Sweatman - Psoriasis Flashcards
1
Q
What is the underlying genesis of a psoriatic reaction?
A
- Involves a # of inflam mediators and signals, incl. INF-alpha, interleukins, TNF-alpha, TGF-beta, and other chemokines
- Net effect is the recruitment of T-cells, polys, dendritic cells, and fibroblasts
- Proliferation of keratinocytes and change in organization of the affected area
2
Q
Adalimumab
A
- SC TNF-alpha MAb
- MOA: binds TNF-alpha, blocking its interaction w/p55 and p75 cell surface receptors
-
AEs: INC susceptibility to malignancy and infection
1. CHF, or hypoTN/angina/dysrhythmia
2. Lupus-like syndrome
3. Pt counseling regarding injection site rotation for self-administration
3
Q
Alefacept
A
- IM recombinant human LFA-3/IgG1 fusion protein
- MOA: binds CD2 on memory effector T-cells, preventing activation; promotes apoptosis
-
AEs: INC susceptibility to infection and malignancy
1. Pt. counseling regarding rotation of injection site for self-admin
4
Q
Apremilast
A
- Only biologic PO
- Phosphodiesterase 4 (PDE4) INH
- MOA: INC cAMP, consequences poorly understood
- AEs: INC susceptibility to infection and malignancy
5
Q
Etanercept
A
- SC EC ligand-binding portion of human p75 TNF receptor linked to part of human IgG Fc (2:1 ratio p75:Fc)
-
MOA: endogenous p75 acts as TNF antagonist; as a recombinant TNFR p75 bound to Fc fragment of IgG, etanercept binds and inactivates TNF, but does NOT affect TNF production or serum levels
1. Decoy receptor: mimics INH effects of naturally occuring soluble TNF receptors, but much longer 1/2 life and more profound effect -
AEs: INC susceptibility to infection and malignancy
1. Lupus-like syndrome
2. Pt. counseling on rotation of injection site in self-admin
6
Q
Infliximab
A
- IV chimeric (mouse-human) IgG1k MAb against TNF-alpha
- MOA: binds to and neutralizes both soluble and transmembrane TNF-alpha
-
AEs: INC susceptibility to infection and malignancy
1. CHF, hypotension, angina, dysrhythmia (mod to severe heart failure a CONTRAINDICATION)
2. Lupus-like syndrome
3. LFTs
7
Q
Uztekinamab
A
- IV human IgG1-kappa MAb
- MOA: binds to p40 subunits of IL-12 and IL-23 cytokines
- AEs: INC susceptibility to infection and malignancy
1.
8
Q
What are the hallmarks AEs for biologic use in the treatment of psoriasis?
A
- Immunosuppression = INC susceptibility to fungal, bacterial, and parasitic infection
1. Some carry BBWs in this context: don’t initiate tx in pt with active infection
2. URIs could be esp problematic or occur more freq in asthma/COPD
3. Advise pts to REPORT SIGNS/SXS OF INFECTION or recurring infection (hepatitis, TB) during tx and for several mos thereafter
4. Avoid live vaccines during tx -
May increase likelihood of malignancy
1. Advise pt of INC risk of lymphoma and other malignancies, and to REPORT persistent fevers, night sweats, or significant weight loss
2. Reported in post-marketing studies with Adalimumab, Etanercept, and Infliximab
9
Q
What are some other AEs associated with the biologics used to tx psoriasis?
A
-
CHF, hypotension, angina, dysrhythmia: reported with Adalimumab, Infliximab, and Rituximab
1. Mod-severe heart failure a contraindication w/Infliximab - Lupus-like syndrome (arthralgias, myalgias, fatigue, skin rashes): most likely with Adalimumab, Etanercept, and Infliximab
- LFTs: Infliximab
- Pt counseling regarding site rotation for self-admin: Adalimumab, Alefacept, Etanercept
10
Q
What are the biologic functions of Vitamin A?
A
- Embryonic growth
- Morphogenesis
- Differentiation and maintenance of epithelial tissues
- Reproduction
- Visual function
11
Q
What are the effects of the retinoids?
A
- Moduleate epithelial cell populations, producing a net proliferation, skin keratinization, and some reduce sebum secretion/sebaceous gland activity
- Modulation of proliferation and differentiation
- INH of keratinization (CONTRADICTORY actions)
- Alterations of cellular cohesiveness
- DEC sebum production/sebaceous gland size (Isotretinoin)
- Immunologic/anti-inflammatory effects
- Tumor prevention and therapy
- Induction of apoptosis
- Effect on ECM components
12
Q
What is the molecular mechanism of retinoid-induced epidermal hyperplasia?
A
- Act on nuclear retinoid receptors (RXR/RAR) in suprabasal keratinocytes (heterodimers)
-
In psoriasis: binding of RXR/RAR modifies transcriptional activity of heparin-binding epidermal growth factor (HB-EGF) and amphiregulin (AR), which bind to their respective receptors
1. Binding of these signaling moieties cuases increase in basal keratinocyte proliferation, thickening epidermis and causing a flaking off of outermost skin layers (stratum corneum)
13
Q
What are the two families of retinoid receptors? In what conditions are they implicated? Drugs?
A
- Exact mech of retinoids in psoriasis UNCLEAR
- Both RAR and RXR families (isoforms alpha, beta, and gamma) have tissue-specific expression
1. Epidermis: RAR-alpha, gamma; RXR-alpha, beta - Targeting RARs predominantly affects cellular differentiation and proliferation
1. Tretinoin, adapalene, tazarotene used in acne, psoriasis, and photoaging (disorders of differentiation and proliferation) - Targeting RXRs predominantly induces apoptosis
1. Bexarotene and alitretinoin used in mycosis fungoides and Kaposi sarcoma
14
Q
Is RAR or RXR binding preferred for dermatologic retinoids?
A
RARs -> predominantly affect cellular differentiation and proliferation
15
Q
What are the systemic toxicities of the retinoids?
A
-
Acute toxicity similar to Vit. A intoxication
1. Dry skin, nosebleeds from dry mucous mem, conjunctivitis, DEC night vision, hair loss - Baseline serum lipids, LFTs, CBC, and pregnancy test should be obtained prior to therapy
1. Lipid elevation most comm lab abnormality - ALL retinoids are potent TERATOGENS
- Monitor isotretinoin pts for depression/suicidal ideation
- RAR-selective: mucocutaneous and MSK sxs
- RXR-selective: physiochemical changes
18
Q
What do GCS do in derm disease? How are they classified? Provide some examples.
A
- Anti-inflam, anti-pruritic, and vasoconstrictive
- INC production of anti-inflam lipocortins + DEC formation & relase of endogenous inflam mediators
1. PGs, kinins, histamine, liposal enzymes, complement - Topical GCS potency based on ability to produce cutaneous bleaching -> mild, moderate, potent, and very potent (docs get used to 1 or 2 drugs per category)
1. See chart for examples
23
Q
What steroids should not be used on the face? Why not?
A
- Fluorinated steroids: can cause rosacea-like skin rash around the mouth (can also be caused by other stressors like food allergies and menopause)
- SHOULD NOT be applied to face
- May give rise to AEs, like perioral dermatitis (see attached image)
- Fluorination INC steroid potency
24
Q
What are the topical AEs of the GCS?
A
- Iatrogenic Cushing’s syndrome w/protracted topical GCS use in lg quantities applied extensively
1. Adverse systemic effects in children, and growth retardation of particular concern in pediatric age group -
Dermal atrophy: shiny, often wrinkled “cigarette paper”-appearing skin w/prominent telangiectasias and tendency for purpura and ecchymosis
1. See attached image of steroid atrophy (chronic use of low-potency or as little as 2-3 wks of super-potent) - Corticoid rosacea: persistent erythema, telangiectatic vessels, pustules, and papules in central facial distribution
- Perioral dermatitis, steroid acne, alterations of cutaneous infections, hypopigmentation, hypertrichosis; INC intraocular pressure; and allergic contact dermatitis
