, Eczema, and Phototherapy

SOODABEH ZANDI, MD FRCPC DISCLOSURES

• LEO, ABBVIE, CELGENE, GALDERMA UV SPECTRUM UV RESPONSIVE DERMATOSIS

• Psoriasis • Pruritus • • PLC • MF • PRP • Eczema • IMH • Photodermatosis • UP • PR • Alopecia • GVHD • GA • • • LP • … 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 RX • Psoriasis, generalized • NB------>BB------>PUVA • Eczema, generalized • NB------>UVA/UVB or UVA1---->PUVA

• Eczema/psoriasis, localized • NB or UVA1 for eczema;tPUVA for both • • PUVA(thick) or NB(BB) • Pruritus • NB(BB) ---->PUVA • Parapsoriasis • NB(BB) ---->PUVA CONTRAINDICATIONS • Photosensitivity Disorders – Genetic syndromes: XP – Porphyria – CTD: LE, DM • History of , 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: , itching, burning, stinging, xerosis • Reactivation of HSV • Photoaging • • Photocarcinogenesis? • ↑ risk of (esp pregnant) © Danderm; www.danderm-pdv.is.kkh.dk.

9 MAJOR TYPES OF PSORIASIS

Guttate Psoriasis

Erythrodermic Psoriasis

Plaque Psoriasis Pustular Psoriasis

Photos from Habif 2004. Clinical : A Color Guide to Diagnosis and Therapy DIFFERENTIAL DIAGNOSIS: PLAQUE PSORIASIS VS. OTHER RED, SCALY LESIONS

Plaque psoriasis

Tinea corporis

Photos © Danderm; www.danderm-pdv.is.kkh.dk. 11 DIFFERENTIAL DIAGNOSIS

• Tinea • Nummular eczema • Seborrheic dermatitis • • Mycosis fungoides • How would you treat/manage body plaque psoriasis of moderate severity?

13 Psoriasis

Moderate to Mild severe

Non Prescription Prescription Phototherapy Systemics Topicals Topicals

Controlled Controlled Yes well? No well? Continue

Yes No Yes No Continue Continue 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 agents

Menter 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 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 COMBINATION TOPICAL: CORTICOSTEROID

+ VITAMIN D3 ANALOGUE Calcipotriol/betamethasone dipropionate combination • Reduces keratinocyte Vitamin D analogue 3 proliferation (calcipotriol, calcitriol) • Induces keratinocyte •Reduces keratinocyte differentiation proliferation • Reduces inflammation and •Induces keratinocyte itchiness differentiation • Has vasoconstrictive properties

Topical corticosteroids Reduce inflammation and itchiness

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. 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 • • Plaque psoriasis • Palmoplantar psoriasis; tPUVA or NB- UVB • Not indicated – Erythrodermic – Pustular – Flextural SYSTEMIC THERAPIES

Vitamin A analogues Methotrexate * Cyclosporine * (Acitretin) *

Administration oral oral oral

inhibit Calcineurin, which slow the growth of skin cells and inhibit cell replication and Mode of action interferes with early events in T- reduce inflammatory markers suppress specific T-cell activities cell activation

cause birth defects, dry skin, loss of appetite or weight, nephrotoxicity, hypertension, eyes and lips, stiff joints and nausea, fatigue, anemia, liver high cholesterol, Side effects sore muscles, hair loss, toxicity, pneumonitis, stomatitis, immunosuppression (increase increase cholesterol, increase teratogen risk of infection or malignancy) skin photosensitivity

do not use in pregnant or do not use in pregnant or do not to use in women of child- nursing women, with liver or nursing women with kidney Considerations bearing age, with high kidney disease, diabetes, disease, high blood pressure or cholesterol or liver disease obesity, low blood cell count, cholesterol, lymphoma or skin alcoholism cancer Canadian Psoriasis Guidelines, 2009 * Regular monitoring recommended with these medications due to side effects Psoriasis, 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 Apremilast: A Oral Small Molecule PDE4 Inhibitor Thought to Work Intracellularly to Modulate Pro- and Anti-inflammatory Mediators

cAMP Pro-Inflammatory cAMP Mediators cAMP (i.e. TNF-α, IL-23, IFN-γ)

Apremilast PDE4

AMP Anti-Inflammatory Mediators AMP AMP (i.e. IL-10)

aVisual representation based on Immune Cell preclinical evidence. 1. Schafer P. Biochem Pharmacol. 2012;83:1583–1590. 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 S/C — 80 mg SC (induction), monoclonal antibody followed by 40mg at eow 10 - 20 days (maintenance), stating 1-wk after 1st dose

Etanercept Human Anti-TNF-α receptor S/C — 50 mg SC biw (3-4 days fusion protein 3 – 5.5 days apart) for 3 months, followed by 50mg q1wk

Infliximab Chimeric anti-TNF-α IV — 5 mg/ kg IV at Wk 0, 2 & 6, 8 – 9.1 days IgG1 monoclonal antibody then q8wks thereafter

Anti- IL-12/ IL-23 Ustekimumab Human monoclonal S/C — 45 mg SC at Wk 0 & 4, then antibody that binds to a 15 - 32 days q12wks thereafter; may use 90 mg polypeptide subunit in patient with body weight > 100 kg common to IL-12 /23

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

• How would you treat/manage of moderate severity?

29 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 fails steroid 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