Faculty/Presenter Disclosure · exanthematous drug eruption due to lamotrigine. • Fortunately,...

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Faculty/Presenter Disclosure

• Faculty/Presenter: Dr. Kirk Barber

• Relationships with commercial interests:

Grants/Research Support: Amgen, Abbvie, Bristol Myer Squibb, Boehringer Ingelheim, Celgene, Dermira, Galderma, Glaxo Smith Klein, Janssen, Leo Pharma, Lilly, National Institute of Health, Novartis, Pfizer, Regeneron, Vitae, Xenon Pharmaceuticals

Speakers Bureau/Honoraria: Amgen, Abbvie, Celgene, Galderma, Janssen, Kirk Barber P.C., Kirk Barber Research, Sanofi, Sun Pharmaceuticals, Valeant

Consulting Fees: Not applicable

Other: This presentation has received support from the Alberta College of Family Physicians in the form of a speaker fee and/or expenses.

ACFP 63rd ASADisclosure of Commercial Support

This program has received financial support in the form of sponsorship from:

• Potential for conflict(s) of interest: Those speakers/faculty who have made COI disclosure are noted in the 63rd ASA Program and on the Salon A/B slide scroll.

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Mitigating Potential Bias

• ACFP: → The ACFP’s Sponsorship Guidelines apply to ASA Sponsorship. The ACFP abides by the College of

Family Physicians of Canada’s Understanding Mainpro+ Certification Guidelines, the Canadian Medical Association’s Policy Guidelines for Physicians in Interactions With Industry and the Innovative Medicines Canada Code of Ethical Practices (2016). As a non‐profit organization, the ACFP complies with Canada Revenue Agency regulations. When deliberating acceptance of sponsorship, the ACFP considers and accepts sponsorship only from those whose products, services, policies, and values align with the ACFP vision, values, goals, and strategies priorities.

• ASA Planning Committee: → Consideration was given by the 63rd ASA Planning Committee to identify when Planning

Committee members’ and speakers’ personal or professional interests may compete with or have actual, potential, or apparent influence over program content.

→ Material/Learning Objectives and/or session description were developed and reviewed by a Planning Committee composed of experts/family physicians responsible for overseeing the program’s needs assessment and subsequent content development to ensure accuracy and fair balance.

→ The 63rd ASA Planning Committee reviewed Sponsorship Agreements to identify any actual, potential or apparent influence over the program.

→ Information/recommendations in the program are evidence‐ and/or guidelines‐based, and opinions of the independent speakers will be identified as such.

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Clinical Practice

Exanthematous Drug Eruptions

Robert S. Stern, M.D.

N Engl J MedVolume 366(26):2492-2501

June 28, 2012

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Case Vignette

• A 50-year-old woman with bipolar depression presents with a widespread pruritic rash of 1 day's duration.

• She is afebrile and otherwise well.

• She has a history of childhood eczema and is allergic to sulfonamide antibiotics.

• Her medications include thyroxine daily, naproxen intermittently, and lamotrigine, which she began taking 3 weeks earlier.

• How should this case be evaluated and treated?

Clinical Presentations of Common Drug Reactions and Measles.

Stern RS. N Engl J Med 2012;366:2492-2501

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Clinical Presentations of Severe Cutaneous Reactions to Drugs.


Selected Infections and Other Conditions that Often Include an Exanthem and Characteristics that Help Differentiate Them from an Exanthematous Drug Eruption.


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Features of Selected Severe Cutaneous Adverse Reactions to Drugs.


Conclusions and Recommendations

• The patient described in the vignette almost certainly has an exanthematous drug eruption due to lamotrigine.

• Fortunately, she has no signs or symptoms suggestive of a severe cutaneous reaction, but she should be informed that if fever, mucosal symptoms, blisters, or malaise develops, she should seek immediate medical attention.

• She should also be advised to stop taking lamotrigine and to ask her psychiatrist to prescribe an alternative agent that is not an aromatic amine.

• Since lamotrigine has a long half-life, the patient should be informed that the eruption may take a week or longer to fade.

• I would recommend that she apply emollients and take sedating antihistamines at bedtime.

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Conclusions and Recommendations

• If the rash is very itchy, I would recommend treatment with a potent topical glucocorticoid for 1 week; although data from randomized trials are lacking, clinical experience suggests that this treatment should reduce secondary skin inflammation and pruritus.

• Oral glucocorticoids are not indicated, and no further tests are necessary.

• She should be counseled to avoid this drug and other aromatic amines, including phenytoin and carbamazepine.

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ECZEMA“Eczema is a reaction pattern of the skin characterizedby a series of elementary lesions which succeed each other, combine or coexist in neighboring localities. These elementary lesions are erythema, edema,papulation, vesiculation, exudation, crusting, lichenification, desquamation, and sometimes brown pigmentation.”

Morphological Diagnosis of Skin DiseaseRobert Jackson MD FRCPC

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Inflammatory T cell infiltrateInflammatory T cell infiltrate

.

Published in: Melinda Gooderham; Charles W. Lynde; Kim Papp; Marc Bourcier; Lyn Guenther; Wayne Gulliver; Chih-ho Hong; Yves Poulin; Gordon Sussman; Ronald Vender; Journal of Cutaneous Medicine and Surgery 21, 31-39.DOI: 10.1177/1203475416670364Copyright © 2016 Canadian Dermatology Association

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“Atopic Dermatitis is a common, chronic, inflammatory skin disease. It is characterized by intense itching, dry skin, inflammation and relapses and causes physical and emotional distress for patients and their families”

Second International Consensus Conference on Atopic Disease (ICCAD II)BJD (2003) 148 (Supp 63: 1-2)

Life Course Epidemiology

“The study of long term biological, behavioural, and psychological processes that link adult health and disease risk to physical or social exposures acting during gestation, childhood, adolescence, earlier in adult life, or across generations”

Cumulative Life Course Impairment

Linder MD et al, Acta Derm Venereol 2016; Suppl 217: 102–108

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Adverse effects of not treating atopic eczema effectively

Courtesy of Prof. M. Meurer, Dresden, Germany

Atopic DermatitisDiagnostic Criteria

Hanifin – Rajka

Pruritus Early age of onset Typical morphology Chronically relapsing Xerosis Personal\Family Atopy

UK Working Group

PRURITUS Onset before 2 years Hx Flexural Eczema Visible flexural

eczema Xerosis Personal Hx Atopy

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Atopic DermatitisAsthmaAllergic Rhinitis

Age

Prev

alen

ce

~1yrs ~22yrs

Adapted from Spergel et al. , 2003

The Atopic March

Presentation in infants

• Intense pruritis and irritability

• Commonly seen on face, neck, cheeks, extensor surfaces of limbs

• diaper area sparing

• Eczematous changes

• Poorly demarcated scaly papules

• Crusts and excoriation Illustration by Carlos Machado, M.D.

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Presentation in children

• Dry, pruritic, papular eruption;

increased lichenification

• Less involvement on face, more

flexural involvement

• Exudation, crusting, infections

• Chronic and relapsing course

Illustration by Carlos Machado, M.D.

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Presentation in adolescents and adults

• More diffuse involvement

• Hand and eyelid eczema

become more common

• Triggers become more

important

• Severity and flares

decreases with ageIllustration by Carlos

Machado, M.D.

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“… likelihood is that 60% of children with atopic dermatitis may recover free of the disease, the remainder having recurrences for long periodsof time.”

Graham – Brown RAC J Am Acad Dermatol 2001;45:561-3

“The emphasis should be on long term control andnot just reactive management of relapses.”

ICCAD II 2003

You need a Plan

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The Plan

Remove irritants and triggers Hydrate the Skin Identify and Treat Infection Treat the Inflammation Proactive Treatment Education

The Plan

Remove the Triggers and Irritants Stress Allergens

FoodsHouse dust mite

IrritantsSoapsLow environmental humidity

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The Plan

Empiric trial of egg and milk exclusion(child and \or maternal)

Seek food antigen specific IgE antibodies(prick tests, RAST)

Eliminate identified food for 3 weeks

Bath Paradox

GOOD

Hydration

Remove Crusts

Playtime\Bonding

BAD

Soap

Evaporation

Pain

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The Plan

Daily

Tepid

Soapless

Pat Dry

Emollients

Lotions Creams Ointments

Bland

Volume

Application

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The Plan

If you cannot cream do not bathe

3 minute rule

Treat Infections

Staph Aureus

Herpes Simplex

Molluscum

Papilloma Virus

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Management Principles

Remove irritants and triggers Hydrate the Skin Identify and Treat Infection Treat the Inflammation Proactive Treatment Education

Tacrolimus preventing and treating flares of atopic dermatitis

0

50

100

Time

FLARE

Complete Emollient Therapy

TCS – 2 x day

Tacrolimus – 2 x dayTacrolimus – 2 x day

Tacrolimus – nightTCS ‐morning

Tacrolimus – nightTCS ‐morning

Tacrolimus – 2 x week Tacrolimus – 2 x week

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Topical corticosteroids (“steroids”)(TCSs) Topical immunomodulators (TCIs)

Tacrolimus (Protopic) Pimecrolimus (Elidel )

Systemic Azathioprine \Methotrexate Light (UVB, narrow band UVB, PUVA) Cyclosporine

Anti-inflammatories

.

Published in: Julia N. Mayba; Melinda J. Gooderham; Journal of Cutaneous Medicine and Surgery Ahead of PrintDOI: 10.1177/1203475416685077Copyright © 2016 Canadian Dermatology Association

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Skin Atrophy Striae Acne Tachyphylaxis Allergy Eyes – Increased Intraocular Pressure Systemic Effects

Corticosteroids –Common Side Effects

.


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Optimizing AD Therapy in Infants with Elidel® PETITE Study

Safety and Efficacy of Pimecrolimus inAtopic Dermatitis: A 5-Year Randomized Trial in Pediatrics

(PETITE Study)

Methods Primary End Points Measure

• 2418 infants were enrolled in a 5-year, multicenter, open-label, randomized, parallel group study

• Age group ≥3–<12 months (Mild to Moderate Patients)

• Infants were randomized to PIM (n = 1205 with short-term TCSs for disease flares) or TCSs (n = 1213).

• Patients were randomized in a 1:1ratio to either PIM 1% cream or TCSBID at first signs & symptoms

• The primary objective was to compare safety

• The secondary objective was to document PIM’s long-term efficacy

• Treatment success was defined as an Investigator’s Global Assessment score of 0 (clear) or 1 (almost clear).

Sigurgeirsson and al.; Safety and Efficacy of Pimecrolimus in Atopic Dermatitis: A 5-Year Randomized Trial; PEDIATRICS Volume 135, number 4, April 2015

Longest and largest intervention study ever conducted in infants with mild-to-moderate AD

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A 5-Year Randomized Trial in Pediatrics (PETITE Study)

Baseline & Clinical Characteristics of Patients

SAFETY AND EFFICACY OF PIMECROLIMUS INATOPIC DERMATITIS: A 5-YEARRANDOMIZED TRIAL IN PEDIATRICS(PETITE STUDY)

• Both PIM (n=1205) and TCSs (n=1213) had a rapid onset of action with >50% of patients achieving treatment success by week 3.

• After 5 years of as-needed treatment, 88.7% PIM-treated and 92.3% TCS treated infants had only minimal disease

Overall Treatment Success


P < .001

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• PIM was associated with a steroid sparing effect. • 36% (n=434) of patients in the PIM group did not use any TCSs over 5

years• Overall, the patients in the PIM group used TCSs for a median of only 7

days• Patients in the PIM group used PIM for a median of 224.5 days

SAFETY AND EFFICACY OF PIMECROLIMUS INATOPIC DERMATITIS: A 5-YEAR RANDOMIZED TRIAL INPEDIATRICS(PETITE STUDY)


P < .001

SAFETY AND EFFICACY OF PIMECROLIMUS INATOPIC DERMATITIS: A 5-YEAR RANDOMIZED TRIAL INPEDIATRICS(PETITE STUDY)


• Freq of most common AE were similar

• No difference in growth rate

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Conclusions from PETITE study

Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. No cases of T-cell lymphoma or skin malignancies with

PIM during the study

PIM was steroid-sparing.

The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to moderate AD


Long-Term Management of Atopic Dermatitis in Children with Elidel®

1 Year Study

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Long-Term Management of Atopic Dermatitis in Children with Elidel®: 1

Year studyMethods Primary End Points Other Measures

• 1-year, controlled, double-blind study, 713 AD patients (2–17 years)

• Randomized 2:1 to a pimecrolimus-based or conventional regimen.

• BID to affected areas at the first signs (ie, erythema) or symptoms (ie, pruritus) of AD to prevent the progression to flare

• Second-line moderately potent topical corticosteroids were allowed in both groups for flares not controlled by study medication

• Incidence of flares was chosen as the primary efficacy endpoint at 6 months

• Secondary efficacy variables included ranked AD flares in 12 months

• Time to first flare• IGA• Eczema Area and

SeverityIndex (EASI)

Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Manjra A et al. Efficacy and Safety of Pimecrolimus in Cream the Long-Term Management of Atopic Dermatitis in Children; Pediatrics 2002; 2002;110(1 Pt 1):e2.

Long-Term Management of Atopic Dermatitis in Children with Elidel®: 1 Year study

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61

34.2

50.8

28.3

Elidel 6 Month(n=360)

Control 6Months(n=123)

Elidel 1 Year(n=324)

Control 1 Year(n=115)

% of Patients Who Completed 6 or 12 Months With NO Flares

Long-Term Management of Atopic Dermatitis in Children with Elidel®: 1 Year studyIncidence of Flares

P < .001

Proportion of patients who completed 6 or 12 months with NO flares was approximately twice as high in the Elidel® group compared with

control regardless of baseline severity


Long-Term Management of Atopic Dermatitis in Children with Elidel®: 1 Year study Steroid Sparing Effect

Proportion of Patients that Required No TCS was approximately Twice as high for Elidel patients vs. Control


65

37.1

57.4

31.6

Elidel 6 Month(n=360)

Control 6Months (n=123)


Control1 Year(n=115)

% Of Patients That Did Not Require TCS

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Long-Term Management of Atopic Dermatitis in Children with Elidel®: 1 Year study Steroid Sparing Effect

17.1

27.5



% of Patients Requiring a TCS for 1‐14 Days

25.5

41



% of Patients Requiring a TCS for >14 Days


57.4

31.6

Elidel 1 Year (n=324) Control 1 Year(n=115)

% of Patients That Did Not Use TCS During 1 Year

More Than Half the Patients on Elidel Did Not Use a TCS Over 1 Year & Elidel Patients Spent Fewer Days on TCS vs

Control

TCI preventing and treating flares of atopic dermatitis

0

50

100

Time

FLARE

Complete Emollient Therapy

TCS – 2 x day

TCI – 2 x dayTCI – 2 x day

TCI – nightTCS ‐morning

TCI – nightTCS ‐morning

TCI – 2 x week TCI – 2 x week

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Canadian Dermatology Association: Position Statement on Topical Calcineurin

Inhibitors1

There is no evidence of an increased rate of lymphoma when compared to the general population.

The clinical and histological patterns of the observed lymphomas are not consistent with typical immunosuppression- related lymphomas.

There is minimal absorption of topical calcineurin inhibitors, with non-detectable or negligible blood levels, making long-term intense immunosuppression unlikely.

There is no evidence of interference with effectiveness of immunization, delayed hypersensitivity skin responses, or rates of systemic infections.

1. http://www.dermatology.ca/wp-content/uploads/2012/01/TopicalCalcineurinInhibitorsEN.pdf

.


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CHRONOS: DupilumabP

atie

nts

Wit

h IG

A (

0,1)

and

≥2-

Poi

nt I

mpr

ovem

ent

From

Bas

elin

e (%

)

*P<0.0001

12.5

36.0

40.0

0

10

20

30

40

50

60

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Time (weeks)

*

*

Dup 300 mg qw + TCS (n=270)

Dup 300 mg q2w + TCS (n=89)

Placebo qw + TCS (n=264)

1. Sanofi Genzyme, Regeneron. Data on file.

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Management of Chronic Hand Eczema (Dermatitis)

1. Lynde CW, et al. Canadian Hand Dermatitis Management Guidelines. J Cutan Med Surg 2010;14(6):267‐284;2. Diepgen TL, et al. Contact Dermatitis 2007;57:203‐210.

Chronic Hand Dermatitis Inflammatory skin disease characterized

by:1,2

Scaling Hyperkeratinization Erythema Vesicles Deep, painful fissures

Chronic disease1

Persists for >3 months or Reoccurs ≥2 times within 12 months Even with adequate treatment and adherence

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Diepgen TL et al. Contact Dermatitis 2007;57:203–210

Prevalence of Hand Dermatitis

1-year prevalence rate of acute hand dermatitis ~10% (general population): Includes mild cases 50% seek treatment 5% on sick leave

5-7% of all patients have chronic, severe dermatitis 2-4% refractory to topical treatment

High Risk Occupations

Prevalence is ~30% in high-risk occupations1

E.g. hairdressers, caterers, cleaners, healthcare workers, homemakers, etc.

15% of hand dermatitis cases result in exclusion from the labour market2

1. Diepgen TL et al. Contact Dermatitis 2007;57:203–210;

2. Coenraads PJ, Smit H. Epidemiology of Work Related Diseases 2nd edn; BMJ Books, 2000;175–194

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Physical Burden of CHD

Painful fissures can affect daily life and prevent manual work

Leads to: Significant disability Substantial

economic loss


Chronicity and Persistence Swedish 12-year follow-up study 517 patients with occupational hand

dermatitis (from an original cohort of 2,895): 28% considered themselves recovered 70% reported skin symptoms during previous

year 52% had symptoms for ≥50% of the time 37% reported continuous symptoms

Meding B et al. Contact Dermatitis 2005;53:308–313

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Prognostic Factors

Factors associated with poor long-term prognosis: Extensive involvement at initial examination History of childhood eczema Age <20 years at disease onset All 3 risk factors doubles chance of still having

hand dermatitis after 15 years vs. none

Meding B. J Invest Dermatol 2005;124:893–897

Multifactorial Etiology

Allergic contact dermatitis (ACD)

(n=244) 50.7%

Irritant contact dermatitis (ICD)

(n=260) 54%

Atopic Skin Diathesis (ASD) (n=229) 47.6%

ACD+ASD n=11223%

ICD+ASD n=143 29.7%

Occupational HD (Health service, n=482)

*Some patients had >1 etiologyDiepgen TL et al. Personal Communication 2008

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Atopic Predisposition

70-80% of childhood eczema may be due to inherited susceptibility1

3-fold greater risk of hand dermatitis among patients with childhood eczema1

Atopic skin diathesis is a major risk factor2

1. Menne T and Maibach H. Hand Eczema 2nd edn. Dermatology: Clinical and Basic Science Series. 2000;

2. Diepgen TL et al. Contact Dermatitis 2007;57:203–210

Location

Etiology Morphology

• Exogenous (irritant, allergic)

• Endogenous (atopic, other endogenous)

• Dorsum of hands• Palmar• Sides of fingers• Finger tips• Finger webs• Wrists

• Scaling / hyperkeratotic• Erythemato-squamous• Vesicular / pompholyx• Fissures


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Severity of CHDMild CHD Moderate CHD Severe CHD

Lynde CW, et al. Canadian Hand Dermatitis Management Guidelines. J Cutan Med Surg 2010;14(6):267‐284

CHRONIC HD

ACUTE HD

*Ensure patient education and check compliance. Consider reassessment to rule out infection andinfestation, or consider differential diagnosis.HD, Hand dermatitis; CHD, chronic hand dermatitis; TCS, topical corticosteroids

Control the flare with potent TCS or systemic CSTreat any infection

Find cause an identify allergan

Cyclosporine

Onrelapse

ESTABLISH DIAGNOSIS OF HAND DERMATITIS

MODERATE CHDMILD CHD SEVERE CHD

PREVENTION, AVOIDANCE STRATEGIES, AND EDUCATION

EMOLLIENT/MOISTURIZER THERAPY

TCS4–6 weeks

Improved Not improved

Maintainwith TCS prn

EducationCheck complianceIncrease potency

of TCS4–8 weeks

Not improvedImproved


Considertreatment asmoderate HD


Improved Not improved*

Considerphototherapy,or treatmentas severe HD

TCS moderate to super potentModerate to high potency 4–8 weeks

(2 weeks if dorsal location)or super potent TCS for 2 weeks




Onrelapse

EducationAlitretinoinPhototherapy

Potent or superpotent TCS 4‐8 weeks

(2 weeks is super potent)

Lynde CW, et al. Canadian Hand Dermatitis Management Guidelines. J Cutan Med Surg 2010;14(6):267‐284

Canadian Treatment Algorithm:

Chronic Hand Dermatitis

The algorithm suggests that products:• Have an approved indication for this state or,• Have evidence based literature to support their use for this disease state, or• Have significant positive clinical experience that justifies their use for this disease state, based on expert opinion.

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Life Course Epidemiology

“The study of long term biological, behavioural, and psychological processes that link adult health and disease risk to physical or social exposures acting during gestation, childhood, adolescence, earlier in adult life, or across generations”

Cumulative Life Course Impairment

Linder MD et al, Acta Derm Venereol 2016; Suppl 217: 102–108

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1. acne can have an insidious effect on psychological well-being,1 with visible disfigurement of the face eliciting feelings of embarrassment, frustration and anger.2. clinical depression was found to be twice to thrice more prevalent in acne patients of any age than in the general population.3. suicidal ideation and suicide attempts are also approximately twice as common in individuals affected by acne. 4. effective treatment results in an improvement of the patients’ quality of life (QOL).

Rowe C, Australasian Journal of Dermatology (2014) 55, 162–167

Australian Consensus

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Newer Concepts on the Pathogenesis of Acne: Early Subclinical Inflammation Plays a Role

Weiss JS. J Drugs Dermatol. 2013;12(suppl(6):s70-s72

Sebaceous cellsFollicular keratinocytes

• Sebum accumulates

• Follicle enlarges• Keratinous materialbuilds up

Subclinicalinflammation

P acnesMonocyteInflammatory mediators

Neutrophil

T cell

Microcomedoneformation

• P acnes proliferatesand generates inflammatory mediators

• Immune reactions

Closedcomedone

Opencomedone

Inflammatorylesion

90

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Eichenfield L F et al. Pediatrics 2013;131:S163-S186

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Eichenfield L F et al. Pediatrics 2013;131:S163-S186

CMAJ, February 2, 2016, 188(2)

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Clinical treatment algorithm for acne.

Yuka Asai et al. CMAJ 2016;188:118-126

©2016 by Canadian Medical Association

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Tetracyclines are generally well tolerated but can cause mild gastrointestinal disturbances.[182, 183] In addition to nausea, diarrhea and stomach upset, Doxycycline is associated with dose‐dependent photosensitivity and esophageal erosion.[183] Minocycline has been associated with a number of rare but severe side‐effects, including hypersensitivity reactions and auto‐immune disorders, such as lupus‐like syndrome, autoimmune hepatitis, arthritis, thyroiditis, and polyarteritis nodosa.[184, 185]


Eichenfield L F et al. Pediatrics 2013;131:S163‐S186

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Isotretinoin ‐ 1984

Strauss et all ,J Am Acad Derm 10, 490 -494, 1984

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J Am Acad Dermatol2013;69:762‐7

Isotretinoin ‐ Lidose

J Drugs Dermatol 2014: 13(6): 665‐670

Isotretinoin ‐ Lidose

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CMAJ, July 12, 2016, 188(10)

“From Statistics Canada data for the relevant age group, we estimate an annual unplanned pregnancy rate of about 50 per 1000 female patients. These estimates imply that contraceptive measures during isotretinoin treatment in Canada are achieving an effectiveness of about 50% to 70%, short of the ideal when a potent teratogen is being ingested. ”

CMAJ, July 12, 2016, 188(10)

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Isotretinoin and Depression

Psychological side-effects, such as suicide and depression, have been reported in studies but a causal relationship has not been demonstrated[206] and suicidal ideation has been correlated with acne severity.[53] The treating physician should monitor for signs and symptoms of psychiatric disturbance among acne patients before, during, and after isotretinoin therapy.[206]


Tan J, BJD (2014) 171, pp1508–1516

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BJD (2014) 171, pp1508–1516

Fig 2. Percentage change in (a) nodule, (b)papules/pustules and (c) total lesion countsfrom baseline. (d) Percentage of subjects withinvestigator global assessment success.*P < 005. D+A/BPO, doxycycline hyclate +adapalene/benzoyl peroxide; ISO, isotretinoin

PSORIASIS more than just skin deep

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PSORIASIS KILLS

Mortality in Psoriasis1987–2002 GPRD (UK) database

1Gelfand J, et al. Arch Dermatol 2007;143:1493–1499; 2Mehta NM, et al. Eur Heart J 2010;31:1000–1006; 3Abuabara K, et al. Br J Dermatol 2010 163:586–592

Psoriasis(n=3,603)

Controls(n=14,330)

Per

cen

t o

f su

bje

cts

Age (years)

Age at death • Men with severe

psoriasis die 3.5 years earlier than men without psoriasis1

• Women with severe psoriasis die 4.4 years earlier than women without psoriasis1

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PSORIASIS The “heartbreak”

Risk of Myocardial Infarction (MI) in Patients with Psoriasis

Incidences of MI per 1000 patient‐years: (controlled for major cardiovascular risk factors)

•Control patients: 3.58 (95% CI: 3.52‐3.65)

•Mild psoriasis: 4.04 (3.88‐4.21)

•Severe psoriasis: 5.13 (4.22‐6.17)

•Psoriasis may confer an independent risk of MI

•Relative risk was greatest in young patients with severe PsO

Gelfand JM, et al. JAMA 2006;296:1735‐1741.

Adjusted Relative Risk of MI in PsO Patients Based on Age

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Copyright © 2012 American Medical Association. All rights reserved.

Systemic and Vascular Inflammation in Patients With Moderate to Severe Psoriasis as Measured by [18F]-Fluorodeoxyglucose Positron Emission Tomography –Computed Tomography (FDG-PET/CT): A Pilot Study

Arch Dermatol. 2011;147(9):1031-1039. doi:10.1001/archdermatol.2011.119

Figure 1. [18F]-Fluorodeoxyglucose positron emission tomography –computed tomographic (FDG-PET/CT) imaging of skin correlates with observed skin inflammation. A, Photograph of a patient with psoriasis showing extensive multifocal plaques. B, Corresponding PET image from a FDG-PET/CT study in the same patient demonstrates skin inflammation in similar distribution (arrows).

5

FDG-PET/CT

Mehta NN, et al. Arch Dermatol. 2011;147:1031–9.

Psoriasis ControlAorta

Liver

Vasculature

Joints

Skin

FDG = fluorodeoxyglucose; PET/CT = Positron emission tomography/computed tomography

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PSORIASIS CRIPPLES

PsA vs PsO BSA

Degree of skin psoriasis

Prevalenceof PsA

All psoriasis patients 11%

No or little psoriasis 6%

1–2 palms of psoriasis 14%

3–10 palms of psoriasis 18%

10+ palms of psoriasis 56%

Gelfand J, et al. J Am Acad Dermatol 2005;53:573–77

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Demographics Psoriatic Arthritis

Peak age of onset: 34–40 yearsMean age of onset 38 yearsGender distribution — 1.1 F : 1 M

Gladman DD. Rheum Dis Clin North Am. 1998;24(4):829-843. Espinoza LR. Am J Med Sci. 1998;316(4):271-276. Stern RS. In: Fitzpatrick TB, ed. Textbook of Dermatology and General Medicine. 1987:6-10.

20% have destructive, disabling diseaseRemission in 69/391 (~18%)

Lasted on average 2.6 years~50% flared

6/391 had “complete remission”

Gladman DD, J Rheumatol 2001:28:1045

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1. Mease PJ. Ann Rheum Dis. 2001;60(Suppl 3):iii37-iii40. 2. Gladman DD. In: Isenberg DA, et al. Oxford Textbook of Rheumatology. 3rd ed. New York, NY: Oxford University Press. 2004:766-778. 3. Tankosic T, et al. In: Welter R, et al. Psoriasis and Associated Arthropathy. Waltham, Mass: Decision Resources, Inc. 2001:53-54. 4. Mease P, et al. J Am Acad Dermatol. 2005;52:1-19. 5. National Psoriasis Foundation. About Psoriatic Arthritis. Available at: http://www.psoriasis.org/netcommunity/psoriatic_arthritis. 6. Reich K, et al. Br J Dermatol. 2009;160:1040-1047. 7. Prey S, et al. J Eur Acad Dermatol Venereol. 2010;24(Suppl 2):31-35. 8. Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864.

Skin symptoms occur first in ~ 70% of patients1,3,4

Joint and skin symptoms occur together in ~ 15% of psoriatic arthritis patients1,3,4

Joint symptoms occur first in ~ 15% of psoriatic arthritis patients1-4

Years0 5 10 15 20 25

Up to 30% of psoriasis

patients mayactually have

psoriatic arthritis5-7

Skin Symptoms

"Because PsA can be a very severe disease with significant functional impairment, early diagnosis is critical ...Therefore, we

strongly encourage dermatologists to actively seek signs and symptoms of PsA at every patient visit.”8

—AAD guidelines on psoriatic arthritis

Joint Symptoms

Early Detection Joint Symptoms

Clinical PatternsPsoriatic Arthritis

Oligoarthritis Distal Arthritis

Courtesy of Dr. D. Gladman Director, Psoriatic Arthritis Program, UHN, Toronto Western Hospital

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Polyarticular Pattern



Arthritis Mutilans


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Psoriatic Arthritis Dactylitis and Nail Changes



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Metabolic Syndrome in Psoriasis

• 581 adult patients hospitalized for psoriasis compared to 1,044 hospital-based controls

• Odds ratio (OR) for– Diabetes mellitus: 2.48– Hypertension: 3.27– Hyperlipidemia: 2.09– Coronary heart disease:1.95

• Combined presence of these conditions together with obesity (metabolic syndrome (WHO criteria)) had Odds Ratio of 5.29

• PsO patients more likely to be smokers (OR = 2.96) and imbibe regular or heavy consumption of EtOH (OR = 3.33 and 3.61, respectively)

Sommer DM, et al. Arch Dermatol Res. 2006; 298(7):321‐328

Nurses Health Study II

0.811

1.191.4 1.48

2.69

0

0.5

1

1.5

2

2.5

3

3.5

<21.0 21.0–22.9 23.0–24.9 25.0–29.9 30.0–34.9 ≥35.0

Rel

ativ

e ri

sk o

f in

cide

nt p

sori

asis

n = 78,626 BMI

aPatients were followed for 14 years. A total of 892 newly diagnosed cases of psoriasis were reported. p-value for trend <0.001.BMI: Body mass index.

Setty AR, et al. Arch Intern Med 2007;167:1670–5

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Severe plaquepsoriasis

Psoriatic arthritis

Metabolicsyndrome

Myocardial infarctionStroke

The Psoriatic Fingerprint

Gisondi P et al. Inter Emerg Med 2013 in press

Psychologicalmorbidities

Inflammatorybowel diseases

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Gisondi P, et al. J Hepatol. 2009;51:758−64.

NAFLD

NA

FL

D p

reva

len

ce (

%)

100

20

60

0

80

40

PASI ≥10PASI <10

100

40

60

80

20

NA

FL

D p

reva

len

ce (

%)

Controls0

Psoriasis

48%

25%

Natural History of NASH

NAFLD ~30% of western populations

NASH~3% general population;

20-40% of pts w/BMI >35 kg/m2

Cirrhosis

~12-20% risk of progression over 8

years

1-2% risk of progression over 15-20

years

Adams LA et al. J Hepatol. 2005;42:132-138; Dam-Larsen S et al. Gut. 2004;53:750-755;

Sanyal AJ et al. Hepatology. 2006;43:682-689; Adams LA et al. Gastroenterology. 2005;129;113

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Natural History of NASH

Cirrhosis

End-Stage Liver

Disease Complications

Liver-Related

Death

39-62%

22-33%

5%-6.8% yearly

Hui J et al. Hepatology. 2003;38:420-427; Dam-Larsen S et al. Gut. 2004;53:750-755;

Adams LA, Gastro. 2005; Sanyal AJ, Hepatology. 2006.

Bissonnette R, Bourcier M, Gooderham M, et al. J Cutan Med Surg. 2017;21(suppl 2):2S-40S.

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Figure 5. Best response rates in placebo-controlled phase III clinical trials: 1-year data. *PASI 75 is from AMAGINE 2 trial (PASI 75 rates were not reported in AMAGINE 1). PASI, Psoriasis Area Severity Index. 1. Langley RG, et al. N Engl J Med. 2014;371(4):326-338. 2. Gordon KB, et al. N Engl J Med. 2016;375(4):345-356. 3. Papp KA, et al. Br J Dermatol. 2016;175(2):273-286.

Published in: Robert Bissonnette; Marc Bourcier; Melinda Gooderham; Chih-ho Hong; Ian Landells; Charles Lynde; Kim Papp; Yves Poulin; Ronald Vender; Marni C. Wiseman; J Cutan Med Surg 21, 2S-40S.DOI: 10.1177/1203475417722552Copyright © 2017 Canadian Dermatology Association

Dermoscopy – 3 point checklist

Asymmetry: asymmetry of color and structure in one or two perpendicular axes

Atypical Network: pigment network with irregular holes and thick lines

Blue-White structures: any type of blue and\or white colour, i.e. combination of blue-white veil and regression structures

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Clinical and dermoscopic characterization of pediatric and adolescent melanomas: Multicenter study of 52 cases

Cristina Carrera, MD, PhD, Alon Scope, MD, Stephen W. Dusza, DrPH, Giuseppe Argenziano, MD, PhD, Gianluca Nazzaro, MD, Alice Phan, MD, Isabelle Tromme, MD, PhD, Pietro Rubegni, MD, Josep Malvehy, MD, PhD, Susana Puig, MD, PhD, Ashfaq A. Marghoob,

MD

Journal of the American Academy of DermatologyVolume 78, Issue 2, Pages 278-288 (February 2018)

DOI: 10.1016/j.jaad.2017.09.065

Copyright © 2017 Terms and Conditions

Fig 1

Journal of the American Academy of Dermatology 2018 78, 278-288DOI: (10.1016/j.jaad.2017.09.065) Copyright © 2017 Terms and Conditions

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Fig 2


Fig 3


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Fig 4



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