(12/5) Babul Lecture: Psoriasis Psoriasis: The most common immune-modulated chronic inflammatory disease in NA and Europe

- Onset: Affects majority before age 40, there are 2 peak stages, 20-30 and 50-60. Males and females equally - Cx: T-lymphocyte mediated systemic inflammatory disease. Often risk + environmental influence to trigger an

abnormal immune response resulting in initial psoriatic skin lesions o Risk Factors: Genetic (36-91%, PSOR1 > HLA, TNFa, IL-23) o Influence: Injury to skin, infection, drugs, smoking/booze, obesity, stress

§ Drugs: Lithium, NSAIDs, HCQ/CQ, b-blockers, Fluoxetine, Roid withdrawal - Comorbidities: Psoriatic Arthritis (PsA – 30%), Metabolic Syndrome, CD, MS, Lymphoma/Melanoma - Types of Psoriasis:

o Guttate: Presents as dot-like lesions, most often triggered by strep infection or anti-malarials o Pustular: Blisters of non-infectious pustules surrounded by red skin. (Pus = WBC). Triggered by light o Inverse: Red lesions in the body folds (behind

knee, groin) o Erythrodermic: Very severe fiery redness, itchy and

HRÝ, TÝß. May be due to severe sunburn, booze o Plaque Psoriasis (Psoriasis vulgaris): The

concentration of this lecture, affecting 90% of Psoriasis pt.

Psoriasis vulgaris: - Clinical Presentation: Erythematous, well-

demarcated plaque lesions covered by silver flaking scales. Appear on the scalp, knees, elbows, and lower back. Sometimes there is nail involvement (psoriatic onychodystrophy)

- Dx: There is no laboratory tests, just identified by characteristic psoriatic lesions, classify as mild/mod/severe - Tx: Mild-Moderate Patients are to use moisturizers throughout therapy, at lowest effective dose. 80% of

patients have mild-moderate disease, and thus the majority can be treated with topicals (standard of care) alone o Step 1: Topical Agents o Step 2: Topicals + Phototherapy o Step 3: Topicals + Systemic agent

- Tx: Moderate-Severe Patients are to use moisturizers throughout therapy, at lowest effective dose. o Step 1: Systemic Agent ± Topical ± Phototherapy (+BRM if comorbidities, ie: Kidney or Liver disease) o Step 2: More potent Systemic Agent, or 2 systemic agents in rotation ± Topical o Step 3: Biological Response Modifier (BRM) ± other agents.

Non-Pharmacologic Therapy - Stress reduction strategies, moisturizers, oatmeal baths, skin protection (SPF 30+), avoid bad soaps

Pharmacologic Therapy - Topicals – Standard for mild-moderate

o Corticosteroids: Mainstay of therapy, though patient adherence may be the largest barrier § MoA: Bind to intracellular corticoid receptors and regulate gene transcription, providing anti-

inflammatory, anti-proliferative, immunosuppressive, vasoconstrictive effects § Formulation: Ointment (thicker, stick better, more potent), Cream/Lotion (people like,less greasy) § Potency: Drug depends on severity, location, and age. Once receiving a clinical response, the

dose should be gradually reduced, though no tapering regimens have been established. 7 classes • Potency Class I: Superpotent ~ Clobetasol, Halobetasol, Betamethasone • Potency Class VII: Least potent ~ Hydrocortisone • Low Potency: Infants, Face, intertriginous areas è Hydrocortisone 1% • Mid-High Potency: Adults, Scalps, other areas è Clobetasol 0.05% foam/wash/spray • Highest Potency: Thick plaques on thick skin (palms/soles)è Clobetasol/Betamethasone

§ Dosing: Pulse Dosing- Heavy doses upon initiation, lowered slowly, then d/c. Helps minimize tachyphylaxis (acute sudden reduction in response to medication)

o Vitamin D3 analog: Considered the Safest long-term topical treatment, though more expensive § Product: Calcipotriol (Calcipotriene) cream. § MoA: Bind to Vitamin D receptors, resulting in inhibition of keratinocyte proliferation and

enhancement of keratinocyte differentiation. Also inhibits T-lymphocyte activity. § AE: Product may be inactivated by UVA light, so apply after UVA exposure (after phototherapy)

o Retinoids: Quite effective at clearing psoriatic plaque lesions and achieving remission § Product: Tazarotene 0.1%/0.5% cream/gel – Use once daily § MoA: Normalize abnormal keratinocyte differentiation, diminish hyperproliferation, and clear

inflammatory infiltrate in the psoriatic plaque. § Pregnancy category X – do not use in women of child-bearing age unless on contraception § AE: High incidence of irritation at application site. Burn, sting, itch

o Salicyclic Acid: This product enhances steroid penetration and thus efficacy § Indication: Scalp Psoriasis (shampoo or bath oil) § AVOID: Using in children, UVB phototherapy

o Calcineurin Inhibitors (CNI): Rarely used, unless specifically intertriginous areas (Inverse Psoriasis) § Product: Pimecrolimus (Elidel) and Tacrolimus § Less irritating than Calcipotriol and avoids steroid AE, though roid therapy is more effective. § Black box warning: These products may cause lymphoa or skin cancer (not proven)

- Phototherapies - These are administered by trained dermatologists o UVA: Treatment is known as PUVA (psoralen plus ultraviolet A photochemotherapy), requires co-

administration of a photosensitizer (psoralens) to enhance efficacy § This is the most efficacious phototherapy treatment.

o UVB: Given with crude coal tar or anthralin, though risk of carcinogenesis - Systemic Therapies – Standard for moderate-severe, use topicals as adjuncts

o Methotrexate (MTX): Gold-standard for oral systemic therapy, safer than CSA (unless liver disease) § Dosing: Can be used for years to decades with sustained benefits. NO BOOZING

• Monitor for cumulative liver toxicity, cough, N, fever. § ContraX: Pregnancy Category X. Avoid in liver disease pt

o Retinoids: Acetretin, with active metabolite etretinate § Place in Therapy: High dose monotherapy may have more rapid response than MTX

• Not recommended as low-dose monotherapy, recommended with phototherapy § Pregnancy Category X, unless using BC and willing to use it for 3 years post-treatment § Do not donate blood for 1 year. Don’t booze.

o CNI: Cyclosporine (CSA) § Effective in short-term therapy (<12w) – early d/c because nephrotoxicity risk § Discontinuation method: 1mg/kg/day each week to prolong relapse. Abrupt discontinuation has

shown dramatic rebound of psoriasis o PDE-4I: Apremilast (Otezla) Newest approved therapy, reduces cytokine production

§ Dosing: Increase dosage gradually over 5 days until reaching recommended dose (30mg BID) • Why? TOXICITY and Diarrhea (short-term)

- Systemic Biologic Response Modifiers (BRMs): Expensive! Modification of the immune response o Indication: Used in moderate-severe psoriasis when other systemics are inadequate or contraindicated o Live vaccines are contraindicated (Zostavax, MMR) o High Risk Assessment: Infection, Hepatotoxic, Cancer, Pregnancy

§ Monitor: ANC, LFT, TB test, COPD, CHF, GI perforation o Anti-TNFa: Adalimumab (SubQ), Etenercept (SubQ), Infliximab (IV infusion at MD)

§ Adalimumab (Humira): BBW: Infection, Lymphoma, Hepatosplenic T cell lymphoma § Eternercept (Enbrel): BBW: Infection

o Pharmacist Role: Ensuring access (PA), Refills, Education, Training Special Populations:

- Children: Topical treatment is standard of care, and first-line is topical corticosteroids - Pregnancy: Hormonal changes can improve Sx of psoriasis, beware Pregnancy Category X. Use BC. - Elderly: Increased risks of AE

Hey good luck. Apologies for the excess, I will be making a reduced version (hopefully), focused more on what I think will actually be exam material