The Chronicle of Skin & Allergy February 2016

T h e r a p i e s

IPC calls forstandardizedassessment ofbiosimilars forpsoriasisnMinimum set ofstandards needed tocompare biosimilarsagainst originatorsby LYNN BRADSHAW,Senior Associate Editor, The Chronicle

The International PsoriasisCouncil (IPC) recently suggest-ed the need for guidelines to

aid in the standardization of pre-clinicalassessments to determine similarity ofemerging biosimilars for the treatmentof psoriasis in a report published onlineahead of print (Nov. 1, 2015 in theBritish Journal of Dermatology).

“Biosimilars are new to Canadaand dermatolo-gists have littleexperience withbiosimilars forthe treatment ofpsor iasis. There-fore, it is impor-tant for dermatol-ogists to realizeand rememberthat these [simi-lar bio logics] arenot the same as the original biolog-ics,” Dr. Ron Vender, associate clini-cal professor of medicine atMcMaster University in Hamilton, toldTHE CHRONICLE OF SKIN & ALLERGY.

“In other specialties biosimilarshave been used, but right now thereare a lot of unknowns regarding theeffects [of biosimilars] in dermatol-ogy,” he said.

Clinical trials ongoingDr. Vender added that “Biologics con-sist of large complex molecules thatrequire a difficult manufacturingprocess. The biosimilar that is present-ly available has not been tested inpatients who have psoriasis at the pre-sent time. However, there are ongoing

Please turn to Biosimilars page 16à

melanoma that may produce amore durable clinical response,Dr. Norris reported during a pre-sentation at the semi-annualBuffalo-Rochester DermatologySociety Meeting hosted by theDepartment of Dermatology, Uni -versity at Buffalo.

Dr. Norris, professor andchairman of the Department ofDermatology at the University ofColorado’s Anschultz MedicalCampus in Denver, has for yearsbeen studying melanoma’s resis-

PRACTICAL THERAPEUTICS and CLINICAL NEWS from the WORLD of DERMATOLOGY n FEBRUARY 2016

by JOHN EVANS,Associate Editor, The Chronicle

A combination treatmentinvolving a BCL-2/BCL-XL/BCL-W inhibitor and a

synthetic retinoid appears to effec-tively interfere with the resistance toapoptosis typical of melanoma cells,showing promising results both invitro and in vivo, according to Dr.David A. Norris. The combinationpotentially represents an effectivenew treatment strategy for

M e l a n o m a

Activating cell death pathwaymay lead to durable responsen Presentation by Dr. David Norris highlights apoptosis resistance

o f & A L L E R G YSKINSKINThe Chronicle

All rights reserved. C

hronicle Inform

ation Resources Ltd.Canada Post C

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umber 40016917

tance to cell death and how it mightbe overcome. In a paper published inJournal of Investigative Dermatology(Mar. 2015; 135(3): 842:850), Dr.Norris and his colleagues describehow the smallmolecule ABT-737, combinedwith fenretinideN - ( 4 - h y d r o x -yphenyl) reti-namide (4-HPR),synerg is t ica l l ydecreased cellviability andcaused cell death in multiple mela-

Please turn to Melanoma page 24àC l i n i c a l p r a c t i c e

Mid-dermal elastolysis termeda female-centric conditionn Case report and literature reviewprovide insight into rare condition by EMILY INNES,Associate Editor, The Chronicle

Mid-dermal elastolysis (MDE), while rare, has been deter-mined to be a female-centric disease, according to acase report and updated review of the literature pub-

lished in the Please turn to MDE page 10à

Dr. David Norris

Dr. RonaldVender

n The Chronicle is committed tomaintaining leadership in envi-ronmentally sustainable poli-cies, and to encouraging theadoption of “green-aware” prac-tices in healthcare. We inviteyour comments via e-mail, at:[email protected]

See page 4See page 4

Six Essential Topics

2016for

Clinical advancesinclude new

approved therapyfor HS

Skin_February_2016,rar7_ms_9-1,rar_Skin_March_2014,rar1.qxd 02/03/2016 4:49 PM

THERE IS A NEW TREATMENT FOR CHRONIC IDIOPATHIC URTICARIA (CIU)1*

XOLAIR ®

A new option to

treat CIU

PrXOLAIR® (omalizumab) is indicated for the treatment of adults and adolescents (12 years of age and above) with chronic idiopathic urticaria (CIU) who remain symptomatic despite H1-antihistamine treatment.1Please refer to the study parameters and reference list at http://www.eppendix.com/APS-Xolair-14XOL062EXOLAIR® 150 mg also showed a reduction in itch and hives: 56% reduction from baseline in weekly ISS seen at week 12 with XOLAIR® 150 mg vs. 36% for placebo. Mean change from baseline to week 12 in weekly ISS: -8.1 vs. -5.1 for placebo (p<0.0011). 57% reduction from baseline in weekly number of hives score seen at week 12 with XOLAIR® 150 mg vs. 31% with placebo (secondary endpoint). Mean change from baseline to week 12 in weekly hives score: -9.8 vs. -5.2 for placebo.1,2†

*CIU is sometimes referred to as chronic spontaneous urticaria (CSU).†ASTERIA II

Clinical use:

other conditions. There is limited experience with XOLAIR® in patients over 65 years of age. Most serious warnings and precautions:Anaphylaxis: Anaphylaxis, presenting as angioedema of the throat or tongue, bronchospasm, hypotension, syncope, and/or urticaria has been reported to occur after administration of XOLAIR®.

but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, patients should be closely observed for an appropriate period of time after XOLAIR® administration, and healthcare providers administering XOLAIR® should be prepared to manage anaphylaxis that can be life-threatening. Patients should also be informed of the signs and symptoms of anaphylaxis and instructed to seek immediate medical care should symptoms occur.Other relevant warnings and precautions:• Cardiovascular and cerebrovascular disorders

• Corticosteroid reductions• Immune system disorders: Churg-Strauss syndrome and

hypereosinophilic syndrome; serum sickness; immunogenicity• Information for patients on anaphylaxis; driving or using machines• Caution in other IgE-associated disorders• Patients at high risk of parasitic (helminth) infections• Patients with renal or hepatic impairment• Pregnant women• Nursing women• Fertility • Pediatrics (<12 years of age)• Monitoring and laboratory tests: elevated serum total IgEFor more information:Consult the Product Monograph at http://www.novartis.ca/XolairMonograph for important information relating to adverse drug reactions, drug interactions, and dosage and administration information which have not been discussed in this piece. The Product Monograph is also available by calling 1-800-363-8883. Consult the references and study parameters at http://www.eppendix.com/APS-Xolair-14XOL062E

from baseline in weekly itch severity score (ISS)

seen at week 12 with XOLAIR® 300 mg vs. 36% for placebo2

Mean change from baseline to week 12 in weekly ISS: -9.8 vs. -5.1 for placebo (p<0.0001)1†

ITCH: 71%reduction

from baseline in weekly number of hives score

seen at week 12 with XOLAIR® 300 mg vs. 31% for placebo (secondary endpoint)2

Mean change from baseline to week 12 in weekly hives score: -12.0 vs. -5.2 for placebo1†

HIVES:

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THE CHRONICLE of SKIN & ALLERGY

Vol. 22, No. 1 February 2016 · 3

R e s e a r c h

Desktop sterilization developed

TOP ofthe MONTH

Laser treatment of glomuvenousmalformation produces long-lastingtumour involutionMay obviate need for surgical exci-sion, sclerotherapy; case describesan acquired, biopsy-proven GVM ofthe heel not amenable to surgicalexcision treated with a long pulsed1064-nm Nd:YAG laser. . . . . . . . . . . 8

Insect saliva trigger identified asculprit in cases of endemic BrazilianpemphigusClinical detective work may havetracked down protein contributingto autoimmune condition, acccord-ing to presentation at the 23rdWorld Congress of Dermatology inVancouver. . . . . . . . . . . . . . . . . . . 14

Research of note: the order ofapplication of emollients, topicalcorticosteroids appears to make nodifference in atopic eczema A total of 46 patients (ages fourmonths to five years) with AE weredivided into two groups, with no signif-icant difference seen in Eczema Areaand Severity Index (EASI) scores, per-centage of body surface area (BSA)affected, or itch score when the emol-lient or the corticosteroid was appliedfirst, after two weeks. . . . . . . . . . . . .26

Chronicle Postgraduate Educational SupplementIn this month’s Chronicle Post -graduate Educational Supplement,Austrian researchers investigateurine as a novel source of mes-enchymal stem cells for patientswith epidermolysis bullosa . . . . 19

“With globalization and with global warming,we are starting to see outbreaks of disease that

are vector transmitted.”Dr. Gail Nield, a dermatologist in Woodbridge, Ont.

(see page 4)

Researchers from Weill CornellMedical College at Cornell Universityin New York have found thatpathogens responsible for many com-mon skin infections can be destroyedon cell phones with a 10-minutecycle using a new desktop room-tem-perature-plasma sterilization device.The device may be a quick, easy, andinexpensive tool for sterilizing manytypes of electronics and medicalequipment, according to findingspublished in Plasma Medicine (Feb.2016; 5(1):57-70).

In a press release from Cornell,principal investigator Dr. Jason A.Spector, a professor of surgery and ofplastic surgery in otolaryngology atWeill Cornell Medicine and a plasticsurgeon at New York-Presbyterian/Weill Cornell Medical Center, said “Thisis something that’s innately relevant toall of our lives. I could imagine having

one of these sterilization devicesthroughout every hospital or any patientcare facility for that matter for treatingelectronic devices and biomedicalequipment at the end of every day.”

Traditional methods of sterilizingequipment, such as high-pressuresteam or toxic gasses, would damagemost electronic devices.

The device, known as theSterifire Countertop Sterilizer, couldalso be effective at sterilizing medicalmonitors, as well as other portableelectronics found in clinical settings,such as laptops and tablets, whichare potential vectors for bacterialtransfer but cannot be sterilized usingtraditional methods. Dr. Spector isalso testing the technology’s potentialas a means to disinfect wounds,using animal models. “There’s thepotential for this device to have ahuge impact in the biomedical fieldat large,” he said.

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February 2016 • Vol. 22 No. 1

Medical EditorWayne Gulliver, MD, FRCPC

Editor, Cosmetic DermatologySheldon V. Pollack, MD, FRCPC

PublisherMitchell ShannonEditorial Director R. Allan Ryan

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Comptroller Rose Arciero

A Message from theMedical Editor

In this issue of THE CHRONICLE wecontinue to bring our readersinformation on groundbreaking

international research related to theelucidation of both theenvironmental andgenetic basis forBrazilian pemphigus(see page 14) andnovel research intonew potential targetsfor melanoma thera-

pies that combine synthetic retinoidswith PCL inhibitors (see page 1).

In the article ‘Six essential topicsfor 2016’ (see page 4), Drs.Gooderham, Barankin and Linzonhighlight the importance of adali-mumab as the “first ever approvedtherapy for hidradenitis suppurativain Canada”. As we know manypatients with HS will wait as long aseight years and see an average ofseven physicians before finding a der-matologist who can diagnose and ini-tiate therapy. We’ll bring you moreinformation on this treatment andthis difficult condition in the issues tocome.

On the acne front Dr. Dytoc notesthat monthly monitoring of bloodtests may not be warranted in allpatients on Isotretinoin. Monthlypregnancy tests for childbearingfemales is certainly required. Iremember data from a similar studyby Drs. Zip and Rosenthal 20 years

Please turn to Message page 24à

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Dr. Jason Spector with the Sterifre CountertopSterilizer. Photo credit: Studio Brooke


by LOUISE GAGNON,Correspondent, The Chronicle

4 · April/May 2015

Lead article THE CHRONICLE of SKIN & ALLERGY

A C L E A R L O O K A T P S O R I A S I S

MEET SOME OFTHE KEY PLAYERSIN PSORIASISThese cytokinesplay an importantrole in PsO1

IL: interleukin; PsO: psoriasis; TNF: tumor necrosis factor.Reference: 1. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361(5):496–509.

14COS007E© Novartis Pharmaceuticals Canada Inc. 2014

C l i n i c a l p r a c t i c e

n Calgary study to compare rates of skin cancer detection by GPs versus dermatologists

Studying the im -pact of popula-tion screening tocurb the inci-dence of aggres-

sive mela-nomas, usingMohs surgery to reducerecurrence of specifictypes of melanoma, andidentifying groups at ele-vated risk for developingmelanoma are some ofthe latest advancements inthe prevention and treat-ment of the most lethal ofskin cancers.

One state in Germany with anorganized skin cancer screening pro-gram showed a cumulative drop of52% in mortality during years of skincancer screening, compared to adja-cent areas where such skin cancerscreening was absent (Skin CancerResearch to Provide Evidence forEffectiveness of Screening inNorthern Germany [SCREEN]).Canadian clinicians in Alberta arenow conducting a similar study todetermine if population screeningwill affect outcomes, including earlierdiagnosis of skin cancer and mortali-ty due to skin cancer (Cancer 2012Nov 1; 118(21):5395–5402).

“They [German study investiga-tors] found more than a 50 per cent

decrease in melanoma mortality thatwas only occur-ring in that stateof Germany[ S c h l e s w i g -Holstein],” saidDr. Lynne Rob-ertson, one ofthe Albertastudy’s investiga-tors, a dermatol-ogist and clinicalassistant profes-sor of dermatol-ogy at theUniversity ofCalgary inCalgary. “This hasprovided the bestevidence thatearly detection ofmela-noma canreduce the number of deaths frommelanoma.”

Skin cancer detection rates for GPsThe study will compare an Albertapopulation served by dermatologistsas well as family physicians who willreceive specific, rigorous training inskin cancer detection to an Albertapopulation of patients who will beserved by dermatologists and familyphysicians who do not receive specif-ic, rigorous training in skin cancerdetection.

“They will be taking an eight-hour training course,” noted Dr.Robertson.

Identifying populations at greaterrisk of developing melanoma and

then targeting those populations ispart of an effec-tive melanomaprevention pro-gram. Transplantpatients havebeen identifiedat elevated riskof developingnon-melanomaskin cancers likesquamous cellcancer, but a sys-tematic reviewhas found thatmelanoma isalso occurringwith greater fre-quency andaggressiveness insolid organ trans-plant recipients

compared to the general population. Canadian researchers examined

the incidence and relative risk ofmelanoma detected subsequent tosolid organ transplantation comparedto the general population, the out-comes of melanoma diagnosed aftersolid organ transplantation, and theoutcomes of melanoma diagnosedprior to transplantation. They con-cluded, among other findings, thatcompared to the general population,there is a 2.4-fold increased inci-dence of melanoma after transplan-tation (Transplantation Research2014 May 6; 3:10).

“This highlights the relationship

Dr. ChristianMurray

Dr. David Zloty

Dr. Cheryl RosenDr. JenniferBeecker

Please turn to Melanoma page 6à

Melanomaincidence continues to rise


A C L E A R L O O K A T P S O R I A S I S

MEET SOME OFTHE KEY PLAYERSIN PSORIASISThese cytokinesplay an importantrole in PsO1

IL: interleukin; PsO: psoriasis; TNF: tumor necrosis factor.Reference: 1. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361(5):496–509.

14COS007E© Novartis Pharmaceuticals Canada Inc. 2014


6 · April/May 2015


between melanoma and people withlowered immune systems, specifical-ly those who had undergone solidorgan transplantation” said Dr.Christian Murray, an author on thestudy and Mohs Surgery FellowshipDirector at the University of Toronto.“There is an increased risk [in thispopulation] of getting melanomas,and when they get it, it’s a worseprognosis. We need to watch formelanoma in patients with solidorgan transplantation.”

Skin cancer detection rates for GPsThe emergence of systemic thera-pies, such as ipilimumab and anti-PD-1 and anti-PD-L1 agents, are makinginroads in the management of unre-sectable and metastatic melanoma,according to Dr. Murray. One of thenewest additions to the metastaticmelanoma armamentarium isnivolumab, which was approved inlate 2014 by the U.S. Food and DrugAdministration based on data pre-sented at the 2014 European Societyfor Medical Oncology Congress inMadrid. Patients previously treatedwith ipilimumab and patients withmelanoma who have BRAF muta-tions who progressed despite therapywith ipilimumab and a BRAF inhibitorare candidates for nivolumab.

“There are multi-modal therapeu-tic options,” explained Dr. Murray.“There is new hope based on [theexistence] of systemic therapies formetastatic melanoma.”

The Canadian Cancer Societyreleased statistics last year revealingthat the incidence of melanoma isincreasing. The CCS estimated 6,500new cases of malignant melanomawould be diagnosed in 2014, with1,050 Canadians expected to die frommalignant melanoma, according toCanadian Cancer Statistics 2014.

Overall, the incidence rate formelanoma among men rose 2%annually between 1986 and 2010, andthe mortality rate rose 1.2% per year.For women, the incidence rate formelanoma rose 1.5% annually in thesame time period and the death rate

rose 0.4% annually.The Canadian Dermatology

Association (CDA) continues to holdan annual Sun Awareness Week inJune as well as other events through-out the year to raise awareness regard-ing sun protection, screening for skincancer, and sun-safe behaviour.

Dr. Jennifer Beecker, chair andnational spokesperson for the CDA’sSun Awareness Program and a derma-tologist in the Division of Dermatologyat the Ottawa Hospital, noted that thisyear’s focus of the Sun Awareness

Program is the outdoor enthusiast.“We want to stop the rising inci-

dence of skin cancer,” said Dr.Beecker in an interview with THECHRONICLE OF SKIN & ALLERGY. “Wewant to support the idea of peoplepracticing sun protection while theyare active.”

The CDA has teamed up withBaseball Canada, the national govern-ing body for baseball in the countrythat includes 10 provincial associa-tions, to distribute tip sheets on sunprotection to players, coaches andumpires across Canada. Events suchas Melanoma Monday, held on May 4,

2015, saw Ottawa-area dermatolo-gists on Parliament Hill offer screen-ing for skin cancer to MPs, senatorsand staff and tips on how to performself examination.

Still another measure from theCDA, noted Dr. Beecker, has been theproduction of a video on sun aware-ness, emphasizing the importance ofusing sunscreen and seeking shade,which has been airing on SunwingAirlines. Nearly one million Canadianswill be exposed to the video whileaboard the airline’s fleet. The video

has also been shown at other localevents such as the Toronto Golf Showin February and will run at TorontoRibfest in late June.

Excision of melanomas can requireapproaches such as Mohs surgery,observed Dr. David Zloty, president ofthe CDA, clinical associate professor,Department of Dermatology and SkinScience at the University of BritishColumbia (UBC), director, MohsFellowship, UBC, director, SurgicalEducation, Department of Dermatology,and director, Dermatologic SurgeryCentre, Vancouver General Hospital inVancouve.

Looking at the value of Mohssurgery in treating lentigo malignamelanoma has been controversialbecause interpretation of frozen tis-sue section slides is required,explained Dr. Zloty.

“Frozen section processing caninduce artifacts that can make ker-atinocytes look like melanocytes,”said Dr. Zloty. “Also, the resolution offrozen section [tissue] may not be ashigh as [with] standard paraffin-[embedded tissue].”

Mohs still best surgical approachBut with the addition of certainimmunohistochemistry, it should helpraise the sensitivity and specificity offrozen section Mohs analysis, said Dr.Zloty. “The main challenge is the inter-pretation of frozen section [tissues]and making sure you are not missinginvasive disease,” said Dr. Zloty.

Lentigo maligna, in particular,can have features that make it trickyto distinguish between normal, sun-damaged skin, noted Dr. Zloty. “Mostof the time you can differentiate onefrom the other,” he said.

Mohs is superior to staged exci-sion of lentigo maligna in terms ofachieving better local control, notedDr. Zloty. In terms of melanomas thatoccur on the face, Mohs surgeonsstrive to excise the lesions while stillmaintaining a satisfactory cosmeticand functional result guided by therecommended margins required forexcision, taking into account themelanoma thickness.

In an increasingly digital worlddotted with a landscape of mobiledevices, apps have emerged in der-matology, some of which weredesigned to help patients detectmelanoma, but dermatologists andorganizations such as the CDA and theAmerican Academy of Dermatologyhave not endorsed such mobile apps.

“The claims [of the apps] are notfounded scientifically,” said Dr.Cheryl Rosen, head, Division ofDermatology, Toronto WesternHospital and University HealthNetwork Hospitals. “Self-diagnosisusing an app is something to be con-cerned about.”

Melanoma incidence, mortality rates continue to climbContinued from page 4

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“The claims of the apps are notfounded scientifcally. Self-diagnosisusing an app is something to beconcerned about.”

—Dr. Cheryl Rosenq


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OTEZLA® (apremilast), alone or in combination with methotrexate, is also i

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by JOHN EVANS,Associate Editor, The Chronicle

Treating a glomuvenous malformation(GVM) using a neodymium-doped yttriumaluminum garnet (Nd:YAG) laser alone,

rather than in conjunction with surgical excisionand sclerotherapy, may be a viable technique withgood long-term results, according to a case studypublished in Journal of Cutaneous Medicine andSurgery (Jan. 2016; 20(1):80–83).

In the report, lead author Dr. Jason Rivers andhis colleagues describe a case of a patient with anacquired, biopsy-proven GVMof the heel not amenable tosurgical excision, that wastreated with a long pulsed1064-nm Nd:YAG laser.

“Our patient had been[experiencing] significant painfor many years, since child-hood. [The pain] was madeworse when pressure wasapplied to the affected area,”said Dr. Rivers about thepatient’s GVM.

Dr. Rivers is a clinical professor of dermatologyand a past director of the dermatology residencytraining program at the University of BritishColumbia. At present, Dr. Rivers’ practices medicaland cosmetic dermatology at PacificDermaesthetics in Vancouver.

Treatment approachDr. Rivers told THE CHRONICLE that there were a numberof factors about the case that suggested to him it was

worth trying to treat the GVM using a Nd:YAG laser. He explained that in the existing literature,

laser treatments have been tested as an adjunct tosurgical treatment for these types of vascular mal-formations, reduc-ing the size of thelesion prior to exci-sion. He added thatthis particular GVMwas of a colour sim-ilar to that seen invenous malforma-tions in other areas.“That is really whatmade me think ofusing a vascularlaser on the lesionin the first place.More specifically, Ichose the Nd:YAGlaser, because it penetrates more deeply into theskin compared to pulsed dye lasers.”

After a test spot showed improvement withouttoo much tissue damage, Dr. Rivers treated theremainder of the GVM with the long-pulsed Nd:YAGlaser. Five follow-up sessions spaced between two-to six-month intervals were used to completelyclear any residual disease.

Tumour involution achievedNine months after the patient’s final treatment, thetumour had completely resolved with minimal scar-ring, and no recurrence has been seen in the subse-quent three years of follow up. “The fact that wewere able to induce the involution of this type oftumour with laser was fairly unique,” said Dr. Rivers.

The patient’s pain resolved as well, he said.“Between sessions, while there was still residualtumour, she would experiene episodic pain.However, once the entire lesion became flat, she

became pain-free—basi-cally for the first time inher life.”

“She was very happybecause she was, basi-cally for the first time inher life, pain-free.”

During the treatmentitself, Dr. Rivers and histeam pre-treated thearea with lidocaine, butdid not use epinephrine.

“I did not want tocause any vasoconstric-tion. That is the mainthing, the one trick, if you

will. This ensured I was not reducing the targetchromophore in the tumour.”

GVM are quite rare, said Dr. Rivers, but thiscase does suggest that treatment with a long-pulsed Nd:YAG laser is a safe and effective way ofdealing with them, especially when they are surgi-cally challenging to treat.

Other vascular lesions more common thanGVM, such as subungual glomous tumours, couldalso be amenable to this type of Nd:YAG laser ther-apy, Dr. Rivers said.

R e s e a r c h

Laser treatment of a glomuvenousmalformation produces tumour involutionn Involution of tumour is long-lasting; may obviate need for surgical excision, sclerotherapy

8 · February 2016

V THE CHRONICLE of SKIN & ALLERGY

Dr. Jason Rivers

“Our patient had been

[experiencing]significant painfor many years,

since she was a child. [The pain]was made worse whenpressure was placedon the area primarily.”

—Dr. Jason Riversq

Share yourknowledgeand opinionswith world-wide peers.Visit

derm.city

www.derm.city

Have a comment about any of the articles in this issue of The Chronicle?

Where dermatology lives

Visit

Seen an unusual clinical presentation? Toshare it with your colleagues, send anemail to [email protected] and aneditor will contact you to discuss.


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International Journal of Women’sDermatology (Aug. 2015; 1(3):126–130).

A 45-year-old female was referredto Dr. Richard M.Haber, with theDivision ofDermatology atthe University ofCalgary, for asecond opinionregarding whatwas initiallythought to be acase of general-ized atrophoderma by the referringdermatologist. The patient had wide-spread papules and plaques withwrinkling and mild protrusion fromthe surface of the skin predominantlyover her abdomen, trunk, and proxi-mal arms and legs.

The patient’s past medical histo-ry was unremarkable (of note, shewas nulliparous), and she had norecent travel. She was active out-doors and often exercised withoutsun protection. Dr. Haber diagnosedMDE, and became interested inopportunities to further investigatethis condition.

“I have seen the occasionalcases [of MDE] presented at meet-ings, but it is the first one that [mycolleagues and I] have diagnosed,”said Dr. Haber.

“We thought it was a bit unusual

and we thought we would perhapslook at the fact that it more commonin females—it has been reportedbefore, but it has not been theemphasis of cases in the past,” hesaid.

Possible role of UVGerman dermatologist Dr. ThiloGambicheler reported an 83.5%female prevalence in his review ofMDE (Arch Dermatol Res 2010;302(2):85–93).

“Interestingly, of the publica-tions since 2009, six of the 10 werereports of Type III MDE. Unlike TypeI and Type II MDE, type III demon-strates a strong male predominance,with only three reported casesaffecting females,” the authors state

in the report. “Therefore i f the six recent

reports of Type III MDE are removed,three of the four cases of Type I andII MDE since 2009 have beenfemales.”

The authors report that whileultraviolet radiation or hormonalroles remain elusive in MDE, “theycould potentially explain theunequivocal proportion of femalepatients, as well as the significanthistory of sun tanning bed exposureamongst them.” The investigatorsnote that in almost half of the casesreported sun exposure was implicat-ed.

“It is unusual that [the conditioncould be] sun-induced because itrarely affects the face,” said Dr.Haber. “However, there are othersun-induced conditions where theface is spared, for example . . . poly-morphous light eruption [in whichthe face] may be involved, but it may

be spared. Therefore [this feature]does not preclude [MDE] from beingsun-induced.”

No effective treatmentDr. Haber said that there is currently

no evidence for effective treatments.According to the literature, topicaltretinoin is most widely used and-while there is some evidence that itreduces the winkles, it does not alterthe natural history of the disease.The use of tretinoin has been foundto be more effective in more mildcases.

“Other patients, where they havesigns of inflammation, there havebeen reports of using anti-inflamma-tory drugs to prevent this from [devel-oping],” said Dr. Haber.

“However, most of the time youdo not see a lot of inflammation inthis condition. [If the patient] pre-sents with redness and itching, it is inthis situation that treatment with anti-inflammatory agents—such as dap-sone—has been used.”

The authors note that there is apotential role for soybean extract inenhancing elastic fiber network andinhibition of elastases, though it hasso far only been tested on mice.

“[My case] patient just wanted toknow what she had. She had been tonumerous doctors in the past andwas not diagnosed,” said Dr. Haber.

“She was certainly happy to haveat least a diagnosis and she was ableto go read about it . . . That is alwaysa good thing, but having a diagnosisunfortunately does not mean that wecan actually . . . treat it, which is veryfrustrating in a number of cases.”

Psychosocial implicationsDr. Haber said it was important to beable to reassure his patient that thecondition was unlikely to appear onthe face, since the cosmetic implica-tions of MDE can be life-altering forpatients.

The researchers noted that clini-cians should not diminish the severi-ty of a diagnosis because there areno systemic manifestations. Theynoted that clinicians should notneglect the psychosocial impact ofthis diagnosis.

“We are hoping just by makingclinicians more aware of this condi-tion then perhaps they will recognize[MDE] and hopefully we can get aseries of these patients. [Up until nowthere have only] been isolated cases,so it has been almost impossible todo any evidence-based trial for anytype of therapies,” said Dr. Haber.“And there are occasionally serendip-itous [incidents] where patients havetaken a drug for other reasons andthe condition gets better.”

Greater awareness of MDE,according to Dr. Haber, is criticalbecause the clinician must know toprompt the pathologist to pursueorcein or van Gieson staining.

“Biopsies sent for hematoxylinand eosin staining are commonlyreported as normal,” Dr. Haber point-ed out.

© 2015 P&G

10 · February 2016


MDE should be considered a female-centric conditionContinued from page 1

“We are hoping just by makingclinicians more aware of thiscondition then perhaps they

will recognize [MDE] and maybe we can

get a series of these patients.”—Dr. Richard M. Haberq

Dr.Richard M.Haber


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INDICATIONS AND CLINICAL USE:ACTIKERALLTM (fluorouracil and salicylic acid) is indicated for the topical treatment of slightly palpable and/or moderately thick hyperkeratotic actinic keratosis (Grade I/II) of the face, forehead, and balding scalp in immunocompetent adult patients.Safety and efficacy has not been established in a pediatric population. Analysis of efficacy by age, i.e. < or 65 years, has not been conducted.

CONTRAINDICATIONS:• ACTIKERALLTM is not for oral,

ophthalmic, intranasal, intravaginal, intra-auditory canal or intra-anal use

• Hypersensitivity to fluorouracil or capecitabine; salicylic acid or other salicylates; or any ingredient in the formulation or container

• Pregnancy or when pregnancy cannot be excluded; lactation

• Renal insufficiency• In conjunction with brivudine,

sorivudine and analogues that are inhibitors of the fluorouracil-degrading enzyme dihydropyrimidine dehydrogenase (DPD)

• DPD deficiency

RELEVANT WARNINGS AND PRECAUTIONS:• Safety and efficacy of ACTIKERALLTM

treatment has not been evaluated in clinical trials on body areas apart from the face, forehead and bald scalp

• Safety and efficacy of treating recurrent lesions, basal cell carcinoma, or Bowen’s disease with ACTIKERALLTM has not been evaluated in clinical trials

• Should not be used on bleeding lesions

• Patients with sensory disturbances (e.g. those with diabetes mellitus) should be closely monitored

• Concurrent use of ACTIKERALLTM with other topical products that have drying, peeling, desquamating, or abrasive effects may result in excessive skin irritation

ADVERSE EVENTS:Most frequent adverse reactions were categorized as application site reactions: irritation/burning (86.1%), inflammation (73.3%), pruritus (44.9%), pain (25.1%) and erythema (11.2%). Although most adverse events were mild to moderate in intensity, some patients also experienced severe local adverse events including irritation (21.4%), inflammation (15.5%), pruritus (4.8%), pain (4.3%), erythema (1.6%), erosion (1.1%) and ulcer (1.1%).

FOR MORE INFORMATION:Please see Product Monograph at http://www.cipherpharma.com/ca_en/wp-content/uploads/ 2015/07/150807-Actikerall-PM-English.pdf for important information relating to adverse reactions, drug interactions and dosing information. The Product Monograph is also available by calling 1-888-361-7207.

REFERENCES: 1. ActikerallTM Product Monograph.

Cipher Pharmaceuticals Inc. August 7, 2015.2. Stockfleth E, Kerl H, Zwingers T, Willers C.

Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratosis: histological and clinical study results. BJD DOI 10.1111/j.1365 2133.2011. 10387.x

12 · February 2016


ACCESS TO BIOLOGICS FOR PSORIASISA study of U.S. Medicare beneficiaries identified several potential financial and racial barri-ers to patients receiving biologic therapies, according to a paper published online in Journalof Investigative Dermatology (July 27, 2015).

The authors note that knowledge of both the epidemiology of psoriasis and its treatmentamong elderly patients is limited. To try and address this, the investigators examined data on a U.S. nationally-represen-tative sample of Medicare beneficiaries in 2011, focusing on psori-asis, biologic treatments, and factors associated with the use ofthose treatments. Looking at the data using different algorithms toidentify psoriasis cases, the authors found claims-based prevalenceof psoriasis in the U.S. of 0.51 to 1.23%. Some 27.3% of the identifiedpsoriasis sample received treatments for moderate-to-severe pso-riasis, including phototherapy, oral systemics, or biologic therapies.Biologics were used by 37.2% of the patients receiving moderate-tosevere psoriasis treatments.

When the authors looked at access to treatment, they foundthat psoriasis patients who did receive a Medicare Part D low-in-come subsidy were 70% less likely to have received biologic ther-apy than those who had the subsidy (odds ratio (OR) 0.30; 95%confidence interval (CI), 0.19–0.46). Black patients were 69% lesslikely to receive biologics for their psoriasis compared to white pa-tients (OR 0.31; 95% CI, 0.16–0.60).

BMI AND SEVERITY OF PSORIASISResearchers have identified an association between excess weight loss and an improvement in symptoms in cases ofsevere psoriasis, with factors including age at diagnosis and severity of psoriasis helping to identify which patients mightbe more likely to see an improvement in their psoriasis symptoms after weight loss, according to findings presented atthe 2015 annual meeting of the American College of Rheumatology (ACR) on Nov. 8, 2015.

The investigators conducted a retrospective database review of 9,073 bariatric surgeries performed at a single centrebetween 2002 and 2013, and identified patients with a psoriasis diagnosis before their surgery. These patients were thencontacted and surveyed regarding their history of psoriasis, psoriatic arthritis (PsA), and any changes in their psoriaticsymptoms or treatment modalities pre- and post-bariatric surgery. The primary outcome of the study was the percentage

of patients in the sample who reported an improvement in their pso-riasis and PSA greater than five on a zero to 10 scale following sur-gery.

Of the 128 patients with preoperatively diagnosed psoriasis, 86(67%) completed the study. Mean time from surgery to questioningwas 6.1 years, and the mean excess weight loss was 46.2%. Therewere 21 (24%) psoriasis patients who also had a diagnosis of PsA be-fore their operations. Subjective improvement in disease was re-ported by 55% of psoriasis patients and 62% of PsA patients whenthey were contacted. Significant decreases were seen between pre-surgery and one year post-surgery in psoriasis severity (5.6 vs. 4.4,p<0.01) and PsA (6.4 vs. 4.5, p=0.01). The difference was larger inmore severe cases of psoriasis (rating >5) (7.7 vs. 5.7, p<0.01) andPsA (8.2 vs. 4.8, p<0.01).

PSORIASIS AND MAJOR DEPRESSIONSelf-reported psoriasis history, regardless of severity, is independently associated with major depression even after con-trolling for co-morbidities such as a history of cardiovascular events, researchers report in JAMA Dermatology (Jan. 2016;152(1):73–79).

In order to clarify the association between psoriasis and major depression in the U.S. population, investigators con-ducted a population-based study using data from the National Health and Nutrition Examination Survey from 2009 to 2012.From the 12,382 U.S. citizens included in the study, 351 (2.8%) cases of psoriasis and 968 (7.8%) cases of major depressionwere identified. Among the identified psoriasis patients, 58 (16.5%) also met the criteria for a diagnosis of major depression.Mean (SD) Patient Health Questionnaire-9 scores were significantlyhigher among patients with a history of psoriasis (4.54 [5.7] vs. 3.22[4.3] in those without psoriasis, p<0.001).

Even after adjusting for sex, age, race, body mass index, physicalactivity, smoking history, alcohol use, history of myocardial infarction(MI), history of stroke, and history of diabetes mellitus, there was asignificant association between psoriasis and major depression(odds ratio (OR) 2.09, 95% confidence interval (CI), 1.41–3.11,p<0.001). Interaction term analyses in patients with a history involv-ing both psoriasis and MI or stroke did not show a further increasein major depression risk (psoriasis and MI: OR, 1.09 (95% CI, 0.28–3.60), p=0.91; psoriasis and stroke: OR, 0.67 (95% CI, 0.12–3.66),p=0.63). There was also no significant difference in risk of majordepression seen between individuals with limited vs. extensive pso-riasis (OR, 0.66 (95% CI, 0.18–2.44), p=0.53).

We invite your comments and questions about this feature at www.derm.city. Dr. Ron Vender is a certified dermatologist with 23 years ofclinical practice experience and over 50 clinical trials in psoriasis. He is founder and director of Venderm Innovations in Psoriasis, a cen-tre of excellence for Psoriasis offering a comprehensive management solution for individuals with psoriasis. www.venderm.ca

R e s e a r c h

psoriasis� Assessing clinical advances in Pso care and research

Comment: Although the results of the study is notsurprising in the United States, it would be difficultto determine or extrapolate the results to the Cana-dian population because of the universal healthcaresystem. Most provinces have a system where thosein need have access to biologics in a limited usefashion. The Canadian healthcare system offers amore equal opportunity to obtain biologics that isless dependent upon financial classes. The mainissue in Canada seems to be psoriasis patients real-izing that better treatment is available, and havingeasy access to a dermatologist willing to prescribebiologics.

Comment: The more that we know about psoriasis,the more of a mystery of its comorbidities we dis-cover. This important study again reveals an inde-pendent risk factor for psoriasis. We certainlyappreciate the improvement in depressive symp-toms with the improvement of psoriasis. Howevermaybe one day an exact mechanism of actionshowing a link between depression occurring be-fore the development of psoriasis will be discov-ered. Also future discoveries may reveal thatspecific inflammatory mediators and cytokines re-sponsible for depression are also responsiblespecifically for psoriasis.

Comment: There is no doubt that a healthierlifestyle usually leads to improvement in psoriasis. Itis possible that with weight loss these patients exer-cise more and take care of their overall health in abetter fashion with respect to diet and better overalllifestyle. However, it may also be important that thereduction in overall adipocytes or fat cells decreasethe inflammatory state associated with psoriatic dis-ease. Long term randomized double blind studiesmay better elucidate and confirm the scientific rea-son behind this study.

Venderon

Skin_February_2016,rar7_ms_9-1,rar_Skin_March_2014,rar1.qxd 02/03/2016 11:07 AM

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APPRILON® is a registered trademark of Galderma Canada Inc.

MISSING

An oral anti-infl ammatory therapy indicated in rosacea


14 · April/May 2015


foot ulcers and present withmultiple risk factors such asperipheral vascular disease,neuropathy, elevated glucose,and smoking, according toDr. Zahedi.

“When a diabetic patienthas a wound and has poor[glycemic] control, if you canbring down the patient’s glu-cose level, you can improvethe healing process,” she said.“The majority of these patientsare on insulin or find out that

they have to be on insulin.”In order to dramatically

reduce glucose levels in ashort amount of time,patients with diabetes may beadmitted to hospital for briefperiods, noted Dr. Zahedi.

Angiogenesis can be inhibitedWhen a patient has sugarsthat are elevated, angiogene-sis is inhibited, said Dr.Zahedi. In addition, there aredecreased levels of urokinaseplasminogen activator and

increased levels of plasmino-gen activator inhibitor, as wellas decreased basement mem-brane degradation needed fornew capillary growth.

Dressings have beendesigned to address the prob-lem of slow healing of ulcersin diabetic patients, using bio-engineered human dermalsubstitute, but one studyshows that in the presence ofhyperglycemia, these dress-ings are not effective.

“If [the patients] have poor

[glycemic] control, these dress-ings won’t work,” she said.

A prospective study of 245patients saw 130 treated with adermal substitute and 115serving as control subjects.Despite being designed withgrowth factors and living skinsubstitutes, the innovativedressings were not observedto accelerate healing in thepresence of hyperglycemia.

Investigators found no dif-ference in healing whenusing dermal substitute-man-

aged wounds in the presenceof elevated A1c (measure ofaverage glucose over lastthree months). Whenpatients had stable orreduced A1c, 26.3% of allwounds and 47% of dermalsubstitute-managed woundssuccessfully healed (p<0.05)(Ostomy Wound Manage-ment 2006 Mar; 52(3):26–28).

HbA1C better biomarkerAnother study found a linearrelationship between bloodglucose and wound healing.Investigators looked at factorsthat affected the wound-areahealing rate. Previous studieshave looked at the impact ofnon-modifiable factors andwound healing such as age orgender. Reports previouslypublished found rapid woundhealing was associated withsmaller wound size, but thisstudy found A1c was a betterbiomarker to predict healingthan baseline wound size.

From this investigation,glycemia, as measured byA1c, was significantly linkedwith wound-area healingrate. In particular, for every1.0% elevation in A1c, thedaily wound-area healing ratefell by 0.028 cm2 per day(Journal of InvestigativeDermatology 2011 Oct;131(10):2121–2127).

Given the importance ofaccurate A1c measurements inwound healing, she cautionedclinicians to be aware of clini-cal scenarios or factors thatmight interfere with capturingaccurate A1c measurement.Medications such as ribavirinand interferon-alpha and sup-plements like Vitamin E canfalsely reduce hemoglobin A1cmeasurements (Journal ofGeneral Internal Medicine 2014Feb; 29(2):388–394). Othercommon factors that mayinterfere with A1c measure-ment include anemia and kid-ney disease.

The presence of neuropa-thy, which can make patientswith diabetes unable to senseif they have an ulcer of thefoot, means they have to takepreventive measures such asthe avoidance of walkingbarefoot, even in the house,and wearing socks regularly.

Patients with diabetesshould be seeing a chi-ropodist if they have corns orcalluses that need to beremoved; they should notremove them themselves, hesaid. They should learn to fre-

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Control of glucose key to successful wound healingContinued from page 1

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Picato® Gel (ingenol mebutate) is indicated for topical treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis (AK) in adults.

Picato® Gel is about treatment time in actinic keratosis.

C O V E R E DO N M O S TP R I V A T EP L A N S

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and international experts in dermatol-ogy and other related clinical fieldson a wide-ranging selection of topics.Following are highlights of selectedplenary sessions delegates canattend. Please check your final pro-gram to ensure that times or venueshave not changed.

How the data revolution willchange the scientific method

WHEN: Tuesday June 9, 10:30 a.m.WHERE: West Ballroom ABCDData scientist and physician Dr. AtulButte is scheduled to discuss hiswork and research that makes use ofthe “data driven revolution” during aplenary session on Tuesday, June 9.

Dr. Butte, chief of the Division ofSystems Medicineand associate pro-fessor in pedi-atrics, medicine,and by courtesycomputer scienceat StanfordUniversity andLucile PackardChildren’s Hosp-ital in Palo Alto,

Calif., told THE CHRONICLE OF SKIN &ALLERGY that his primary goal is tocommunicate that this is an excitingtime to be in science and researchbecause there is so much information

available online. Dr. Butte added thatmedicine in the future is going torequire doctors to have a muchgreater understanding of DNAsequencing and data analysis—orprecision medicine.

“The DNA and analysis are thereand today we would never expect aradiologist to interpret radiologyimages by just looking at ones andzeros on a computer file. We givethem tools to analyse this data, and itis the same thing with precision med-icine,” Dr. Butte said.

“In dermatology, whether it isapps to look at moles, whether it isgenome analysis to try to figure outsomeone’s risk for psoriasis, we arenot expecting physicians of the futureto do this all by themselves, but to beready for the world with tools and tolearn how to use those tools to helppatients.”

In 2012, Dr. Butte gave a TEDMEDtalk where he discussed his workusing an online marketplace for sci-entific and pharmaceutical researchservices (assaydepot.com) to deter-mine potential new uses for therapiesthat are already available (i.e., drugrepositioning) such as an anticonvul-sant (topiramate) as a therapy forCrohn’s disease.

“Finding new uses for drugs,especially connecting a rare diseaseto a commonly treated disease

makes me feel good about thefuture of how we can suggest thera-pies in the future for our patients.But the idea is that we as scientistsnow have to share our data to get topredictions and drug uses like this,”said Dr. Butte during his TEDMEDtalk.

Autoinflammatory syndromesand the skin

WHEN: Thursday, June 11, 10:30 a.m.WHERE: West Ballroom ABCDOn Thursday, June 11, Dr. DanielKastner of the Division of IntramuralResearch at the National HumanGenome Research Institute inBethesda, Md., will be presenting a

talk on a group ofrelated geneticdisorders thatimpact the innateimmune systemand can producecutaneous mani-festations, as wellas other issues,and can potential-ly be fatal.

“The autoin-flammatory diseases are a group ofdisorders in which people haveseemingly unprovoked inflammationthat can be either systemic or local-ized without the high titre antibodiesor antigen-specific T-cells that wewould usually see in the more classicautoimmune diseases,” says Dr.Kastner.

Dr. Kastner and his colleaguesproposed the concept of autoinflam-matory disease in 1999 after they dis-covered a new disease they calledTRAPS: TNF Receptor-AssociatedPeriodic Syndrome. TRAPS, as well asother autoinflammatory diseases,such as the recently-describedDADA2 (Deficiency of ADA2) areassociated with a recurrent fever,migratory skin rashes, severe abdomi-nal pain, severe chest pain, arthritis,as well as other manifestations.“Some of the patients go on to devel-op kidney failure from a build-up ofsome inflammatory proteins of thekidney,” says Dr. Kastner.

The doctors who attend the ple-nary session can hope to “take awayan understanding of the concept ofautoinflammatory disease and itsrelationship to the different branch-es of the immune system,” says Dr.Kastner. “They will take away someunderstanding of how new geneticapproaches can lead to the discov-ery of the genes that can causethese diseases. Thirdly, that they willhave at least the familiarity withsome of the cutaneous manifesta-tions of at least some of these dis-eases.”

And finally Dr. Kastner says hehopes the audience will come to gain

an understanding of the pathogenesisof these diseases and, in some cases,the possible treatments.

Because of the cutaneous mani-festations associated with theseautoinflammatory diseases, derma-tologists may be the first physiciansto encounter these patients, says Dr.Kastner. As a result, familiarity withthese manifestations and thinkingabout them as part of a differentialdiagnosis, and knowing whichgenetic tests to request in the pres-ence or absence of an autoinflam-matory disease, could help to makea significant difference in patientoutcomes.

“Some of the patients that wesee with this disease DADA2 canhave strokes at the age of two, so it isa serious thing,” says Dr. Kastner.“And a dermatologist who recognizesthat early on and makes the diagno-sis and recommends getting thepatient on treatment that can make ahuge difference in their lives–not onlyof the patients, but of their families aswell.”

Role of stem cellsin dermatology

WHEN: Friday, June 12, 10:30 a.m.WHERE: West Ballroom ABCDProfessor and investigator ElaineFuchs, PhD, will be presenting detailsregarding her research relating to therole of stem cells in dermatology, dur-ing a plenary session at the WCD onFriday, June 12, 2015.

“I am excited about having theopportunity to present at the WorldCongress of Dermatology inVancouver,” said Dr. Fuchs, aRebecca Lancefield Professor inMammalian Cell Biology andDevelopment at The RockefellerUniversity and Investigator, HowardHughes Medical Institute at ColumbiaUniversity in New York, NY.

“My research for many years hasbeen on the basic science of skinbiology. For a long time now, my col-leagues and I have had a stronginterest in taking our work to thelevel where it would be of interest todermatologists who would be able totake our work the next step andhopefully develop new andimproved diagnostic and therapeutictools with clinical applications,” Dr.Fuchs told THE CHRONICLE OF SKIN &ALLERGY.

Dr. Fuchs said that much of herrecent work has centered on identify-ing, characterizing and understandingstem cells that exist within the skinranging from the stem cells of the epi-dermis, hair follicles and sweatglands.

“We have had a long standinginterest in understanding the basicbiology behind how stem cells func-

WCD preview: Highlights of Vancouver plenary sessionsContinued from page 1

Clinical dermatologistsneed to be aware thattheir patients maynot be getting ex-pected results from

prescribed topical medicationsdue to differences in vehicle for-mulations between brandedproducts and the generics thatpatients may be using in theirplace, says Dr. Leon H. Kircik,Clinical Associate Professor ofDermatology at the Mount SinaiMedical Center, Indiana Univer-sity School of Medicine.

The issue, Dr. Kircik ex-plains, is that the various meth-ods North American drugregulatory bodies such as HealthCanada or the FDA use to evalu-ate whether a generic topicalproduct is bioequivalent to abranded drug do not take intoaccount the role vehicle formu-lation plays in the therapeutic ef-fect of the active agents.

Bioequivalent Does Not Equal Therapeutically Equivalent Health Canada’s guidance docu-ment Comparative BioavailabilityStandards: Formulations Used forSystemic Effects indicates that sub-sequent-entry medications mustdemonstrate bio-equivalence tothe reference product for areaunder curve (AUC) for the bloodconcentration vs. time curve, andmaximum blood concentration.Yet, to be considered bioequiva-lent, the 90% Confidence Intervals(CI) of the subsequent-entry prod-ucts’ AUC can fall anywherewithin a range of 80% to 125% ofthe reference product, and the90% CIs of the maximum bloodconcentration doesn’t even haveto fall within this range.

“Let’s say there is a [clobetasolpropionate] cream and the origi-nator made a really good cream,with a good base, so it is both ele-gant and stable. Then a genericcomes out. The generic doesn’thave to do a clinical trial,” saysDr. Neil Shear, Division Head ofDermatology at Toronto’s Sunny-brook Hospital and Director of

the University of Toronto DrugSafety Research Group.

As long as the generic manu-facturer can show an analysisthat proves their product has thesame active agents at the sameconcentrations as the brandedproduct and a similar viscosity,the generic will likely be ap-proved, he says. “But nobody hasseen whether the generic creamis more potent, less potent, orwhether it is even going to beused [by the patient].”

With oral formulations, as-suring therapeutic equivalence iscomparatively simple, says Dr.David Gratton, a dermatologist inprivate practice in Montreal.“Getting creams to be bio-equiva-lent is much more tricky,” hesays. The vehicle carries the ac-tive agent to the skin, but thenhas to both let it go so the activeagent can have its effect, and as-sist in the penetration of the skin.“That’s why, even if you have thesame amount of, say, betametha-sone valerate, a different vehiclewill give you different penetra-tion rates. The occlusive natureof an ointment allows for ahigher penetration than a cream,and the cream more so than agel, for instance,” he says.

Your Patients May Not Get What You PrescribedPatients end up with differenttopical formulations than thoseprescribed by dermatologists

when they take those prescrip-tions to be filled at the pharma-cist, says Dr. Shear. “The issuehas been around a long time,” hesays, but over the yearsprovinces have changed theirdispensing regulations, permit-ting pharmacists more ability toadapt prescriptions. “For exam-ple, they can say ‘Oh you had theointment, we’ll just give you thecream,’” says Dr. Shear.

But dermatologists base theirprescriptions on what they knowworks, says Dr. Gratton. “When adermatologist chooses a steroidcream for a particular skinproblem it is based a lot on expe-rience. When I see psoriasis ofthe palms, I know from my last250 palm psoriasis patients that Iget good results with [brandedbetamethasone diproprionate]cream. Now the patient may get[generic] betamethasone dipro-prionate. What he is going to get[from the pharmacist], I don’tknow. So it is a bit of an un-known territory,” he says.

“If you feel strongly that youwant this specific cream andnothing else, you can try andwrite ‘do not substitute’ on theprescription and hope the patientwill get what you prescribe,”

says Dr. Gratton.Some pharmacists do ask Dr.

Shear if it is acceptable to changethe vehicle a patient’s medicationis formulated with, he says. Thiscould be due to availability, pa-tient request or other reasons.Asking the prescibing doctor thisquestion is not required in On-tario but it is appreciated, says Dr.Shear, noting that in Ontariopharmacists are only legallybound to advise him that the sub-stitution has been done. Otherprovinces may have different reg-ulations, however, and cliniciansshould be aware of these regula-tions in case a patient appears togetting unexpected results.

Generic Variability“Let’s say you take somethingthis week or this month that is at100 per cent par with your refer-ence product, which is thebranded product,” says Dr. Kir-cik. “Then next month you havesomething that is at 80 per centof that branded product, so youhave 20 per cent less efficacy. Orit can be the exact opposite.

“You can have somethingthat is at 125 per cent strength ofthe branded product now, so youhave something that is 25 per

Not all topical preparationsare created the same

S P E C I A L R E P O R T

Your patients may not be getting the results you expect from topical therapies

Dr. Gratton Dr. Kircik Dr. Shear

“[N]obody has seen whether the generic cream is morepotent, less potent, or whether it is even going to be used[by the patient]”

—Dr. Neil Shear

Treatment as Prevention: Building on the HIV experienceto promote healthcare sustainability

WHEN: Wednesday, June 10, 10:30 a.m.WHERE: West Ballroom ABCDDr. Julio Montaner, the director of the BC Centre for Excellence in HIV/AIDS,a professor and head of the Division of AIDS at the University of BritishColumbia in Vancouver, will be giving a plenary session on Wednesday,June 10, on his Treatment as Prevention (TasP) strategy.

“Since 1996, when we discovered [highly active antiretroviral therapy orHAART as a therapy for HIV], we were able to deploythat in the community and we saw significant decreas-es in morbidity and mortality, but then unexpectedly wealso saw that the treatment was uniquely able todecrease the likelihood of transmission of an HIV-infect-ed person to his or her peers,” Dr. Montaner told THECHRONICLE OF SKIN & ALLERGY. “We became interested in[HAART] HIV treatment as a prevention approach.”

Dr. Montaner said the TasP’s “seek and treat”approach calls for proactive testing of the community atlarge and proactive engagement of people on treatmentthrough support. The method involves a slight increase

of investment upfront with a long term “dramatic return on investment.” Hehas been sharing TasP with his colleagues in other fields for the goal of itbecoming the cornerstone for a disease elimination strategy.

“I welcome the opportunity to discuss this with our dermatology col-leagues, first because it is an interesting story . . . and there were multiple . .. skin related complications of HIV that unfortunately my colleagues sawand hopefully they do not see anymore because our strategy has been sosuccessful. So I suspect that they would be interested in knowing about thisfrom that perspective. But beyond that, we would like them to start thinking,‘is there anything in the repertoire of the diseases that we will deal with thatwould be amenable to this type of treatment?’”

In Dec. 2014, Dr. Montaner was appointed an Officer of the Order ofCanada. “Being a foreign graduate who has been here for about 30 years,this kind of recognition from my adopted country really means twice asmuch to me,” he said.

Dr. Atul Butte

Dr. DanielKastner

Dr. Julio Montaner

Please turn to WCD Preview page 26à


Clinical dermatologistsneed to be aware thattheir patients maynot be getting ex-pected results from

prescribed topical medicationsdue to differences in vehicle for-mulations between brandedproducts and the generics thatpatients may be using in theirplace, says Dr. Leon H. Kircik,Clinical Associate Professor ofDermatology at the Mount SinaiMedical Center, Indiana Univer-sity School of Medicine.

The issue, Dr. Kircik ex-plains, is that the various meth-ods North American drugregulatory bodies such as HealthCanada or the FDA use to evalu-ate whether a generic topicalproduct is bioequivalent to abranded drug do not take intoaccount the role vehicle formu-lation plays in the therapeutic ef-fect of the active agents.

Bioequivalent Does Not Equal Therapeutically Equivalent Health Canada’s guidance docu-ment Comparative BioavailabilityStandards: Formulations Used forSystemic Effects indicates that sub-sequent-entry medications mustdemonstrate bio-equivalence tothe reference product for areaunder curve (AUC) for the bloodconcentration vs. time curve, andmaximum blood concentration.Yet, to be considered bioequiva-lent, the 90% Confidence Intervals(CI) of the subsequent-entry prod-ucts’ AUC can fall anywherewithin a range of 80% to 125% ofthe reference product, and the90% CIs of the maximum bloodconcentration doesn’t even haveto fall within this range.

“Let’s say there is a [clobetasolpropionate] cream and the origi-nator made a really good cream,with a good base, so it is both ele-gant and stable. Then a genericcomes out. The generic doesn’thave to do a clinical trial,” saysDr. Neil Shear, Division Head ofDermatology at Toronto’s Sunny-brook Hospital and Director of

the University of Toronto DrugSafety Research Group.

As long as the generic manu-facturer can show an analysisthat proves their product has thesame active agents at the sameconcentrations as the brandedproduct and a similar viscosity,the generic will likely be ap-proved, he says. “But nobody hasseen whether the generic creamis more potent, less potent, orwhether it is even going to beused [by the patient].”

With oral formulations, as-suring therapeutic equivalence iscomparatively simple, says Dr.David Gratton, a dermatologist inprivate practice in Montreal.“Getting creams to be bio-equiva-lent is much more tricky,” hesays. The vehicle carries the ac-tive agent to the skin, but thenhas to both let it go so the activeagent can have its effect, and as-sist in the penetration of the skin.“That’s why, even if you have thesame amount of, say, betametha-sone valerate, a different vehiclewill give you different penetra-tion rates. The occlusive natureof an ointment allows for ahigher penetration than a cream,and the cream more so than agel, for instance,” he says.

Your Patients May Not Get What You PrescribedPatients end up with differenttopical formulations than thoseprescribed by dermatologists

when they take those prescrip-tions to be filled at the pharma-cist, says Dr. Shear. “The issuehas been around a long time,” hesays, but over the yearsprovinces have changed theirdispensing regulations, permit-ting pharmacists more ability toadapt prescriptions. “For exam-ple, they can say ‘Oh you had theointment, we’ll just give you thecream,’” says Dr. Shear.

But dermatologists base theirprescriptions on what they knowworks, says Dr. Gratton. “When adermatologist chooses a steroidcream for a particular skinproblem it is based a lot on expe-rience. When I see psoriasis ofthe palms, I know from my last250 palm psoriasis patients that Iget good results with [brandedbetamethasone diproprionate]cream. Now the patient may get[generic] betamethasone dipro-prionate. What he is going to get[from the pharmacist], I don’tknow. So it is a bit of an un-known territory,” he says.

“If you feel strongly that youwant this specific cream andnothing else, you can try andwrite ‘do not substitute’ on theprescription and hope the patientwill get what you prescribe,”

says Dr. Gratton.Some pharmacists do ask Dr.

Shear if it is acceptable to changethe vehicle a patient’s medicationis formulated with, he says. Thiscould be due to availability, pa-tient request or other reasons.Asking the prescibing doctor thisquestion is not required in On-tario but it is appreciated, says Dr.Shear, noting that in Ontariopharmacists are only legallybound to advise him that the sub-stitution has been done. Otherprovinces may have different reg-ulations, however, and cliniciansshould be aware of these regula-tions in case a patient appears togetting unexpected results.

Generic Variability“Let’s say you take somethingthis week or this month that is at100 per cent par with your refer-ence product, which is thebranded product,” says Dr. Kir-cik. “Then next month you havesomething that is at 80 per centof that branded product, so youhave 20 per cent less efficacy. Orit can be the exact opposite.

“You can have somethingthat is at 125 per cent strength ofthe branded product now, so youhave something that is 25 per

Not all topical preparationsare created the same


Your patients may not be getting the results you expect from topical therapies

Dr. Gratton Dr. Kircik Dr. Shear

“[N]obody has seen whether the generic cream is morepotent, less potent, or whether it is even going to be used[by the patient]”

—Dr. Neil Shear


cent stronger. I don’t know if thatis good or bad, but the bottomline is you’re not getting thesame. And remember, now,there is more than one generic.So it depends on the generic dujour at the pharmacy.”

“So patients will sometimescome in and say ‘Hey Doc, thatstuff you gave me last monthworked really well, but it stoppedworking all of a sudden,’” saysDr. Kircik. “Well, it stoppedworking because [the patientwas] not getting the same thing.”

However, it can be hard totrace a patient’s poorer treat-ment results to a change in thebrand of medication they ob-tained from their pharmacist,says Dr. Shear. “People don’tbring their cream in. They don’tknow if it has been changed. Ifit was in a jar or somethingthey wouldn’t know if it wasbrand name x in the jar whenthey first used it, and the nexttime it was generic y.” The pa-tient just notices the rash isworse in spite of continuingtreatment, and the doctor doesn’tknow the cause.

With topical agents, changesin brand are not obvious, says Dr.Shear. “It’s not like being treatedwith a pill, and they say ‘I used tohave a green pill and now I havea white pill.’” That might make aclinician think a patient’s brandhad been changed. But if a patienthas switched between two whitecreams, they aren’t likely to re-mark on it.”

Vehicle Can Affect AdherenceA differently formulated vehiclecan impact a patient in a num-ber of ways, says Dr. Shear. Ve-hicle texture can impacttreatment adherence, for exam-ple, he says. “You’re going to putstuff on much of your body. Yourface, your chest, your back, yourhands. It would be nice if themedication went on and feltgood, as opposed to feelinggoopy,” he says. “If it’s just asticky mess, sometimes peopledon’t use it. And if they don’t useit, it is not going to work.”

A clinician can try the prod-ucts to help understand the pa-tient experience, says Dr. Gratton.“Get a bunch of samples and seehow they feel on your hand oryour forearm. Smell them.” Thiswill give a clinician some ideawhat patients are being asked todo to their skin, which can in-form your prescriptions, he says.

For skin conditions such asacne, eczema, or psoriasis wherethe moisturizing, skin-barriersupporting traits of the emollientin the vehicle can be a strongcomplement to the active drug, achange in product might resultin noticeable drying of the pa-tient’s skin and all that entails,says Dr. Shear.

“When you are putting theproduct on the skin, you are im-pacting on the moisture lossfrom the skin,” he says. “Youcould tell a patient ‘oh by theway, buy this moisturizer anduse this treatment,’ or ‘just usethis treatment, it will moisturize

at the same time.’”And, of course, if

a change in vehicleis altering howmuch of the activeagent is available inthe skin, that willchange the patientexperience, says Dr.Shear.

“Patients willlearn, with a topical,what they need to doto get their eczemabetter, or psoriasis,”how much to applywhere, how fre-quently, and so on. Ifthat’s changed [due toa change in vehicle],then suddenly theyhave to relearn.

“The treatment isnot necessarily goingto be a failure, but itmight not work and

then they’re not sure why, andthey might have to use it moreoften. They have to experiment.Patients don’t want to do that. Ifsomething is really itchy or redand disfiguring, scaly and in-fected, they want to be able toget it under control. So for peo-ple’s own self-care, they need toknow the product they’re gettingis pretty much the same.”

Generic Formulations and Side EffectsIf the generic formulation deliv-ers more active agent than ex-pected, it increases the possibilityof side-effects, says Dr. Shear. Forexample, with a topical steroid,“you might see more steroid side-effects like thinning of the skinand bruising,” though those side-effects are rare, he says.

Side effects could also arisefrom components of the vehicle,including preservatives or pene-tration enhancers. These compo-nents may be allergens for thepatient, or may be irritants ontheir own.

For example, Dr. Kircik says,many topical products containpropylene glycol. “Propylene gly-col is, at low concentrations, ac-tually a good thing. It’s a goodhumectant, and it has antibioticproperties.” It also works as apenetration enhancer, makingthe active agent in the topicalformulation more available tothe body.

“But at higher concentrationsit is one of the biggest irritants,”says Dr. Kircik. “It is actually

sometimes the contact allergen ofthe year. And the generic compa-nies like to put propylene glycol,a lot of it, in the steroids becauseit is a penetration enhancer.”

Being aware that patients maybe receiving and using differentformulations of their medicationsthan they are being prescribeddoes not mean that the problem iseasily fixed, says Dr. Kircik.

“Patients always have a bet-ter relationship with the phar-macist than the doctor,” he says.

Pharmacy SubstitutionThrough that relationship phar-macists can convince the patientthat a different brand than theone prescribed would either bebetter for the patient or equiva-lent and less expensive. The pa-tient will likely take thepharmacist’s advice “unless youhave a very sophisticated con-sumer that, when they go to thepharmacy, they tell the pharma-cist exactly what they want andthey won’t budge,” says Dr. Kir-cik. “That’s a very infrequentpopulation, unfortunately.”

However, with a good under-standing of the therapies on themarket you may be able to miti-gate this substitution processthrough a choice of what prod-ucts you prescribe, says Dr. Kir-cik. Dermatologists can achievethis “by writing prescriptions fortherapies for which genericsaren’t available.

“I have nothing againstgenerics. I just like to know whatmy patients are getting,” Dr. Kir-cik says.

Supplement to THE CHRONICLE OF SKIN &

ALLERGY, April 2015. Chronicle is an inde-

pendent medical news service that pro-

vides educational updates regarding

medical developments around the world.

Views expressed are those of the partici-

pants and do not necessarily reflect those

of the publisher or sponsor.

Support for distribution of this re-

port was provided by Valeant Canada

through an unrestricted educational

grant without conditions. Information

provided in this report is not intended to

serve as the sole basis for individual care.

Printed in Canada for Chronicle In-

formation Resources Ltd., 555 Burn-

hamthorpe Rd., Suite 306, Toronto, Ont.

M9C 2Y3.Telephone 416.916.2476; facsimile

416.352.6199; e-mail: [email protected].

Copyright 2015 by Chronicle Information

Resources Ltd., except where noted. All

rights reserved. Reproduction in any

form is expressly prohibited without

written permission of the publisher.


Kircik L: Understanding Generics. JDD; 13(7):s75-76.

�� Substitute generics can have bbiiooeeqquuiivvaalleennccee vvaarriiaabbiilliittyy ooff uupp ttoo4455%% when compared to branded products (anywhere within arange of 80% to 125% of the reference product)*

Not all topical preparations are created the same:�� Generic preparations can result in decreased efficacy of an active

agent as well as lead to adverse events when compared to brandedpreparations

VVeehhiiccllee iiss tthhee kkeeyy ttoo ttrreeaattmmeenntt ssuucccceessss oorr ffaaiilluurree�� Vehicle can affect penetration, permeation, absorption, reservoir

and compartmentalization of active ingredients in addition toaffecting drug stability and shelf life

With a good understanding of the therapies on the market you may beable to mitigate this substitution process through a choice of whatproducts you prescribe. Dermatologists can achieve this “by writingprescriptions for therapies for which generics aren’t available.”

—Dr. Leon Kircik


cent stronger. I don’t know if thatis good or bad, but the bottomline is you’re not getting thesame. And remember, now,there is more than one generic.So it depends on the generic dujour at the pharmacy.”

“So patients will sometimescome in and say ‘Hey Doc, thatstuff you gave me last monthworked really well, but it stoppedworking all of a sudden,’” saysDr. Kircik. “Well, it stoppedworking because [the patientwas] not getting the same thing.”

However, it can be hard totrace a patient’s poorer treat-ment results to a change in thebrand of medication they ob-tained from their pharmacist,says Dr. Shear. “People don’tbring their cream in. They don’tknow if it has been changed. Ifit was in a jar or somethingthey wouldn’t know if it wasbrand name x in the jar whenthey first used it, and the nexttime it was generic y.” The pa-tient just notices the rash isworse in spite of continuingtreatment, and the doctor doesn’tknow the cause.

With topical agents, changesin brand are not obvious, says Dr.Shear. “It’s not like being treatedwith a pill, and they say ‘I used tohave a green pill and now I havea white pill.’” That might make aclinician think a patient’s brandhad been changed. But if a patienthas switched between two whitecreams, they aren’t likely to re-mark on it.”

Vehicle Can Affect AdherenceA differently formulated vehiclecan impact a patient in a num-ber of ways, says Dr. Shear. Ve-hicle texture can impacttreatment adherence, for exam-ple, he says. “You’re going to putstuff on much of your body. Yourface, your chest, your back, yourhands. It would be nice if themedication went on and feltgood, as opposed to feelinggoopy,” he says. “If it’s just asticky mess, sometimes peopledon’t use it. And if they don’t useit, it is not going to work.”

A clinician can try the prod-ucts to help understand the pa-tient experience, says Dr. Gratton.“Get a bunch of samples and seehow they feel on your hand oryour forearm. Smell them.” Thiswill give a clinician some ideawhat patients are being asked todo to their skin, which can in-form your prescriptions, he says.

For skin conditions such asacne, eczema, or psoriasis wherethe moisturizing, skin-barriersupporting traits of the emollientin the vehicle can be a strongcomplement to the active drug, achange in product might resultin noticeable drying of the pa-tient’s skin and all that entails,says Dr. Shear.

“When you are putting theproduct on the skin, you are im-pacting on the moisture lossfrom the skin,” he says. “Youcould tell a patient ‘oh by theway, buy this moisturizer anduse this treatment,’ or ‘just usethis treatment, it will moisturize

at the same time.’”And, of course, if

a change in vehicleis altering howmuch of the activeagent is available inthe skin, that willchange the patientexperience, says Dr.Shear.

“Patients willlearn, with a topical,what they need to doto get their eczemabetter, or psoriasis,”how much to applywhere, how fre-quently, and so on. Ifthat’s changed [due toa change in vehicle],then suddenly theyhave to relearn.

“The treatment isnot necessarily goingto be a failure, but itmight not work and

then they’re not sure why, andthey might have to use it moreoften. They have to experiment.Patients don’t want to do that. Ifsomething is really itchy or redand disfiguring, scaly and in-fected, they want to be able toget it under control. So for peo-ple’s own self-care, they need toknow the product they’re gettingis pretty much the same.”

Generic Formulations and Side EffectsIf the generic formulation deliv-ers more active agent than ex-pected, it increases the possibilityof side-effects, says Dr. Shear. Forexample, with a topical steroid,“you might see more steroid side-effects like thinning of the skinand bruising,” though those side-effects are rare, he says.

Side effects could also arisefrom components of the vehicle,including preservatives or pene-tration enhancers. These compo-nents may be allergens for thepatient, or may be irritants ontheir own.

For example, Dr. Kircik says,many topical products containpropylene glycol. “Propylene gly-col is, at low concentrations, ac-tually a good thing. It’s a goodhumectant, and it has antibioticproperties.” It also works as apenetration enhancer, makingthe active agent in the topicalformulation more available tothe body.

“But at higher concentrationsit is one of the biggest irritants,”says Dr. Kircik. “It is actually

sometimes the contact allergen ofthe year. And the generic compa-nies like to put propylene glycol,a lot of it, in the steroids becauseit is a penetration enhancer.”

Being aware that patients maybe receiving and using differentformulations of their medicationsthan they are being prescribeddoes not mean that the problem iseasily fixed, says Dr. Kircik.

“Patients always have a bet-ter relationship with the phar-macist than the doctor,” he says.

Pharmacy SubstitutionThrough that relationship phar-macists can convince the patientthat a different brand than theone prescribed would either bebetter for the patient or equiva-lent and less expensive. The pa-tient will likely take thepharmacist’s advice “unless youhave a very sophisticated con-sumer that, when they go to thepharmacy, they tell the pharma-cist exactly what they want andthey won’t budge,” says Dr. Kir-cik. “That’s a very infrequentpopulation, unfortunately.”

However, with a good under-standing of the therapies on themarket you may be able to miti-gate this substitution processthrough a choice of what prod-ucts you prescribe, says Dr. Kir-cik. Dermatologists can achievethis “by writing prescriptions fortherapies for which genericsaren’t available.

“I have nothing againstgenerics. I just like to know whatmy patients are getting,” Dr. Kir-cik says.

Supplement to THE CHRONICLE OF SKIN &

ALLERGY, April 2015. Chronicle is an inde-

pendent medical news service that pro-

vides educational updates regarding

medical developments around the world.

Views expressed are those of the partici-

pants and do not necessarily reflect those

of the publisher or sponsor.

Support for distribution of this re-

port was provided by Valeant Canada

through an unrestricted educational

grant without conditions. Information

provided in this report is not intended to

serve as the sole basis for individual care.

Printed in Canada for Chronicle In-

formation Resources Ltd., 555 Burn-

hamthorpe Rd., Suite 306, Toronto, Ont.

M9C 2Y3.Telephone 416.916.2476; facsimile

416.352.6199; e-mail: [email protected].

Copyright 2015 by Chronicle Information

Resources Ltd., except where noted. All

rights reserved. Reproduction in any

form is expressly prohibited without

written permission of the publisher.


Kircik L: Understanding Generics. JDD; 13(7):s75-76.

� Substitute generics can have bioequivalence variability of up to45% when compared to branded products (anywhere within arange of 80% to 125% of the reference product)*

Not all topical preparations are created the same:� Generic preparations can result in decreased efficacy of an active

agent as well as lead to adverse events when compared to brandedpreparations

Vehicle is the key to treatment success or failure� Vehicle can affect penetration, permeation, absorption, reservoir

and compartmentalization of active ingredients in addition toaffecting drug stability and shelf life

With a good understanding of the therapies on the market you may beable to mitigate this substitution process through a choice of whatproducts you prescribe. Dermatologists can achieve this “by writingprescriptions for therapies for which generics aren’t available.”

—Dr. Leon Kircik

Autoimmune diseasenot a positiveprognosticator in MM

WHILE THERE HAVE BEEN REPORTS IN THE LITERATURE that autoimmune disease is a positive prognos-tic factor in malignant melanoma (MM), findings from a recent study in Clinical andExperimental Dermatology (April 2015; 40(3):254-259) show that neither tumour-associat-

ed nor drug-induced autoimmune disease was associated with better prognosis in patients withmalignant melanoma.

In the study, researchers categorized autoimmune disease as tumour-associated, drug-induced, or paraneoplastic.Patients were then enrolled based on clinicopathologic features and matched with control groups. Disease-free sur-vival (DFS) and overall survival (OS) were estimated, and a log-rank test was used to evaluate the difference betweenthe survival curves. The analysis included 49 patients with tumour-associated MM. No cases of paraneoplastic autoim-mune disease were detected. A range of results were seen in the survival analysis, from a worsening of both DFS andOS to no difference at all.

A second analysis looking only at patients who had developed autoimmune disorders only after starting interferon-� adjuvant treatment found no significant difference between this groups and untreated patients. The researchers sug-gest that the association between autoimmune disease and MM reported in the literature may be due to individualvariation in sensitivity to the autoimmune disease, tumour, or treatment.

—For more information visit http://tinyurl.com/mu5tdqh

Wound healing maybe prevented by per-manent deregulationof the extracellularmatrix

THE FLUID IN CHRONIC WOUNDS APPEARS TO DIFFER FROM THAT IN ACUTE WOUNDS, excessively inducingmatrixmetalloproteinase (MMP)-9 expression which might lead to permanent deregulation ofthe extracellular matrix and prevent wound healing, researchers report in International

Wound Journal (Apr. 2015; 12(2):143-149). Wound healing, according to the researchers, requiresa proper functioning of keratinocytes that migrate, proliferate and that ultimately lead to a compe-tent wound closure.

The authors note that proper functioning of keratinocytes including migration, proliferation and competent woundclosure are vital to wound healing and that impaired wound healing might be due to a disturbed keratinocyte functiondue to the wound environment.

To analyze the effects of acute wound fluid (AWF) and chronic wound fluid (CWF) on keratinocyte function,investigators examined keratinocyte proliferation and migration using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] test and a scratch assay. As well, qRT-PCR was used to analyse gene expression of growth fac-tors and MMPs involved in regeneration processes. They found that AWF positively impacted keratinocyte proliferationover time, while CWF impaired such proliferation. Keratinocyte migration was also significantly impaired under CWFcompared to an undisturbed wound closure influenced by AWF. CWF strongly upregulated MMP-9, and significantlyimpaired keratinocyte function compared to AWF.

—For more information visit http://tinyurl.com/mjrjl7r

Study analyses oxybutynin inpatients with plantarhyperhidrosis

ALONG-TERM FOLLOW UP STUDY of patients being treated with oxybutynin for plantar hyperhydrosishas found that more than 82% of patients who had a good initial response to the drug had amoderate to great improvement in excessive sweating on plantar or other sites, with tolera-

ble side effects that did not interrupt treatment, according to findings published in InternationalJournal of Dermatology (May 2015; 54(5):605-611).

A total of 85 consecutive patients were enrolled from Sept. 2007 to Sept. 2013 in a pharmacologic-first institutionaltreatment protocol for primary plantar hyperhydrosis using oxybutynin. Of those, eight were lost to follow up, and 15had not yet been under treatment for six months. Data on 39 patients—all female—who had been under treatment forat least six months was available, with data from the start of protocol, after six months, and at final treatment beinganalysed for the study. Some 23 of the 77 patients who were not lost to follow up (29.87%) did not improve underpharmacologic therapy.

Of the 39 responders with more than six months of follow up (median follow-up 16.9 months, ranging from nine to71 months), 79.5% reported moderate to great improvement in their excessive plantar sweating after six weeks oftreatment. This percentage rose to 84.7% at the last follow up visit, and 82.85% had improvement in other sites ofexcessive sweating as well. The most commonly reported side effect was dry mouth, with 51.6% reporting it to bemoderate to severe on the last visit..

—For more information visit http://tinyurl.com/lcaybvo

Surveying the current

Dermatologic literature

Recently come across something from the peer-review literature that you consider to be interesting orimpactful? Share it with your colleagues. E-mail your clippings, along with your comments, to:

[email protected]

THE CHRONICLE of SKIN & ALLERGY

Vol. 20, No. 5 April/May 2015 19



Acne research THE CHRONICLE of SKIN & ALLERGY

R e s e a r c h

Spironolactone updaten Routine K monitoring unneeded in women

Rates of hyperkalemia in healthy young women taking spironolactone foracne are comparable to the baseline rate of the condition in this popula-tion, suggesting that routine potassium monitoring is unnecessary forhealthy women taking this medication for acne, according to a paper pub-lished online in JAMA Dermatology (March 22, 2015).

The study’s authors carried out a retrospective study including recordsof 974 healthy young women taking spironolactone for acne, using datafrom a clinical data repository from Dec. 1, 2000 through Mar. 31, 2014.The outpatient data was collected from two U.S. tertiary care centres.Data from 1,165 healthy young women taking and not taking spironolac-tone were also analysed to develop a profile of the baseline rate of hyper-kalemia in this population. Cardiovascular disease, renal failure, and theuse of medications which impact the renin-angiotensin-aldosterone sys-tem were exclusion criteria. Among the 1,802 serum potassium measure-ments taken among young women receiving spironolactone therapy, 13were abnormal, yielding a hyperkalemia rate of 0.72%. This was equiva-lent to the 0.76% baseline rate in this population. Repeat testing in six ofthose 13 patients produced normal values, suggesting the measurementsmay have been erroneous.


R e s e a r c h

RAGA combo for scarsn Topical gel may cut need for proceduresFrom the News Resources of The Chronicle

A combination of retinoic acid and glycolic acid (RAGA) effectivelytreats acne scars in a majority of patients, reducing the need for proce-dural treatments, according to f indings published in IndianDermatology Online Journal (Mar.-Apr. 2015; 6(2):84-88).

The authors note that retinoic acid is said to improve acne scarsand reduce postinflammatory hyperpigmentation, and that glycolicacid is known to have keratolytic properties that can reduce atrophicacne scars. While there are prior studies that have shown a combina-tion of retinaldehyde and glycolic acid has produced positive results inthe reduction of acne scars, the RAGA combination has not previouslybeen explored. Researchers conducted a retrospective assessment of35 patients who used the RAGA combination for their acne scars. Theassessment included case records and photographs of each patient,with acne scars graded per Goodman and Baron’s global scarring grad-ing system (GSGS) before RAGA treatment and at 12 weeks of treat-ment. Improvement was noted as the difference between the scargrades.

At the 12 week mark, 91.4% of patients had a significant improve-ment in their acne scars.

Acne updateTWICE-DAILY ISOTRETINOIN DOSEMAY REDUCE SIDE EFFECTSDividing isotretinoin dosage in acnetreatment into a twice-daily regimeninstead of a once-daily regimen mayhelp to reduce the incidence of sideeffects without reducing clinical effi-cacy, researchers report online inDermatologic Therapy (March 5,2015).

To compare the efficacy andsafety of oral isotretinoin treatmentfor acne vulgaris in a twice-dailyadministration vs. once daily admin-istration of the same total daily dose,researchers randomized 58 patientsinto two groups. Group I (26) receiv-ing a single dose per day, and GroupII (32) receiving medication twiceper day. Laboratory changes inserum lipids and liver function weremonitored, and the global acne scor-ing system was used to evaluateseverity of the acne as well as post-treatment improvement. In botharms, highly significant clinicalimprovement in acne was seen,with no significant differencebetween the two. In Group I, howev-er, side effects were significantlymore common. Both arms saw arise in serum cholesterol, alaninetransaminase (ALT), and aspartateaminotransferase (AST), and a moreprominent rise of triglycerides espe-cially on the twice-daily regimen.

CLINDAMYCIN PHOSPHATE/BPOCOMBINATION FOUND MOREEFFECTIVE IN FEMALE PATIENTSFemale patients appear to experi-ence superior efficacy from a combi-nation treatment of clindamycinphosphate 1.2% and benzoyl perox-ide (BPO) 3.75% in a gel formula-tion, though in all patients the com-bination treatment has a significantlygreater efficacy in the treatment offacial acne vulgaris than vehiclealone, researchers report online inThe Journal of DermatologicalTreatment (March 2015; 20:1-5).

The authors conducted a posthoc analysis of the clindamycinphosphate/BPO gel combinationtreatment in 498 male and femalepatients who had moderate tosevere acne. Patients received eitherthe combination treatment or the gelvehicle alone for 12 weeks. In bothgenders, the efficacy of the combi-nation product was significantlygreater than that of the vehicle(p<0.001). However, in the activegroup, the mean percent changefrom baseline in both inflammatoryand non-inflammatory lesion countswas higher in females than in males.A higher percentage of female sub-jects in the active group achieved atwo-grade reduction in theEvaluators Global Severity Score(EGSS) than males, as well(p=0.049). The authors note thatdue to the nature of the study it isimpossible to determine the contri-butions of the individual active ingre-dients.

POSSIBLE ROLE FOR IGF-1 INACNE PATHOGENESISInsulin-like growth factor 1 (IGF-1)may contribute to the pathogenesisof acne vulgaris through its roles inthe proliferation of keratinocytes,sebaceous lipogenesis, and andro-gen synthesis, according to researchpublished in Analytical andQuantitative Cytopathology andHistopathology (Oct. 2014; 36(5):267-278). An observed significant associ-ation between IGF-1, a high bodymass index (BMI), and severe acnesupports the importance of dietaryintervention in the management ofacne vulgaris.

Researchers examined 60 indi-viduals with acne and 40 gender-and age-matched healthy controls.Compared to normal skin, IGF-1 wasoverexpressed in both acne lesions(p<0.0001) and pilo-sebaceous units(p<0.0001). Strong expression ofIGF-1 was significantly associatedwith high BMI values (30 or greater)in acne cases compared to controls.Strong IGF-1 intensity was also sig-nificantly associated with highermean BMI values (p=0.01) andsevere acne (p=0.04). Significantassociations were also seenbetween high BMI values and acneseverity (p=0.001) and aggravationof acne due to consumption of dairyproducts (p=0.03).

NANOGEL TRETINOIN BETTERTOLERATED, MORE EFFECTIVEA nanogel formulation of tretinoinappears to be both more effectiveand better tolerated than conven-tional gel formulations for treatingfacial acne vulgaris, according to astudy published in Journal ofClinical and Diagnostic Research(Jan. 2015; 9(1): WC04-09).

A total of 207 patients wereincluded into the phase IV clinicaltrail, which aimed to compare anovel nanogel formulation oftretinoin to a more conventionalgel. Patients topically applied eitherthe standard gel or the nanogel for-mulation of tretinoin once a day atnight for 12 weeks. Acne lesions(inflammatory, non-inflammatory,and total) were counted, tolerabilityassessments, and severity gradingwas done on scheduled monthlyvisits. Reductions in total lesioncount was higher with the nanogelformulation vs. the standard gel(72.9% vs. 65.0%, p=0.03).Inflammatory lesion count reduc-tion was also significantly betterwith the nanogel (78.1% vs 66.9%,p=0.02). The nanogel was also sig-nificantly safer, with only 13.3% ofthe nanogel group reporting localadverse events vs. 24.7% of the gelgroup (p=0.04). Dryness was themost commonly reported adverseevent in both groups, while only theconventional group reported burn-ing sensations and photosensitivity.


by NANCY WALSH,Special to The Chronicle

Serologic status should beadded to extent of skin involve-ment for more accurate classi-

fication of disease phenotype in sys-temic sclerosis (SSc), Canadianresearchers report.

Systemic sclerosis, also known asscleroderma, has traditionally beendivided into two subtypes: limitedcutaneous and diffuse cutaneous,with the limited form being character-ized by involvement distal to theknees and elbows, with or withoutfacial involvement, and the diffuseform having involvement proximal tothe knees andelbows, with orwithout involve-ment of thetrunk. The limitedform is typicallyassociated withpulmonary hyper-tension, while thediffuse type typi-cally is character-ized by interstitial lung disease andgastrointestinal involvement.

In addition, distinctive autoanti-body patterns also have emerged, withanti-centromere antibody (ACA) mostoften being present in patients with thelimited form and anti-topoisomeraseantibody (ATA) typically being associat-ed with the diffuse form, according toDr. Marie Hudson of McGill Universityin Montreal, and colleagues.

However, in a subset of patients, areverse serologic pattern is seen, with

ACA being identified in patients withdiffuse cutaneous SSc and ATA beingdetected in those with limited cuta-neous disease. Few data are availableon those atypical patients, and less isknown about clinical phenotypes andprognosis, the researchers explainedonline in Seminars in Arthritis andRheumatism.

Moreover, some SSc experts havesuggested that serologic status mightbe a more accurate way of classifyingdisease subtypes and outcomes thanskin involvement.

Correlations with disease subtypeTo examine more closely the relation-ships between these serologic andclinical findings and to test thehypothesis that serology would besuperior to extent of skin involve-ment, Dr. Hudson and colleaguesanalysed data from the CanadianScleroderma Research Group’scohort, which includes 551 patientswho have either ACA or ATA. Theiranalysis divided patients into fourgroups for comparison: limited cuta-neous with ACA (297), limited cuta-neous with ATA (52), diffuse cuta-neous with ACA (91), and diffusecutaneous with ATA (111).

For each patient, demographics,skin scores, and types and degrees oforgan involvement were recorded. Asexpected, skin scores more stronglycorrelated with disease subtype, withmodified Rodnan skin scores beinglower, at 4 and 5.5 in ACA-positiveand ATA-positive limited cutaneousgroups, respectively, compared with12 and 15 in the diffuse groups.

In contrast, organ system involve-

ment was more clearly associatedwith serologic status. For example,79.1% of diffuse and 75.4% of limitedpatients positive for ACA hadesophageal dysmotility, comparedwith 71.1% and 67.4% of diffuse andcutaneous patients with ATA. Andinterstitial lung disease was morecommon in both diffuse and limitedpatients with ATA (56.4% and 49%)than in diffuse and limited patientswith ACA (22.1% and 13.3%).

Pulmonary hypertension also wasmore common in ACA-positivepatients, at 13.7% and 16.3% of thelimited and diffuse subtypes, respec-tively, than in ATA-positive patients, at4.8% and 9.9%. But certain other dis-ease features, such as digital ulcers,polyarthritis, and finger contractures,were more clearly associated withskin subtypes, being more commonin patients with the diffuse subtyperegardless of serologic pattern.

Combination assessment importantDemographic factors also were asso-ciated more with serology. Those pos-itive for ACA typically were older, withmedian ages of 58 years for the diffusegroup and 60 for the limited group,compared with 51 and 53 for the ATAdiffuse and limited groups. The ACA-positive patients also had longer dis-ease duration, at 12 years for the dif-fuse group and nine years for the lim-ited group, compared with five yearsfor both limited and diffuse ATA-posi-tive patients. The researchers alsolooked at survival among those withless than four years’ disease durationat baseline (to limit the possibility ofsurvival bias), and found that, “inter-

estingly, survival seemed to be associ-ated with both skin and serologic sub-sets.” The worst survival was seenamong patients with the ATA-positivediffuse subtype.

The data in this analysis “suggestthat, contrary to our initial hypothesisthat subsetting based on autoantibodymarkers would be a better predictorof outcome than based on skin, sub-setting using autoantibodies in addi-tion to extent of skin involvementmay predict clinical outcomes betterthan skin alone,” Dr. Hudson and col-leagues observed.

“I absolutely agree that doctorsshould use the combination of boththe autoantibody and the extent ofskin disease to monitor treatment,”said Dr. Virginia D. Steen, ofGeorgetown University in Washington,who was not involved in the study butwho is an expert in this area.

“This is particularly important inlung disease, because although, ingeneral, limited scleroderma patientsget pulmonary hypertension and dif-fuse patients get fibrosis, the antibodyis a better predictor of that,” she said.

A limitation of the study was thepossibility of measurement error indefining disease characteristics such asinterstitial lung disease and pulmonaryhypertension. The study was funded bythe Canadian Institutes of HealthResearch, the Scleroderma Society ofCanada, and educational grants fromActelion Pharmaceuticals and Pfizer.

Copyright MedPage Today, LLC. Allrights reserved. Reprinted with per-mission.

Dr. Marie Hudson


Serology helps pinpoint scleroderma typenWould be helpful to have antibody pattern added to disease classification, researchers say



four months, or experimental biologics within fourweeks/five half-lives prior to baseline.

The study participants during the trial assess-ment period were instructed to apply the calcipotri-ol 50 mcg (g-1) plus betamethasone 0.5 mg (g-1)gel to the scalp once-daily for up to eight weeks.During the treatment period patients were permit-ted the concomitant use of other topical antipsori-atic treatments (including vitamin D analogues),except for corticosteroids, on the trunk, limbs orface, but no other scalp products were allowedduring the duration of the assessment.

Patients whose scalp psoriasis had clearedafter four weeks of treatment were asked to leavethe trial (n=13). Similarly, those patients who hadremaining signs of scalp psoriasis after four weekscontinued treatment for an additional four weeks.

Overall, the findings revealed that 56% of theparticipants (n=46) were fully compliant or missed<10% of the applications. The mean weekly use ofthe gel was 36 g (range four to 69 g), and, compar-ing the first four weeks with the second four weeksof treatment, there was no decrease in weekly use

over time, the authors reported.In all, the authors wrote that 27 patients (35%)

reported a total of 64 adverse events (AEs); mostwere mild (33/64) or moderate (22/64) in severityand there were no serious AEs. No cases of hyper-calcaemia were reported, and the mean changesfrom baseline to end of treatment in albumin-cor-rected serum calcium (0.00 mmol L(-1)), 24-h uri-nary calcium excretion (-0.03 mmol per 24 h) andurinary calcium-to-creatinine ratio (-0.12 mmol g(-1)were not considered clinically relevant.

Gel applied once daily“We were pleased to find out that the safety andtolerability profile of [calcipotriol plus betametha-sone dipropionate gel] was similar to what has pre-viously been reported in adult studies,” said Dr.Gooderham.

At the end of treatment, data revealed that 66patients (85%) were clear or almost clear accordingto IGA. In addition, the researchers reported thatthere was an 80% improvement in mean Total SignScore from baseline to end of treatment. In total, atthe end of treatment, 87% of patients rated theirscalp psoriasis as clear or very mild, and 75 patients

(96%) had no or mild pruritus compared with 14participants (18%) at baseline.

“It was reassuring and surprising to find out thatthis gel worked as well as it has in adults for thetreatment of scalp psoriasis, because adolescentsare notoriously non-adherent to treatment,” she said.

“I have to admit that sometimes in a clinicalsetting such as this one, the results can be some-what artificial due to the adolescent participants’frequent office clinical visits and patient treatmentreminders.”

She said calcipotriol plus betamethasone dipro-pionate gel is cosmetically appealing and easy forpatients to use, which is expected to help toencourage patient treatment compliance.

“We already know that pediatric patients gener-ally are not going to follow through with using prod-ucts that are not cosmetically acceptable or unap-pealing. Young patients are more likely to use prod-ucts that are easy to use,” she said.

Non-proprietary and brand name of therapy: cal-cipotriol/betamethasone dipropionate gel (DovobetGel, LEO Pharma Canada).

Scalp psoriasis: Combination gel may boost complianceContinued from page 10

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Hand dermatitis (HD) is a common prob-lem for patients; Swedish studies haveestimated that prevalence is 9.7% withan incidence of five cases per 1,000person-years (J Invest Dermatol 2002)(Am J Contact Dermatol 2003).

A roundtable meeting was con-vened in Toronto to discuss hand der-matitis and evaluate a variety oftreatments. The session, chaired by Dr.Sandra Skotnicki (pictured right), anassistant professor of dermatology atthe University of Toronto, exploredatopic dermatitis and related conditions.

During the discussion and a blinded“taste test” sampling, CeraVe® Thera-peutic Hand Cream was selected by thegroup of dermatologists as theirfavourite moisturizer—out of eight handcreams evaluated—based on factorssuch as odour, texture, permeability, for-mat, price, and quality of ingredients.CeraVe® Therapeutic Hand Cream con-tains dimethicone as a protective agent,with the addition of a ceramide complex.

Dr. Skotnicki reported that theprevalence of atopic dermatitis has re-cently more than doubled in industrial-ized countries, although the cause forthis increase is still unknown (Dermatitis2007; 18:82–91).

Hand dermatitis has significant impact on QoL Dr. Skotnicki reported that hand dermati-tis has a high impact on quality of life,and can limit the ability of patients tocarry out their work and often requiresthem to take sick days.

“[I] see mostly hand dermatitis in[my] contact [allergy] clinic and it has asignificant impact on quality of life,” saidDr. Skotnicki. “Even just one fissure, onecrack on an index finger, will impede [apatient] from cooking a meal or chang-ing [their] child’s diaper.”

Although there are a variety ofways to classify hand dermatitis, Dr.Skotnicki referred to the system pub-lished by the American Journal of Con-tact Dermatitis (2003; 14:119–137),which categorized hand dermatitis as:atopic, nummular, pompholyx, chronicvesicular, contact allergic or irritant,frictional, and hyperkeratotic.

“One of the most important things[clinicians] should always rememberfrom a clinical aspect and assessmentof [their] patients with hand dermatitis isthat almost all cases are multifactorial,”said Dr. Skotnicki. “They never have justone diagnosis.”

She noted that knowing the pa-tient’s occupational environment andtheir susceptibility to hand dermatitis isalso important when making a diagno-sis. Patch testing can be a valuable di-agnostic in some situations.

Irritant hand dermatitis is the mostcommon form, according to Dr. Skotnicki,and it is caused by repeated exposure tothe irritant. The cumulative clinical sub-type is the most prevalent and often oc-curs in nurses or new mothers who arerepeatedly washing their hands.

Because “the etiology is multifactor-ial, [physicians] have to make [their]treatment multifactorial,” said Dr. Skot-nicki. Dermatologists “have to look atevery potential cause and make sure[they] are treating each potential cause.”

Patients need to be educated onprevention of hand dermatitis and how to

avoid irritants, she said. They might needto wear gloves with liners if they will bewearing them for more than 20 minutes.

Moisturizers should be used as Tx in all HD patientsTopical therapies for hand dermatitis in-clude moisturizers, emollients, and kera-tolytic agents. The Canadian HandDermatitis Management Guidelinestates that “moisturizers or emollientsshould be used in all patients in additionto other treatments, as they providebasic barrier protection of the skin fromirritants or allergens” (J Cutan Pathol2010; 14(6):267–284).

“There is no evidence to suggestphysiologic moisturizers are more effec-tive than petrolatum. The studies havenot been done, but I think intuitively, asdermatologists, we know that if someonelikes something than the compliance isgoing to be higher,” said Dr. Skotnicki,who added that the results of the “tastetest” sample done by the roundtable par-ticipants lends credibility to this theory.

Other treatments for hand dermati-tis can include topical corticosteroids,phototherapy, and short courses of sys-temic corticosteroids, said Dr. Skotnicki.

Additional clinical data highlightsevidence for the use of barrier handcreams for patients with hand dermatitis.In a randomized, open-label study of 21subjects with hand dermatitis, patientsusing Tetrix (the same formulation asCeraVe® Therapeutic Hand Cream, butwithout the ceramide component) twice-daily for 14 days had a significantlygreater reduction in burning and itchthan controls (J Clin Aesthetic Derm2008; 1(4):18–21).

Aluminum/magnenisum hydroxidestearate (AMHS) is another critical in-gredient found in CeraVe® TherapeuticHand Cream, which has been demon-strated to have a repelling qualityagainst allergens. In a review study,AMHS-based creams were found to pro-tect against nickel sulfate, neomycin,and fragrances; reduce severity ofsymptoms associated with contact der-matitis; and exhibit protection against re-moval by water (J Clin Aesthet Dermatol

Nov 2008; 1(4):18-21).The effectiveness of

dimethicone was demon-strated in a non-random-ized, investigator-blinded,controlled study with 35participants that testedthe ability of Tetrix to actas a barrier against com-mon allergens such asnickel, sulfate, neomycin,and a fragrance mixture(J Clin Aesthetic Derm2008; 1(4):18–21).

After six hours ofocclusion patients usingTetrix had no positive al-lergy reactions and after24 hours only half asmany patients usingTetrix as the controlswere affected.

Barrier functionprotectsWhile the barrier func-

tion provided by a cream is typicallythought of as a reduction in transepider-mal water loss, in this study barrier func-tion provided by the cream was shown toalso protect against some known irri-tants. The cream acted as a physicalbarrier without being sticky or other is-sues that would limit its use.

The benefits of ceramides were ex-amined in a cohort study that looked atceramide-containing cleansers andmoisturizers used for atopic dermatitis(Lynde C, Andriessen A: Cutis Apr 2014;93(4):207–213).

In this study, 151 participants withatopic dermatitis in more than one body

location were treated twice daily with aceramide-containing cleanser (CeraVe®

Hydrating Cleanser) and a ceramide-con-taining moisturizer (CeraVe® MoisturizingCream) for six weeks. The SCORADindex was used to measure treatmentoutcome by comparing severity at base-line versus the end of treatment. Partici-pants were divided into two groups: 12years and older (group one, n=118) andyounger than 12 years (group two, n=33).

In group one, symptoms evaluated bydermatologists showed significant reduc-tions in severity: While 100% of partici-pants showed AD symptoms at day 1,only 26.3% showed symptoms at 42 days.

The group two participants’ skinconditions were evaluated by theirguardians, who noted the moisturizerssignificantly improved the participants’skin conditions.

Ceramides might improve skin barrier synthesisIn the study, the authors provide a possi-ble explanation for the potential role ofceramides in repairing skin barrier dys-function in patients with AD. “Defectiveceramide synthesis is thought to play animportant role in skin barrier dysfunctionin AD,” the investigators stated. “The ce-ramide skin care products evaluated inthis study deliver three skin-identical ce-ramides—cholesterol, fatty acids, andphytosphingosine—which are essentialto skin repair and skin barrier functionrecovery.” They note in their conclusionthat similar results may have been ob-tained with a cleanser and moisturizerwithout ceramides.

The takeaway is that it works“The takeaway is that it works,” said Dr.Melanie Pratt, professor of clinical medi-cine, University of Ottawa, who runs acontact dermatitis clinic at The OttawaHospital. “I think [the] blinded test wasimpressive. [The cream] is relatively costeffective compared to competitors and itis safer from an allergen point of view—parabens being not a very common con-tact allergen. [In terms of] prevention,there is a role not just for treatment, butfor prevention and maintenance.”

In response to the water drop testportion of evaluation, Dr. Kucy Pon, anassistant professor with the Division ofDermatology at the University of Toronto,said “I think the important point was theimpenetrability test. It does not have thepetrolatum in it, but it was still was quiteimpermeable to water, so that was good.”

Dr. Gillian Catherine de Gannes, aVancouver-based dermatologist, agreedsaying, “I have to emphasize that per-meability—that was a very dramaticshow. That hit home for me because it isalso a very cosmetically pleasingcream.” She added that another avail-able cream on the market had a similarpermeability result, but patients do com-plain about its stickiness.

“It tends to be cosmetically very ac-ceptable for patients and theoreticallyhas an advantage because of the addedceramides combined with the imperme-ability,” added Dr. Joel DeKoven, a con-sultant dermatologist at SunnybrookHealth Sciences and an associate pro-fessor in medicine at the University ofToronto.

CeraVe® Therapeutic Hand Creamplays role in treatment, prevention of hand dermatitis

Supplement to The Chronicle of Skin & Allergy, {month] 2015. Chronicle is an independent medicalnews service that provides educational updates regarding medical developments around the world.Views expressed are those of the participants and do not necessarily reflect those of the publisheror sponsor.

Support for distribution of this report was provided by Valeant Canada through an unrestrictededucational grant without conditions. Information provided in this report is not intended to serve as

the sole basis for individual care. Printed in Canada for Chronicle Information Resources Ltd., 555 Burnhamthorpe Rd., Suite

306, Toronto, Ont. M9C 2Y3.Telephone 416.916.2476; facsimile 416.352.6199; e-mail:[email protected]. Copyright 2015 by Chronicle Information Resources Ltd., except wherenoted. All rights reserved. Reproduction in any form is expressly prohibited without written permis-sion of the publisher

Special Report

Examples of hand dermatitis


Rosacea research THE CHRONICLE of SKIN & ALLERGY

R e s e a r c h

Rosacea in darker skinn Under-diagnosed in spite of symptoms

Patients with skin of colour are rarely being diagnosed with rosacea evenwhen symptoms suggest the condition, and diagnosis of rosacea in thispopulation has not become more common in recent years, researchersreport in Dermatology Online Journal (Oct. 15, 2014; 20(10)).

The authors analysed data from the National Ambulatory Medical CareSurvey collected between 1993 to 2010 to determine racial and ethnic distri-bution of patients with rosacea. They tabulated the common reasons for vis-its in rosacea patients, and then compared the frequency of rosacea diagno-sis in patients of each race with the relevant reasons for the visit. Among allthe patients who were diagnosed with rosacea, 2.0% were black, 2.3% wereAsian or Pacific Islander, and 3.9% were Hispanic or Latino of any race. Themain reasons given for visit associated with rosacea included ‘other diseasesof the skin’, skin rash, and discolouration or abnormal pigmentation. Amongthose who complained about ‘other diseases of the skin’, rosacea was theprimary diagnosis in 8.3% of whites and 2.2% of blacks. For skin rash,rosacea was diagnosed in 2.0% of whites and 0.6% of blacks, and for dis-colouration or abnormal pigmentation 3.0% of whites and 0.0% of blacks.The percentage of rosacea patients who were black or Asian/Pacific Islanderdid not significantly change over time.


R e s e a r c h

Quantifying Demodexn RCM to track reduction in mites during TxFrom the News Resources of The Chronicle

Reflectance confocal microscopy (RCM) can be used to non-invasivelymonitor and quantify reduction of Demodex mite density in the facialskin of rosacea patients undergoing therapy, which can correlate withclinical improvement, researchers report online in the British Journal ofDermatology (Mar. 20, 2015).

RCM was conducted both before and after rosacea therapy in 25patients with facial rosacea. Investigators scanned 5x5 mm2 and 8x8mm2 mosaics, and counted total mites per follicle, mites per area, andfollicles per area. Demodex folliculorum was detected and quantified inall patients using RCM. The scanning revealed significant differences pre-and post-treatment (p=0.0053 for 5x5 mm2 and 0.0003 for 8x8 mm2).Before treatment, the 8x8 mm2 mosaic scan showed a mean number ofmites per follicle of 0.632—ranging from 0.157 to 2.276—and after treat-ment 0.405 (0.074 to 1.745). For the 5x5 mm2 mosaic, mites per folliclewas 0.704 (0.106 to 2.200) before treatment and 0.505 (0.094 to 1.704)after. The mean total number of mites was 155.2 (45 to 446) for 8x8 mm2

pre-treatment and 96.2 (18 to 363) post-treatment, and for 5x5 mm2 pre-treatment the count was 86.2 (12 to 286) and post-treatment it was 58.5(12 to 230).

Rosacea updateCLEARING H. PYLORI REDUCESSYMPTOMS OF ROSACEAPatients with rosacea have a higherprevalence of H. pylori infection, anderadication of the infection led to asignificant improvement in skin symp-toms, according to findings publishedin United European GastroenterologyJournal (Feb. 2015; 3(1):17-24).

Recent research has suggested arelationship between rosacea andeither H. pylori infection or smallintestinal bacterial overgrowth(SIBO), so the authors assessed theprevalence in patients with rosaceaand the impact on symptoms oferadicating them. A total of 90patients with rosacea were enrolledfrom Jan. 2012 through Jan. 2013, aswere 90 controls. Clarithromycin-containing sequential therapy wasused to treat H. pylori infection, andrifaximin was used to treat SIBO.Some 44 (48.9%) of rosacea patientsand 24 (26.7%) controls were infect-ed with H. pylori (p=0.003), andnine (10%) patients and seven(7.8%) controls had SIBO (p=0.6).Within 10 weeks of the end of antibi-otic therapy, rosacea lesions had dis-appeared or markedly decreased in35/36 patients (97.2%) who haderadicated their H. pylori infections,and in three of eight (37.5%) ofpatients who had not eradicatedtheir infection (p<0001). Lesionsdecreased markedly in six of seven(85.7%) patients after SIBO eradica-tion, and one patient who did noteradicate SIBO saw improvement(p=0.284).

BRAF MUTATION DOES NOT SPEEDMELANOMA TUMOUR GROWTHNasal involvement may be an indica-tion of greater severity in rosacea,and rosacea isolated to the noseappears to be a separate spectrumof the condition with different clini-cal features, researchers report inDermatology (Jan. 2015; 230(2):177-183).

The authors note that the clinicalfeatures of nasal rosacea have notpreviously been described in detail.To clarify this, the authors classified599 patients with rosacea into threegroups. Group A included patientswith rosacea in both the nasal andextra-nasal areas, Group B had local-ized nasal rosacea, and Group C hasrosacea with no nasal involvement.More patients in Group A had themixed subtype of rosacea (n=337)than did in Group C (n=231). GroupA also had a higher average severityscore than Group C. The most com-mon rosacea subtype seen in GroupC was erythematotelangiectatic(n=31). This subtype was also morecommon in Group B than in GroupA. Rosacea mainly affected thelower half of the nose in Group B,and the entire nose in Group A.

ROSACEA UNDERREPORTEDFindings from the direct observationof individuals in community settingssuggest that rosacea is more com-mon than previously reported in theU.S., researchers report in theJournal of Cutaneous Medicine andSurgery (Mar. 2015; 19(2):149-152).

To gather data, a clinicalresearch fellow and a medical stu-dent stood in public places, includ-ing a shopping mall, an office of theU.S. Department of Motor Vehicles,and a grocery store, and examinedconsecutive individuals whoapproached within 1.8 metres, tally-ing demographic and descriptivedata. Subjects were included intoone of three categories, whichincluded clearly rosacea, possiblerosacea, and definitely no rosacea.The data was sub-analysed by per-ceived gender, age, race, androsacea subtype, and the Fischerexact test was used to comparebetween groups. Some 5.4% (95%CI, 3.6-7.8) of individuals had 'possi-ble’ rosacea, and 6% (95% CI 4.1-8.5)had ‘definite’ rosacea. While therewas no higher disposition to rosaceabetween genders, older individualswith Fitzpatrick skin types I throughIII were more likely to have rosacea.The authors note that distance madeit difficult to assess individuals whomay have had mild or ocularrosacea, or just a few telangiec-tasias, and could not assess individu-als too upset by their rosacea to trav-el to public places. As well, someindividuals may have concealedtheir rosacea with makeup.

PROPRANOLOL/DOXYCYCLINECOMBO THERAPY FOR ROSACEA A comparative study of propranololand doxycycline monotherapies andcombination therapy with bothagents for the treatment of rosaceahas found the combination treat-ment safe, effective, and successfulat reducing flushing and, in particu-lar, papulation, according to findingspublished in the Journal ofDermatology (Jan. 2015; 42(1):64-69).

In the study, 78 patients diag-nosed with rosacea who visitedPusan National University Hospitalwere included in three treatmentgroups: 28 treated with propranolol,22 with doxycycline, and 28 withboth agents. Patient GlobalAssessment (PGA), InvestigatorGlobal Assessment (IGA),Assessment of Rosacea ClinicalScore (ARCS), and adverse eventswere evaluated. All groups sawimprovement in their IGA and PGAscores, with the combination thera-py showing the best results, thoughnot significantly so. The combinationgroup also had the largest reductionof ARCS during the treatment period(57.4%), followed by doxycyclinemonotherapy (52.2%) and propra-nolol (51.0%). Three patients receiv-ing the combination therapy didexperience mild, transient gastroin-testinal disturbances, but there wasnot a significant difference inadverse events between the threetreatment groups.


Hand dermatitis (HD) is a common prob-lem for patients; Swedish studies haveestimated that prevalence is 9.7% withan incidence of five cases per 1,000person-years (J Invest Dermatol 2002)(Am J Contact Dermatol 2003).

A roundtable meeting was con-vened in Toronto to discuss hand der-matitis and evaluate a variety oftreatments. The session, chaired by Dr.Sandra Skotnicki (pictured right), anassistant professor of dermatology atthe University of Toronto, exploredatopic dermatitis and related conditions.

During the discussion and a blinded“taste test” sampling, CeraVe® Thera-peutic Hand Cream was selected by thegroup of dermatologists as theirfavourite moisturizer—out of eight handcreams evaluated—based on factorssuch as odour, texture, permeability, for-mat, price, and quality of ingredients.CeraVe® Therapeutic Hand Cream con-tains dimethicone as a protective agent,with the addition of a ceramide complex.

Dr. Skotnicki reported that theprevalence of atopic dermatitis has re-cently more than doubled in industrial-ized countries, although the cause forthis increase is still unknown (Dermatitis2007; 18:82–91).

Hand dermatitis has significant impact on QoL Dr. Skotnicki reported that hand dermati-tis has a high impact on quality of life,and can limit the ability of patients tocarry out their work and often requiresthem to take sick days.

“[I] see mostly hand dermatitis in[my] contact [allergy] clinic and it has asignificant impact on quality of life,” saidDr. Skotnicki. “Even just one fissure, onecrack on an index finger, will impede [apatient] from cooking a meal or chang-ing [their] child’s diaper.”

Although there are a variety ofways to classify hand dermatitis, Dr.Skotnicki referred to the system pub-lished by the American Journal of Con-tact Dermatitis (2003; 14:119–137),which categorized hand dermatitis as:atopic, nummular, pompholyx, chronicvesicular, contact allergic or irritant,frictional, and hyperkeratotic.

“One of the most important things[clinicians] should always rememberfrom a clinical aspect and assessmentof [their] patients with hand dermatitis isthat almost all cases are multifactorial,”said Dr. Skotnicki. “They never have justone diagnosis.”

She noted that knowing the pa-tient’s occupational environment andtheir susceptibility to hand dermatitis isalso important when making a diagno-sis. Patch testing can be a valuable di-agnostic in some situations.

Irritant hand dermatitis is the mostcommon form, according to Dr. Skotnicki,and it is caused by repeated exposure tothe irritant. The cumulative clinical sub-type is the most prevalent and often oc-curs in nurses or new mothers who arerepeatedly washing their hands.

Because “the etiology is multifactor-ial, [physicians] have to make [their]treatment multifactorial,” said Dr. Skot-nicki. Dermatologists “have to look atevery potential cause and make sure[they] are treating each potential cause.”

Patients need to be educated onprevention of hand dermatitis and how to

avoid irritants, she said. They might needto wear gloves with liners if they will bewearing them for more than 20 minutes.

Moisturizers should be used as Tx in all HD patientsTopical therapies for hand dermatitis in-clude moisturizers, emollients, and kera-tolytic agents. The Canadian HandDermatitis Management Guidelinestates that “moisturizers or emollientsshould be used in all patients in additionto other treatments, as they providebasic barrier protection of the skin fromirritants or allergens” (J Cutan Pathol2010; 14(6):267–284).

“There is no evidence to suggestphysiologic moisturizers are more effec-tive than petrolatum. The studies havenot been done, but I think intuitively, asdermatologists, we know that if someonelikes something than the compliance isgoing to be higher,” said Dr. Skotnicki,who added that the results of the “tastetest” sample done by the roundtable par-ticipants lends credibility to this theory.

Other treatments for hand dermati-tis can include topical corticosteroids,phototherapy, and short courses of sys-temic corticosteroids, said Dr. Skotnicki.

Additional clinical data highlightsevidence for the use of barrier handcreams for patients with hand dermatitis.In a randomized, open-label study of 21subjects with hand dermatitis, patientsusing Tetrix (the same formulation asCeraVe® Therapeutic Hand Cream, butwithout the ceramide component) twice-daily for 14 days had a significantlygreater reduction in burning and itchthan controls (J Clin Aesthetic Derm2008; 1(4):18–21).

Aluminum/magnenisum hydroxidestearate (AMHS) is another critical in-gredient found in CeraVe® TherapeuticHand Cream, which has been demon-strated to have a repelling qualityagainst allergens. In a review study,AMHS-based creams were found to pro-tect against nickel sulfate, neomycin,and fragrances; reduce severity ofsymptoms associated with contact der-matitis; and exhibit protection against re-moval by water (J Clin Aesthet Dermatol

Nov 2008; 1(4):18-21).The effectiveness of

dimethicone was demon-strated in a non-random-ized, investigator-blinded,controlled study with 35participants that testedthe ability of Tetrix to actas a barrier against com-mon allergens such asnickel, sulfate, neomycin,and a fragrance mixture(J Clin Aesthetic Derm2008; 1(4):18–21).

After six hours ofocclusion patients usingTetrix had no positive al-lergy reactions and after24 hours only half asmany patients usingTetrix as the controlswere affected.

Barrier functionprotectsWhile the barrier func-

tion provided by a cream is typicallythought of as a reduction in transepider-mal water loss, in this study barrier func-tion provided by the cream was shown toalso protect against some known irri-tants. The cream acted as a physicalbarrier without being sticky or other is-sues that would limit its use.

The benefits of ceramides were ex-amined in a cohort study that looked atceramide-containing cleansers andmoisturizers used for atopic dermatitis(Lynde C, Andriessen A: Cutis Apr 2014;93(4):207–213).

In this study, 151 participants withatopic dermatitis in more than one body

location were treated twice daily with aceramide-containing cleanser (CeraVe®

Hydrating Cleanser) and a ceramide-con-taining moisturizer (CeraVe® MoisturizingCream) for six weeks. The SCORADindex was used to measure treatmentoutcome by comparing severity at base-line versus the end of treatment. Partici-pants were divided into two groups: 12years and older (group one, n=118) andyounger than 12 years (group two, n=33).

In group one, symptoms evaluated bydermatologists showed significant reduc-tions in severity: While 100% of partici-pants showed AD symptoms at day 1,only 26.3% showed symptoms at 42 days.

The group two participants’ skinconditions were evaluated by theirguardians, who noted the moisturizerssignificantly improved the participants’skin conditions.

Ceramides might improve skin barrier synthesisIn the study, the authors provide a possi-ble explanation for the potential role ofceramides in repairing skin barrier dys-function in patients with AD. “Defectiveceramide synthesis is thought to play animportant role in skin barrier dysfunctionin AD,” the investigators stated. “The ce-ramide skin care products evaluated inthis study deliver three skin-identical ce-ramides—cholesterol, fatty acids, andphytosphingosine—which are essentialto skin repair and skin barrier functionrecovery.” They note in their conclusionthat similar results may have been ob-tained with a cleanser and moisturizerwithout ceramides.

TThhee ttaakkeeaawwaayy iiss tthhaatt iitt wwoorrkkss“The takeaway is that it works,” said Dr.Melanie Pratt, professor of clinical medi-cine, University of Ottawa, who runs acontact dermatitis clinic at The OttawaHospital. “I think [the] blinded test wasimpressive. [The cream] is relatively costeffective compared to competitors and itis safer from an allergen point of view—parabens being not a very common con-tact allergen. [In terms of] prevention,there is a role not just for treatment, butfor prevention and maintenance.”

In response to the water drop testportion of evaluation, Dr. Kucy Pon, anassistant professor with the Division ofDermatology at the University of Toronto,said “I think the important point was theimpenetrability test. It does not have thepetrolatum in it, but it was still was quiteimpermeable to water, so that was good.”

Dr. Gillian Catherine de Gannes, aVancouver-based dermatologist, agreedsaying, “I have to emphasize that per-meability—that was a very dramaticshow. That hit home for me because it isalso a very cosmetically pleasingcream.” She added that another avail-able cream on the market had a similarpermeability result, but patients do com-plain about its stickiness.

“It tends to be cosmetically very ac-ceptable for patients and theoreticallyhas an advantage because of the addedceramides combined with the imperme-ability,” added Dr. Joel DeKoven, a con-sultant dermatologist at SunnybrookHealth Sciences and an associate pro-fessor in medicine at the University ofToronto.

CeraVe® Therapeutic Hand Creamppllaayyss rroollee iinn ttrreeaattmmeenntt,, pprreevveennttiioonn ooff hand dermatitis

Supplement to The Chronicle of Skin & Allergy, {month] 2015. Chronicle is an independent medicalnews service that provides educational updates regarding medical developments around the world.Views expressed are those of the participants and do not necessarily reflect those of the publisheror sponsor.

Support for distribution of this report was provided by Valeant Canada through an unrestrictededucational grant without conditions. Information provided in this report is not intended to serve as

the sole basis for individual care. Printed in Canada for Chronicle Information Resources Ltd., 555 Burnhamthorpe Rd., Suite

306, Toronto, Ont. M9C 2Y3.Telephone 416.916.2476; facsimile 416.352.6199; e-mail:[email protected]. Copyright 2015 by Chronicle Information Resources Ltd., except wherenoted. All rights reserved. Reproduction in any form is expressly prohibited without written permis-sion of the publisher

Special Report

Examples of hand dermatitis


by JOHN EVANS,Assistant Editor, The Chronicle

Astudy of 31 patients who pre-sented at a single tertiarycare centre for treatment of

in-transit melanoma with intralesion-al IL-2 found that nearly one-thirdachieved pathologic completeresponse (pCR) and had significantlyimproved progression-free survival,according to a paper publishedonline in Annals of Surgical Oncology(Nov. 1, 2014).

“When you have a large practiceof patients with melanoma, whenyou get a larger group of patients, yousee more of these patients with in-transit disease, which is essentiallydeposits of melanoma between theprimary site and the nearest lymphnode basin. I was looking for ways totreat them with relatively low morbid-ity or few side effects,” says studyauthor Dr. Frances Wright, head ofBreast and Melanoma Surgery at theLouise Temerty Breast Cancer Centreof Sunnybrook Health SciencesCentre, and an affiliate scientist at theSunnybrook Research Institute inToronto.

“One of my colleagues inLondon was doing Interleukin-2injections. We collaborated, and I

started doing these injections toserve this patient need in about2009,” Dr. Wright reported.

Clinico-pathological data from 31consecu t i vepatients wascollected ret-rospect ively ,and Kaplan-Meier survivalcurves andmultivariableCox regressionanalysis wereperformed. Aswell, immuneresponse tothis therapywas examined, and the tumourswere genomically characterized.

Called a positive findingOf the 31 patients, 10 (32%) achievedpCR, and another 17 (55%) had par-tial response, with four (19%) havingprogressive disease. Achieving pCRfrom this IL-2 therapy was also asso-ciated with overall survival (log-rankp=0.004) as well as improved pro-gression-free survival (adjusted haz-ard ratio (HR) 0.11; 95% CI 0j.02–0.47,p=0.003).

This is a very positive finding, saysDr. Wright. “For patients with these

in-transit metastases, which happenin five to ten per cent of patients withmelanomas greater than 1 mm indepth, the Interleukin-2 injections

offer a verylow morbidity,or minimal risktreatment. Andabout 32 percent ofpatients willhave a pro-longed res-ponse, mean-ing they mayeffectively becured.”

Dr. Wrightand her team have also been study-ing the cellular responses in the IL-2treated patients to see if they couldidentify commonalities.

“One of my collaborators, Dr.Hassan, had a lot of expertise inmolecular bench skills,” says Dr.Wright. “We were talking about,with all of the new markers comingout for melanoma—B-raf markersand N-raf and C-kit—we were won-dering if there was a pattern to thepatients who were developing thesein-transit metastases, if they had acertain kind of combination ofmarkers. So that’s why we looked to

see if this very discrete population ofpatients with melanoma had some-thing different about them with theprimary site.”

While the authors did not findanything that significantly indicatedthat persons with B-raf positivemelanoma were at higher risk ofdeveloping the sort of in-transitmetastases studied, they did observethat patients in the study who had agood response in the number of T-cells around the in-transit melanomaafter IL-2 treatment were more likelyto have good, long-term response tothe IL-2.

“It is like the IL-2 can somehowactivate the body’s immune system incertain groups of patients, and thoseare the patients who have the bestresponse,” says Dr. Wright.

Patients typically had melanomaon a limbThe response to IL-2 therapy maybe explained by a systemic CD8+T-cell response, according to thefindings. In in-transit lesions witha pCR, a higher CD8+ T-cell infil-t rate was identi f ied (mean IHCscore 3 .78) compared to whatwas seen in other lesions (meanIHC score 2 .61) (p=0.01) . Thepatients with a higher CD8+ infil-trate also had an improved pro-gression-free survival (unadjustedHR 0 .08 ; 95% C I 0 .01–0 .52 ,p=0.008).

As for which patients might besuitable for this type of IL-2 treatment,Dr. Wright says the patients her teamis treating with this method typicallyhave had a melanoma on a limb—80% of their patients have a limb orleg melanoma—with more than fourin-transit metastases or in-transitmetastases that rapidly return.

“So you remove them and by thetime the patient comes back to gettheir sutures out, there are more ofthem, then you probably need tomove away from surgery as yourtreatment and move on to somethingelse for them,” Dr. Wright said. “Wefind, in our patients, the IL-2 is verywell tolerated and is a good kind ofsecond step after surgery. For somepatients, the IL-2 may be the first stepif they present with many [metas-tases].”

The team is continuing to followthe studied patients, as well as newpatients receiving the IL-2 treatment,so the research cohort will grow, saysDr. Wright.

The team will also be trying dif-ferent medications for the patients inthe cohort who do not respond to IL-2 therapy, she says.


Approach targets in-transit melanomanOne-third of patients achieved pCR, improved progression-free survival with intralesional IL-2 therapy



t ion. We began to realize that stem cells play anabsolutely critical role in not only maintaining the sort ofwear and tear that we subject our skin to on a dailybasis but also in terms of repairing wounds,” said Dr.Fuchs.

Ultimately, without functional stem cells, wounds donot repair as well, she noted.

“It turns out that this basic ability of stem cells tomake and repair tissues is the very mechanism that can-cers use in their malignant transformation. And so wehave learned that both basal cell carcinoma and squa-mous cell carcinoma have hijacked certain fundamentalprinciples that normal stem cells use to repair woundsand we must keep those mechanisms in order to repairwounds,” Dr. Fuchs added.

“We have also learned that the stem cells in cancerare very different than the stem cells in normal skin. Weare now developing methods where we can hopefullycome up with some avenues for new and improvedmethods of diagnosis and therapies for these differenttypes of non-melanoma skin cancers.”

Skin cancers and viruses:Lessons from Kaposi’s sarcomaand Merkel cell carcinoma

WHEN: Saturday, June 13, 10:30 a.m.WHERE: West Ballroom ABCDOn Saturday, June 13, Dr. Patrick S. Moore, co-discovererwith Yuan Chang of two of the seven known human can-cer viruses (Kaposi’s sarcoma herpesvirus (KSHV/HHV8)

and Merkel cell polyomavirus (MCPyV)), will be giving aplenary talk on the causal role of newly discovered virus-es in cancers in the skin. He will also discuss a numberof recently discovered viruses associated with skin dis-eases. Dr. Moore is a Distinguished Professor in theDepartment of Molecular Microbiology and Genetics atthe University of Pittsburgh, and director of the CancerVirology Program at the Hillman Comprehensive CancerInstitute.

Attendees will hear how the advent of new technolo-gies, such as genomic sequencing,have empowered scientists to uncov-er hundreds of new viruses that areresident in human skin and other tis-sues that the medical community hadpreviously been unaware of, says Dr.Moore.

In the last year or two, says Dr.Moore, a large number of these virus-es have been discovered to be associ-ated with various diseases, particularly

in immunocompromised patients. The identification ofthese pathogens “suggests there is a large number ofviruses that we are continuously exposed to that may becausing some of the idiopathic diseases that occur in der-matology populations,” says Dr. Moore.

“Many of these viruses could be the causes not only ofrare cancers such as the ones I’ll be talking about . . . butalso may be the cause of much more common diseaseswhich we’ll learn about in the future as we continueinvestigating these hundreds of viruses that have beenfound,” says Dr. Moore.

“And about 32 percent of patientswill have aprolonged

response [to interleukin 2injections] meaning they may

effectively be cured.”—Dr. Frances Wrightq

Dr. Patrick Moore

WCD: Highlights of plenary sessionsContinued from page 16

What could Olux®-E Foam do for your patients?

IN MODERATE-TO-SEVERE ATOPIC DERMATITIS,

THE ONLY FOAM CORTICOSTEROID INDICATED IN MODERATE-TO-SEVERE ATOPIC DERMATITIS FOR PATIENTS 12 YEARS OF AGE*

Indications and Clinical Use:• OLUX®-E Foam is indicated for the treatment of infl ammatory and

pruritic manifestations of moderate to severe atopic dermatitis in patients 12 years of age or older.

• Treatment should be limited to a period of 2 weeks and should not use greater than 50 grams per week. Intermittent use has not been studied.

• Safety and effi cacy have not been established in patients 65 years of age.

Contraindications:• Hypersensitivity to other corticosteroids• Viral (e.g. herpes or varicella) lesions of the skin, bacterial or

fungal skin infections, parasitic infections, skin manifestations relating to tuberculosis or syphilis, eruptions following vaccinations

• Treatment of rosacea, acne vulgaris, pruritus without infl ammation, perianal and genital pruritus, perioral dermatitis, or infections of the scalp

• Topical application to the eyeMost serious warnings and precautions:• HPA axis suppression: should not be used under occlusion, over

extensive areas, or on the face, scalp, axillae, groin, scrotum or other intertriginous areas

• Prior use of corticosteroids: patients should inform physicians• Extremely fl ammable propellant: avoid fi re, open fl ame, spark

or smoking during and immediately following application• Pediatric patients: not recommended in patients <12 years of

ageOther relevant warnings and precautions:• Caution in stasis dermatitis and other skin diseases with impaired

circulation• Use around chronic leg ulcers may be associated with higher

occurrence of local hypersensitivity reactions and increased risk of local infection

• Risk of hypercortisolism (Cushing’s syndrome), hyperglycemia,

glucosuria and reversible hypothalamic-pituitary adrenal (HPA) axis suppression leading to glucocorticosteroid insuffi ciency as a result of increased systemic absorption

• Risk of systemic absorption and increased systemic effects related to the formulation, potency, frequency of application, prolonged use, increased hydration of the stratum corneum, use on thin skin areas, application to intertriginous areas, application over large surface areas, addition of occlusive dressings, use on broken skin or use in conditions where the skin barrier may be impaired, which are not recommended

• Monitor for HPA-axis suppression in conditions which augment systemic absorption

• Pediatric patients may be more susceptible to systemic toxicity• Risk of serious adverse events in patients with acute illness or

injury: patients/caregivers should be instructed to use OLUX®-E Foam for the minimum amount of time necessary to achieve the desired results

• Increased risk of infections• Use of OLUX®-E Foam on the face is not recommended; risk of

increased intraocular pressure, glaucoma or cataracts when used on lesions close to the eye

• Local hypersensitivity reactions may resemble symptoms of the condition under treatment

• Risk of irritation, striae or atrophy of the skin or subcutaneous tissue; OLUX®-E should not be used on lesions of the face, scalp, groin, scrotum, axillae and other intertriginous areas

• Should not be administered during pregnancy or lactation unless the expected benefi ts to the mother outweigh the potential risks to the fetus or the infant; if used during lactation, do not apply to the chest so as to avoid accidental ingestion by the infant

• Caution in elderly• Safety has not been established in patients with renal or hepatic

impairment• Minimum quantity/duration in elderly patients and patients with

renal/hepatic impairment• Caution in psoriasis

Dosage and method of administration:• Apply a thin layer of OLUX®-E Foam to the affected area(s) twice

daily, morning and evening for a maximum of 2 weeks and patients should not use greater than 50 grams per week.

• Dispense the smallest amount of foam necessary (up to a maximum of a golf-ball-size) to adequately cover the affected area(s) with a thin layer.

• Do not use on the eye, orally or intravaginally, or on other mucus membranes.

Adverse reactions:• In a controlled clinical trial, the most frequently reported

treatment-related adverse reactions with OLUX®-E Foam were application site reaction in 2%, application site atrophy in 2% and application site pigmentations changes (1%).

For more information: Please consult the product monograph at http://webprod5.hc-sc.gc.ca/dpd-bdpp/ for important information relating to contraindications, warnings and precautions, adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-800-387-7374. * Comparative clinical signifi cance has not been established.† Double-blind study of 377 patients aged 12 years with moderate-to-severe atopic

dermatitis. Patients were randomized to OLUX®-E Foam twice daily for 2 weeks or vehicle foam. Treatment success was defi ned as the proportion of patients who had all of the following: an Investigator’s Static Global Assessment (ISGA) score of clear or almost clear, a minimum improvement in the 5 point ISGA score of 2 grades from baseline to Week 2, and a score of absent or minimal for both erythema and induration/papulation at Week 2. The majority of the subjects enrolled (87%, 328/377) had a baseline ISGA score of 3 and 12% (44/377) had a baseline ISGA score of 4. The mean extent of atopic dermatitis (% BSA) at baseline was 14.9% for the EF clobetasol foam group and 13.8% for the vehicle foam group.

‡ Clinical signifi cance has not been established.§ For a list of additional ingredients, please refer to the Product Monograph.Reference: 1. OLUX®-E Foam Product Monograph. GlaxoSmithKline Inc., March 3, 2014.

® OLUX is a registered trademark of Stiefel Laboratories Inc., used under license by GlaxoSmithKline Inc.® VERSAFOAM is a registered trademark of Stiefel Laboratories Inc., used under license by GlaxoSmithKline Inc.Stiefel, a GSK company, Mississauga (Ontario) L5N 6L4 © 2015

®Pr

®Pr

Fictitious case. May not be representative

of results in all patients.

0060801/15

mineral oil1‡§

Can be easily applied by patients1

Petrolatum-based emulsionaerosol foam that also contains

Demonstrated effi cacy and tolerability profi les• Signifi cantly more OLUX®-E Foam patients demonstrated

treatment success at week 2 versus vehicle foam (52% vs 14%, respectively, p<0.0001)1†

• The most frequently reported treatment-related adverse reactions were:1

– application site reaction (2%) – application site atrophy (2%) – application site pigmentation changes (1%)

OLUX®-E:A super-high potent‡ topical corticosteroid (clobetasol propionate) delivered in a foam format*


What could Olux®-E Foam do for your patients?

What could

IN MODERATE-TO-SEVERE ATOPIC DERMATITIS,

THE ONLY FOAM CORTICOSTEROID INDICATED IN MODERATE-TO-SEVERE ATOPIC DERMATITIS FOR PATIENTS 12 YEARS OF AGE*

Indications and Clinical Use:• OLUX®-E Foam is indicated for the treatment of infl ammatory and

pruritic manifestations of moderate to severe atopic dermatitis in patients 12 years of age or older.

• Treatment should be limited to a period of 2 weeks and should not use greater than 50 grams per week. Intermittent use has not been studied.

• Safety and effi cacy have not been established in patients 65 years of age.

Contraindications:• Hypersensitivity to other corticosteroids• Viral (e.g. herpes or varicella) lesions of the skin, bacterial or

fungal skin infections, parasitic infections, skin manifestations relating to tuberculosis or syphilis, eruptions following vaccinations

• Treatment of rosacea, acne vulgaris, pruritus without infl ammation, perianal and genital pruritus, perioral dermatitis, or infections of the scalp

• Topical application to the eyeMost serious warnings and precautions:• HPA axis suppression: should not be used under occlusion, over

extensive areas, or on the face, scalp, axillae, groin, scrotum or other intertriginous areas

• Prior use of corticosteroids: patients should inform physicians• Extremely fl ammable propellant: avoid fi re, open fl ame, spark

or smoking during and immediately following application• Pediatric patients: not recommended in patients <12 years of

ageOther relevant warnings and precautions:• Caution in stasis dermatitis and other skin diseases with impaired

circulation• Use around chronic leg ulcers may be associated with higher

occurrence of local hypersensitivity reactions and increased risk of local infection

• Risk of hypercortisolism (Cushing’s syndrome), hyperglycemia,

glucosuria and reversible hypothalamic-pituitary adrenal (HPA) axis suppression leading to glucocorticosteroid insuffi ciency as a result of increased systemic absorption

• Risk of systemic absorption and increased systemic effects related to the formulation, potency, frequency of application, prolonged use, increased hydration of the stratum corneum, use on thin skin areas, application to intertriginous areas, application over large surface areas, addition of occlusive dressings, use on broken skin or use in conditions where the skin barrier may be impaired, which are not recommended


• Pediatric patients may be more susceptible to systemic toxicity• Risk of serious adverse events in patients with acute illness or

injury: patients/caregivers should be instructed to use OLUX®-E Foam for the minimum amount of time necessary to achieve the desired results

• Increased risk of infections• Use of OLUX®-E Foam on the face is not recommended; risk of

increased intraocular pressure, glaucoma or cataracts when used on lesions close to the eye

• Local hypersensitivity reactions may resemble symptoms of the condition under treatment

• Risk of irritation, striae or atrophy of the skin or subcutaneous tissue; OLUX®-E should not be used on lesions of the face, scalp, groin, scrotum, axillae and other intertriginous areas

• Should not be administered during pregnancy or lactation unless the expected benefi ts to the mother outweigh the potential risks to the fetus or the infant; if used during lactation, do not apply to the chest so as to avoid accidental ingestion by the infant

• Caution in elderly• Safety has not been established in patients with renal or hepatic

impairment• Minimum quantity/duration in elderly patients and patients with

renal/hepatic impairment• Caution in psoriasis

Dosage and method of administration:• Apply a thin layer of OLUX®-E Foam to the affected area(s) twice

daily, morning and evening for a maximum of 2 weeks and patients should not use greater than 50 grams per week.

• Dispense the smallest amount of foam necessary (up to a maximum of a golf-ball-size) to adequately cover the affected area(s) with a thin layer.

• Do not use on the eye, orally or intravaginally, or on other mucus membranes.

Adverse reactions:• In a controlled clinical trial, the most frequently reported

treatment-related adverse reactions with OLUX®-E Foam were application site reaction in 2%, application site atrophy in 2% and application site pigmentations changes (1%).

For more information: Please consult the product monograph at http://webprod5.hc-sc.gc.ca/dpd-bdpp/ for important information relating to contraindications, warnings and precautions, adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-800-387-7374. * Comparative clinical signifi cance has not been established.† Double-blind study of 377 patients aged 12 years with moderate-to-severe atopic

dermatitis. Patients were randomized to OLUX®-E Foam twice daily for 2 weeks or vehicle foam. Treatment success was defi ned as the proportion of patients who had all of the following: an Investigator’s Static Global Assessment (ISGA) score of clear or almost clear, a minimum improvement in the 5 point ISGA score of 2 grades from baseline to Week 2, and a score of absent or minimal for both erythema and induration/papulation at Week 2. The majority of the subjects enrolled (87%, 328/377) had a baseline ISGA score of 3 and 12% (44/377) had a baseline ISGA score of 4. The mean extent of atopic dermatitis (% BSA) at baseline was 14.9% for the EF clobetasol foam group and 13.8% for the vehicle foam group.

‡ Clinical signifi cance has not been established.§ For a list of additional ingredients, please refer to the Product Monograph.Reference: 1. OLUX®-E Foam Product Monograph. GlaxoSmithKline Inc., March 3, 2014.

® OLUX is a registered trademark of Stiefel Laboratories Inc., used under license by GlaxoSmithKline Inc.® VERSAFOAM is a registered trademark of Stiefel Laboratories Inc., used under license by GlaxoSmithKline Inc.Stiefel, a GSK company, Mississauga (Ontario) L5N 6L4 © 2015

®Pr

®Pr

Fictitious case. May not be representative

of results in all patients.

0060801/15

mineral oil1‡§

Can be easily applied by patients1

Petrolatum-based emulsionaerosol foam that also contains

Demonstrated effi cacy and tolerability profi les• Signifi cantly more OLUX®-E Foam patients demonstrated

treatment success at week 2 versus vehicle foam (52% vs 14%, respectively, p<0.0001)1†

• The most frequently reported treatment-related adverse reactions were:1

– application site reaction (2%) – application site atrophy (2%) – application site pigmentation changes (1%)

OLUX®-E:A super-high potent‡ topical corticosteroid (clobetasol propionate) delivered in a foam format*


* vs. Embrace † vs. 3 blades on Venus Original

© 2014 P&G www.gillettevenus.ca

Contours better* to tricky areas for a fl awless shave

5 Contour blades are 6X more fl exible†

Water-activated MoistureGlide serum for incredible glide

MicroFine comb guides hair to the blades that capture virtually every hair

Gillette Venus, the #1 selling female razor brand in the world, introduces NEW Venus Swirl, a razor that sets a new standard in shaving. Designed by women for women, Venus Swirl combines the innovative four-way movement of FlexiBall technology and Gillette’s most advanced blades.

EASY MANEUVERABILITY. EASY CONTROL.


INTRODUCTION

Urticaria and angioedemalasting more than sixweeks have been designat-ed as chronic urticaria(CU). It encompasses twomajor subtypes: chronic

spontaneous urticaria (CSU) (previ-ously known as chronic idiopathicurticaria) (CIU) and chronic inducibleurticaria. CSU has been defined aswheals and/or angioedema that areendogenous and independent of anyexternal physical stimulus. It affects0.5 to 1% of the population.1 In 40 to45% of patients with CSU autoanti-bodies to the high affinity IgE receptor(Fcc- RI) or to IgE itself are thought toplay a psathogenic role, whereas 55 to60% of cases are considered idiopath-ic.2 Inducible urticarias include allforms of physical urticarias (cold-induced, heat-induced, solar, andpressure urticaria).

According to the InternationalGuidelines for the management ofurticaria and angioedema non-sedat-ing, second generation antihistamines(NSAHs) are recommended for thetreatment of CU.3 Nevertheless, a con-siderable proportion of patients do notrespond sufficiently to NSAHs.According to Humphreys and Hunter,up to 40% of patients with CU may notachieve good control with antihista-minic therapy.4 They reported that outof 390 CU patients who were treatedwith antihistamines 44% responded

well, 29% became asymptomatic, and15% showed partial improvement. In arecent paper from Japan it wasobserved that the improvement rates(defined as a urticaria symptom scoreUAS<=3) in 117 CU patients whoreceived standard doses of AHs were36.6% at 12 months, 51.2% at 24months, and 66.1% at 60 months, whilethe remission rates were 11.5%, 13.9%,and 27.7%, respectively.5

In patients that do not respond tostandard doses, the next step in guide-line-based therapy is to increase AHdoses up to four times.3 Investigationsassessing the response to variousNSAHs have demonstrated that up-dosing is significantly more effective inreducing symptoms of CU than stan-dard-dose treatment.6 According toKaplan, high-dose antihistamines areeffective in 45 to 60% of patients withCSU,7 while about one-third are anti-histamine resistant regardless of whichdose is used.8,9

The present article is a review ofthe literature on the treatment of CUwith increased doses of NSAHs inorder to investigate if there are differ-ences in efficacy between the varioussecond generation AHs that have beenstudied in controlled protocols. It mustbe noticed, however, that it is difficultto find clinical investigations that strict-ly follow the criteria recommended bythe guidelines on the management ofurticaria, and therefore studies includ-ed in this review were those in whichhigher doses of NSAHs were usedregardless of the clinical response toconventional doses.

AHs included in this review aredesloratadine, levocetirizine, fexofena-dine, and the recently introduced

NSAHs rupatadine and bilastine.Bilastine belongs to the piperidineclass of antihistamines as do lorata-dine, desloratadine, and fexofenadine.Like other antihistamines bilastine isan H1 receptor inverse agonist. Invitro studies have shown that bilastinehas a high specific affinity for the H1-receptor but it has no or very lowaffinity for 30 other tested receptors.The affinity for the H1 receptor isthree and six times higher than for cet-irizine and fexofenadine, respective-ly.10,11 Rupatadine fumarate is a newpotent, long acting, orally active dualantagonist of both histamine H1 andPlatelet-Activating Factor (PAF) recep-tors. In in vivo and in vitro studiesrupatadine was as potent or evenmore potent than other second gener-ation antihistamines (loratadine, terfe-nadine and cetirizine) or selective PAFantagonists.12

METHODS A literature search of PubMed/MED-LINE looking specifically at the studiesthat investigated the effects ofincreased doses of NSAHs in patientswith all subtypes of CU was conduct-ed. For analysis of the efficacy, onlydouble-blind, placebo-controlled stud-ies were selected, whereas uncon-trolled studies were excluded.

Data on study drug, doses, studydesign, treatment duration, subtype ofurticaria being treated, number ofpatients, and main parameter of effica-cy, were collected. When available, effi-cacy data were pooled from differentstudies that utilized the same drugdose. The proportions of patientsresponding to the therapy were com-pared using the Fisher’s exact test witha significance level of p<0.05.

RESULTS Twelve studies that investigated theeffects of higher doses of NSAHs wereidentified in this search. Among those,three papers dealing with the treat-ment of patients with CSU wereexcluded from analysis because oftheir open design, two employing ceti-rizine and one that utilized ebas-tine.13-15 Another study by Metz, et alwas also excluded because it assessedexclusively the effects of a 20 mg doseof rupatadine in patients withacquired cold urticaria whereas nocomparisons with other doses of thedrug were done.16

Table 1 summarizes the detailsfrom a total of eight double-blind,placebo-controlled studies included inthis report. Two investigations usedfexofenadine, rupatadine, or deslorata-dine, and one study was done withlevocetirizine or bilastine. In most stud-ies, NSAHs were administered for 28days, although in the papers bySiebenhaar (with desloratadine) andKrause (with bilastine) the drugs weregiven for seven days. Six articles

included patients with CSU/CIU andother two studied patients withacquired cold urticaria. Four investiga-tions chose mean pruritus scores as themain outcome, and the other four uti-lized the percentage of symptom-freepatients as the main parameter of effi-cacy.

Table 2 presents the results of theeight studies in regard to efficacy ofthe treatment. It can be observed thatthe proportion of symptom improve-ment was highly variable, rangingfrom 3.4% to 71.6%, depending on thedrug and dose. The best responseswere obtained with fexofenadine,rupatadine, and bilastine. The statisti-cal comparison of the data is shown inFigure 1.

There were not significant differ-ences in efficacy between fexofenadineand bilastine, rupatadine and bilastine,and desloratadine and levocetirizine.However, fexofenadine, rupatadine,and bilastine showed significantlyhigher efficacy than desloratadine orlevocetirizine, and rupatadine hadhigher efficacy than fexofenadine.

DISCUSSIONAccording to current recommenda-tions, patients with CU who do notrespond to licensed doses of NSAHsshould be switched to higher doses inorder to obtain a better disease control.A number of publications that evaluat-ed different NSAHs in increasing doseshave clearly demonstrated that a high-er proportion of patients previouslyuncontrolled exhibit significantimprovements of their symptoms aftergoing through this approach.6 It isimportant to mention that theseenhanced results have generally beenaccomplished without compromisingpatient’s safety, since no increasedrates of side effects, including somno-lence, have been observed.

The mechanisms explainingpatient’s benefits from up-dosing arenot completely understood, butincreased in vivo receptor occupan-cy,24,25 and effects of antihistamines onadditional receptors have been pro-posed.26 Observed differences inresponse to different NSAHs cannot beexplained by terminal elimination half-life, duration of action, highertissue/plasma concentration ratios orthe presence of active metabolites inthe skin.27 An alternative hypothesiswould be a differential H1-receptoroccupancy by free (unbound) H1 anti-histamine.25,28 The results discussed inpresent paper are in agreement with aprevious report by Church andMaurer29 who proposed that althoughthe Ki may be an indicator of anti-H1antihistamine potency in vitro, thelarge differences in volume of distribu-tion and tissue accumulation inhumans preclude this from being agood predictor of clinical efficacy inCSU.

POSTGRADUATEEDUCATIONAL SUPPLEMENTComparativeefficacy

of non-sedating antihistamine

updosing in patientswith chronic urticariaMario Sánchez-Borges,1,* Ignacio Ansotegui,2Jorge Montero Jimenez,3 Maria Isabel Rojo,4

Carlos Serrano,5 and Anahí Yañez6from 1Allergy and Clinical Immunology Department, Centro Médico-Docente la, Trinidad

and Clínica El Avila, 6a transversal Urb. Altamira, piso 8, consultorio 803, Caracas 1060,

Venezuela, 2Department of Allergy and Immunology, Hospital Quirón Bizkaia, Erandio,

Spain, 3Unidad de Alergia, Hospital Mexico, CCSS, San Jose, Costa Rica, 4Allergy, Juarez

Hospital, Mexico City, Mexico, 5Allergy Unit, Hospital Fundación Valle del Lili, Cali,

Colombia, and 6Investigaciones en Alergia y Enfermedades Respiratorias, InAER, Buenos

Aires, Argentina. *Corresponding author.

Chro

nicle

Reprinted with permission from: Sánchez-Borges, et al: World AllergyOrganization Journal 2014; 7:33 © 2014Sánchez-Borges, et al; licensee BioMedCentral Ltd. http://www.waojournal.org/con-tent/7/1/33

* vs. Embrace † vs. 3 blades on Venus Original

© 2014 P&G www.gillettevenus.ca

Contours better* to tricky areas for a fl awless shave

5 Contour blades are 6X more fl exible†

Water-activated MoistureGlide serum for incredible glide

MicroFine comb guides hair to the blades that capture virtually every hair

Gillette Venus, the #1 selling female razor brand in the world, introduces NEW Venus Swirl, a razor that sets a new standard in shaving. Designed by women for women, Venus Swirl combines the innovative four-way movement of FlexiBall technology and Gillette’s most advanced blades.

EASY MANEUVERABILITY. EASY CONTROL.


In a previous review article wehad proposed that favourableresponses to high doses of NSAHs inpatients with CU were not uniformlyobserved, and it was likely that there

would be dissimilar results when out-comes from different studies werecompared.6 The present article showsthat in fact some higher doses ofNSAHs, notably fexofenadine, rupata-

dine, and bilastine, induced betterobjective improvements than deslo-ratadine and levocetirizine (Table 2,Figure 1). The reasons for these differ-ences are not clear at this time, but

may depend on differential propertiesof the drugs, such as their chemicalstructure, in vivo anti-inflammatoryactions, metabolism, blockade of vari-ous receptors, and interactions withtransporter systems (e.g., P-glycopro-tein).30 In the case of fexofenadine,however, two studies demonstratedthat higher doses were not more effi-cacious than the standard 60 mg twicea day dose.17,18

Since more than 30% of CUpatients are refractory to antihista-mine therapy, additional pharmaco-logical strategies are available.Alternative drugs inducing betterresponses in AH-resistant CU, asbased on scientific evidences, includethe addition of leukotriene receptorantagonists, corticosteroids,cyclosporine, or omalizumab.7,31,32

The choice of alternative, off-labelagents, should be based on availabili-ty, relative safety, and socioeconomicconsiderations.

When administering high dosesof antihistamines questions regardingtheir safety are usually put forward.Studies conducted up to now havenot demonstrated important concernson predictable or newer adverseeffects of up to four times recom-mended doses of NSAHs. Headachewas the most frequent adverse effectreported for fexofenadine17 andrupatadine,19 but its incidence was nothigher than in placebo-treatedpatients. Somnolence, drowsiness, orsedation was uncommon, althoughfor patients treated with rupatadine 20mg somnolence was observed moreoften than in the placebo group intwo studies.19,20 The utilization ofincreased doses of desloratadine, levo-cetirizine, and bilastine has not beenassociated with adverse effects.Additionally, Staevska, et al reportedthat patients taking higher doses oflevocetirizine or desloratadine showeda paradoxical decrease in somnolencethat was attributed to the relief fromurticaria-related discomfort leading toa better quality of sleep although analternative explanation would be thedevelopment of tolerance to the cen-tral nervous sedative effects of theantihistamines.22

The results presented in thispaper must be taken into considera-tion cautiously because there is alarge heterogeneity between studiesincluded in regard to various aspectsof the investigation such as the sub-type of chronic urticaria under study,duration of the treatment, studydesign, drug doses, and primary out-comes.

We can conclude that increaseddoses of NSAHs show an improvedefficacy in patients with CU who donot respond to approved doses.According to the studies presented inthis paper, this conclusion would beapplicable to CSU/CIU and acquiredcold urticaria, but more researchwould be necessary to be able to eluci-date if this approach is valid for othertypes of urticaria. There are differ-ences in efficacy of these drugs that

POSTGRADUATE EDUCATIONAL SUPPLEMENTTable 1: Studies included in this comparative analysis

Table 2: Efficacy of increased doses of non-sedating antihistamines in patients with chronic urticaria


should be taken into account in theclinical setting. The use of doubleapproved doses of fexofenadine,rupatadine, or bilastine shows anobjective improvement in most(>50%) of patients that respond toantihistamines. Desloratadine requiresfour times the approved dose to reachsimilar results.

There is still the need for addi-tional studies designed to investigatethe response to high doses of NSAHsin patients who do not respond to rec-ommended doses, adapted to currentguideline recommendations.

COMPETING INTERESTS MSB, IA, JMJ, MIR, CS and AY havebeen advisors for FAES Farma, Sanofi,Menarini and Pfizer.

AUTHORS’ CONTRIBUTIONS

All authors contributed equally indrafting the manuscript. All authorsread and approved the final manu-script.

REFERENCES

1. Maurer M, Weller K, Bindslev-Jensen C,Giménez-Arnau A, Bousquet PJ,Bousquet J, Canonica GW, ChurchMK, Godse KV, Grattan CE, GreavesMW, Hide M, Kalogeromitros D,Kaplan AP, Saini SS, Zhu XJ,Zuberbier Y: Unmet needs in chronicspontaneous urticaria. A GA2LENtask force report. Allergy 2011, 66:317-330.

2. Kaplan AP, Greaves M: Pathogenesis ofchronic urticaria. Allergy 2009; 39:777-787.

3. Zuberbier T, Aberer W, Asero R,Bindslev-Jensen C, Brzoza Z,Canonica GW, Church MK, EnsinaLF, Giménez-Arnau A, Godse K,Gonçalo M, Grattan C, Hebert J, HideM, Kaplan A, Kapp A, Abdul Latiff H,Mathelier Fusade P, Metz M, Nast A,Saini SS, Sánchez-Borges M, Schmid-Grendelmeier P, Simons FER,Staubach P, Sussman G, Toubi E,Vena GA, Wedi B, Zhu XJ, Maurer M:The EAACI/GA(2)LEN/EDF/WAOguidelinefor the definition, classifica-tion, diagnosis and management ofurticarial: the 2013 revision andupdate. Allergy 2014; 69:868-887.

4. Humphreys F, Hunter JA: The character-istics of urticaria in 390 patients. Br J

Dermatol 1998; 138:635-638.5. Hiragun M, Hiragun T, Mihara S, Akita

T, Tanaka J, Hide M: Prognosis ofchronic spontaneous urticaria in 117patients not controlled by a standarddose of antihistamine. Allergy 2013,68:229-235.

6. Sánchez-Borges M, Caballero-FonsecaF, Capriles-Hulett A: Treatment ofrecalcitrant chronic urticaria withnonsedating antihistamines: is thereevidence for updosing? J InvestigAllergol Clin Immunol 2013, 23:141-144.

7. Kaplan AP: Treatment of chronic sponta-neous urticaria. Allergy AsthmaImmunol Res 2012, 4:326-331.

8. Zuberbier T, Balke M, Worm M,Edenharter G, Maurer M:Epidemiology of urticaria: a represen-tative cross-sectional population sur-vey. Clin Exp Dermatol 2010, 35:869-873.

9. Giménez-Arnau A, Izquierdo I, MaurerM: The use of a responder analysis toidentify clinically meaningful differ-ences in chronic urticaria patients fol-lowing placebo-controlled treatmentwith rupatadine 10 and 20 mg. J EurAcad Dermatol Venereol 2009, 23:1088-1091.

10. Corcostegui R, Labeaga L, Berisa A,Orjales A: Preclinical pharmacologyof bilastine, a new selective histamineH 1 receptor antagonist: receptorselectivity and in vitro antihistaminicactivity. Drugs in R and D 2005, 6:371-384.

11. Simons FER, Simons KJ: Histamine andH1-antihistamines: celebrating a cen-tury of progress. J Allergy ClinImmunol 2011, 128:1130-1150.

12. Merlos M, Giral M, Balsa D, Ferrando R,Queralt M, Puigdemont A, Garcia-Rafanell J, ForN J: Rupatadine, a newpotent, orally active dual antagonistof histamine and platelet-activatingfactor (PAF). J Pharmacol Exp Ther1997, 280:114-121.

13. Kameyoshi Y, Tanaka T, Mihara S,Takahagi S, Niimi N, Hide M:Increasing the dose of cetirizine maylead to better control of chronic idio-pathic urticaria: an open study of 21patients. Br J Dermatol 2007, 157:803-804.

14. Asero R: Chronic unremitting urticaria:is the use of antihistamines above thelicensed dose effective? A preliminarystudy of cetirizine at licensed andabove-licensed doses. Clin ExpDermatol 2006, 32:34-38.

15. Godse KV: Ebastine in chronic sponta-neous urticarial in higher doses.Indian J Dermatol 2011, 56:597-598.

16. Metz M, Scholtz E, Ferran M, IzquierdoI, Giménez-Arnau A, Maurer M:Rupatadine and its effects on symp-tom control, stimulation time, andtemperature tresholds in patients withacquired cold urticaria. Ann AllergyAsthma Immunol 2010, 104:86-92.

17. Finn AF, Kaplan AP, Fretwell R, Qu R,Long J: A double-blind, placebo-con-trolled trial of fexofenadine HCl in thetreatment of chronic idiopathicurticarial. J Allergy Clin Immunol 1999,103:1071-1078.

18. Nelson HS, Reynolds R, Mason J:Fexofenadine HCl is safe and effectivefor treatment of chronic idiopathicurticaria. Ann Allergy Asthma Immunol2000, 84:517-522.

19. Giménez-Arnau A, Pujol RM, Ianosi S,Kaszuba A, Malbran A, Poop G,Donado E, Perez I, Izquierdo I, ArnaizE, the Rupatadine Urticaria StudyGroup: Rupatadine in the treatmentof chronic idiopathic urticaria: a dou-

ble-blind, randomized, placebo-con-trolled multicenter study. Allergy 2007,62:539-546.

20. Dubertret L, Zalupca L, Cristodoulo T,Benea V, Medina I, Fantin S, Lahfa M,Pérez I, Izquierdo I, Arnaiz E: Once-daily rupatadine improves the symp-toms of chronic idiopathic urticaria: arandomized, double-blind, placebo-controlled study. Eur J Dermatol 2007;17:223-228.

21. Siebenhaar F, Degener F, Zuberbier T,Martus P, Maurer M: High-dosedesloratadine decreases wheal vol-ume and improves cold provocationtresholds compared with standard-dose treatment in patients withacquired cold urticaria: a random-ized, placebo-controlled, crossoverstudy. J Allergy Clin Immunol 2009;123:672-679.

22. Staevska M, Popov T, Kralimarkova T,Lazarova C, Kraeva S, Popova D,Church DS, Dimitrov V, Church MK:The effectiveness of levocetirizine anddesloratadine in up to 4 times conven-tional doses in difficult-to-treaturticaria. J Allergy Clin Immunol 2010;125:676-682.

23. Krause K, Spohr A, Zuberbier T,Church MK, Maurer M: Up-dosingwith bilastine results in improvedeffectiveness in cold contact urticaria.Allergy 2013; 68:921-928.

24. Gillard M, Benedetti MS, Chatelain P,Baltes E: Histamine H1 receptor occu-pancy and pharmacodynamics of sec-ond generation h1-antihistamines.Inflamm Res 2005; 54:367-369.

25. Simons KJ, Benedetti MS, Simons FE,Gillard M, Baltes E: Relevance of H1-receptor occupancy to H1-antihista-mine dosing in children. J Allergy ClinImmunol 2007; 119:1551-1554.

26. Queralt M, Merlos M, Giral M,Puigdemont A: Dual effect of a newcompound, rupatadine, on edemainduced by platelet-activating factorand histamine in dogs: comparisonwith antihistamines and PAF-antago-nists. Drug Dev Res 1996; 39:12-18.

27. Simons FER, Akdis CA: Histamine andAntihistamines. In Middleton’s Allergy.Principlesa and Practice. Chapter 94 edi-tion. Edited by Adkinson NF, BochnerBS, Burks AW, Busse WW, HolgateST, Lemanske RF, O’Hehir RE.Philadelphia: Elsevier Saunders, 2014;1503-1533.

28. Gillman S, Gillard M, Strolin BM: Theconcept of receptor-occupancy topredict clinical efficacy: a comparisonof second-generation H1 antihista-mines. Allergy Asthma Proc 2009:30:366-376.

29. Church MK, Maurer M: H(1)-antihista-mines and urticaria: how can we pre-dict the best drug for our patient? ClinExp Allergy 2012: 42:1423-1429.

30. Bailey DG: Fruit juice inhibition ofuptake transport: a new type of food-drug interaction. Br J Clin Pharmacol2010: 70:645-655.

31. Sánchez-Borges M, Asero R, AnsoteguiIJ, Baiardini I, Bernstein JA, CanonicaGW, Gower R, Kahn DA, Kaplan AP,Katelaris C, Maurer M, Park HS,Potter P, Saini S, Tassinari P, TedeschiA, Ye YM, Zuberbier T, WAOScientific and Clinical Issues Council:Diagnosis and treatment of urticariaand angioedema: a worldwide per-spective. World Allergy Organ J 2012:5:125-147.

32. Khan DA: Alternative agents in refrac-tory chronic urticaria: evidence andconsiderations on their selection anduse. J Allergy Clin Immunol In Practice2013: 1:433-440.

Figure 1:

Efficacy of increased doses of nonsedating antihistamines in patients withchronic urticaria. A). According to mean pruritus score (MPS): *fexofenadine120 mg vs. fexofenadine 240 mg p=0.01, ¶ fexofenadine 120 mg vs. rupatadine20 mg p=0.0001, (diamond) fexofenadine 240 mg vs. rupatadine 20 mg p=0.03.B). According to percentage of symptom-free patients: *desloratadine 10 mg vs.desloratadine 120 mg, desloratadine 10 mg. vs levocetirizine 10 mg, deslorata-dine 10 mg vs. levocetirizine 20 mg, desloratadine 20 mg vs. levocetirizine 10mg, desloratadine 20 mg vs. levocetirizine 20 mg, levocetirizine 10 mg vs. levo-cetirizine 20 mg, bilastine 40 mg vs. bilastine 80 mg p n.s. Desloratadine 10 mgvs. bilastine 40 mg p=0.006. (diamond) desloratadine 10 mg vs. bilastine 80 mgp=0.002. (spade) Desloratadine 20 mg vs. bilastine 40 mg, desloratadine 20 mgvs. bilastine 80 mg, levocetirizine 10 mg vs. bilastine 40 mg, p=0.02. (club)Levocetirizine 10 mg vs. bilastine 80 mg p=0.01.


32 · April/May 2015ol. 21, No. 2 THE CHRONICLE of SKIN & ALLERGY

Message from the Medical Editor

Contraindications:• Hypersensitivity to other corticosteroids• Viral (e.g. herpes or varicella) lesions of the skin, bacterial or fungal skin infections, parasitic infections, skin manifestations relating to tuberculosis or syphilis, eruptions following vaccinations

• Treatment of rosacea, acne vulgaris, pruritis without inflammation or perioral dermatitis

• Topical application to the eye

Most serious warnings and precautions:• Pediatric patients: safety and effectiveness have

not been established in patients <18 years of age

Other relevant warnings and precautions:• Patients should inform physicians of prior use

of corticosteroids• Should not be used under occlusion• Use under occlusive dressing or over extensive

areas of the scalp may result in sufficient absorption which may result in adrenal suppression and other systemic effects

• Caution in stasis dermatitis and other skin diseases with impaired circulation

• Systemic absorption may result in hypothalamic- pituitary-adrenal (HPA) axis suppression, glucocorticosteroid insufficiency, Cushing’s syndrome, hyperglycemia and glucosuria


• Patients/caregivers should be instructed to use LUXIQ® Foam for the minimum amount of time necessary to achieve the desired results

• Increased risk of infections• Caution on lesions close to the eye, risk of

increased intraocular pressure, glaucoma or cataracts

• Hypersensitivity reactions• Caution in psoriasis• Risk of irritation, striae or atrophy of the skin or

subcutaneous tissue• Should not be administered during pregnancy

or lactation unless the expected benefits to the mother outweigh the potential risks to the fetus or the infant

• Cautious dose selection in elderly• Minimum quantity/duration in elderly patients

and patients with renal/hepatic impairment

Dosage and method of administration: • Apply a thin layer of LUXIQ® Foam to the

affected area(s) twice daily, morning and evening for a maximum of 4 weeks.

• Dispense the smallest amount of LUXIQ® Foam (typically a dollop the size of a golf ball, approximately 3 g) necessary to adequately cover the affected area(s) onto a saucer or other cool surface. Do not dispense directly onto hands as foam will begin to melt immediately upon contact with warm skin.

• LUXIQ® Foam is extremely flammable, avoid fire, open flame, spark or smoking during and immediately following application.

Adverse reactions:• In a controlled clinical trial, the most frequently

reported treatment-related adverse reactions were local skin reactions (burning, stinging, itching) and included mild to moderate: pruritus (2%), psoriasis (2%), acne (2%), and alopecia (2%)

For more information: Please consult the product monograph at http: //webprod5.hc-sc.gc.ca/dpd-bdpp/ for important information relating to contraindications, warnings and precautions, adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-800-387-7374.

To report an adverse event, please call 1-800-387-7374.

by JOHN EVANS,Assistant Editor, The Chronicle

The World Doctors Orchestra will be per-forming at The Chan Centre for ThePerforming Arts in Vancouver on Monday,

June 8.The orchestra is comprised of medical doc-

tors from around the world who practice a varietyof different specialties, but who come togetherapproximately three times a year to perform con-certs with the proceeds going to charity, accordingto dermatologist Dr. Mark Lupin of Victoria.

There are currently more than 820 internationalphysicians, including 11 fromCanada, who are part of theorchestra. This includes a coregroup which is supported by arotating selection of additionaldoctor-musicians says Dr.Lupin, who is one of theorchestra’s three ConcertMasters.

“The concert master is the lead violinist, whohelps to tune the orchestra and helps communi-cate between the conductor and the orchestra,”says Dr. Lupin.

Founded in 2007 by epidemiologist Dr. StefanWillich from Germany, who is also the conductor,the orchestra performs classical selections as wellas pieces from composers native to the cities theyare performing in, says Dr. Lupin.

Proceeds to B.C. Children’s Hospital Foundation“[The orchestra’s] mission is to bring like-mindedindividuals together that are already playing at areasonably high standard to perform, and at thesame time raise awareness through sponsors anddonations, and donating the proceeds of the con-certs to local and international charities.” As part ofgiving to the local medical community, the orches-tra will also typically perform at a local hospital inaddition to the main performances, he says.

To select the local charity, the local organiz-er—Dr. Lupin holds this role for the Vancouverconcert—speaks with the local medical commu-

nity to try and identify a specific need. All of theproceeds go to the charities selected, since theparticipating musicians pay the entire cost of theirown travel and accommodation.

“In Vancouver, it was the B.C. Children’sHospital Foundation that was selected,” says Dr.Lupin. In the past, the World Doctor’s Orchestra hasdonated to the Hugo Tempelman Foundation inSouth Africa to support AIDS research and patients.

The day before the Vancouver concert theOrchestra will be playing in Seattle, with proceedsgoing to the Seattle Times Fund for the Needy, hesays. Typically, the orchestra raises between$20,000 and $50,000 per performance.

Dr. Lupin, in addition to being the ConcertMaster for the event, will feature prominently in theperformance. “I’m performing with the orchestra asolo violin concerto by the composer AntonínDvorák,” he says. In addition to this piece, theViolin Concerto in A minor, the orchestra will beperforming Dmitri Shostakovich’s Symphony No. 5in D minor and a piece by Seattle-based composerSamuel Jones called ‘Overture for a City.’

There are some interesting logistics involvedin bringing together roughly 100 medical profes-sionals to play the same, often complex, musicalpieces at a high level of artistry. “A few monthsbefore each concert, we are provided with themusic, and the individuals will practice theirparts,” says Dr. Lupin.

“We have about three days of rehearsalsbefore each concert.”

Working with the World Doctors Orchestrahas been enriching both musically and profession-ally, says Dr. Lupin. “How many places do we mixwith physicians of many different specialties, andin such a collegial atmosphere? It is nice to talkabout music and it is nice to play music, but it isalso nice to ask what can we bring to the localcommunity in a professional way.”

Audio and video samples of the WorldDoctors Orchestra’s performance are available ontheir web page at http://www.world-doctors-orchestra.org and on their Youtube channel atwww.youtube.com/user/WD01channel.

M y O w n T i m e

World Doctors Orchestra in Vancouvern Victoria dermatologist one of three concert masters

Dr. Mark Lupin

instrumental in realizing this global celebration ofdermatology.

The outstanding lineup of international speak-ers include some that we have highlighted in thispreview issue to the World Congress ofDermatology. If the plenary sessions are any indi-cation of the outstanding science, the attendeeswill be able to experience first-hand the innova-tive and exciting advances being made on manydermatology fronts. To name a few: Dr. AtuleButte will be highlighting the IT-driven revolutionin medicine, and, from Canada, our own Dr. JulioMontaner will share his experience in the use of“treatment as prevention”. Other internationalspeakers include Dr. Daniel Kastner who will bespeaking on auto inflammatory syndromes of theskin, and Prof. Elaine Fuchs who will be present-ing on the role of stem cells in dermatology.Other exciting events include the launch of Dr.

Stuart Maddin’s latest book called To Heal theSkin, with co-editor Dr. Eileen Murray.

Just like this issue of THE CHRONICLE (diverseand informative), we expect the World Congresswill help to satisfy the educational needs of theinternational dermatology community.

As you will find in this issue of THE CHRONICLE,we include many important aspects of dermatol-ogy care including pearls for the pediatric der-matologist. Articles on both melanoma and non-melanoma skin cancer, contact dermatitis, andwound care are also included, just to name afew.

All of us at THE CHRONICLE are very excitedabout the upcoming World Congress ofDermatology and expect it will provide materialthat will be of significant interest to our readers formany issues to come.

—Wayne P. Gulliver, MD, FRCPCMedical Editor

Continued from page 3


FARNESOL AND CANDIDA YEASTSA study released in the journal mBiosuggests that farnesol, a communi-cation molecule produced byCandida yeasts on the skin whichretards colony members from enter-ing the more aggressive hyphae-pro-ducing fungal stage, also retards theimmune system in the skin, reportsPopular Science (March 24, 2015).

Researchers first looked at poly-morphonuclear neutrophilic granu-locytes (PMNs), immune cellsknown to interact with Candidae,since previous studies had shownthat PMNs became less active whenthe yeast cells were nearby. Whenthe researchers isolated PMNs fromhuman blood and cultured themalongside either farnesol alone orfarnesol and Candidae, the PMNsreleased chemical signals known toalert the immune system to threats,but did not attack the yeast. This ledthe researchers to look at howmonocytes, which migrate throughthe body to carry the alert of anattack, react to farnesol. The mono-cytes’ movement was restricted,and they were unable to spreadtheir alert. These findings throw coldwater on proposals that farnesolmight be used as a therapy to inhibitaggressive Candidae infections.

SKIN CANCER APPS DEEP-SIXEDThe U.S. Federal Trade Commission(FTC) is cracking down on compa-nies that market mobile device appsthat promise to detect skin cancer,reports NBC News (Feb. 25, 2015).

Two lawsuits have been settledagainst the marketers of MoleDetective and MelApp, and bothcompanies are now prohibited frommaking health claims about theseapps or any they develop in thefuture unless the claims are support-ed by—in the words of the ruling—“reliable scientific evidence” fromhuman trials, the news outlet reports.

The two apps claimed to be ableto calculate the risk that a pho-tographed mole was melanoma,even in the early stages of disease,with the help of some user-providedinformation. The FTC claimed in itslawsuits that the companies hadinadequate evidence to supportthose claims, and ruled the advertise-ments were deceptive, reports NBC.

Dr. Laura Ferris, a dermatologistat the University of Pittsburgh MedicalCenter, co-author of a 2013 study onthe accuracy of similar apps, said“Our study showed these apps are notaccurate. They missed melanomasand many of the melanomas theymissed were actually quite obvious,so that’s very concerning.”

BANDAGE RECOGNIZES SKINULCERS AT AN EARLY STAGEAn adhesive bandage that useschanges in electrical resistance inthe skin to detect tissue changesthat are the first stages in the devel-opment of pressure ulcers has beendeveloped, potentially allowingpatients to avoid the wounds,reports the BBC (Mar. 17, 2015).

Researchers at the University ofCalifornia, Berkley, led by Prof.Michel Maharbiz, developed thebandage. Damage to cells in theskin or apoptosis changes the struc-ture of the outer layers of the skin,making them more conductive toelectricity, the bandage detects thischange in resistance. So far, the BBCreports, results in animal modelshave been promising and the teamhopes to move on to clinical trialssoon to test the device in bandagesand wound dressings.

“You can imagine a futurewhich is very close, where the ban-dages that you put on or the dress-ing that a surgeon or physicianmight put on would actually be ableto really report on a lot of interestinginformation about the progress ofthe wound,” Maharbiz told the BBC.

TARGETED MELANOMA THERAPYCustom-designed vaccines thatgenetically target a patient’s uniquemelanomas could represent a newapproach for treating the commoncancer, according to a report inExpress UK (Apr. 3, 2015).

In a preliminary U.S. trial,researchers sequenced the com-plete genomes of three patients’melanoma cells, in order to identifyseven proteins on the surface of thecells unique to that individual’s can-cer, the news outlet reports. Oncethose are identified, a vaccine canbe developed to induce killer-T cellsto attack the tumour. In all threepatients, the immune response wasreported to be ‘very strong’, andExpress quotes Dr. Gerald Linette, aWashington University oncologistand one of the researchers on theproject as saying “Our results arepreliminary, but we think the vac-cines have therapeutic potentialbased on the breadth and remark-able diversity of the T-cell response.”

While the trial hasn’t reportedfinal outcomes yet, the threepatients’ melanomas have stabi-lized, but Dr. Linette said“Melanoma likes to grow andspread and it hasn’t done that inthese patients, but we don’t notwhether it will.”

Research of NoteSPECIFICALLY TARGETING IL-23

While ustekinumab targets cytokine interleukin (IL)-23 in the inflammatory process ofmany chronic autoimmune disorders, including psoriasis, it also inhibits the p40 sub-unit shared by IL-23 and IL-12. There are no treatments that exclusively inhibit the IL-

23 inflammatory response. To address this, researchers developed small IL-23R-specific antago-nists, selecting one—2305 (teeeqqly)—from those developed for its soluble properties and its abil-ity to inhibit IL-23-induced STAT3 phosphorylation in spleen cells. In testing, peptide 2305 showedfunctional selectivity, modulating IL-23-induced gene expression in Jurkat cells and in cellsexpressing IL-23R and IL-12Rß1. The peptide 2305 did so without inhibiting IL-12-inducedcytokine expression in IL-12Rß/IL-12Rß2/HEK-293 cells. This peptide may be more convenient,less cumbersome, less costly, and more specific than current biologics for treating inflammatoryconditions and may complement other therapies for chronic, debilitating inflammatory diseases.Quiniou C, Dominguez-Pinaro M, Cloutier F, et al: Specific targeting of the IL-23 receptor, using a novelsmall peptide noncompetitive antagonist, decreases inflammatory response, in The American Journal ofPhysiology: Regulatory, Integrative and Comparative Physiology (Nov. 15, 2014; 307(10):R1216-1230).

IMIQUIMOD AS ALTERNATIVE TO SURGICAL RESECTION OF LENTIGO MALIGNA

In older patients, the surgical resection of lentigo maligna (LM) can be complicated bynon-contiguous subclinical extensions and actinic melanocytic hyperplasia, soresearchers explored the use of topical imiquimod as either a primary or adjuvant therapy

for LM. They retrospectively identified patients with LM, early or evolving LM, or LM melanomawho had used 5% imiquimod cream between Jan. 1, 2003 and Dec. 31, 2013, as either primarytherapy after a diagnostic biopsy or as an adjuvant treatment after narrow-margin surgicalresection or complete clinical—but not histologic—resection. This totalled 61 patients with 63cases of disease; 58 were analysed for local recurrence. In 22 of the cases (34.9%), imiquimodwas the primary therapy, and it was an adjuvant to therapy in 41 (65.1%) of cases. Mean treat-ment duration was 11.7 weeks (ranging from two to 60). Clinical clearance was seen in 50(86.2%) cases, with a mean follow up of 42.1 (27.4) months. The authors conclude thatimiquimod cream seems to be a viable choice for either primary or adjuvant use in treating LMin older patients who are not good candidates for surgery.Swetter SM, Chen FW, Kim DD, Egbert BM: Imiquimod 5% cream as primary or adjuvant therapyfor melanoma in situ, lentigo mealigna type, in Journal of the American Academy of Dermatology

(Mar. 17, 2015 online edition).

What THE LAY PRESS is saying about . . .

Department Editor: John Evans

Diagnostic Quiz

A. Erythema nodosumB. DermatophytidC. Erysipelas

D. Granuloma faciale

THE EDITORS invite your participation in thisregular feature of the journal.Please send all images and

correspondence to:Medical Editor,

The Chronicle of Skin & Allergy555 Burnhamthorpe Road, Suite 306,

Toronto, Ont. M9C 2Y3.Telephone: (416) 916-2476

E-mail: [email protected]

Correct answer: Erysipelas


Journal Club THE CHRONICLE of SKIN & ALLERGY

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* Clinical signifi cance has not been established.† Comparative clinical signifi cance has not been established.

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The Chronicle of Skin & Allergy February 2016

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