psoriasis Flashcards
whyh do we get it (3)
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%))
Pathogenesis/Triggers
- Genetic
- 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
Pathogenesis/Triggers
2. Environmental
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
Clinical Features
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
ee slide 14 types of psoriasis
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
Variation in Dermatological
Presentation
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
Diagnosis
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
PASI Score: Various Calculators Available
lknow what the score means
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
Dermatology Life Quality Index
DLQI
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...’
Patients with Psoriasis live with disease
activity that significantly impacts well being.
stigma
psycholigcal
social kimpacts
discrimination, refused service
cohabitants also have anxierty/depression
BURDEN OF PSORIASIS BEYOND THE SKIN
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
Treatment
Principles:
- Hydration / Moisturization
- Avoiding triggers
- Topical or Systemic treatment
i. Topical
i. Creams and lotions
ii. Systemic
i. Phototherapy
ii. Oral pills
iii. Biologics
Summary of Pharmacological
Psoriasis Treatment
mild mod severe
see slide 30
Treatment
Avoiding Triggers
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)
Treatment
Hydration/Moisturize
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
Treatment
Topical options
Topical Options Salicylic acid (5‐20%) Coal tar Corticosteroids (50 different types!) Calcineurin inhibitors Vitamin D3 analogues Topical retinoids
treatment systemic options
Systemic Options Phototherapy = UVB Patient stands in the photobooth! Methotrexate Cyclosporine Retinoids Apremilast Biologics (injections)
Miscellaneous Topicals for Psoriasis
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
Topical Corticosteroids for Psoriasis
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
Recall Adverse Effects from TCS
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
Treatment
Topical Anti‐inflammatory Agents
(Calcineurin Inhibitors)
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
Treatment
Topical Calcineurin Inhibitors and Cancer
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.
Treatment
Topical Vitamin D Analogues
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
What is Dovobet?
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
Additional Topical Therapies
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)
Treatment
UV Light
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
Treatment
Methotrexate
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
Treatment
Cyclosporine
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
Treatment
Acitretin (Soriatane)’
dont need to know dosing
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
Treatment
Apremilast (Otezla)
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
Treatment
Biologics
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
Starting a Biologic: Tests, Procedures
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)
Treatment
Adalimumab (Humira)
pick up unique AE
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
Treatment
Infliximab (Remicade)
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
Treatment
Ustekinumab (Stelera)
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
Treatment
Secukinumab (Cosentyx)
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)
Treatment
Ixekizumab (Taltz)
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
Treatment
Brodalumab (Siliq)
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)
Treatment
Guselkumab (Tremfya)
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
Treatment
Risankizumab (Skyrizi)
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
Treatment
Bimekizumab
(Bimzelx)
higest ranked treatment for PASI 75. 90, 100 vs oether approved tx
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