Psoriasis Flashcards
Describe a typical lesion of psoriasis
Sharply demarcated, Micaceous (silver) scale, erythematous plaques characterize the most common form of psoriasis; occasionally, sterile pustules are seen
Typical histologic findings (five total things) of Psoriasis
- Acanthosis with elongated rete ridges
- Hypogranulosis
- Hyper and Parakeratosis
- Dilated blood vessels
- Perivascular infiltrate of lymphocytes with neutrophils in the epidermis
Which HLA is most associated with Psoriasis
HLA-Cw6, increased risk of 13 in caucasians and 25 in Japanese
- 90% of early onset patients had this HLA subtype
Type 1 psoriatic patients = those with Cw6 , early onset psoriasis and positive family history
Type 2 = None of the above but have psoriasis
Aside from HLA-Cw6, which alleles variant is associated w/ psoriasis
ERAP1 (encodes for antigen presenting and processing)
HLA B13 and B17
Which APC is implicated in psoriatic lesions in the epidermis
Dendritic cells
Which Th1 cytokines early in the cascade are increased in psoriasis, is there any lower?
IFN-gamma and IL-2 are upregulated and IL-10 is decreased (anti-inflammatory)
Ustekinumab blocks what?
p40 subunit of Il-12 and 23, which helps with the cytokine pathway
In psoriasis, which cells produces IL-23, what does it normally stimulate
Dentritic cells/ macrophages/ keratinocytes
It stimulates Th17 cells to release IL-17 and 22 which proliferate keratinocytes and inflammation of the dermis
Name some roles of IFN-Gamma in psoriasis
- Released by
- Drives expression of
Released by Activated T cells/ NK T cells in epidermis
Drives STAT transcription factor family which increases immune related genes
Vasodilation
Typical lag-time of Koebner phenomenon ?
Which types of trauma
2-6 weeks after trauma
sunburn, morbilliform drug eruption, viral exanthem, trauma
Infections a/w psoriasis
Strep Pharyngitis
HIV
Endocrine disorder a/w psoriatic aggravation and which type of psoriasis is it a/w
Hypocalcemia triggers generalized pustular psoriais
Which drugs are commonly associated with psoriasis and what life factors
SIC LABS
Systemic steroids (rapid taper from)
IFNs
Cigarettes
Lithium
Antimalarials/ Alcohol
B-Blockers
OBESITY
Describe guttate psoriasis vs regular
bonus: pale blanching ring surrounding lesions?
guttate = widely disemminated paps and plaques vs. usually annular sharply demarcated erythematous papulosqaumous micaceous lesions
= Woronoff’s ring
What indicates an unstable phase of disease?
Pinpoint papules surrounding existing psoriatic plaques
Guttate psoriasis seen mostly in _____ and lab findings frequently have positive _____. ____ or ____ following a recent ___
adolescents, elevated antistreptolysin O, anti-DNase B or streptozyme titer after recent URI
classic findings in erythrodermic psoriasis include (3 things)
plaques in previous locations, facial sparing and characteristic nail changes
Five (bolognia) causes/ triggers of generalized pustular psoriasis
Pregnancy, rapid steroid taper (systemic therapies), hypocalcemia, infections and topical irritants
Generalized pustular psoriasis of pregnancy is aka __
Impetigo herpetiformis
What is seen here
von Zombusch pattern generalized pustular psoriasis
- generalized eruption starting abruptly with erythema and pustulation
- commonly causes illness/ fever in pt
- relapsing/ remitting
What is seen here
Annular pattern pustular psoriasis
- Eruption of annular lesions, erythema and scaling with pustulation at advancing edge
- Healing occurs centrally
Pustulosis of the palms and soles patients typically have history of generalized pustular psoriasis but triggers include _____
This condition is associated with what syndrome
smoking, stress and infections
SAPHO syndrome - Synovitis, Acne, Pustulosis, Hyperostosis, osteitis
What is this condition called?
Acrodermatitis continua of Hallopeau
- Pustules on distal fingers/ sometimes toes
- Transition into other forms of psoriasis may occur, can cause annulus migrans of the tongue
What is it called when psoriasis scales adhere to hair follicles in clumps?
Pityriasis amiantacea
Describe lesion, what causes it?
Flexural psoriasis, shiny pink-red sharply demarcated thin plaques in the inframammary folds
- often a central fissure is seen
- when only flexural areas are involves, the term is known as inverse psoriasis
- triggers include : localized dermatophyte infections, candidal, bacterial infections
- when only flexural areas are involves, the term is known as inverse psoriasis
Risk factors for more severe psoriatic arthritis course include (5)
early age onset
female
polyarticular involvement
genetic predisposition
radiographic signs early on
Mono- asymmetic oligoarthritis psoriatic arthritis is characterized by
Most common type of Psoriatic arthritis
inflammation of DIP and PIP (may cause sausage digit)
may involve large joints
unlikely to involve MCP
A type of psoriatic arthritis
What is Sneddon-Wilkinson disease?
annular or polycyclic lesions in flexures with superficial (subcorneal) sterile pustules
this disease is AKA subocorneal pustular dermatosis
The cause of subcorneal pustular dermatosis is not known.
However, it is associated with some other conditions. The most frequent are:
IgA monoclonal gammopathy (accumulation of abnormal proteins in the blood)
Multiple myeloma
Pyoderma gangrenosum.
Treatment
Treatment is aimed at preventing complications. Dapsone is often successful, with the lesions resolving over a month. Ongoing maintenance with a lower dose is sometimes needed.
Other treatment options include:
Acitretin
Sulfapyridine or sulfamethoxypyridazine (not available in New Zealand)
Phototherapy including UVB and PUVA
Colchicine
Ciclosporin or other immune suppressants such as mycophenolate mofetil
Biological response mediators including infliximab and adalimumab
Which inflammatory cytokines may be the reason there is metabolic syndrome tendencies in psoriatic patients?
What other systemic conditions are frequently appreciated in psoriatic pts?
TNF-alpha and IL-6 which target adipocytes
Also CRP which increases CV risk
Non-Alcoholic steatohepatitis
Cronhs, ulcerative colitis, psoriasis all share an association with sacroiliitis and _____ positivity
HLA-B27
Common differentials with psoriaisis (for thought)
Seb Derm
Lichen simplex chronicus
Koebner phenomenon may cause psoriatic lesions at sites of contact derm
Consider SCC in-situ (Bowen’s disease, erythroplasia of Queyrat)
MF
Erythrodermic causes
Sezary syndrome, Psoriasis, pityriasis rubra pilaris, drug reactions
Histologically talk about some features of an early psoriatic lesion vs guttate lesions?
Initial lesions show superficial perivascular infiltrate of lymphocytes/ macrophages in the dermis with papillary edema and dilation of capillaries
- mild epidermal acanthosis, mild focal spongiosis
guttate lesions show mast cell degranulation
Two pathognomonic findings histologically for both psoriasis and AGEP in early lesions
- Accumulation of neutrophils within a spongiotic pustule (aka spongiform pustule of Kogoj)
- Accumulation of neutrophil remnants in the stratum corneum surrounded by parakeratosis (microabscess of Munro)
What is this and what are you seeing
A stable psoriatic lesion
Hyperplasia of the epidermis with squared off rete ridges (some coalescing at the base)
Elongation of dermal papillae
dilated superficial blood vessels
hypogranulosis
parakeratosis plus remnants of neutrophils
Which vehicle of corticosteroid has the best efficacy in psoriatic lesions and why
Ointment formulations have the highest efficacy by increasing lipophilicity via masking of hydrophilic 16 or 17- hydroxy groups or by introducing acetonides/ valerates or propionates
Bonus: occlusion enhances penetration
How do vitamin D analogues work in psoriatic plaques
During hyperproliferative epidermal phases: vit D3 analogues inhibit proliferation of epidermis, induces normal differentiation by enhancing cornified envelope formation and activate Transglutaminase
Also inhibit neutrophils
Calcipotriene
How does Anthralin work
Inhibits mitogen induced T lymphocyte proliferation and neutrophilic chemotaxis
Usually used inpatient
Tazarotene MOA and how it works in psoriasis
acetylene retinoid that selectively binds retinoic acid receptor RAR-B/ Y
Decreases epidermal proliferation, inhibits psoriasis associated differentiation
Can cause skin burning/ pruritus, erythema
combine with steroidal topicals
contraindications to phototherapy
>150-200 lifetime treatments
genetic predisposition to skin cancer
concurrent cyclosporine use
pregnancy
fitzpatrick type 1 skin
photosensitivie dermatoses
Vitiligo
immunosuppression
cataracts
impaired liver function
Contraindications to MTX
any severe cytopenia’s
liver abnormalities, severe alcohol use
kidney function impairments
TMP-SMX use
decreased lung function
pregnancy, trying to get pregnant
infections
peptic ulcers/ gastritis
Side effects of MTX
hepatic toxicity , pancytopenia, alopecia, oral erosions, rarely causes urticaria, angiodema, vasculitis
interstitial pneumonitis, birth defects
in RA pts, increases risk of lymphoma
cyclosporine MOA and risks of its use/ side effects
Contraindications?
calcineruin inhibitor, prevents t cell activation which prevents IL-2 cytokine activation
nephrotoxic effects (GFR, tubular atrophy), increased risk of SCC (due to decreased surveillance of the skin)
Max length of use 1 yr
Can cause hypertrichosis, GI discomfort, paresthesia, gingival hyperplasia, vertigo, tremor
Can cause hyperK, uric acid, hypoMG2+, elevated cholesterol/TGS
CI: kidney problems, HTN, malignancy hx, >200 PUVA treatments, immunodeficiency, pregnancy, MTX use, hepatic disease, hyperuricemia/ kalemia, sz disorder,
Acitretin
How long teratogenic?
side effects
Pre-use tests/ labs
1month -3yrs after use teratogenic!
SE’s : liver/ kidney abnrmlties, teratogenic, HLD/ TG’s, worsening of T2DM, pancreatitis, eye issues, atherosclerosis
Pre treatment: good pt HX, CBC, LFTs, serum TG/Cholesterol, glucose, Creatinine, pregnancy test,
during Tx: preg test 2x year, spine xray 1x, serum Creatinine, serum Tg/s LFTs every month for first 2-3 months then quarterly
maximum effect achieved after 2-3 months
Etanercept (Enbrel) , Infliximab (Remicade), Adalimumab (Humira) block ____
Ustekinumab (Stelara) blocks ___
Secukinumab (Cosentyx), Ixekizumab (Taltz), Brodalumab (Siliq) blocks ____
Guselkumab (Tremfya), Tildrakizumab (Ilumya), Risankizumab (Skyrizi) blocks ___
Etanercept (Enbrel) , Infliximab (Remicade), Adalimumab (Humira) block TNF-alpha
Ustekinumab (Stelara) blocks ILp40 subunit of IL-23
Secukinumab (Cosentyx), Ixekizumab (Taltz), Brodalumab (Siliq) blocks IL17 (Bordalumab blocks IL17 receptor)
Guselkumab (Tremfya), Tildrakizumab (Ilumya), Risankizumab (Skyrizi) blocks P19 subunit of IL23
Absolute contraindications to biologic therapy
Viral, bacterial or fungal infction
Increased risk of sepsis
active TB
- Selective for TNF-α inhibitors: Elevated ANA, autoimmune disease, CHF, demyelinization disorders*
- Selective for ustekinumab: BCG vaccine within last 12 months*
- Selective for secukinumab, ixekizumab, and brodalumab: Active Crohns*
For any:
Hx of Hep B, C, immunosuppressed, pregnancy, recent malignancy
Apremilast
Oral PD4 inhibitor that blocks cAMP degradation in immune cells (decreased activation)
Sequence of therapies after topicals for psoriasis
UVB, PUVA, MTX, acitretin, cyclosporine → biologics?
Th1 cells are stimulated by _____ and promote ____ cells to produce cytokines
Th1 cells stimulated by IL-12 and promote CD8 cytotoxic cells
CD8 T cells produce 5 cytokines important in psoriasis
IFN gamma, IL2, Il6, IL8, IL12
IFN gamma activates ____ cells to secrete two important cytokines
activates macrophages to secrete tnf Alpha and IL23
Th1 cells produce IL2 which generates two types of inflammatory cells
Cytotoxic T lymphocytes and NK cells
Th1 cells stimulate production of IL6 and IL8 which do ____
activate acute phase proteins and recruit neutrophils
Th17 cells are stimulated by which two cytokines?
Once activated what cytokines to Th17 cells release?
IL12 and 23 stimulate Th17 activation (Stelara/ Ustekinumab)
Th17 cells release IL 17, 22 and Tnf alpha
IL17 and 22 increase what in psoriatic lesion pathway?
keratinocyte proliferation
Th2 cells are stimulated by which interleukin, what main cytokine do they release?
stimulated by IL4, release IL-10 which is anti inflammatory
Th1 cells, stimulated by ____, promote ___ cells to produce which cytokines
TH1 stimulated by IL-12
Promotes CD8 T cell differentiation and production of IFN-gamma, IL 2, 6, 8 and 12
What is IFN-gammas role in psoriasis
Produced by CD8 T cells
IFN-gamma activates macrophages to secrete IFN-alpha, IL-23
IL-2’s role in psoriasis
generates CTL’s and NK cells
IL-8 in psoriasis
recruits neutrophils
TH17 cells stimulated by _____
IL 12 and 23
TH17 cells, once stimulated produce____
IL17, 22 and TNF-alpha
What are hBD 1-2 and Cathelicidin LL37?
Antimicrobial proteins released by keratinocytes in increased levels in psoriasis
Which HLA is most commonly associated with psoriatic arthritis patients?
HLA-B27 (50%)
PTICSS means what?
Collections of neutrophils within the stratum corneum
Psoriasis
Tinea
Impetigo
Candid
Seborrheic Dermatitis
Syphilis
What is the acronym for subcorneal pustules on histology?
CAT SIPS
Candida
Acropustulosis of Infancy
Transient neonatal pustular melanosis
Sneddon-Wilkinson
Impetigo
Pustular Psoriasis
Staph scalded-skin syndrome
