Phar 351 - Psoriasis

Front 1

What types of psoriasis are acute forms?

Back 1

1. Guttate

2. Pustular

3. Erythrodermic

Front 2

What are non-acute forms of psoriasis?

Back 2

1. Psoriatic arthritis (distal joints of fingers (asymmetrical) and on feet)

2. Nail psoriasis ("oil spots", punctate pitting, and crumbling)

Front 3

Describe guttate psoriasis:

Back 3

- Explosive tear drop eruptions

- Trunk and extremities

- Precipitated by streptococcal infection, typically in children with no prior exposure

Front 4

Describe pustular psoriasis:

Back 4

Sterile pustules on palms and soles

Front 5

Describe erythrodermic psoriasis:

Back 5

Spontaneous, extensive peeling

Can be a medical emergency, causing electrolyte imbalance and septicemia.

Front 6

What is considered mild, mild-moderate, and severe psoriasis?

Back 6

Mild: <3%

Mild to moderate: 3-10%

Severe: >10%

Severity is also based on thickness, scaliness, and redness.

Front 7

Treatment options for mild to moderate disease?

Back 7

Topical treatment:

Emollients, keratolytics, corticosteroids, calcipotriol, tazarotene, coal tar, anthralin

Note: nails, palms, and soles do not respond well to topical treatment - need oral.

Front 8

Treatment options for severe disease?

Back 8

1. Phototherapy

2. Systemic immunomodulators

3. Systemic biologic agents

Front 9

How is phototherapy used?

Back 9

- used in conjunction with other treatment

- dermatological referral

- proposed mechanism: electromagnetic therapy that depletes cells involved in immune response

Front 10

Which immunomodulators are used?

Back 10

1. Methotrexate

2. Cyclosporine

3. Acitretin

(Combination therapy in a rotational cycle is required for 1-2 years intervals)

Front 11

Which biologic agents are used?

Back 11

1. Anti-TNFs (infliximab, adalimumab, etanercept)

2. T-cell targeted (alefacept)

3. Monoclonal antibodies (ustekinumab)

Front 12

When should psoriatic patients be referred?

Back 12

1. All patients with psoriasis should be under care of doctors

2. Refer patients with moderate to severe psoriasis:

- who has generalized disease, is acutely ill, or requires special treatment

- who has localized disease that doesn't respond to treatment

Front 13

Which emollients are used?

Back 13

1. Vaseline

2. Silicone

3. Ceramides (occlusive bases)

Front 14

How do emollients treat psoriasis?

Back 14

Alleviate dryness by hydrating the stratum corneum and reducing water evaporation. They are applied after a 15 minute bath in water.

Front 15

Which keratolytics are commonly used?

Back 15

1. Salicylic acid

2. Sulfur

3. Urea

4. Lactic acid

Front 16

How are salicylic used?

Back 16

Salicylic acid and other keratolytics are used to remove scales. Can be used alone or with topical steroids or tar.

Can also enhance penetration of other drugs.

Front 17

Define: salicylism

Back 17

When salicylic acid is acid is extensively applied and systemically absorbed, nausea, vomitting, tinnitis or hyperventilation can occur.

Front 18

Purpose and mechanism of action of coal tar?

Back 18

Coal tar (e.g. crude coal tar 5% or LCD (liquid carbonis detergens) have antimitotic and antipruritic activity. They can be combined with corticosteroids, anthralin, UVB light or oral therapy for psoriasis.

Also useful for corticosteroid resistance.

Front 19

Adverse effects of coal tar?

Back 19

- Messy/ stains

- Malodor

- Irritating and can cause folliculitis (when applied in circular motion)

Front 20

Describe: plaque psoriasis

Back 20

Most common form (chronic and stable)

Affects scalp, elbows, knees, back, and is symmetrical.

Auspit'z sign (punctate bleeding when scales are scraped off)

Front 21

Describe: Inverse (flexural) psoriasis

Back 21

Affects gluteal folds, genitals, perianal, axillary

No visible scaling

Front 22

Which areas of the body require 1. low 2. moderate and 3. high potency for corticosteroid use?

Back 22

Low: face, groin, intertriginous areas (skin folds) can be treated with 1%Hydrocortisone

Moderate: Scalp, elbows, knees can be treated with 0.1% betamethasone

High: very resistant plaques

Other: intralesion injections used for dormant, solitary lesions

Front 23

Regimen of topical corticosteroids?

Back 23

Use BID until skin is normal (3-4 weeks), then reduce potency and use on weekends only (intermittently) for maintenance.

If insufficient:

1. Occlusion (CS + plastic wrap QHS - caution with atrophy)

2. Combine CS with calcipotriene or tazarotene

3. Combine with coal tar and/or anthralin

Front 24

Side effects of topical corticosteroids?

Back 24

1. Stinging and burning

2. Skin atrophy, striae, purpura (easy bruising), local hair growth

3. Tachyphylaxis (decreased effect of drug over time)

4. Flares upon abrupt withdrawal

5. Pituitary-adrenal axis suppression

Front 25

What is calcipotriol, MOA, therapeutic use?

Back 25

- Topical vitamin D3 analogue, which affects calcium metabolism and regulates epidermal growth

- Regulates keratinocyte proliferation and differentiation

- Unpredictable response (70%), and takes 4-6 weeks

- No stains, tachyphylaxis, atrophy or mess

Front 26

Cons of using calcipotriol?

Back 26

1. Unpredictable response and costly

2. Irritant (burns and stings)

3. Hypercalcemia risk (don't exceed 100g/ week)

Front 27

MOA and therapeutic use of anthralin?

Back 27

- Interferes with DNA synthesis, preventing proliferation

- Used for widespread plaques

- Can be used alone or in combo with UVB, topical steroids, coal tar, or oral therapy

Front 28

Cons of anthralin?

Back 28

Stains and burns, messy as a thick paste (Lassar's), and difficult to apply.

Front 29

What is the long contact time regimen for anthralin?

Back 29

Apply at bedtime, then rinse off in the morning.

Gradually increase concentration from 0.1% to 0.5% as tolerated.

Front 30

What is the short time contact regimen for anthralin?

Back 30

Begin with 0.1% for 5 minutes once daily, then increase with tolerance up to 30 minutes once daily, then 2%. Wipe off oil before showering.

Front 31

Anthralin application method?

Back 31

1. Apply daily, then once or twice weekly for maintenance

2. Wear plastic gloves

3. Apply petrolatum to surround skin to avoid irritation

4. Don't apply to face, genitalia, or intertriginous skin areas

5. Remove skin stains with salicylic acid 5% ointment

Front 32

MOA of tazarotene?

Back 32

Vitamin A derivative.

- Binds to retinoid receptors

- Normalizes keratinocyte differentiation

- Decreased proliferation and infl.

- Similar in efficacy to moderate potency CS (slow onset but extended response)

Front 33

Disadvantages of tazarotene?

Back 33

- Burning, stinging, erythema, pruritis, dryness, peeling, photosensitizing

- Expensive

Pregnancy category X (contraception advised)

Front 34

When is tazarotene topical cream/ gel 0.05-0.1% used?

Back 34

Used to prevent steroid flair upon D/C (63% occurence using steroids alone, vs. 14% occurence with tazarotene)

- Use with med-high potency topical steroid QD-BID and tazarotene gel QHS

- after 2-4 weeks, decrease potent topical steroids to weekend use only

- use for >4-6 weeks before d/c

Front 35

Indications for systemic therapy?

Back 35

- Failure to respond to adequate trial of topical treatment
- Repeated hospital admissions for topical treatment
- Generalized pustular or erythrodermic psoriasis
- Severe psoriatic arthropy
- Requires and informed and coorperative patient

Front 36

Which agent is more effective, vit. D or coal tar?

Back 36

- Vitamin D

Front 37

How does efficacy compare between use of steroid alone, versus steroid + vitamin D?

Back 37

- Combination therapy is more effective than steroid or vitamin D use alone

Front 38

Which agent causes more adverse skin events (such as skin irritation), potent corticosteroids or vitamin D agents?

Back 38

- Potent CS are less likey to cause local adverse events than vitamin D agents

Front 39

MOA of methotrexate?

Back 39

Folic acid antagonist

- Binds to dihydrofolate reductase and inhibits pyrimidine synthesis

- Decreased DNA replication, immunosuppression on activated T-cells, and antiproliferation in epidermal cells.

Front 40

Use of methotrexate?

Back 40

- Induction and maintaining remission for psoriatic arthritis and nails

Front 41

Dosing regimen of methotrexate?

Back 41

- 7.5-25mg divided TID every 12 hours once weekly

- When D/C, contraception needed for 1 month (women) and 3 months for men (oligospermia)

Front 42

Adverse events of methotrexate?

Back 42

- Bone marrow suppression

- Hepatic fibrosis (hepatotoxicity >1.5g cumulative dose)

- Infection

- Teratogenic

Front 43

Contraindications of methotrexate?

Back 43

- Abnormal liver or renal function
- Alcohol abuse
- Active infections
- Immunodeficiency states
- Pregnancy
- Lactation

Front 44

Monitoring parameters for methotrexate use?

Back 44

- Perform baseline and blood count every 4 weeks
- Liver and renal function tests ever 2-4 months

Front 45

What other medication should be used in conjunction with methotrexate therapy?

Back 45

Folic acid, 1mg daily

- Protects against SEs such as stomatitis

Front 46

Drugs interactions with methotrexate?

Back 46

- Sulfonamides

- ASA, NSAIDS, Penicillin (decreased renal elimination of methotrexate; toxicity)

Front 47

MOA of Acitretin?

Back 47

Systemic retinoid (vit. A derivative)

- Etretinate metabolite (t1/2=120 days) with shorter half life (t1/2=2-4 days)

- Regulates:

1. Epithelial cell proliferation + differentiation

2. Immunologic function

Front 48

Use of Acitretin?

Back 48

Faster response than methotrexate in acute inflammatory forms of psoriasis

Front 49

Disadvantages of Acitretin?

Back 49

- Poor (20-30%) response for psoriasis vulgaris (use with UVB, PUVA or CS)

- Elevated liver enzymes (hepatitis)

- Elevated lipids (TG and chol.)

- Muscles aches

- Teratogenic (3 yers DC tx(

- Mucocutaneous (dry lips, nose, eyes, skin, alopecia)

- Ossification disorder (hyperostosis)

Front 50

Dosing regimen for Acitretin?

Back 50

25-50mg daily with food until lesions resolve (8 – 12 weeks)

Front 51

Monitoring parameters for Acitretin?

Back 51

Liver function tests and lipids at baseline, every 1-2 weeks until stable

Front 52

MOA of cyclosporine?

Back 52

Immunosuppressive agent

- inhibits calcineruin --> decreased IL-2 --> decreased helper T-cells --> immunosuppression

Front 53

Use of cyclosporine?

Back 53

- induces remission (90% clearance of lesions) within 10 weeks

Front 54

Dosing regimen of cyclosporine?

Back 54

- 2-5 mg/kg/day (based on ideal body weight)
- Treat 1-3 months with higher dose; lower dose for maintenance

- Do not give continuously for longer than 1 year

Front 55

Monitoring parameters of cyclosporine?

Back 55

BP and renal function

Front 56

Disadvantages of cyclosporine?

Back 56

- when D/C, disease recurs within 2-4 months

- Renal impairment (reversible)
- Hypertension (renal vasoconstriction)
- Elevated TG/ cholesterol
- Gingival hyperplasia
- Paresthesias
- Hypertrichosis
- Skin cancer, lymphoma risk

Front 57

What are the 3 types of biologic therapies?

Back 57

1. T-cell modulators (Alefacept /Amevive)

2. TNF-a inhibitors (Infliximab /Remicade, Etanercept /Enbrel, Adalimumab /Humira)

3. Cytokine (interleukin) inhibitors (Ustekinumab /Stelara)

Front 58

Drugs ending with mab:

Back 58

Monoclonal antibodies

Front 59

Drugs ending with ximab:

Back 59

Chimeric (mouse + human) monoclonal antibodies and may for neutralizing antibodies

Front 60

Drugs ending with zumab:

Back 60

Humanized monoclonal antibodies, less likely to form neutralizing antibodies

Front 61

Drugs ending with cept:

Back 61

Involve the fushion of a receptor to antibody (the Fc portion of the humaN IgG1)

Front 62

Dosing regimen for Infliximab?

Back 62

5mg/kg IV at week 0, 2, 6

Maintenace: 5mg/kg every 8 weeks (IV over 2-3 hours)

Front 63

Dosing regimen for Etanercept?

Back 63

(Plaque) Initial: 50mg SC twice weekly x 3 months

Maintenance: 50mg SC weekly

Front 64

Dosing regimen for adalimumab?

Back 64

80mg/week SC, then 40mg Q2 weeks

Front 65

Dosing regimen for alefacept?

Back 65

IM: 15mg once weekly x 12 weeks

IV: 7.5mg once weekly x 12 weeks (follow by 12 weeks no tx)

Front 66

Dosing regimen for ustkinumab?

Back 66

SC: 45mg week 0, 4, then q12 weeks

Front 67

Treatment options for mild disease (= max 5% of BSA)

Back 67

Moisturizers, emollients, topical CS, coal tar, anthralin, calcipotriol, tazarotene

Front 68

Treatment options for moderate disease (= 10>PASA>8; 10%>BSA>5%)

Back 68

Mild treatment plus:

phototherapy, systemic therapy (e.g. methotrexate, cyclosporine), oral retinoids, biologic agents

Front 69

Treatment options for severe disease (= PASI >10; BSA >10%)

Back 69

Mild treatment plus:

phototherapy, systemic therapy (e.g. methotrexate, cyclosporine), oral retinoids, biologic agents

Front 70

MOA of UVB phototherapy?

Back 70

UVB radiation (290-320nm)

- Reduces DNA synthesis of epidermal cells via an immunomodulatory effect

Front 71

UVB therapy regimen?

Back 71

UVB light exposure, 30s to 10min 3 x weekly for 20 sessions

- 80% clearing of extensive psoriasis

Front 72

Define: Goeckerman technique

Back 72

Coal tar + UVB

- Apply tar preparation; leave overnight

- Remove tar in AM with mineral oil and bathe

- Expose skin to UVB (minimal erythema)

- Bathe and gently scrub scales

- Apply tar or steroids under occlusion

Front 73

Define: Ingram Technique

Back 73

Coal tar + UVB + Anthralin

- bathe in coal tar bath

- expose to UVB light

- Apply anthralin paste with spatula

- Dust with talc, cover with gauze

- Remove paste with mineral oil and base after 8-12 hours

Front 74

MOA of PUVA?

Back 74

Oral psoralens + UVA light (320-400nm)

- suppress cell division

- psoralen activated by UVA to chelate DNA

Front 75

Dosing regimen for PUVA?

Back 75

Methoxsalen (8-MOP): 0.6-0.8mg/kg given 2 hours before exposure to UVA. Repeat 2-4 times a week for 6 – 8 weeks. Clears 90% patients.

- restrict to 150-200 treatments

- use sunscreen at least 8 hours after treatment

Front 76

Disadvantages of PUVA?

Back 76

Cataracts, skin cancer (basal and squamous cell cancers, melanomas)

Front 77

Which treatment do you use first?

a. TAR+UVB or NBUVB or PUVA

b. Systemic treatment (acitretin, methotrexate, cyclosporine, etc.)

Back 77

A. Switch to B when no improvement.