Plaque Psoriasis Study Guide

Introduction to Psoriasis and Pathophysiology

• Definition: Psoriasis is a chronic, progressive, T-lymphocyte-mediated systemic inflammatory disease characterized by periods of exacerbations and remissions.

• Pathogenesis: It is considered an autoimmune disease resulting from accelerated epidermal proliferation.

• Clinical Forms:

  • Plaque Psoriasis: The most common form.

  • Guttate Psoriasis: Characterized by numerous erythematous scaling papules.

Clinical Presentation of Plaque Psoriasis

• Symptoms and Lesion Characteristics:

  • Plaques: Well-demarcated, light pink to bright red or maroon in color.

  • Scales: Overlying the plaques are opaque, thick, adherent white scales that can be pulled off in layers.

  • Auspitz Sign: When the scale is lifted from the base, the lesion bleeds.

  • Progression: Lesions start as smaller papules that eventually coalesce to form larger plaques.

• Common Locations:

  • Extensor surfaces of the elbow and knee.

  • Lumbar region of the back.

  • Scalp.

  • Posterior auricular area.

• Aggravating Factors and Triggers:

  • Environmental: Physical injury, UV exposure, or chemical injury.

  • Infections.

  • Medications: Beta blockers, Lithium, Antimalarials, Indomethacin, Quinidine, and withdrawal from systemic steroids.

  • Lifestyle & Stress: Stress, obesity, alcohol use, and tobacco use.

  • Physiological: Endocrine and hormonal changes.

• Coexisting Conditions: Frequently associated with obesity, metabolic disorders, and other immune-mediated disorders such as Crohn’s disease and Multiple Sclerosis (MS).

Goals of Treatment and Self-Care Exclusions

• General Goals: Minimize and control symptoms. Note that there is currently no cure for psoriasis.

• Self-Care Limitations: Self-care has a limited role. Most patients require professional referral.

• Exclusions to Self-Care (Referral Required):

  • Age: Children < 2 years of age.

  • Severity: Psoriasis involving > 5\% Body Surface Area (BSA).

  • Treatment Failure: Worsening of the condition or no improvement after $2$ weeks of proper OTC medication use.

Grading Psoriasis Severity

• Mild: < 5\% BSA.

• Moderate: PASI (Psoriasis Area and Severity Index) score > 8.

• Severe: Defined by the "Rule of Tens": PASI > 10 or BSA > 10\%.

Topical Agents: Pharmacologic Categories and Details

Topical Corticosteroids (TCS)

• Role: First-line option for mild-to-moderate psoriasis.

• Mechanism of Action (MOA): Anti-inflammatory, anti-proliferative, immunosuppressive, and vasoconstrictive.

• Adverse Effects (ADRs):

  • Cutaneous: Acne, skin atrophy, striae (stretch marks), dermatitis, telangiectasias (spider veins), hair growth or loss, and pigment changes.

  • Systemic (risk increases with high BSA, thin skin, high potency, or long duration): HPA axis suppression, growth suppression in children, glaucoma, cataracts, and osteoporosis.

• Clinical Management: Taper use to minimize tachyphylaxis and prevent rebound flares.

Vitamin D Analogs (VDA)

• First-line Option: Bind to Vitamin D receptors to inhibit keratinocyte proliferation and enhance differentiation; also immunosuppressive.

• Agents:

  • Calcipotriene (Calcipotriol): Brand names Dovonex, Sorilux (foam). Dosing: Apply once to BID.

  • Calcitriol: Brand name Vectical. Dosing: Apply once to BID.

• Efficacy: Comparable to all but very high potency TCS.

• Pros: Fewer long-term ADRs than TCS; can be used on face and skin folds (Calcipotriol is often better tolerated in sensitive areas).

• Cons: Slower onset than TCS, expensive, photosensitizing, risk of hypercalcemia, contraindicated in pregnancy, and avoid in renal dysfunction. Local irritation (stinging, burning, peeling) is common.

Topical Retinoids

• Agent: Tazarotene (Tazorac).

• Dosing: Apply once daily; start at $0.05\%$ and titrate to $0.1\%$.

• Efficacy: Extended response; efficacy can be maintained for $12$ weeks after discontinuation.

• Note: Often used with moisturizers to reduce irritation. Cannot be used on skin folds or genitals. Contraindicated in pregnancy.

Aryl Hydrocarbon Receptor (AhR) Agonist

• Agent: Tapinarof (Vtama)

• Usage: Once daily application; can be used anywhere except eyes or intravaginally.

• ADRs: Folliculitis, contact dermatitis, headache, and pruritus. High cost.

Phosphodiesterase 4 (PDE4) Inhibitors

• Agent: Roflumilast (Zoryve).

• Usage: Once daily; suitable for intertriginous areas (skin folds).

• ADRs: Pain at application site, nausea, diarrhea, insomnia, and headache.

• Interactions: Potential CYP 3A4 interactions; contraindicated in moderate-to-severe liver impairment.

Other Topicals (Cytostatics and Keratolytics)

• Coal Tar (Neutrogena T-Gel): Cytostatic/Cytotoxic; targets AhR. Inexpensive but stains hair/skin and has a strong odor. Can cause folliculitis and photosensitivity.

• Salicylic Acid: Keratolytic; loosens keratin aggregates to remove scales. Used in combinations to increase the penetration of other topicals. Can cause salicylism (tinnitus).

• Anthralin (Dritho-Crme, Zithranol): Second-line. Short Term Anthralin Therapy (SCAT) is preferred to minimize severe irritation. Use zinc oxide or petrolatum to protect surrounding healthy skin.

• Calcineurin Inhibitors (TCI): Tacrolimus and Pimecrolimus. Used off-label for maintenance on the face, genitals, or skin folds to avoid steroid atrophy.

Topical Steroid Potency Classification

• Very High Potency (Superpotent):

  • Clobetasol propionate (Temovate).

  • Halobetasol propionate (Ultravate).

  • Betamethasone dipropionate (Diprolene).

  • Usage Restrictions: Max duration $2$ to $4$ weeks; max quantity $50\,gm$ per week. Do not use with occlusion or on skin folds/face.

• High Potency:

  • Amcinonide (Cyclocort).

  • Fluocinonide (Lidex).

  • Halocinonide (Halog).

  • Diflorasone diacetate (Psorcon).

• Medium/Mid-Potency:

  • Betamethasone valerate (Valisone).

  • Fluticasone propionate (Cutivate).

  • Hydrocortisone valerate (Westcort).

  • Mometasone furoate (Elocon).

  • Triamcinolone acetonide (Kenalog).

• Low Potency:

  • Aclometasone (Aclovate).

  • Desonide (DesOwen).

  • Fluocinolone acetonide (Synalar).

  • Hydrocortisone (OTC: Cortizone, Cortaid; Rx: Hytone).

Selection of Dosage Forms

• Ointment: Occlusive, greasy, thick. Best for thick plaques and lichenified areas. Not for skin folds.

• Cream: Can be rubbed in. Suitable for face and skin folds.

• Gel: Alcohol or water-based. Good for oily skin; leaves less residue.

• Foam/Lotion/Solution: Thinner consistency; ideal for hairy areas (scalp).

• Spray: Useful for hard-to-reach areas; propellants may sting.

• Shampoo: Contains surfactants; used for scalp involvement.

• Tape: Embedded with medication; occlusive, which increases drug potency.

• Fingertip Method: Utilized to determine the specific quantity of topical medication to dispense based on the area covered.

Systemic Pharmacotherapy (Oral Agents)

• Generally used as second-line for moderate and first-line for severe psoriasis.

Biological Therapies

• General Features: Very effective; suitable for Psoriatic Arthritis (PsA); Parenteral (mostly SQ, Remicade is IV); High cost.

• General Warnings: Increased risk of infections (TB screening required); No live vaccines; Potential malignancy risk.

TNF-Alpha Blockers

• Agents: Infliximab (Remicade - IV), Adalimumab (Humira), Etanercept (Enbrel), Certolizumab pegol (Cimzia), Golimumab (Simponi - indicated for PsA).

• Specific Warnings: Worsening of autoimmune diseases (Lupus, MS), heart failure (CHF) exacerbation, and liver toxicity (highest with Infliximab).

IL-12/23 & IL-17A Inhibitors

• IL-12/23: Ustekinumab (Stelara). Risk of infection and malignancy.

• IL-17A: Secukinumab (Cosentyx), Ixekizumab (Taltz), Brodalumab (Siliq), Bimekizumab (Bimzelx).

  • Secukinumab/Ixekizumab: Faster onset; risks of neutropenia and IBD flares.

  • Brodalumab (Siliq): REMS for suicidal ideation/behavior.

IL-23 Inhibitors

• Agents: Guselkumab (Tremfya), Tildrakizumab (Ilumya), Risankizumab (Skyrizi).

• Novel Oral Agent: Icotrokinra (Icotyde).

• Characteristics: Lower infection risk; warning for elevated liver enzymes.

Treatment Algorithms

• Mild-Moderate:

  1. Topical Agents (TCS, VDAs, Tazarotene).

  2. If inadequate: Alternative topical $\pm$ Phototherapy.

  3. If inadequate: Topical + Systemic agent.

• Moderate-Severe:

  • Moderate: Start with topical; add/switch to systemic if inadequate. Consider biologic if PsA present.

  • Severe: Start with systemic agent or biologic (especially if PsA). If inadequate response, use biologic $\pm$ other agents.

Non-Pharmacologic and Lifestyle Management

• Emollients: Moisturize frequently (Urea and Ammonium Lactate are very helpful).

• Diet: Weight reduction (hypocaloric diet) for obese patients; Mediterranean diet (fruits, veggies, whole grains, healthy fats) may assist.

• Supplementation: Vitamin D if deficient.

• Avoidance: Eliminate exacerbating factors and triggers.

Questions & Discussion

• Q: Are psoriatic plaques always itchy?

  • Implicit Answer: Symptoms vary; while plaques are well-demarcated and scaly, itchiness is common but not the only defining symptom.

• Q: Can psoriasis be cured?

  • No, it is a chronic condition with no current cure.

• Q: Do patients with severe psoriasis have an increased mortality rate?

  • Yes, systemic inflammation is linked to increased cardiovascular risks and other comorbidities.

• Q: Which medications require lab monitoring?

  • Methotrexate (CBC, LFTs), Cyclosporine (Renal/SCr, BP, TGs), Acitretin (TGs, LFTs).

• Q: Which are contraindicated in pregnancy?

  • Methotrexate, Tazarotene, Acitretin (REMS requirement), Vitamin D Analogs.