Ch. 8 - Psoriasis Flashcards
Prevalence of psoriasis
2%
What % patients with psoriasis develop arthritis
5-30%
When does psoriasis occur?
Any time, peaks are 2nd and 5th decade
Which HLA is most strongly associated with psoriasis?
HLA-Cw6
How many times risk increased if HLA Cw6
15x
What are the genomic regions associated with psoriasis? What chromosome? Which is more important?
PSOR1-PSOR9 region on chromosome 6
PSOR1 strongest (contains Cw6 region)
Name 5 HLA haplotypes associated with psoriasis
HLA CW6
HLA B27–> sacrolitis and PsA
HLA DR7
HLA B13 + HLA B17 : erythrodermic and guttate
HLA-B8, Bw35, Cw7, and DR3: pustular
Which T Helper cells are increased in psoriasis?
Th1
Th17
Th22
What are the Th1 cytokines
IFN-gamma, TNF, IL-2, IL-6, IL-8, IL-12
What cytokines stimulates production of Th1 cells ?
IL-12/IFN-gamma
What are the Th17 cytokines
IL-17A/17F
IL-22
TNF-alpha,
IL-23receptor–> perpetuate th17
IL-21–>perpetuate th17
What cytokines stimulate Th17 cells
Il-6,TGF-Beta primarily
IL-23, IL-21 further self amplify
What is an antimicrobial peptide seen increased in psoriasis
Cathelicidin LL37
What cytokine to plasmacytoid dendritic cells release to trigger dermal dendritic cells to migrate to lymph nodes
INF
What is the general explanation of psoriasis pathophysiology
Triggering event (stress, trauma, etc.) –> release of antigen (e.g. cathelicidin LL37 complexes with DNA/RNA) –> TLR-9/7 activated and causes plasma DC’s secrete INTERFERON to activate dermal DC’s–> dDCs to lymph node and present neo-antigen to naive T-cells:
1) DC’s secrete IL-12/IFN–> Th1 –> IL-2, TNF, INF–> macrophages
2) DC’s secrete IL-12/23–> Th17 –> IL-17A, 17F, IL-22 –> Neutrophils, proliferate
3) Some degree IL-4–> Th2 activation–> Macrophage M2 cells–> vEGF/angiogenesis
4) CD8+ cytotoxic cells with some Th1 and Th17 properties, move to epidermis (hence why epidermis mostly CD8)
What is the main T-cell type in epidermis? Dermis?
Epidermis CD8
Dermis CD4 and CD8
What is the name of neutrophils in stratum corneum? Stratum spinsosum?
Munroe microabcesses (corneum)
Spongiform pustules of Kojog
List 6 clinical variants of Psoriasis
- Plaque
- Inverse
- Pustular (multiple)
- Guttate
- Erythrodermic
- Special sites: Palmoplantar, scalp, nails, genitals, oral mucosa
List 5 potential triggers for psoriasis
SICK NAILS
Stress
Smoking, Alcohol, Obesity/Pregnancy
Infection-strep
HypoCalcemia
CD4+ disease -HIV
Koebner
NSAIDS
AntiHTN: ACEi, BB
Anti-malarials
Imiquimod
INF
Inflixmab/TNFs
Lithium
Steroids/CsA withdrawal
Other than direct cutaneous trauma, name 3 other ways the koebner phenomenon may elicit psoriasis
Sunburn
Drug eruption
Viral eruption
Which 3 sites in a patient with psoriasis are highly associated with psoriatic arthritis?
- Scalp
- Nails
- Gluteal cleft
+ psoriasis severity
List 10 histopathological features of psoriasis.
- Regular acanthosis
- Confluent parakeratosis
- Munroe’s micro abscesses (stratum corneum)
- Micro pustules of Kojog (stratum spinosum)
- Squirting papillae (neutrophils discharge from papillary capillaries)
- Thinning suprapapillary plates
- Dilated and tortuous capillaries in dermal papillae
- Elongation dermal papillae
- Superficial perivascular infiltrate w/ lymphocytes and macrophages
- Decreased or absent granular layer
- Elongated and squared off rete ridges
What are 10 cytokines that are elevated in Psoriasis?
IL-2, IFN
IL-17, IL-22, IL-23
IL-15
IL-1, IL-6, TNF-alpha
What does PASI stand for? What are its 3 main components? What is the maximum and minimum PASI score?
Psoriasis Area and Severity Index
Erythema, scale, thickness/induration
Minimum: 0, Max: 72
List 5 variants of Pustular Psoriasis.
- Generalized pustular psoriasis of von Zombusch
- Impetigo herpetiformis
- Annular psoriasis of LaPierre
Localized:
- Acrodermatitis continua of Hallopeau
- Acrodermatitis repens of Crocker
- Linear pustular psoriasis
- Pustular psoriasis of palms and soles
List 5 CLASSES of SYSTEMIC treatments for generalized psoriasis.
PDE-4 inhibitor (Apremilast)
Retinoids (Acitretin)
Immunosuppressants (MTX, Cyclosporine)
Biologics (TNF, 12/23, 23, 17)
JAK inhibitor (Tofacitinib)
Which cytokine elevation correlates with disease activity
IL-22
What is the auspitz sign
pinpoint bleeding when scale is removed
What is Woronoffs ring
psoriatic lesions are sometimes surrounded by a pale blanching ring
What are the main sites of psoriasis
Scalp
Periumbilical
Gluteal cleft/lumbosacral
Elbows
Knees
Hands/feet
What % psoriasis patients have genital involvement
up to 45%
How to tell genital psoriasis vs. atopic dermatitis
Involves the folds vs AD spares diaper area
Name 4 possible triggers for generalized psoriasis
Steroids withdrawl
Pregnancy
HypoCalcemia
Infections
Topical irritants-localized
How does palmar-plantar psoriasis present?
sterile pustules admixed with brown and yellow macula’s
What syndrome is palmar-plantar pustulosis associated with?
SAPHO
synovitis, acne, pustulosis, hyperostosis and osteitis
How does acrodermatitis continua of hallopeau present? How does it differ from acrodermatitis repent of Crocker?
Pustules on distal fingers, may replace nail plate or partial shed of nail plate
How does acrodermatitis continua of hallopeau present? How does it differ from acrodermatitis repent of Crocker?
Pustules on distal fingers, may replace nail plate or partial shed of nail plate
What is annulus migrans of the tongue? What psoriasis variants are associated?
Resembles geographic tongue, migratory annular erythematous lesions with hydrated white scale
Seen in arcodermatitis continua of hallopeau and generalized pustular psoriasis
Name 6 nail findings in psoriasis
Subungual hyperkeratosis
Oil spots
Onycholysis
Irregular pitting
Splinter hemorrhages
Total dystrophy of the nail
Leukonychia
What % patients with psoriasis have arthritis
5-30%
List 4 RF for more severe PsA course
initial presentation at an early age
female gender
polyarticular involvement
genetic predisposition
radiographic signs of the disease early on.
What are the 5 types of psoriatic arthritis
- Mono and oligoarthritis
- Spondylitis and sacroilitis
- RA-like
- Asymetric DIP
- Arthritis mutilans
What are the 5 types of psoriatic arthritis
- Mono and oligoarthritis
- Spondylitis and sacroilitis
- RA-like
- Asymetric DIP
- Arthritis mutilans
How does mono and oligarthritis PsA present?
DIP and PIP joints of the hands and feet
Often spares MCP
May have some larger joints
Most common form
Name 3 disorders related but distinct to psoriasis
Reactive arthritis
Sneddon-Wilkinson (subcorneal pustular dermatosis)-excellent response to dapsone and sub corneal > spongiform pustules
Inflammatory linear verrucous epidermal nevus
Name 6 diseases patients with psoriasis are at an increased risk for?
CV disease
Metabolic syndrome
HTN
Diabetes
NASH
IBD
What condition is associated with rupioid psoriasis
Hypothyroidism
Name 6 topical therapies for psoriasis
Topical steroids
Vitamin D analogues
Topical retinoids-Tazarotene
Anthralin (dithranol)
Topical tar/LCD
Salicyclic acid -scalp
Topical calcineurin inhbitors-face/flexures
Name 2 phototherapy options for psoriasis
nbUVB
PUVA
What % patients reach PASI 75 on MTX by 12-16 weeks
24-60% (low-high dose)
What % patients reach PASI 75 on MTX by 12-16 weeks
24-60% (low-high dose)
What PASI reduction is expected with cyclosporine at 4 weeks
60–70%
Other than the side effects, what is one drawback of CsA
Not effective for PsA
What non-biologic systemic therapy can be used for both PsA and PsO
MTX
Name 4 oral systemic treatments for psoriasis
MTX
Cyclosporine
Apremilast
Acitretin
Target dose for MTX?
25 mg po daily
Starting and target dose acitretin for plaque, erythrodermic and pustular?
Plaque-0.5mg/kg–> mild cheilitis
Erythrodermic- 0.25 mg/kg
Pustular- 1 mg/kg (max )
Which psoriasis variants is acitretin most effective for?
pustular
erythrodermic
Starting and target dose for CsA
3 mg/kg/day in divided doses–> 5 mg/kg/day in divided doses after 2 weeks
What % patients on apremilast achieve PASI 75
33%
What is the starting and target dosage for apremilast
10 mg po BID
30 mg po BID
Name 5 other non biologic systemic therapies (other than MTX/CsA/Acitretin/Apremilast)
Hydroxyurea
Fumarates
MMF
Oral calcitriol
6-Thioguanine
Name 5 other non biologic systemic therapies (other than MTX/CsA/Acitretin/Apremilast)
Hydroxyurea
Fumarates
MMF
Oral calcitriol
6-Thioguanine
Compare and contrast:
Calcitriol
Calcipotriol
Calcipotriene
Calcitriol=natural vitamin D
Calcipotriol and calcipotriene are the same, both vitamin D derivatives
Compare and contrast:
Calcitriol
Calcipotriol
Calcipotriene
Calcitriol=natural vitamin D
Calcipotriol and calcipotriene are the same, both vitamin D derivatives
Name 3 Vitamin D products for psoriasis
Dovonex (calcipotriene) ointment or
Dovobet (calcipotriol + betamethasone diprop) as an ointment
Enstilar (calcipotriene and betamethasone diproprionate) as a foam
What is the most efficacious topical product for psoriasis
Vitamin D3 + steroid>
High potency steroids>
Vitamin D analogues alone
Name 4 combinations that are more efficacious together than alone
ultra potent TCS + calcipotriene
CsA + calcipotriene
Acitretin + calcipotriene
PUVA + calcipotriene
Etanercept weekly + acitretin
Name 3 combination therapies that should not be used
Acitretin (inhibits cyP450) + CsA = risk accumulation CsA
CsA + PUVA = risk SCC
Coal tar + PUVA = phototoxic
Cautious with:
-MTX+ CsA
-MTX + Acitretin
What is systemic TOC in juvenile psoriasis
MTX
What is therapy of choice in juvenile psoriasis after MTX or CsA/acitretin
Etanercept
Systemic TOC in HIV+
Acitretin
Systemic TOC in liver disease
Biologic
(Can’t do CsA/MTX/acitretin)
Systemic TOC in Hep B or C infection +
Biologics
Etanercept> adalimumab>ustekinumab>secukinumab
Systemic TOC in patient with history internal malignancy
Retinoids
