Psoriasis (Plaque Psoriasis Emphasis)

Psoriasis is a chronic, immune-mediated disease characterized by well-demarcated, erythematous plaques with silvery scale, driven primarily by the IL-23/Th17 axis. It affects skin, nails, scalp, intertriginous areas, and may involve joints (psoriatic arthritis). Management depends on severity, distribution, comorbidities, and patient preference, with options spanning topical agents, phototherapy, conventional systemic drugs, targeted biologics, and small-molecule inhibitors.

Epidemiology

• Global prevalence ~2–3%; variable by ethnicity and geography.
• Onset peaks in early adulthood and again later in life; positive family history in ~30%.
• Comorbidities: psoriatic arthritis (up to 30%), metabolic syndrome, obesity, NAFLD, cardiovascular disease, depression, inflammatory bowel disease.

Pathophysiology

• Genetic predisposition (HLA-Cw6 and others) plus environmental triggers (trauma/Koebner phenomenon, infections—especially streptococcal for guttate, medications, stress).
• Cytokine cascade dominated by IL-23, IL-17A/F, TNF-α; keratinocyte hyperproliferation and altered differentiation.

Clinical Features

• Plaque psoriasis: sharply demarcated erythematous plaques with micaceous scale on extensor surfaces, scalp, lumbosacral, umbilicus, and gluteal cleft.
• Variants: guttate, inverse (intertriginous), pustular (generalized or palmoplantar), erythrodermic.
• Nail disease: pitting, onycholysis, subungual hyperkeratosis, oil drop discoloration.
• Scalp involvement is common; can be refractory and socially disabling.

Severity Assessment

• Body surface area (BSA), PASI, PGA/IGA; consider DLQI for impact.
• Moderate-to-severe: generally BSA >10%, PASI >10, or significant involvement of face, scalp, hands, feet, genitals (special sites) regardless of BSA.

Differential Diagnosis

• Seborrheic dermatitis (overlap “sebopsoriasis”), tinea corporis (KOH to exclude), pityriasis rubra pilaris, nummular dermatitis, secondary syphilis, cutaneous T-cell lymphoma.

Diagnostic Workup

• Clinical diagnosis; biopsy if atypical.
• Screen for psoriatic arthritis (joint pain, morning stiffness, dactylitis, enthesitis).
• Baseline labs guided by treatment choice (e.g., for methotrexate, cyclosporine); TB, hepatitis B/C screening prior to biologics; HIV screening where indicated.

Management

1. Topical therapy (mild, or adjunctive)

• Corticosteroids by potency and site; consider weekend or pulse strategies to minimize tachyphylaxis.
• Vitamin D analogs (calcipotriol/calcitriol) often in combination with steroids; fixed-dose combinations improve efficacy.
• Keratolytics (salicylic acid) and tar preparations as adjuncts.
• Calcineurin inhibitors for inverse/facial psoriasis.
• For scalp: high-potency steroid solutions/foams, calcipotriol; medicated shampoos.

2. Phototherapy

• Narrowband UVB for widespread disease; excimer for localized plaques.
• PUVA less commonly used due to long-term risks/logistics.

3. Conventional systemic therapies

• Methotrexate (monitor CBC, LFTs; consider folate supplementation).
• Cyclosporine (short-term rescue; monitor BP/renal function).
• Acitretin (keratinization disorders or pustular psoriasis; teratogenic with prolonged contraception requirements).

4. Targeted biologics (moderate-to-severe)

• TNF inhibitors: adalimumab, infliximab, etanercept.
• IL-12/23 inhibitor: ustekinumab.
• IL-23 p19 inhibitors: guselkumab, risankizumab, tildrakizumab.
• IL-17 pathway: secukinumab, ixekizumab, brodalumab (monitor for neutropenia, Candida risk; suicidality warning for brodalumab).
• Selection considers comorbidities (e.g., IBD favors IL-12/23 or IL-23 blockade; recurrent Candida may avoid IL-17 blockade).

5. Small molecules

• Apremilast (PDE4 inhibitor): oral, modest efficacy, favorable safety; watch for GI effects, weight loss, mood changes.
• Deucravacitinib (TYK2 inhibitor): oral, effective for moderate-to-severe plaque psoriasis; monitor for acne, mild lab changes; favorable safety versus broader JAKs.

6. Special areas and subtypes

• Inverse/genital: low-potency steroids, calcineurin inhibitors; consider IL-17/IL-23 biologics for refractory.
• Nail psoriasis: intralesional steroids, topical calcipotriol/tacrolimus; systemic therapy often needed for significant nail disease.
• Pustular and erythrodermic: urgent evaluation; systemic therapy (e.g., IL-36 inhibitors emerging for GPP where approved), cyclosporine or infliximab for acute control.

7. Comorbidity and lifestyle management

• Weight optimization improves response; screen and manage cardiometabolic risk.
• Smoking cessation, alcohol moderation; mental health screening.
• Vaccinations up to date prior to immunosuppression.

Monitoring and Safety

• Regular labs based on agent; infection risk counseling; TB and hepatitis screening for biologics; pregnancy considerations (avoid methotrexate, acitretin; certain biologics have supportive pregnancy registry data).

References (recent guidelines and key reviews)

• AAD–NPF Joint Clinical Guidelines for Psoriasis Management, 2020–2024 updates.
• European S3 Guidelines on the Systemic Treatment of Psoriasis, 2023–2024.
• NPF/AAD guidance on special site disease and psoriatic arthritis screening, 2022–2024.
• Key RCTs and long-term safety data for IL-23, IL-17, and TYK2 inhibitors, 2021–2024.