Mar / April 2012 by jo-ann kalaka-Adams

March/April 2012 • Volume 10 • Issue 2

EDITORIAL Scabies Then and Now Lavery, Parish, and Wolf

ORIGINAL CONTRIBUTIONS Erlotinib-Induced Scalp Perifolliculitis Rallis, Petronic-Rosic, and Korfitis

New Findings in Delusions of Parasitosis Fellner

REVIEW Wound Care in Short-Term Rehabilitation Facilities and Long-Term Care: Special Needs for a Special Population White-Chu and Reddy

CASE STUDIES Malignant Melanoma Arising Within Nevus Spilus Karam and Jackson

Pseudocyst of the Auricle: An Uncommon Entity of the Ear Sheaffer, Sahu, and Lee

Necrotic Ulcer: A Manifestation of Leukemia Cutis Aksu, Saracoglu, Sabuncu, Ciftci, Gulbas, and Isiksoy

Inflammatory Linear Verrucous Epidermal Nevus With Genital Involvement Balci, Yenin, Çelik, Sarikaya, and Atik

Oral Frictional Hyperkeratosis (Morsicatio Buccarum): An Entity to Be Considered in the Differential Diagnosis of White Oral Mucosal Lesions Cam, Santoro, and Lee

CORE CURRICULUM Cutaneous Tuberculosis: A Diagnostic Dilemma—Laboratory Inputs

Vesicular Palmoplantar Pityriasis Rosea Singh, Sharma, Narang, and Madan

Sehgal, Verma, Bhattacharya, Sharma, Singh, and Verma

DEPARTMENTS PERILS OF DERMATOPATHOLOGY Sometimes It Takes Darkness to See the Light: Pitfalls in the Interpretation of Cell Proliferation Markers (Ki-67 and PCNA) Castilla, McDonough, Tumer, Lambert, and Lambert

INFECTIOUS DISEASE CAPSULES The Lion Is NOT Sleeping Tonight Carr, Bernstein, and Trevino

PHOTO CAPSULES Actinomycetoma Dlova and Mosam

BOOK REVIEW Hall’s Manual of Skin as a Marker of Underlying Disease Reviewed by Scheinfeld

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TABLE OF CONTENTS .BSDI "QSJM t 7PMVNF t *TTVF

EDITORIAL Scabies Then and Now .................................................................................................................................. 67 Michael Joseph Lavery, MB BCh BAO; Lawrence Charles Parish, MD, MD (Hon); Ronni Wolf, MD

ORIGINAL CONTRIBUTIONS Erlotinib-Induced Scalp Perifolliculitis ............................................................................................................ 70 Efstathios Rallis, MD, PhD; Vesna Petronic-Rosic, MD, MSc; Chrysovalantis Korfitis, MD

New Findings in Delusions of Parasitosis ........................................................................................................ 72 Michael J. Fellner, MD

REVIEW Wound Care in Short-Term Rehabilitation Facilities and Long-Term Care: Special Needs for a Special Population ..................................................................................................................................... 75 E. Foy White-Chu, MD; Madhuri Reddy, MD, MSc Self-Test Review Questions (p. 81)

CORE CURRICULUM Virendra N. Sehgal, MD, Section Editor

Cutaneous Tuberculosis: A Diagnostic Dilemma—Laboratory Inputs ................................................................ 82 Virendra N. Sehgal, MD; Prashant Verma, MD; Sambit N. Bhattacharya, MD; Sonal Sharma, MD; Navjeevan Singh, MD; Nishant Verma, MD

DEPARTMENTS PERILS OF DERMATOPATHOLOGY W. Clark Lambert, MD, PhD, Section Editor

Sometimes It Takes Darkness to See the Light: Pitfalls in the Interpretation of Cell Proliferation Markers (Ki-67 and PCNA) ............................................................................................................................ 90 Carmen Castilla, BS; Patrick McDonough, BA; Gizem Tumer, MD; Peter C. Lambert, BA, MS; W. Clark Lambert, MD, PhD

INFECTIOUS DISEASE CAPSULES Jack M. Bernstein, MD, Section Editor

The Lion Is NOT Sleeping Tonight................................................................................................................... 94 David R. Carr, MD; Jack M. Bernstein, MD; Julian Trevino, MD

PHOTO CAPSULES Ncoza C. Dlova, MBChB, FCDerm, Section Editor

Actinomycetoma ........................................................................................................................................... 98 Ncoza C. Dlova, MBChB, FCDerm; Anisa Mosam, MBChB, FCDerm

CASE STUDIES Vesna Petronic-Rosic, MD, MSc, Section Editor

Malignant Melanoma Arising Within Nevus Spilus ......................................................................................... 100 Susan L. Karam, BS; Scott M. Jackson, MD

Pseudocyst of the Auricle: An Uncommon Entity of the Ear ........................................................................... 104 Alexis Sheaffer, BS; Joya Sahu, MD; Jason B. Lee, MD

Necrotic Ulcer: A Manifestation of Leukemia Cutis ....................................................................................... 108 Ayse Esra Koku Aksu, MD; Zeynep Nurhan Saracoglu, MD; Ilham Sabuncu, MD; Evrim Ciftci, MD; Zafer Gulbas, MD; Serap Isiksoy, MD

Inflammatory Linear Verrucous Epidermal Nevus With Genital Involvement ................................................... 112 Didem Didar Balci, MD; Jülide Zehra Yenin, MD; Ebru Çelik, MD; Gökhan Sarikaya, MD; Esin Atik, MD

TABLE OF CONTENTS .BSDI "QSJM t 7PMVNF t *TTVF Oral Frictional Hyperkeratosis (Morsicatio Buccarum): An Entity to Be Considered in the Differential Diagnosis of White Oral Mucosal Lesions .......................................................................... 114 Kristin Cam, MD; Anthony Santoro, MD; Jason B. Lee, MD

Vesicular Palmoplantar Pityriasis Rosea....................................................................................................... 116 Varinder Singh, MD; Meghna Sharma, MD; Tarun Narang, MD; Manas Madan, MD

BOOK REVIEW Noah S. Scheinfeld, MD, JD, Section Editor

Hall’s Manual of Skin as a Marker of Underlying Disease .............................................................................. 120 Edited by John C. Hall and Brian J. Hall. 300 pages. Shelton, CT; People’s Medical Publishing House–USA; 2011. $89.95. ISBN 1607951029

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March/April 2012

EDITORIAL BOARD

EDITOR IN CHIEF

Lawrence Charles Parish, MD, MD (Hon) Philadelphia, PA

DEPUTY EDITORS William Abramovits, MD Dallas, TX

W. Clark Lambert, MD, PhD Newark, NJ

Larry E. Millikan, MD Meridian, MS

Vesna Petronic-Rosic, MD, MSc Chicago, IL

Marcia Ramos-e-Silva, MD, PhD Rio de Janeiro, Brazil

Jennifer L. Parish, MD Philadelphia, PA

EDITORIAL BOARD Mohamed Amer, MD Cairo, Egypt

Howard A. Epstein, PhD Philadelphia, PA

Jasna Lipozencic, MD, PhD Zagreb, Croatia

Noah S. Scheinfeld, MD, JD New York, NY

Robert L. Baran, MD Cannes, France

Ibrahim Hassan Galadari, MD, PhD, FRCP Dubai, United Arab Emirates

Eve J. Lowenstein, MD, PhD New York, NY

Virendra N. Sehgal, MD Delhi, India

Anthony V. Benedetto, DO Philadelphia, PA

Anthony A. Gaspari, MD Baltimore, MD

George M. Martin, MD Kihei, HI

Charles Steffen, MD Oceanside, CA

Brian Berman, MD, PhD Miami, FL

Michael Geiges, MD Zurich, Switzerland

Marc S. Micozzi, MD, PhD Bethesda, MD

Alexander J. Stratigos, MD Athens, Greece

Jack M. Bernstein, MD Dayton, OH

Michael H. Gold, MD Nashville, TN

George F. Murphy, MD Boston, MA

James S. Studdiford III, MD Philadelphia, PA

Sarah Brenner, MD Tel Aviv, Israel

Lowell A. Goldsmith, MD, MPH Chapel Hill, NC

Oumeish Youssef Oumeish, MD, FRCP Amman, Jordan

Robert J. Thomsen, MD Los Alamos, NM

Joaquin Calap Calatayud, MD Cadiz, Spain

Aditya K. Gupta, MD, PhD, FRCP(C) London, Ontario, Canada

Joseph L. Pace, MD, FRCP Naxxar, Malta

Julian Trevino, MD Dayton, OH

Henry H.L. Chan, MB, MD, PhD, FRCP Hong Kong, China

Seung-Kyung Hann, MD, PhD Seoul, Korea

Art Papier, MD Rochester, NY

Snejina Vassileva, MD, PhD Sofia, Bulgaria

Noah Craft, MD, PhD, DTMH Torrance, CA

Roderick J. Hay, BCh, DM, FRCP, FRCPath London, UK

Johannes Ring, MD, DPhil Munich, Germany

Daniel Wallach, MD Paris, France

Ncoza C. Dlova, MBChB, FCDerm Durban, South Africa

Tanya R. Humphreys, MD Philadelphia, PA

Roy S. Rogers III, MD Rochester, MN

Michael A. Waugh, MB, FRCP Leeds, UK

Richard L. Dobson, MD Mt Pleasant, SC

Camila K. Janniger, MD Englewood, NJ

Donald Rudikoff, MD New York, NY

Wm. Philip Werschler, MD Spokane, WA

William H. Eaglstein, MD Palo Alto, CA

Abdul-Ghani Kibbi, MD Beirut, Lebanon

Robert I. Rudolph, MD Wyomissing, PA

Joseph A. Witkowski, MD Philadelphia, PA

Boni E. Elewski, MD Birmingham, AL

Andrew P. Lazar, MD Highland Park, IL

Vincenzo Ruocco, MD Naples, Italy

Ronni Wolf, MD Rechovot, Israel

Charles N. Ellis, MD Ann Arbor, MI

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March/April 2012

EDITORIAL

Scabies Then and Now Michael Joseph Lavery, MB BCh BAO;1 Lawrence Charles Parish, MD, MD (Hon);2 Ronni Wolf, MD3 CONTRIBUTING FACTORS

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March/April 2012

Figure 3. Red papules on the penile corona indicating scabies, until proven otherwise.

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Figure 1. The scabies mite, showing 8 legs.

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Figure 2. The characteristic red papules on the finger webs.

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Figure 4. Crusted scabies in an older man who had neglected himself.

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March/April 2012 5

Vandergriff T, Harting M, Rosen T. Venereal diseases. In: Hall JC, Hall BJ. Skin Infections: Diagnosis and Treatment. Cambridge, England; Cambridge University Press; 2009; Part VI, Ch 24; 317â&#x20AC;&#x201C;318.

Scabies Homepage. (American incidence) http://www.stanford.edu/ group/parasites/ParaSites2005/Scabies/SCABIES.html. Accessed July 30, 2011.

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Lassa S, Campbell MJ, Bennett CE. Epidemiology of scabies prevalence in the UK from general practice records. Br J Dermatol. 2011;164; 1329â&#x20AC;&#x201C;1334.

Downs AMR, Harvey I, Kennedy CTC. The epidemiology of head lice and scabies in the UK. Epidemiol Infect. 1999;3;471â&#x20AC;&#x201C;477.

Johnston G, Sladden M. Scabies: diagnosis and treatment. Clinical review. BMJ. 2005;331:619

Poor Giovanni Bonomo, Would be filled with such woe, To have this tiny little mite, Still causing affliction by its bite.

11 Harrison S, Knott H, Bergfeld WF. Infections of the Scalp. In: Hall JC, Hall BJ. Skin Infections: Diagnosis and Treatment. Cambridge, England; Cambridge University Press: 2009; Part V, Ch 20; 260.

PGUFO UIBO OPU MBDL PG DPNQMJBODF PS SF JOGFTUBUJPO IBT CFFO DPOTJEFSFE SFTJTUBODF XIJDI JU JT OPU 17 CONCLUSIONS

10 Parasites and Health. Accessed July 30, 2011.

Scabies.

www.cdc.gov/scabies/risk.html.

12 Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. New Engl J Med. 2010;362;717â&#x20AC;&#x201C;725. 13 Cestari TF, Martignago BF. Scabies, pediculosis, bedbugs and stinkbugs: uncommon presentations. Clin Dermatol. 2005;23;545â&#x20AC;&#x201C;554.

REFERENCES

14 Wolf R, Davidovici B. Treatment of scabies and pediculosis: facts and controversies. Clin Dermatol. 2010;28;511â&#x20AC;&#x201C;518.

Graham-Brown RAC, Burns T. Lecture notes. Dermatology. 9th ed. Malden, MA: Blackwell Publishing; 2007:41â&#x20AC;&#x201C;45.

Cheese mites and other wonders. BBC News Online. http://news.bbc. co.uk/1/hi/magazine/7423847.stm. Accessed July 30, 2011.

15 Currie BJ, Harumal P, McKinnon M, et al. First documentation of in vivo and in vitro ivermectin resistance in sarcoptes scabiei. Clin Infect Dis. 2004;39;e8â&#x20AC;&#x201C;e12.

Arthur Conan Doyle. A Parable 1916. http://rpo.library.utoronto.ca/ poem/3284.html. Accessed July 30, 2011.

16 Wolf R, Davidovici B, Parish LC. Can the scabies mite be tamed? SKINmed. 2006;5:214â&#x20AC;&#x201C;216.

Ramos-e-Silva M. Giovan Cosimo Bonomo (1663-1696): discoverer of the etiology of scabies. Int J Dermatol. 1998;37;625â&#x20AC;&#x201C;630.

17 Cox NH. Permethrin treatment in scabies infestation: importance of the correct formulation. Clinical Review. BMJ. 2000;320:37.

WAX MOULAGE

Candidiasis, Infection with Candida albicans. Moulage No 238â&#x20AC;&#x201C;239, made by Lotte Volger in the Dermatology Clinic in Zurich in 1923. Museum of Wax Moulages Zurich, www.moulagen.ch Courtesy of Michael Geiges, MD

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ORIGINAL CONTRIBUTION

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March/April 2012

ORIGINAL CONTRIBUTION

New Findings in Delusions of Parasitosis Michael J. Fellner, MD ABSTRACT 5XP OFX DBTFT BSF QSFTFOUFE XJUI EFMVTJPOT PG QBSBTJUPTJT #PUI XFSF XPNFO POF NJEEMF BHFE BOE POF FMEFSMZ BOE FYIJCJUFE DMBTTJD TZNQUPNT PG QBSBTJUFT BOE iTUSJOHTw JO UIF TLJO JOEJDBUJWF PG .PSHFMMPOT EJTFBTF &BDI IBE BO BEEJUJPOBM QTZDIJBUSJD EJTPSEFS ESVH BEEJDUJPO UP DPDBJOF BOE TFOJMF EFNFOUJB É¨FZ BMTP JMMVTUSBUF UIF EJÃ¯DVMUZ FODPVOUFSFE CZ UIF EFSNBUPMPHJTU JO QSPWJEJOH BEFRVBUF UIFSBQZ CFDBVTF PG SFTJTUBODF UP QTZDIJBUSJD SFGFSSBM BT XFMM BT UP TUBOEBSE BDDFQUFE NFEJDBUJPO /FXFS QTZDIPUSPQJDT TVDI BT SJTQFSEBM BOE MFYBQSP TIPX QSPNJTF JO IFMQJOH UIFTF QBUJFOUT BOE BEE UP UIF UIFSBQFVUJD BSNBNFOUBSJVN PG QJNP[JEF SKINmed. o

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É¨F QBUJFOU XBT FODPVSBHFE UP WFOUJMBUF BCPVU IFS QSPCMFNT -JEPDBJOF QSJMPDBJOF DSFBN XBT QSFTDSJCFE GPS EZTFTUIFTJBT BOE 4IF SFQPSUFE UP CF JO PUIFSXJTF HPPE IFBMUI FYQFDU GPS BO BMMFSHZ GFFMJOHT PG GPSNJDBUJPO BOE TIF XBT FODPVSBHFE UP JODSFBTF UIF UP JPEJOF "GUFS UIF SFMBUJPOTIJQ CSFBLVQ TIF XBT CSJFÃ¬Z USFBUFE EPTF PG FTDJUBMPQSBN UP NH BU OJHIU From the Metropolitan Hospital, New York Medical College, New York, NY Address for Correspondence: Michael J. Fellner, MD, Metropolitan Hospital, New York Medical College, 50 East 89th Street, New York, /:Ã¹ t & NBJM GSFEEBHG!BPM DPN

SKINmed. 2012;10:72â&#x20AC;&#x201C;74

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March/April 2012

ORIGINAL CONTRIBUTION

CASE 2 A 90-year-old woman was referred from a major medical dermatology center with a diagnosis of delusions of parasitosis. On the first visit she described worms and strings coming out of her body including the skin, eyes, and mouth. She reported the onset as September 2009 following a bout of diarrhea during the summer that lasted for 2 months. She was treated with albendazole by a noted parasitologist for trichuris infection. The diarrhea abated with the treatment. By September 2009, she had described worms and strings coming out of her body, causing her great discomfort. She first went to her primary care physician at the medical school center. He examined the material she brought and told her there were no parasites or strings but only mucous. This angered her and she refused to return to the physician. She brought a drawing of the worms and strings on her first dermatology visit (Figure 1). Examination revealed a thin elderly woman in no acute distress whose stream of thought was verbose and rambling. The skin showed a reddened and ulcerated area on the right thigh (Figure 2). The remainder of the physical examination was within normal limits. Results from laboratory tests were within normal limits. The patient was given mupirocin ointment for the ulcer and ammonium lactate 12% lotion for the skin on the body and was reassured there was some possibility that the disturbance might abate.

Figure 2. The patient’s thigh lesion on first visit.

On follow-up 2 weeks later, she claimed the parasites had started in June 2009, contradicting her previous statement that they had started in September 2009. She now claimed slight improvement with the treatment. There were, however, new lesions on the right thigh (Figure 3). Once again she was unclear about

Figure 3. The patient’s thigh lesions on second visit.

whether these resulted from the parasites. She indicated that the strings and worms were coming out of her ears, eyes, nose, and skin on the face.

Figure 1. The patient’s drawing of string and parasite coming out of her skin. SKINmed. 2012;10:72–74

She was encouraged to take doxepin 25 mg at night and continue with ammonium lactate 12% lotion and mupirocin ointment. She was also encouraged to ventilate about her multiple social problems, including her family, her will, and her eating problems. She said she weighed 87 pounds because she was unable to eat any carbohydrates since she believed the parasites lived on sugars. She said she was in the process of getting assistance in daily-living activities at home.

Delusions of Parasitosis

March/April 2012

ORIGINAL CONTRIBUTION

On third follow-up, she said she felt considerably better (2 weeks after second visit) using emollients. She did not mention parasites, but said the problem was improving. She was encouraged to seek psychologic or psychiatric counseling but was not accepting of this suggestion. She said she was going to make an appointment for a visit at a nearby medical center geriatric unit to help her with nutrition and memory problems. She was encouraged to take doxepin at bedtime and to use emollients. DISCUSSION These cases are the first to exhibit findings of Morgellons disease and delusions of parasitosis at the same time. Morgellons is a pattern of dermatologic symptoms very similar, if not identical, to those of delusions of parasitosis, and many patients with Morgellons are diagnosed with another psychosomatic illness.2 In delusional parasitosis, patients hold a delusional belief that they are infested with parasites. They may experience formication, the sensation that insects are crawling under the skin. It is a common symptom in cocaine abusers as well. Individuals who experience this condition may develop elaborate rituals of inspection and cleansing to locate and remove parasites and fibers, resulting in a form of self-mutilation; they injure themselves in attempts to be rid of the “parasites” by picking at the skin, causing secondary lesions. Continuous picking of the lesions prevents healing. Patients with delusional parasitosis often present at the doctor’s office with what physician’s term the matchbox sign, a medical sign characterized by the patient making collections of fibers and other foreign objects supposedly retrieved from the skin, and, because of “unshakeable delusional ideation,” strongly reject diagnoses that do not involve parasites. The Morgellons Research Foundation, a nonprofit organization, considers Morgellons to be a newly emerging infectious disease, but the medical community disagrees, noting that the described symptoms of Morgellons are associated with the psychotic disorder known as delusional parasitosis.2

Due to the second patient’s age, it was deemed inappropriate to give pimozide or treatment with an SSRI medication since sudden death in the elderly has been reported.3 The treatment plan was to gain the patient’s confidence before attempting to refer her for psychologic or psychiatric care, since there did not appear to be any insight on her part at the first 2 visits. Therapy is often unsuccessful because many patients, such as those reported here, refuse consultation with a psychiatrist either because they believe the problem is organic or because they fear mental illness and the stigma of psychiatry. In extremely severe cases, suicide has been reported, illustrating the urgency of corrective medication and prompt psychiatric referral.4 Standard treatment with pimozide risks substantial side effects.3 This has led to trial with additional psychotropic agents. Recent success has been reported with the use of risperdal5 and olanzapine.6 Nowhere have these diseases been more graphically illustrated than in the Oscar-nominated 2010 film “Black Swan” wherein the heroine played by Natalie Portman suffers from the delusion that parasites and strings are coming out of her skin. This is a must-see film for dermatologists and psychiatrists alike. REFERENCES 1

Fellner MJ, Majeed MH. Tales of bugs, delusions of parasitosis, and what to do. Clin Dermatol. 2009;27:135–138.

Savely VR, Leitao MM, Stricker RB. The mystery of Morgellon’s disease: infection or delusion? Am J Clin Dermatol. 2006;7:1–5.

van Vloten WA. Pimozide use in dermatology. Dermatol Online J. 2003;9:3.

Monk BE, Rao YJ. Delusions of parasitosis with fatal outcome. Clin Exp Dermatol. 1994;19:341–342.

Friedmann AC, Ekeowa-Anderson A, Taylor R, Bewley A. Delusional parasitosis presenting as folie a trois: successful treatment with risperidone. Br J Dermatol. 2006;155:841–842.

Atilganoglu U, Ugurad I, Arikan M, Ergun SS. Monosymptomatic hypochondriacal psychosis presenting with recurrent oral mucosal ulcers and multiple skin lesions responding to olanzapine treatment. Int J Dermatol. 2006;45:1189–1192.

VINTAGE LABEL

Courtesy of BuyEnlarge, Philadelphia, PA SKINmed. 2012;10:72–74

Delusions of Parasitosis

7PMVNF t *TTVF

March/April 2012

REVIEW

Wound Care in Short-Term Rehabilitation Facilities and Long-Term Care: Special Needs for a Special Population E. Foy White-Chu, MD; Madhuri Reddy, MD, MSc ABSTRACT $ISPOJD XPVOET DBO QPTF B DIBMMFOHJOH EJBHOPTUJD BOE USFBUNFOU EJMFNNB JO UIF PMEFS GSBJM BEVMU QPQVMBUJPO É¨F CFOFÃ«UT PG TIPSU UFSN SFIBCJMJUBUJPO BOE MPOH UFSN DBSF TFUUJOHT BSF UIF BDDFTT UP JOUFSEJTDJQMJOBSZ SFTPVSDFT 3FIBCJMJUBUJWF TQFDJBMJTUT EJFUJDJBOT BOE TLJMMFE OVSTFT BSF SFBEJMZ BWBJMBCMF UP NFFU UIF QBUJFOUT OFFET BT UIFZ USBOTJUJPO UP IPNF PS SFNBJO JO B MPOH UFSN DBSF TFUUJOH GPS UIFJS IJHIFS MFWFM PG DBSF OFFET É¨JT BSUJDMF GPMMPXT DBTFT B TLJO UFBS DPNQMJDBUFE CZ WFOPVT VMDFSBUJPO B QSFTTVSF VMDFS XJUI GFWFS BOE BSUFSJBM VMDFST JO B QBUJFOU XIP PQUT GPS DPNGPSU DBSF É¨F DBTFT JMMVTUSBUF UIF IJHIFS OFFET PG UIJT QPQVMBUJPO BOE FNQIBTJ[F UIF BUUFOUJPO UIBU NVTU CF QBJE UP SFTQFDU OVSTJOH UJNF JOUFOTJWFOFTT JODPSQPSBUF SFBMJTUJD HPBMT PG DBSF GPS XPVOE IFBMJOH BOE FOTVSF FYDFMMFOU DPNNVOJDBUJPO XJUI UIF UFBN NFNCFST QBUJFOUT BOE GBNJMZ SKINmed. o

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CASE 1: SKIN TEAR THAT IS SLOW TO HEAL

5IF CFOFGJUT PG TIPSU UFSN SFIBCJMJUBUJPO BOE MPOH UFSN DBSF TFUUJOHT BSF UIF BDDFTT UP JOUFSEJTDJQMJOBSZ SFTPVSDFT 3FIB CJMJUBUJWF TQFDJBMJTUT EJFUJDJBOT BOE TLJMMFE OVSTFT BSF SFBEJMZ BWBJMBCMF UP NFFU UIF QBUJFOUT OFFET BT UIFZ USBOTJUJPO UP IPNF PS SFNBJO JO B MPOH UFSN DBSF TFUUJOH GPS UIFJS IJHIFS MFWFM PG DBSF OFFET %VF UP UIFTF IJHIFS OFFET BUUFOUJPO NVTU CF QBJE UP SFTQFDU OVSTJOH UJNF JOUFOTJWFOFTT JODPS QPSBUF SFBMJTUJD HPBMT PG DBSF GPS XPVOE IFBMJOH BOE FOTVSF FYDFMMFOU DPNNVOJDBUJPO XJUI UIF UFBN NFNCFST QBUJFOUT BOE GBNJMZ

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From the Wound Healing Center, Hebrew Senior Life Department of Medicine, Boston, MA Address for Correspondence: E. Foy White-Chu, MD, Director of Wound Healing Center, Hebrew Senior Life Department of Medicine, 1200 $FOUSF 4USFFU #PTUPO ." t & NBJM GPZXIJUFDIV!ISDB IBSWBSE FEV

SKINmed. 2012;10:75â&#x20AC;&#x201C;81

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3&7*&8

March/April 2012

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Figure 1. Venous ulcer status post-debridement. Photo courtesy of E. Foy White-Chu, MD.

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Figure 2. Proper wrapping technique on the right leg. Note the inclusion of the heel from toes to knee. Photo courtesy of E. Foy White-Chu, MD.

SKIN TEARS É¨F HSFBUFTU OVNCFS PG TLJO UFBST JO PMEFS BEVMUT PDDVS JO UIF QBUJFOU T CFESPPN BOE UIF NPTU DPNNPO PCKFDUT UP DBVTF TLJO UFBST BSF XIFFMDIBJST GPMMPXFE CZ CFESBJMT BOE HFSJBUSJD SFDMJOFST .PCJMF QBUJFOUT UFOE UP IBWF UFBST PO UIF MFHT XIJMF OPONPCJMF QBUJFOUT IBWF TLJO UFBST PO UIF FMCPXT BSNT BOE MFHT 8IFO QBUJFOUT BSF JNNPCJMF USBOTGFST BOE SF QPTJUJPOJOH QMBZ HSFBUFS SPMFT JO DBVTJOH TLJO UFBST É¨F MPXFS CBDL BOE TBDSBM BSFB BSF FTQFDJBMMZ BU SJTL PG TLJO UFBST DBVTFE CZ TIFBSJOH GSPN USBOTGFST 3JTL GBDUPST GPS TLJO UFBST JODMVEF JODSFBTFE BHF VTF PG BO BTTJTU EFWJDF DPHOJUJWF JNQBJSNFOU BOE TFOTPSZ JNQBJSNFOU 5â&#x20AC;&#x201C;7 4LJO UFBST PGUFO DBO CF NJTUBLFO GPS TUBHF ** QSFTTVSF VMDFST FTQFDJBMMZ JG UIFZ PDDVS PO UIF CBDL BOE CVUUPDLT IPXFWFS TLJO UFBST EP SKINmed. 2012;10:75â&#x20AC;&#x201C;81

Table I. Prevention of Skin Tears

DON â&#x20AC;&#x2122; T

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3&7*&8

March/April 2012

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CASE 2: STAGE IV PRESSURE ULCER AND FEVER É¨F XPVOE DBSF UFBN XBT BTLFE UP TFF B ZFBS PME XPNBO SFHBSEJOH B TUBHF *7 QSFTTVSF VMDFS BOE GFWFS 4IF IBE B TJHOJÃ« DBOU NFEJDBM IJTUPSZ PG EJBCFUFT NFMMJUVT BOE FOE TUBHF SFOBM EJT FBTF PO IFNPEJBMZTJT É¨F XPVOE EFWFMPQFE BU IPNF XIFO TIF SFGVTFE UP QBSUJDJQBUF JO SFIBCJMJUBUJWF UIFSBQZ BGUFS IFS GFNPSBM GSBDUVSF XIJDI PDDVSSFE BU MFBTU NPOUIT QSJPS UP IFS BENJTTJPO UP UIF TIPSU UFSN SFIBCJMJUBUJWF GBDJMJUZ É¨F QBUJFOU XBT OPU BEIFS FOU UP IFS SFIBCJMJUBUJWF SFHJNFO TUBUJOH TIF XBT UPP UJSFE 5P BEESFTT UIJT IFS TFEBUJOH NFEJDBUJPOT XFSF SFEVDFE CZ UIF HFSJ BUSJDJBO BOE IFS EJBMZTJT SFHJNFO XBT PQUJNJ[FE CZ UIF OFQISPMP HJTU UP DVSUBJM MPX CMPPE QSFTTVSFT 4IF DPOUJOVFE OPU UP FOHBHF JO UIFSBQZ BOE UIF QBUJFOU JOTJTUFE PO TJUUJOH VQ JO CFE PS JO B DIBJS

Table II. Venous Ulcer Challenges and Treatments

PROBLEM

APPROACH

&EFNB

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Figure 5: Worsening arterial ulcers. Photo courtesy of E. Foy White-Chu, MD. 8PVOE $BSF JO B 4QFDJBM 1PQVMBUJPO

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Belowitz DR, Brandeis GH, Anderson J, Du W, Brand H. Effect of presTVSF VMDFST PO UIF TVSWJWBM PG MPOH UFSN DBSF SFTJEFOUT J Gerontol A Biol Sci Med Sci. 1997;52:M106â&#x20AC;&#x201C;M110.

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$FOUFST GPS .FEJDBSF .FEJDBJE 4FSWJDFT IUUQ XXX DNT HPW %BUB $PNQFOEJVN @ @%BUB@$PNQFOEJVN BTQ 5PQ0G1BHF7 6UJMJ[BUJPO ;JQ%SJWF 6UJMJ[BUJPO5BCMF7 Ã¥OBM QEG "DDFTTFE +VMZ

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3PCFSUT .+ 1SFWFOUJOH BOE NBOBHJOH TLJO UFBST B SFWJFX J Wound Ostomy Continence Nurs. 2007;34:256â&#x20AC;&#x201C;259.

8JQLF 5FWJT %% 3BOU[ .+ .FIS %3 FU BM 1SFWBMFODF JODJEFODF NBOBHFNFOU BOE QSFEJDUPST PG WFOPVT VMDFST JO UIF MPOH UFSN DBSF QPQVMBtion using MDS. Adv Skin Wound Care. 2000;13:218â&#x20AC;&#x201C;224.

,BO ., %FMJT ,5 )FNPEZOBNJD FGGFDUT PG TVQFSWJTFE DBMG NVTDMF FYFSDJTF JO QBUJFOUT XJUI WFOPVT MFH VMDFSBUJPO B QSPTQFDUJWF DPOUSPMMFE study. Arch Surg. 2001;136:1364â&#x20AC;&#x201C;1369.

10 :BOH % 7BOEPOHFO :, 4UBDFZ .$ &GGFDU PG FYFSDJTF PO DBMG NVTDMF QVNQ GVODUJPO JO QBUJFOUT XJUI DISPOJD WFOPVT EJTFBTF Br J Surg. 1999;86:338â&#x20AC;&#x201C;341. 11 ,SBTOFS % 1BJOGVM WFOPVT VMDFST UIFNFT BOE TUPSJFT BCPVU UIFJS JNQBDU PO quality of life. Ostomy Wound Manage. 1998;44:38â&#x20AC;&#x201C;49. 12 1FSTPPO " )FJOFO .. WB EFS 7MFVUFO $+ FU BM -FH VMDFST B SFWJFX PG their impact on daily life. J Clin Nurs. 2004;13:341â&#x20AC;&#x201C;354. 13 .PGGBUU $+ .D$VMMBHI - 0 $POOPS 5 FU BM 3BOEPNJ[FE USJBM PG GPVS MBZFS BOE UXP MBZFS CBOEBHF TZTUFNT JO UIF NBOBHFNFOU PG DISPOJD WFOPVT ulceration. Wound Repair Regen. 2003;11:166â&#x20AC;&#x201C;171. 14 'MFUDIFS " $VMMVN / 4IFMEPO 5" " TZTUFNBUJD SFWJFX PG DPNQSFTTJPO USFBUNFOU GPS WFOPVT MFH VMDFST BMJ. 1997;315:576â&#x20AC;&#x201C;580. 15 4JCCBME 3( "MBWJ " /PSUPO - #SPXOF "$ $PVUUT 1 $PNQSFTTJPO UIFSBQJFT *O ,SBTOFS %- 3PEFIFBWFS (5 4JCCBME 3( FET Chronic Wound Care: A Clinical Source Book for Healthcare Professionals. 4th ed. Wayne, PA: Health Management Publications, Inc; 2007:481â&#x20AC;&#x201C;488. 16 Romanelli M, Dini V, Willliamson D, et al. Measurement: lower MFH VMDFS WBTDVMBS BOE XPVOE BTTFTTNFOU *O ,SBTOFS %- 3PEFIFBWFS (5 4JCCBME 3( FET Chronic Wound Care: A Clinical Source Book for Healthcare Professionals, Fourth Edition. Wayne, PA: Health Management Publications, Inc; 2007:463â&#x20AC;&#x201C;480. 17 Palfreyman SSJ, Nelson EA, Lochiel R, Michaels JA. Dressings for healing WFOPVT MFH VMDFST Cochrane Database Syst Rev. 2006;(3):CD001103. 18 Second European Consensus Document on chronic critical leg ischemia. Circulation. 1991;84(4 suppl):IV1â&#x20AC;&#x201C;IV26. 19 /BUJPOBM 1SFTTVSF 6MDFS "EWJTPSZ 1BOFM IUUQ OQVBQ PSH "@6" 1SFTT 3FMFBTF QEG "DDFTTFE +VMZ 20 Langemo DK, Brown G. Skin fails too: acute, chronic, and end-stage skin failure. Adv Skin Wound Care. 2006;19:206â&#x20AC;&#x201C;211. 21 1SFTTVSF VMDFST JO "NFSJDB QSFWBMFODF JODJEFODF BOE JNQMJDBUJPOT GPS UIF GVUVSF "O FYFDVUJWF TVNNBSZ PG UIF /BUJPOBM 1SFTTVSF 6MDFS "EWJsory Panel monograph. Adv Skin Wound Care. 2001;14:208â&#x20AC;&#x201C;215. 22 Allman RM, Goode PS, Patrick MM, et al. Pressure ulcer risk facUPST BNPOH IPTQJUBMJ[FE QBUJFOUT XJUI BDUJWJUZ MJNJUBUJPO JAMA. 1995;273:865â&#x20AC;&#x201C;870. 23 #FOOFUU 3( 0 4VMMJWBO + %F7JUP &. FU BM 5IF JODSFBTJOH NFEJDBM NBMQSBDUJDF SJTL SFMBUFE UP QSFTTVSF VMDFST JO UIF 6OJUFE 4UBUFT J Am Geriatr Soc. 2000;48:73â&#x20AC;&#x201C;81. 24 4JCCBME 3( 8JMMJBNTPO % 0STUFE )- FU BM 1SFQBSJOH UIF XPVOE CFEÂ&#x2030; debridement, bacterial balance and moisture balance. Ostomy Wound Manage. 2000;46:14â&#x20AC;&#x201C;22, 24â&#x20AC;&#x201C;28, 30â&#x20AC;&#x201C;35. 25 Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systemic approach to wound management. Wound Rep Reg. 2003;11:1â&#x20AC;&#x201C;28. 26 $PSDPSBO 1+ 6TF JU PS MPTF JUÂ&#x2030;UIF IB[BSET PG CFE SFTU BOE JOBDUJWJUZ West J Med. 1991;154:219â&#x20AC;&#x201C;223.

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March/April 2012 27 Allen C, Glasziou P, Del Mar C. Bed rest: a potentially harmful treatment OFFEJOH NPSF DBSFGVM FWBMVBUJPO Lancet. 1999;354:1229â&#x20AC;&#x201C;1233.

34 )PVBOH &5 (JMNPSF 0+ 3FJE $ 4IBX &+ "CTFODF PG CBDUFSJBM SFTJTUBODF UP QPWJEPOF JPEJOF J Clin Pathol. 1976;29:752â&#x20AC;&#x201C;755.

28 &VSPQFBO 1SFTTVSF 6MDFS "EWJTPSZ 1BOFM BOE /BUJPOBM 1SFTTVSF 6MDFS "EWJTPSZ 1BOFM Treatment of Pressure Ulcers: Quick Reference Guide. 8BTIJOHUPO %$ /BUJPOBM 1SFTTVSF 6MDFS "EWJTPSZ 1BOFM

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29 3FEEZ . (JMM 44 ,BMLBS 43 5SFBUNFOU PG QSFTTVSF VMDFST B TZTUFNBUJD SFWJFX JAMA. 2008;300:2647â&#x20AC;&#x201C;2662.

36 )PMMPXBZ (" "SUFSJBM VMDFST BTTFTTNFOU DMBTTJÃ¥DBUJPO BOE NBOBHFNFOU *O ,SBTOFS %- 3PEFIFBWFS (5 4JCCBME 3( FET Chronic Wound Care: A Clinical Source Book for Healthcare Professionals, Fourth Edition. Wayne, PA: Health Management Publications, Inc; 2007:443â&#x20AC;&#x201C;449.

30 Cullum N, McInnes E, Bell-Syer SEM, Legood R. Support surfaces GPS QSFTTVSF VMDFS QSFWFOUJPO $PDISBOF %BUBCBTF 4ZTU 3FW $% %0* $% QVC 31 Sibbald RG, Woo K, Ayello EA. Increased bacterial burden and infection: the TUPSZ PG /&3%4 BOE 450/&4 Adv Skin Wound Care. 2006;19:447â&#x20AC;&#x201C;461. 32 Drosou A, Falabella A, Kirsner RS. Antiseptics on wounds: an area of DPOUSPWFSTZ Wounds. 2003;15:149â&#x20AC;&#x201C;166.

37 :VFO ,$+ #BLFS /3 3BZNBO ( 5SFBUNFOU PG DISPOJD QBJOGVM EJBCFUJD neuropathy with isosorbide dinitrate spray: a double-blind placeboDPOUSPMMFE DSPTT PWFS TUVEZ Diabetes Care. 2002; 25:1699.

33 ;BNPSB +- $IFNJDBM BOE NJDSPCJPMPHJD DIBSBDUFSJTUJDT BOE UPYJDJUZ PG QPWJEPOF JPEJOF TPMVUJPOT Am J Surg. 1986;151:400â&#x20AC;&#x201C;406.

38 8IFFMBOE 3( (JMDISJTU 38 +S :PVOH $+ +S 5SFBUNFOU PG JTDIFNJD EJHJUBM ulcers with nitroglycerin ointment. J Dermatol Surg Oncol. 1983;9:548.

SELF-TEST REVIEW QUESTIONS W. Clark Lambert, MD, PhD, Section Editor Instructions: For each of the following numbered questions, choose the appropriate lettered response(s). Unless directed to choose only one lettered response, all, some, or none of the responses may be correct.

a. b. c. d. e. 2)

e. f.

CFESBJMT XJUI JOKVSJFT TVTUBJOFE JO IPTQJUBM JOUFOTJWF DBSF facilities. HFSJBUSJD SFDMJOFST XJUI JOKVSJFT TVTUBJOFE JO EPDUPST PGÃ¥DFT BOE XBJUJOH SPPNT HFSJBUSJD SFDMJOFST XJUI JOKVSJFT TVTUBJOFE JO IPTQJUBM JOUFOTJWF DBSF GBDJMJUJFT XIFFMDIBJST XJUI JOKVSJFT TVTUBJOFE JO EPDUPST PGÃ¥DFT and waiting rooms. XIFFMDIBJST XJUI JOKVSJFT TVTUBJOFE JO UIF QBUJFOU T bedroom.

c. d. e.

Which of the following statements regarding treatment of WFOPVT MFH VMDFST JT BSF DPSSFDU (Answer as many as apply.) a. b. c.

Compression is the most important aspect for QSFWFOUJPO &MFWBUJPO JT UIF NPTU JNQPSUBOU BTQFDU GPS USFBUNFOU Arterial disease is not a contraindication for treatment with compression.

elderly patients. patients with diabetes mellitus. QBUJFOUT XJUI OPO DPNQSFTTJCMF WFTTFMT QBUJFOUT XJUI WBTDVMBS DBMDJÃ¥DBUJPOT all of these are correct.

Nitroglycerin patches should be applied: (Answer as many as apply.) a.

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6ODPNQFOTBUFE DPOHFTUJWF IFBSU GBJMVSF JT B DPOUSBJOEJcation for treatment with compression. "O 6OOB CPPU FYFSUT IJHI QSFTTVSF XJUI XBMLJOH POMZ 5ISPNCPFNCPMJD TUPDLJOHT BSF BO FYDFMMFOU DIPJDF GPS compression treatment.

"OLMF CSBDIJBM JOEJDFT "#*T NBZ PWFSFTUJNBUF UIF BNPVOU PG blood flow in: (Choose the single best response.) a. b. c. d. e.

" TLJO UFBS JO BO FMEFSMZ QBUJFOU TIPVME CF FYQFDUFE UP IFBM JO BQQSPYJNBUFMZ (Choose the single best response.) a. b. c. d. e.

5IF NPTU DPNNPO PCKFDU BOE MPDBUJPO BTTPDJBUFE XJUI skin tears in elderly patients are: (Choose the single best response.)

early in management of all symptomatic ulcers in QBUJFOUT PWFS ZFBST PG BHF early in management of all symptomatic ulcers in patients who smoke more than one pack of cigarettes per day. for pain management only. POMZ JO VMDFST DBVTFE CZ OFHBUJWF QSFTTVSF EFWJDFT POMZ JO VMDFST UIBU IBWF CFFO KVEHFE OPU UP IBWF UIF potential to heal.

ANSWERS TO SELF-TEST REVIEW QUESTIONS: 1) e 2) c; 3) a, d, e; 4) e; 5) c, e

'SPN UIF %FQBSUNFOUT PG 1BUIPMPHZ BOE %FSNBUPMPHZ 6.%/+ /FX +FSTFZ .FEJDBM 4DIPPM /FXBSL /+ "EESFTT GPS $PSSFTQPOEFODF 8 $MBSL -BNCFSU .% 1I% 3PPN $ .4# 6.%/+ /+.4 4PVUI 0SBOHF "WFOVF /FXBSL /+ t & NBJM MBNCFSXD!VNEOK FEV

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CORE CURRICULUM Virendra N. Sehgal, MD, Section Editor

Cutaneous Tuberculosis: A Diagnostic Dilemmaâ&#x20AC;&#x201D;Laboratory Inputs Virendra N. Sehgal, MD; Prashant Verma, MD; Sambit N. Bhattacharya, MD; Sonal Sharma, MD; Navjeevan Singh, MD; Nishant Verma, MD Bacterial cultures are the gold standard for diagnosing cutaneous tuberculosis, but there are limitations, despite the advances embracing the innovative technologies, including interferon Îł release assays, enzyme-linked immunoabsorbant assay, and molecular diagnostics, in addition to conventional skin tests and microscopic pathology. The results and their interpretation of cultures are reviewed for use in day-to-day practice.

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MICROSCOPIC PATHOLOGY FINE-NEEDLE ASPIRATION CYTOLOGY

T-SPOT.TB TEST

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A Figure 2. Tuberculosis verrucosa cutis: Section showing marked hyperkeratosis and acanthosis. Epithelioid cell granulomas mixed with neutrophilic abscesses is prominent in the upper dermis (hematoxylin-eosin stain, original magnification Ã&#x2014;40). Inset: hematoxylin-eosin stain, original magnification Ã&#x2014;400.

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B Figure 1. (A) Cohesive epithelioid cell granuloma in an aspirate from a cervical lymph node (May-Grunwald-Giemsa stain, magnification Ã&#x2014;400). (B) Single acid-fast bacillus in a fine-needle aspirate smear from a lymph node (Ziehl-Neelsen stain, magnification Ã&#x2014;400).

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Figure 5. Erythema induratum: Section showing septal pannicultis, vascular damage, neutrophil and macrophage infiltrate in the vessel wall, and thrombosis (hematoxylin-eosin stain, original magnification Ã&#x2014;40). Inset: hematoxylin-eosin stain, original magnification Ã&#x2014;400.

Figure 3. Lupus vulgaris: Section showing epithelioid cell granulomas with conspicuous prominent giant cells extending to mid-dermis along with hyperplastic epithelium depicting hyperkeratosis and acanthosis (hematoxylin-eosin stain, original magnification Ã&#x2014;40). Inset: hematoxylin-eosin stain, original magnification Ã&#x2014;100.

MJPJE DFMMT BOE JOGSFRVFOUMZ -BOHIBO T HJBOU DFMMT BSF TFFO "O PCMJUFSBUJWF HSBOVMPNBUPVT WBTDVMJUJT XJUI Ã«CSJO QSFTFOU JO WFTTFM XBMMT BOE MVNFO JT UZQJDBM

IMMUNOHISTOCHEMISTRY *NNVOPIJTUPDIFNJTUSZ IBT HBJOFE QSPNJOFODF BT B EJBHOPTUJD TVQQMFNFOU "DDPSEJOHMZ UIF QSFTFODF PG M tuberculosis BOUJHFO XBT EFNPOTUSBUFE JO PG UIF DBTFT FYBNJOFE JO B TFSJFT CZ JNNVOPIJTUPDIFNJDBM TUBJOJOH QSPDFEVSFT VTJOH BOUJoM tuberculosis BOUJTFSVN É¨F BOUJHFO DPVME CF EFUFDUFE XJUIJO UIF HJBOU DFMMT BOE BMTP JO BO FYUSBDFMMVMBS MPDBUJPO JOUFSTQFSTFE CFUXFFO UIF NPOPOVDMFBS DFMM JOÃ«MUSBUF *O BOPUIFS TUVEZ JNNVOPIJTUPDIFNJTUSZ XBT VTFE UP EFUFDU UIF TFDSFUFE NZDPCBDUFSJBM BOUJHFO .1# PO GPSNBMJO Ã«YFE UJTTVF CJPQTJFT GSPN TVTQFDUFE UVCFSDVMPVT MZNQI OPEFT É¨JT BOUJHFO IBT OPU CFFO EFUFDUFE JO Figure 4. Lichen scrofulosorum: Section showing perifollicular OPOUVCFSDVMPVT NZDPCBDUFSJB 1PMZNFSBTF DIBJO SFBDUJPO 1$3 epithelioid cell granulomas with relative sparing of arrector pili GPS BNQMJÃ«DBUJPO PG *4 GSPN %/" PCUBJOFE GSPN UIF CJPQmuscle (hematoxylin-eosin stain, original magnification Ã&#x2014;100). TJFT XBT VTFE BT B HPME TUBOEBSE É¨F PCTFSWFE BHSFFNFOU CFUXFFO 1$3 BOE JNNVOPIJTUPDIFNJTUSZ XBT *O BOPUIFS TUVEZ ERYTHEMA INDURATUM OF BAZIN FNQMPZJOH UIF BOUJ #$( JNNVOPTUBJO QPTJUJWF SFTVMUT XFSF É¨SFF PG UIF GPVS NJDSPTDPQJD Ã«OEJOHT OBNFMZ TFQUBM QBOOJDV- SFQPSUFE JO PG DBTFT PG NZDPCBDUFSJBM JOGFDUJPOT TVDI BT MJUJT GBU OFDSPTJT TNBMM MBSHF WFTTFM WBTDVMJUJT BOE QSFTFODF PG 5# MFQSPNBUPVT MFQSPTZ BOE BUZQJDBM NZDPCBDUFSJBM JOGFDUJPOT HSBOVMPNBT BSF DPOTJEFSFE FTTFOUJBM GPS FOUFSUBJOJOH JUT EJBHOP- 3FHVMBS TLJO TUSVDUVSFT DFMMVMBS EFCSJT BOE OFDSPUJD NBUFSJBM XFSF OPU JNNVOP TUBJOFE CZ UIF BOUJ #$( BOUJCPEZ É¨JT TUBJO TJT UIF EFUBJMT PG XIJDI BSF JMMVTUSBUFE JO 'JHVSF DSPTT SFBDUT XJUI NBOZ CBDUFSJB BOE GVOHJ BOE QSPEVDFT NJOJNBM PAPULONECROTIC TUBERCULIDS CBDLHSPVOE TUBJOJOH *O DPODMVTJPO UIF BOUJ #$( JNNVOPTUBJO -FTJPOT TIPX B XFEHF TIBQFE OFDSPTJT PG UIF VQQFS BTQFDU PG NBZ CF QBSUJDVMBSMZ FÃªFDUJWF JO UIF EFUFDUJPO PG PSHBOJTNT XIFO UIF EFSNJT FYUFOEJOH UP BOE JOWPMWJOH UIF FQJEFSNJT &QJUIF- PCTDVSFE CZ B EFOTF SPVOE DFMM JOÃ«MUSBUF BOE NBDSPQIBHFT 26 SKINmed. 2012;10:82â&#x20AC;&#x201C;89

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ISOLATION AND IDENTIFICATION OF M TUBERCULOSIS, IN VITRO CULTURE AND GUINEA PIG INOCULATION

SFDPWFSZ SBUFT PG M tuberculosis CZ CPUI .# DIFL BOE #"$5&$ IBWF CFFO OPUFE CZ PUIFST

IN VITRO RECOVERY OF M 5uberculosis

GUINEA PIG INOCULATION

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HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

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ENZYME-LINKED IMMUNOSORBENT ASSAY

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JO UIFTF QBUJFOUT UJTTVFT XBT TFOTJUJWF BOE TQFDJÃ«D IBWJOH B QPTJUJWF QSFEJDUJWF WBMVF PG BOE OFHBUJWF QSFEJDUJWF WBMVF PG *O BEEJUJPO TFWFSBM BOFDEPUBM SFQPSUT PG UIF VUJMJUZ PG 1$3 JO UIF EJBHOPTJT PG DVUBOFPVT 5# BSF BWBJMBCMF É¨FTF EBUB JOEJDBUF UIBU 1$3 BNQMJÃ«DBUJPO JT VTFGVM GPS EFUFDUJOH É¨F QSFDFEJOH UFTUT TIPVME UIFSFGPSF GPSN B DPNQPOFOU PG UIF M tuberculosis %/" JO GPSNBMJO Ã«YFE UJTTVF TQFDJNFOT BOE UIBU JU CBUUFSZ PG JOWFTUJHBUJPOT DBO CF VTFE UP JODSFBTF EJBHOPTUJD BDDVSBDZ JO QBUJFOUT XIP IBWF B EJBHOPTUJD EJMFNNB

MOLECULAR DIAGNOSIS

É¨F BEWFOU PG NPMFDVMBS EJBHOPTUJDT IBT BEEFE JOOPWBUJWF EJNFOTJPOT UP DVSSFOU QSBDUJDF UIF NBKPSJUZ SFWPMWJOH BSPVOE EFUFDUJPO PG OVDMFJD BDJET %/" BOE 3/" UIBU BSF TQFDJÃ«D UP M tuberculosis CZ 1$3 JODMVEJOH PUIFS BNQMJÃ«DBUJPO UFDIOJRVFT BOE EFUFDUJPO PG NVUBUJPOT JO UIF HFOFT UIBU BSF BTTPDJBUFE XJUI ESVH SFTJTUBOU M tuberculosis CZ FJUIFS TFRVFODJOH PS OVDMFJD BDJE IZCSJEJ[BUJPO M tuberculosis TQFDJFT JEFOUJÃ«DBUJPO CZ 4 S3/" HFOF TFRVFODF BOBMZTJT PMJHPIZCSJEJ[BUJPO BOE TUSBJO UZQJOH BSF JO VTF GPS EJSFDU BOE SBQJE EFUFDUJPO PG NZDPCBDUFSJB BT XFMM BT GPS ESVH TVTDFQUJCJMJUZ QBUUFSO *O DPOUSBTU UP QVMNPOBSZ TBNQMFT 1$3 QFSGPSNFE PO FYUSBQVMNPOBSZ TBNQMFT NBZ CF MFTT TFOTJUJWF EVF UP TNBMM TBNQMF WPMVNF BOE BO JSSFHVMBS EJTQFSTJPO PG UIF PSHBOJTNT JO QBVDJ CBDJMMBSZ TQFDJNFOT

É¨JT JT DPOTJEFSBCMZ TJNQMFS BOE GBTUFS XJUI SFTQFDU UP UIF TUBOEBSE 1$3 UFDIOJRVF IPXFWFS TPNF QSPCMFNT PG TFOTJUJWJUZ XIFO UIF TBNQMFT DPOUBJO TNBMM BNPVOUT PG M tuberculosis %/" NBZ BSJTF *U DPVME CF B VTFGVM NFUIPE GPS BTTFTTJOH USFBUNFOU SFTQPOTF JO QBUJFOUT XJUI 5# 3FBM UJNF 1$3 BTTBZ IBT TIPXO B IJHI EFHSFF PG TQFDJÃ«DJUZ TFOTJUJWJUZ BOE FTQFDJBMMZ SBQJEJUZ PG EFUFDUJPO PG 5# UIF MBUUFS CFJOH B WFSZ JNQPSUBOU GBDUPS JO QBUJFOU NBOBHFNFOU JO UFSNT PG JOJUJBUJOH BQQSPQSJBUF BOUJ UVCFSDVMBS UIFSBQZ

DNA PROBES

É¨F QSFTFODF PG 1$3 JOIJCJUPST FTQFDJBMMZ JO FYUSBQVMNPOBSZ TQFDJNFOT NBZ QSPEVDF GBMTF OFHBUJWF SFTVMUT É¨F JOIFSFOU TFOTJUJWJUZ PG 1$3 NBZ MFBE UP BNQMJÃ«DBUJPO PG OPOTQFDJÃ«D TFRVFODFT BOE DPOUBNJOBOUT DPNQPVOEFE CZ UIF JOBCJMJUZ UP EJÃªFSFOUJBUF CFUXFFO MJWF BOE EFBE PSHBOJTNT 1$3 IBT CFFO GPVOE UP CF UIF NPTU TFOTJUJWF BOE TQFDJÃ«D UFTU GPS UIF EJBHOPTJT PG DVUBOFPVT 5# DPSSPCPSBUFE CZ BOPUIFS TUVEZ JO XIJDI PG MVQVT WVMHBSJT PG 5# WFSSVDPTB DVUJT BOE PG TDSPGVMPEFSNB XFSF GPVOE UP CF 1$3 QPTJUJWF *O BEEJUJPO POF DBTF FBDI PG MJDIFO TDSPGVMPTPSVN BOE FSZUIFNB JOEVSBUVN UFTUFE QPTJUJWF " 1$3 CBTFE BTTBZ GPS M tuberculosis XBT FWBMVBUFE JO GPSNBMJO Ã«YFE UJTTVF TQFDJNFOT UIF UBSHFU GPS UIF BNQMJÃ«DBUJPO CFJOH B TFHNFOU PG *4 JO UIF CBDUFSJBM DISPNPTPNF " UPUBM PG PG UIF TQFDJNFOT TIPXFE HSBOVMPNBUPVT JOÃ¬BNNBUJPO BOE XFSF SFDPWFSFE JO WJUSP PG XIJDI XFSF QPTJUJWF GPS M tuberculosis BOE GPS PUIFS NZDPCBDUFSJB PG TQFDJNFOT EFNPOTUSBUFE "'# 8IFO QFSGPSNFE DPNQBSBUJWFMZ PO B QPTJUJWF DVMUVSF GPS M tuberculosis 1$3 XBT TFOTJUJWF BOE TQFDJÃ«D IBWJOH B QPTJUJWF QSFEJDUJWF WBMVF PG BOE OFHBUJWF QSFEJDUJWF WBMVF PGÎ&#x2030; 1$3 GPS M tuberculosis %/" EPOF PO UJTTVF TBNQMFT XBT QPTJUJWF JO PG QBUJFOUT XIP IBE B DMJOJDBM EJBHOPTJT PG 5# OFHBUJWF GPS BMM UIF QBUJFOUT XJUI OPOUVCFSDVMPVT NZDPCBDUFSJBM JOGFDUJPOT BOE OFHBUJWF GPS BMM QBUJFOUT XIP IBE B EJBHOPTJT PG B EJTFBTF PUIFS UIBO NZDPCBDUFSJBM JOGFDUJPO 8IFO DPNQBSFE XJUI UIF DMJOJDBM EJBHOPTJT PG 5# 1$3 GPS M tuberculosis %/" SKINmed. 2012;10:82â&#x20AC;&#x201C;89

REAL-TIME PCR TECHNIQUE

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RIBOSOMAL RRNA-BASED PROBES *O SFDFOU ZFBST SJCPTPNBM 3/" HFOF SFHJPO IBT CFFO FYUFOTJWFMZ FYQMPSFE GPS EFTJHOJOH TZTUFNT GPS SJCPTPNBM %/" Ã«OHFSQSJOUJOH BOE GPS EFWFMPQNFOU PG QSPCFT BT XFMM BT HFOF BNQMJÃ«DBUJPO BTTBZT GPS WBSJPVT NZDPCBDUFSJBM TQFDJFT JODMVEJOH M tuberculosis, Mycobacterium leprae BOE M avium. É¨FTF QSPCFT BSF UP GPME NPSF TFOTJUJWF UIBO %/" UBSHFUJOH BOE NBZ CF VTFE UP DPOÃ«SN UIF EJBHOPTJT EJSFDUMZ JO UIF DMJOJDBM TQFDJNFOT JO B HPPE QSPQPSUJPO PG DBTFT UIF MPXFTU EFUFDUJPO MJNJU JT BSPVOE PSHBOJTNT "U QSFTFOU UIFTF BSF VTFGVM NBJOMZ GPS SBQJE JEFOUJÃ«DBUJPO PG NZDPCBDUFSJBM JTPMBUFT

GENE AMPLIFICATION METHODS FOR IDENTIFICATION

.PMFDVMBS UFDIOJRVFT NBZ BMTP CF VTFE GPS DPOÃ«SNBUJPO PG UIF JEFOUJUZ PG JTPMBUFT É¨F PSJHJOBM JOPDVMVN OFFET UP CF LFQU JO $VUBOFPVT 5VCFSDVMPTJT

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March/April 2012 NJOE EJĂŞFSFOU TUSBUFHJFT UP JEFOUJGZ UIF JTPMBUFT GSPN DVMUVSFT BOE EJSFDUMZ GSPN UIF DMJOJDBM TQFDJNFOT JODMVEF BNQMJĂŤDBUJPO PG TQFDJĂŤD HFOF SFHJPOT GPMMPXFE CZ IZCSJEJ[BUJPO XJUI TQFDJFT TQFDJĂŤD QSPCFT TFRVFODJOH BOE SFTUSJDUJPO GSBHNFOU MFOHUI QPMZNPSQIJTN 3'-1 BOBMZTJT TVDI BT ITQ L%B HFOF kat( BOE S3/" HFOFT É¨FTF 1$3 3'-1 BTTBZT IFMQ JO UIF RVJDL JEFOUJĂŤDBUJPO PG QBUIPHFOJD NZDPCBDUFSJB JODMVEJOH M tuberculosis GSPN UIF DVMUVSF JTPMBUFT BT XFMM BT EJSFDUMZ GSPN UIF DMJOJDBM TQFDJNFO

10 National Tuberculosis Controllers Association; Centers for Disease Control and Prevention (CDC) Guidelines for the investigation of contacts of persons with infectious tuberculosis. Recommendations from the National Tuberculosis Controllers Association and CDC. MMWR Recomm Rep. 2005;54(RR-15).

ANTITUBERCULAR THERAPY AS A DIAGNOSTIC ADJUNCT

13 Ribeiro S, Dooley K, Hackman J, et al. T-SPOT.TB responses during treatment of pulmonary tuberculosis. BMC Infect Dis. 2009;9:23.

É¨F EJBHOPTJT PG DVUBOFPVT 5# NBZ QPTF B DIBMMFOHF EVF FJUIFS UP B MBDL PG TFOTJUJWJUZ PG DVMUVSF PS UP BO JOBCJMJUZ UP UBLF VQ UIF NPMFDVMBS EJBHOPTUJDT BT B SFTVMU PG MJNJUFE SFTPVSDFT JO EFWFMPQJOH DPVOUSJFT PS UP FRVJWPDBM MBCPSBUPSZ SFTVMUT 5P UIJT FOE B UIFSBQFVUJD USJBM PG UIF ESVH BOUJUVCFSDVMBS USFBUNFOU NBZ CF B WBMJE EJBHOPTUJD NFUIPE JO VODFSUBJO DBTFT PG DVUBOFPVT 5# 'PVS ESVH BOUJUVCFSDVMBS UIFSBQZ DPNQSJTJOH JTPOJB[JE SJGBNQJDJO QZSB[JOBNJEF BOE FUIBNCVUPM NBZ CF TUBSUFE XJUI XFFLT CFJOH BO BEFRVBUF EVSBUJPO UP BTTFTT UIF DMJOJDBM SFTQPOTF *O UIF FWFOU PG BO VOGBWPSBCMF SFTQPOTF FJUIFS UIF EJBHOPTJT TIPVME CF SFDPOTJEFSFE PS UIF QPTTJCJMJUZ PG NVMUJESVH SFTJTUBOU 5# TIPVME CF DPOTJEFSFE 1BUJFOUT XJUI UVCFSDVMJET BOE UIPTF XJUI NJOJNBMMZ BDUJWF EJTFBTF NBZ UBLF MPOHFS UIBO XFFLT UP SFTQPOE "T B SFTVMU JU NBZ CF XPSUIXIJMF UP QSPMPOH UIF UIFSBQFVUJD USJBM JO TVDI DBTFT CFGPSF DPOTJEFSJOH BMUFSOBUJWF EJBHOPTFT

14 Huo FF, Zhang LF, Liu XQ. Sensitivity of interferon-gamma release assay T-SPOT.TB in diagnosing extrapulmonary tuberculosis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009;31:449â&#x20AC;&#x201C;452.

CONCLUSIONS

21 Singal A, Bhattacharya SN. Lichen scrofulosorum: a prospective study of 39 patients. Int J Dermatol. 2005;44:489â&#x20AC;&#x201C;493.

%JBHOPTUJD EJMFNNB DPOUJOVFT UP MPPN MBSHF JO DVUBOFPVT 5# MFBEJOH UP SFRVJTJUJPO PG TFWFSBM MBCPSBUPSZ JOOPWBUJPOT XIJDI BSF SFRVJSFE UP CF NBEF VTF PG EVSJOH JUT EJTDPVSTF

22 Sehgal VN, Sardana K, Bajaj P, Bhattacharya SN. Tuberculosis verrucosa cutis: antitubercular therapy, a well-conceived diagnostic criterion. Int J Dermatol. 2005;44:230â&#x20AC;&#x201C;232.

REFERENCES 1

World Health Organization: The WHO standard tuberculin test 1963. WHO/TB/Tech guide/3, Chahda VK. Tuberculin test. Ind J Â Paed. 2001;68:53â&#x20AC;&#x201C;58.

Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a practical case report and review for the dermatologist. J Clin Aesthet Dermatol. 2009;2:19â&#x20AC;&#x201C;27.

Brown FS, Anderson RH, Burnett JW. Cutaneous tuberculosis. JÂ Am Acad Dermatol. 1982;6:101â&#x20AC;&#x201C;106.

MacGregor RR. Cutaneous tuberculosis. Clin Dermatol. 1995;13:245â&#x20AC;&#x201C;255.

Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a practical case report and review for the dermatologist. J Clin Aesthet Dermatol. 2009;2:19â&#x20AC;&#x201C;27.

Pereira J. Tuberculids. Rev Port Pneumol. 2004;10:97â&#x20AC;&#x201C;105.

Marcoval J, Servitje O, Moreno A, et al. Lupus vulgaris. Clinical, histopathologic, and bacteriologic study of 10 cases. J Am Acad Dermatol. 1992;26:404â&#x20AC;&#x201C;407.

Nakamura RM, Einck L, Velmonte MA, et al. Detection of active tuberculosis by an MPB-64 transdermal patch: a field study. Scand J Infect Dis. 2001;33:405â&#x20AC;&#x201C;407.

Nakamura RM, Velmonte MA, Kawajiri K, et al. MPB64 mycobacterial antigen: a new skin-test reagent through patch method for rapid diagnosis of active tuberculosis. Int J Tuberc Lung Dis. 1998;2:541â&#x20AC;&#x201C;546.

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11 Bocchino M, Chairadonna P, Matarese A, et al. Limited usefulness of QuantiFERON-TB Gold In-Tube for monitoring anti-tuberculosis therapy. Respir Med. 2010;104:1551â&#x20AC;&#x201C;1556. 12 Centers for Disease Control and Prevention. Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium Tuberculosis Infection, United States. MMWR. 2010;59(No.RR-5).

15 DomĂnguez J, De Souza-GalvĂŁo M, Ruiz-Manzano J, et al. T-cell responses to the Mycobacterium tuberculosis-specific antigens in active tuberculosis patients at the beginning, during, and after antituberculosis treatment. Diagn Microbiol Infect Dis. 2009;63:43â&#x20AC;&#x201C;51. 16 Kathuria P, Agarwal K, Koranne RV. The role of fine-needle aspiration cytology and Ziehl Neelsen staining in the diagnosis of cutaneous tuberculosis. Diagn Cytopathol. 2006;34:826â&#x20AC;&#x201C;829. 17 Bezabih M, Mariam DW, Selassie SG. Fine needle aspiration cytology of suspected tuberculous lymphadenitis. Cytopathology. 2002;13:284â&#x20AC;&#x201C; 290. 18 Elder DE, Elenitsas R, Ioffreda MD, et al. Atlas and Synopsis of Leverâ&#x20AC;&#x2122;s Histopathology of the Skin. 2nd ed. Philadelphia, PA: Lipincott Willams & Wolters Kluwer; 2007:230. 19 Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol. 2007;25:173â&#x20AC;&#x201C;180. 20 Baek SE, Kang WH, Lee KH. Tuberculosis cutis orificialis. Korean J Dermatol. 1985;23:667â&#x20AC;&#x201C;671.

23 Sehgal VN. Lichen scrofulosorum: current status. Int J Dermatol. 2005;44:521â&#x20AC;&#x201C;523. 24 Padmavathyi L, Rao LL, Ramanadhan, et al. Mycobacterial antigen in tissues in diagnosis of cutaneous tuberculosis. Indian JÂ Tuberc. 2005;52:31â&#x20AC;&#x201C;35. 25 Mustafa T, Wiker HG, Mfinanga SG, et al. Immunohistochemistry using a Mycobacterium tuberculosis complex specific antibody for improved diagnosis of tuberculous lymphadenitis. Mod Pathol. 2006;19:1606â&#x20AC;&#x201C; 1614. 26 Kutzner H, Argenyi ZB, Requena L, et al. A new application of BCG antibody for rapid screening of various tissue microorganisms. J Am Acad Dermatol. 1998;38:56â&#x20AC;&#x201C;60.

27 FariĂąa MC, Gegundez MI, PiquĂŠ E, et al. Cutaneous tuberculosis: a clinical, histopathologic, and bacteriologic study. J Am Acad Dermatol. 1995;33:433â&#x20AC;&#x201C;440. 28 Brown FS, Anderson RH, Burnett JW. Cutaneous tuberculosis. JÂ Am Acad Dermatol. 1982;6:101â&#x20AC;&#x201C;106. 29 API TB Consensus Guidelines 2006: Management of pulmonary tuberculosis, extra-pulmonary tuberculosis and tuberculosis in special situations. J Assoc Physicians India. 2006;54:219â&#x20AC;&#x201C;234. 30 Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med. 2000;161:1376â&#x20AC;&#x201C;1395.

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March/April 2012 31 Aggarwal P, Singal A, Bhattacharya SN, et al. Comparison of the radiometric BACTEC 460 TB culture system and Löwenstein-Jensen medium for the isolation of mycobacteria in cutaneous tuberculosis and their drug susceptibility pattern. Int J Dermatol. 2008;47:681–687. 32 Tortoli E, Cichero P, Piersimoni C, et al. Use of BACTEC MGIT 960 for recovery of mycobacteria from clinical specimens: multicenter study. J Clin Microbiol. 1999;37:3578–3582. 33 Piersimoni C, Scarparo C, Cichero P, et al. Multicenter evaluation of the MB-Redox medium compared with radiometric BACTEC system, mycobacteria growth indicator tube (MGIT), and Löwenstein-Jensen medium for detection and recovery of acid-fast bacilli. Diagn Microbiol Infect Dis. 1999;34:293–299. 34 Luquin M, Gamboa F, Barcelo MG, et al. Comparison of a biphasic non radiometric system with Lowenstein Jensen and BACTEC 460 system for recovery of mycobacteria from clinical samples. Tuber Lung Dis. 1996;77:449–453. 35 Piersimoni C, Morbiducci V, De Sio G, et al. Comparative evaluation of the MB-check system for recovery of mycobacteria from clinical specimens. Eur J Clin Microbiol Infect Dis. 1992;11:1174–1177. 36 Abe C, Hosojima S, Fukasawa Y, et al. Comparison of MB chek, BACTEC and egg-based media for recovery of mycobacteria. J Clin Microbiol. 1992;30:878–881. 37 Pallen MJ. The inoculation of tissue specimens into guinea-pigs in suspected cases of mycobacterial infection does it aid diagnosis and treatment? Tubercle. 1987;68:51–57. 38 Peluffo G, de Kantor IN. Bacteriologic diagnosis of extrapulmonary tuberculosis in a general hospital. Rev Argent Microbiol. 1982;14:91–96. 39 Schneider JW, Jordaan HF, Geiger DH, et al. Erythema induratum of Bazin. A clinicopathological study of 20 cases and detection of Mycobacterium tuberculosis DNA in skin lesions by polymerase chain reaction. Am J Dermatopathol. 1995;17:350–356. 40 Hasegawa N, Miura T, Ishii K, et al. New simple and rapid test for culture confirmation of Mycobacterium tuberculosis complex: a multicenter study. J Clin Microbiol. 2002;40:908–912. 41 Jost KC, Chiu SH, Kenney TM, et al. American Society for Microbiology. General Meeting. Identification and quantitation of Mycobacterium tuberculosis directly from clinical specimens by fluorescence detection highperformance liquid chromatography. Abstr Gen Meet Am Soc Microbiol. 1997;97:568. 42 Charpin D, Herbault H, Gevaudan MJ, et al. Value of ELISA using A 60 antigen in the diagnosis of active pulmonary tuberculosis. Am Rev Respir Dis. 1990;142:380–384. 43 Arya L, Koranne RV, Deb M. Cutaneous tuberculosis in children a clinicomicrobiological study. Indian J Dermatol Venereol Leprol. 1999;65:137– 139. 44 Rao L, Padmavathy L. Utility of MycoDot test in the diagnosis of cutaneous tuberculosis. Indian J Dermatol Venereol Leprol. 2003;69:428–429. 45 Balasingham SV, Davidsen T, Szpinda I, et al. Molecular diagnostics in tuberculosis: basis and implications for therapy. Mol Diagn Ther. 2009;13:137–151.

46 Honoré-Bouakline S, Vincensini JP, Giacuzzo V, et al. Rapid diagnosis of extrapulmonary tuberculosis by PCR: impact of sample preparation and DNA extraction. J Clin Microbiol. 2003;41:2323–2329. 47 Cheng VC, Yew WW, Yuen KY. Molecular diagnostics in tuberculosis. Eur J Clin Microbiol Infect Dis. 2005;24:711–720. 48 Abdalla CM, de Oliveira ZN, Sotto MN, et al. Polymerase chain reaction compared to other laboratory findings and to clinical evaluation in the diagnosis of cutaneous tuberculosis and atypical mycobacteria skin infection. Int J Dermatol. 2009;48:27–35. 49 Padmavathy L, Rao L, Veliath A. Utility of polymerase chain reaction as a diagnostic tool in cutaneous tuberculosis. Indian J Dermatol Venereol Leprol. 2003;69:214–216. 50 Salian NV, Rish JA, Eisenach KD, et al. Polymerase chain reaction to detect Mycobacterium tuberculosis in histologic specimens. Am J Respir Crit Care Med. 1998;158:1150–1155. 51 Ortu S, Molicotti P, Sechi LA, et al. Rapid detection and identification of Mycobacterium tuberculosis by Real Time PCR and Bactec 960 MIGT. New Microbiol. 2006;29:75–80. 52 Katoch VM. Newer diagnostic techniques for tuberculosis. Indian J Med Res. 2004;120:418-428. 53 Katoch VM, Kanaujia GV, Shivannavar CT, et al. Progress in developing ribosomal RNA and rRNA gene(s) based probes for diagnosis and epidemiology of infections diseases specially leprosy. In: Sushil Kumar, Sen AK, Dutta GP, Sharma RN, eds. Tropical Diseases—Molecular Biology and Control Strategies. 1st ed. New Delhi, India: Council for Scientific and Industrial Research; 1994:581–587. 54 Roth A, Reischl U, Streubel A, Naumann L, et al. Novel diagnostic algorithm for identification of mycobacteria using genus specific amplification of 16S-23S rRNA gene spacer and restriction endonucleases. J Clin Microbiol. 2000;38:1094–1104. 55 Sehgal VN, Sardana K, Bajaj P, et al. Tuberculosis verrucosa cutis: antitubercular therapy, a well-conceived diagnostic criterion. Int J Dermatol. 2005;44:230–232. 56 Sehgal VN, Sardana K, Sehgal R, et al. The use of anti-tubercular therapy (ATT) as a diagnostic tool in pediatric cutaneous tuberculosis. Int J Dermatol. 2005;44:961–963. 57 Ramam M, Mittal R, Ramesh V. How soon does cutaneous tuberculosis respond to treatment? Implications for a therapeutic test of diagnosis. Int J Dermatol. 2005;44:121–124. 58 Sehgal VN, Sardana K, Sharma S. Inadequacy of clinical and/or laboratory criteria for the diagnosis of lupus vulgaris, re-infection cutaneous tuberculosis: fallout/implication of 6 weeks of anti-tubular therapy (ATT) as a precise diagnostic supplement to complete the scheduled regimen. J Dermatolog Treat. 2008;19:164–167.

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PERILS OF DERMATOPATHOLOGY W. Clark Lambert, MD, PhD, Section Editor

Sometimes It Takes Darkness to See the Light: Pitfalls in the Interpretation of Cell Proliferation Markers (Ki-67 and PCNA) Carmen Castilla, BS;1 Patrick McDonough, BA;1 Gizem Tumer, MD;2 Peter C. Lambert, BA, MS;3 W.Â Clark Lambert, MD, PhD2 â&#x20AC;&#x153;[Clarity], like a photograph, develops in the dark.Â&#x2030;:PVTVG ,BSTI

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Figure 1. (A) Multiple nests of melanocytes are shown in malignant melanoma. (B) Ki-67 immunostain showing increased reactivity. Black arrowhead indicates a melanin pigment. Red arrowheads indicate increased Ki-67 labeling in or above the basal layer, indicative of cell proliferation or of ultraviolet exposure within the previous 24 hours. Full black arrows indicate a hypocellular dermis, indicative of long term ultraviolet exposure.

Figure 3. DNA replication fork illustrating DNA synthesis along the leading and lagging strand. Proliferating cell nuclear antigen (PCNA) is shown in pink acting as a clamp to secure polymerase delta (shown in green) and polymerase epsilon (shown in teal) to the DNA strand, allowing for greater efficiency of nucleotide addition.

Figure 2. /PSNBM TLJO BEKBDFOU UP UIF NFMBOPDZUJD MFTJPO showing increased Ki-67 proliferation index above the basal layer (arrowheads) due to ultraviolet exposure.

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carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma. Histopathology. 2005;46:614â&#x20AC;&#x201C;621. 6

Chen GS, Wu TM, Yang SA, Yu HS. Quantitative assessments of physiological and biological parameters in psoriatic lesions and its correlations to the clinical severity of psoriasis. Kaohsiung JÂ Med Sci. 2001;17:408â&#x20AC;&#x201C;418.

Yazici AC, Tursen U, Apa DD, et al. The changes in expression of icam-3, ki-67, pcna, and cd31 in psoriatic lesions before and after methotrexate treatment. Arch Dermatol Res. 2005;297:249â&#x20AC;&#x201C;255.

#PWFOTDIFO )+ 0UFSP .& -BOHFXPVUFST ". FU BM 0SBM SFUJnoic acid metabolism blocking agent rambazole for plaque psoriasis: an immunohistochemical study. Br J Dermatol. 2005;156: 263â&#x20AC;&#x201C;270.

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CONCLUSIONS %FSNBUPQBUIPMPHJTUT NVTU CF BXBSF PG UIF QPTTJCJMJUZ PG VQSFHVMBUJPO PG ,J BOE 1$/" GPMMPXJOH 67 FYQPTVSF É¨JT FMFWBUJPO DBO MFBE UP JODPSSFDU UVNPS HSBEJOH PS QTPSJBTJT SBUJOH BOE TVCTFRVFOU QSPKFDUFE QSPHOPTJT *O BO JEFBM TFUUJOH QBUJFOUT TIPVME BWPJE 67 FYQPTVSF CFGPSF UIF CJPQTZ PG B TVTQFDUFE DVUBOFPVT NBMJHOBODZ IPXFWFS UIJT JT OPU BMXBZT QSBDUJDBM 8F SFDPNNFOE UIBU DMJOJDJBOT SPVUJOFMZ BTL QBUJFOUT BCPVU UIFJS SFDFOU 67 FYQPTVSF CFGPSF B TLJO CJPQTZ BOE SFQPSU UIJT JOGPSNBUJPO UP UIF EFSNBUPQBUIPMPHJTU UP BWPJE NJTJOUFSQSFUBUJPO PG ,J BOE PS 1$/" MFWFMT REFERENCES 1

Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311â&#x20AC;&#x201C;322.

Duchrow M, Schluter C, Wholenberg C, Flad HD, Gerdes J. Molecular characterization of the gene locus of the human cell proliferationassociated nuclear protein defined by monoclononal antibody Ki-67. Cell Prolif. 1996;29:1â&#x20AC;&#x201C;12.

Schmidt M, Broll R, Bruch H, Duchrow M. Proliferation marker pKi-67 affects the cell cycle in a self regulated manner. J Cell Biochem. 2002;87:334â&#x20AC;&#x201C;341.

10 3VEPMQI 1 5SPOOJFS . .FO[FM 3 .PMMFS . 1BSXBSFTDI 3 &OIBODFE expression of Ki-67, topoisomerase IIalpha, PCNA, p53 and p21WAF1/ Cip1 reflecting proliferation and repair activity in UV-irradiated melanocytic nevi. Hum Pathol. 1998;29:1480â&#x20AC;&#x201C;1487. 11 Overmeer RM, Gourdin AM, Giglia-Mari A, et al. Replication factor C recruits DNA polymerase delta to sites of nucleotide excision repair but is not required for PCNA recruitment. Mol Cell Biol. 2010;30: 4828â&#x20AC;&#x201C;4839. 12 .PPS +0 1BMFQ 43 4BMBEJ 3/ FU BM &GGFDUT PG VMUSBWJPMFU # FYQPTVSF on the expression of proliferating cell nuclear antigen in murine skin. Photochem Photobiol. 2004;80:587â&#x20AC;&#x201C;595. 13 #BVN )1 .FVSFS * 6OUFSFHHFS ( &YQSFTTJPO PG QSPMJGFSBUJPO BTTPDJBUFE proteins (proliferating cell nuclear antigen and Ki-67 antigen) in Bowenâ&#x20AC;&#x2122;s disease. Br J Dermatol. 1994;131:231â&#x20AC;&#x201C;236.

Soyer HP. Ki 67 immunostaining in melanocytic skin tumors. Correlation with histological parameters. J Cutan Pathol. 1991;18:264â&#x20AC;&#x201C;272.

'FSOBOEF[ 'JHVFSBT .5 1VJH - .VTVMFO & FU BM 1SPHOPTUJD TJHOJĂĽDBODF of p27kip1, p45skp2 and Ki67 expression profiles in Merkel cell

14 Hall PA, McKee PH, Menage HD, Dover R, Lane DP. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993;8:203â&#x20AC;&#x201C;207. 15 Freudenthal BD. Studies of proliferating cell nuclear antigen and its role in translesion synthesis [PhD dissertation]. Iowa City: University of Iowa; 2010. 16 McDonough P, Castilla C, Tumer G, Lambert WC. Interpretation of Ki-67 stain confounded by patient exposure to ultraviolet radiation prior to skin biopsy. J Euro Acad Venereol Dermatol. [In press.]

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The most common adverse events associated with MINOCIN are nausea, vomiting, and diarrhea. CNS adverse effects may include dizziness, vertigo, and headache. Important Information The most common adverse events associated with MINOCIN are nausea, vomiting, and diarrhea. Central nervous system adverse events including light-headedness, dizziness, or vertigo have been reported with minocycline therapy, but are generally transient in nature. Other adverse events include tinnitus, headache, sedation, and skin pigmentation, particularly on the face and mucous membranes. MINOCIN is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or to any of the components of the product formulation. WARNING: MINOCIN PelletFilled Capsules, like other tetracycline-class antibiotics, can cause fetal harm when administered to a pregnant woman. The use of drugs of the tetracycline class during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of teeth (yellow-gray-brown). Concurrent use of tetracyclines may render oral contraceptives less effective. References: 1. SapadinAN,Fleischmajer R.Tetracyclines:nonantibiotic properties and their clinical implications. JAmAcad Dermatol. 2006;54(2):258-265. 2. Leyden JJ,McGinley KJ,KligmanAM.Tetracycline and minocycline treatment. Arch Dermatol. 1982;118(1):19-22. 3. Hubbell CG,Hobbs ER,RistT,White JW Jr.Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris. Arch Dermatol.1982;118(12):989-992. *In vitro activity does not necessarily correlate to in vivo activity. ©2010 Triax Pharmaceuticals, LLC

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INFECTIOUS DISEASE CAPSULES Jack M. Bernstein, MD, Section Editor

The Lion Is NOT Sleeping Tonight David R. Carr, MD;1,4 Jack M. Bernstein, MD;2,3 Julian Trevino, MD1,4

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DVUBOFPVT TJUFT 4PMJUBSZ TIPSU UFSN DPOUBDU XJUI BO JOGFDUFE QBUJFOU JT VTVBMMZ JOTVÃ¯DJFOU GPS USBOTGFS PG UIF CBDJMMVT É¨F SJTL PG JOGFDUJPO JO UIF HFOFSBM QPQVMBUJPO IBT CFFO BQQSPYJNBUFE BU XIFSFBT JU JODSFBTFT UP JO JOEJWJEVBMT XIP IBWF MPOH UFSN DMPTF DPOUBDU XJUI JOGFDUFE QFSTPOT 4 5

"MUIPVHI MFQSPTZ IBT B XPSMEXJEF EJTUSJCVUJPO JU JT NPTU QSFWBMFOU JO *OEJB #SB[JM UIF %FNPDSBUJD 3FQVCMJD PG $POHP 5BO[BOJB /FQBM .P[BNCJRVF .BEBHBTDBS "OHPMB BOE UIF $FOUSBM "GSJDBO 3FQVCMJD 1 2 *O UIF 6OJUFE 4UBUFT DBTFT PG MFQSPTZ BSF QSJNBSJMZ TFFO JO JNNJHSBOUT BT JO UIF DBTF QSFTFOUFE BMUIPVHI NVMUJQMF DBTFT BSF SFQPSUFE JO JOEJWJEVBMT OBUJWF UP UIF 6OJUFE 4UBUFT É¨F /BUJPOBM )BOTFO T %JTFBTF 3FHJTUSZ SFQPSUFE DBTFT JO UIF 6OJUFE 4UBUFT JO PG XIJDI XFSF JEFOUJÃ«FE BT JNNJHSBOUT

NBUPVT MFQSPTZ -- BT TFFO JO UIJT DBTF JT UIF DMJOJDBM QSFTFOUBUJPO É¨F CPSEFSMJOF GPSNT PG UIF EJTFBTF EFOPUF UIF TQFDUSVN PG JNNVOPMPHJD SFTQPOTFT CFUXFFO UIF QVSFMZ DFMM NFEJBUFE BOE BOUJCPEZ NFEJBUFE SFTQPOTFT TFFO JO 55 BOE -- SFTQFDUJWFMZ

DIAGNOSIS -FQSPTZ JT B EJÃ¯DVMU EJBHOPTJT UP NBLF QSJNBSJMZ EVF UP UIF SBSJUZ PG UIJT EJTFBTF JO UIF 6OJUFE 4UBUFT É¨JT TVHHFTUT UIBU B IJHI JOEFY PG TVTQJDJPO JT SFRVJSFE GPS NBLJOH UIF DPSSFDU EJBHOPTJT *U JT JNQPSUBOU GPS UIF QSBDUJUJPOFS UP VOEFSTUBOE UIF SBOHF PG DMJOJDBM NBOJGFTUBUJPOT BOE BWBJMBCMF EJBHOPTUJD UPPMT 8JUI FBSMJFS EFUFDUJPO BQQSPQSJBUF NVMUJESVH UIFSBQZ NBZ CF JOTUJUVUFE BOE NPSCJEJUZ SFEVDFE

CLINICAL PRESENTATION

-FQSPTZ IBT UXP DMBTTJÃ«DBUJPO TZTUFNT É¨F 3JEMFZ +PQMJOH 4ZTUFN EJWJEFT MFQSPTZ JOUP DBUFHPSJFT BDDPSEJOH UP DMJOJDBM BOE IJTUPQBUIPMPHJD Ã«OEJOHT BOE OVNCFS PG CBDUFSJB JO UIF MFTJPOT 5BCMF * XIFSFBT UIF 8PSME )FBMUI 0SHBOJ[BUJPO 8)0 IBT DSFBUFE B NPSF QSBHNBUJD TZTUFN UIBU EJWJEFT MFQSPTZ JOUP UISFF -FQSPTZ )BOTFO T JTFBTF JT B DISPOJD JOGFDUJPVT EJTFBTF DBVTFE HSPVQT QBVDJCBDJMMBSZ TJOHMF MFTJPO QBVDJCBDJMMBSZ MFQCZ UIF CBDJMMVT Mycobacterium leprae *U JT SBSFMZ GBUBM CVU JU JT SPTZ o MFTJPOT BOE NVMUJCBDJMMBSZ MFQSPTZ MFTJPOT BTTPDJBUFE XJUI EJTBCMJOH TFRVFMBF É¨F DISPOJD HSBOVMPNBUPVT É¨F DMJOJDBM NBOJGFTUBUJPOT BSF EFQFOEFOU PO UIF IPTU T JNNVOF JOGFDUJPO QSFGFSFOUJBMMZ BÃªFDUT UIF TLJO BOE QFSJQIFSBM OFSWFT SFTQPOTF UP UIF CBDJMMVT 5VCFSDVMPJE MFQSPTZ 55 PDDVST XIFO É¨F LFZT UP FÃªFDUJWF USFBUNFOU BSF FBSMZ EJBHOPTJT BOE SBQJE DFMM NFEJBUFE JNNVOJUZ QSFWBJMT É¨ DZUPLJOFT IPXFWFS JOTUJUVUJPO PG NVMUJESVH UIFSBQZ JGÎ&#x2030;UIFSF JT QSJNBSJMZ BO BOUJCPEZ SFTQPOTF É¨ DZUPLJOFT MFQSP-

M leprae QSJNBSJMZ BÃªFDUT UIF TLJO BOE QFSJQIFSBM OFSWFT *O -- POF DBO TFF OVNFSPVT QPPSMZ EFÃ«OFE NBDVMFT QBQVMFT PS QMBRVFT QSJNBSJMZ PWFS UIF GBDF EJTUBM FYUSFNJUJFT BOE UIF CVUUPDLT *G UIFSF JT EJÃªVTF JOÃ«MUSBUJPO MFPOJOF GBDJFT DBO CF BQQSF5SBOTNJTTJPO PG UIF EJTFBTF JT QSFEPNJOBOUMZ WJB OBTBM BOE PSBM DJBUFE "EEJUJPOBM DMJOJDBM TJHOT DBO JODMVEF UIJDLFOJOH PG UIF ESPQMFUT GSPN BO JOGFDUFE JOEJWJEVBM BOE MFTT GSFRVFOUMZ GSPN FBSMPCFT MPTT PG UIF FZFMBTIFT BOE FZFCSPXT NBEBSPTJT MPXFS From Medical1 and Research2 Services, VA Medical Center, Dayton, OH; and the Department of Medicine3 and the Department of Dermatology,4 Boonshoft School of Medicine, Wright State University, Dayton, OH "EESFTT GPS $PSSFTQPOEFODF +VMJBO 5SFWJOP .% 0OF &MJ[BCFUI 1MBDF 4VJUF %BZUPO 0) t & NBJM KVMJBO USFWJOP!XSJHIU FEV

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Figure 2. Multiple, 2â&#x20AC;&#x201C;8 mm dermal papules over the dorsal surface of the feet.

Figure 1. Multiple, 2â&#x20AC;&#x201C;8 mm dermal papules over the ears.

FYUSFNJUZ FEFNB BOE BDRVJSFE JDIUIZPTJT PG UIF MPXFS FYUSFNJUJFT *O 55 UIFSF JT B TJOHMF PS WFSZ GFX MFTJPOT É¨FZ BSF XFMM EFÃ«OFE FSZUIFNBUPVT UP IZQPQJHNFOUFE NBDVMFT PS QMBRVFT XJUI B SBJTFE FEHF UIF QSFGFSSFE TJUF GPS CJPQTZ 0GUFO UIF MFTJPOT BSF IBJSMFTT XJUI IZQFTUIFTJB PS BOFTUIFTJB /FVSBM JOWPMWFNFOU DBO SFTVMU JO TFOTPSZ NPUPS BOE BVUPOPNJD JNQBJSNFOU (SBOVMPNBUPVT JOÃ¬BNNBUJPO DBO MFBE UP QBMQBCMF UIJDLFOJOH PG UIF OFSWFT NPTU DPNNPOMZ UIF QPTUFSJPS UJCJBM OFSWF 7 É¨FTF QBMQBCMF OFSWFT DBO CF QBJOGVM BOE BSF BU BO JODSFBTFE SJTL PG CFDPNJOH EBNBHFE 4FRVFMBF PG OFSWF JOWPMWFNFOU BSF TJNJMBS UP UIPTF TFFO JO BOZ QFSJQIFSBM OFVSPQBUIZ JODMVEJOH USBVNBUJD VMDFSBUJPO BOE JOGFDUJPO "OPUIFS NBOJGFTUBUJPO PG MFQSPTZ JT UZQF * BOE UZQF ** SFBDUJPOT .PTU DPNNPOMZ TFFO BGUFS CFHJOOJOH BOUJNJDSPCJBM UIFSBQZ UIFZ BSF BMTP TFFO XJUI TUSFTTPST TVDI BT JOGFDUJPOT BOE QSFHOBODZ 5ZQF Figure 3. *OEVSBUFE QMBRVFT PWFS UIF GPSFIFBE XJUI NPEFSBUF * SFBDUJPOT PS SFWFSTBM SFBDUJPOT PDDVS XIFO UIF JNNVOPMPHJD MPTT PG UIF FZFCSPXT SFTQPOTF UP M leprae DIBOHFT JF GSPN B DFMM NFEJBUFE É¨ UP B IVNPSBM É¨ SFTQPOTF PS WJDF WFSTB .PTU DPNNPOMZ UIJT NBUPVT QBUJFOUT *U JT QSJODJQBMMZ B DVUBOFPVT TNBMM WFTTFM WBTDVMJQSFTFOUT BT BDVUF JOÃ¬BNNBUJPO JO TLJO MFTJPOT BOE PS OFSWFT UJT DBVTFE CZ BO FYVCFSBOU IVNPSBM SFTQPOTF É¨F NPTU DPNNPO 5ZQF ** SFBDUJPOT BSF QSJNBSJMZ TFFO JO -- BOE CPSEFSMJOF MFQSP- NBOJGFTUBUJPO JT FSZUIFNB OPEPTVN MFQSPTVN É¨FTF QBUJFOUT SKINmed. 2012;10:94â&#x20AC;&#x201C;97

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Table I. Ridley-Jopling Leprosy Classification

CATEGORIES

CLINICAL FINDINGS

NERVE INVOLVEMENT

BACILLI PRESENCE

-FQSPNBUPVT MFQSPTZ

/VNFSPVT QPPSMZ EFÃ«OFE TZNNFUSJD NBDVMFT QBQVMFT OPEVMFT BOE PS EJÃªVTF JOÃ«MUSBUJPO $BO MFBE UP MFPOJOF GBDJFT MPTT PG FZFMBTIFT TBEEMF OPTF BOE PS BDRVJSFE JDIUIZPTJT

â&#x2C6;&#x2019; -FTJPO BOFTUIFTJB .BZ IBWF TZNNFUSJD OFSWF UIJDLFOJOH BOE B TUPDLJOH BOE HMPWF BOFTUIFTJB

.BOZ

#PSEFSMJOF MFQSPNBUPVT

4JNJMBS UP MFQSPNBUPVT MFQSPTZ

+/â&#x2C6;&#x2019; -FTJPO BOFTUIFTJB .BZ IBWF TZNNFUSJD OFSWF .BOZ UIJDLFOJOH

.JE CPSEFSMJOF

.BOZ QPPSMZ EFÃ«OFE QMBRVFT

+/â&#x2C6;&#x2019; -FTJPO BOFTUIFTJB /FSWF NBZ CF UIJDLFOFE UFOEFS

.BOZ

#PSEFSMJOF UVCFSculoid

*OÃ«MUSBUFE QMBRVF XJUI OVNFSPVT TBUFMMJUF MFTJPOT

+ -FTJPO BOFTUIFTJB /FSWF JT VTVBMMZ UIJDLFOFE UFOEFS

'FX

5VCFSDVMPJE MFQSPTZ

0OF PS TFWFSBM XFMM EFÃ«OFE JOÃ«MUSBUFE IBJSMFTT QBQVMFT PS QMBRVFT 0GUFO IZQPQJHNFOUFE

+ -FTJPO BOFTUIFTJB /FSWF JT VTVBMMZ UIJDLFOFE UFOEFS

/POF

*OEFUFSNJOBUF

0OF PS TFWFSBM IZQPQJHNFOUFE NBDVMFT XJUI WBSJBCMF EFÃ«OJUJPO GSPN TVSSPVOEJOH TLJO

+/â&#x2C6;&#x2019; -FTJPO BOFTUIFTJB /FSWF NBZ CF UIJDLFOFE UFOEFS

/POF

IBWF UFOEFS SFE QBQVMFT PS OPEVMFT PWFS UIF GBDF BOE FYUFOTPS DMJOJDBM QSBDUJDF JT NJOJNBM É¨F NBJO EFUSBDUPS JT UIBU JO UIF FYUSFNJUJFT " TFWFSF WBSJBOU PG UIF UZQF ** SFBDUJPO JT -VDJP T QIF- NPTU EJÃ¯DVMU UP EJBHOPTF GPSNT PG MFQSPTZ JF 55 BOE CPSEFSMJOF OPNFOPO EFTDSJCFE BT B OFDSPUJ[JOH WBTDVMJUJT BTTPDJBUFE XJUI UVCFSDVMPJE UIFTF UFTUT EP OPU SFMJBCMZ EFUFDU M leprae. WBTDVMBS UISPNCPTJT BOE TVCTFRVFOU JTDIFNJD OFDSPTJT 9 'JOBMMZ UIF MFQSPNJO PS .JUTVEB UFTU JT QFSGPSNFE CZ JOKFDUJOH IFBU LJMMFE M leprae JOUSBEFSNBMMZ " UFTU SFTVMU JT EFFNFE QPTJDIAGNOSTIC TOOLS É¨F EJBHOPTJT PG MFQSPTZ JT QSJNBSJMZ DMJOJDBM BMUIPVHI NVMUJQMF UJWF XIFO B OPEVMF GPSNT BU UIF JOKFDUJPO TJUF BQQSPYJNBUFMZ UP XFFLT MBUFS JOEJDBUJOH B DFMM NFEJBUFE SFTQPOTF É¨JT UFTU JT JOWFTUJHBUJPOT BSF BWBJMBCMF QPTJUJWF JO 55 BOE CPSEFSMJOF UVCFSDVMPJE MFQSPTZ "MUIPVHI JU *G QPTTJCMF B TLJO CJPQTZ TIPVME BMXBZT CF QFSGPSNFE QSFGFSFOIBT TPNF QSPHOPTUJD WBMVF JU IBT OP EJBHOPTUJD WBMVF BOE JT OPU UJBMMZ GSPN UIF BDUJWF FEHF É¨F UXP NPTU JNQPSUBOU Ã«OEJOHT SPVUJOFMZ QFSGPSNFE PO IJTUPQBUIPMPHJD TUVEZ BSF M leprae JO UIF UJTTVF BOE HSBOVMPNBUPVT JOÃ¬BNNBUJPO BSPVOE UIF OFSWFT 10 É¨F CBDJMMJ BSF NPTU DPNNPOMZ TUBJOFE XJUI UIF 'JUF 'BSBDP UFDIOJRVF BMUIPVHI TREATMENT ;JFIM /FFMTFO BOE 8BEF DBO BMTP CF VTFE "OPUIFS NFBOT GPS É¨F DVSSFOU USFBUNFOU PG MFQSPTZ JT DFOUFSFE PO NVMUJESVH UIFSBQZ JEFOUJGZJOH CBDJMMJ JT TMJU TLJO TNFBST " TNBMM TMJU JT NBEF JO BO *O UIF 6OJUFE 4UBUFT UIF /BUJPOBM )BOTFO T %JTFBTF $MJOJDBM JOWPMWFE BSFB BOE TNFBSFE PO B HMBTT TMJEF É¨F TMJEF JT TUBJOFE $FOUFS JO #BUPO 3PVHF -PVJTJBOB JT BO JNQPSUBOU SFTPVSDF BOE FYBNJOFE GPS CBDJMMJ É¨F TMJU TLJO JT QPTJUJWF JO OFBSMZ IUUQ XXX ISTB HPW IBOTFOT DMJOJDBMDFOUFS IUN *U TFSWFT BT B TPVSDF PG JOGPSNBUJPO BOE NFEJDBUJPOT *O FOEFNJD DPVOUSJFT PG DBTFT PG -- PG CPSEFSMJOF MFQSPTZ BOE PG 55 4 UIF 8)0 TQFBSIFBET UIF FÃªPSU JO EFMJWFSJOH GSFF NVMUJESVH 4FSPMPHJD UFTUJOH GPS M leprae JODMVEFT BOUJQIFOPMJD HMZDPMJQJE * UIFSBQZ UP QBUJFOUT BOUJ 1(* BOUJCPEZ OFPQUFSJO BOE MJQPBSBCJOPNBOOBO "T POF NJHIU FYQFDU UIF MFWFMT PG BOUJ 1(* BOUJCPEJFT BSF IJHIFS É¨F 8)0 SFDPNNFOEBUJPOT PO MFQSPTZ BSF CBTFE PO UIF OVNJO UIF NVMUJCBDJMMBSZ QBUJFOU DPNQBSFE XJUI QBVDJCBDJMMBSZ CFS PG TLJO MFTJPOT BOE CBDJMMJ OPUFE PO FYBNJOBUJPO 5BCMF ** 14 " SFDFOU SFQPSU QSPQPTFE GPMMPXJOH BOUJ 1(* BOUJCPEZ USFOET É¨FTF HVJEFMJOFT BSF DPOUSPWFSTJBM BOE NBOZ TUJMM SFDPNNFOE BOE NBZ CF VTFGVM JO NPOJUPSJOH SFTQPOTF UP USFBUNFOU JO -- NPOUIT PG USFBUNFOU GPS NVMUJCBDJMMBSZ EJTFBTF XIFSFBT DVSQBUJFOUT 11 "EEJUJPOBMMZ TFWFSBM NPMFDVMBS CJPMPHJD UFDIOJRVFT SFOU 8)0 HVJEFMJOFT SFDPNNFOE NPOUIT .VMUJESVH UIFSIBWF CFFO EFWFMPQFE JODMVEJOH NPMFDVMBS QSPCFT UBSHFUJOH CPUI BQZ XBT TUBSUFE JO BGUFS ESVH UIFSBQZ XJUI B TJOHMF BHFOU %/" BOE 3/" PG M leprae BOE QPMZNFSBTF DIBJO SFBDUJPO UFDI- XBT BTTPDJBUFE XJUI EBQTPOF SFTJTUBODF 1 15 "MUIPVHI SFTJTUBODF OJRVFT S3/" BOE S%/" QSPCFT NBZ CF IFMQGVM JO FWBMVBUJOH DPOUJOVFT UP CF B DPODFSO NVMUJESVH UIFSBQZ MFBET UP POMZ SBSF TNFBS OFHBUJWF FWPMWJOH NVMUJCBDJMMBSZ EJTFBTF BOE SFTQPOTF UP USFBUNFOU GBJMVSFT 3FMBQTF SBUFT IBWF CFFO BQQSPYJNBUFE UP USFBUNFOU 12 6OGPSUVOBUFMZ UIF VUJMJUZ PG UIFTF JOWFTUJHBUJPOT JO SBOHF GSPN UP PG QFSTPO ZFBST "EEJUJPOBM BHFOUT SKINmed. 2012;10:94â&#x20AC;&#x201C;97

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REFERENCES

Table II. Multidrug Therapy: World Health Organization Guidelines14

TYPE OF LEPROSY

TREATMENT REGIMEN

TREATMENT DURATION

.VMUJCBDJMMBSZ 3JGBNQJDJO NH FWFSZ MFTJPOT

NPOUI %BQTPOF NH EBJMZ $MPGB[JNJOF NH EBJMZ BOE NH FWFSZ NPOUI

NPOUIT

1BVDJCBDJMMBSZ 3JGBNQJDJO NH FWFSZ o MFTJPOT NPOUI %BQTPOF NH EBJMZ

NPOUIT

1BVDJCBDJMMBSZ 3JGBNQJDJO NH PODF TJOHMF MFTJPO 0Ã¬PYBDJO NH PODF .JOPDZDMJOF NH PODF

0OF EPTF

UIBU BSF BDUJWF BHBJOTU M leprae PUIFS UIBO UIPTF NFOUJPOFE JO 5BCMFÎ&#x2030; ** BSF DMBSJUISPNZDJO BOE Ã¬VPSPRVJOPMPOF BOUJCJPUJDT FTQFDJBMMZ QFÃ¬PYBDJO OPU BWBJMBCMF JO UIF 6OJUFE 4UBUFT 5SFBUNFOU PG UZQF * SFBDUJPOT JT XJUI PSBM QSFEOJTPOF É¨F BJN JT UP EFDSFBTF UIF JOÃ¬BNNBUJPO BOE FZF OFSWF EBNBHF É¨F USFBUNFOU GPS UZQF ** SFBDUJPOT FSZUIFNB OPEPTVN MFQSPTVN JT JNNVOPTVQQSFTTJPO É¨F NPTU DPNNPO UIFSBQZ JT UIBMJEPNJEF UP NH EBJMZ *O TFWFSF SFBDUJPOT QSFEOJTPOF NBZ CF OFFEFE

8BMLFS 4- -PDLXPPE %/+ -FQSPTZ Clin Dermatol. 2007;25: 165â&#x20AC;&#x201C;172.

Global leprosy situation. Wkly Epidemiol Rec. 2005;80:289â&#x20AC;&#x201C;295. 25:165â&#x20AC;&#x201C;172.

Global leprosy situation. Wkly Epidemiol Rec. 2005;80:289â&#x20AC;&#x201C;295.

3BNPT F 4JMWB . EF $BTUSP .$3 .ZDPCBDUFSJBM JOGFDUJPOT *O #PMPH nia J, Jorizzo JL, Rapini RP. Dermatology /FX :PSL /: .PTCZ 1145â&#x20AC;&#x201C;1152.

Canizares O, Harman R, Adriaans B. Leprosy. In: Clinical Tropical Dermatology OE FE #PTUPO ." #MBDLXFMM 4DJFOUJÃ¥D 165â&#x20AC;&#x201C;200.

3JEMFZ %4 +PQMJOH 8) $MBTTJÃ¥DBUJPO PG MFQSPTZ BDDPSEJOH UP JNNVOJUZ Int J Lepr. 1966;34:255â&#x20AC;&#x201C;273.

$SPGU 31 3JDIBSEVT +) /PDIPMMT 1( 4NJUI 8$ /FSWF GVODUJPO impairment in leprosy: design, methodology, and intake status of a QSPTQFDUJWF DPIPSU TUVEZ PG OFX MFQSPTZ DBTFT JO #BOHMBEFTI Lepr Rev. 1999;70:140â&#x20AC;&#x201C;159.

Quismorio FP, Rea T, Chandors, et al. Lucioâ&#x20AC;&#x2122;s phenomenon: an immune complex deposition syndrome in lepromatous leprosy. Clin Immunol Immunopathol. 1978;9:184â&#x20AC;&#x201C;193.

Kaur C, Thami GP, Mohan H. Lucio phenomenon and Lucio leprosy. Clin Exp Dermatol. 2005;30:525â&#x20AC;&#x201C;527.

10 Job CK 3FDFOU IJTUPQBUIPMPHJDBM TUVEJFT JO MFQSPTZ XJUI QBSUJDVMBS reference to early diagnosis and leprous neuropathy. Indian J Lepr. 2007;79:75â&#x20AC;&#x201C;83. 11 Silva EA, Iyer A, Ura S, et al. Utility of measuring serum levels of BOUJ 1(- * BOUJCPEZ OFPQUFSJO BOE $ SFBDUJWF QSPUFJO JO NPOJUPSJOH MFQSPTZ QBUJFOUT EVSJOH NVMUJ ESVH USFBUNFOU BOE SFBDUJPOT Trop Med Int Health. 2007;12:1450â&#x20AC;&#x201C;1458. 12 Kamal R, Dayal R, Katoch VM, Katoch K. Analysis of gene probes and HFOF BNQMJÃ¥DBUJPO UFDIOJRVFT GPS EJBHOPTJT BOE NPOJUPSJOH PG USFBUNFOU in childhood leprosy. Lepr Rev. 2006;77:141â&#x20AC;&#x201C;146.

CONCLUSIONS -FQSPTZ JT B DISPOJD JOGFDUJPO UIBU IBT CFDPNF RVJUF SBSF JO UIF 6OJUFE 4UBUFT UIFSFGPSF UIF QSBDUJUJPOFS NVTU IBWF B IJHI JOEFY PG TVTQJDJPO JO PSEFS UP NBLF UIF BQQSPQSJBUF EJBHOPTJT 8JUI FBSMJFS EFUFDUJPO BOE SBQJE JOEVDUJPO PG NVMUJESVH UIFSBQZ UIF FYUSFNF NPSCJEJUJFT BTTPDJBUFE XJUI MPOH TUBOEJOH JOGFDUJPO DBO CF BWPJEFE

SKINmed. 2012;10:94â&#x20AC;&#x201C;97

13 Scollard DM, Adams LB, Gillis TP, et al. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19:338â&#x20AC;&#x201C;381. 14 8PSME )FBMUI 0SHBOJ[BUJPO SFDPNNFOEFE .%5 SFHJNFOT IUUQ XXX XIP JOU MFQ NEU SFHJNFOT FO JOEFY IUNM "DDFTTFE PO +BOVBSZ 15 World Health Organization. Chemotherapy of leprosy for control programmes. Tech Rep Ser Geneva. 1982:675.

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March/April 2012

PHOTO CAPSULES Ncoza C. Dlova, MBChB, FCDerm, Section Editor

Actinomycetoma Ncoza C. Dlova, MBChB, FCDerm; Anisa Mosam, MBChB, FCDerm

O ZFBS PME CPZ QSFTFOUFE XJUI B NPOUI IJTUPSZ PG 0DDBTJPOBM ESBJOJOH TJOVTFT XFSF PCTFSWFE É¨F QBUJFOU XBT IVNBO BTZNQUPNBUJD NVMUJQMF OPEVMFT QBQVMFT BOE TPNF JNNVOPEFÃ«DJFODZ WJSVT OFHBUJWF 4LJO CJPQTZ BOE GVOHBM DVMUVSF VMDFSBUFE QMBRVFT JOWPMWJOH UIF HSPJO BOE SJHIU GPPU DPOÃ«SNFE BDUJOPNZDFUPNB DBVTFE CZ Norcadia brasiliensis

Figure 2. Actinomycetoma of the groin.

Figure 1. Actinomycetoma of the right foot.

From the Department of Dermatology, Nelson R. Mandela School of Medicine, Durban, South Africa "EESFTT GPS $PSSFTQPOEFODF /DP[B $ %MPWB .#$I# '$%FSN t & NBJM EMPWBO!VL[O BD [B

VINTAGE LABEL

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University of Athens Medical School, Athens, Greece

WORLD CONGRESS

OF COSMETIC

DERMATOLOGY BY THE INTERNATIONAL ACADEMY OF COSMETIC DERMATOLOGY

ATHENS, GREECE JUNE 27-30, 2013 www.wcocd2013.com info@wcocd2013.com Congress Organising Bureau ERASMUS CONFERENCES TOURS & TRAVEL S.A. E-mail: info@wcocd2013.com Website: www.erasmus.gr

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CASE STUDY Vesna Petronic-Rosic, MD, MSc, Section Editor

Malignant Melanoma Arising Within Nevus Spilus Susan L. Karam, BS; Scott M. Jackson, MD " ZFBS PME $BVDBTJBO NBO QSFTFOUFE XJUI B TVTQJDJPVT MFTJPO OFBS UIF MFGU BYJMMB EVSJOH B GVMM TLJO FYBNJOBUJPO UIBU XBT QFSGPSNFE GPS B QSFTFOUBUJPO GPS EFSNBUJUJT É¨F QBUJFOU TUBUFE UIBU IF IBE UIF MFTJPO GPS TFWFSBM EFDBEFT CVU UIBU JU NBZ IBWF CFDPNF NPSF SBJTFE PWFS UIF QBTU GFX NPOUIT )F EJE OPU UIJOL NVDI PG UIF DIBOHFT IPXFWFS CFDBVTF JU XBT UP IJN iKVTU B CJSUINBSL w É¨F QBUJFOU IBE OP QFSTPOBM PS GBNJMZ IJTUPSZ PG NFMBOPNB 0O FYBNJOBUJPO UIF QBUJFOU IBE B DN CZ DN PWBM MJHIU UBO QBUDI TUVEEFE XJUI NVMUJQMF IZQFSQJHNFOUFE NBDVMFT SFHVMBSMZ EJTUSJCVUFE XJUIJO UIF MFTJPO *O BEEJUJPO BU UIF MBUFSBM BTQFDU PG UIF MFTJPO UIF QBUJFOU IBE B DN JSSFHVMBSMZ QJHNFOUFE CMBDL QBQVMF UIBU XBT TVTQJDJPVT GPS NFMBOPNB 'JHVSF " EFFQ TBVDFSJ[BUJPO CJPQTZ PG UIF MFTJPO XBT QFSGPSNFE BOE IJTUPQBUIPMPHJDBM FYBNJOBUJPO SFWFBMFE NBMJHOBOU NFMBOPNB XJUI B #SFTMPX EFQUI PG NN 'JHVSF BOE 'JHVSF *U XBT SFDPNNFOEFE UIBU UIF QBUJFOU IBWF B XJEF MPDBM FYDJTJPO PG UIF CJPQTZ TJUF BOE UIF BEKBDFOU SFNBJOJOH QPSUJPOT PG UIF OFWVT TQJMVT " TFOUJOFM MZNQI OPEF CJPQTZ BOE BO PODPMPHJD FWBMVBUJPO XFSF BMTP QFSGPSNFE É¨F TFOUJOFM MZNQI OPEF CJPQTJFT BT XFMM BT B DPNQVUFE UPNPHSBQIJD TDBO QFSGPSNFE CZ PODPMPHZ TIPXFE OP FWJEFODF PG NFUBTUBUJD EJTFBTF 4JODF UIF QSPDFEVSF UIF QBUJFOU IBT TIPXO OP TJHOT PG EJTFBTF SFDVSSFODF

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Figure 1. Oval tan patch studded with hyperpigmented macules and melanoma at the margin of lesion.

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7JEBVSSJ EF MB $SV[ ) )BQQMF 3 5XP EJTUJODU UZQFT PG TQFDLMFE MFOUJHJ OPVT OFWJ DIBSBDUFSJ[FE CZ NBDVMBS WFSTVT QBQVMBS TQFDLMFT Dermatology o Cohen JH, Minkin W, Frank SB. Nevus spilus. Arch Dermatol. 1970; o

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.FHVFSEJUDIJBO "/ $IFOFZ 35 ,BOF +. SE /FWVT TQJMVT XJUI TZODISP nous melanomas: case report and literature review. JÂ Cutan Med Surg. o

Sigg C, Pelloni F, Schnyder UW. Frequency of congenital nevi, nevi spili BOE DBGĂ? BV MBJU TQPUT BOE UIFJS SFMBUJPO UP OFWVT DPVOU BOE TLJO DPNQMFY JPO JO DIJMESFO Dermatologica o

.D-FBO %* (BMMBHIFS 31 i4VOCVSOw GSFDLMFT DBGĂ? BV MBJU NBDVMFT BOE other pigmented lesions of schoolchildren: the Vancouver Mole Study. J Am Acad Dermatol o

,PQG "8 -FWJOF -+ 3JHFM %4 FU BM 1SFWBMFODF PG DPOHFOJUBM OFWVT like nevi, nevi spili, and cafĂŠ au lait spots. Arch Dermatol o

7BTRVF[ %VWBM + 4PMB ." $POUSFSBT .FKVUP ' FU BM .BMJHOBOU NFMB noma developing in a speckled lentiginous nevus. Int J Dermatol. o

$PSSBEJO .5 ;BUUSB & 'JPSFOUJOP 3 FU BM /FWVT TQJMVT BOE NFMBOPNB case report and review of the literature. J Cutan Med Surg. 2010;14: o

10 4DIBGGFS +7 0SMPX 4+ -B[PWB 3 FU BM 4QFDLMFE MFOUJHJOPVT OFWVT within the spectrum of congenital melanocytic nevi. Arch Dermatol. o 11 4UFSO +# )BVQU ) "BSPOTPO $ .BMJHOBOU NFMBOPNB JO B TQFDLMFE [PT teriform lentiginous nevus. Int J Dermatol o 12 3IPEFT "3 .JIN .$ +S 0SJHJO PG DVUBOFPVT NFMBOPNB JO B DPOHFOJUBM dysplastic nevus spilus. Arch Dermatol o 13 ,VSCBO 3' 1SFGGFS '* 4PCFS "+ FU BM 0DDVSSFODF PG NFMBOPNB JO iEZTQMBTUJDw OFWVT TQJMVT SFQPSU PG DBTF BOE BOBMZTJT CZ Ă˝PX DZUPNFUSZ J Cutan Pathol o 14 8FJOCFSH +. 4DIVU[FS 1+ )BSSJT 3. FU BM .FMBOPNB BSJTJOH JO OFWVT spilus. Cutis o 15 #PMPHOJB +- 'BUBM NFMBOPNB BSJTJOH JO B [PTUFSJGPSN TQFDLMFE MFOUJHJ nous nevus. Arch Dermatol o 16 Haenssle HA, Kaune KM, Buhl T, et al. Melanoma arising in segmental OFWVT TQJMVT EFUFDUJPO CZ TFRVFOUJBM EJHJUBM EFSNBUPTDPQZ J Am Acad Dermatol o 17 1JBOB 4 (FMMJ .$ (SFO[J - FU BM .VMUJGPDBM NFMBOPNB BSJTJOH PO OFWVT spilus. Int J Dermatol o 18 ;FSFO #JMHJO * (Ă S 4 "ZEJO 0 FU BM .FMBOPNB BSJTJOH JO B IBJSZ OFWVT spilus. Int J Dermatol o 19 :POFZBNB , ,BNBEB / .J[PHVDIJ . FU BM .BMJHOBOU NFMBOPNB BOE acquired dermal melanocytosis on congenital nevus spilus. J Dermatol. o 20 #PSSFHP - )FSOBOEF[ 4BOUBOB + #BF[ 0 FU BM /BFWVT TQJMVT BT B QSF cursor of cutaneous melanoma: report of a case and literature review. Clin Exp Dermatol o 21 3Ă UUFO " (PPT . /FWVT TQJMVT XJUI NBMJHOBOU NFMBOPNB JO B QBUJFOU XJUI OFVSPĂĽCSPNBUPTJT Arch Dermatol o 22 8BHOFS 3' +S $PUUFM 8* *O TJUV NBMJHOBOU NFMBOPNB BSJTJOH JO B TQFDLMFE lentiginous nevus. J Am Acad Dermatol o 23 Kaur TD, Kanwar AJ. Giant nevus spilus and centrofacial lentiginosis. Pediatr Dermatol o 24 8BMUPO 3( +BDPCT ") $PY "+ 1JHNFOUFE MFTJPOT JO OFXCPSO JOGBOUT Br J Dermatol o 25 $SBNFS 4' 4QFDLMFE MFOUJHJOPVT OFWVT OFWVT TQJMVT UIF iSPPUTw PG UIF iNFMBOPDZUJD HBSEFO w Arch Dermatol o 26 Cohen LM. Nevus spilus: congenital or acquired? Arch Dermatol. o

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CASE STUDY

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From the Department of Dermatology and Cutaneous Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA Address for Correspondence: Alexis Sheaffer, BS, 1000 Walnut Street, Orlowitz Apartment 609, Philadelphia, PA 19107 t & NBJM BMFYJT TIFBGGFS!HNBJM DPN

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Figure 1. Pseudocyst at the junction of the scaphoid fossa and superior DSVT PG UIF SJHIU BVSJDMF DJSDMF

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Figure 2. -PX NBHOJÃ¥DBUJPO SFWFBMT UIF surface of an intracartilagenous cystic cav ity at the base of the specimen (hematoxy MJO FPTJO PSJHJOBM NBHOJÃ¥DBUJPO Â¨ SKINmed. 2012;10:104â&#x20AC;&#x201C;106

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March/April 2012

CASE STUDY

Necrotic Ulcer: A Manifestation of Leukemia Cutis Ayse Esra Koku Aksu, MD; Zeynep Nurhan Saracoglu, MD; Ilham Sabuncu, MD; Evrim Ciftci, MD; Zafer Gulbas, MD; Serap Isiksoy, MD " ZFBS PME NBO QSFTFOUFE UP PVS EFSNBUPMPHJDBM DMJOJD XJUI B NPOUI IJTUPSZ PG B XPVOE PO IJT MFH )F DPNQMBJOFE PG XFBLOFTT GPS UIF QBTU GFX NPOUIT 0O IJT EFSNBUPMPHJDBM FYBNJOBUJPO IF IBE B Â¨ DN OFDSPUJD VMDFS PO IJT MFGU UJCJB 'JHVSF 0O QIZTJDBM FYBNJOBUJPO UIFSF XBT Â¨ DN BYJMMBSZ MZNQIBEFOPQBUIZ É¨FSF XBT OP PUIFS MZNQI OPEF FOMBSHFNFOU IFQBUPTQMFOPNFHBMZ PS HJOHJWBM IZQFSUSPQIZ 1FSJQIFSBM CMPPE SFTVMUT TIPXFE Â¨ NN MFVLPDZUFT OPSNBM SBOHF o Â¨ NN XJUI OFVUSPQIJMT É¨F IFNPHMPCJO WBMVF XBT H E- o H E- BOE UIF QMBUFMFU DPVOU XBT Â¨ NN o Â¨ NN /P CMBTUT XFSF EFUFDUFE JO B QFSJQIFSBM CMPPE TNFBS )JT MBDUBUF EFIZESPHFOBTF MFWFM XBT 6 - o 6 - "MM PUIFS SFTVMUT PG CMPPE DIFNJTUSZ XFSF XJUIJO OPSNBM MJNJUT 1VODI CJPQTZ PG UIF TLJO MFTJPO TIPXFE VMDFSBUJPO BOE EFOTF EFSNBM BDVUF BOE DISPOJD JOÃ¬BNNBUJPO É¨FSF XBT B TVQFSÃ«DJBM BOE EFFQ QFSJWBTDVMBS BOE QFSJBEOFYBM JOÃ«MUSBUF PG OFPQMBTUJD DFMMT DPNQPTFE PG SFMBUJWFMZ BCVOEBOU FPTJOPQIJMJD DZUPQMBTN BOE MBSHF OVDMFJ XJUI CMBTUJD DISPNBUJO BOE PDDBTJPOBM TNBMM OVDMFPMJ 'JHVSF .JUPUJD Ã«HVSFT XFSF QSPNJOFOU *NNVOPIJTUPDIFNJDBM TUBJOT XFSF QFSGPSNFE BOE UIF OFPQMBTUJD DFMMT XFSF $% $% $% BOE 4 QSPUFJO OFHBUJWF .ZFMPQFSPYJEBTF BOE $% XFSF QPTJUJWF É¨F IJTUPQBUIPMPHJDBM Ã«OEJOHT XFSF DPOTJTUFOU XJUI MFVLFNJD JOÃ«MUSBUJPO &YBNJOBUJPO PG CPOF NBSSPX CJPQTZ SFWFBMFE UIBU UIF CMBTUJD DFMMT DPOTUJUVUFE NPSF UIBO PG UIF CPOF NBSSPX DFMMVMBSJUZ $ZUPHFOFUJD BOBMZTJT PG CPOF NBSSPX BTQJSBUJPO XJUI Ã¬VPSFTDFODF JO TJUV IZCSJEJ[BUJPO XBT OFHBUJWF GPS JOWFSTJPO U BOE U )JTUPDIFNJDBM TUBJOT GPS NZFMPQFSPYJEBTF TVEBO CMBDL QFSJPEJD BDJE 4DIJÃª BOE BMQIB OBQIUIZM BDFUBUF XFSF BMTP OFHBUJWF #MBTUJD DFMMT XFSF %3 $% $% BOE $% QPTJUJWF BOE $% $% $% $% $% $% $% $% $% $% BOE $% OFHBUJWF BDDPSEJOH UP Ã¬PX DZUPNFUSZ JNNVOPQIFOPUZQJOH #MBTUJD DFMMT XFSF JO UIF CPOF NBSSPX #BTFE PO UIF Ã«OEJOHT PG CPOF NBSSPX FYBNJOBUJPO UIF QBUJFOU XBT EJBHOPTFE BT IBWJOH BDVUF NZFMPCMBTUJD MFVLFBNJB ".- XJUI NJOJNBM EJÃªFSFOUJBUJPO TVCUZQF . BDDPSEJOH UP 'SFODI "NFSJDBO #SJUJTI BOE 8PSME )FBMUI 0SHBOJ[BUJPO DMBTTJÃ«DBUJPO 2 É¨F FYBNJOBUJPO PG BCEPNJOBM VMUSBTPOPHSBQIZ BOE UIPSPDJD BOE BCPNJOBM DPNQVUFE UPNPHSBQIZ SFWFBMFE OP NFUBTUBTFT É¨F QBUJFOU XBT USFBUFE XJUI DIFNPUIFSBQZ UIBU DPOTJTUFE PG DZUBSBCJO BOE EBVOPSVCJDJO "GUFS DIFNPUIFSBQZ UIF MFTJPO SFHSFTTFE 0OF NPOUI BGUFS DIFNPUIFSBQZ UIF QBUJFOU QSFTFOUFE UP UIF IPTQJUBM XJUI B DPNQMBJOU PG GFWFS )F XBT EJBHOPTFE XJUI GFCSJMF OFVUSPQFOJB )F EJFE PG DBSEJBD GBJMVSF NPOUIT BGUFS BQQFBSBODF PG TLJO JOÃ«MUSBUJPO

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From the Department of Dermatology, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey Address for Correspondence: Ayse Esra Koku Aksu, MD, Eskisehir Osmangazi University Faculty of Medicine, Department of Dermatology, &TLJTFIJS 5VSLFZ t & NBJM FTSBBLTV!HNBJM DPN

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March/April 2012

CASE STUDY

Inflammatory Linear Verrucous Epidermal Nevus With Genital Involvement Didem Didar Balci, MD;1 JÃ¼lide Zehra Yenin, MD;1 Ebru Ã&#x2021;elik, MD;1 GÃ¶khan Sarikaya, MD;1 Esin Atik, MD2 "O ZFBS PME XPNBO XBT BENJUUFE UP PVS DMJOJD DPNQMBJOJOH PG QSVSJUJD MFTJPOT PO IFS JOHVJOBM BOE HFOJUBM BSFBT UIBU IBE CFFO QSFTFOU TJODF CJSUI 4IF IBE QSFWJPVTMZ VTFE UPQJDBM TUFSPJET BOE B DPNCJOBUJPO PG UPQJDBM TUFSPJET BOE DBMDJQPUSJPM GPS BQQSPYJNBUFMZ NPOUIT IPXFWFS UIF USFBUNFOU XBT VOTVDDFTTGVM )FS NFEJDBM IJTUPSZ XBT VOSFNBSLBCMF 0O EFSNBUPMPHJD FYBNJOBUJPO NJME FSZUIFNBUPVT MJDIFOJÃ«FE BOE WFSSVDPVT QBQVMFT PDDVSSJOH JO B MJOFBS QBUUFSO PO UIF SJHIU JOHVJOBM BSFB BOE PO UIF SFHJPO FYUFOEJOH GSPN UIF SJHIU MBCJVN NBKVT UP UIF QFSJBOBM BSFB XFSF OPUFE 'JHVSF "EEJUJPOBMMZ BO FSZUIFNBUPVT BSFB XJUI DFOUSBM FSPTJPO TVSSPVOEFE CZ NBDFSBUJPO XBT OPUFE PO UIF JOUFSHMVUFBM BSFB 5XP TFQBSBUF QVODI CJPQTZ TBNQMFT XFSF PCUBJOFE GSPN UIF FSZUIFNBUPVT MJDIFOJÃ«FE WFSSVDPVT QBQVMBS MFTJPO PO UIF JOHVJOBM BSFB BOE GSPN UIF FSZUIFNBUPVT FSPEFE NBDFSBUFE MFTJPO PO UIF JOUFSHMVUFBM BSFB )JTUPQBUIPMPHJDBM FYBNJOBUJPO PG CPUI CJPQTZ TQFDJNFOT SFWFBMFE B UIJO PSUIPLFSBUPUJD MBZFS BOE TDBUUFSFE QBSBLFSBUPUJD MBZFST BT XFMM BT QBQJMMPNBUPTJT BOE BDBOUIPTJT PG UIF FQJEFSNJT XJUI B TMJHIU IZQFSQJHNFOUBUJPO PG UIF CBTBM MBZFS " NJME QFSJWBTDVMBS DISPOJD JOÃ¬BNNBUPSZ DFMM JOÃ«MUSBUJPO XBT OPUFE JO UIF EFSNJT #BTFE PO UIF DMJOJDBM BOE IJTUPQBUIPMPHJDBM Ã«OEJOHT UIF QBUJFOU XBT DPOTJEFSFE UP IBWF JOÃ¬BNNBUPSZ MJOFBS WFSSVDPVT FQJEFSNBM OFWVT BOE DSZPUIFSBQZ XBT JOJUJBUFE "U UIF XFFL GPMMPX VQ BGUFS UIF Ã«STU BQQMJDBUJPO JU XBT PCTFSWFE UIBU UIF JUDIJOH DPNQMBJOU EFDSFBTFE TVCTUBOUJBMMZ BOE UIF FSPEFE MFTJPOT JO UIF JOUFSHMVUFBM BSFB XFSF SF FQJUIFMJBMJ[FE 0O DMJOJDBM GPMMPX VQ OP JNQSPWFNFOU XBT PCTFSWFE JO UIF QBQVMBS DPNQPOFOU PG UIF MFTJPO BGUFS TFTTJPOT PG DSZPUIFSBQZ É¨F QBUJFOU WPMVOUBSJMZ EJTDPOUJOVFE UIF GPMMPX VQ BGUFS TFTTJPOT PG DSZPUIFSBQZ

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From the Departments of Dermatology,1 and Pathology,2 Mustafa Kemal University, Hatay, Turkey Address for Correspondence: Didem Didar Balci, MD, Associate Professor, Mustafa Kemal University, Faculty of Medicine, Department of %FSNBUPMPHZ "OUBLZB )BUBZ 5VSLFZ t & NBJM EJEFNBMUJOFS!ZBIPP DPN

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REFERENCES

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Chronic Lymphocytic Leukemia Revealed by a Granulomatous Zosteriform Eruption Sondes Trojjet, MD; Houda Hammami, MD; Inès Zaraa, MD; Alia Bouzguarrou, MD; Meriem Joens, MD; Slim Haouet, MD; Amel Ben Osman, MD; Mourad Mokni, MD " XPSE (SBOVMPNBUPVT JO UIF UJUMF PG UIJT $BTF 4UVEZ XBT JODPSSFDUMZ QSFTFOUFE PO UIF DPWFS SKINmed. 2012;10:112–113

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CASE STUDY

Oral Frictional Hyperkeratosis (Morsicatio Buccarum): An Entity to Be Considered in the Differential Diagnosis of White Oral Mucosal Lesions Kristin Cam, MD;1 Anthony Santoro, MD;2 Jason B. Lee, MD1 " ZFBS PME NBO QSFTFOUFE XJUI EFTRVBNBUJOH MFTJPOT PO IJT CJMBUFSBM CVDDBM NVDPTB JOUFSNJUUFOUMZ GPS BQQSPYJNBUFMZ ZFBST É¨F BMUFSB UJPO JO UFYUVSF XJUIJO IJT NPVUI DSFBUFE BO VODPNGPSUBCMF TFOTBUJPO BOE BU UJNFT UIF MFTJPOT TQPOUBOFPVTMZ QFFMFE BXBZ SFRVJSJOH IJN UP TQJU SFQFBUFEMZ É¨F QBUJFOU EFOJFE BOZ IJTUPSZ PG USBVNB DIFFL CJUJOH PS VTF PG UPCBDDP QSPEVDUT 0O JOJUJBM FYBNJOBUJPO UIF QBUJFOU XBT BTZNQUPNBUJD BOE UIF PSBM NVDPTB IBE OP BCOPSNBM Ã«OEJOHT CVU PO SFQFBU FYBNJOBUJPO XIFO TZNQUPNT XFSF QSFTFOU UIF QBUJFOU IBE TIBHHZ XIJUF QMBRVFT PO UIF CJMBUFSBM CVDDBM NVDPTB MJNJUFE UP UIF MJOF PG EFOUBM PDDMVTJPO 'JHVSF É¨F QMBRVFT DPVME CF FBTJMZ QFFMFE BXBZ GSPN UIF VOEFSMZJOH TLJO XJUI B DPUUPO TXBC XJUIPVU BOZ QBJO MFBWJOH CFIJOE OPSNBM VOEFSMZJOH NVDPTB " SFWJFX PG UIF QSJPS CJPQTZ PG UIF BÃªFDUFE NVDPTB SFWFBMFE BO JSSFHVMBSMZ IZQFSQMBTUJD FQJUIFMJVN XJUI GPDJ PG CBMMPPOFE FQJUIFMJBM DFMMT XJUIJO UIF VQQFS MBZFS QBSBLFSBUPTJT BOE CBDUFSJBM PWFSHSPXUI 'JHVSF .JDSPTDPQJD FYBNJOBUJPO PG GSBHNFOUT PG NVDPTB QFFMFE BXBZ GSPN UIF BÃªFDUFE BSFB SFWFBMFE GSBHNFOUT PG QBSBLFSBUPUJD DPSOJÃ«FE NBUFSJBM DPMPOJ[FE CZ OVNFSPVT CBDUFSJB 'JHVSF 3FTVMUT GSPN QFSJPEJD BDJE 4DIJÃª TUBJO SF WFBMFE OP GVOHBM FMFNFOUT É¨F EJBHOPTJT PG PSBM GSJDUJPOBM IZQFSLFSBUPTJT XBT FTUBCMJTIFE CBTFE PO UIF DMJOJDBM BOE NJDSPTDPQJD Ã«OEJOHT *U XBT DPODMVEFE UIBU UIF IZQFSLFSBUPTJT XBT MJLFMZ DBVTFE CZ CJUF USBVNB PS HSJOEJOH PG UIF UFFUI XIJMF UIF QBUJFOU XBT BTMFFQ 5SJBNDJOPMPOF PJOUNFOU JO 0SBCBTF BOE USFUJOPJO HFM XFSF JOFÃªFDUJWF É¨F QBUJFOU GPVOE UIBU SJOTJOH XJUI IZESPHFO QFSPYJEF TPMVUJPO XBT NPTU IFMQGVM JO SFEVDJOH UIF MFTJPOT " CJUF HVBSE XBT SFDPNNFOEFE CZ BO PSBM BOE NBYJMMPGBDJBM TVSHFPO CVU UIF QBUJFOU IBT ZFU UP VTF JU

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From the Department of Dermatology and Cutaneous Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA;1 and Doylestown Dermatology, Doylestown, PA2 Address for Correspondence: Jason B. Lee, MD, Department of Dermatology and Cutaneous Biology, Jefferson Medical College of Thomas +FGGFSTPO 6OJWFSTJUZ Ã¹$IFTUOVU 4USFFU 4VJUF 1IJMBEFMQIJB 1" t & NBJM KBTPO MFF!KFGGFSTPO FEV

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Figure 3. Swabbed specimen from the buccal mucosa show JOH CBDUFSJB MBEFO JSSFHVMBSMZ TVSGBDFE TIBHHZ QBSBLFSBUPTJT (hematoxylin and eosin stain, original magnification Ã&#x2014;100). *OTFU IJHI QPXFS WJFX IJHIMJHIUJOH UIF CBDUFSJB MBEFO QBSB keratosis (hematoxylin and eosin stain, magnification Ã&#x2014;400).

Figure 2. A biopsy of the lesion showing psoriasiform hyper plasia, surface epithelium with ballooning degeneration,* and parakeratosis colonized by numerous bacteria** (hematoxylin and eosin stain, magnification Ã&#x2014;100).

TJEFT PG UIF UPOHVF 0') IPXFWFS IBT B DIBSBDUFSJTUJD BQQFBS BODF TFUUJOH JU BQBSU GSPN PUIFS PSBM MFTJPOT OBNFMZ SPVHI TIBHHZ TVSGBDF FQJUIFMJVN UIBU FBTJMZ QFFMT PÃª CJMBUFSBMJUZ BOE MPDBUJPO PO NPWBCMF OPOLFSBUJOJ[FE NVDPTB UIBU DBO CF SFBDIFE CZ UIF UFFUI 4 )JTUPQBUIPMPHJDBMMZ 0') JT DIBSBD UFSJ[FE CZ BO JSSFHVMBS TIBHHZ IZQFSQBSBLFSBUPUJD FQJUIF MJVN UIBU JT DPMPOJ[FE PO UIF TVSGBDF CZ CBDUFSJB JOUSBDFM MVMBS FEFNB PS CBMMPPOJOH OFBS UIF TVSGBDF BOE B WBSJBCMF EFHSFF PG BDBOUIPTJT 4

"XBSFOFTT PG UIJT SFMBUJWFMZ DPNNPO BOE CFOJHO DPOEJUJPO PG UIF PSBM NVDPTB XJMM BMMPX GPS HSFBUFS SFDPHOJUJPO PG 0') CBTFE PO DMJOJDBM GFBUVSFT PCWJBUJOH UIF OFFE GPS BO JOWBTJWF CJPQTZ É¨F DMJOJDBM EJBHOPTJT DBO CF DPOÃ«SNFE CZ FYBNJOBUJPO PG EFT RVBNBUJOH UJTTVF PCUBJOFE QBJOMFTTMZ GSPN UIF QBUJFOU XJUI UIF VTF PG B DPUUPO TXBC " CJPQTZ NBZ CF JOEJDBUFE JO DBTFT PG 0') XJUI BUZQJDBM DMJOJDBM GFBUVSFT REFERENCES 1

Obermayer M. Cheekbiting (morsicatio buccarum). Arch Dermatol. 1964;90:185â&#x20AC;&#x201C;190.

"M .PCFFSJFL " "M%PTBSJ " 1SFWBMFODF PG PSBM MFTJPOT BNPOH 4BVEJ EFO tal patients. Ann Saudi Med. 2009;29:365â&#x20AC;&#x201C;368.

Krahl D, Altenburg A, Zouboulis CC. Reactive hyperplasias, precancer ous and malignant lesions of the oral mucosa. J Dtsch Dermatol Ges. 2008;6:217â&#x20AC;&#x201C;232.

Woo S and Lin D. Moriscatio mucosae orisâ&#x20AC;&#x201D;a chronic oral frictional keratosis, not a leukoplakia. J Oral Maxillofac Surg. 2009;67:140â&#x20AC;&#x201C;146.

CONCLUSIONS %FQFOEJOH PO UIF DBVTBUJWF GBDUPST USFBUNFOU NBZ JODMVEF UIF VTF PG B CJUF HVBSE EVSJOH TMFFQ UP QSFWFOU UIF HSJOEJOH PG UFFUI EFOUBM FWBMVBUJPO GPS UIF USFBUNFOU PG SPVHI TIBSQ PS NBMQP TJUJPOFE UFFUI PS PUIFS QTZDIPMPHJDBM UIFSBQZ UP IFMQ CSFBL UIF IBCJU PG CJUJOH

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CASE STUDY

Vesicular Palmoplantar Pityriasis Rosea Varinder Singh, MD;1 Meghna Sharma, MD;1 Tarun Narang, MD;1 Manas Madan, MD2 " ZFBS PME ZPVOH NBO QSFTFOUFE XJUI JOUFOTFMZ JUDIZ FSZUIFNBUPVT EFSNBUJUJT PO UIF CPEZ GPS XFFL BOE WFTJDVMBS MFTJPOT PO UIF QBMNT BOE TPMFT GPS UP EBZT -FTJPOT PO UIF QBMNT BOE TPMFT XFSF BDDPNQBOJFE CZ TFWFSF CVSOJOH BOE JUDIJOH É¨F QBUJFOU HBWF B IJTUPSZ PG TPSF UISPBU BOE GFWFS XFFL QSJPS UP UIF POTFU PG MFTJPOT " HFOFSBM QIZTJDBM FYBNJOBUJPO XBT OPSNBM BOE DVUBOFPVT FYBNJOBUJPO SFWFBMFE NVMUJQMF XFMM EFÃ«OFE FSZUIFNBUPVT TDBMZ QMBRVFT XJUI DPMMBSFU TDBMJOH PO UIF USVOL BOE FYUSFNJUJFT 'JHVSF 7FTJDVMBS MFTJPOT XFSF TFFO PO UIF QBMNT BOE TPMFT 'JHVSF É¨F EJÃªFSFOUJBM EJBHOPTFT XF DPOTJEFSFE XFSF QJUZSJBTJT SPTFB BOE TFDPOEBSZ TZQIJMJT É¨F QPTTJCJMJUZ PG EFSNBUPQIZUJE WFTJDVMBS QJUZSJBTJT SPTFB BOE QPNQIPMZY XBT MJNJUFE UP UIF QBMNT BOE TPMF MFTJPOT $PNQMFUF CMPPE DFMM DPVOU XBT XJUIJO OPSNBM MJNJUT 3FTVMUT GSPN BOUJTUSFQUPMZTJO 0 UJUFS QPUBTTJVN IZESPYJEF NPVOU BOE WFOFSFBM EJTFBTF SFTFBSDI MBCPSBUPSZ XFSF OFHBUJWF 4LJO CJPQTJFT XFSF UBLFO GSPN UIF CBDL BOE MFGU QBMN É¨F CJPQTZ TQFDJNFO GSPN UIF CBDL SFWFBMFE GPDBM TQPOHJPTJT MZNQIPDZUF FYPDZUPTJT WBDVPMBS DIBOHFT JO UIF CBTBM MBZFS BOE QFSJWBTDVMBS MZNQIPDZUJD JOÃ«MUSBUF JO UIF EFSNJT 'JHVSF É¨F CJPQTZ PCUBJOFE GSPN UIF WFTJDVMBS MFTJPO PO UIF MFGU QBMN SFWFBMFE BO JOUSBFQJEFSNBM WFTJDMF XJUI OP FWJEFODF PG BDBOUPMZUJD QSPDFTT 'JHVSF " EJBHOPTJT PG QJUZSJBTJT SPTFB XBT NBEF BOE UIF QBUJFOU XBT TUBSUFE PO DMBSJUISPNZDJO NH PODF B EBZ GPS EBZT BMPOH XJUI BOUJIJTUBNJOFT BOE FNPMMJFOUT É¨F MFTJPOT GBEFE ESBNBUJDBMMZ JO B WFSZ TIPSU QFSJPE BOE UIFSF XBT TJHOJÃ«DBOU JOWPMVUJPO PG BMNPTU BMM PG UIF MFTJPOT BGUFS EBZT PG DMBSJUISPNZDJO %VSJOH UIF NPOUIT PG GPMMPX VQ OP SFDVSSFODF XBT PCTFSWFE

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.JSBOEB 4# -VQJ 0 -VDBT & 7FTJDVMBS QJUZSJBTJT SPTFB SFTQPOTF UP FSZUI SPNZDJO USFBUNFOU J Eur Acad Dermatol Venereol. o

(SJGÃ¥UIT " 7FTJDVMBS QJUZSJBTJT SPTFB Arch Dermatol.Ã¹

$IVI "" %PÃ¥UBT #- $PNJTFM (( FU BM *OUFSWFOUJPOT GPS QJUZSJBTJT SPTFB Cochrane Database Syst Rev. $%

3BTJ " 5BK[JFIDIJ - 4BWBCJ /BTBC 4 0SBM FSZUISPNZDJO JT JOFGGFDUJWF JO UIF USFBUNFOU PG QJUZSJBTJT SPTFB J Drugs Dermatol. o

10 #VLIBSJ *" 0SBM FSZUISPNZDJO JT JOFGGFDUJWF JO UIF USFBUNFOU PG QJUZSJBTJT SPTFB J Drugs Dermatol. 11 -BCSP .5 "OUJ JOÃ½BNNBUPSZ BDUJWJUZ PG NBDSPMJEFT B OFX UIFSBQFVUJD potential? J Antimicrob Chemother. o 12 $IVI "" $IBO )) 1SPTQFDUJWF DBTF DPOUSPM TUVEZ PG DIMBNZEJB MFHJP OFMMB BOE NZDPQMBTNB JOGFDUJPOT JO QBUJFOUT XJUI QJUZSJBTJT SPTFB Eur J Dermatol. o

VINTAGE LABELS

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BOOK REVIEW Noah S. Scheinfeld, MD, JD, Section Editor

Hallâ&#x20AC;&#x2122;s Manual of Skin as a Marker of Underlying Disease Edited by John C. Hall and Brian J. Hall. 300 pages. Shelton, CT; Peopleâ&#x20AC;&#x2122;s Medical Publishing Houseâ&#x20AC;&#x201C;USA; 2011. $89.95. ISBN 1607951029 4PNF EBZ BMM TLJO EJTFBTFT * UIJOL XJMM CF VOEFSTUPPE CZ QIZTJDJBOT BT nosocological mobius TUSJQT É¨BU JT JOGFDUJPVT EJTFBTFT XJMM CF TFFO BT BCFSSBUJPOT PG JNNVOJUZ BOE SFJÃ«DBUJPOT PG NVUBUFE %/" $BODFS XJMM CF WJFXFE BT B QIFOPNFOPMPHJDBM 7FOO EJBHSBN PG NVUBUJPOT WJSBM JOUFSQPMBUJPOT BOE JNNVOPMPHJDBM VOEFSBDIJFWFNFOU Î&#x2030;%JTFBTFT PG JNNVOJUZ XJMM CF VOEFSTUPPE BT B DPMMFDUJPO PG JOGFDUJPOT BOE OFPQMBTUJD TJOT UIBU DBOOPU CF VOEPOF 6OUJM UIBU UJNF BOE QFSIBQT FWFO JO UIBU UJNF UIF QIZTJDJBO XJMM CF XFMM BEWJTFE UP DBSSZ BOE review Hallâ&#x20AC;&#x2122;s Manual of Skin as a Marker of Underlying Disease B TLJMMGVMMZ FEJUFE CPPL XJUI BO JOUFSOBUJPOBM UBMFOU TIPX PG DPOUSJCVUPST É¨JT EFSNBUPMPHJD UFYU XIJDI SFBET MJLF B SPNBO Ã&#x2039; DMFG UBLFT JUT QMBDF XJUI UIF PUIFS OFDFTTBSZ XPSLT UIBU IBWF BEESFTTFE EFSNBUPMPHZ BOE TZTUFNJD EJTFBTF CZ #SBWFSNBO 1 $BMMFO 2 BOE 1SPWPTU 3 *O POF JNQPSUBOU XBZ )BMM T CPPL TVSQBTTFT UIFN )BMM T QSJDF QPJOU JT VOEFS XIJDI NFBOT UIBU )BMMT CPPL DBO CF QSFTFOUFE CZ UIF QIBSNBDFVUJDBM DPNQBOJFT BT BO FEVDBUJPOBM BJE +VTU BT B +FXJTI TDIPMBS LFFQT B .JTIOBI 5PSBI BVUIPSFE CZ UIF 3BNCBN PO IJT EFTL UIF 5VS "SCB BI 5VSJN CZ +BDPC CFO "TIFS JO IJT BSDIJWF 3BCCJ :JU[DIBL "MGBTJ T UIF JOUFMMJHFOU EJHFTU iUIF 3JGw JO UIF BQQFOEJY TFDUJPOT PG IJT 5BMNVE BOE UIF 4IVMDBO "SVDI CZ :PTFG ,BSP PO IJT XBMM XJUI UIF IBOEZ HMPTTFT PG UIF 3FNB .PTFT *TTFSMFT PO ,BSP T QBHFT UIF TDIPMBS JT BEWJTFE JG IF DBO UP LFFQ BMM UIFTF CPPLT PO TZTUFNJD EJTFBTF XJUIJO BSN T MFOHUI )BMMT CPPL DPWFST UIF UPQJDT PG JOUFSOBM EJTFBTFT BOE TLJO JO B CSJFG CVU FÃªFDUJWF GBTIJPO XJUI TFDUJPOT PO OFVSPMPHJDBM JOGFDUJPVT QFEJBUSJD HFOFUJD BOE PUIFS UPQJDT EJWJEFE JOUP DIBQUFST PO UIF NBOJGFTUBUJPO PG UIF TQFDJÃ«D EJTFBTF TUBUFT &BDI DIBQUFS JT VOJRVF BOE SFQMFUF XJUI FYDFMMFOU JOGPSNBUJPO * QBSUJDVMBSMZ FOKPZFE UIF TFDUJPO PO OFVSPMPHJDBM EJTFBTFT BOE UIF TLJO Î&#x2030;*Î&#x2030;GPVOE UIF EJTDVTTJPO PO SFÃ¬FY TZNQBUIFUJD EZTUSPQIZ 34% FOMJHIU FOJOH Î&#x2030;*Î&#x2030;DPOGFTT UIBU * IBE OFWFS QBSTFE 34% JOUP JUT TUBHFT VOUJM * SFBE UIF DIBQUFS JO )BMM T CPPL É¨FTF TUBHFT BSF

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REFERENCES

t 4UBHF POF 34% DIBSBDUFSJ[FE CZ TFWFSF CVSOJOH QBJO BU UIF TJUF PG UIF JOKVSZ XJUI NVTDMF TQBTN KPJOU TUJÃªOFTT SFTUSJDUFE NPCJMJUZ SBQJE IBJS BOE OBJM HSPXUI BOE WBTPTQBTN

Braverman IM. Skin Signs of Systemic Disease. 3rd ed. Philadelphia, PA: W.B. Saunders Co; 1998.

Callen, JP, Jorizzo, JL, Bolognia, JL, Piette, W, Zone JJ. Dermatological Signs of Internal Disease. 4th ed. Philadelphia, PA: W.B. Saunders Co; 2009.

Provost TT, Flynn JA. Cutaneous Medicine: Cutaneous Manifestations of Systemic Disease. Hamilton, Ontario: BC Decker Inc; 2001.

Reviewed by Noah S. Scheinfeld, MD, JD From the Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY Address for Correspondence: Noah S. Scheinfeld, MD, JD, Department of Dermatology, Columbia University, College of Physicians and Surgeons, 150 West UI 4USFFU /FX :PSL /: t & NBJM TDIFJOGFME!FBSUIMJOL OFU

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Locoid Lipocream® Cream, 0.1% (hydrocortisone butyrate 0.1% cream) For Topical Use Only

Rx Only

BRIEF SUMMARY INDICATIONS AND USAGE Locoid Lipocream is a topical corticosteroid indicated for: relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adults and the treatment of mild to moderate atopic dermatitis in patients 3 months to 18 years of age. WARNINGS AND PRECAUTIONS Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression may occur, with the potential for glucocorticosteroid insufficiency. Consider periodic evaluations for HPA axis suppression if Locoid Lipocream is applied to large surface areas or used under occlusion. If HPA axis suppression is noted, reduce the application frequency, discontinue use, or switch to a lower potency corticosteroid. Systemic effects of topical corticosteroids may also include manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria. Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface-to-body-mass ratios. Initiate appropriate therapy if concomitant skin infections develop. Discontinue use if irritation develops. ADVERSE REACTIONS The most common adverse reactions (>1%) are HPA axis suppression and application site reactions. The following additional local adverse reactions have been reported infrequently with topical corticosteroids, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions included: irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria and telangiectasia. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.There are no adequate and well-controlled studies in pregnant women. Therefore, Locoid Lipocream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Please refer to full prescribing information for detailed information regarding systemic embryofetal development studies. Nursing Mothers Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Locoid Lipocream is administered to a nursing woman. Pediatric Use Safety and efficacy in pediatric patients below 3 months of age have not been established. Because of higher skin surface-to-body-mass ratios, pediatric patients are at a greater risk than adults of HPA axis suppression when they are treated with topical corticosteroids. They are therefore also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment. Eighty-six (86) pediatric subjects (5 months to less than 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (BSA) treated with Locoid Lipocream three times daily for up to 4 weeks were assessed for HPA axis suppression. The disease severity (moderate to severe atopic dermatitis) and the dosing regimen (three times daily) in this HPA axis study were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (two times daily) for which Locoid Lipocream is indicated. Five of the 82 evaluable subjects (6.1%) demonstrated laboratory evidence of suppression, where the sole criterion for defining HPA axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter after cosyntropin stimulation. Suppressed subjects ranged in age from 5 months to 16 years and, at the time of enrollment, had 25% to 95% BSA involvement. These subjects did not develop any other signs or symptoms of HPA axis suppression. At the first follow up visit, approximately one month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. This last subject recovered adrenal function by the second post treatment visit, 65 days post-treatment. Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have also been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Geriatric Use Clinical studies of Locoid Lipocream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Carcinogenesis, Mutagenesis, Impairment of Fertility No studies were conducted to determine the photococarcinogenic or dermal carcinogenic potential of Locoid Lipocream. Hydrocortisone butyrate revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames test and L5178Y/TK+ mouse lymphoma assay) and one in vivo genotoxicity test (mouse micronucleus assay). No evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to and including 1.8 mg/kg/day (0.7X maximum topical human dose [MTHD]). Mild effects on maternal animals, such as reduced food consumption and a subsequent reduction in body weight gain, were seen at doses ≥0.6 mg/kg/day (0.2X MTHD). PATIENT COUNSELING INFORMATION Patients using Locoid Lipocream should receive the following information and instructions: Apply a thin layer to the affected skin two or three times daily for corticosteroidresponsive dermatoses in adults. Consult with your physician to determine if treatment is needed beyond 2 weeks. Apply a thin film to the affected skin areas two times daily for atopic dermatitis in patients 3 months of age and older. Safety of Locoid Lipocream in pediatric patients has not been established beyond 4 weeks of use. Rub in gently. Avoid contact with the eyes. Do not bandage, otherwise cover, or wrap the affected skin area so as to be occlusive unless directed by your physician. Do not use Locoid Lipocream in the diaper area, as diapers or plastic pants may constitute occlusive dressings. Do not use Locoid Lipocream on the face, underarms, or groin areas unless directed by your physician. If no improvement is seen within 2 weeks, contact your physician. Do not use other corticosteroid-containing products while using Locoid Lipocream without first consulting your physician. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from freezing. Keep out of the reach of children.

Manufactured for: Triax Pharmaceuticals, LLC Cranford NJ 07016 By: Ferndale Laboratories, Inc. Ferndale MI 48220 Locoid Lipocream is a registered trademark of Astellas Pharma Europe BV licensed to Triax Pharmaceuticals, LLC.

Marketed and Distributed By: Triax Pharmaceuticals, LLC Cranford NJ 07016 www.Locoid.com

131B301 Rev 11/09

Now younger eczema patients have something to smile about

Now approved for use in children down to 3 months of age

The power of an ointment with the elegance of a cream Locoid Lipocream is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, including the treatment of mild to moderate atopic dermatitis in patients 3 months of age and older. Safety and effectiveness in pediatric patients below 3 months of age have not been established. Reversible HPA axis suppression may occur, with the potential for corticosteroid insufficiency. Consider periodic evaluations for HPA axis suppression if applied to large surface areas or used under occlusion. Systemic effects of topical corticosteroids may also include manifestations of Cushingâ&#x20AC;&#x2122;s syndrome, hyperglycemia, and glucosuria. Pediatric patients may be more susceptible to systemic toxicity due to their large skin surface-to-body-mass ratios. Initiate appropriate therapy if concomitant skin infection develops. Discontinue use if irritation develops. Please see full Prescribing Information on adjacent page. Visit us at www.locoid.com (hydrocortisone butyrate 0.1%) Cream ÂŠ2010 Triax Pharmaceuticals, LLC. All rights reserved. Locoid is a registered trademark of Astellas Pharma Europe B.V. licensed to Triax Pharmaceuticals, LLC. LOC-0410-01