Dermatitis/Psoriasis/Acne/Sunburn Pharmacology

Types of Topical MX

hydrocarbon

• for driest skin

• no water content→pure hydrocarbons

• strong barrier

• ex: vaseline

ointment

• 80% hydrocarbon+20% water

• strong barrier

• common drug vehicle

• ex: aquaphor

cream

• for dry skin

• more water than ointment

• decent barrier

• replenishes moisture

• ex: cerave

lotion

• for dry-normal skin

• higher water content

• good for hairy skin

• slightly less drying than gels

• ex: cetaphil

gel

• for oily skin

• highest water/alcohol content

• good for young skin

• strong protective topical agent

• drying dosage form

• ex:
  -aloe
  -cosmetic+drug products

solution

• for oiliest skin

• no oil content+some alcohol content

• for large areas of skin

• ex: witch hazel

Topical Corticosteroids

MX:
highest
clobetasol propionate 0.05%
fluocinonide 0.01%

high
bethamethasone dipropionate 0.05% (high)
mometasone furoate 0.1%

high-medium
fluocinocide 0.05%

medium
triamcinolone actenoide 0.1%

mild
desonide 0.05%
fluocinolone acetonide 0.01%

lowest
hydrocortisone 0.5%
OTC hydrocortisone 1%
hydrocortisone 2.5%

MOA:
anti inflammatory
antipruritic
vasoconstrictive

ROA:
1st line for skin irritation
dosage→“finger-tip” unit (1st joint=adult hand)
don’t overuse→risks

AE:
local
skin thinning
pigment changes
telagniectasia
rosacea
delayed wound healing
irritation
burning
peeling

systemic
HPI suppression
iatrogenic cushing’s
peds→growth retardation
glaucoma

Ointments vs. Creams

ointment

• mostly oil based

• greasy+thicker consistency+occlusive

• slower+stays on surface longer

• difficult to spread evenly

• dry skin conditions (ex: psoriasis)

cream

• less oil based

• lighter texture+consistency

• water evaporates→faster

• easier to apply→larger areas+less mess

• wet/oozing skin conditions (ex: eczema)

Atopic Dermatitis NP TX

avoid triggers

• environmental irritants

• allergens

• pollution

• stress

• weather changes

hydration

• essential to reducing severity of disease

• use moisturizers with petrolatum/lanolin
  -aquaphor
  -eurcerin
  -keri

• wet wrap therapy

no food diets

Atopic Dermatitis MX TX

1st line

• topical mid-high potency steroids x titrate as needed

• itch→PRN antihistamines

2nd line

• topical calcineurin inhibitors

• topical phosphodiesterase-4 inhibitor

• aryl hydrocarbon receptor antagonist

allergy/ineffective/can’t use

• PO cyclosporine

• PO methotrexate

• IL-4 antagonist

• IL-13 monoclonal antibody

• JAK1 inhibitors

Topical Corticosteroids

MX: hydrocortizone 1%→OTC/lower potency
mometasone furoate 0.1%→high potency

I: acute inflammation→higher potency+lower potency (maintenance)

ROA:
OTC/lower potency→1-2x daily
high potency→daily

CI: don’t use longer than 2-4 weeks

Topical Calcineurin Inhibitors

MX: tacrolimus
pimecrolimus

MOA: blocks calcineurin cytokines→decreased epidermis hyperproliferation

I: second line
short-term tx
intermittent tx

ROA:
tacrolimus→affected spot x 2x/day

pimecrolimus:
-smallest amount possible
-wash hands after use

takes weeks to work+continue using

AE: headache
skin burns
pruritis
cough
flu-like sx

Topical Phosphodiesterase-4 Inhibitor

MX: crisaborole

MOA: inhibits PDE-4→increased intracellular cAMP levels

I: mild-moderate atopic dermatitis
-adult
-3+ months
second line (can’t use topical corticosteroids)

ROA: thin film to affected areas x 2x/day

AE: hypersensitivity rxn
application site pain
no long-term effectiveness after 1 year

pruritis:
few days after start of tx
further clearings after 1 wk

Topical PDE4 Inhibitor

MX: roflumilast
-cream
-foam

MOA: similar to potent corticosteroids

I: 6+ y/o

ROA: daily

AE: rare (~1%)
diarrhea
headache
insomnia
application site pain
URI
UTI

CI: moderate/severe liver impairment
CYP3A4
CYP1A2

IL-4 Antagonist/Monoclonal Antibody

MX: dupilumab

I: 6+ months
moderate-severe atopic dermatitis
-no tx with topical mx
-can be used w/w.o. topical steroids

ROA:
1st dose→600mg SQ
maintenance dose→300mg SQ

AE: injection site rxn
hypersensitivity rxn
conjunctivitis
eye issues
alrthralgia
rhinosinusitis

CI: live vaccines
pregnancy

Adbry/Trakilumab

MX: SQ biologic

MOA: blocks IL-13

I: over 12+ y/o
uncontrollable moderate-severe atopic dermatitis
-no tx with topical mx

ROA:
1st dose: 4 injections
maintenance dose: 2 injections x biweekly
can do normal vaccinations

AE: URI
eye+eyelid inflammation
injection site rxn
eosinophilia

CI: live vaccines

Aryl Hydrocarbon Receptor Agonist

MX: tapinarof

MOA: decreases IL-17
effective as potent corticosteroid
no systemic absorption

ROA: daily

AE: folliculitis
nasopharyngitis
contact dermatitis
headache
pruritus
influenza

JAK1 inhibitors

MX: upadacitinib
abrocitinib

I:
U: adults
12+ y/o
uncontrollable moderate-severe atopic dermatitis
-not controlled with systemic+biologic mx

A: adults
uncontrollable moderate-severe atopic dermatitis
-not controlled with systemic+biologic mx

ROA: PO

AE:
U: URI
herpes zoster
herpes simplex
bronchitis
nausea
cough
pyrexia
acne
etc.

A: cold
nausea
headache
herpes simplex+cold sores
increased creatine phosphokinase
dizziness
URI
etc.

CI:
U: pregnancy
lactation
hepatic impairment
GI perforations

black box:
increased opportunistic infection→do TB test before starting
50 y/o+RF→sudden CV death
increased MI/CHF/stroke risk
increased malignancy risk
increased thromboembolic event risk
increased cholesterol
retinal detachment
RBC/neutrophil/lymphocyte/platelet changes

Psoriasis TX Overview

chronic→lifelong tx

no universal tx formula→many tx options

switching tx is common

combination of tx is common

low pt adherence

location of body affects tx choice
-ex: scalp only

Psoriasis TX Factors

effectiveness of tx

AE+long-term risks

comorbidity (psoriatic arthritis)

severity

mx CIs

pt adherence

cost

Psoriasis TX Approaches

monotherapy

• mild-moderate

• tx fail/toxicity→mx combination/rotation/sequencing tx

• older agents→higher dose toxicity

• newer agents→safer

combination therapy

• lower dose of each agent

• more dangerous mx can be discarded→safer mx used for mtn tx

• both RF of mxs carried

sequential therapy

• transitions from initial rapid tx→long-term tx

• old

Psoriasis TX (General)

1st line:
moisturizer
NP tx
topical steroids+plastic wrap BID x 2 weeks

2nd line:
1-week rest from topical corticosteroids→topical corticosteroids x 4 weeks

high-potency topical corticosteroids 2x/week+vitamin D analog BID

3rd line:
dermatologist referral
-UVB
-antimetabolites
-entanercept
-psoralens+UVA light tx

Psoriasis NP TX

decrease stress

avoid irritants
-sensitive skin products
-fragrance-free soaps

skin protection
-loose-fitting garments
-skin wraps
-SPF 15+
-sunburn→exacerbation

moisturizers
-apply throughout day
-fragrance free

oatmeal baths

stop smoking

UVA
UVB
narrow UVB
PUVA

Psoriasis MX TX

mild-moderate:
topical→topical+phototherapy→topical+systemic

moderate-severe:
systemic+topical/phototherapy→more-potent systemic+topical/phototherapy→biological response modulator (BRM)+other mx

all dx:
moisturizers PRN
continue current tx if controlled
step down to lowest effective dose/potency

Mid-High Potency Topical Corticosteroids

MOA: anti-inflammatory
anti-proliferative
immunosuppression
vasoconstriction

I: mild-moderate psoriasis (m/c)

ROA: thin layer x OID/BID

AE: acne
skin atrophy
contact dermatitis
fungal infection
rosacea
striae

CI: tachyphylaxis
abruptly stop tx→rebound flares
more than 4+ weeks
high potency→BID up to 2-4 wks→reduce dosease
limit use as much as possible

Topical Vitamin D Analogues

MX: calcipotriene
calcipotriene+betamethasone dipropionate

MOA: binds to vitamin D receptors→inhibits keratinocyte production+enhances keratinocyte differentiation

I: psoriasis

ROA:
C: BID x 8 weeks
C+BD: OID x 4-12 weeks
after UVA light exposure
can be used on face+genitals without atrophy risk

AE: skin irritation
erythema
dryness
stinging
burning

CI: tachyphylaxis
less effective than mid-potency topical steroids
used with topical steroids→enhance efficiency+reduce steroid atrophy
lesions gone in 4-6 weeks

Topical Retinoids

MX: tazarotene

MOA: normalizes keratinocyte differentiation
anti-proliferative
anti-inflammatory

I: psoriasis

ROA:
T: gel
cream
daily x 8-12 weeks

AE: erythema
itching
burning

CI: UVB stronger
pregnancy

AE TX:
-reduce concentrations
-switch to cream tazarotene
-use moisturizers
-vary application sites
-short contact time

Topical Calcineurin Inhibitors

MX: tacrolimus
pimecrolimus

MOA: blocks cytokines→hyperproliferation of epidermis→localized immuno-modulating effect

I: off-label psoriasis

AE: skin irritation (less than vitamin D analogues)

CI: must be occluded
after bath
no skin atrophy

BB: malignancy

Topical PDE4 Inhibitor

MX: roflumilast

MOA: similar to potent corticosteroid

I: psoriasis
12+ y/o

ROA: once daily

AE: diarrhea
headache
insomnia
application site pain
URI
UTI

CI: moderate-severe liver impairment
CYP3A4
CYP1A2

Aryl Hydrocarbon Receptor Antagonist

MX: tapinarof

MOA: decreases IL-17

ROA: daily

AE: folliculitis
nasopharyngitis
contact dermatitis
headache
pruritis
influenza
no systemic absorption

Methotrexate

MOA: t-cell gene expression affects→anti-inflammatory+cytostatic effects

I: moderate-severe psoriasis

ROA:
initial:
2.5-5 mg PO/week→normal DX→7.5-25 mg PO/week
increase 2.5 mg Q 2-4 weeks

single dosage
GI ADE→divided dosage

AE: nausea
vomiting
mucosa ulcers
headaches
anemia

severe: hepatotoxicity
pulmonary fibrosis
bone marrow toxicity
immunosuppressive
increased levels of digoxin

DX: CBC
renal function
hepatic function
pulmonary toxicity
pregnancy test (avoid in pregnancy)

CI: pregnancy
lactation
renal disorders
hepatic disorders
leukopenia

4+ weeks for tx response
+folic acid supplementation
no abrupt discontinuation

Cyclosporine

MOA: inhibits production+release of IL-2→inhibits activation of resting T-lymphocytes

I: psoriasis
mono tx
or
combination tx

ROA: PO Q2 divided doses
increase dose Q2-4 weeks
short term→12 weeks intermittent
relapse→restart at previous dose
max use→1 year

AE: impaired renal function
HTN
hypertriglycemia
hypomagnesia
hyperuricemia
hypertrichosis

DX: BP
SCr
-baseline+biweekly x 12 weeks→x monthly

CI: pregnancy
CYP3A4
over 1+ year use

Systemic Non-Biologic Phosphodiesterase 4 Inhibitors

MX: apremilast

MOA: unknown
reduced inflammation

I: mild-severe psoriasis
adults

ROA: 5 day titration→BID
renal impairment→daily

AE: diarrhea (first 2 weeks→20%)
nausea
URI
headache
65+ y/o→dehydration
depression+worsening
weight loss

DX: no baseline screening
monitor labs
weight loss→5%+ from baseline→discontinue

CI: weight loss
CYP450

Systemic Non-Biologics Selective TYK2 Inhibitor (SOTYKTU)

MX: Deucravacitinib

MOA: TYK2 pairs with JAK1/JAK2→mediates cytokine pathways→produces pro-inflammatory cytokines+IL-17

I: moderate-severe plaque psoriasis
adults

ROA: PO daily

AE: URI
blood creatine phosphokinase increase
HSV
mouth ulcers
folliculitis
acne

DX: triglycerides
liver enzymes
creatine phosphokinase
TB
infection risk
viral reactivation

TNF-Alpha Inhibitors

MX: etanercept
adalimumab
infliximab
certolizumab pegol

MOA: binds to TNF-alpha→blocks activity→blocks excess production in skin→stops inflammatory cycle of psoriasis

I: psoriasis
E: 4+y/o

ROA:
E:
initial→SQ BID x 12 weeks
mtn→SQ weekly

I:
IV Q2-3 hours x weeks 0,2,6→continuous IV Q8 hours

A:
week 1-2→SQ
week 3+→SQ x 2 weeks

CL-P:
SQ biweekly

can be used with topicals/phototherapy

AE:
E: injection site reaction
headache
URI
GI sx

severe: hep b reactivation
CHF+worsening

I: hemolytic abnormalities
hepatotoxicity
hypersensitivity
eye toxicity
CHF+worsening

A: hemolytic abnormalities
injection site rxn (itchy rash)

CL-P: URI
rash
UTI

DX: baseline
TB PPD x yearly
CBC x periodic
LFT

BB: serious infections
lymphoma malignancy
lupus
demyelinating disorders
give live vaccines before tx

IL-12+23 Inhibitors

MX: ustekinumab

MOA: selectively targets IL-12+23

I: psoriasis inflammation
12+ y/o

ROA: SQ x weeks 0,4+ Q every 12 weeks after

AE:
URI
headaches
fatigue

serious:
serious infxns
malignancies
RPLS

IL-17 Inhibitors

MX: ixekizumab
secukinumab
brodalumab

MOA: inhibits IL-17→blocks pro-inflammatory cytokines+chemokines

I: psoriasis
I→6+ y/o

ROA:
I:
SQ x weeks 0,2,4,6,8,10,12
weeks 13+→SQ q4 weeks

S:
SQ x weeks 0-4
weeks 5+→SQ q4 weeks

B:
SQ x weeks 0-2
weeks q2 weeks

AE:
I: injection site rxn
URI
nausea
tinea infxns

S: nasopharyngitis
diarrhea
URI

B: arthralgia
headache
fatigue
diarrhea
oropharyngeal pain
nausea
myalgia
injection site rxn
influenza
neutropenia
tinea infxns

CI: inflammatory bowel disease

IL-17A+17F Inhibitors

MX: bimekizumab

MOA: inhibits IL-17A+17F from IL-23+23-independent sources→decreased psoriasis inflammation

I: adults
moderate-severe plaque psoriasis

ROA:
SQ x weeks 0,4,8,12,16
weeks 18+→SQ q8 weeks

120 kg+→weeks 16+→SQ q4 weeks

AE: nasopharyngitis
URI
injection site rxns
PO candidiasis

IL-23 Inhibitors

MX: tildrakizumab-asmn
risankizumab-rzaa
guselkumab

MOA: inhibits IL-23 receptor interaction→stops inflammation+immune response

ROA:
t-a:
SQ x weeks 0-4
weeks 5+→SQ q12 weeks

r-r:
SQ x weeks 0-4
weeks 5+→SQ q12 weeks

g:
SQ x weeks 0-4
weeks 5+→SQ q8 weeks

AE:
t-a: URI
injection site rxn
diarrhea

r-r: URI
headache
fatigue
injection site rxns
tinea infxn

g: URI
headache
injection site rxns
arthralgia
bronchitis
diarrhea
gastroenteritis
tinea infxns
HSV infxns

ACNE NP TX

avoid aggravation (touching w. fingers)

decrease stress

wash x 2-3 per day

good shaving

UV light

avoid harsh drying cleansers

Acne MX TX Options

OTC:

• benzoyl peroxide

• salicylic acid

• differin

RX:

• retinoid

• abx

• other topicals

Acne MX TX Algorithm

mild:

1st line:

• topical BPO+ topical retinoid

• combination recommended

alternative:

• add topical retinoid/topical BPO

• switch to retinoid/topical dapsone

moderate:

1st line:

• topical combination

• PO abx+topical BPO+topical retinoid

• ± topical abx

alternative:

• another combination

• switch PO abx

• add OCP combo/spironolactone (female only)/PO isotretinoin

severe:

1st line:

• topical+PO abx

• PO isotretinoin

alternative:

• PO abx

• add combined OCP/spironolactone (no females)/PO isotretinoin (if not tried)

Benzoyl Peroxide (BPO)

MX: OTC agent
Rx agent

MOA: increases epithelial cells sloughing rate→loosens follicular plug+comedolytic+bactericidal to c. acnes

I: C. acnes
acne

ROA:
1st week→daily
weeks 2+→BID
start with 2.5-5%→avoids skin irritations

AE: drying
erythema
peeling
bleached hair
bleached clothing
photosensitivity→burns easier

Salicylic Acid

MX: OTC agent
Mx pads

MOA: increases epithelial cell sloughing rate→loosens follicular plug

I: acne

AE: drying
erythema
peeling

Topical Retinoids

MX: Rx tretinoin
OTC adapalene

MOA: vitamin A derivatives
decreases adherence of keratinocytes (outer skin cells) in oil gland
4-12 weeks for tx to work
worsens sx initially

I: acne

ROA: daily HS (at night)
~20 minutes post washing face→don’t wash off until morning
irritation→lower strength/every other night+use non-comedogenic moisturizer

AE: burning
stinging
dryness
scaling
photosensitivity

CI: salicylic acid scrubs→worsens irritation
mild soap BID only
pregnancy

Azelaic Acid

MX: OTC
Rx

MOA: increases epithelial cell sloughing rate→loosens follicular plug

I: acne

ROA:
1st week→daily
weeks 2+→BID

AE: drying
erythema
peeling

Topical Antibiotics

MX: clindamycin
erythromycin
dapsone
+benozyl peroxide

MOA: inhibits bacterial protein synthesis
2-6 weeks for tx to work→12 weeks for full tx benefit

I: C. acnes

ROA: daily/BID
don’t use as monotherapy

AE: dryness
burning
itching
peeling
erythema

Oral Antibiotics

MX:
1st line→doxycycline
2nd line: bactrim
erythromycin

MOA: decreases C. acnes→inhibits bacterial lipases→suppresses neutrophils→decreases inflammation

I: C. acnes

ROA: PO x daily/BID
don’t use as monotherapy

AE: photosensitivity
rash
dizziness
diarrhea

CI: tetracyclines+pregnancy→fetal dmg
long term use

Oral Retinoic Acid Derivatives

MX: PO isotretinoin (acutane)

MOA: vitamin A derivative
inhibits sebum synthesis→decreases C. acnes concentration→decreases inflammation+comedolytic effects

I: C. acnes

ROA: PO BID

Black Box: birth defect
increased aggressive behavior

DX:
baseline: CBC
LFT
lipid panel
female→monthly pregnancy tests
iPledge registration

AE: dry eyes
decreased night vision
dry skin
chapped lips
triglyceride increase
blood glucose increase
liver enzymes changes
arthralgias
osteoporosis
psych sx

CI: teens before puberty ends
pregnancy

PO Contraceptives

MX: hormonal agents

MOA: inhibits androgen production→decreases androgens in sebaceous glands
3 months for tx to be apparent→6 months for maximum efficiency

I: C. acnes

ROA: PO daily

AE: nausea
vomit
headache
weight gain
breast tenderness
thromboembolic risk

Spironolactone

MX: hormonal agents

MOA: aldosterone receptor antagonist
antiandrogen effects
3 months tx apparent→6 months maximum tx efficacy

I: C. acnes
females+hormonal acne on jawline

ROA: PO x daily+titration

AE: hyperkalemia
dry mouth
dizziness

Acne Maintenance TX/Follow-Up

follow up→ 3-4 months after starting tx

PO abx→6-12 weeks

topical acne:
indefinite/forever use
preferred long-term mx

relapse→re-initiate tx with previous regimen/at least some of its elements

Sunburn Prophylaxis

stay out of sun when it’s strong (10AM-4PM)

wear protective clothing

broad-spectrum sunscreen:
where skin is exposed
UVA→aging+SQ damage
UVB→burning

pt education:

abx:
-ciprofloxacin
-dapsone
-tetracyclines

hydroxychloroquine
furosemide
NSAIDS
retinoids

Sunscreen

MX:
ingredients:

• avobenzone

• cinoxate

• ecamsule

• menthyl anthranilate

• octyl salicylate

• oxybenzone

• sulisobenzone

I: sunburn prophylaxis

AAD recommendations:

• minimum SPF 30

• apply liberally q2 hours

• reapply after swimming/sweating

Sun Protection Factor (SPF)

a measure of how well sunscreen deflects UVB rays

TTB (with sunscreen in minutes)=SPF x TTB (without sunscreen)

how SPF works:

• 10 minutes→SPF of 5→50 (10×5=50)

• intensity of the sun varies during day

• sunscreen doesn’t last more than a couple of hours

Sunburn Supportive Care TX

cool baths+showers

aloe vera/soy moisturizer

inflammation/pain→aspirin/ibuprofen

drink extra water

blisters→allow blisters to heal+don’t pop

protect sunburned skin