Tx of Psoriasis and Acne

Question 1

What causes psoriasis?

Answer 1

A trigger causes recruitment of a number of inflammatory mediators including interferon-alpha, ILs, TNFa, and TGF-b. The net effect of this inflammatory process is recruitment of T cells, neutrophils, dendritic cells, and fibroblasts to the area and ultimately a proliferation of keratinocytes at the affected area

Question 2

What are some drugs available for psoriasis?

Answer 2

• Adalimumab
• Alefacept
• Etanercept
• Infliximab
• Ustekinumab
• Calcipotriene and Calcitriol

others

Question 3

How does Adalimumab work?

Answer 3

SC drug that acts as a TNFa monoclonal that binds TNFa and blocks its interactions with the p55 and p75 cell surface receptors

Question 4

How does Alefacept work?

Answer 4

IM recombinant human LFA-3/IgG1 fusion protein that binds to CD2 on memory effector T-cells, which prevents T-cell activation and promotes apoptosis

Question 5

How does Apremilast work?

Answer 5

PO drug that is a phosphodiesterase 4 inhibitor which increases cellular cAMP (consequences poorly understood)

Question 6

How does Etancercept (Enbrel) work?

Answer 6

SC drug that consists of the extracellular ligand-binding portion of human p75 TNF receptor linked to IgG FC that binds to TNF to inactivate it (but does not affect TNF production or serum levels)

Question 7

How does Infliximab work?

Answer 7

IV drug that is a chimeric (mouse-human) IgG1k monoclonal against TNFa to bind and neutralize both soluble and transmembrane TNFa

Question 8

How does Uztekinamab work?

Answer 8

Human IgG1-kappa monoclonal Ab that binds to the p40 subunits IL-12 and Il-23 for treatment of psoriasis

Question 9

How should patients be adviced when taking biologicals like etancercept or infliximab?

Answer 9

These drugs cause immunosuppression (dont initiate in a patient with active infection) and could potentiate infection (partiuclarly URI). Advise patients to report any signs/symptoms of infection and avoid live vaccines during use.

These can also increase the likelihood of malignancy

Question 10

AEs reported in biologicals like etancercept, infliximab, and adalimumab?

Answer 10

• CHF or hypotension/angina and LFT elevation (especially in Infliximab)
• lupus-like syndrome (myalgias, skin rashes, fatigue)
• injection site rxns in those injected SC or IM (adal, alefacept, etancercept)

Question 11

Another class of agents used to treat psoriasis (and some for acne) are the retinoids. How do they work?

Answer 11

Retinoids produce anti-inflammatory, anti-tumoral, and immunomodulatory effects and on the skin can stimulation keratinization and decrease sebum secretion and sebaceous gland size (isotretinoin)

Question 12

What malignancy are retinoids used for?

Answer 12

acute promyelocytic leukemia (act on the nuclear retinoid receptors (RXR/RARa)

Question 13

How do retinoids cause increased basal keratinocyte proliferation?

Answer 13

Topical application of a retinoid activates RXR/RAR heterodimers in suprabasal heratinocytes, causing activation of yet unidentified transcription factors. These, in turn, activate the synthesis of heparin-binding epidermal growth factor (HB-EGF) and amphiregulin (AR). Throguh activation of EGF-r, HB-EGR and AR cause keratinocte proliferation.

Question 14

Note about RAR/RXR receptors

Answer 14

Targeting RARs predominantly affects cellular differentiation and proliferation (i.e. tretinoin, adapalene, and tazarotene are primarily used in acne, psoriasis, and photoaging) while targeting RXRs predominantly induces apoptosis are better suited for tumor related use (Bexarotene and alitretinoin used in mycosis fungoides and Kaposi sarcoma)

Question 15

What are some of the toxicities of retinoids?

Answer 15

Acute toxicity resembles vitamin A toxicity including dry skin, nosebleeds, reduced night vision, and hair loss

ALL oral retinoids are potent teratogens

Question 16

What should be monitored if giving retinoids?

Answer 16

Baseline serum lipids, serum transaminases, CBC and a pregnancy test should be obtained prior to therapy

Question 17

What symptoms are more selective to RAR-selective retinoids?

Answer 17

mucocutaneous and musculoskeletal symptoms

Question 18

What symptoms are more selective to RXR-selective retinoids?

Answer 18

physiochemical changes

Question 19

What are the uses of topical retinoids?

Answer 19

These are 1st line agents for non-inflammatry (comedonal) acne (and can be used in combo for inflammatory acne) that work by correcting abnormal follicular keratinization, reducing P. acnes counts, and reducing inflammation

Also effective in reducing fine wrinkles and dyspigmentation associated with photoaging by inhibiting MMP activation via UV radiation and reducing keratinocyte atypia

Question 20

AEs of topical retinoids?

Answer 20

Erythema, desquamation, buring and stinging as well as icnreases suceptibility to sunburn

Question 21

How does Calcipotriene work for psoriasis treatment?

Answer 21

This is a topical agent that binds to vitamin D receptors and complexing with RXRa and binding DNA vitamin D response elements to modulate epidermal differentiations and inflammation, leading to improvement in psoriatic plaques

Question 22

AEs of Calcipotriene (Dovonex)?

Answer 22

1) Irritation when applied topically
2) Hypercalcemia and/or hypecalciuria at high doses that can present as GI disturbances, HTN, weight loss, muscle weakness, and polydipsia
2) Increased susceptibility to UV-induced skin cancer

Question 23

Alternative to Calcipotriene?

Answer 23

Calcitriol for sensitive areas of skin

Question 24

Corticosteroids are another treatment option for acne. How do they help?

Answer 24

They are commonly employed in inflammatory acne syndromes and are anti-pruritic and vasoconstrictive

the potency of these drugs are based on their ability to blanch skin

Question 25

How do corticosteroids work?

Answer 25

Cortisol binds to the cytoplasmic glucocorticoid receptor resulting in migration to the nucleus and anti-inflammatory properties then follow via several mechanisms including inactivation of NFkB

Question 26

Note that the effectiveness of corticosteroids varies based on conditions of skin involvement. What are some situations that are highly responsive to steroids?

Answer 26

• Intertriginous psoriasis
• atopic dermatitis
• Seborrheic dermatitis
• Intertrigo

Question 27

What are some situations that are not very responsive to steroids?

Answer 27

• psorasis of nails and palmo/plantar surfaces
• SLE
• pemphigus
• insect bites
• sarcoidosis

Question 28

Which areas of skin are assoicated with more systemic absorption than others?

Answer 28

scrotal skin > forehead > scalp > palm > forearm > plantar foot

Question 29

What are fluorinated steroids?

Answer 29

preparations that are designed for increased potency but should NOT be applied to the face for risk of rosacea-like skin rash that can be precipitated by various triggers including stress, menopause, and food allergies

Question 30

AEs of Topical Corticosteroid use?

Answer 30

• Iatrogenic Cushing’s syndrome with protracted use
• Dermal atrophy (cigarette paper appearing skin with tendency for purpura and ecchymosis) (below)
• Corticoid rosacea

others

Question 31

What is Benzoyl Peroxide?

Answer 31

Topical pro-drug for acne that is converted to benzoic acid and liberates free radicals that are lethal to propiobacterium acnes (the predominant organism in sebaceous follicles and comedones) that typically results in resolution of acen within 4-6 weeks.

Question 32

What is another noteworthy effect of Benzoyl Peroxide?

Question 33

T or F. Benzoyl Peroxide commonly bleaches hair or colored fabrics

Answer 33

T. Avoid contact with eyes and mucous membranes

Question 34

How does Salicyclic Acid work?

Answer 34

Topical keratolytic agent that causes desquamation of skin for hyperkeratonic skin disorders such as psoriasis, calluses, and acne

Question 35

AEs of Salicylic Acid?

Answer 35

May cause contact irritation and prolonged exposure over large areas, especially in childrens and patients with renal and heptic impairment may increase risk of salicyclism

Neonatal toxicity via breast milk and contact toxicity possible

Question 36

What are the symptoms of salicyclism?

Answer 36