psoriasis

Question 1

whyh do we get it (3)

Answer 1

Chronic and relapsing inflammatory skin disorder with
strong genetic skin basis
 It is NOT ‘contagious’

 Classified as a papulo‐squamous condition
 Rashes that cause ‘raised spots’ and ‘flaky skin’

 Why do we get psoriasis?
 Genetic (genes that predispose us to develop this)
 Environmental (an external factor that triggers it)
 Immunologic (OVER activity of the immune system)

 Peaks in 20‐30yrs and 50‐60yrs (less common in kids (0.5‐1%))

Question 2

Pathogenesis/Triggers

1. Genetic

Answer 2

1. Genetic
    We ‘inherit’
   a tendency to develop psoriasis
    That’s why some people develop it and others
   never will
    Studies varya lot and suggest anywhere from
   a 35‐90% positive family history
    PSORS1 (chromosome 6p21.3) involved in up to
   50% of psoriasis

just know there is a genetic tendency

Question 3

Pathogenesis/Triggers

2. Environmental

Answer 3

Emotions Stress can initially flare or exacerbate existing psoriasis (academic)

Trauma Psoriasis can appear in areas of the skin that have been injured or traumatized (eg injury during car crash). This is called the Koebner Phenomenon.
Sunburns can cause trauma

Medications  Lithium

 Antimalarials (chloroquine and hydroxychloroquine)
 B‐Blockers
 NSAIDS
 Systemic steroids

Infections Streptococcus infection is associated with guttate psoriasis
Other Smoking, alcohol, obesity

Question 4

Clinical Features

Answer 4

 In general, most people with psoriasis have a
well defined, red, silvery‐white flaky rash on
various parts of their bodies – especially the
elbows, knees and scalp
 But, there are many different types of psoriasis
that can develop and patients with different
skin phenotypes may present atypically

Question 5

ee slide 14 types of psoriasis

Answer 5

fexural
nail
scalp

plaquevs non-plawue forms

guttate: UTI, strep infection common before
- can become a chronic condition,
abx, treating strep thraot doesnt change the guttate psor

pustular: coalescing pustules that form a lake?
need med atention

psoriatic arthritis imay develop

Question 6

Variation in Dermatological

Presentation

Answer 6

Psoriasis
 In Fitzpatrick Skin Types
V, VI redness may be
masked by melanin and
may start to look a little
more purple or
violaceous than red
 Plaques found on
extensorsmore scalp psor in Asian and Black patients

prefernece for forms and lotiosn for scalp
sunscreen for hyperpigmentation prevention

Question 7

Diagnosis

Answer 7

 Clinical presentation
 Mainly its visual combined with
family history
\
 Assessment Tools
 Clinician tools
 PASI, Psoriasis Area and Severity
Index
- score over 10 is severe -> needed for coverage sometimes

 PGA, Physician Global Assessment
 Patient‐reported tools
 DLQI, Dermatology Life Quality
Index
 Biopsy

Question 8

PASI Score: Various Calculators Available

lknow what the score means

Answer 8

Skin Area Involvement: Various Scaling: On a scale of 0 to 4
Calculators, palm method

Redness: On a scale of 0 to 4 Thickness (Induration): On a scale of 0 to 4

Skin Area Involvement: Various Scaling: On a scale of 0 to 4

PASI 75 is a 75 %
improvement in the
baseline PASI score and is
used as a benchmark of
improvement in clinical
studies

Question 9

Dermatology Life Quality Index

DLQI

Answer 9

 Sum the score of each
question
 Maximum score of 30 and
minimum of 0

 The higher the score the
greater the impairment of
QoL
 DLQI has been adapted to
time frame – ‘over the last
week...’, ‘over the last
year...’, ’over your lifetime
with psoriasis...’

Question 10

Patients with Psoriasis live with disease

activity that significantly impacts well being.

Answer 10

stigma
psycholigcal
social kimpacts

discrimination, refused service
cohabitants also have anxierty/depression

Question 11

BURDEN OF PSORIASIS BEYOND THE SKIN

Answer 11

Psychological and psychiatric disorders

Obesity and metabolic syndrome

Gastrointestinal disorders
• Depressive symptoms reported in over 23%
of patients with psoriasis1
• HR 1.50 for depression in patients with
severe psoriasis2

• Psoriasis associated with metabolic
syndrome (OR 1.41) and its components,
including obesity (OR 1.25)3

• Patients with psoriasis at increased risk of
developing Crohn’s disease (2.49‐fold) and
ulcerative colitis (1.64‐fold)4

Cardiovascular diseases
• RR to general population in patients with
severe psoriasis:
• MI 1.70–30.45
• Stroke 1.38–1.595
• CV mortality 1.37–1.395

Joint disease
• Nearly 40% of patients with psoriasis
suffer from arthralgia6
• 20% have been diagnosed as having
PsA6

Question 12

Treatment

Principles:

Answer 12

1. Hydration / Moisturization
2. Avoiding triggers
3. Topical or Systemic treatment
   i. Topical
   i. Creams and lotions
   ii. Systemic
   i. Phototherapy
   ii. Oral pills
   iii. Biologics

Question 13

Summary of Pharmacological
Psoriasis Treatment

mild mod severe

Answer 13

see slide 30

Question 14

Treatment

Avoiding Triggers

Answer 14

 Irritants
 Some patients with psoriasis can be irritated by:
 Soaps, solvents, fabrics (wool, nylon)

 Modify activities and surroundings to minimize
sweating
 Once again, this is an exacerbating factor in only a minority
of psoriasis patients
 We still encourage people to be active and exercise

 Avoid trauma to the skin (recall Koebner phenomena)

Question 15

Treatment

Hydration/Moisturize

Answer 15

 Recommend good moisturizers to replenish the skin barrier, reduce xerosis and help with pruritus
 Try to apply within a few minutes of bathing (‘lock’ in the moisture)
 Cetaphil, Cerave, Spectro, Aveeno, La Roche Posay, Glaxal base, etc…
 Use minimally de‐fatting soaps (more alkaline soaps disrupt skin barrier)
 Dove, Cetaphil, Spectro, Aveeno, Avene, La Roche Possay
 May ↓ need for topical steroids by 50%
 May enhance response to treatment with topical steroid

Question 16

Treatment

Topical options

Answer 16

Topical Options
 Salicylic acid (5‐20%)
 Coal tar
 Corticosteroids (50
different types!)
 Calcineurin inhibitors
 Vitamin D3 analogues
 Topical retinoids

Question 17

treatment systemic options

Answer 17

Systemic Options
 Phototherapy = UVB
 Patient stands in the
photobooth!
 Methotrexate
 Cyclosporine
 Retinoids
 Apremilast
 Biologics (injections)

Question 18

Miscellaneous Topicals for Psoriasis

Answer 18

Salicylic acid
 Product are used to break down thick scale and psoriatic plaques
 Especially helpful in scalp, elbows and knees

Coal tar
 Suppresses keratinocyte proliferation
 Reduces inflammation
 Tar can stain clothing, bed linen, and light‐colored hair. Tar makes skin more sensitive to sunlight, so be sure to wash it off thoroughly, use sunscreen and monitor sun exposure
 Tar remains active on the skin for at least 24 hours, and patient
is at increased risk of sunburn during this period
 Can cause dermatitis or folliculitis

Question 19

Topical Corticosteroids for Psoriasis

Answer 19

 Corticosteroids exert anti‐inflammatory, antiproliferative and
immunosuppressive actions by affecting gene transcription
 Potency of topical corticosteroids using a scale of I (high) to VII (low)
 Apply once‐twice daily to thick, active lesions
 Decrease frequency once clinical improvement occurs
 Limit duration of high potency agents to 2‐4 weeks
 To minimize adverse effects and maximize compliance, site of
application is considered in choosing corticosteroid:
 For scalp or external ear canal – solution, foam, shampoo or spray
 Use low potency on face
 For thick plaques on extensor surfaces use potent preparations
 Can be used in pregnancy

Question 20

Recall Adverse Effects from TCS

Answer 20

Corticosteroid Side‐Effects
 Skin thinning
 1 year study of unrestricted continual use of potent corticosteroids on limbs
and trunk with weak preparation on face or both, showed that stretch
marks only developed in 3/330 adults

 Glaucoma
 If used around periocular area, rarely reported in adults

 Steroid rosacea / perioral dermatitis
 If used around mouth or nose can get different rashes

 Secondary infections
 Can worsen a fungal or bacterial infection if used inappropriately

 Secondary adrenal suppression/growth inhibition
 Biochemical suppression of hypothalamic‐pituitary adrenal axis
 Only in children with severe eczema who used potent or very potent topical
steroids who also received oral glucocorticoids from other routes
 Not in those who had used topical steroids of mild/moderate strength for as long
as average of 7 years

Question 21

Treatment

Topical Anti‐inflammatory Agents

(Calcineurin Inhibitors)

Answer 21

 Topical immunomodulators: tacrolimus (Protopic®), pimecrolimus (Elidel®)
 These are NOT steroids!
 MOA:
 Reduces T‐cell activation and proliferation through ― inhibition of the calcineurin enzyme.
 Recommendations:
 Indications: unresponsive to 1st line or in areas of body where skin thinning a concern
 Protopic®:
 0.03%
 0.1% more effective in black skin > pediatric
 Elidel®:
 1% cream
 Pharmacist Notes:
 Use twice daily until clear
 Does NOT cause skin thinning
 More expensive
 Not as powerful as topical steroids

Question 22

Treatment

Topical Calcineurin Inhibitors and Cancer

Answer 22

 Black Box Warnings have been removed
 CDA position statement:
 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.

Question 23

Treatment

Topical Vitamin D Analogues

Answer 23

Pharmacist Notes:
 What are possible side effects?
 Irritation, hypercalcemia

 What is the maximum weekly amount of 50 mcg/g
preparation?
 100 g of 50 ug/g preparation per week.

 What are contraindications to its use?
 Pregnancy (category C), breast feeding, kidney problems, large surface area

 Which other psoriasis treatment may it interfere with?
 UV therapy – do not apply within 2 hrs of UVB or immediately
before PUVA

 Is this effective?
 Less effective than TCS
 Can be used in conjunction with retinoids and TCSs

Question 24

What is Dovobet?

Answer 24

 Calcipotriol, vitamin D3 analogue + Betamethasone dipropionate (a strong steroid)
 Available as ointment, gel and now foam spray

What are possible side effects?
 Irritation, hypercalcemia and corticosteroid side effects
What are contraindications to its use?
 Pregnancy, breast feeding, kidney dysfunction, large body surface area
Is this effective?
 Very much so, one of the most effective treatments, only needs to be
used once daily
Newest agent on the block:
 Enstilar (calcipotriol/betamethasone dipropionate) aerosol foam

Question 25

Additional Topical Therapies

Answer 25

 Tazarotene (already discussed‐see Acne notes)  Duobrii® (tazarotene 0.045% + halobetasol propionate 0.01%) lotion  Applied once daily and use up to 8 weeks, if patient in remission – stop therapy or go to maintenance regimes (2‐3x weekly)

Question 26

Treatment | UV Light

Answer 26

NBUVB (311nm) is preferred  Think of this treatment like a ‘stand up sun‐tan booth’  But, it has a filtered light in it, which cuts out the harmful UV (tanning booths are a NO! They have harmful UV rays)  Shown to be one of the most effective at clearing psoriatic lesions  Therapy can be continued in pregnancy  Most studies show no increased risk of skin cancer to date  Usually 2‐3 treatments / week  Most patients clear after 20‐30 sessions, and can then maintain patients on a regimen of: every 1‐2 weekly basis or stop  Treatments are fast – usually a few minutes  No blood work monitoring required  Free treatment covered by Alberta health care

Question 27

Treatment | Methotrexate

Answer 27

 MOA:  Inhibits dihydrofolate reductase and DNA synthesis  Workhorse of psoriasis treatment  Pharmacist Notes:  15‐20mg orally once weekly  Need folic acid supplementation (1mg daily or 5 mg weekly=various regimens) to prevent toxicity  Side effects  Hepatotoxicity, pulmonary fibrosis, pancytopenia, GI issues (N/V, diarrhea), teratogenic, renal toxicity  Lots of monitoring = weekly blood work when first starting  New guidelines suggest possible need for liver biopsy at cumulative dose of 3.0 grams  Costs about $20 / month

Question 28

Treatment | Cyclosporine

Answer 28

 MOA:  Inhibit calcineurin  decrease T cell proliferation  Pharmacist Notes:  50‐200mg orally twice daily  Good / rapid clearance in acute flares, allows you time to switch to other agents  Side effects:  Renal failure, hypertension, tremor, headache, paresthesia, hypertrichosis, gingival hyperplasia, myalgia, lethargy, hyperkalemia, hyperlipidemia  Not used very much chronically due to limitation of 1‐2 year of therapy maximum  Requires blood work monitoring periodically  Costs about $500‐700 / month  Requires special authorization for coverage  see Atopic Dermatitis notes for additional information

Question 29

Treatment Acitretin (Soriatane)' dont need to know dosing

Answer 29

 MOA:  An oral retinoid / vitamin A analogue  Helps to regulate skin synthesis and proliferation  Pharmacist Notes Side effects:  Headache, dryness, rashes, high cholesterol, nausea, vomiting, muscle aches, can harm pregnant women and unborn children  Long t 1⁄2 (recall Acne lecture) --> know why!!!  Not to be used in pregnancy  Requires blood work monitoring periodically  Costs about $100 / month  Covered by most public and private insurance plans

Question 30

Treatment Apremilast (Otezla)

Answer 30

 MOA:  Blocks the PDE4 (phosphodiesterase pathway)  A new oral therapy developed for psoriasis  Pharmacist Notes:  Taken as 30mg orally twice daily  Titrate from 10 mg daily up to 30 mg BID over 5 days to minimize GI side effects  Side effects:  Headache, nausea/vomiting, insomnia, increased or irregular heart rate, weight loss, mood changes  Considered a bit of a ‘safer’ choice as no blood work monitoring is required  Not to be used in pregnancy  Can cost between $12‐13,000 / year  Requires special insurance coverage  Covered if patient has failed one systemic therapy

Question 31

Treatment | Biologics

Answer 31

 Newest group of therapies  All are injectable needle type medications  Due to immune suppression all have fairly similar side effects and require similar screening and monitoring  All require pre‐screening for hepatitis C, hepatitis B, HIV, baseline blood counts and serum chemistry, a chest x‐ray and a TB skin test  All are quite expensive, generally $20‐30,000 / year  Coverage based on BSA involvement, severity, a quality of life index questionnaire, previously tried therapies, specifics of the insurance plan  Reserved for moderate‐severe disease  Check immunization history, do not give live vaccines during treatment  Many approved for use in Psoriatic Arthritis

Question 32

Starting a Biologic: Tests, Procedures

Answer 32

rule out TB, there could be latent TB Clinical assessments • Adequate evaluation of psoriasis • Medical history Other assessments • TST (PPD) for detection of latent TB or QuantiFERONTB Gold or T‐SPOT‐TB • Chest radiograph to rule out signs of TB Recommended tests and procedures Clinical assessments • BSA (with special note of psoriasis in sensitive areas, i.e., face, hands–feet, and groin–genitals), PASI, DLQI • Review of vaccination status, especially live vaccines Laboratory assessments • Serology for hepatitis B and HIV in patients at risk • Routine blood work: CBC, LFTs, creatinine (and eGFR), repeated regularly Other tests that may be done * CRP, sedimentation rate (highly suggested if arthritis is present) * Fasting blood glucose and blood lipids (screening tests for metabolic syndrome)

Question 33

Treatment Adalimumab (Humira) pick up unique AE

Answer 33

 What is adalimumab?  Recombinant human IgG1 monoclonal antibody against TNF‐alpha (one of the main inflammatory pathways involved in psoriasis)  How does it work?  Binds TNF‐alpha and blocks its interaction with cell surface receptors  Given as 80 mg, then 40mg subcutaneous injection every 2 weeks  What are the serious side effects?  Hypersensitivity, injection reaction, confusion, MS, paresthesia, infections/sepsis, TB, cancer (?5.4x for lymphoma, skin cancers), worsening of congestive heart failure (CONTRA) recent cancer or active cancer

Question 34

Treatment Infliximab (Remicade)

Answer 34

 Mouse‐human chimeric antibody against TNF‐ alpha  How does it work?  Binds to soluble and bound TNF‐alpha  Given as 5 mg/kg IV infusion at 0, 2 and 6 wk and then every 8 wk thereafter  Infusion at clinic (not favorable)  What are the serious side effects?  Almost identical to adalimumab  Infusion reactions – headaches, chills, fever, drop in blood pressure  Due to mouse antibodies, higher chance of developing resistance over time

Question 35

Treatment Ustekinumab (Stelera)

Answer 35

 What is ustekinumab?  A biologic drug that blocks IL12/23  Approved in 2009 to treat psoriasis  How does it work?  Inhibits these cytokines and the body’s inflammatory response that leads to hyper‐proliferation (over growth of skin)  One injection at 0, 4 , then given as one injection every three months (45mg dosing for < 100kg and 90mg dosing for > 100kg)  What are the serious side effects?  Nasopharyngitis, upper respiratory tract infection, headache, infections, malignancy

Question 36

Treatment Secukinumab (Cosentyx)

Answer 36

 What is secukinumab?  A newly developed and approved biologic that blocks the IL‐17 pathway in the body  How does it work?  Inhibits these cytokines and the body’s inflammatory response that leads to hyperproliferation  300 mg SC (given as 2 injections of 150 mg each at different sites) at weeks 0, 1, 2 and 3, followed by 300 mg SC monthly maintenance starting at wk 4  What are the serious side effects?  Nasopharyngitis, upper respiratory tract infections, rhinitis, oral herpes, rhinorrhea, diarrhea.  Do not use in patients with IBD (worsening of IBD)

Question 37

Treatment Ixekizumab (Taltz)

Answer 37

 What is ixekizumab?  Recombinant humanized IgG4 kappa monoclonal antibody specific for IL‐17A.  How does it work?  Inhibitor of interleukin‐17A (IL‐17A), a proinflammatory cytokine  SC 160 mg (two 80‐mg injections) at week 0 and then 80 mg at weeks 2, 4, 6, 8, 10, and 12, followed by 80 mg every 4 weeks thereafter  What are the serious side effects:  Increased risk of infections, monitor for IBD

Question 38

Treatment Brodalumab (Siliq)

Answer 38

 What is brodalumab?  An IL17 receptor blocker  How does it work?  Inhibitor of interleukin‐17A, C, E and F (proinflammatory cytokines)  SC 210 mg at weeks 0, 1, and 2, 210 mg every two weeks thereafter  What are the serious side effects:  Increased risk of candida infections, monitor for IBD  Has a warning about the risk of suicidal ideation and behavior on the label (Boxed Warning)

Question 39

Treatment Guselkumab (Tremfya)

Answer 39

 What is guselkumab?  A biologic drug that inhibits the p19 subunit of IL23  Newest biologic on the market  How does it work?  Inhibitor of interleukin‐23, a proinflammatory cytokine  SC 100mg at week 0, 4 and then q 8 weekly  What are the serious side effects?  URTI, headache, injection site reaction, arthralgia, GI upset, tinea infection, herpes infection

Question 40

Treatment Risankizumab (Skyrizi)

Answer 40

 What is risankizumab?  A biologic drug that inhibits the p19 subunit of IL23  One of the newest biologic on the market  How does it work?  Inhibitor of interleukin‐23, a proinflammatory cytokine  SC 150mg (2 x 75 mg) at week 0, week 4 and then 150mg q 12 weekly  What are the serious side effects?  URTI, headache, injection site reaction, arthralgia, GI upset, tinea infection, herpes infection

Question 41

Treatment Bimekizumab (Bimzelx) higest ranked treatment for PASI 75. 90, 100 vs oether approved tx

Answer 41

 What is bimekizumab?  A biologic drug (monoclonal antibody) that inhibits the IL‐17A, F, AF  Newest biologic on the market  How does it work?  Inhibits the IL‐17A, F, AF (proinflammatory cytokines)  320 mg (given as 2 subcutaneous injections of 160 mg each) at week 0, 4, 8, 12, 16 and every 8 weeks thereafter  Thus far has the highest PASI rates (90‐100)  What are the serious side effects?  URTI most common SE, risk of development of oral candidiasis, ear infections, herpes simplex, i.e. risk of infections, headache, dermatitis/acne  Cases of IBD (new and exacerbation) though uncommon, monitor