Psoriasis Flashcards
Which part of normal skin layers does psoriasis originate from?
Epidermis
How is psoriasis different from acne and dermatitis?
Has an auto-immune component and hyperproliferation
What are the 4 components of the epidermal cells
- Keratinocytes
- Melanocytes
- Langerhans cells
- gatekeepers, immune defense - Merkel cells
- nerve cells sensitive
Differentiate between primary and secondary lesions
Primary skin lesion:
- the early stage of the lesion (how it looks before evolving)
- Hard to classify/describe unless this is the patient’s FIRST presentation
Secondary lesion:
- the evolution of the primary lesion (after being modified by external forces/scratching, infection OR healing)
Differentiate between non-palpable and palpable skin eruptions
Non-palpable skin eruptions (flat)
- Macule: less than 1 cm
- Patch: 1cm+
Palpable skin eruptions (bumpy, non-flat)
- Papule: less than 1cm
(Pustule if filled with purulent material)
- Plaque: 1cm+
Define Psoriasis
What cells is it mediated by (3)
What other diseases is it associated with (3)
What is its clinic presentation
More common in male/females
A genetic, systemic, chronic and RELAPSING inflammatory skin disease that primarily affects skin/joints and can be altered by environmental factors
Mediated:
- T cells
- dendritic cells
- inflammatory cytokines
Associated with
- IBD
- Psoriatic Arthritis
- NAFLD (non-acloholic fatty liver)
- CAD (CVS, metabolic syndrome, stroke, MI)
- Malignancy (skin cancer)
- Psychological disorders (depression)
- Onycholysis (nail loosening/splitting)
Impacts
- Equal in male and female
Is sunlight and psoriasis a bad thing?
Sunlight is related to less frequent/severe psoriasis
Which demographic is psoriasis rare in?
Rare in N/S American aboriginal or indigenous people
What are the 2 age onsets of psoriasis
15-30 yo
50-60 yo
Pathogenesis of Psoriasis (3)
Genetic predisposition
Auto-immune activation
Triggers such as (stress, infections, drugs)
How do genetics play a role in psoriasis
Twins
1 parent
2 parents
- Identical twins have concordance rates of approx 80%
- risk of psoriasis with 1 parent affected: 14-20%
- risk of psoriasis with 2 parents affected: 41%
Which gene is Psoriasis linked to
PSORS1 mapped to chromosome 6
What environmental triggers are associated with psoriasis? (5) What drugs? (3)
- Injury/trauma ‘Koebner response”
- Smoking
- Alcohol
- Obesity
- Stress
Medications:
- Lithium
- Anti-malarials
- Beta blockers
T/F psoriasis reduces life expectancy
True
What are the 3 characteristic features of psoriatic plaque
- Hyperplasia of poorly differentiated epidermal cells (keratinocytes) with thickening of epidermis and formation of scales and plaques
- Angiogenesis (increased growth) of superficial blood vessels -> makes plaque red
- Infiltration of T-lymphocytes (T cells), dendritic cells, neutrophils, macrophages into psoriasis plaques
How long does shedding of keratinocytes in normal vs psoriasis patient take?
Normal: 26 days
Psoriasis: 4 days
Which inflammatory cytokines is associated with psoriasis? (5) What is secreting it?
Activated Th1 cells secrete
- IL 12
- IL 17
- IL 22
- IL 23
- TNF-alpha
What is the net effect of psoriasis?
What is the result?
Net effect of psoriasis:
- PREVENTS keratinocyte differentiation
- PROMOTES rapid/excessive keratinocyte and epidermal proliferation
Net result of psoriasis:
- LACK of cell maturation -> increased keratinization -> characteristic skin changes
Classification of Psoriasis
Plaque (P. Vulgaris)
Guttate
Pustular
Palmar Plantar
Scalp
Inverse (flexural)
Erythrodermal
Psoriatic Arthritis
Plaque (P. Vulgaris)
- red, thick, scaly, lesions with silvery scales
Guttate
- pink plaques or papules on truk
- presents after group A strep resp. infection
Pustular
- erythematous plaques with on palms/soles
Palmar Plantar
- psoriasis only onhands/soles
Scalp
- often first place plaques are seen
Inverse (flexural)
- plaques seen in skinfolds: groin, armpit, genitals
Erythrodermal
- severe, intense, generalized erythema and scaling entire body
- medical emergency
Psoriatic Arthritis
- involving joints
What is the auspitz sign (“Grattage” test)
Removing the scale of the plaque reveals smooth/red/glossy membrane with tiny dotted bleeding points
Very unique to psoriasis
T/F All patients with psoriasis will have pruritis
False
How do we measure the severity of Psoriasis? (3)
- BSA
- PASI
- index of severity plus extent of BSA involvening 4 key areas: (DOES NOT INCLUDE FACE, PALMS)
- head and neck
- upper limbs
- Trunk
- Lower limbs - PASI-CHANGE score
- change in severity from baseline
- PASI 75 = 75% decrease in severity
- PASI 100 = complete remission
What is the golden standard PASI-CHANGE score in psoriasis
PASI-75
75% improvement in 12 weeks
Define mild psoriasis in BSA
3-5%
What are some non-pharmacologic therapies for psoriasis (5)
- Stress reduction/relaxation techniques
- screen for depression/ other comorbidities - Moisturizers
- reduce skin shedding, control scaling, imrpove pruritus
- apply 1 hr before rx topical - Oatmeal baths
- helps with pruritus - Sunscreens with SPF 30+
- sunburn triggers psoriasis - Avoid harsh soaps, fragrance, and us tepid water for washing
What is the first line if less than 5% BSA is affected
Topical corticosteroids
- want to be aggressive at first
Rate the effectiveness of
Medium potency steroids
High potency steroids
D3 analogues
- High potency steroids
- D3 analogues
- Medium potency steroids
What are adverse dermatologic effects of corticosteroids (7)
- Atrophy
- Telengiectasia (spider veins)
- Contact dermatitis
- Acne
- Hypopigmentation
- Hypertrichosis
- Striae (groove surface)
- Tachyphylaxis
When will HPA Axis suppression occur in a psoriasis patient
- only if high potency
- large BSA > 10%
- prolonged use
- under occlusion
- older age
- liver/renal disease
How do TCS suppress inflammation by (2)
- Upregulates ANTI-inflammatory genes
OR - Downregulates INFLAMMATORY genes (prostaglandins cytokines, chemokines)
Alter synthesis of mRNA and the DNA
What is the MOA of topical steroids
- inhibit release of enzyme phospholipase A2 with inhibition of PG synthesis
- Reduces mitotic activity in epidermis, get flattening of basal cell layer
- can cause thinning of stratum corneum layer as a side effect
What are very high potency steroids
Cyclocort
Topicort
Lidex
Halog OINT
Elocom OINT
What are low potency steroids used for (3)
face
skinfold areas
thin skin found in elderly & infants
What are mid-high potency in adults used for
adults as initial therapy to gain disease control
- often applied with occlusion method (plastic wrap)
When are high potency used?
Thick, chronic plaques
- max 2-4 weeks
- limit to 50g/week = 14 FTU
Strategies for Topical corticosteroids in pregnancy & breastfeeding
Pregnancy Category C
- transition to weaker potency
- use intermittent dosing
- on the smallest surface area
Not studied in breastfeeding
How much does 1 FTU equal in BSA?
and how much % BSA makes 1g?
1 FTU = 2% BSA
4% BSA = 1g
What is the benefit of Topical Vitamin D3 Analogues?
Examples
- Similar in efficacy to class 2 potency (high potency)
- odourless, easy to apply
- no tachyphylaxis and no skin atrophy
- see improvement within 2 weeks
Ex. Caclipotriol
Calcitriol
What are the adverse effects of D3 analogues (4)
What is the limit
Burning
pruritis
peeling
redness (erythema)
100g/week limit
- if over, watch for hypercalcemia
What is the best treatment in terms of faster response time, increased patient satisfaction?
What to avoid?
Pregnancy?
Max dose?
Examples?
Combo therapy
- D3 Analogue + topical steroids
- Dosed once daily
- More corticosteroid potency sparing
Pregnancy
- reasonable option for mild psoriasis
Avoid: Face, genitals, flexual areas
Max: 100g weekly
Ex. Dovobet, Enstilar
Compare between topical retinoids and topical steroids. Give an example of the retinoid
Pregnancy?
Tazarotene
- higher rates of ADRs
- efficacy is similar to class 2 TCS
DO NOT use in pregnancy
Topical Calcineurin inhibitors
Examples?
How long is it used for?
When is it used?
Side effects?
Examples?
- Tacrolimus (protopic)
- Pimecrolimus (elidel)
How long is it used for?
- max 6 weeks
When is it used?
- used for thinning skin eg. face, genitalia
Side effects?
- mild local irritation, secondary skin infection
- blackbox warning: rare occurence of skin malignancies + lymphoma
PDE4 inhibitor
Example?
When is it used?
Side effects?
Contraindication?
Example?
- Roflumilast 0.3%
When is it used?
- if 1st line agents fail
Side effects?
- GI side effects, headache
Contraindication?
- mod-severe liver disease
Why is salicylic acid not used anymore?
What did it benefit for in the past?
- Prolonged use over large areas may lead to salicylate toxicity
- May potentially help remove scales and increase penetration of other drugs,
Why is Anthralin not used today (2)
Inferior to TCS
- stains the skin, uncomfortable
Why is topical Coal Tar not used anymore
Not very effective
- similar efficacy to D3 analgoues
Safe in pregnancy
Which oral systemic therapy is the most effective in terms of PASI75
Cyclosporine
What is the dosing for methotrexate for psoriasis?
Onset
Start low (10mg) and titrate up to minimize side effects (over 16 weeks)
- 15mg+ is better to switch from PO to Injection as bioavailability is better
- can be taken off during remission and restarted during flares
Side effects of methotrexate (8)
Depletes folate + affects healthy cells
(Must give folate supplementation 5mg/week - NOT on methotrexate day)
NVD
Anorexia
Hair loss
Fatigue
Dizziness
Mouth sores & ulcers
LIVER TOXICITY
Why do dermatologists have stricter guidelines for methotrexate than rheumatologists
Hepatic toxicity is 3x more likely in patients with psoriasis than RA
- resembles non-alcoholic steatohepatitis (NASH)
- leads to cirrhosis and hepatocellular carcinoma
- common in obese, hyperlipidemic, diabetic
When is cyclosporine indicated?
What groups of patient is it useful in?
Pregnancy
SEVERE psoriasis in non-immunocompromised patients who did not respond to other treatments
- fast acting
- Severe pustular, erythrodermic, severe NAIL psoriasis
Avoid in pregnancy (but category C)
* Lower birth weight + shorter duration of pregnancy reported
Avoid in breastfeeding
What are the side effects of cyclosporine (5)
NEPHROTOXICITY (due to vasoconstrictive effects on arterioles)
* Usually reversible
* May have permanent scarring
* CAUTION in pre-existing renal issues
Hypertension
Hypertriglyceridemia
Increases risk of lymphoma, SCC, non-melanoma skin cancer
Hepatotoxicity (rare)
What is the baseline monitoring for cyclosporine
- History/physical exam/BP
- BUN + SCr
- Urinalysis
- Blood: CBC, lipids, Mg, Uric acid, Potassium
Pregnancy test
What is the ongoing monitoring for cyclosporine
q2weeks during the first 3 months
- BP
- BUN + SCr
- yearly eGFR
Acitretin
Class
When is it used?
Side effects (5)
Pregnancy
Class
- Synthetic Vit A (oral retinoid)
When is it used?
- combined with TCS or Calcipotriol
Side effects
- HEPATOTOXICITY
- Mucocutaneous dryness, burning, chapped lips, - nose bleeds
- Headaches, joint pain
- Increased triglycerides
Avoid in Pregnancy
Apremilast (otezla)
Class
Side effects (4)
Monitoring
Pregnancy
Class
- Oral PDE4 inhibitor
Side effects
NVD
Weight loss
Arrhythmia
Depression, suicidal ideation
Monitoring
- No monitoring required
Avoid in pregnancy
Decravacatinib (sotyktu)
Class
Efficacy
Side effects (5)
Class
- Tyrosine kinase 2 inhibitor
- similar to JAK
Efficacy
- better than PDE4i apremilast
Side effects
- Infection, URTI
- HSV (reactivation)
- Oral ulcers
- Rhabdomyolysis
- CV events
AVOID in severe hepatic impairment and active infection
Which proteins are blocked in the immune system that play a major role in psoriasis (4)
IL-12
IL-17
IL-23
TNF-a
What are baseline tests prior to initiating a biologics (7)
CBC with platelets
LFTs
SCr
Hepatitis panel
TB testing + Chest X-ray
HIV in high-risk patients
Immunization complete
Which class of biologics are the most effective in Psoriasis?
What are the top 3 drugs in order
Class: IL-17 & IL-23 inhibitors
Drugs
1. Bimekizumab (Bimzelx)
2. Risankizumab (skyrizi)
3. Ixekizumab (Taltz)
What side effect is unqiue to infliximab
Infusion reactions
What side effect is unique to seckinumab (cosentyx)
URIs
hypersensitivity
cause/worsen IBD
What is a unique side effect to ustekimunab (Stelara)
Posterior reversible encaphalopathy syndrome (PRES)
What is a unique side effect to ixekizumab (taltz)
May cause or worsen IBD
What is a unique side effect to risankizumab
Drug induced liver injury (DIU)
What is a unique side effect Bimekizumab
Injection site rxn
oral candidiasis
URI
What is a unique side effect to brodalumab
Suicidal ideation
What is the risk for JAK inhibitors
- increase risk of CVS events (heart attack, stroke)
- Cancer (lymphoma, lung cancer)
- Thrombosis (clot)
- Death
What are the 2 types of phototherapy
UVB
PUVA
Explain UVB phototherapy
Safety profile
Found in natural sunlight (penetrates skin and depletes dermal lymphocytes, dendritic cells, macrophages)
- This is a standing booth (not a tanning bed)
Safety profile
- rare erythema or blistering
- cancer risk
Explain PUVA therapy
In which type of psoriasis is it the most responsive in (3)
Safety profile
Uses photoactive compounds (psoralens)
* 5/8-methoxypsoralens sensitize dermal cells to longer wavelength of UVA light
Psoralens can be applied topically or taken PO 2 hours prior to treatment (NOT IN PREGNANCY)
Most responsive to PUVA treatment:
- stable plaque psoriasis
- guttate psoriasis
- psoriasis of the palms/soles
Safety profile
- premature aging
-freckling
- cumulative risk of SCC/BCC
What is the first-line choice for psoriasis in children
2nd-line
Topical corticosteroids
Systemic agents for severe REFRACTORY psoriasis
What is the first line treatment in Elderly patients
Which biologic is the only one with published findings in elderly
- TCS + D3 analogue (dovobet, Enstillar)
Biologic
- Etanercept
How long does remission last in psoriasis
1-12 months
- important to use it long-term
