Psoriasis

Psoriasis – High‑Yield Study Guide for Medical Students

Definition

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by well-demarcated, erythematous plaques with silvery-white scale, most commonly affecting extensor surfaces, scalp, and lumbosacral area. It is associated with systemic inflammation and multiple comorbidities, including psoriatic arthritis and cardiometabolic disease.

Epidemiology

Psoriasis is common worldwide and can present at any age, with two incidence peaks: early-onset (15–30 years) and late-onset (>50 years). Prevalence varies by geography and ethnicity.

• Global prevalence: ~2–3% of the population, higher in Western and Northern European populations.
• Sex: Affects males and females roughly equally.
• Age of onset: Type I (early onset, <40 years, strong HLA association); Type II (late onset, weaker genetic component).
• Family history: Positive in up to one-third of patients, supporting a strong genetic predisposition.
• Comorbidities: Psoriatic arthritis, obesity, metabolic syndrome, type 2 diabetes, dyslipidemia, hypertension, nonalcoholic fatty liver disease, anxiety and depression.

Pathophysiology

Psoriasis is driven by complex interactions between genetic susceptibility, environmental triggers, and immune dysregulation, resulting in keratinocyte hyperproliferation and chronic skin inflammation.

• Genetic factors: Strong association with HLA-Cw6 and loci within the PSORS (psoriasis susceptibility) regions. Family clustering is common.
• Innate and adaptive immunity: Activation of dendritic cells, macrophages, and T cells leads to production of proinflammatory cytokines.
• Key cytokine axes: IL-23/Th17 and TNF-α pathways are central. Th17 cells produce IL-17A, IL-17F, and IL-22, promoting keratinocyte proliferation and neutrophil recruitment.
• Keratinocyte changes: Markedly shortened epidermal turnover (from ~28 days to 3–5 days), parakeratosis, acanthosis, and impaired barrier function.
• Angiogenesis: Increased dermal vascularity contributes to erythema and Auspitz sign (pinpoint bleeding when scale is removed).
• Environmental triggers: Streptococcal infection (especially in guttate psoriasis), skin trauma (Koebner phenomenon), certain medications (e.g., β-blockers, lithium, antimalarials), stress, smoking, alcohol, and withdrawal of systemic corticosteroids.

Clinical Presentation

The classic picture is that of chronic, relapsing-remitting erythematous plaques with overlying scale. Clinical phenotypes and associated features are important for exams and practice.

Major Clinical Types

• Chronic plaque psoriasis (psoriasis vulgaris)
  • Most common type (~80–90%).
  • Well-demarcated, erythematous plaques with thick, silvery-white scale.
  • Typical sites: extensor surfaces (elbows, knees), lumbosacral region, scalp, umbilicus, gluteal cleft.
  • Auspitz sign: Pinpoint bleeding when adherent scale is removed.
  • Koebner phenomenon: New lesions at sites of skin trauma (e.g., scratches, surgical scars).
• Guttate psoriasis
  • Numerous small (<1 cm), droplet-like erythematous papules and plaques with fine scale.
  • Often acute onset in children or young adults.
  • Classically triggered by streptococcal pharyngitis 1–3 weeks prior.
  • May resolve or evolve into chronic plaque psoriasis.
• Pustular psoriasis
  • Generalized type (von Zumbusch): Widespread erythema and sheets of sterile pustules, often with systemic symptoms (fever, malaise). Potentially life-threatening.
  • Localized type: Palmoplantar pustulosis involving palms and soles, often in smokers.
• Erythrodermic psoriasis
  • Generalized erythema and scaling involving >90% of body surface area.
  • May be associated with systemic symptoms (fever, chills) and significant fluid/electrolyte and thermoregulatory disturbances.
  • Represents a dermatologic emergency.
• Inverse (flexural) psoriasis
  • Well-demarcated, erythematous, shiny plaques with minimal scale in intertriginous areas (axillae, inframammary folds, inguinal/perineal regions).
  • Often misdiagnosed as candidal intertrigo or tinea.
• Nail psoriasis
  • Common in patients with psoriatic arthritis.
  • Findings: pitting, onycholysis (distal nail plate separation), subungual hyperkeratosis, “oil drop” (salmon patch) discoloration, nail crumbling.

Psoriatic Arthritis (PsA)

Psoriatic arthritis is a chronic inflammatory arthropathy associated with psoriasis, typically seronegative for rheumatoid factor.

• Occurs in up to 20–30% of patients with cutaneous psoriasis.
• Patterns include asymmetric oligoarthritis, symmetric polyarthritis, distal interphalangeal (DIP) predominant disease, spondylitis, and arthritis mutilans.
• Clinical features: dactylitis (“sausage digits”), enthesitis (Achilles, plantar fascia), morning stiffness, nail changes.

Diagnosis

Diagnosis is primarily clinical based on characteristic morphology and distribution. Histopathology is supportive when needed.

• History: Chronic, relapsing-remitting plaques; family history; triggers (infection, drugs, trauma); joint symptoms; impact on quality of life.
• Examination:
  • Well-demarcated erythematous plaques with silvery scale on extensor surfaces, scalp, and trunk.
  • Check scalp, nails, umbilicus, gluteal cleft, and intertriginous areas.
  • Look for Auspitz sign and Koebner phenomenon.
  • Assess joints for swelling, tenderness, dactylitis, enthesitis.
• Laboratory tests:
  • No specific diagnostic blood test.
  • Inflammatory markers (ESR, CRP) may be elevated in moderate-severe disease or PsA.
  • Screen for comorbidities: fasting lipids, glucose/HbA1c, liver function, etc., especially before systemic therapy.
• Skin biopsy (if needed):
  • Regular acanthosis with elongation of rete ridges.
  • Parakeratosis with loss of granular cell layer.
  • Munro microabscesses (neutrophils in stratum corneum) and spongiform pustules of Kogoj.
  • Dilated, tortuous capillaries in dermal papillae.
• Differential diagnosis:
  • Chronic eczematous dermatitis (less well-demarcated, flexural in adults, more pruritic).
  • Seborrheic dermatitis (greasy, yellowish scale, less well-defined; overlaps in “sebopsoriasis”).
  • Tinea corporis (annular lesions with central clearing; positive KOH).
  • Pityriasis rubra pilaris, lichen simplex chronicus, secondary syphilis, cutaneous T-cell lymphoma.

Assessing Severity

Severity assessment informs treatment choices and is often tested.

• Body surface area (BSA):
  • Mild: <3% BSA.
  • Moderate: 3–10% BSA.
  • Severe: >10% BSA.
• PASI (Psoriasis Area and Severity Index): Combines lesion severity (erythema, thickness, scaling) and area involvement; mainly used in research and specialist practice.
• DLQI (Dermatology Life Quality Index): Assesses impact on quality of life; high scores support systemic therapy even if BSA is modest.

Management

Management of psoriasis is individualized based on disease severity, distribution, comorbidities, and patient preference. Broadly, treatment options include topical therapies, phototherapy, and systemic agents (traditional and biologic).

General Principles

• Educate patients about chronic relapsing course and treatment goals (control rather than cure).
• Identify and manage triggers: infections, trauma, medications, stress, smoking, obesity.
• Screen for and address comorbidities, including psoriatic arthritis and cardiovascular risk factors.
• Use emollients regularly to reduce scale and improve barrier function.

Topical Therapy (First-Line for Mild Disease)

• Topical corticosteroids
  • Cornerstone of therapy for localized psoriasis.
  • Potency chosen based on site and thickness of lesions: high-potency for thick plaques on elbows/knees; low-potency for face, flexures, and genitalia.
  • Apply once or twice daily; limit duration of continuous high-potency steroid use (e.g., 2–4 weeks) to reduce risk of skin atrophy, striae, telangiectasia, and tachyphylaxis.
• Vitamin D analogues (e.g., calcipotriol/calcipotriene)
  • Normalize keratinocyte proliferation and differentiation.
  • Often combined with topical steroids for synergistic effect and steroid-sparing.
  • Applied once or twice daily; avoid excessive body surface area to reduce risk of hypercalcemia (rare).
• Topical retinoids (e.g., tazarotene)
  • Modulate keratinocyte differentiation and reduce inflammation.
  • Useful as adjunct therapy, but can be irritating; often used with topical steroids.
  • Contraindicated in pregnancy.
• Calcineurin inhibitors (tacrolimus, pimecrolimus)
  • Primarily used off-label for inverse/facial psoriasis where steroids carry higher risk of atrophy.
  • Good safety profile for sensitive areas; can sting on application.
• Keratinolytics (e.g., salicylic acid, urea)
  • Help remove thick scale and enhance penetration of other topicals.
  • Use with caution on large BSA or in children (risk of salicylate toxicity).

Phototherapy

• Narrowband UVB (NB-UVB)
  • Preferred phototherapy for moderate psoriasis not adequately controlled with topicals.
  • Typically administered 2–3 times weekly over several weeks.
• Broadband UVB or PUVA (psoralen + UVA)
  • PUVA is more potent but carries higher risks (phototoxicity, photoaging, increased skin cancer risk).
  • Consider in refractory cases or certain phenotypes (e.g., palmoplantar).

Systemic Non-Biologic Therapy

Used for moderate-to-severe psoriasis, extensive body surface involvement, or significant impact on quality of life, and for many cases of psoriatic arthritis.

• Methotrexate
  • Antimetabolite that inhibits dihydrofolate reductase and has immunomodulatory effects.
  • Effective for both skin and joint disease.
  • Given weekly (oral, subcutaneous, or intramuscular) with folic acid supplementation.
  • Monitor CBC, LFTs, renal function; contraindicated in pregnancy, significant liver disease, and severe renal impairment.
• Ciclosporin (cyclosporine)
  • Calcineurin inhibitor with rapid onset; effective for severe, unstable, or erythrodermic psoriasis.
  • Short-term use (months) due to nephrotoxicity, hypertension, and other adverse effects.
  • Monitor blood pressure, renal function, lipids.
• Acitretin
  • Oral retinoid most useful for pustular and erythrodermic psoriasis and in combination with phototherapy.
  • Teratogenic with long elimination; women of childbearing potential require strict contraception and prolonged avoidance of pregnancy after discontinuation (commonly 3 years, varies by guideline).
  • Monitor lipids and liver function.
• Apremilast
  • Oral phosphodiesterase-4 (PDE4) inhibitor.
  • Moderate efficacy for plaque psoriasis and psoriatic arthritis.
  • Common adverse effects: GI upset, weight loss, headache.

Biologic and Targeted Synthetic Therapies

Biologic agents are indicated in moderate-to-severe psoriasis, especially when refractory or intolerant to traditional systemic therapy, and in psoriatic arthritis. They target specific cytokines or immune pathways.

• TNF-α inhibitors (e.g., etanercept, infliximab, adalimumab, certolizumab)
  • Effective for both skin lesions and psoriatic arthritis.
  • Screen for latent TB and hepatitis B before initiation.
• IL-12/23 inhibitor (ustekinumab)
  • Targets p40 subunit shared by IL-12 and IL-23.
  • Effective for plaque psoriasis and psoriatic arthritis.
• IL-17 inhibitors (secukinumab, ixekizumab, brodalumab)
  • Highly effective and rapid onset for plaque psoriasis.
  • Caution in patients with inflammatory bowel disease (may exacerbate).
• IL-23 inhibitors (guselkumab, tildrakizumab, risankizumab)
  • Target p19 subunit of IL-23.
  • Excellent skin responses and favorable dosing schedules.
• JAK inhibitors and other emerging agents
  • Target intracellular signaling pathways; used more in psoriatic arthritis and other immune diseases, with some role in psoriasis.

Supportive and Multidisciplinary Care

• Address psychological impact: screening for depression and anxiety; consider referral to mental health services where needed.
• Encourage lifestyle measures: smoking cessation, weight reduction, exercise, limiting alcohol, optimizing cardiovascular risk.
• Coordinate care with rheumatology for psoriatic arthritis and with primary care for comorbidity management.

Key Clinical Pearls (Exam-Focused)

• Classic lesion: Well-demarcated erythematous plaques with silvery scale on extensor surfaces and scalp.
• Pathognomonic signs:
  • Auspitz sign (pinpoint bleeding after scale removal).
  • Koebner phenomenon (lesions at sites of trauma).
• HLA association: HLA-Cw6 in early-onset disease.
• Guttate psoriasis: Sudden eruption of “drop-like” lesions in children/young adults after streptococcal pharyngitis.
• Nail involvement and dactylitis strongly suggest psoriatic arthritis; always ask about joint symptoms in psoriasis patients.
• Corticosteroid caution: Systemic corticosteroids can precipitate severe rebound flares, including pustular and erythrodermic psoriasis, after withdrawal.
• Inverse psoriasis often lacks prominent scale and is easily confused with candidiasis; lack of central clearing and presence of psoriasis elsewhere help differentiate.
• Comorbidities matter: Psoriasis is a systemic inflammatory disease; screen for metabolic syndrome, cardiovascular disease, and mental health disorders.
• Severity assessment (BSA, PASI, DLQI) guides choice between topical, phototherapy, and systemic treatments.
• Biologics are reserved for moderate-to-severe disease or psoriatic arthritis, especially after failure or contraindication to conventional systemic therapy.

Summary for Exams

Psoriasis is a chronic, immune-mediated skin disease characterized by well-demarcated erythematous plaques with silvery scale, driven mainly by IL-23/Th17 and TNF-α pathways. Diagnosis is clinical, supported by classic signs (Auspitz, Koebner) and histology when necessary. Management ranges from topical corticosteroids and vitamin D analogues for mild disease to phototherapy, systemic agents, and biologics for moderate-to-severe disease, with attention to psoriatic arthritis and cardiometabolic comorbidities.