27 - Psoriasis Flashcards
Which PSORIASIS DRUG is
PREGNANCY CATEGORY X?
TOPICAL RETINOIDS
Tazarotene 0.1% & 0.05% cream/gel
Also:
Methotrexate** + **Acretin
Which SYSTEMIC PSORIASIS Drug?
Calcineurin Inhibitor + Blocks Lymphocytes
T-cells & IL-2 containing lymphokines
Short Term Therapy < 12 weeks
to reduce risk of nephrotoxicity
also need to TAPER off dose for D/C
1mg/kg/day each week to prolong relapse
Rebound Psoriasis very likely
CYCLOSPORINE
Moderate - Severe Plaque Psoriasis
for inducing remission & maintanence
CYP34A SUBSTRATE
AMJEVITA
is a Biosimilar to BRM?
ADALIMUMAB = Humira
starts with A
TNF-a inhibitor
ACRETIN - ADRs / Monitoring
oral Retinoid
- *PREGNANCY CATEGORY X**
- unless using BC & willing to continue 3 years after treatment*
- *Avoid ALCOHOL**
- *during** & for 2 months after DC
Monitor:
TG’s & Liver Chemistry
ADR:
- *Opthalmic** - photosensitivity / color vision / night vision
- *GI** - hepatitis / jaundice / liver enzyme elevation
- *Common**: HIGH TG’s / dry mouth/eyes/lips / brittle nails / alopecia
TOPICAL RETINOIDS
Tazarotine 0.1% & 0.05% cream/gel
ADR’s
HIGH incidence of irritation @ Application Site
DOSE DEPENDENT
causes : burning / stinging / itching / erythema
- can be MINIMIZED by using:*
- *creme formulation / alternate day app**
- LIMIT treatment to 30-60 min*
- *use moisturizers**
can be used in combo with topical corticosteroids
Biologic Response Modifiers = BRMs
Psoriasis Indications
Contraindications / Risks
Considered for patients with:
Moderate - Severe Psoriasis
when Other systemic agents are
INADEQUATE or CONTRAINDICATED
Immunomodulatory effects cause an:
- *Increased Risk of INFECTION**
- *Sepsis / TB reactivation / Opportunistic Infections**
NO LIVE VACCINES
Cyclosporine
ADR / Monitoring
Short Term Therapy <12weeks
Due to NEPHROtoxicity
Monitor
baseline BP, Scr, serum urea nitrogen, TG, CBC, uric acid, K, Mg should be taken, and rechecked every 2 weeks for first 12 weeks and monitored monthly after
AE:
renal toxicity, hypertension, hypertriglyceridemia (reversible upon discontinuation), hirsutism, risk of non- melanoma skin cancers increases with duration of treatment
Which PSORIASIS Drug?
Useful for patients with:
Moderate-Severe inverse psoriasis
VVV
affects INTERTRIGINOUS AREAS or FACE
- *TOPICAL CALCINEURIN INHIBITORS = CNI**
- *Pimecrolimus 1% cream (elidel) // Tacrolimus 0.1%**
LESS irritating vs Calcipotriol
- *&**
- AVOIDS* steroid ADR’s like skin atrophy
- but steroids still may be more effective*
BBW = link between lymphoma & skin cancer
HIGHEST Potency Topical Steroid
for Psoriasis
Indications / Drug
indicated for:
VERY THICK PLAQUES
Plaques on:
PALMS or SOLES
BETAMETHASONE 0.5%
CLOBETASOL 0.05%
Topical CorticoSteroid ADRs
Psoriasis
Cutaneous ADRs
skin atrophy / acne / dermatitis / folliculitus
hypopigmentation / striai
Systemic ADRs
super potent // WIDE-SPREAD use of mid-potency agents
HPA axis suppression / cushings syndrome
Osteonecrosis / cataracts / glaucoma
TachyPhylaxis with prolonged use
Pregnancy CAT C
Which PSORIASIS DRUG is a:
CYP3A4 SUBSTRATE?
CYCLOSPORINE
Inhibitors –> INCREASE CSA concentration
veramapil / diltiazem / amiodarone / macrobide abx
allopurinol / SSRI / antifungals / CIPRO / grapefruit
Inducers –> decrease CSA conc.
anticonvulsnats / phenytoin / phenobarbital
rifAMPin / st johns / efavirenz
NON-Pharmacological Therapy
Psoriasis
Recommended THROUGHOUT ALL TREATMENT
along with anything else
STRESS reduction strategies
Moisturizers // Oatmeal Baths
- *SPF 30**
- *Skin Protection**
AVOID HARSH SOAPS // Detergents
Cyclosporine
Dosing Considerations
- *Calcineurin Inhibitor**
- blocks lymphocytes*
Dose should be:
Titrated to LOWEST effective dose for maintanence
to PREVENT RELAPSE
For DISCONTINUATION:
decrease dose 1mg/kg/day each week to prolong relapse
to avoid REBOUND PSORIASIS
- *Short Term Therapy <12weeks**
- reduce risk for nephrotoxcity*
MTX
Risk Factors for Hepatotoxcity
If they have these RISK FACTORS:
Consider LIVER BIOPSY
or if they have
MTX cumulative dose of 3.5-4g,
Hepatotoxicity Risk Factors:
H/O of moderate alcohol consumption
persistantly abnormal liver chem
history of liver disease = Hep B/C
FamHistory of liver disease
diabetes / Obesity / no FOLATE while on MTX
What is the MoA of these BRMs for Psoriasis?
Ustekinumab = Stelara
IL-12 / IL-23
inhibitor
Other Types of Psoriasis
except of PLAQUE psoriasis
Gluttate
small DOT like lesions = 2nd most common
- *Pustular**
- NOT infectious, pus has WBC*
Inverse
in SKIN FOLDS –> obese people
Erythrodermic
VERY SEVERE –> entire body / painful / temperature
Topical Vitamin D Analogs
ADRs
Cutaneous
Mild Irritant Contact dermatitis
others:
burning / pruritis / edema / itching / peeling /dryness
SYSTEMIC:
HYPERcalcemia // PTH SUPRESSION
rare unless using >5mg calcipotriol
Pregnancy Category C
Lower Potency Topical Steroid
for Psoriasis
Indications / Drug
indicated for:
INFANTS
face / interriginous / thin skin
HYDROCORTISONE 1%
Anthralin
Indication / ADR
Psoriasis Treatment
typically with UVB Phototherapy
Short Contact Athralin Therapy = SCAT
is preferred, AAA for 2 hours –> wipe off
- not commonly used*
- risk of* severe skin irritation
- do NOT use on FACE or Intertriginous areas*
Which TOPICAL PSORIASIS DRUG
has a BLACK BOX WARNING?
- possible link between the drug and:*
- *lymphoma & skin cancer**
CALCINEURIN INHIBITORS
Pimecrolimus 1% (Elidel)
Tacrolimus 0.1%
INFLECTRA
is a Biosimilar to BRM?
INFLIXIMAB = Remicade
TNF-a inhibitor
Phototherapy
UVB
Indications / Treatments
for Moderate - Severe Psoriasis
Narrowband UVB or Broadband UVB
given with:
Crude Coal Tar or Anthralin
for enhanced efficacy
LASER treatment has HIGHER UVB dose = FASTER results
Contraindicated in patients with
history of melanoma or multiple nonmelanoma skin cancers
Which PSORIASIS drug
can NOT be used with
UVB LIGHT PHOTOTHERAPY
- *TOPICAL SALICYLIC ACID**
- *keratoytic properties –> SCALP PSORIASIS**
may reduce EFFICACY
when used with UVB light phototherapy
BRMs
Monitoring / Screening
BBW = Fatal Infections / Malignancies
Monitoring:
TB Testing // ANC
Baseline LFT & periodically
H/o or signs of Malignancy
COPD / CHF / GI perforation
Which PSORIASIS drug?
MoA:
Binds to receptors, which results in
inhibition of KERATINOCYTE proliferation
&
enhancement of KERATINOCYTE differentiation
Inhibits T-lymphocyte Activity
TOPICAL VITAMIN D ANALOGS
Calcipotriol / CalcipoTriene
cream / solution / ointment foam
- *Calcitriol Ointment**
- for sensistive skin / skin folds*
- *Which PSORIASIS drug is
- INACTIVATED by UV-A LIGHT?***
TOPICAL VITAMIN D ANALOGS
Calcipotriol / CalcipoTriene / Calcitriol Ointment
Apply AFTER UVA light exposure
Which SYSTEMIC THERAPY of PSORIASIS
is the GOLD STANDARD?
and when is there an EXCEPTION?
METHOTREXATE
is gold standard
SAFER alternative to CSA
unless PRE-EXISTING LIVER DISEASE
Which Psoriasis Drug?
Keratolytic Properties
Used in various:
- *shampoo / bath oil formulations** for patients with:
- *SCALP PSORIASIS**
TOPICAL SALYCYLIC ACID
Typically used in:
COmbination w/ topical corticosteroids
VVV
ENHANCES steroid penetration –> increase efficacy
CAN BE USED IN PREGNANCY
BUT:
AVOID in CHILDREN
also Systemic Absorption with 20% BSA & RENAL IMPAIRMENT
Which PSORIASIS Drug?
Indication?
- *PHOSPHODIESTERASE-4 INHIBITOR
- reduces* production of CYTOKINES**
APREMILAST = Otezla
Indicated for treatment of:
Moderate - Severe Plaque Psoriasis
for those who are
candidates for phototherapy or systemic therapy
What is the MoA of these BRMs for Psoriasis?
Etnercept = Enbril
Certolizumab Pegol = Cimzia
TNF-a Inhibitor
Also:
Adalimumab = Humira
Infliximab = Remicade IV
What is the MoA of these BRMs for Psoriasis?
Secukinumab = Cosentyx
Brodalumab = Siliq
Ixekizumab = Talz
IL-17
inhibitor
Which Psoriasis DRUG?
MoA:
Normalizes abnormal keratinocyte differentiation
diminishes keratinocyte HYPERproliferation
CLEARS inflammatory infiltrate in psoriatic plaque
TOPICAL RETINOIDS
Tazarotine 0.1% & 0.05% cream/gel
ONCE DAILY
CATEGORY X
Effective in:
CLEARING psoriatic plaque Lesions
&
Achieving REMISSION
- *Genetic Factors:**
- *Psoriasis**
Family History
PSORs1
on chromosome 6p is KEY gene –> 50% of heritability
Major Psoriasis Susceptibility genes:
- *HLA**
- *Cw6 TNF-a Interleukin-23**
Pharmacologic Therapy for Psoriasis
Mild-Moderate Severity
TOPICAL TREATMENTS
are std of care
CorticoSteroids
Vitamin D Analogs
Retinoids
Salycylic Acid
Calcineurin Inhibitors = CNI
Phototherapy
UVA
Indications / Treatments
for Moderate - Severe Psoriasis
- *P+UVA**
- *Psoralens** = Photosensitizer to ENHANCE efficacy
MOST EFFICACIOUS PHOTOTHERAPY TREATMENT
_topical VITAMIN D analogs
are INACTIVATED by UVA light_
Contraindicated in patients with
history of melanoma or multiple nonmelanoma skin cancers
MTX
Monitoring for those WITHOUT hepatoxicity Risk factors
Hepatotoxicity Risk Factors:
H/O of moderate alcohol consumption
persistantly abnormal liver chem
history of liver disease = Hep B/C
FamHistory of liver disease
diabetes / Obesity / no FOLATE while on MTX
Patients W/O hepatotoxic risk factors
Liver Chemistry check every 1-3 months
Still:
consider LIVER BIOPSY if 5/9 AST levels
are ELEVATED over course of 12 months
Which PSORIASIS drug is considered the
Safest LONG-TERM topical treatment?
- *Topical VITAMIN-D Analogs**
- *Calcipotriol** = cream / solution / ointment / foam
- *Calcitriol OINTMENT**
- less irritation in* sensitive skin areas = skin folds
Can be used in COMBINATION w/ topical steroid
more effective with comination
more expensive though
Which PSORIASIS drug?
Direct anti-inflammatory benifits
due to its effects on
T-Cell Gene Expression & cytotoxic Effects
blocks DIHYDROFOLATE REDUCTASE
Inhibits FOLATE Synthesis
METHOTREXATE
Gold Standard for Psoriasis
safer alternative vs CSA, unless pre-existing liver disease
Pregnancy Catagory X
Which SYSTEMIC THERAPY of PSORIASIS?
Active metabolite of:
aetretinate, Vitamin A acid derivative, oral retinoid
As MONOtherapy, initial response may be MORE rapid than MTX
In patients with SEVERE inflammatory psoriasis
low dose (25mg/day) is not recommended as monotherapy
Commonly used in COMBO w/ PHOTOTHERAPY
ACRETIN
Oral Retinoid
Moderate-Severe Psoriasis
often WITH PHOTOTHERAPY
Which DRUG THERAPY for Psoriasis?
Anti-Inflammatory // Antiproliferative
Immunosuppresive / Vasoconstrictive
mech:
binds to intracellular corticoid receptors
&
regulates gene transcription
TOPICAL CORTICOSTEROIDS
Ointmets –> ENHANCE drug penetration
& have the most potent formulations
patients might prefer lotion/cream for daytime use
3 Levels of Potency
Epidemiology / Etiology
Psoriasis
Male = Female
- *Two Peaks**:
- *20-30** & 50-60 y/o
T-lymphocyte-mediated systemic inflammatory disease
Epidermal HYPERplasia & Dermal Inflammation
Caused by:
Genetic & Environmental Influences
Apremilast = Otezla
Dosing / ADR
PHOSPHODIESTERASE-4 INHIBITOR
Gradually INCREASE dose over 5 days
until
Dose of 30mg BID
for SEVERE renal impairment –> 30mg QD
ADR:
DIARRHEA - shortterm initial Treatment // Nausea / headache
Mid-High Potency Topical Steroid
for Psoriasis
Indications / Drug
indicated for:
ADULTS
+ other areas of the body
NOT face / interriginous / thin skin
CLOBETASOL 0.05%
for scalp - foam / shampoo / spray
Spray / Foams = patient preferred, but higher cost
Comorbidities with Psoriasis
Patients with Psoriasis have significant associated comorbidities:
Psoriatic Arthritis=PsA
- *Metabolic Syndrome:**
- *3x** more likely to have MI or STROKE
- *5x** more likely to develop Diabetes
Crohn’s Disease / MS / T-cell lymphoma
- *Psychiological Illnesses**
- *ANX / Depression / Alcoholism**
Clinical Presentation of
PLAQUE PSORIASIS
Appear on:
Scalp / Knees / Elbows / Lower Back
NAIL INVOLVEMENT
50% have fingernail / 35% have toenail
30% of patients have PsA = Psoriatic Arthritis
90% of patients with Psa have Nail involvement
Systemic Therapies
Indication
- *Mainstay of treatment for**
- *Moderate - Severe Psoriasis**
- topical therapies are adjuncts*
Traditional Agents:
Acetretin / Cyclosporine / MTX
NEWER AGENTS:
- *Phosphodiesterase-4 Inhibitor**
- *BRM Biologic Response Modifer Agents -Injectables**
Appropriate Use of TOPICAL STEROIDS
for Psoriasis
- *Potency Class 1**
- LIMIT* duration to 2-4 weeks due to risk of:
- *cutaneous / systemic ADRs**
Frequency of use should be gradually reduced once
clinical response is seen = TAPE
BID application is common
Pule Dosing also
Environmental Risk Factors
Psoriasis
Drugs as well
Drugs that exacerbate pre-existing psoriasis:
Lithium / NSAIDs / Chloroquine
B-adrenergic blockers / Fluoxetine / CORTICOSTEROID withdrawal
INFECTION / Injury to Skin
OBESITY / STRESS
Methotrexate
Drug Interactions / ADR
Pregnacy Category X
DI due to ALBUMIN binding:
Salicylates / phenytoin / trimethoprim / ciprofloxacin / thiazides
DI from Acidic Drugs:
Salicylates or VITAMIN C –> INCREASE MTX
ADR:
liver toxicity / nausea / pulmonary toxicity / pancytopenia
Coal Tar
Indication / ADR
Psoriasis Treatment
typically with UVB Phototherapy
Can be helpful as a:
Adjunct w/ TOPICAL CORTICOSTEROIDS
- LIMITED EFFICACY*
- *WITHOUT PRESCRIPTION** as a:
- *shampoo / cream / lotion / oil / oinmetn**
Classification of
MODERATE - SEVERE
Plaque Psoriasis
NO LAB TEST FOR PSORIASIS
>5 - 10% of BSA
What is the MoA of these BRMs for Psoriasis?
Tildrakizumab = Ilumya
Guselkumab = Tremfya
IL-23
inhibitor
ELREZI
is a Biosimilar to BRM?
Enbrel = Etanercept
Also starts with E
TNF-a inhibitor
