Treatments for mild-moderate psoriasis
- Topical corticosteroids
- Coal tar
Treatments for severe psoriasis
- immunomodulatory agents
What are emollients usually made from?
- "oil, water, and wax"
- mineral oil
What is the mechanism of action of emollients?
- form an occlusive layer
- prevent water loss
- softens the scaly, hyperkeratotic surface of the psoriatice plaques
- Some contain alpha or beta hydroxy acids such as salicyclic acid, urea, or lactic acid
What are the side effects of emollients?
- soft, smooth skin
- possible folliculitis
- contact dermititis
What type of psoriasis are emollients used for?
What can emollients reduce?
itching and some discomfort
How effective are emollients?
What do emollients do to the stratum corneum?
hydrates the stratum corneum to minimize hydration loss by evaporation
What are emollients available as?
How are emollients dosed?
apply 4 times a day
Name the 2 keratolytics
- beta-hydroxy acid
- salicuclic acid
What is the mechanism of action of keratolytics?
- solubilizes intracellular cement
- decreases corneocyte adhesion --> desquamation
What are the side effects of keratolytics?
- salicylism (rare with topical; due to excessive systemic absorption)
- metabolic acidosis
Describe the effectiveness of keratolytics.
lacks superior clinical efficacy
What do keratolytics do? (Not MOA)
- removes scales
- smoothes skin
- lowers hyperkeratosis
- can enhance penetration of other topical agents due to breakdown of keratin
What can keratolytics be used in combination with?
- topical steroid
- coal tar
What are keratolytics available as?
How are keratolytics dosed?
- apply 2-3 times a day in concentrations 2-10%
- 3-4% may be added to oils or shampoos for scalp
What is the mechanism of action of topical sulfur compounds?
- keratolytic, desquamation
- forms hydrogen sulfide bonds with keratinized skin cells
- loosens extracellular matrix/"cement" between cells
What are the side effects of topical sulfur compounds?
What do glucocorticoids produce and where is it synthesized?
- produce cortisol
- synthesized in the zona fasciculata of adrenal cortex
What does cortisol impact the regulation and function of?
- metabolism (catabolism)
- stress response
- immune system
What do mineralocorticoids produce and where is it synthesized?
- synthesized in the zona glomerulosa
What does aldosterone impact the regulation of?
- Na and K concentrations in extracellular fluids
- cardiovascular and CNS function
What are the principal therapeutic benefits of corticosteroids?
- anti-inflammatory effects
- immunosuppressive effects on the immune system
What is the mechanism of action of topical corticosteroids?
- decrease transcription/translation of pro-inflammatory mediatiors, which indirectly decreases synthesis of prostaglandins
- increase transcription/translation of anti-inflammatory factors
- ultimately decreases migration of T-cells
What actions of leukocytes are impaired by glucocorticoids?
proliferation, activation, and chemotaxis of multiple leukocytes
What are the catabolic effects of corticosteroids?
breakdown connective tissue, lymph tissue, muscle, fat, and skin
What does halogenation of a corticosteroid do?
What are the local side effects from topical use of corticosteroids?
- skin thinning (atrophy)
- stretch marks (striae)
- easy bruising and tearing of skin (purpura)
- delayed healing of wounds/erosions
- susecptibility to skin infections
- perioral dermitits
- hypertrichosis, hair growth
- telangiectasia, enlarged blood vessels (spider veins)
- cataracts and glaucoma (rare)
What systemic effect can happen as a result of chronic use or corticosteroids?
suppression of HPA
What do topical corticosteroids do? (Not MOA)
reduce itching and inflammation
How are topical corticosteroids dosed?
- varies depending on potency, dosage form, salt form, and strength.
- based on USP potency ratings and vasoconstrictive ptoency ratings
- apply sparingly
- ideally no more than BID for higher potency
What does a vasocontrictive potency rating of I indicate? What is the lowest potency?
- highest potency
- VII is lowest potency
How long should highly potent corticosteroids be used for?
less than 4 weeks
What can topical steroid use mask?
fungal and bacterial infections
How can tachyphylaxis of corticosteroids be minimized?
reserve potent steroids for 1-2 days/week
What can happen if corticosteroid use is d/c after long term use?
acute flare up
How is occlusion used with topical corticosteroids?
- do not use for more than 12 hours
- generally used for 6 hours
- do not use for higher than class III
What class is usually a starting point of standard care when selecting a topical steroid?
Class III-IV (medium potency)
When are class I topical steroids used? How can they be applied? How long can they be used?
- for severe cases
- used on small area of body
- thickened skin (palms, soles)
- applied for 2 consecutive days each week for maintainence
- safer to use less than 2 weeks
What are class II topical steroids used for?
longer duration allowed for thick scales
How long can class III-IV topcial steroids be used for? What also can be used to help increase absorption in these classes?
- limit to 4-6 weeks
- may use occlusive dressing
What class of topical steroids are safest for face, groin, and children?
What can topical corticosteroids be used in combination with?
- practically any topical therapy
- helps reduce irriation with calcipotriene and tazarotene
What should a patient do to reduce flare up?
What are examples of Coal tar?
Denorex, Tegrin, Nutragena-T/Gel, Balnetar
What is the MOA of coal tar?
- decreases DNA synthesis --> anti-mitotic decreases proliferation
- phenols have anti-pruritic effects and are counter-irritants
What are the side effects of coal tar?
- irritant folliculitis
- stain and odor
- carcinogenic potential
What does coal tar do? (Not MOA)
reduces plaque formation by slowing epidermal proliferation
What is coal tar available as?
How is coal tar dosed?
apply 1-2 times a day usually at night and allowed to stay on overnight
What can help the mechanism of coal tar? What is this regimen called?
- UVB light + coal tar, 3-4 weeks treatment, obtain 90% remission
- called Goeckerman regimen
What are the main counseling points of coal tar?
- minimize staining
- allow coal tar to dry before bed
- gels may cause less staining
- sweat can carry stains
- consider wearing socks to prevent staining
- masking odor --> perfumes, aftershave
How is shale tar (ichthammol) produced?
degradtion of coal shale with ammonia and sulfur
What is the MOA of ichthammol (shale tar)?
- emollient and demulcent properties in an ointment vehicle
- unknown efficacy
What are the side effects of of ichthammol?
- less irritating than coal tar
- no photosensitization
What are examples of anthralin?
- Dritho-scalp cream
What does anthralin do? (not MOA)
- penetrates damaged skin more readily than intact skin
- short-contact therapy
- metabolized by oxidation at C10
What is the MOA of anthralin?
- *generates free radicals
- *generates reactive oxygen species --> degrades DNA and forms "adducts" / anti-mitotic
- inhibits release of cytokines --> IL-6, IL-8, TNF-a
- down-regulates epidermal growth factor (EGF)
What are the side effects of anthralin?
- violet-brown staining
- *extremely irritating to undamaged skin
What types of psoriasis is anthralin mostly used for?
- plaque and guttate
- can yield remissions as long as 4-6 months
What can anthralin be used in combination with?
UV light and coal tar
What is the Ingram regimen?
anthralin, UVB/PUVA, +/- coal tar bath
What can be used with anthralin to reduce its irritation?
- topical steroids
- zinc oxide can be used to protect non-affected areas
How is anthralin dosed?
- based on titration upwards, applied in evening and kept on overnight
- Start 0.1-0.2% up to 3-5% for overnight application
- SCAT involves less than one hour contact (1-4%)
What is SCAT and how is it used?
- short-contact anthralin therapy
- use small amount of drug on localized area for 10 min then gradually increase contact time up to one hour
What is calcipotriene (Dovonex)?
- synthetic Vitamin D analog
- endogenous vitamin D/calcitrol increases absorption of Ca2+ in GI
What is the MOA of calcipotriene?
- binds to calcitrol receptors
- inhibits keratinocyte proliferation
- induces terminal differentiation of keratinocytes
- anti-inflammatory? - decreases cytokine release and CAM levels
What are the side effects of calcipotriene?
- dry skin
- skin atrophy (rare)
- hypercalcemia (rare)
What are the structural differences between calcipotriene and calcitriol?
- modified side chain compared to calcitriol
- causes rapid transformation to inactive metabolites
- no significant systemic absorption
How is calcipotriene dosed? When do you see results? Max dose? clearance time? failure of therapy?
- applied 1-2 times a day
- results in 2-8 weeks
- max 100 g/week
- clearance usually seen in 4-6 weeks
- failure of therapy if no response in 8 weeks
What is calcipotriene available as?
cream ointment solution
What can calcipotriene be used in combination with?
What should you consider monitoring when a patient is on calcipotriene?
Ca levels and urine excretion
What may a patient notice when using calcipotriene?
peripheral scaling around plaque - sign that psoriasis is clearing
What should NOT be used with calcipotriene? Why?
salicyclic acid will inactive this drug
What is the MOA of Tazarotene?
- binds to RARs
- Exfoliative - promotes cellular differentiation, NOT MITOSIS, normalizes keratiniazation, anti-inflammatory actions
What are the side effects of Tazarotene?
- dry skin
What is Tazarotene available as?
What can tazarotene be combined with? How? Why?
- corticosteroid AM
- tazarotene HS
- decrease side effects
What are the benefits of using tazarotene cream?
- help with dry skin
- consider using is >35% BSA is affected
What are the benefits of using tazarotene gel?
- may dry skin
- consider using if 20% BSA affected
True/False: Retinoids are teratogenic.
How is tazarotene dosed? How long can it reduce the disease for? How long does it take to see results?
- applied once daily before bed
- use minimal amount
- may reduce disease for up to 12 weeks
- results usually within 2 weeks but can take up to 8-12
When is tazarotene used?
- primarily <20% BSA
- used a lot in scalp