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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
Q

Describe lesion, what causes it?

A

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
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26
Q

Risk factors for more severe psoriatic arthritis course include (5)

A

early age onset

female

polyarticular involvement

genetic predisposition

radiographic signs early on

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27
Q

Mono- asymmetic oligoarthritis psoriatic arthritis is characterized by

A

Most common type of Psoriatic arthritis

inflammation of DIP and PIP (may cause sausage digit)

may involve large joints

unlikely to involve MCP

28
Q

A type of psoriatic arthritis

A
29
Q

What is Sneddon-Wilkinson disease?

A

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
Q

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?

A

TNF-alpha and IL-6 which target adipocytes

Also CRP which increases CV risk

Non-Alcoholic steatohepatitis

31
Q

Cronhs, ulcerative colitis, psoriasis all share an association with sacroiliitis and _____ positivity

A

HLA-B27

32
Q

Common differentials with psoriaisis (for thought)

A

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
Q

Erythrodermic causes

A

Sezary syndrome, Psoriasis, pityriasis rubra pilaris, drug reactions

34
Q

Histologically talk about some features of an early psoriatic lesion vs guttate lesions?

A

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
Q

Two pathognomonic findings histologically for both psoriasis and AGEP in early lesions

A
  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
Q

What is this and what are you seeing

A

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
Q

Which vehicle of corticosteroid has the best efficacy in psoriatic lesions and why

A

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
Q

How do vitamin D analogues work in psoriatic plaques

A

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
Q

How does Anthralin work

A

Inhibits mitogen induced T lymphocyte proliferation and neutrophilic chemotaxis

Usually used inpatient

40
Q

Tazarotene MOA and how it works in psoriasis

A

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
Q

contraindications to phototherapy

A

>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
Q

Contraindications to MTX

A

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
Q

Side effects of MTX

A

hepatic toxicity , pancytopenia, alopecia, oral erosions, rarely causes urticaria, angiodema, vasculitis

interstitial pneumonitis, birth defects

in RA pts, increases risk of lymphoma

44
Q

cyclosporine MOA and risks of its use/ side effects

Contraindications?

A

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
Q

Acitretin

How long teratogenic?

side effects

Pre-use tests/ labs

A

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
Q

Etanercept (Enbrel) , Infliximab (Remicade), Adalimumab (Humira) block ____

Ustekinumab (Stelara) blocks ___

Secukinumab (Cosentyx), Ixekizumab (Taltz), Brodalumab (Siliq) blocks ____

Guselkumab (Tremfya), Tildrakizumab (Ilumya), Risankizumab (Skyrizi) blocks ___

A

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
Q

Absolute contraindications to biologic therapy

A

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
Q

Apremilast

A

Oral PD4 inhibitor that blocks cAMP degradation in immune cells (decreased activation)

49
Q

Sequence of therapies after topicals for psoriasis

A

UVB, PUVA, MTX, acitretin, cyclosporine → biologics?

50
Q

Th1 cells are stimulated by _____ and promote ____ cells to produce cytokines

A

Th1 cells stimulated by IL-12 and promote CD8 cytotoxic cells

51
Q

CD8 T cells produce 5 cytokines important in psoriasis

A

IFN gamma, IL2, Il6, IL8, IL12

52
Q

IFN gamma activates ____ cells to secrete two important cytokines

A

activates macrophages to secrete tnf Alpha and IL23

53
Q

Th1 cells produce IL2 which generates two types of inflammatory cells

A

Cytotoxic T lymphocytes and NK cells

54
Q

Th1 cells stimulate production of IL6 and IL8 which do ____

A

activate acute phase proteins and recruit neutrophils

55
Q

Th17 cells are stimulated by which two cytokines?

Once activated what cytokines to Th17 cells release?

A

IL12 and 23 stimulate Th17 activation (Stelara/ Ustekinumab)

Th17 cells release IL 17, 22 and Tnf alpha

56
Q

IL17 and 22 increase what in psoriatic lesion pathway?

A

keratinocyte proliferation

57
Q

Th2 cells are stimulated by which interleukin, what main cytokine do they release?

A

stimulated by IL4, release IL-10 which is anti inflammatory

58
Q

Th1 cells, stimulated by ____, promote ___ cells to produce which cytokines

A

TH1 stimulated by IL-12

Promotes CD8 T cell differentiation and production of IFN-gamma, IL 2, 6, 8 and 12

59
Q

What is IFN-gammas role in psoriasis

A

Produced by CD8 T cells

IFN-gamma activates macrophages to secrete IFN-alpha, IL-23

60
Q

IL-2’s role in psoriasis

A

generates CTL’s and NK cells

61
Q

IL-8 in psoriasis

A

recruits neutrophils

62
Q

TH17 cells stimulated by _____

A

IL 12 and 23

63
Q

TH17 cells, once stimulated produce____

A

IL17, 22 and TNF-alpha

64
Q

What are hBD 1-2 and Cathelicidin LL37?

A

Antimicrobial proteins released by keratinocytes in increased levels in psoriasis

65
Q

Which HLA is most commonly associated with psoriatic arthritis patients?

A

HLA-B27 (50%)

66
Q

PTICSS means what?

A

Collections of neutrophils within the stratum corneum

Psoriasis

Tinea

Impetigo

Candid

Seborrheic Dermatitis

Syphilis

67
Q

What is the acronym for subcorneal pustules on histology?

A

CAT SIPS

Candida

Acropustulosis of Infancy

Transient neonatal pustular melanosis

Sneddon-Wilkinson

Impetigo

Pustular Psoriasis

Staph scalded-skin syndrome

derm (14 decks)

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