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`ACRUX DDS PTY LTD. et al.
`
`EXHIBIT 1500
`
`IPR Petition for
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`U.S. Patent No. 7,214,506
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`

`Clinical Infectious Diseases
`An Official Publication of the Infectious Diseases Society of America
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`Page 2 of 14
`
`

`

`Clinical Infectious Diseases
`
`Volume 2 3
`
`• Number 2
`
`August 1996
`
`Checklist for Submitted Manuscripts
`
`n List of Abbreviations
`
`State-of-the-Art Clinical Article
`
`219 Acute Encephalitis
`Richard ~ Johnson
`
`AIDS Commentary
`
`227 Early Initiation of Antiretroviral Therapy for Infection
`with Human Immunodeficiency Virus: Considerations in
`1996
`Jeffrey P. Nadler
`
`231 Photo Quiz
`
`Modern Imaging Technology
`
`232 Computed Tomography in the Management of Chest
`Infections: Current Status
`Jane H. Wheeler and Elliot K. Fishman
`
`Clinical Articles
`
`241 Changing Patterns of Infections in Patients with AIDS: A
`Study of 279 Autopsies of Prison Inmates and
`Nonincarcerated Patients at a University Hospital in
`Eastern Texas, 1984-1993
`Robert Lyon, Abida K. Haque, David M. Asmuth,
`and Gail L. Woods
`
`248 Editorial Response: The Importance of the Autopsy in
`Emerging and Reemerging Infectious Diseases
`David A. Schwartz and Chester J. Herman
`
`255 Nosocomial and Community-Acquired Staphylococcus
`aureus Bacteremias from 1980 to 1993: Impact o.f
`Intravascular Devices and Methicillin Resistance
`James P. Steinberg, Catherine C. Clark,
`and Betsy 0. Hackman
`
`260 Editorial Response: Increasing Rates of Staphylococcus
`aureus Bacteremia-A Medical Device Is a Merit in
`Disguise and Methicillin Resistance Is Merely a Vice
`Rabih 0. Darouiche and Daniel M. Musher
`
`262 Neurocysticercosis Among Children in Chicago
`Elaine A. Rosenfeld, Sharon E. Byrd,
`and Stanford ~ Shulman
`
`269 Detection of Toxin Production by Bacteroides fragilis:
`Assay Development and Screening of Extraintestinal
`Clinical Isolates
`Linda M. Mundy and Cynthia L. Sears
`
`277 Toxoplasmic Chorioretinitis in the Setting of Acute
`Acquired Toxoplasmosis
`Jose G. Montoya and Jack S. Remington
`
`283 Evidence Against Infection with Hantaviruses Among
`Forest and Park Workers in the Southwestern United
`States
`Charles R. Vitek, Thomas G. Ksiazek, C. J. Peters,
`and Robert F. Breiman
`
`286 Can Aggressive Treatment of Diabetic Foot Infections
`Reduce the Need for Above-Ankle Amputation?
`James S. Tan, Norman M. Friedman,
`Carolyn Hazelton-Miller, J. Patrick Flanagan,
`and Thomas M. File, Jr.
`
`292 Primary Cytomegalovirus Infection in Liver Transplant
`Recipients: Comparison of Infections Transmitted Via
`Donor Organs and Via Transfusions
`Matthew E. Falagas, David R. Snydman,
`Robin Ruthazer, John Griffith, Barbara G. Werner,
`and the Boston Center for Liver Transplantation
`CMVIG Study Group
`
`298 The Duke Criteria for Diagnosing Infective Endocarditis
`Are Specific: Analysis of 100 Patients with Acute Fever
`or Fever of Unknown Origin
`Bruno Hoen, Isabelle Beguinot, Christian Rabaud,
`Roland Jaussaud, Christine Selton-Suty, Thierry May,
`and Philippe Canton
`
`303 Editorial: Diagnostic Criteria for Identifying Cases of
`Endocarditis-Revisiting the Duke Criteria Two Years
`Later
`Arnold S. Bayer
`
`305 Update on the Management of Onychomycosis:
`Highlights of the Third Annual International Summit on
`Cutaneous Antifungal Therapy
`Boni E. Elewski and Roderick J. Hay
`
`314 Central Nervous System Manifestations of Human
`Ehrlichiosis
`Nathaniel Ratnasamy, E. Dale Everett,
`William E. Roland, Gregory McDonald,
`and Charles W. Caldwell
`
`320 Causes of Fever in Patients Infected with Human
`Immunodeficiency Virus Who Were Admitted to Boston
`City Hospital
`Lawrence M. Barat, Julia E. Gunn, Kathleen A. Steger,
`Chris J. Perkins, and Donald E. Craven
`
`Page 3 of 14
`
`

`

`329 Relevance of Digestive Tract Colonization in the
`Epidemiology of Nosocomial Infections Due to
`Multiresistant Acinetobacter baumannii
`Xavier Corbella, Miquel Pujol, Josefina Ayats,
`Montserrat Sendra, Carmen Ardanuy,
`M. Angeles Dominguez, Josefina Linares,
`Javier Ariza, and Francese Gudiol
`
`335 Capnocytophaga canimorsus Sepsis Complicated by
`Myocardial Infarction in Two Patients with Normal
`Coronary Arteries
`Hans-Ulrich Ehrbar, Jacques Gubler, Stefan Harbarth,
`and Bernhard Hirschel
`
`337 Experience with the Use of an Investigational F(ab')2
`Heptavalent Botulism Immune Globulin of Equine Origin
`During an Outbreak of Type E Botulism in Egypt
`Richard G. Hibbs, J. Todd Weber, Andrew Corwin,
`Ban Mishu Alios, Mohammed Sobhi Abd El Rehim,
`Said El Sharkawy, James E. Sarn,
`and Kelly T. McKee, Jr.
`
`llevievv J\rticle
`
`341 Managed Care and the Infectious Diseases Specialist
`Alan D. Tice, Thomas G. Slama, Steve Berman,
`Peter Braun, John P. Burke, Alison Cherney,
`Peter A. Gross, Peter Harris, Melinda Reid-Hatton,
`Robert Hoffman, Patrick Joseph, Stephan Lawton,
`R. Michael Massanari, Zachary /. Miller,
`William J. Osheroff, Donald Poretz, Mervin Shalowitz,
`Bryan Simmons, James P. Turner, Barbara Wade,
`and Barbara R. Nolet
`
`International Report
`
`369 Cryptococcus neoformans Infection in France:
`Epidemiologic Features of and Early Prognostic
`Parameters for 76 Patients Who Were Infected with
`Human Immunodeficiency Virus
`Clemence Darras-Joly, Sylvie Chevret, Michel Wolff,
`Sophie Matheron, Pascale Longuet, Enrique Casalino,
`Veronique Joly, Christian Chochillon,
`and Jean-Pierre Bedos
`
`377 J\nsvver to Photo Quiz
`
`Notes
`
`378 Failure of Cefonicid Prophylaxis for Infectious
`Complications Related to Endoscopic Retrograde
`Cholangiopancreatography
`Renata Finkelstein, Kamel Yassin, Alan Suissa,
`Alexandra Lavy, and Shmuel Eidelman
`
`380 Editorial Response: Failure of Cefonicid Prophylaxis for
`Infectious Complications Related to Endoscopic
`Retrograde Cholangiopancreatography
`Simon K. Lo
`
`385 Postinfectious Chronic Fatigue: A Distinct Syndrome?
`Dedra Buchwald, Jovine Umali, Tsilke Pearlman,
`Phalla Kith, Rhoda Ashley, and Mark Wener
`
`388 Clinical Spectrum of Urinary Tract Infections Due to
`Nontyphoidal Salmonella Species
`Jose M. Ramos, Jose M. Aguado,
`Pilar Garda-Corbeira, Jose M. Ales,
`and Francisco Soriano
`
`391 Paecilomyces Sinusitis in an lmmunocompromised Adult
`Patient: Case Report and Review
`R. Gucalp, P. Carlisle, P. Gialanella, S. Mitsudo,
`J. McKitrick, and J. Dutcher
`
`Brief Reports
`
`394 Long-Term Follow-Up of Multifocal Osteoarticular
`Sporotrichosis Treated with Itraconazole
`Andrew D. Badley and Robert E. Van Scoy
`
`395 An Unusual Case of Hydatid Disease: Localization to the
`Gluteus Muscle
`Rodolfo D. Casero, Mariano Gomez Costas,
`and Emilia Mensa
`
`396 Trichosporon inkin Endocarditis: Short-Term Evolution
`and Clinical Report
`G. Chaumentin, A. Boibieux, M. A. Piens, C. Douchet,
`P. Buttard, J. L. Bertrand, and D. Peyramond
`
`397 Acute Encephalitis Due to Human Herpesvirus 6
`Donatella Moschettini, Paolo Balestri, Alberto Fois,
`and Pier Egisto Valensin
`
`398 Prevalence of Bartonella henselae Antibodies Among
`Human Immunodeficiency Virus-Infected Patients from
`Bahrain
`Aziz Yousif, !man Farid, Badr Baig, Jean Creek,
`Patrick Olson, and Mark Wallace
`
`399 Peritonitis Due to a Ruptured Splenic Abscess
`Miguel Pera, Manuel Pera, and Asuncion Moreno
`
`400 Chronic Subdural Empyema: A New Presentation of
`Neurobrucellosis
`Yigal Shoshan, Shlomo Maayan, Moshe J. Gomori,
`and Zvi Israel
`
`401 Endocarditis Due to Haemophilus influenzae Serotype f
`Husn H. Frayha, Avedis K. Kalloghlian,
`and Michael M. A. deMoor
`
`402 Progressive Multifocal Leukoencephalopathy After
`Autologous Bone Marrow Transplantation in a Patient
`with Chronic Myelogenous Leukemia
`David Seong, Janet M. Bruner, Kyoo Hyung Lee,
`Nadeem Mirza, Byung Duck Kwon, Jae Hong Lee,
`Ya-Yen Lee, Jae Ro, Moshe Talpaz, Richard Champlin,
`and Albert B. Deisseroth
`
`404 Salmonella Neck Abscess in a Patient with (3-Thalassemia
`Major: Case Report and Review
`M. A. Behr and J. McDonald
`
`405 Catheter-Related Bacteremia Due to Mycobacterium
`avium Complex
`Michael P. Dube and Fred R. Sattler
`
`Page 4 of 14
`
`

`

`406 Kaposi's Sarcoma Herpesvirus-Like DNA Sequences in
`the Saliva of Individuals Infected with Human
`Immunodeficiency Virus
`Istvan Boldogh, Peter Szaniszlo, Wade A. Bresnahan,
`Catherine M Flaitz, Mark C. Nichols,
`and Thomas Albrecht
`
`408 A Cluster of Cases of Chronic Fatigue and Chronic
`Fatigue Syndrome: Clinical and Immunologic Studies
`Paul H. Levine, Janet K. Dale, Eileen Benson-Grigg,
`Scott Fritz, Seymour Grufferman,
`and Stephen E. Straus
`
`Correspondence
`
`410 Comparable Sensitivity of the Duke Criteria and the
`Modified Beth Israel Criteria for Diagnosing Infective
`Endocarditis
`F. Martos-Perez, J. M. Reguera, and J. D. Colmenero
`
`410 Reply
`Bruno Hoen
`
`416 Serum Therapy for Cryptococcal Meningitis
`R. A. Seaton
`
`417 Reply
`Arturo Casadevall and Morris Gordon
`
`417 Septic Thrombophlebitis of the Portal Vein
`Veronique Joly, Nadia Belmatoug, Annie Sibert,
`Claude Carbon, and Patrick Yeni
`
`418 Antibiotic-Lock Technique for the Treatment of Central
`Venous Catheter Infections
`A. Kentos, M. J. Struelens, and J. P. Thys
`
`419 Listeriosis in Bone Marrow Transplant Recipients
`Rodrigo Martino, Rosario Lopez, Roser Pericas,
`Isabel Badell, Anna Sureda, and Salut Brunet
`
`Book Reviews
`
`421 Differential Diagnosis of Infectious Diseases
`Written by David Schlossberg and Jonas A. Shulman
`Reviewed by Ed Septimus
`
`411 Chronic Granulomatous Disease Presenting as Severe
`Sepsis Due to Burkholderia gladioli
`Simon Hoare and Andrew J. Cant
`
`421 Manson's Tropical Diseases
`Edited by Gordon C. Cook
`Reviewed by Claire B. Panosian
`
`412 Lack of Predictive Value of Isolating Coagulase-Negative
`Staphylococci from Blood Cultures
`Riad Khatib
`
`413 Defining True Bacteremia Due to Coagulase-Negative
`Staphylococci
`James R. Johnson
`
`413 Reply
`Loreen A. Herwaldt and Michael A. Pfaller
`
`415 Management of Coinfection with Human
`Immunodeficiency Virus and Human T-Cell
`Lymphotropic Virus Type I
`Jeffrey P. Nadler, Michael C. Bach, and Eliot Godofsky
`
`416 Oral Azoles Versus Bladder Irrigation with Amphotericin
`B for the Treatment of Fungal Urinary Tract Infections
`James R. Johnson
`
`423 Notices
`
`423 Errata
`
`424 Omissions from Reviewer List for Volume 22
`
`425 Statement of Editorial Policy
`
`427 Checklist of Information for Inclusion in Reports
`of Clinical Trials
`
`Instructions to Authors
`
`Page 5 of 14
`
`

`

`Update on the Management of Onychomycosis: Highlights of the Third Annual
`International Summit on Cutaneous Antifungal Therapy
`
`Boni E. Elewski and Roderick J. Hay
`
`From the University Hospitals of Cleveland, Cleveland, Ohio, USA ;
`and St. John's Institute of Dermatologv, Guy 's f-lmpital.
`London. United Kingdom
`
`305
`
`Onychomycosis is an increasingly common fungal infection of the nail, which has traditionally
`been difficult to diagnose and treat and has physical and psychological consequences for the patient.
`Onychomycosis can be caused by dermatophytes, nondermatophytic filamentous fungi, and yeasts.
`The relative percentages of cases due to these etiologic agents vary with geographic location; however,
`in the United States, dermatophytes are the most common pathogens. Toenails are affected four
`times as often as fingernails. Microscopy and culture are the diagnostic "gold standards" for onycho(cid:173)
`mycosis, although biopsy of the nail may be required to obtain a definitive diagnosis when conditions
`that mimic onychomycosis, such as psoriasis, are suspected. The treatment of onychomycosis in(cid:173)
`cludes a combination of topical therapy, surgical or chemical nail avulsion, and systemic therapy.
`The new generation of systemic agents (itraconazole, fluconazole, and terbinafine) is associated with
`a higher cure rate and shorter courses of treatment than are the older systemic antifungal drugs (i.e.,
`griseofulvin and ketoconazole); these characteristics have sparked new interest in onychomycosis. Of
`these newer antifungals, itraconazole and terbinafine are the only agents currently approved by the
`U.S. Food and Drug Administration for the treatment of onychomycosis.
`
`Onychomycosis is a fungal infection of the nail unit. Al(cid:173)
`though the exact incidence of onychomycosis is unknown, stud(cid:173)
`ies estimate that between 2% and 18% ofthe population world(cid:173)
`wide is affected [I]. The results of a recent survey of persons
`with nail dermatophytosis in the United Kingdom suggested a
`prevalence of2.7% in the general population [2]. In the previ(cid:173)
`ous century, onychomycosis was rare and generall y occurred
`in the fingernai ls of persons with tinea capitis and in their care
`givers. Both onychomycosis and tinea pedis are now common
`and have been estimated to occur in 15% - 20% of persons
`aged 40 - 60 years [3].
`The rise in the incidence in onychomycosis is caused by a
`variety of factors including the aging of the population, an
`increase in the use of immunosuppressive therapies, an increase
`in exposure to organisms through communal bathing and health
`spas, and the use of tight-fitting occlusive footgear for many
`ath letic activities [4]. The increasing incidence of infection
`due to HIV also contributes to the ri se in the incidence of
`onychomycosis [5] because nails are commonly infected and
`are one of the important dermatologic signs of the progression
`of HIV disease. Toenail in fections are four times more common
`than fingernail infections [6].
`
`Received 27 December 1995; revised 15 March 1996.
`This work was presented in part at th e Third Annual International Summit
`on Cutaneous Antifungal Therapy held 24 - 27 August 1995 in New York.
`Grant support: Janssen Phannace utica.
`Reprints or co rrespondence: Dr. Bani E. Elewski, Associate Professor of
`Dermatology, University Hospitals ofCleveland, 11100 Euc lid Aven ue, Cleve(cid:173)
`land, Ohio 44106.
`
`Clinical Infectious Diseases 1996;23:305-13
`© 1996 by The University of Chicago. All rights reserved.
`I 058-4838196/2302 - 0015$02.00
`
`An accurate diagnosis of onychomycosis depends on proper
`co llection of the specimen, suitab le transport of the specimen
`to the laboratory, correct interpretation of the findings on direct
`microscopic examination, use of appropriate culture media, and
`correct identification of the causative organism. Treatment of
`the infection includes a combination of topical therapy, surgical
`or chemical nail avul sion, and systemic therapy. The new gen(cid:173)
`eration of system ic antifunga l agents is associated with a hi gher
`cure rate and shorter courses of treatment than are griseofulvin
`and ketoconazole. Of these newer agents, itraconazole and ter(cid:173)
`binafine are approved by the U.S. Food and Drug Administra(cid:173)
`tion (FDA) for the treatment of onychomycosis.
`
`The Etiology of Onychomycosis
`
`Onychomycosis is caused by dennatophytes, yeasts, and
`nondermatophytic molds. The dern1atophytes Trichophyton ru(cid:173)
`brum and Trichophyton mentagrophytes cause ;;. 80% of all
`cases of onychomycosis in temperate zones [7]. Approximately
`5%- 17% of fungal nail infections are caused by yeasts, and
`Candida albicans is isolated in > 70% of these cases [6].
`C. albicans is more frequently cultured from fingernai ls than
`from toenail s. Nondermatophytic molds such as Scopulari(cid:173)
`opsis, Scytalidium, Acremonium, and Fusarium cause approxi(cid:173)
`mately 3%- 5% of cases of fungal nail disease, which may
`develop secondary to dermatophytic infection, trauma, or direct
`invasion into the nail [8]. The rel ati ve percentages of cases
`due to these etiologic agents vary according to geographic
`location (table I) [7, 9 - 12]. For examp le, scytalidium infec(cid:173)
`tions have been reported as a major cause of nail disease in
`tropical and subtrop ical countries and may account for 50% of
`cases of onychomycosis in Southeast Asia [ 13]. It is important
`to identify fungal nail infections due to nondermatophytic
`
`Page 6 of 14
`
`

`

`306
`
`Elewski and Hay
`
`CID 1996; 23 (August)
`
`Table I. Geographic variations in etiologic agents.
`
`Canada
`(Sumerbell ; n = 3,000)
`
`USA
`(Greer; n = 43 I)
`
`UK
`(Clayton ; 11 = 699)
`
`Belgium
`(Willemsen; 11 = 700)
`
`Dermatophytes
`Yeasts
`Nondermatophyte molds
`Mixed
`
`90.5
`5.5
`4
`
`23
`63
`4
`8
`
`81
`17
`2
`
`40
`43
`14
`3
`
`NOTE. All data are in percent. This table is reprinted with permission from the lnternario11al Journal of Dermarology [12] .
`' Not specified.
`
`molds because the nondermatophytes are not effectively eradi(cid:173)
`cated by most of the available antifungal agents.
`Preexisting cases of tinea pedis predispose an individual
`to onychomycosis. The condition usually starts when trauma
`weakens the seal between the nail plate and the nail bed,
`allowing fungal organisms to penetrate the nail unit. The in(cid:173)
`creased incidence of onychomycosis, which is associated with
`aging, may be due to slower growth of the nail, increased
`trauma to the nail plate, decreased circulation, and changes in
`the size and width of the foot. Exposure to heat and moisture
`worsens the condition, and immunosuppression alters the
`body' s ability to combat the infection. Some investigators have
`suggested that estrogen exerts a protective effect against ony(cid:173)
`chomycosis, as the infection is observed more frequently in
`postmenopausal women [14]. On the other hand, testosterone
`might aggravate the condition, since onychomycosis is seen
`more frequently in boys older than 14 years and is rarely seen
`in children under the age of 12 years . Indeed, increased age
`itself- not hormonal factors - may be a major contributor to
`the development of onychomycosis.
`Genetic etiologic factors that predispose individuals to ony(cid:173)
`chomycosis may include an autosomal dominant transmission
`with incomplete penetrance, leading to variable clinical expres(cid:173)
`sion; a selective T cell nonrecognition factor, which could lead
`to differences in immunologic response to infection or to atopy;
`or a genetic influence on the keratin itself. The presence of these
`genetically variant patterns alters the keratin protein within
`the nail structure, making the nail more susceptible to fungal
`invasion [15].
`
`Clinical Manifestations of Onychomycosis
`
`Four patterns of onychomycosis have been described: distal
`lateral subungual onychomycosis; superficial white onycho(cid:173)
`mycosis; proximal subungual onychomycosis; and onychodys(cid:173)
`trophy, which is associated with candida! infection. The latter
`category is further classified as candida! paronychia, onycho(cid:173)
`lysis, chronic mucocutaneous candidiasis, and distal lateral sub(cid:173)
`ungual onychomycosis. The clinical presentations of each form
`of the disease are presented in figure I. The relative percentages
`of etiologic agents that cause each clinical manifestation vary
`according to geographic location. Total dystrophic onycho-
`
`mycosis is sometimes considered an additional category that
`is associated with an advanced stage of any of the four patterns
`of onychomycosis.
`Distal lateral subungual onychomycosis. This manifesta(cid:173)
`tion of the disease begins with initial fungal penetration of the
`stratum corneum from the hyponychial area or from the lateral
`nail fold. It is characterized by yellow-brown discoloration of
`the nail plate, onycholysis, and subungual hyperkeratosis. It is
`the most common clinical presentation of onychomycosis and
`is most often caused by T rubrum or T mentagrophytes. A
`small percentage of cases are caused by Epidermophyton flo c(cid:173)
`cosum, Trichophyton tonsurans, Trichophyton violaceum, and
`miscellaneous Microsporum species.
`Superficial white onychomycosis. Fungi directly invade the
`nail plate in superficial white onychomycosis, creating a white,
`crumbly appearance. The most common agent is T. mentagro(cid:173)
`phytes, but species of Fusarium or Acremonium may also be
`the etiologic agents. Superficial white onychomycosis is almost
`always found in toenails. The initial lesions may be randomly
`dispersed but will eventually coalesce to include the entire
`surface of the nail. This infection is capable of producing pro(cid:173)
`gressive dystrophy of the nails and will invade the cornified
`layer of the nail bed and hyponychium.
`Proximal subungual onychomycosis. Proximal subungual
`onychomycosis is the least common clinical presentation of
`onychomycosis in healthy individuals. The infection penetrates
`the proximal portion of the nail, resulting in hyperkeratosi s
`and onycholysis. The characteristic clinical appearance is a
`white hue that extends distally from under the proximal nail
`fold. The distal portion of the nail unit remains normal until
`late in the course of the disease, when the entire nail plate is
`affected. This infection occurs in both fingernails and toenails
`and is primarily caused by T rubrum. The proximal white
`subungual pattern particularly affects immunocompromised pa(cid:173)
`tients. A recent study showed that 87 .I % of 62 patients with
`AIDS had proximal white subungual onychomycosis [16] .
`Candida! onychomycosis. There are
`three
`recognized
`fom1s of nail dystrophy associated with candida! infection.
`Candida! paronychia results in swelling and erythema of the
`proximal and lateral nail folds, with secondary involvement of
`the nail plate; this condition is common in persons whose hands
`are constantly immersed in water. Onycholysis is often a result
`
`Page 7 of 14
`
`

`

`Figure I. Manifestations of onychomycosis. Top lefl: Distal lateral subw1gual onychomycosis. Top right: Superficial white onychomy(cid:173)
`eosis. Bottom lefl: Proximal subW1gual onychomycosis. Bottom right: Candida! infection (courtesy of Dr. Gary D. Palmer, Dayton, Ohio).
`
`Figure 2. Psoriasis of the nail (courtesy of Dr. Gary D.
`Palmer).
`
`Figure 3. Chronic onycholysis (courtesy of Dr. C. Ralph Daniel
`Ill, University of Mississippi Medical Center, Jackson, Mississippi).
`
`Page 8 of 14
`
`

`

`308
`
`Elewski and Hay
`
`CID 1996;23 (August)
`
`of the hyperkeratosis that forms in the subungual area in pa(cid:173)
`tients with candida! paronychia. C. albicans is isolated in
`> 70% of onychomycosis cases that are caused by yeasts; Can(cid:173)
`dida parapsilosis, Candida tropicalis, and Candida krusei are
`less frequently the causative agents [8]. It has also been sug(cid:173)
`gested that other mechanisms, including chronic contact derma(cid:173)
`titis, contribute to the pathogenesis of this condition.
`Distal and lateral onychomycosis due to Candida species
`occurs when there is separation of the nail plate from the nail
`bed, with erosion of the nail plate. The infection is not common
`but is seen particularly in patients with Raynaud 's disease or
`Cushing's syndrome.
`The third form of candida! onychomycosis, which occurs in
`the nail and as a cutaneous infection, is chronic mucocutaneous
`candidiasis (also known as candida! granuloma). The organism
`directly invades the nail plate, and the proximal and lateral nail
`folds become increasingly thick, until the nail becomes totally
`dystrophic. This condition is also seen in immunocompromised
`individuals, including HIV-infected patients, who are deficient
`in specific T cell responses to Candida antigen [5].
`
`Diagnosis of Onychomycosis
`
`Findings on microscopy and the results of fungal cultures
`confirm the diagnosis of onychomycosis. Confirmation of fun(cid:173)
`gal infection of the nail is required so that appropriate therapy
`can be initiated, since other nail diseases such as psoriasis
`and lichen planus can mimic onychomycosis clinically. When
`culturing nails, subungual debris shou ld be collected as proxi(cid:173)
`mally as possible, since the outermost debris may contain con(cid:173)
`taminants and nonviable hyphae.
`Before the nail specimen is viewed, it should first be softened
`and cleared in 20%- 30% KOH . The detection of spores and
`fungal hyphae can be enhanced by using stains such as Parker's
`blue-black ink (I part KOH to I part ink), Polychrome Multiple
`Stain, or ftuorochromes [8]. Chlorazol black E may also be
`added as a counterstain because it is chitin specific and, unlike
`the blue-black ink, is less likely to stain other potential contami(cid:173)
`nants such as cotton or elastic fibers. Calcofluor white is a
`nonspecific fluorochrome stain that binds with ,8-configuration
`polysaccharides. It has been used for detecting fungi in clinical
`specimens and has been found to be significantly more sensitive
`than the KOH wet mount in observing fungal pathogens [I 7].
`The limitation of the KOH procedure is that it is only a screen(cid:173)
`ing test for the presence or absence of fungi and cannot identify
`specific pathogens.
`The identity of the pathogen can be confinned only by fungal
`culture. Cultures can be done using dermatophyte test media,
`Mycosel (BBL Becton Dickinson Microbiology Systems,
`Cockeysville, MD), or Sabouraud dextrose agar. Overgrowth
`by nondem1atophytes and bacteria is avoided by modifying the
`chosen medium with antibacterial agents (chlortetracycline and
`gentamic in) and by using media with and without cyclohexi(cid:173)
`mide.
`
`Table 2. Nail diseases that may mimic onychomycosis.
`
`• Traumatic onychodystrophies
`• Pachyonychia co ngenita
`• Contact dermatitis
`• Nail bed tumors
`• Yellow-nail synd rome
`• Idiopathic onycholysis
`
`Conditions that Mimic Onychomycosis
`
`The differential diagnosis of onychomycosis includes several
`nail diseases that may be clinicall y indistinguishable from ony(cid:173)
`chomycosis (table 2). The most common of these diseases is
`psoriasis. A nail biopsy may be required to obtain a definitive
`diagnosis.
`Distinguishing between onychomycosis (figure I) and psori(cid:173)
`asis (figure 2) can be difficult, since subungual hyperkeratosis,
`onycholysis, splinter hemotThages, and diffuse crumbling are
`clinical signs of both conditions. The finding of a positive
`fungal culture does not mle out psoriasis because dermato(cid:173)
`phytes or other fungi can occasionally colonize psoriatic nails,
`especially when the nail plate is grossly deformed. Three clini(cid:173)
`cal symptoms of psoriasis (the presence of fine pitting, the small
`salmon-colored oi l-drop sign of onycholysis that is present
`in psoriasis but absent in onychomycosis, and the frequent
`involvement of nails in both hands in cases of psoriasis), in
`addition to evidence of psoriasis at another site such as the
`elbows and/or knees, are helpful in differentiating between the
`two conditions.
`Lichen planus, an infla