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Psoriasis Flashcards

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1
Q

Describe a typical lesion of psoriasis

A

Sharply demarcated, Micaceous (silver) scale, erythematous plaques characterize the most common form of psoriasis; occasionally, sterile pustules are seen

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2
Q

Typical histologic findings (five total things) of Psoriasis

A
  1. Acanthosis with elongated rete ridges
  2. Hypogranulosis
  3. Hyper and Parakeratosis
  4. Dilated blood vessels
  5. Perivascular infiltrate of lymphocytes with neutrophils in the epidermis
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3
Q

Which HLA is most associated with Psoriasis

A

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

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4
Q

Aside from HLA-Cw6, which alleles variant is associated w/ psoriasis

A

ERAP1 (encodes for antigen presenting and processing)

HLA B13 and B17

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5
Q

Which APC is implicated in psoriatic lesions in the epidermis

A

Dendritic cells

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6
Q

Which Th1 cytokines early in the cascade are increased in psoriasis, is there any lower?

A

IFN-gamma and IL-2 are upregulated and IL-10 is decreased (anti-inflammatory)

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7
Q

Ustekinumab blocks what?

A

p40 subunit of Il-12 and 23, which helps with the cytokine pathway

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8
Q

In psoriasis, which cells produces IL-23, what does it normally stimulate

A

Dentritic cells/ macrophages/ keratinocytes

It stimulates Th17 cells to release IL-17 and 22 which proliferate keratinocytes and inflammation of the dermis

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9
Q

Name some roles of IFN-Gamma in psoriasis

  1. Released by
  2. Drives expression of
A

Released by Activated T cells/ NK T cells in epidermis
Drives STAT transcription factor family which increases immune related genes
Vasodilation

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10
Q

Typical lag-time of Koebner phenomenon ?

Which types of trauma

A

2-6 weeks after trauma

sunburn, morbilliform drug eruption, viral exanthem, trauma

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11
Q

Infections a/w psoriasis

A

Strep Pharyngitis

HIV

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12
Q

Endocrine disorder a/w psoriatic aggravation and which type of psoriasis is it a/w

A

Hypocalcemia triggers generalized pustular psoriais

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13
Q

Which drugs are commonly associated with psoriasis and what life factors

A

SIC LABS

Systemic steroids (rapid taper from)
IFNs
Cigarettes
Lithium
Antimalarials/ Alcohol
B-Blockers

OBESITY

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14
Q

Describe guttate psoriasis vs regular

bonus: pale blanching ring surrounding lesions?

A

guttate = widely disemminated paps and plaques vs. usually annular sharply demarcated erythematous papulosqaumous micaceous lesions

= Woronoff’s ring

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15
Q

What indicates an unstable phase of disease?

A

Pinpoint papules surrounding existing psoriatic plaques

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16
Q

Guttate psoriasis seen mostly in _____ and lab findings frequently have positive _____. ____ or ____ following a recent ___

A

adolescents, elevated antistreptolysin O, anti-DNase B or streptozyme titer after recent URI

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17
Q

classic findings in erythrodermic psoriasis include (3 things)

A

plaques in previous locations, facial sparing and characteristic nail changes

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18
Q

Five (bolognia) causes/ triggers of generalized pustular psoriasis

A

Pregnancy, rapid steroid taper (systemic therapies), hypocalcemia, infections and topical irritants

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19
Q

Generalized pustular psoriasis of pregnancy is aka __

A

Impetigo herpetiformis

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20
Q

What is seen here

A

von Zombusch pattern generalized pustular psoriasis

  • generalized eruption starting abruptly with erythema and pustulation
  • commonly causes illness/ fever in pt
  • relapsing/ remitting
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21
Q

What is seen here

A

Annular pattern pustular psoriasis

  • Eruption of annular lesions, erythema and scaling with pustulation at advancing edge
  • Healing occurs centrally
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22
Q

Pustulosis of the palms and soles patients typically have history of generalized pustular psoriasis but triggers include _____

This condition is associated with what syndrome

A

smoking, stress and infections

SAPHO syndrome - Synovitis, Acne, Pustulosis, Hyperostosis, osteitis

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23
Q

What is this condition called?

A

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
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24
Q

What is it called when psoriasis scales adhere to hair follicles in clumps?

A

Pityriasis amiantacea

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25
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
26
Risk factors for more severe psoriatic arthritis course include (5)
early age onset female polyarticular involvement genetic predisposition radiographic signs early on
27
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**
28
A type of psoriatic arthritis
29
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
30
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
31
Cronhs, ulcerative colitis, psoriasis all share an association with sacroiliitis and _____ positivity
HLA-B27
32
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
33
Erythrodermic causes
Sezary syndrome, Psoriasis, pityriasis rubra pilaris, drug reactions
34
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
35
Two pathognomonic findings histologically for both psoriasis and AGEP in early lesions
1. Accumulation of neutrophils within a spongiotic pustule (aka spongiform pustule of Kogoj) 1. Accumulation of neutrophil remnants in the stratum corneum surrounded by parakeratosis (microabscess of Munro)
36
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
37
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*
38
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
39
How does Anthralin work
Inhibits mitogen induced T lymphocyte proliferation and neutrophilic chemotaxis *Usually used inpatient*
40
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
41
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
42
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
43
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
44
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,
45
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*
46
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
47
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_**
48
Apremilast
Oral PD4 inhibitor that blocks cAMP degradation in immune cells (decreased activation)
49
Sequence of therapies after topicals for psoriasis
UVB, PUVA, MTX, acitretin, cyclosporine → biologics?
50
Th1 cells are stimulated by _____ and promote ____ cells to produce cytokines
Th1 cells stimulated by IL-12 and promote CD8 cytotoxic cells
51
CD8 T cells produce 5 cytokines important in psoriasis
IFN gamma, IL2, Il6, IL8, IL12
52
IFN gamma activates ____ cells to secrete two important cytokines
activates macrophages to secrete tnf Alpha and IL23
53
Th1 cells produce IL2 which generates two types of inflammatory cells
Cytotoxic T lymphocytes and NK cells
54
Th1 cells stimulate production of IL6 and IL8 which do \_\_\_\_
activate acute phase proteins and recruit neutrophils
55
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
56
IL17 and 22 increase what in psoriatic lesion pathway?
keratinocyte proliferation
57
Th2 cells are stimulated by which interleukin, what main cytokine do they release?
stimulated by IL4, release IL-10 which is anti inflammatory
58
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**
59
What is IFN-gammas role in psoriasis
Produced by CD8 T cells IFN-gamma activates macrophages to secrete IFN-alpha, IL-23
60
IL-2's role in psoriasis
generates CTL's and NK cells
61
IL-8 in psoriasis
recruits neutrophils
62
TH17 cells stimulated by \_\_\_\_\_
IL 12 and 23
63
TH17 cells, once stimulated produce\_\_\_\_
IL17, 22 and TNF-alpha
64
What are hBD 1-2 and Cathelicidin LL37?
Antimicrobial proteins released by keratinocytes in increased levels in psoriasis
65
Which HLA is most commonly associated with psoriatic arthritis patients?
HLA-B27 (50%)
66
PTICSS means what?
Collections of neutrophils within the stratum corneum Psoriasis Tinea Impetigo Candid Seborrheic Dermatitis Syphilis
67
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

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