SOODABEH ZANDI, MD FRCPC

Psoriasis, Eczema, and Phototherapy

DISCLOSURES

• LEO, ABBVIE, CELGENE, GALDERMA

UV SPECTRUM

UV RESPONSIVE DERMATOSIS

• Psoriasis• Vitiligo• MF• Eczema• Photodermatosis• PR• GVHD• Acne• LP

• Pruritus• PLC• PRP• IMH• UP• Alopecia• GA• Parapsoriasis• …

MECHANISM OF ACTION OF UVB

• ↓ proliferation of epidermal keratinocytes

• Affects cytokines and adhesion molecules

• Inhibits action of langerhans cells• Apoptosis of Tcells• Switch from Th1 to Th2 phenotype• Inhibits Th17 cells

CHOOSING UV THERAPY TYPE

DX• Psoriasis, generalized• Eczema, generalized

• Eczema/psoriasis, localized

• Mycosis Fungoides• Pruritus• Parapsoriasis

RX• NB------>BB------>PUVA• NB------>UVA/UVB or

UVA1---->PUVA

• NB or UVA1 foreczema;tPUVA for both

• PUVA(thick) or NB(BB)• NB(BB) ---->PUVA• NB(BB) ---->PUVA

CONTRAINDICATIONS

• Photosensitivity Disorders– Genetic syndromes: XP– Porphyria– CTD: LE, DM

• History of melanoma, NMSC??• Immunosuppressed patients (eg. transplant

patients)• PUVA: type 1 skin, arsenic intake, previous IR

(X-ray or grenz ray), severe liver disease, cyclosporine

SIDE EFFECTS

• Short term: erythema, itching, burning, stinging, xerosis

• Reactivation of HSV• Photoaging• Hyperpigmentation• Photocarcinogenesis?• ↑ risk of melasma (esp pregnant)

© Danderm; www.danderm-pdv.is.kkh.dk.

9

MAJOR TYPES OF PSORIASIS

Inverse Psoriasis

Erythrodermic Psoriasis

Guttate Psoriasis

Plaque Psoriasis Pustular Psoriasis

Photos from Habif 2004. Clinical Dermatology: A Color Guide to Diagnosis and Therapy

DIFFERENTIAL DIAGNOSIS: PLAQUE PSORIASIS VS.

OTHER RED, SCALY LESIONS

Photos © Danderm; www.danderm-pdv.is.kkh.dk.

Tinea corporis

Plaque psoriasis

11

DIFFERENTIAL DIAGNOSIS

• Tinea• Nummular eczema• Seborrheic dermatitis• Contact dermatitis• Mycosis fungoides

• How would you treat/manage body plaque psoriasis of moderate severity?

13

Psoriasis

Mild

Non Prescription

Topicals

Controlled well?

YesContinue

No

Prescription Topicals

Controlled well?

YesContinue

No

Moderate to severe

Phototherapy

YesContinue

No

Systemics

TREATMENT OF PSORIASIS

• May follow a traditional “stepwise” approach or be customized to patient’s severity and personal history

• Three major types of therapies

– External therapy using topical agents

– Phototherapy– Internal therapy using

systemic agentsMenter A & Griffiths CEM. Current and future management of psoriasis. Lancet 2007; 370: 272-284.Schematic of psoriasis treatment ladder. Available at : en.wikipedia.org/wiki/Psoriasis

SEVERITY OF PSORIASIS

– Candidates for localized therapy– Candidates for systemic therapy

• Candidates for systemic therapy may have one or more of the following features:– BSA greater than 10%– Involvement of vulnerable areas of the body,

including palms, soles and genitals– Significant impact on quality of life– Failure of localized therapy– Concomitant psoriatic arthritis

PSORIASIS TREATMENT

• Simplify treatment• Provide enough medication • Consider combination treatment• Be aware of side effects• Rotational therapy

CANADIAN PSORIASIS GUIDELINES: MEASURING TREATMENT SUCCESS

Clearance• No signs of disease• With current treatment options, this is an achievable goal

for many patients, even those with moderate/severe psoriasis

Control• Patient and health care provider define response to

therapy as “satisfactory”, which does not necessarily mean clearance

Remission• Signs/symptoms are suppressed (not necessarily cleared)

over a period of time during which no treatment is prescribed other than routine skin care

Canadian Psoriasis Guidelines Committee. June 2009. 18

TOPICAL THERAPIES FOR PSORIASIS

• Corticosteroids• Calcipotriene (Dovonex)• Dovobet (Combination)• Tazorotene (Tazorac)• Tacrolimus (Protopic) or

Pimecrolimus(Elidel) for facial and inverse• Tar• Anthralin

• Ointments, creams, gels, foams, sprays, shampoos, and medicated tape all available

Topical corticosteroidsReduce inflammation and itchiness

Vitamin D3 analogue (calcipotriol, calcitriol)•Reduces keratinocyte proliferation •Induces keratinocyte differentiation

Calcipotriol/betamethasone dipropionate combination• Reduces keratinocyte

proliferation• Induces keratinocyte

differentiation• Reduces inflammation and

itchiness• Has vasoconstrictive

properties

Canadian Guidelines for the Management of Plaque Psoriasis; Calcipotriol product monograph 2007; Calcipotriol/betamethasone dipropionate product monograph 2008; Calcitriol product monograph 2009; Guenther LC, Skin Ther Lett 2002.

COMBINATION TOPICAL: CORTICOSTEROID + VITAMIN D3 ANALOGUE

PRACTICAL FACTORS INVOLVED IN CHOOSING SYSTEMIC THERAPY

• Efficacy• Potential side effects of drug• Type of psoriasis• Impact on quality of life/patient needs• Presence/absence of psoriatic arthritis• Concomitant morbidities• Ease of administration• Insurance coverage/out of pocket costs• FDA approved for indication

SYSTEMIC THERAPIES FOR PSORIASIS

• Phototherapy: UVB, narrow-band UVB, PUVA, Excimer laser

• Methotrexate• Acitretin (Soriatane)• Cyclosporine• Apremilast• Biologics

Which forms of psoriasis can be treated with narrow band UVB (NB UVB) phototherapy?

• Psoriasis vulgaris • Guttate Psoriasis • Plaque psoriasis• Palmoplantar psoriasis; tPUVA or NB-

UVB• Not indicated

– Erythrodermic– Pustular– Flextural

SYSTEMIC THERAPIES

Vitamin A analogues (Acitretin) * Methotrexate * Cyclosporine *

Administration oral oral oral

Mode of action slow the growth of skin cells and reduce inflammatory markers

inhibit cell replication and suppress specific T-cell activities

inhibit Calcineurin, which interferes with early events in T-

cell activation

Side effects

cause birth defects, dry skin, eyes and lips, stiff joints and

sore muscles, hair loss, increase cholesterol, increase

skin photosensitivity

loss of appetite or weight, nausea, fatigue, anemia, liver

toxicity, pneumonitis, stomatitis, teratogen

nephrotoxicity, hypertension, high cholesterol,

immunosuppression (increase risk of infection or malignancy)

Considerationsdo not to use in women of child-

bearing age, with high cholesterol or liver disease

do not use in pregnant or nursing women, with liver or

kidney disease, diabetes, obesity, low blood cell count,

alcoholism

do not use in pregnant or nursing women with kidney

disease, high blood pressure or cholesterol, lymphoma or skin

cancerCanadian Psoriasis Guidelines, 2009Psoriasis, 2nd Edn. Key Porter Books Ltd., Langley RGB. Revised Edn (Apr 23, 201). Pp. 122-39.The Canadian Guide to Psoriasis.. Papp KA. John Wiiley & sons Canada, Ltd 2011. p.79-84

* Regular monitoring recommended with these medications due to side effects

Apremilast: A Oral Small Molecule PDE4 Inhibitor Thought to Work Intracellularly to Modulate Pro-

and Anti-inflammatory Mediators

cAMP

cAMPcAMP

AMP

PDE4Apremilast

Anti-InflammatoryMediators(i.e. IL-10)

Pro-InflammatoryMediators

(i.e. TNF-α, IL-23, IFN-γ)

Immune Cell1. Schafer P. Biochem Pharmacol. 2012;83:1583–1590.

AMP AMP

aVisual representation based on preclinical evidence.

Baseline Week 16

PASI-85

PASI-69

1. Data on file, Celgene Corporation Individual results may vary

BIOLOGIC THERAPIES

Agents Mode of action Half-life Administration & dosing

Anti-TNF-α

Adalimumab Human Anti-TNF-α IgG1 monoclonal antibody

10 - 20 days

S/C — 80 mg SC (induction), followed by 40mg at eow

(maintenance), stating 1-wk after 1st

dose

Etanercept Human Anti-TNF-α receptor fusion protein 3 – 5.5 days

S/C — 50 mg SC biw (3-4 days apart) for 3 months, followed by

50mg q1wk

Infliximab Chimeric anti-TNF-αIgG1 monoclonal antibody 8 – 9.1 days IV — 5 mg/ kg IV at Wk 0, 2 & 6,

then q8wks thereafter

Anti- IL-12/ IL-23

Ustekimumab Human monoclonal antibody that binds to a polypeptide subunit common to IL-12 /23

15 - 32 daysS/C — 45 mg SC at Wk 0 & 4, then q12wks thereafter; may use 90 mg in patient with body weight > 100 kg

Please refer to respective Product monographs for full prescribing informationAdapted from respective Product Monographs. Comparative clinical significance has not been established

• How would you treat/manage atopic dermatitis of moderate severity?

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RECOMMENDATIONS FOR NONPHARMACOLOGIC INTERVENTIONS

• Application of moisturizers• Bathing is suggested for patients with AD as

part of treatment and maintenance

• Moisturizers should be applied soon after bathing to improve skin hydration in patients.

• Limited use of nonsoap cleansers

• Use of wet-wrap therapy with or without a topical corticosteroid

RECOMMENDATIONS FOR TOPICAL ANTIMICROBIALS AND ANTISEPTIC

• Except for bleach baths and intranasal mupirocin, no topical antistaphylococcal treatment has been shown to be clinically helpful in patients with AD.

RECOMMENDATIONS FOR TOPICAL CORTICOSTEROIDS

Recommended for individuals who have failed to respond to good skin care and regular use of emollients

Choosing a topical corticosteroid :

patient age, areas of the body to which the medication will be applied, and other patient factors such as degree of xerosis, patient preference, and cost .

Twice-daily application of corticosteroids is generally recommended.

RECOMMENDATIONS FOR TOPICAL CORTICOSTEROIDS

• Proactive, intermittent use of topical corticosteroids as maintenance therapy (1-2 times/wk) on areas that commonly flare is recommended to help prevent relapses and is more effective than use of emollients

• The potential for both topical and systemic side effects, including possible hypothalamic-pituitary-adrenal axis suppression, should be considered.

RECOMMENDATIONS FOR TOPICAL CALCINEURIN INHIBITORS

• TCI are recommended and effective for acute and chronic treatment, along with maintenance.

• Indications:• Recalcitrance to steroids • Sensitive areas (eg, face, anogenital, skin

folds)• Steroid-induced atrophy• Long-term uninterrupted topical steroid

use

RECOMMENDATIONS FOR PHOTOTHERAPY

• Phototherapy can be used as maintenance therapy in patients with chronic disease.

• The light modality chosen should be guided by factors such as availability, cost, patient skin type, skin cancer history, patient use of photosensitizing medications, etc

PHOTOTHERAPY

• Indication: Conservative RX failssteroid side effects, widespread

• NB-UVB, UVA/B , BB-UVB, UVA1 and PUVA

• Pruritus improves first; also first sign of relapse

• Missing Rxs Rapid return of eczema• Maintance is QW

RECOMMENDATIONS FOR THE USE OF SYSTEMIC ANTIMICROBIALS

• The use of systemic antibiotics in the treatment of non-infected AD is not recommended. Systemic antibiotics are appropriate and can be recommended for use in patients with clinical evidence of bacterial infections in addition to standard and appropriate treatments for AD disease.

RECOMMENDATIONS FOR SYSTEMIC IMMUNOMODULATORY AGENTS

• Optimized topical regimens and/or phototherapy do not adequately control the signs and symptoms of disease.

• The patient’s skin disease has significant negative physical, emotional, or social impact.

RECOMMENDATIONS FOR SYSTEMIC IMMUNOMODULATORY AGENTS

• All immunomodulatory agents should be adjusted to the minimal effective dose once response is attained and sustained.

• Adjunctive therapies should be continued in order to use the lowest dose and duration of systemic agent possible.

SYSTEMIC IMMUNOMODULATORY AGENTS

• Methotrexate

• Cyclosporine • Azathioprine.

• Mycophenolate mofetil