of, 534t. 534-537
`pregnancy and, 609
`sodium and, 534-538
`hypernatremia and, 537t, 537-538
`hyponatretnia and. 534t, 534-537
`urinary, 1222, 1223
`vasopression regulation of, 1222. I223
`Osmoreccptors, 1222-1223
`Osmostat, absence of, 1224
`hypothalamic, 1222, I222
`Osmotic pressure, pulmonary edema and, 476, 477
`Ossification, muscular, 2165
`Osteitis deformans. See Pagetir dz'.veu.re, of bone.
`Osteitis fibrosa, 1376
`parathyroid hormone in, 1376, 13761
`renal failure and, 1376, 13761
`Osteoarthiitis, 1517-1521
`clinical features of, 1518- 1520. 15l9t, I520
`epidemiology of, 1517-1518
`etiology of, l519t
`foot, 151% 1519-1520
`hand, 1518-1519. l5l9t, 1520
`hip, 1519, 15191
`imaging of, 1520
`knee, 1519, 15191
`laboratory findings in, 1520
`
`INDEX
`
`I
`
`LXVII
`
`Osteoarthritis ( Comirmed)
`ncuropathic (Ch11rcnt’s_ioint), 1518, 1526, 1526
`pathogenesis of, 1518, 1519
`pathology findings in, 1518
`secondary. 1519t
`Spine, 1519t, 1520
`synovial lluid in, 1465t
`treatment of. 1520-1521
`Ostcoarthropathy, hypertrophic, 1388, 1527
`pulmonary malignancy with, 1020, 1035
`Osleoblasts, 1352
`glucocorticoid inhibition of, 1384
`parathyroid hormone action on, 1366
`Osteoealein, 1352
`Osteochondromatosis, 1528
`Osteoclasts, 1353
`bisphosplionate inhibition of, 1383
`calcitonin inhibition of, 1373
`defective function of, 1388-1389
`Pagct’s disease role of, 1384-1385
`phagocytosis by. 900. 9001
`Osteocytes, 1352-1353, 1353
`Osteodystrophy, A1brig1it’s hereditary, 1372, 1372-1373
`renal, 557t, 559, 562, 1375-1379, 1376t
`biochemical features of, 1376t, 1376-1377
`clinical manifestations of, 1377
`radiographic findings in, 1377-1378, 1378
`treatment of, l376t. 1376-1378
`vitamin D therapy in, 1378, 1378t
`Osteogenesis imperfecta, 1122-1123
`clinical manifestations of, 1122, 11221
`definition of, 1122
`di1Terential diagnosis of. 1122-1123
`genetics of, 138t. 1122, 1122!
`prevalence of, 1122
`treatment of, 1123
`types of, 1122, 1122t
`Osteoid, 1352, I36]
`osteomalacia, 1360, I361
`Osteolysis, Paget’s, 1384-1385, 1385, 1386
`Osteomalaeia, 1359- 1365
`biopsy in, 136]
`classification of, 1359t, 13621, 13631
`clinical manifestations of, 1360-1361
`definition of, 1359
`differential diagnosis of, 1361-1365, 1362t, 1363t
`drug—induced, 1365
`elderly affected by, 23
`etiology of, 1359t, 1359-1360
`hypophosphatasia in, 1365
`hypophosphatemia in, 1362t, 1363t, 1363-1364
`inflammatory bowel disease and, 710t, 711
`laboratory lindings in, 1362:, 1363t
`oneogenic, 1026
`pathogenesis of, 1359-1360, /36']
`radiographic features in, 1377
`renal failure and, 1362, 1363-1364, 13761,
`1376-1377
`tumor-induced, 1363t, 1364
`vitamin D in, 11451. 1361-1363, l362t. 13631
`Osteomyelitis, 1625-1627
`childhood, 1625t, 1625-1626
`clinical manifestations of, 16251, 1626, 1626
`contiguous infection ‘with, l625t, 1625-1626
`definition of. 1625
`diagnosis of, 1626 - 1627
`etiologic agents of, 1625, 1625t
`imaging procedures for, 1626, 1626-1627
`incidence of, 1625-1626
`pathogenesis of. 1626, I626
`prognosis in, 1627
`spinal, 16251, 1625-1626, 1626
`staphylococcal, 1608
`treatment of, 1627
`Osteon. 1353. 1353
`Osteonecrosis. 1387
`diagnosis of, 1387
`etiology of, 1387, 13871
`pathogenesis of, 1387
`sickle syndrome in, 889
`treatment of, 1387
`Osteopathia striata, 1390
`Osteopetrosis, 1388 1389
`clinical ntanifestations of, 1389
`diagnosis of, 1389, I389
`etiology of. 1388-1389
`pathogenesis of, 1388-1389
`treatment of, 1389
`
`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2046 - 3/6
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2046 - 3/6
`
`

`
`2214
`
`/
`
`XXVI
`
`SKIN DISEASES
`
`TABLE 475-9. ALBINISM
`
`Skin
`
`This material may be protected by Copyright law [Title 17 us. Code]
`
`Pigmented
`Nevi
`Freckles
`Hair
`Color
`Color
`Red Reflex
`Inheritance Frequency
`
`Oculocutaneous Albinism
`Tyrosinase—negative
`
`pink/white
`
`none
`
`white
`
`gray-blue
`
`present
`
`AR*
`
`I
`
`in 34,000
`
`Tyrosinase—positive
`
`AR
`
`blacks: l in 15,000
`whites:
`l in 40,000
`
`white—cream
`
`PICSCIII
`
`white-
`yellow
`red; dark-
`ens
`
`white—birth
`red/yellow
`6 mos
`
`blond-dark
`brown-steel
`gray
`white blond
`
`blue-yellow
`brown
`
`present but may
`be absent in
`dark races
`
`blue at birth;
`darkens
`
`present
`
`present but
`diminishes
`with time
`present
`
`blue to brown
`
`blue
`
`blue
`
`blue
`
`Yellow—mutant
`
`Chédiak—l-ligashi
`syndrome
`
`Oeulocutaneous Albinoidism
`Ocular Albinism
`Vogt
`
`Forsius—Eriksson
`
`rare—Amish, Polish, German-Ameri-
`can; blacks (American, Ceylonese,
`African)
`
`rare in most countries; none in blacks
`
`white at
`birth,
`slightly tan
`possible
`pink/white
`
`present
`
`present
`
`pink/white
`
`?
`
`uncommon
`
`less common
`
`nonnal
`
`normal
`
`present
`
`normal
`
`present
`
`normal
`
`blue
`normal
`normal
`10 families
`Autosomal recessive
`present
`present
`:uum1:
`
`A common localized form of hypopigmentation, pizyriasis alba,
`appears as slightly pink and hypopigmented, oval to round patches
`with mild, fine scaling. These occur on the checks of children, but
`they may also be found on the trunk, mimicking the hypopig—
`mented, scaling patches seen in tinea versicolor (a KOH examina-
`tion of the scales may be necessary to differentiate these two condi-
`tions). Pityriasis alba is most frequently seen in atopic dermatitis
`patients.
`Tuberous sclerosis, an autosomal dominant condition, displays
`white macules in almost all cases. The depigmented macules in-
`volve the trunk or buttocks in an oval or mountain ash-leaf configu-
`ration. The presence of three or more macules strongly suggests
`tuberous sclerosis, and because the hypomelanotic patches are pres-
`ent at birth, they represent one of the earliest signs of the condition.
`Examination with Wood’s light is often useful in visualizing the le-
`sions, which histologically contain melanocytes with decreased
`numbers of melanosomes. Newborns with unexplained seizures or
`mental retardation should be screened with a Wood’s light for the
`presence of the white spots. Ch. 417 gives details of the systemic
`disorder. CT brain scans are also useful in defining the tumorous
`dysplasia.
`Certain chemicals, particularly phenol derivatives, when applied
`to the skin, may cause permanent depigmentation. Hypo1nelano-
`sis has been observed on the hands of black—skinned individuals
`wearing rubber gloves in which hydroquinone is used as an anti-
`oxidant.
`(Albinism). Table
`GENERALIZED HYPOPIGMENTATION.
`475-9 lists these hereditary disorders, all of which produce general-
`ized hypomelanosis of the skin, hair, and eyes.
`
`REGIUNAL DIAGNOSIS OF SKIN D|SEASES—CDMMONLY ENCIIUNTERED
`PROBLEMS BY ANATDMIG REEIDN
`
`Many skin diseases have a predilection for certain areas or re-
`gions of the body, often related to variations in the structure and
`function of the integument (Table 475-10).
`
`Disorders of the Nails
`
`The nail is a plate of hard keratin synthesized from an invagina-
`tion of the epidermis. The proximal nail fold houses the matrix of
`the nail where basal cells rapidly proliferate and differentiate into
`
`the nail plate, which grows over the nail bed. Nails grow continu-
`ously throughout life. The average fingernail grows 0.5 to l.2 mm
`per week, whereas toenails grow at one half to one third this rate. It
`takes a fingernail about 5.5 months and the toenails 12 to 18
`months to regrow from the matrix, although rate of growth slows as
`the individual gets older. Table 475—ll provides a terminology to
`describe defects in nail formation.
`SKIN DISEASES INVOLVING NAILS. Nail changes in psori-
`asis have been described above. Fingernails are more frequently in-
`volved than toenails. Fungal infection must be ruled out.
`In 10% of lichen planus patients, accentuated longitudinal nail
`ridging occurs as well as pterygium formation resulting from de-
`structive foeal scarring of the matrix. Early treatment with oral
`steroids is indicated.
`Atopic eczema and other eczematous entities may cause pitting,
`transverse striations, and onycholysis.
`Onychomycosis, or fungal
`infections of the nail, may be caused
`by dermatophyte (tinea unguium) or candidal
`infections. Infection
`of toenails is more frequent
`than fingernails, but all nails may
`be involved. The nail plate is discolored, thickened, crumbly, and
`onycholytie with accumulation of debris. White superficial ony-
`chomycosis appears as white patches in the toenail plate due to
`organisms growing on the surface barely penetrating the nail.
`Scrapings reveal hyphae upon KOH examination. An unusual con-
`dition, chronic mucocutaneous candidiasis, is caused by widespread
`Candida albicans infection leading to diffuse white thickening of
`all nails.
`
`ineffective. Oral griseofulvin is
`therapy is
`Topical antifungal
`given for dermatophyte infection until the nails appear clear. Keto—
`conazole (200 mg daily) is an alternative should griseofulvin fail or
`when Candida is the causative agent. Oral therapy requires 4 to 6
`months for fingernails and 12 to 16 months for toenails. In older in-
`dividuals toenail problems may never be eradicated because the
`nails grow so slowly. Residual fungal spores in shoes and the envi-
`ronment no doubt cause frequent recurrences;
`topical antifungal
`powders may be helpful in long-term prophylaxis.
`is usually
`Paronychia, or painful, rcd swelling of the nail fold,
`caused by C. albicans. At times a small abscess or purulent dis-
`charge is seen. This infection usually occurs in hands constantly ex-
`posed to a wet environment (bartenders, janitors). Therapy consists
`
`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2046 - 4/6
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2046 - 4/6
`
`

`
`TABLE 475-9. ALBINISM (Continued)
`Eyes
`
`475
`
`SKIN DISEASES UF GENERAL IMPORTANCE
`
`/
`
`22l5
`
`Visual
`Acuity
`
`Pigment in
`Fundus
`
`Other
`
`Hair Bulb
`Incubation
`(Tyrosine)
`
`Defect
`
`Melanosome
`Maturation
`by Stage
`
`Complications
`or Associated
`Problems
`
`Nystzzgmus
`
`Photophabia
`
`marked
`
`SCVCFC
`
`present but less
`
`present but
`variable
`
`present but
`variable
`
`present but
`variable
`
`absent or slight
`
`absent or slight
`
`legally blind
`
`scvere defect in
`children; may
`improve with
`age
`marked defect;
`may improve
`with age
`normal or slight
`decrease
`
`negative
`
`no tyrosinase
`
`none; some
`with age
`
`none: some
`with age
`
`pigment cart-
`wheel effect
`pupil, lirnbus
`
`pigment eart-
`wheel effect
`
`positive
`
`neg to pus?
`
`some; increase
`with age
`
`normal for cart-
`wheel effect
`
`positive
`
`no access of en-
`zyme to tyro-
`sine
`
`unknown
`? pheomelano—
`genesis
`giant melano-
`somes, lethal
`defect in
`leukocytes
`
`l—unmclan—
`ized II
`
`I, II, some
`III, rare
`IV
`
`skin malignancy
`basal cell ca
`squamous cell ca
`skin malignancy
`basal cell ca
`squamous cell ca
`
`I, II, III
`
`unknown
`
`I, ll, lll, IV
`
`infections;
`hematologic
`and neuro-
`logie abnor-
`malities; lym-
`phoreticular
`malignancy
`none
`
`no
`
`present
`
`no
`
`severe
`
`normal or slight
`decrease
`marked decrease
`
`unknown
`
`unknown
`
`positive
`
`positive
`
`latent
`
`color blind
`
`absent or slight
`S€V€IC
`marked decrease
`present
`positive
`
`* AR : Autosomal recessive.
`1‘ AD = Autosomal dominant
`Reprinted "from the chapter by Dr. M2trie—Louise Johnson in the 17th edition of the Cecil Textbook of Medicine, with her permission.
`
`positive
`
`of avoidance of water and the use of antifungal solutions two or
`three times a day for a month or two.
`NAIL DISTURBANCES IN SYSTEMIC DISEASES. Splinter
`hemorrhages result from the extravasation of blood from longitudi-
`nally oriented vessels of the nail bed. Although often thought to be
`associated with bacterial endocarditis,
`they are much more com-
`monly associated with trauma. b’ecm’s lines are nonspecific, appear-
`ing as transverse depressions across the nail plates following any
`severe disability that temporarily interferes with nail growth. Longi-
`tudinal pigmented bands occur most often in response to trauma or
`a nevus located iii the matrix. Yellow nail syndrome exhibits yellow
`thickening of the nails with absence of the lunula and variable de-
`grees of onycliolysis accompanying pulmonary conditions such as
`bronchiectasis, pleural effusion, and chronic obstructive pulmonary
`disease. Lymphedema of the extremities may coexist. Clubbing of
`the nails (increased bilateral curvature of the nails with enlargement
`of the soft connective tissue of the distal phalanges resulting in the
`flattening of the obtuse angle formed by the proximal end of the
`nail and the digit) occurs most often with bronchiectasis, lung ab-
`scess,
`and pulmonary neoplasms. Cardiovascular disease
`and
`chronic gastrointestinal diseases (ulcerative colitis, sprue) are also
`associated with clubbing. Clubbing accompanied by bone pain and
`proliferative periostitis is termed /iypertrophic osteoarthropathy. The
`condition is most often associated with bronchogenic squamous cell
`carcinoma.
`TUMORS OF THE NAIL. A variety of benign tumors occur
`around the nail unit. These include perinngual fibromas, myxoid
`cysts, and subzmgual exostoses. Surgical removal is the only certain
`means of cure.
`involving the nails is melanoma,
`tumor
`The main malignant
`which appears as a pigmented area at the base of the nail or as a
`longitudinal pigmented streak in the nail. Nevi can give the same
`appearance, and biopsy of the lesion in the matrix is the only ab-
`solutely certain way of making a diagnosis.
`
`Disorders of the Mucous Membranes
`
`Any abnormality of color, texture, or appearance of the mucous
`membranes should be investigated. Malignant changes should be
`suspected in infiltrated or ulcerated lesions and a biopsy performed.
`
`Ch. 96 discusses disorders of the oral mucous membranes,
`tongue, and the salivary glands.
`
`the
`
`Alterations of Hair Growth
`
`HAIR LOSS (ALOPECIA)
`Physical, chemical, and emotional events cause fluctuations in
`hair growth and if severe enough may stop growth entirely. The
`physical examination is important in noting the pattern of hair loss
`and whether or not scarring is present. Nonscarring alopccia may be
`a temporary phenomenon, whereas scarring is indicative of perma-
`nent hair loss.
`NONSCARRING ALOPECIA. Localized Alopecia. Alope-
`cia areata is characterized by well-circumscribed, round or oval
`patches of nonscarring hair loss, usually over the scalp or in the
`beard, eyebrows, or eyelashes. Erythema may be present early in
`the course of the patches. Characteristically the periphery of patches
`of hair loss is studded with fractured hairs with tapered shafts. His-
`tologic features include small dystrophic hair follicles and a lym-
`phocytie infiltrate around the hair bulbs. Occasionally all the scalp
`hair is lost (alopccia totalis), and all
`the body hair may fall out
`(alopccia universalis). Alopecia areata has a variable, unpredictable
`course. Most patients regrow hair within a few months, but one
`fourth of them experience recurrences. The more extensive the
`alopccia, the poorer the prognosis. Alopecia involving the occipital
`region or eyebrows, lashes, and nasal hairs portends a poor progno-
`sis. Alopecia areata may have an autoimmune pathogenesis, being
`occasionally associated with Hashimoto’s thyroiditis and pernicious
`anemia. Topical,
`intralesional, and systemic steroids give variable
`benefits. Recent modes of therapy include induction of allergic or
`irritant contact dermatitis (1% anthralin, or topical dinitrochloroben—
`zene), photochemotherapy with PUVA, and topical minoxidil.
`Tinea capitis is most likely to be confused with alopccia areata.
`Tinea infection appears as one or more patches of hair loss with
`mild scaling and erythcma and broken hair shafts leaving residual
`black stumps (black dot ringworm). Nonfluorescing Trichophyton
`tonsurans is the usual cause. Griseofulvin is the drug of choice.
`Trichotillomania refers to traumatic, self—indueed alopecia and re-
`sults from compulsive twisting and rubbing, which causes breaking
`
`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2046 - 5/6
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2046 - 5/6
`
`

`
`2216
`
`I
`
`XXVI
`
`SKIN DISEASES
`
`Vesicular
`Nodular
`
`TABLE 475-I0. REGIONAL DERMATOLOGY
`
`Disease Process
`Region of Skin
`Type of Skin Group
`
`Psoriasis, seborrheic dermatitis, tinea capitis, eczema (atopic, contact)
`Scalp
`Papulosquarnous and eczematous
`Pustular
`Folliculitis, kerion
`Nodular
`Nevi, seborrheic keratosis, pilar cysts, verruea
`Connective tissue disease, scleroderrna, discoid LE
`Atropic and telangiectatic
`Pustular
`Acne, rosacea, folliculitis, tinea
`Psoriasis, seborrheie dermatitis, contact dermatitis (cosmetics), atopic dermatitis, im-
`Papulosquamous and eczematous
`petigo, lupus erythematosus, photodermatitis
`Herpes zoster and herpes simplex, insect bites
`Basal cell cancers, squamous cell cancers, melanomas, keratoacanthomas, nevi, ac-
`tinic keratosis
`Psoriasis, atopic and contact eczema, tinea versicolor, pityriasis rosacea, scabies
`Pemphigus, bullous pernphigoid
`Secondary syphilis, drug reaction, viral exanthems
`Nevi, seborrheic keratosis, lipoma, basal cell cancer, keloid, neurofibrorna. angiomas,
`melanoma
`Acne
`Hives
`Contact dermatitis—plants', atopic dermatitis, lichen planus
`Nevi, warts, seborrheic keratosis, actinic keratosis
`Scleroderma, dermatomyositis
`Contact dermatitis, stasis dermatitis, atopic dermatitis, psoriasis, lichen planus
`Erythetna nodosurn, dermatofrbromas, nevi, melanoma, Kaposi’s sarcoma, lipoma
`Vasculitis, Schamberg‘s disease, actinic purpura, pretibial myxedema
`Scleroderma, dermatostasis ulcers, arterial insufficiency
`Contact dermatitis, seborrheic dermatitis, scabies, pediculosis pubis, psoriasis, Reiter’s
`syndrome, erythrasma,
`tinea, eandidiasis,
`lichen planus, intertrigo, lichen simplex
`ehronicus
`Herpes simplex. Stevens-Johnson syndrome
`Syphilis, chancroid, lymphopathia venereum, Behget’s syndrome
`Verrucae vulgaris, erythroplasia of Queyrat, squamous cell cancer, sebaceous cyst,
`molluscum contagiosum
`Hidradenitis suppurativa
`Allergic contact and irritant contact dermatitis, dyshidrosis, pyoderrna, tinea, derTnato-
`phytids, scabies, alopic dermatitis, secondary syphilis
`Erythema multiforme, hand—foot—and—mouth disease, porphyria cutanea tarda, psoriasis
`Warts, squamous cell cancer, actinic keratosis, keratoacanthoma, pyogenic granuloma,
`granuloma annulare, synovial cysts
`Vitiligo
`Hypopigmented
`Seleroderma, dermatomyositis
`Atrophic-telangiectatic
`Contact dermatitis, atopic dermatitis, tinea, psoriasis, lichen planus
`Eezematous and papulosquarnous
`Vesiculobullous
`Tinea, epidermolysis bullosa, erytherna multiformc
`Nodules
`Verruca, corn, nevus
`Scleroderma
`Atrophic—telangiectatic
`
`
`Arms and forearms
`
`Legs
`
`Genitalia and groin
`
`Papulosquarnous and eczernatous
`Vesiculobullous
`Maculopapular
`Nodular
`
`Pustular
`Urticarial
`Eczematous and papulosquamous
`Nodular
`Atrophic telangiectasis
`Eczematous and papulosquamous
`Nodular
`Maculopapular
`Atrophic, telangiectatic, and uleerative
`Eczematous and papulosquamous
`
`Vesiculobullous
`Ulcerative and atrophic
`Nodular
`
`Pustular
`Eczernatous and papulosquamous
`
`Vesiculobullous, pustular
`Nodular
`
`and epilation of the hair shafts. The scalp is usually affected, less
`often the eyebrows and lashes. If the patient can be given insight,
`the condition it
`is self—limited. More severe emotional problems
`should be referred to a psychiatrist.
`the margins of the scalp
`Women who develop hair thinning at
`may be using excessive traction or other traumatic hair styling tech-
`niques (traction alopecia). Overtight hair curling such as corn row-
`ing and the use of hot combs to straighten hair leads to progressive
`hair thinning and even scarring.
`Hair loss is sometimes seen in the scalp of patients with sec-
`ondary syphilis. The hair loss is spotty, often “moth-eaten” in ap-
`pearance.
`involves the
`Androgenic alopecia, or male pattern baldness,
`frontal, vertex, and upper occipital regions of the scalp while spar-
`
`TABLE 475-1 T. POTENTIAL DEFECTS IN NAIL FORMATION
`Brz'ttleness—easy breaking of nail tips
`Leukonychiavwhite discoloration of nails
`Strz'aIi0ns——1ongitudina1 ridges running parallel or perpendicular to the
`length of the nail
`Ortycholysis-separation of the nail plate from the bed
`Onych0gryphosis—hypertrophy and thickening of the nail
`0nych0myc0si.s—-dystrophy, destruction of the nail due to yeast and fungal
`infections
`Pittz'ng—discrete pitlike depressions in the nail surface
`K0il0nychia—spoon—shaped deformity of the nails (concave nail with
`everted edges)
`Pterygium f0rmati0n—growth of cuticle onto the nail plate
`
`ing the posterior and lateral margins. The process may begin at any
`age after puberty, with temporal recession of hair usually noted
`first. There is no actual loss of hair but rather the conversion of
`thick terminal hairs to fine, unpigmented, poorly seen vellus hairs.
`Common baldness is genetically predetermined and androgen de-
`pendent. Males who are castrated prepubertally or men born with
`low testosterone production, as in Klinefelter’s syndrome, do not
`become bald, regardless of their genetic predisposition to balding.
`Women may also show balding, but it is milder with only diffuse
`thinning. Women with elevated androgen levels, as occur in mas-
`culinizing disorders, have baldness in a pattern similar to that in
`men. Surgical
`techniques such as hair transplants (plugs of hair-
`bearing areas from the sides of the scalp placed in the thinned
`frontal and crown areas) or scalp reduction may be useful in some
`patients. Thinning of hair growth is characteristic of old age in both
`genders.
`Diffuse or Generalized Alopecia. Stress alopecia, or relo-
`gen efiluvium,
`is a transient, reversible, diffuse hair loss of scalp
`hair that results from alterations in the normal hair cycle (see Ch.
`472). Severe emotional and physiologic stress (high fever, systemic
`illness, major surgery with general anesthesia, crash diet) and cer-
`tain drugs (heparin, coumarin, allopurinol, amphetamines, B—block-
`ing agents, lithium, probenecid, thiouracil) may cause growing hairs
`to convert to resting hairs, which are subsequently shed. Pregnancy
`and oral contraceptives cause hairs to grow continually, rather than
`cycling at programmed times. After childbirth or discontinuation of
`oral contraceptives, growing follicles “catch up” by simultaneously
`resting; shedding follows 2 to 4 months later. If the stress resolves,
`the hair regrows in 4 to 6 months. Diffuse hair loss may not be no-
`
`CFAD V. Anacor, |PR2015-01776 ANACOR EX. 2046 - 6/6
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2046 - 6/6