Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by hyperproliferation of keratinocytes, resulting in well-demarcated, erythematous plaques with silvery-white scales.

Exam domain	One-glance essentials
Definition / diagnosis	Chronic immune-mediated disease causing keratinocyte hyperproliferation and well-demarcated erythematous plaques with silvery scale ^[1]^[2] Psoriasis is systemic: skin disease clusters with arthritis, metabolic and cardiovascular disease ^[3]
Epidemiology / risks	Genetic susceptibility includes HLA-Cw6; triggers include trauma, infection, stress, smoking and obesity ^[2]^[3] Streptococcal infection → guttate flare; lithium, beta-blockers and antimalarials may worsen disease ^[3]
Core mechanism	Dendritic-cell IL-23 signalling → Th17/IL-17 axis → keratinocyte proliferation and neutrophil recruitment ^[2]^[3] Trauma at uninvolved skin can induce lesions: Koebner phenomenon
Clinical picture	*Well-demarcated plaques with silvery scale on extensor surfaces; Auspitz sign and Koebner phenomenon support diagnosis ^[1] Check scalp, umbilicus, natal cleft and nails for pitting, onycholysis or oil-drop change* ^[2]^[3]
Investigations	Clinical diagnosis; biopsy if uncertain → parakeratosis, regular acanthosis and Munro microabscesses ^[2] Assess severity with BSA/PASI/DLQI; screen for PsA and cardiometabolic disease ^[3] Before biologics: *TB and hepatitis B/C screening* ^[4]
Management	Localised plaque disease: topical corticosteroid + vitamin-D analogue; then NB-UVB if needed ^[3]^[4] Moderate–severe disease: methotrexate, ciclosporin or acitretin; biologics target TNF, IL-17 or IL-23 ^[3]^[4]
Complications	Psoriatic arthritis: dactylitis, enthesitis and nail disease are key clues ^[3] Erythrodermic or generalised pustular psoriasis → skin failure, sepsis and haemodynamic/metabolic compromise ^[4] Increased obesity, diabetes, cardiovascular and depression burden ^[3]
Prevention / follow-up	Avoid smoking, excess alcohol and recognised drug triggers; manage weight and cardiovascular risk ^[2]^[3] Treat streptococcal infection when present and maintain therapy to reduce relapse
Exam traps	*Avoid systemic corticosteroids: withdrawal can precipitate pustular or erythrodermic psoriasis* ^[4] BSA/PASI/DLQI > 10 supports moderate–severe disease and systemic therapy ^[3] Pencil-in-cup change suggests PsA; anti-IL-17 therapy may worsen active IBD ^[3]

References

^[1] Lecture slides: GC 065. I have an itchy rash.pdf; Dermatology I by Dr Chan.pdf ^[2] Senior notes: Maksim Medicine Notes.pdf (Psoriasis, p69) ^[3] Senior notes: Ryan Ho Rheumatology.pdf, p120–124 ^[4] Lecture slides: GC 090. Treatments for skin diseases.pdf, p110, p117–118

Psoriasis

Psoriasis is a chronic, immune-mediated, inflammatory skin disease characterised by a state of keratinocyte hyperproliferation and abnormal differentiation, resulting in well-demarcated, erythematous plaques with silvery-white scale ^[1]^[2].

Breaking down the name: "psoriasis" derives from the Greek psora (itch) — though interestingly, itch is variable and not the defining feature. The condition is best understood as an immune-driven disorder (primarily T-cell and dendritic cell mediated) where the normal epidermal turnover time (~28–30 days) is dramatically shortened to ~3–5 days, leading to an accumulation of immature keratinocytes on the skin surface that clinically presents as the classic silvery scale.

Psoriasis is a chronic inflammatory skin condition characterised by a state of hyperproliferation. ^[2]

Key Concept

Psoriasis is NOT simply a skin disease. It is a systemic inflammatory condition. The same immune dysregulation that drives skin plaques also contributes to psoriatic arthritis (up to 30%), cardiovascular disease, metabolic syndrome, and psychological morbidity. Think of it as a disease with prominent cutaneous manifestations rather than a "skin-only" problem.

2. Epidemiology

The frequency of psoriasis varies among different populations and ethnic groups ^[3]
The highest reported incidence in Europe has been in Denmark (2.9%), with an average of about 2% across northern Europe ^[3]
In the US, psoriasis affects between 1–2% of the population ^[3]
Prevalence ~0.3–0.6% in Hong Kong (more common in Caucasians than East Asians) ^[4]
Overall worldwide prevalence ~2–3% in Caucasians, lower in Asian and African populations
Affects ~125 million people globally

M:F = 1:1 (equal sex distribution) ^[4]
Can occur at any age but shows a bimodal distribution ^[4]:
- Type 1 (Early-onset): teenage/early adult (peak 16–22 years); associated with ↑severity and positive family history ^[2]^[4]
- Type 2 (Late-onset): 50s–60s; associated with ↓severity and no family history, associated with metabolic syndrome ^[2]^[4]
Positive family history in ~40% of cases ^[4]

Type 1: young-onset, FHx +ve. Type 2: late onset, associated with metabolic syndrome. ^[2]

Risk Factor	Mechanism / Detail
Genetic predisposition	~40% have positive first-degree FHx; HLA-Cw6 strongest genetic link
Smoking	Associated with ↑occurrence in predisposed individuals with ↑intensity, ↑duration ^[4]
Obesity	Prevalence of obesity in psoriasis patients significantly higher than general population (34% vs 18%) ^[3]; pro-inflammatory adipokines from visceral fat amplify Th17 responses
Alcohol	↑risk of development, worsening, mortality of psoriasis + associated with ↓effectiveness of Tx (especially dangerous in potentiating toxicity of methotrexate) ^[4]
Infections	β-haemolytic strep infection associated with precipitation of guttate psoriasis flares ^[4]; HIV infection: severe, refractory psoriasis may be the initial presentation ^[4]
Stress / Anxiety	Neuro-immunological axis activation; substance P release from cutaneous nerves
Drugs	Antimalarial, β-blockers, lithium, NSAIDs, anti-TNFα (paradoxical reaction in some) ^[4]
Trauma / Sunlight	Manifest as the well-known Koebner phenomenon ^[4]
Vitamin D deficiency	Vitamin D is anti-proliferative and immunomodulatory; deficiency removes this brake ^[4]

Hong Kong Context

In Hong Kong, psoriasis prevalence is lower (~0.3–0.6%) than in Caucasian populations but is still a significant burden. HK-relevant risk factors include high urban stress levels, alcohol consumption culture, and the rising prevalence of obesity and metabolic syndrome. Streptococcal throat infections in winter months are a common trigger for guttate flares in HK children and young adults.

3. Anatomy and Skin Function Relevant to Psoriasis

Understanding psoriasis requires understanding normal epidermal kinetics:

Epidermis: stratified squamous epithelium with 4 layers (from deep to superficial):
1. Stratum basale (basal layer): stem cells and transit-amplifying keratinocytes; site of cell division
2. Stratum spinosum (prickle cell layer): keratinocytes begin differentiating; connected by desmosomes
3. Stratum granulosum (granular layer): keratinocytes release lamellar bodies (lipid barrier); keratohyalin granules form
4. Stratum corneum (horny layer): fully keratinised, anucleate corneocytes; the barrier
Normal epidermal turnover: ~28–30 days from basal cell division to desquamation from the stratum corneum
Dermal-epidermal junction (DEJ): rete ridges (epidermal pegs) interdigitate with dermal papillae → important because in psoriasis, rete ridges are massively elongated

The papillary dermis contains a superficial vascular plexus of capillary loops within dermal papillae
In psoriasis, these capillaries are tortuous, dilated, and extend close to the skin surface — this is why you see the Auspitz sign (pinpoint bleeding when scale is removed: you're exposing these superficial capillaries)

The skin is an active immunological organ with:
- Langerhans cells (dendritic cells of the epidermis): antigen presentation
- Dermal dendritic cells: bridge innate and adaptive immunity
- Resident T cells: especially in the dermis
- Keratinocytes: not just structural — they produce cytokines, chemokines, and antimicrobial peptides (AMPs)

Psoriasis confers protection against secondary infection due to antimicrobial peptide production ^[5] — this is why psoriatic plaques rarely get secondarily infected compared to eczematous skin (which is frequently colonised/infected by S. aureus).

4. Aetiology and Pathophysiology

Genetic susceptibility appears to play a role in the pathogenesis of psoriasis ^[3].

Genetic Feature	Detail
Family history	40% with positive 1st-degree FHx ^[4]
Twin concordance	MZ concordance 60–75% vs DZ 15–20% ^[4]
Inheritance risk	15–20% risk if 1 parent has psoriasis, 50% risk if both parents ^[4]
Key gene: PSORS1	Located in MHC cluster (HLA-Cw6), accounts for almost 1/2 of heritability ^[4]
Other genes	HLA-B17, IL12B, IL23A, TNIP1, TNFAIP3, LCE3B, LCE3C ^[4]

Why these genes matter:

HLA-Cw6: an MHC class I molecule → presents intracellular peptide antigens to CD8+ T cells. Having HLA-Cw6 means certain self-peptides (e.g., from keratinocytes) may be preferentially presented, triggering autoreactive T cells. It is particularly associated with Type 1 (early-onset) psoriasis and guttate psoriasis.
IL12B / IL23A: encode subunits of IL-12 and IL-23 respectively → these cytokines are critical for Th1 and Th17 differentiation (the key pathogenic T cell subsets in psoriasis)
LCE3B / LCE3C: late cornified envelope genes → deletion of these genes compromises epidermal barrier → may facilitate Koebner phenomenon
TNIP1 / TNFAIP3: negative regulators of NF-κB signalling → loss-of-function variants → excessive NF-κB activation → pro-inflammatory state

Unlike psoriasis which has well-defined genetics, eczema [is] much more complicated ^[6] — this is a high-yield comparison point for exams.

Multiple environmental factors have been implicated including trauma, infection, stress, and various medications ^[3].

Detailed trigger list:

Trauma → Koebner phenomenon (isomorphic response): new psoriatic lesions appear at sites of skin injury (cuts, scratches, tattoos, surgical scars). Mechanism: damaged keratinocytes release self-antigens and DAMPs → local dendritic cell activation → T cell recruitment.
Strep pharyngitis → guttate psoriasis, raindrop appearance ^[5]:
- Mechanism: Molecular mimicry — streptococcal M protein shares epitopes with keratin. Throat infection activates T cells that cross-react with skin keratinocytes. The tonsils serve as the priming site, and T cells then home to skin.
- Clinical pearl: Guttate psoriasis in a child/young adult → always check ASO titre / throat swab for GAS
Drugs: antimalarial, β-blockers, lithium, NSAIDs ^[4]:
- Lithium: inhibits inositol monophosphatase → affects keratinocyte signalling
- β-blockers: reduce cAMP → cAMP normally inhibits keratinocyte proliferation
- Antimalarials (chloroquine/hydroxychloroquine): inhibit transglutaminase → impair normal epidermal differentiation
- NSAIDs: inhibit COX → shunt arachidonic acid towards lipoxygenase pathway → ↑leukotrienes → pro-inflammatory
Corticosteroid taper precipitates very severe psoriatic flare, pustular psoriasis → so that is why systemic corticosteroids [are] not used for this condition ^[5]

Exam Favourite

Never prescribe systemic corticosteroids for psoriasis! While they may initially improve the disease, withdrawal triggers a devastating rebound flare — often converting stable plaque psoriasis into life-threatening generalised pustular psoriasis or erythrodermic psoriasis. This is one of the classic "contraindications" tested in exams.

HIV infection: severe, refractory psoriasis may be the initial presentation ^[4]
- Paradoxical: psoriasis is T-cell mediated, yet worsens in HIV (where CD4 counts drop). The explanation is that HIV causes immune dysregulation with a relative increase in CD8+ T cells and aberrant cytokine profiles, not simply immunosuppression.
Smoking: induces oxidative stress → activates NF-κB in keratinocytes; nicotine stimulates dendritic cells
Alcohol: hepatotoxic (potentiates methotrexate toxicity), immunomodulatory, increases gut permeability → endotoxinaemia
Obesity: adipose tissue is metabolically active → produces TNF-α, IL-6, leptin → amplifies systemic inflammation
Stress: hypothalamic-pituitary-adrenal axis and sympathetic nervous system activation → substance P and nerve growth factor release in skin → mast cell degranulation and T cell activation

In chronic plaque psoriasis, a vicious cycle of continuous T cell and dendritic cell activation has been proposed ^[3].

Complex immune-mediated disease characterised by abnormal proliferation and differentiation ^[4].

Step-by-step:

Initiation phase:
- Antigenic stimuli → activation of dendritic cells and other innate immune cells in skin → cytokine secretion ^[4]
- Plasmacytoid dendritic cells (pDCs) are activated by self-DNA/RNA complexed with antimicrobial peptide LL-37 (cathelicidin) released from damaged keratinocytes
- pDCs produce IFN-α → activates myeloid dendritic cells (mDCs)
Amplification phase:
- T cell activation and recruitment to skin tissues → secrete cytokines esp IL-17A ^[4]
- mDCs produce IL-12 → drives Th1 differentiation → IFN-γ, TNF-α
- mDCs produce IL-23 → drives Th17 differentiation → IL-17A (the key effector cytokine), IL-17F, IL-22
- TNF-α amplifies the entire inflammatory cascade by activating NF-κB in keratinocytes and endothelial cells
Effector phase:
- IL-17A stimulates keratinocytes to hyperproliferate + produce pro-inflammatory proteins → exacerbate inflammation ^[4]
- IL-22 drives keratinocyte proliferation and inhibits terminal differentiation
- IL-17A induces keratinocytes to produce:
  - Chemokines (CXCL1, CXCL8) → neutrophil recruitment → Munro's microabscesses
  - More AMPs (β-defensins, S100 proteins) → further pDC activation
  - Additional cytokines → positive feedback loop
Maintenance / Vicious cycle:
- The cycle self-perpetuates: keratinocyte hyperproliferation → more antigen exposure → more dendritic cell and T cell activation
- Hyperproliferation: traditionally regarded as the primary step but may be secondary to inflammation ^[4]
- Even non-lesional skin and unaffected nails show ↑proliferation rate ^[4] — suggesting a subclinical systemic inflammatory drive

Understanding the histopathology helps you understand the clinical signs:

Histological Feature	Clinical Correlate
Parakeratosis (retention of nuclei in stratum corneum due to rapid transit)	Silvery-white scale
Acanthosis (thickening of epidermis with elongated rete ridges)	Raised, thickened plaques
Loss of granular layer (keratinocytes skip normal maturation)	Abnormal barrier function
Dilated, tortuous capillaries in dermal papillae (close to surface due to thinning of suprapapillary plate)	Auspitz sign (pinpoint bleeding), erythema
Munro's microabscesses (neutrophil collections in stratum corneum)	Pustular variants; subtle in plaque psoriasis
Spongiform pustules of Kogoj (neutrophils within spinous layer)	Characteristic of pustular psoriasis
Perivascular lymphocytic infiltrate in dermis	Chronic inflammation

Why does removing the scale cause pinpoint bleeding (Auspitz sign)?

In psoriasis, the rete ridges are massively elongated, and the dermal papillae (containing dilated capillary loops) extend very close to the surface. The suprapapillary plate (the thin epidermis overlying the papillae) is markedly thinned. When you scrape off the scale, you expose these superficial capillaries → pinpoint bleeding from each dermal papilla tip.

5. Classification / Types of Psoriasis

Type	Frequency	Key Features
Plaque (Psoriasis vulgaris)	MC in adult (~80–90%)	Common on extensor surface of elbows & knees, scalp, trunk; well-demarcated erythematous plaques with silvery scale ^[2]
Guttate	More common in children/young adults (~10%)	Raindrop-like small papules/plaques (< 1 cm) scattered over trunk and proximal limbs; triggered by Strep pharyngitis ^[2]^[5]
Pustular	Rare	Acute onset of pustules, associated with fever, malaise; sterile pustules on erythematous base; precipitated by withdrawal of steroid ^[2]; two forms — generalised (von Zumbusch) and localised (palmoplantar pustulosis)
Erythrodermic	Rare, medical emergency	Generalised erythema & scaling > 75% BSA; precipitated by withdrawal of steroid, infection, alcohol, stress ^[2]; risk of hypothermia, high-output cardiac failure, sepsis
Inverse (Flexural)	~2–6%	On flexor surface — axillae, groin, submammary, intergluteal cleft ^[2]; less scaly due to moisture in skin folds; may mimic fungal infection
Nail psoriasis	~50% at presentation, up to 80–90% lifetime	Pitting, onycholysis, oil-drop sign, subungual hyperkeratosis
Scalp psoriasis	Very common (~50–80%)	Well-demarcated plaques beyond hairline; often the first site affected
Palmoplantar psoriasis		Thick, fissured plaques on palms/soles; significant functional impairment

Paediatric psoriasis: Guttate is the most common initial presentation in children. Napkin psoriasis (diaper area) may be the first sign in infants.
HIV-associated psoriasis: Characteristically severe, treatment-resistant; may be the presenting feature of HIV. Paradoxically severe despite low CD4 counts.

6. Clinical Features

Symptom	Pathophysiological Basis
Pruritus (variable, ~60–90%)	IL-31, substance P, and nerve growth factor release in psoriatic plaques stimulate cutaneous nerve endings; less prominent than eczema because the epidermal barrier, while abnormal, is hyperkeratotic rather than disrupted by spongiosis
Pain / Burning (especially in erythrodermic/pustular)	Direct nerve irritation by inflammatory mediators (TNF-α, IL-1); fissuring in thick plaques exposes dermis
Skin tightness / Cracking	Thick, inflexible plaques over joints → fissures with movement; loss of normal skin elasticity from massive acanthosis and parakeratosis
Cosmetic distress / Psychosocial impact	Highly visible lesions; chronic course; stigma → depression (up to 30%), anxiety, social withdrawal; psoriasis has one of the highest impacts on quality of life of any dermatological condition
Joint pain and stiffness (if psoriatic arthritis ~30%)	Same immune dysregulation (IL-17, TNF-α) targets entheses, synovium, and bone → enthesitis, synovitis, dactylitis, spondylitis
Nail symptoms (brittleness, discolouration, lifting)	Psoriatic inflammation in the nail matrix (→ pitting) or nail bed (→ onycholysis, oil-drop sign)

6.2 Signs (with Pathophysiological Basis)

Sign	Description	Pathophysiological Basis
Well-demarcated, erythematous plaques with silvery scale ^[2]	The hallmark lesion; raised, sharply bordered, bright red/salmon-coloured plaques covered with loosely adherent silvery-white scale	Erythema = dilated dermal capillaries; silvery scale = parakeratotic stratum corneum (nuclei retained due to rapid transit, reflecting light); well-demarcated border = abrupt transition between abnormal and normal epidermis
Auspitz sign ^[2]	Removal of scale from plaques causes pinpoint bleeding	Elongated rete ridges + thinned suprapapillary plate → superficial dilated capillaries exposed upon scale removal → punctate haemorrhage from each papilla
Koebner phenomenon (isomorphic response) ^[2]	Development of skin disease in sites of skin trauma (scratches, surgical wounds, sunburn, tattoos)	Trauma → keratinocyte damage → DAMP release → local dendritic cell activation → T cell recruitment → new psoriatic plaque at site of injury. Occurs in ~25–75% of psoriasis patients. Also seen in lichen planus, vitiligo, viral warts
Candle-wax sign (tache de bougie)	Scratching the surface produces silvery-white flakes resembling candle wax scrapings	Parakeratotic scale is loosely adherent; the layered, laminated arrangement of abnormal corneocytes fractures along planes when scraped
Distribution pattern	Extensor surfaces (elbows, knees), scalp, sacrum, umbilicus, intergluteal cleft	"Outside surfaces" (extensors) — in contrast to eczema which favours flexural surfaces. Scalp involvement often extends beyond the hairline. The predilection is thought to relate to local mechanical stress (Koebner) and differences in local immune environment

Psoriasis vs Eczema — Key Differentiators (Exam Favourite)

Feature	Psoriasis	Eczema (Atopic Dermatitis)
Border	Well-demarcated	Ill-defined
Scale	Silvery, thick, lamellated	Fine, with crusting/weeping
Surface	Extensors (elbows, knees)	Flexors (antecubital, popliteal)
Pruritus	Variable (often less intense)	Intense (hallmark)
Epidermal changes	Hyperkeratosis, no vesicles	Vesicles, weeping (acute), lichenification (chronic)
Auspitz sign	Present	Absent
Koebner	Present	Not typical
Age	Any age (bimodal)	Usually childhood onset
Family history	Psoriasis	Atopy triad

Nail dystrophy (90%) ^[2]

Nail Sign	Description	Pathophysiological Basis
Pitting	Small, regular depressions ("thimble pitting") on nail plate surface	Psoriatic inflammation in the proximal nail matrix → focal parakeratosis in nail plate → parakeratotic cells fall out leaving pits
Onycholysis	Painless separation of nail plate from nail bed, starting distally	Inflammation in the nail bed → disruption of attachment between nail plate and bed; air under nail appears white
Oil-drop sign (salmon patch)	Yellowish-brown discolouration visible through nail plate	Serum-like exudate and glycoprotein accumulation in the nail bed beneath the nail plate
Subungual hyperkeratosis	Thickening of material under the nail plate	Hyperproliferation of nail bed epidermis → accumulated parakeratotic scale lifts the nail
Nail plate crumbling / dystrophy	Complete nail destruction in severe cases	Extensive nail matrix involvement → irregular nail growth
Splinter haemorrhages	Longitudinal lines of haemorrhage within the nail plate	Dilated, tortuous capillaries in the nail bed; disruption by minor trauma
Beau's lines	Transverse grooves across the nail plate	Temporary arrest of nail matrix activity during a severe psoriatic flare

Clinical Pearl

Nail psoriasis is strongly associated with psoriatic arthritis (the distal interphalangeal (DIP) joints lie directly beneath the nail matrix and share a common entheseal structure). If you see nail changes in a psoriasis patient, actively look for DIP joint disease.

Guttate Psoriasis:

Raindrop-like appearance ^[5]
Small (0.5–1.5 cm) salmon-pink papules with fine scale
Widespread, predominantly on trunk and proximal limbs
Often preceded by streptococcal pharyngitis (2–3 weeks prior)
May be self-limiting (~60% resolve within 3–4 months) but ~33% progress to chronic plaque psoriasis

Pustular Psoriasis:

Generalised (von Zumbusch): Sheets of sterile pustules on erythematous skin; associated with fever, malaise, leukocytosis → medical emergency
- Precipitated by withdrawal of steroid ^[2]^[5]
- Can cause high-output cardiac failure and sepsis
Localised (Palmoplantar pustulosis): Sterile pustules confined to palms and soles; strong association with smoking
Pustules are sterile — they contain neutrophils (Munro's microabscesses becoming macroscopic), NOT bacteria

Erythrodermic Psoriasis:

Generalised erythema & scaling > 75% BSA ^[2]
Medical emergency — complications include:
- Hypothermia: loss of thermoregulatory function from widespread vasodilation
- High-output cardiac failure: massive cutaneous vasodilation → ↑cardiac output to maintain BP
- Hypoalbuminaemia: protein loss through inflamed, exfoliating skin → oedema
- Sepsis: disrupted barrier function → bacterial entry
- Electrolyte imbalance: transepidermal water and electrolyte loss

Inverse (Flexural) Psoriasis:

On flexor surface ^[2]: axillae, inguinal folds, submammary, intergluteal cleft
Glazed, red, well-demarcated plaques WITHOUT the typical silvery scale (moisture in skin folds prevents scale formation)
Differential: tinea cruris, candidiasis, intertrigo, seborrhoeic dermatitis

Psoriasis can also affect arteries → stiffness, increased risk of CV disease ^[5]

Comorbidity	Mechanism
Psoriatic arthritis (~30%) ^[2]	Shared IL-17/TNF-α pathway; targets entheses, synovium, bone
Increased risk of CVS disease ^[2]	Chronic inflammatory state → accelerated atherosclerosis; systemic TNF-α, IL-6, CRP → endothelial dysfunction, insulin resistance
Metabolic syndrome (obesity, T2DM, dyslipidaemia, HTN)	Shared inflammatory pathways (TNF-α, IL-6); adipose tissue amplifies inflammation
Depression and anxiety	Biopsychosocial: disfigurement, stigma, chronic pain + neuroinflammatory effects of systemic cytokines
Non-alcoholic fatty liver disease (NAFLD)	Insulin resistance, TNF-α-mediated hepatic steatosis; compounded by methotrexate hepatotoxicity
Inflammatory bowel disease	Shared genetic susceptibility (IL23R variants); gut-skin axis
Lymphoma (modest increase)	Chronic immune stimulation; certain treatments (e.g., cyclosporine) may contribute

Patients with psoriasis had an increased adjusted relative risk (RR) for MI that varied by age. For a 30-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.29 and 3.10, respectively. ^[3]

The Psoriatic March — Exam Concept

The "psoriatic march" hypothesis proposes that chronic cutaneous inflammation → systemic inflammation (↑TNF-α, IL-6, CRP) → insulin resistance → endothelial dysfunction → atherosclerosis → major adverse cardiovascular events. This explains why young patients with severe psoriasis have a disproportionately elevated cardiovascular risk compared to older patients (where traditional CV risk factors dominate). This is why modern psoriasis management increasingly includes cardiovascular risk assessment.

Site	Subtype / Notes
Elbows (extensors)	Classic plaque psoriasis
Knees (extensors)	Classic plaque psoriasis
Scalp	Very common; often first affected site; may extend beyond hairline (cf. seborrhoeic dermatitis which stays within)
Sacrum / Intergluteal cleft	Often overlooked on examination
Umbilicus	Characteristic but often missed
Nails	Pitting, onycholysis, oil-drop sign
Flexures	Inverse psoriasis
Trunk (widespread)	Guttate psoriasis
Palms and soles	Palmoplantar psoriasis / pustulosis

Examination	What to Look For	Why
Skin	Well-demarcated plaques, silvery scale, Auspitz sign, distribution (extensors, scalp, nails, flexures)	Diagnosis is clinical
Nails	Pitting, onycholysis, oil-drop sign, subungual hyperkeratosis	Present in majority; associated with PsA
Joints	DIP tenderness, dactylitis ("sausage digits"), enthesitis (Achilles, plantar fascia), axial symptoms	Screen for psoriatic arthritis
Scalp	Plaques beyond hairline	Distinguishes from seborrhoeic dermatitis
Flexures	Glazed erythema without scale in axillae, groin, submammary	Inverse psoriasis
Body habitus	BMI, waist circumference	Metabolic syndrome association
Cardiovascular	BP, heart sounds	CV risk assessment

Assessment Tool	Parameters
Body Surface Area (BSA)	Patient's palm ≈ 1% BSA; Mild < 3%, Moderate 3–10%, Severe > 10%
PASI (Psoriasis Area and Severity Index)	Composite of erythema, induration, scale, and area in 4 body regions (head, trunk, upper limbs, lower limbs); range 0–72; commonly used in clinical trials
DLQI (Dermatology Life Quality Index)	10-question patient-reported questionnaire; score 0–30; > 10 = significant impact

In clinical practice and for treatment escalation decisions: Moderate-to-severe psoriasis is generally defined as BSA > 10%, PASI > 10, or DLQI > 10 (the "rule of tens").

High Yield Summary

Definition: Chronic immune-mediated inflammatory skin disease with keratinocyte hyperproliferation → well-demarcated erythematous plaques with silvery scale
Epidemiology: 2% Caucasians, ~0.3–0.6% HK; M=F; bimodal onset (Type 1 early + FHx, Type 2 late + metabolic syndrome)
Genetics: 40% FHx+; HLA-Cw6 (PSORS1) accounts for ~50% heritability; IL12B, IL23A implicated
Pathophysiology: Dendritic cell → IL-12/IL-23 → Th1/Th17 → IL-17A → keratinocyte hyperproliferation + neutrophil recruitment → vicious cycle
Triggers: Strep → guttate; drugs (antimalarials, β-blockers, lithium, NSAIDs); steroid withdrawal → pustular/erythrodermic flare; HIV; trauma (Koebner); stress; smoking; alcohol; obesity
NEVER give systemic steroids → rebound flare (pustular/erythrodermic)
Clinical signs: Auspitz sign, Koebner phenomenon, nail changes (pitting, onycholysis, oil-drop sign), distribution (extensors > flexors)
Key subtypes: Plaque (MC), Guttate (Strep-associated), Pustular (steroid withdrawal), Erythrodermic (emergency), Inverse (flexural)
Psoriasis is systemic: ↑CV risk (psoriatic march), psoriatic arthritis (~30%), metabolic syndrome, depression, NAFLD
Contrast with eczema: well-demarcated vs ill-defined, extensors vs flexors, silvery scale vs weeping/crusting

Active Recall - Psoriasis (Definition, Epidemiology, Aetiology, Pathophysiology, Clinical Features)

^[1] Lecture slides: GC 065. I have an itchy rash.pdf; Dermatology I by Dr Chan.pdf ^[2] Senior notes: Maksim Medicine Notes.pdf (Section 4.3 Psoriasis) ^[3] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf (p33, p36) ^[4] Senior notes: Ryan Ho Rheumatology.pdf (Section 4.2.3.1 Psoriasis, p120) ^[5] Senior notes: Block A - Dermatology PBL 1.pdf (p17) ^[6] Senior notes: Block A - I have an itchy rash (eczema, urticaria, tinea infection and psoriasis).pdf (p21) ^[7] Lecture slides: CFB (MED08) Dermatology (I).pdf ^[8] Lecture slides: Derm General Clerkship 2026 Part1.pdf ^[9] Lecture slides: Block A - Dermatology Pictorial Tour.pdf ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1708–1710) ^[11] Senior notes: Adrian Lui Pediatrics Notes.pdf (p456)

Differential Diagnosis of Psoriasis

When you encounter a patient with a scaly erythematous rash, the differential diagnosis depends on the specific morphology, distribution, and clinical context. The key question is: "What else can mimic psoriasis?" — and conversely, when you see a scaly plaque, how do you confirm it IS psoriasis and not something else?

The approach is best structured by thinking about which clinical subtype of psoriasis you are trying to differentiate, because each subtype has its own mimics.

2. Differential Diagnosis by Psoriasis Subtype

This is the most commonly tested scenario: a patient presents with well-demarcated, scaly, erythematous plaques. What else could it be?

Differential	Key Distinguishing Features	Why It Mimics Psoriasis
Atopic dermatitis (Eczema) ^[1]^[2]	Ill-defined border (cf. psoriasis which is well-demarcated); flexural distribution; intense pruritus (hallmark); vesicles/weeping in acute phase, lichenification in chronic; personal/family history of atopy triad; WITHOUT characteristic thick, coarse scale and sharp, raised, well-defined borders of psoriasis ^[4]	Both are chronic, relapsing, scaly, erythematous conditions. However, the border definition, distribution (flexors vs extensors), and epidermal change pattern differ fundamentally.
Seborrhoeic dermatitis ^[3]^[4]	Scaly erythematous patches affecting similar areas [to psoriasis], should show characteristic fine, greasy scale involving seborrhoeic areas (e.g., eyebrows, nasolabial folds, post-auricular), NO nail changes/joint involvement ^[4]; often overlaps with scalp psoriasis ("sebopsoriasis"); scale is yellowish-greasy rather than silvery-white	Seborrhoeic dermatitis can affect the scalp and face similarly to psoriasis. The scale quality differs: greasy/yellowish (seborrhoeic) vs dry/silvery-white (psoriatic). Seborrhoeic dermatitis stays within the hairline; scalp psoriasis extends beyond it. Seborrhoeic dermatitis is caused by Malassezia yeast-driven inflammation in sebaceous gland-rich areas.
Contact dermatitis ^[3]	History of exposure to contactant; well-demarcated if exogenous/irritant; distribution matches area of contact; may have vesicles; patch testing positive; very well demarcated → must be extrinsic ^[6]	Allergic or irritant contact dermatitis can produce well-demarcated, scaly, erythematous plaques. The key is the distribution conforming to the contactant exposure area and a clear temporal relationship.
Lichen simplex chronicus ^[4]	Skin changes secondary to excessive scratching; show thickened plaques with overlying scales/hyperpigmentation and lichenification; should spare areas where the patient cannot reach ^[4]	Chronic scratching produces lichenified, scaly plaques that can resemble chronic psoriasis. However, the distribution follows areas of habitual scratching, and there is no Auspitz sign or silvery scale.
Discoid eczema (Nummular eczema) ^[4]	Well-demarcated erythematous scaly plaques, but usually occur in trunk/extremities sparing face/scalp ^[4]; coin-shaped; more intensely pruritic; may weep/crust	Can closely mimic plaque psoriasis due to well-demarcated borders. However, discoid eczema tends to have a more oozy/crusted surface, spares the scalp, and responds differently to treatment.
Superficial fungal infections (Tinea corporis) ^[4]	Annular with active, slightly raised margin; less thick silvery scales without Auspitz sign; usually differentiated by skin scrapings/nail clippings for fungal culture ^[4]; central clearing ("ringworm" pattern); KOH preparation positive	Tinea can produce scaly, erythematous, well-demarcated patches. The annular morphology with central clearing is the key differentiator. Always do KOH/fungal culture, especially if unilateral or asymmetric. Tinea incognito (fungal infection treated with topical steroids) can particularly mimic psoriasis as the steroids obscure the classic annular pattern.
Lichen planus ^[3]	The "5 Ps": pruritic, polygonal, planar (flat-topped), purple papules; Wickham's striae (fine white lines on surface); mucosal involvement (oral: white lacy pattern); Koebner phenomenon also present	Both lichen planus and psoriasis exhibit Koebner phenomenon. However, lichen planus is violaceous/purple (not salmon-pink), has flat-topped papules (not raised thick plaques), and shows Wickham's striae rather than silvery scale.
Mycosis fungoides (Cutaneous T-cell lymphoma)	Patches → plaques → tumours progression over years; may mimic psoriasis or eczema for years before diagnosis; skin biopsy with Pautrier microabscesses diagnostic	Early-stage mycosis fungoides produces erythematous scaly patches/plaques that can be indistinguishable from psoriasis clinically. Always consider in middle-aged/elderly patients with "psoriasis" refractory to standard treatment. Biopsy is essential.
Pityriasis rubra pilaris	Salmon-coloured palmoplantar keratoderma; follicular hyperkeratosis; erythroderma with characteristic "islands of sparing"; waxy yellow scale	Can mimic erythrodermic psoriasis. The "islands of sparing" (normal-looking skin within the erythroderma) is the classic distinguishing sign.
Subacute cutaneous lupus ^[5]	Annular, papulosquamous type (appears as eczema/psoriasis) ^[5]; photosensitive distribution; anti-Ro/SSA positive; non-scarring	The papulosquamous variant of subacute cutaneous lupus can closely resemble psoriasis. Key differentiators: photosensitive distribution (sun-exposed areas), serological markers (ANA, anti-Ro), and association with systemic lupus features.

High Yield GC Exam Point

Differential diagnosis of atopic eczema includes: Seborrhoeic dermatitis, Contact dermatitis, Psoriasis, Scabies, Genetic or metabolic disorders featuring atopic eczema with or without raised IgE level (e.g., Ataxia telangiectasia, Wiskott-Aldrich syndrome) ^[1]. These differentials work both ways — when you see psoriasis, you should also consider eczema and these other conditions.

Guttate psoriasis presents with widespread small ("raindrop-like") papules. The key differentials are other conditions that produce widespread small lesions:

Differential	Key Distinguishing Features	Why It Mimics Guttate Psoriasis
Pityriasis rosea ^[7]	Tend to be associated with Hx of herald patch and finer scale without herald patch ^[4]; "collarette" of trailing scale; Christmas tree distribution on back; self-limiting (4–6 weeks); herald patch present in 50–90% ^[7]	Both produce crops of small oval lesions on the trunk of young adults. The herald patch preceding the eruption by 1–2 weeks is the key distinguishing feature. The scale in pityriasis rosea has a characteristic peripheral "collarette" pattern, while guttate psoriasis has a more uniform silvery scale.
Secondary syphilis ^[7]	Red/brown macules and papules; characteristically involves palms and soles (psoriasis rarely does unless palmoplantar variant); condylomata lata; mucous patches; generalised lymphadenopathy; positive VDRL/RPR serology; sexual risk history	Both produce widespread papulosquamous lesions. Always check VDRL serology if high-risk ^[7]. The involvement of palms and soles is a major red flag for secondary syphilis.
Drug eruption	Temporal relationship with drug initiation; may have pruritus, eosinophilia; resolves with drug withdrawal	Morbilliform drug eruptions can produce widespread papules/macules resembling guttate psoriasis. History of recent drug commencement is key.
Viral exanthem	Fever, lymphadenopathy, pharyngitis; self-limiting; associated viral prodrome	In children/young adults, widespread maculopapular viral exanthems can occasionally mimic guttate psoriasis. The acute febrile onset and lack of silvery scale differentiate.

Clinical Pearl — The Triad of Widespread Papulosquamous Rash in Young Adults

When a young adult presents with widespread small scaly lesions on the trunk, your top three differentials are:

Guttate psoriasis (Strep throat → 2–3 weeks → silvery raindrop papules)
Pityriasis rosea (herald patch → 1–2 weeks → collarette scale, Christmas tree pattern)
Secondary syphilis (painless chancre weeks prior → palm/sole involvement, lymphadenopathy)

Always check: throat swab/ASO, VDRL, and look for a herald patch.

Generalised pustular psoriasis (GPP) must be differentiated from AGEP ^[6].

Differential	Key Distinguishing Features	Why It Mimics GPP
Acute Generalised Exanthematous Pustulosis (AGEP) ^[6]	Drug history (antibiotics — especially aminopenicillins, macrolides; antifungals); more discrete pustules in AGEP, more merged together (lakes of pus) in GPP; abdomen in AGEP, extremities in GPP ^[6]; both are medical emergencies, require hospital admission ^[6]; very difficult to differentiate clinically ^[6]; neutrophilia and fever in both; AGEP resolves rapidly (< 2 weeks) after drug withdrawal	Both present with acute onset of widespread sterile pustules on erythematous skin with systemic symptoms. The distinction is critical because management differs: AGEP = withdraw offending drug; GPP = systemic immunosuppression. Skin biopsy may help but overlap is common.
Subcorneal pustular dermatosis (Sneddon-Wilkinson)	Flaccid pustules forming "half-and-half" blisters (fluid settles to lower half); flexural predilection; chronic relapsing; associated with IgA paraproteinaemia	Produces sterile pustules but in a more indolent pattern.
Impetigo	Superficial pustules/bullae with honey-coloured crust; bacterial culture positive (S. aureus, GAS); localised	Superficial pustules may mimic localised pustular psoriasis but are infective (culture-positive) and lack the systemic features.

GPP: Fever, deranged LFT. AGEP: Drug history. ^[6] — These are the two key history points that help you differentiate at the bedside.

Erythroderma ("skin failure"): generalised erythema & scaling involving > 90% BSA ^[8]. When psoriasis generalises to erythroderma, the specific morphological features (well-demarcated borders, silvery scale) may be lost, making the differential broader.

5 categories of aetiology for erythroderma ^[8]:

Category	Examples	Key Distinguishing Features
Exacerbation of pre-existing dermatoses	Atopic eczema, psoriasis, lichen planus, immunobullous disorders, GvHD ^[8]	Known preceding skin disease history; previous biopsies
Drug eruptions	Antiepileptics, anti-HT (captopril, frusemide), antibiotics (penicillins, sulphonamides), allopurinol ^[8]; particularly SJS, DRESS	Temporal relationship with drug; mucosal involvement in SJS/TEN; eosinophilia and organ involvement in DRESS
Malignancy	Cutaneous T-cell lymphoma (Sézary syndrome) (MC), Hodgkin's disease (2nd MC), NHL, leukaemias ^[8]	Sézary cells on peripheral blood smear; generalised lymphadenopathy; insidious onset; skin biopsy with T-cell clonality
Infection	Crusted scabies, dermatophytosis, AIDS ^[8]	Scabies: intense itch, burrows, immunocompromised context; dermatophytosis: KOH positive
Idiopathic	No identifiable cause	Diagnosis of exclusion; requires skin biopsy from at least 2 sites

For erythrodermic psoriasis specifically, key differentials include: SJS, TEN, DRESS syndrome ^[3]

Erythroderma Workup

Investigations for erythroderma ^[8]:

CBC D/C, LRFT, ESR ± PBS (Sézary cells), CXR
Skin biopsy from at least 2 sites: histology, DIF (if suspect immunobullous disease)
± Age-appropriate malignancy workup (if indicated)

The skin biopsy is essential because once psoriasis becomes erythrodermic, the clinical features may be indistinguishable from other causes.

Since inverse psoriasis lacks the typical silvery scale (due to moisture in skin folds), it is easily confused with:

Differential	Key Distinguishing Features
Tinea cruris / Candidal intertrigo	Annular with active border; satellite lesions (candida); KOH/fungal culture positive; response to antifungals
Intertrigo	Moist, macerated, erythematous; typically in obese patients; secondary bacterial or candidal infection common
Seborrhoeic dermatitis	Greasy yellowish scale; nasolabial folds, post-auricular involvement
Contact dermatitis	History of contactant exposure (deodorants in axillae, elastic in underwear)
Erythrasma	Coral-red fluorescence under Wood's lamp; caused by Corynebacterium minutissimum; well-demarcated reddish-brown patches

Differential	Key Distinguishing Features
Onychomycosis ^[4]	Usually differentiated by nail clippings for fungal culture ^[4]; tends to involve fewer nails, often asymmetric; subungual debris is more yellowish-brown; no associated joint disease
Lichen planus of nail	Longitudinal ridging; thinning of nail plate; dorsal pterygium (scarring of proximal nail fold to nail bed); twenty-nail dystrophy in children
Alopecia areata	Regular, geometric ("grid-like") pitting — more uniform than the irregular pitting of psoriasis
Trauma	History of mechanical injury; usually isolated to one or two nails

When a patient presents with joint symptoms and skin lesions, the differential of the arthritis itself needs consideration ^[10]:

Differential	Key Distinguishing Features
Rheumatoid arthritis	Only a small number of patients with psoriatic arthritis will test positive for RF and anti-CCP whereas these tests are positive in a majority of patients with RA ^[10]; symmetrical small joint involvement; MCP/PIP (not DIP); no nail changes; no dactylitis
Reactive arthritis	History of antecedent infectious illness with either genitourinary symptoms of urethritis or a dysenteric illness is absent in psoriatic arthritis ^[10]
Arthritis of inflammatory bowel disease	Can usually be suspected based upon clinical findings and confirmed with endoscopic investigation and biopsy ^[10]
Ankylosing spondylitis	Presence of psoriasis and radiological features distinguish ^[10]; predominantly axial; bamboo spine on XR; younger male predominance
Gouty arthritis	Gout is confirmed by finding monosodium urate crystals on examination of synovial fluid. Psoriatic arthritis and gout can coexist ^[10]; note that DIP joint involvement and tophi can mimic psoriatic nail changes
Osteoarthritis	Hard bony swelling (Heberden's/Bouchard's nodes); no inflammatory markers; no dactylitis; Heberden's nodes affect DIP but are bony, not soft

The following clinical features, when present, strongly favour psoriasis over its mimics:

Feature	Diagnostic Value
Silvery-white, lamellar scale	Virtually pathognomonic (not greasy like seborrhoeic, not fine like pityriasis rosea)
Auspitz sign positive	Highly suggestive of psoriasis; not present in other scaly dermatoses
Koebner phenomenon	Also seen in lichen planus, vitiligo, viral warts — but combined with silvery scale, points to psoriasis
Nail pitting + onycholysis	Strong supporting evidence; not present in eczema or seborrhoeic dermatitis
Extensor surface predilection	Classic for psoriasis (cf. eczema = flexors)
Family history of psoriasis	~40% positive; increases pre-test probability dramatically
Response to therapies	Responds to vitamin D analogues and phototherapy; eczema responds to emollients and topical calcineurin inhibitors

ALWAYS look at the scalp, the nails, post-auricular areas and mucosal areas for possible lesions ^[3] — hidden psoriatic plaques in these sites may clinch the diagnosis when the presenting lesion is ambiguous.

Psoriasis Subtype	Top Differentials to Exclude
Plaque	Atopic dermatitis, seborrhoeic dermatitis, lichen planus, discoid eczema, tinea, contact dermatitis, mycosis fungoides, subacute cutaneous lupus
Guttate	Pityriasis rosea, secondary syphilis, drug eruption, viral exanthem
Pustular	AGEP (drug-induced), subcorneal pustular dermatosis, impetigo
Erythrodermic	Drug eruption (SJS/TEN/DRESS), Sézary syndrome (CTCL), eczema flare, pityriasis rubra pilaris, crusted scabies
Inverse	Tinea cruris, candidal intertrigo, erythrasma, seborrhoeic dermatitis, contact dermatitis
Nail	Onychomycosis, lichen planus, alopecia areata, trauma
Psoriatic arthritis	RA, reactive arthritis, gout, OA, ankylosing spondylitis, IBD-associated arthritis

High Yield Summary

Plaque psoriasis DDx: Think "scaly red plaque" — seborrhoeic dermatitis (greasy, nasolabial, no nails), eczema (ill-defined, flexors), tinea (annular, KOH+), lichen planus (purple, flat-topped, Wickham's striae), mycosis fungoides (refractory, biopsy essential), subacute cutaneous lupus (photosensitive, anti-Ro+)
Guttate DDx triad: guttate psoriasis (Strep Hx, silvery) vs pityriasis rosea (herald patch, collarette) vs secondary syphilis (palms/soles, VDRL+)
Pustular DDx: GPP vs AGEP — both emergencies; GPP = steroid withdrawal/psoriasis flare, lakes of pus, extremities; AGEP = drug-induced, discrete pustules, abdomen, resolves with drug withdrawal
Erythroderma DDx: 5 causes — pre-existing dermatosis exacerbation, drug eruption, malignancy (CTCL/Sézary), infection, idiopathic; always biopsy from 2+ sites
Key investigations to differentiate: KOH scraping (tinea), fungal culture (onychomycosis), VDRL (syphilis), skin biopsy (mycosis fungoides, erythroderma), patch testing (contact dermatitis), throat swab/ASO (guttate vs pityriasis rosea)
Never forget: Look at scalp, nails, post-auricular, umbilicus for hidden psoriatic plaques — they may clinch the diagnosis

Active Recall - Psoriasis Differential Diagnosis

References

^[1] Lecture slides: Dermatology I by Dr Chan.pdf (p21) ^[2] Senior notes: Maksim Medicine Notes.pdf (Section 4.2 Dermatitis & eczema, Section 4.3 Psoriasis, p69) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1791–1795) ^[4] Senior notes: Ryan Ho Rheumatology.pdf (p122) ^[5] Senior notes: Block A - Dermatology PBL 2.pdf (p7) ^[6] Senior notes: Block A - Dermatology PBL 1.pdf (p11, p18) ^[7] Senior notes: Ryan Ho Rheumatology.pdf (p129 — Pityriasis Rosea section) ^[8] Senior notes: Maksim Medicine Notes.pdf (Section Erythroderma, p77) ^[9] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf (p33, p35) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1708–1710 — Psoriatic Arthritis)

Diagnostic Criteria, Diagnostic Algorithm, and Investigations for Psoriasis

1. Diagnostic Criteria — Psoriasis (Cutaneous)

Psoriasis is fundamentally a clinical diagnosis. There is no single definitive laboratory test or formal diagnostic criteria set for cutaneous psoriasis (unlike psoriatic arthritis, which has the CASPAR criteria). The diagnosis rests on recognising the characteristic morphology, distribution, and associated features.

The diagnosis of psoriasis is made when the following constellation of clinical features is present:

Feature	Detail	Why It Matters Diagnostically
Well-demarcated, erythematous plaques with silvery scale ^[2]	The hallmark morphology; salmon-pink base with lamellated silver-white scale	This combination is virtually pathognomonic. No other common dermatosis produces this exact appearance.
Characteristic distribution	Extensor surfaces (elbows, knees), scalp, sacrum, umbilicus, intergluteal cleft	Extensor predilection separates psoriasis from eczema (flexors).
Auspitz sign ^[2]	Pinpoint bleeding on removal of scale	Reflects the thinned suprapapillary plate and dilated papillary capillaries — highly specific for psoriasis
Koebner phenomenon ^[2]	New lesions at sites of trauma	Supportive but not pathognomonic (also occurs in lichen planus, vitiligo)
Nail changes ^[3]	Pitting, onycholysis, oil-drop sign, subungual hyperkeratosis	Presence of nail disease is important diagnostically, often providing valuable supportive evidence of disease in difficult cases ^[3]
Family history	Positive in ~40%	Increases pre-test probability substantially

ALWAYS look at the scalp, the nails, post-auricular areas and mucosal areas for possible lesions ^[3] — these are the "hidden sites" that clinch the diagnosis when the presenting lesion is ambiguous or atypical.

Key Principle

Psoriasis is a clinical diagnosis. Investigations are used to: (1) confirm diagnosis when clinical doubt exists (skin biopsy), (2) exclude mimics (KOH scraping, VDRL, fungal culture), (3) assess severity (PASI, DLQI), (4) screen for comorbidities (metabolic syndrome, CV risk, PsA), and (5) monitor systemic therapy safety. You do NOT need blood tests to diagnose psoriasis.

When the clinical picture extends to joints, the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria are applied. This is the validated classification system and is frequently examined ^[3]^[10]^[12].

Entry criterion: Inflammatory musculoskeletal disease (peripheral arthritis, spondylitis, or enthesitis)

PLUS total score ≥ 3 points from the following ^[3]^[10]:

Feature	Detail	Points
Skin psoriasis	Present (current)	2
	Previously present by history	1
	Family history of psoriasis (if patient not affected)	1
Nail lesions	Pitting or onycholysis on current examination	1
Dactylitis	Present or past, documented by a rheumatologist	1
Rheumatoid factor (RF)	Negative	1
Juxtaarticular bone formation on radiography	Distinct from osteophytes	1

CASPAR criteria — Entry: Inflammatory articular disease (joint, spine, enthesitis) PLUS 3 points: Evidence of psoriasis: current (+2), personal history (+1), family history (+1); Psoriatic nail dystrophy (+1); Dactylitis (+1); RF negative (+1); Imaging evidence of juxta-articular new bone formation (+1) ^[12]

Exam Pearl — CASPAR Scoring

The maximum score from psoriasis evidence alone is 2 (if currently present). This means a patient with active psoriasis (+2) and negative RF (+1) already meets the threshold of ≥ 3 — they only need the entry criterion of inflammatory arthritis. Conversely, a patient without any psoriasis history needs points from nail changes, dactylitis, negative RF, AND imaging to reach the threshold.

The following algorithm outlines the systematic approach when a patient presents with a scaly erythematous rash suspicious for psoriasis:

3. Investigation Modalities — Detailed Breakdown

3.1 Investigations for Diagnosis

Physical examination is the cornerstone of diagnosis ^[3].

Examination Step	What to Look For	Interpretation
Skin survey (fully expose)	Well-demarcated plaques, silvery scale, distribution (extensors, scalp, nails, flexures, sacrum, umbilicus)	Pattern recognition is the primary diagnostic method
Scalp ^[3]	Plaques extending beyond hairline	Differentiates from seborrhoeic dermatitis (stays within hairline)
Nails ^[3]	Pitting, onycholysis, oil-drop sign, subungual hyperkeratosis, leukonychia ^[3]	More common in patients with psoriatic arthritis and may be one of the strongest clinical predictors for concomitant psoriatic arthritis ^[3]
Post-auricular areas ^[3]	Hidden plaques	Common occult site
Gluteal cleft / umbilicus ^[3]^[10]	Hidden psoriatic plaques in the scalp, gluteal fold or umbilicus ^[10]	Often missed — always check
Auspitz sign	Gentle scraping of plaque → pinpoint bleeding	Positive = highly suggestive of psoriasis
Joints	DIP tenderness, dactylitis, enthesitis (Achilles, plantar fascia), axial mobility	Screen for psoriatic arthritis

Skin biopsy ^[3] is indicated when:

Clinical diagnosis is uncertain or atypical
Need to exclude mimics (especially mycosis fungoides / CTCL in refractory cases)
Erythroderma (biopsy from ≥ 2 sites recommended)

Technique: 4 mm punch biopsy from an established plaque (not too early/evolving, not treated)

Classic histological findings of psoriasis ^[3]:

Histological Feature	Description	Pathophysiological Basis
Epidermal acanthosis ^[3]	Thickening of the whole epidermis with regular elongation of rete ridges	Keratinocyte hyperproliferation driven by IL-17/IL-22; the rete ridges become club-shaped and elongated
Hyperkeratosis (Parakeratosis) ^[3]	Thickening of stratum corneum; parakeratosis = retention of nuclei in stratum corneum	Proliferation of stratum corneum is too rapid such that epidermal cells did not die when they enter stratum corneum ^[3] — i.e., the transit time is so short (~3–5 days vs normal ~28 days) that keratinocytes retain their nuclei
Hypogranulosis of stratum granulosum ^[3]	Thinning or absence of the granular layer	Keratinocytes skip normal terminal differentiation (granular layer formation) due to accelerated transit
Inflammatory infiltrates in dermis and epidermis ^[3]	Perivascular lymphocytic infiltrate (T cells) and neutrophils	T cell and dendritic cell-driven inflammation; the IL-23/IL-17 axis
Munro's microabscess ^[3]	Collections of neutrophils within the parakeratotic stratum corneum	IL-17A induces keratinocytes to produce CXCL1/CXCL8 → neutrophil chemotaxis → neutrophils migrate through epidermis and collect in the stratum corneum
Pustule of Kogoj ^[3]	Spongiform pustule of neutrophils within the stratum spinosum	Same neutrophil recruitment mechanism but at a deeper epidermal level; more prominent in pustular psoriasis
Dilated, tortuous capillaries in dermal papillae	Capillary loops extend close to skin surface	VEGF-driven angiogenesis from chronic inflammation; explains Auspitz sign
Thinned suprapapillary plate	Epidermis overlying dermal papillae is thin (only 2–3 cell layers)	Combination of elongated rete ridges "stretching" the suprapapillary epidermis thin

Histology Teaching Point

The histological triad that is virtually diagnostic of psoriasis: (1) Parakeratosis with hypogranulosis (= abnormal maturation), (2) Regular acanthosis with club-shaped rete ridges (= hyperproliferation), (3) Munro's microabscesses (= neutrophilic inflammation). If you see all three, you can confidently diagnose psoriasis on biopsy.

Investigation	When to Order	What You're Looking For
KOH scraping + Fungal culture	Annular lesions, nail changes, unilateral/asymmetric	Dermatophyte hyphae (tinea); exclude tinea incognito or onychomycosis
VDRL / RPR serology	Widespread papulosquamous rash, especially if palms/soles involved, sexual risk factors	Secondary syphilis (which can mimic guttate psoriasis)
Throat swab + ASO titre	Guttate psoriasis in children/young adults	Group A Streptococcus pharyngitis is STRONGLY associated with guttate psoriasis ^[3]; guides decision to treat strep throat
Patch testing	Suspected contact dermatitis overlap	Identifies contact allergens
Wood's lamp	Flexural lesions	Coral-red fluorescence → erythrasma (Corynebacterium minutissimum)
HIV testing	Severe, refractory psoriasis	HIV infection: severe, refractory psoriasis may be the initial presentation ^[4]; test especially in atypical, explosive-onset, treatment-resistant cases

These are not diagnostic per se but are essential for guiding treatment decisions and meeting criteria for systemic therapy or biologics.

Indications for systemic therapy according to Guidelines issued by the British Association of Dermatologists ^[9] and AAD Guidelines of Care ^[13] use severity measures to determine treatment escalation.

Tool	What It Measures	Scoring / Thresholds
BSA (Body Surface Area)	Percentage of body affected	Patient's palm ≈ 1% BSA. Mild: < 3%; Moderate: 3–10%; Severe: > 5–10% BSA ^[13]
PASI (Psoriasis Area and Severity Index) ^[4]	Composite of erythema, induration, scaling, and area in 4 body regions (head, trunk, upper limbs, lower limbs)	Range 0–72. Mild: < 10; Moderate: 10–20; Severe: > 20. PASI 75 (75% reduction) is the standard efficacy endpoint in clinical trials
DLQI (Dermatology Life Quality Index) ^[4]	Patient-reported quality of life impact	10 questions, score 0–30. > 10 = significant impact; used to justify systemic therapy

"Rule of Tens": Moderate-to-severe psoriasis = BSA > 10% OR PASI > 10 OR DLQI > 10. Meeting any one of these typically qualifies for systemic therapy consideration.

Once psoriasis is diagnosed, screening for associated comorbidities is essential because psoriasis is a systemic inflammatory disease, not just a skin problem.

Comorbidity	Investigation	Rationale
Psoriatic arthritis	Joint examination; CASPAR criteria; HLA-B27 typing ^[11]; XR joints if symptomatic; MRI joints (more sensitive than routine radiography in detecting articular, periarticular and soft tissue inflammation ^[10])	~30% of psoriasis patients develop PsA; early detection prevents joint destruction
Metabolic syndrome	Fasting glucose / HbA1c, lipid profile, BMI, waist circumference, BP	Diabetes, heart insufficiency, and obesity occur significantly more often in patients with psoriasis ^[9]
Cardiovascular risk	BP, lipid profile, fasting glucose; consider coronary calcium score in high-risk	Psoriasis patients had an increased adjusted RR for MI ^[9]; psoriasis vessels are more stiff ^[9]
Depression / Suicidal ideation	PHQ-9 or similar screening tool	5.5% of patients had suicidal ideation, and 9.7% wished they were dead ^[9]; psoriasis has enormous psychosocial impact
NAFLD / Liver disease	LFT; fibroscan if on methotrexate	Shared inflammatory pathways; methotrexate hepatotoxicity risk
Folate status	Serum/red cell folate	Rapid cell turnover in psoriasis can contribute to folate consumption ^[14]

When joint symptoms are present, the following are indicated ^[10]^[11]^[12]:

Investigation	Key Findings	Interpretation
CBC with differentials ^[10]	Anaemia of chronic disease; leukocytosis reflecting non-specific inflammatory response ^[10]	Supports inflammatory process; also baseline before DMARD therapy
ESR / CRP ^[10]	↑ ESR and CRP ^[10]	Inflammatory markers; monitor disease activity
HLA-B27 ^[11]^[12]	Positive in ~20–50% of PsA (vs ~90% in AS)	Associated with psoriatic and enthesitis types ^[11]; supports SpA classification; particularly relevant for axial disease
RF and anti-CCP ^[10]	RF present in 2–10% of PsA; anti-CCP in 8–16% ^[10]	Usually negative → negative RF scores 1 point in CASPAR; if positive, re-evaluate for RA overlap
ANA ^[10]	Lower titres (≤ 1/40) in 50%; clinically significant titres (≥ 1/80) in 14% ^[10]	Non-specific; does not contribute to CASPAR; may indicate overlap with SLE if high titre
XR joints ^[10]^[12]	Pencil-in-cup deformity at IP joints; coexistence of erosive changes and new bone formation; small joint erosion and fusion; syndesmophytes ^[10]^[12]	Coexistence of erosion and new bone formation is typical ^[10] — this distinguishes PsA from RA (erosion only) and OA (new bone formation/osteophytes only). Juxta-articular new bone formation distinct from osteophytes scores 1 point in CASPAR
MRI joints ^[10]	Synovitis, enthesitis, bone marrow oedema, tenosynovitis	More sensitive than routine radiography ^[10]; detects early/pre-radiographic disease; useful for sacroiliitis
Synovial fluid analysis ^[10]	Inflammatory synovial fluid (WBC > 2000/mm³, ≥ 50% PMNs, culture negative) ^[10]	Excludes septic arthritis (culture positive) and crystal arthritis (MSU/CPPD crystals); PsA and gout can coexist
Ultrasound joints	Power Doppler signal in synovium/entheses; enthesophytes	Non-invasive; good for enthesitis detection; increasingly used in clinic

Radiological Pearl — Pencil-in-Cup Deformity

This classic XR sign of psoriatic arthritis is seen at the DIP joints. It results from:

Pencil: erosion/resorption narrows the head of the middle phalanx to a point
Cup: proliferative new bone formation widens the base of the distal phalanx into a cup shape

This simultaneous destruction AND proliferation is the hallmark of PsA radiology and distinguishes it from RA (destruction only) and OA (proliferation/osteophytes only).

Before initiating systemic agents (methotrexate, cyclosporine, acitretin, biologics), baseline investigations are required both for safety and monitoring:

Investigation	Purpose	Specific Relevance
CBC	Baseline; detect cytopenias	Methotrexate → bone marrow suppression; cyclosporine → lymphopenia
LRFT (Liver + Renal function)	Hepatic/renal safety	Methotrexate → hepatotoxicity; cyclosporine → nephrotoxicity
Hepatitis B surface Ag, anti-HBc, anti-HCV	Screen for viral hepatitis	Risk of reactivation with immunosuppression (especially anti-TNFα)
CXR	Exclude active TB	Required before biologics (anti-TNFα); anti-TNF has more side effects, TB reactivation ^[9]
QuantiFERON-TB Gold / Tuberculin skin test	Screen for latent TB	Mandatory before biologic therapy; treat latent TB before starting biologics
Fasting lipids, glucose	Metabolic baseline	Both disease-associated risk and drug-related (acitretin → hyperlipidaemia)
Pregnancy test	Exclude pregnancy	Methotrexate and acitretin are teratogenic (Category X); acitretin requires contraception for 3 years post-cessation
Varicella zoster IgG	Immune status	JAK inhibitors (tofacitinib) increase risk of herpes zoster reactivation
Fibroscan / Liver biopsy	Hepatic fibrosis assessment	Cumulative methotrexate dose-related fibrosis; fibroscan at baseline and periodically (traditionally liver biopsy at cumulative dose 1.5 g, now largely replaced by non-invasive methods)

Healthy adult males with chronic plaque psoriasis ( > 5% BSA), without PsA: if UV not available → first-line systemic options (alphabetical order): acitretin, adalimumab, alefacept, cyclosporine, etanercept, infliximab, methotrexate, ustekinumab ^[13]. Pre-treatment workup is mandatory before starting any of these.

Stage	Investigations	Purpose
Diagnosis	Clinical examination (primary); skin biopsy if atypical; KOH/fungal culture; VDRL; throat swab + ASO (guttate)	Confirm psoriasis; exclude mimics
Severity assessment	BSA, PASI, DLQI	Guide treatment escalation
Comorbidity screening	Joint exam + CASPAR; metabolic panel (glucose, lipids, BMI, BP); depression screening; HIV (if severe/refractory)	Detect PsA, metabolic syndrome, CV risk, depression
Pre-treatment workup	CBC, LRFT, HBV/HCV serology, CXR, QuantiFERON, pregnancy test, fasting lipids/glucose, fibroscan	Safety before systemic therapy
Monitoring on therapy	Regular CBC, LRFT, lipids (acitretin); BP + creatinine (cyclosporine); fibroscan (methotrexate)	Detect drug-related adverse effects

High Yield Summary

Psoriasis is a clinical diagnosis — no blood test confirms it. Key clinical features: well-demarcated plaques, silvery scale, extensor distribution, Auspitz sign, Koebner phenomenon, nail changes
Always examine hidden sites: scalp (beyond hairline), nails, post-auricular, gluteal cleft, umbilicus
Skin biopsy when in doubt: look for parakeratosis + hypogranulosis, regular acanthosis, Munro's microabscesses, dilated papillary capillaries
Guttate psoriasis: check throat swab + ASO for GAS
Severe/refractory psoriasis: check HIV
CASPAR criteria for PsA: entry = inflammatory musculoskeletal disease; then ≥ 3 points from psoriasis (current +2, Hx +1, FHx +1), nail lesions (+1), dactylitis (+1), RF negative (+1), juxta-articular new bone (+1)
PsA radiology: pencil-in-cup deformity = simultaneous erosion + new bone formation (cf. RA = erosion only, OA = osteophytes only)
Pre-biologic workup: CXR + QuantiFERON (TB screening), Hep B/C serology — anti-TNF carries risk of TB reactivation
Severity thresholds (Rule of Tens): BSA > 10 OR PASI > 10 OR DLQI > 10 → moderate-to-severe → systemic therapy indication
Comorbidity screening: metabolic syndrome, CV risk, depression (5.5% suicidal ideation), NAFLD

Active Recall - Psoriasis Diagnosis and Investigations

References

^[2] Senior notes: Maksim Medicine Notes.pdf (Section 4.3 Psoriasis, p69) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1791–1795 — Psoriasis, Diagnosis) ^[4] Senior notes: Ryan Ho Rheumatology.pdf (p120–122) ^[6] Senior notes: Block A - Dermatology PBL 1.pdf (p11–12) ^[9] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf (p36–41) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1708–1713 — Psoriatic Arthritis, Diagnosis) ^[11] Senior notes: Adrian Lui Pediatrics Notes.pdf (p456) ^[12] Senior notes: Maksim Medicine Notes.pdf (Section 13.6 Spondyloarthritides, p321–324) ^[13] Lecture slides: GC 090. Treatments for skin diseases.pdf (p117–118) ^[14] Senior notes: Block A - Pallor_ diagnosis of anaemia; nutritional anaemia; anaemia of systemic diseases.pdf (p19)

Management of Psoriasis

The management of psoriasis is guided by several overarching principles that must be understood before diving into specific therapies:

Psoriasis is chronic and incurable — the goal is disease control, not cure. Treatment aims to minimise disease activity, prevent complications, and optimise quality of life.
Management is individualised — choice of therapy depends on: age, type of psoriasis, site, extent of involvement, previous treatments, associated medical disorders, life-style of patients ^[15].
General treatment hierarchy: topical → phototherapy → systemic Tx → biologics ^[4] — a step-up approach escalating intensity with disease severity.
Treat the whole patient, not just the skin — screen and manage comorbidities (PsA, CV risk, metabolic syndrome, depression).
Systemic corticosteroids are NOT used — corticosteroid taper precipitates very severe psoriatic flare, pustular psoriasis → so that is why systemic corticosteroids [are] not used for this condition ^[5].

"I hardly ever give systemic steroids to patients — only those with pemphigus/pemphigoid" ^[16]

This is a high-yield GC exam topic.

Indications for systemic therapy ^[13]:

Failure of adequate trial of topical therapy

Repeated hospital admissions for topical therapy

Extensive chronic plaque psoriasis in the elderly or infirm

Generalised pustular or erythrodermic psoriasis

Severe psoriatic arthropathy

Rule of tens: BSA > 10%, or PASI score > 10, or DLQI > 10 ^[13]

GC High Yield — Rule of Tens

The Rule of Tens is the standard threshold for escalation to systemic therapy:

BSA > 10%, OR
PASI > 10, OR
DLQI > 10

Any one of these qualifies. This is a commonly tested concept. PASI 75 = 75% reduction in the PASI score from baseline ^[15] — this is the standard efficacy endpoint used in clinical trials.

Old treatment: 2 out of 3 failures [of conventional systemic agents] before we use biologics ^[9] — historically, patients needed to fail at least 2 conventional systemics before biologic eligibility. Modern guidelines are more flexible, especially with the safety profile of newer IL-17/IL-23 inhibitors.

4. Treatment Modalities — Detailed Breakdown

Measure	Rationale
Emollients ^[4]	Helpful adjunct to keep psoriatic skin soft and moist → ↓itchiness, tenderness → ↓koebnerization with development of new psoriatic lesions at sites of trauma ^[4]; reduces mechanical trauma to scale which would otherwise trigger the Koebner phenomenon
CVS RF control ^[4]	Chronic psoriasis is associated with ↑cardiovascular risk ^[4]; active management of HTN, dyslipidaemia, diabetes, obesity
Smoking cessation	Smoking exacerbates psoriasis severity; especially relevant for palmoplantar pustulosis
Weight loss	Obesity amplifies inflammation via adipokines (TNF-α, IL-6); weight reduction demonstrably improves PASI scores
Alcohol reduction	Worsens psoriasis; increases methotrexate hepatotoxicity; associated with poor treatment compliance
Counselling ^[4]	Counselling on impact of psoriasis on various aspects of life + involvement in treatment decision; reassurance: psoriasis is generally non-life-threatening ^[4]
Psychological support	Depression screening; referral if needed; peer support groups
Avoidance of triggers	Stress management; avoid drugs that exacerbate (β-blockers, lithium, antimalarials, NSAIDs); treat streptococcal infections promptly

4.2 Topical Therapy (Mild Disease — First Line)

Corticosteroid: mainstay of topical treatment → anti-inflammatory, antiproliferative, immunosuppressive ^[4].

Mechanism: Corticosteroids bind intracellular glucocorticoid receptors → translocate to nucleus → (1) transactivation of anti-inflammatory genes (lipocortin-1 → inhibits phospholipase A2 → ↓arachidonic acid → ↓prostaglandins/leukotrienes), (2) transrepression of pro-inflammatory genes (NF-κB, AP-1) → ↓cytokines (IL-1, IL-6, TNF-α), ↓keratinocyte proliferation.

Potency selection based on body site — because skin thickness (and therefore absorption) varies dramatically:

% dose absorbed: sole of foot (0.14%), palm (0.83%), forearm (1%), scalp (3.5%), forehead (6%), mandible (13%), genitalia (42%) ^[4]^[17]

↑absorption by ointment form or occlusive dressing ^[4]^[17]

Steroid ladder in HK ^[4]^[17]:

Potency	Examples	Appropriate Sites
Mild	Hydrocortisone 0.5%, 1%	Face, flexures, infants
Moderate	Clobetasone butyrate (Eumovate) 0.05%, fluocinolone acetonide (Synalar) 0.005%, 0.0125%	Face, flexures (short-term), mild trunk/limb disease
Potent	Betamethasone dipropionate (Diprosone) 0.05%, betamethasone valerate (Betnovate) 0.1%, fluocinolone acetonide (Synalar) 0.025%, mometasone furoate (Elomet) 0.1%	Trunk, limbs — standard potency for plaque psoriasis
Very potent	Clobetasol propionate (Dermovate) 0.05%, diflucortolone valerate (Nerisone) 0.1%	Super-high potency reserved for severe dermatoses especially over palms and soles ^[17]

Commonly prescribed: 0.1% betamethasone ^[12]

Vehicle selection: Lotion < cream < ointment < occlusive dressing (in order of increasing potency due to increasing occlusion and absorption) ^[12]

Side effects of topical corticosteroids ^[4]^[17]:

Skin changes with chronic treatment: atrophy, striae, purpura, telangiectasiae (seen in very potent steroids after 2–3 weeks of use!)
Infection risk
Systemic absorption with Cushing syndrome and HPA suppression
Tolerance (tachyphylaxis) with chronic use
Rebound, unstable or pustular psoriasis with sudden cessation

Critical Safety Point

Rebound, unstable or pustular psoriasis with sudden cessation ^[4]^[17] — this applies to topical steroids too, not just systemic. Always taper, never stop abruptly. The risk is especially high with very potent steroids used over large BSA.

Duration: Usually intermittent with tapering (↓tolerance + ↓rebound flare) ^[4]^[17]. A common approach is "weekend therapy" — potent steroid on weekends only as maintenance.

Vitamin D analogues, e.g., calcipotriol, calcitriol, tacalcitol ^[4].

MoA: Unclear, ?related to hypoproliferative effect on keratinocytes ^[4]. More precisely: Vitamin D binds the vitamin D receptor (VDR) on keratinocytes → (1) inhibits keratinocyte proliferation and promotes terminal differentiation, (2) modulates T-cell function (↓Th1/Th17, ↑Treg), (3) inhibits dendritic cell maturation. The net effect is both antiproliferative and immunomodulatory.
Role: as monotherapy or often in combination with corticosteroids ^[4]. The combination of calcipotriol + betamethasone dipropionate (Daivobet/Enstilar) is a widely used first-line topical for plaque psoriasis — synergistic efficacy and reduced steroid side effects.
Side effects: Local irritation (burning, itching), perilesional erythema; hypercalcaemia (rare, only if used over very large BSA > 30% or > 100 g/week)
Contraindications: Hypercalcaemia, severe renal impairment (impaired calcium metabolism)

Agent	Mechanism	Notes
Coal tar ^[4]^[17]	Anti-inflammatory, antipruritic, anti-acanthotic; suppresses DNA synthesis in epidermal cells	Old but effective topical treatment, seldom used due to apparent messiness + irritative effects ^[4]; available as shampoo, bathing soap, paste; stains clothing
Dithranol (Anthralin) ^[4]^[17]	Inhibits mitochondrial respiration in keratinocytes → antiproliferative; generates free radicals → anti-inflammatory	Old but effective treatment, seldom used due to irritative effects ^[4]; Ingram regimen (dithranol in Lassar's paste applied for short-contact periods); stains skin purple-brown
Tazarotene ^[4]	Topical retinoid, seldom used due to irritative effects ^[4]; binds RAR-β/γ → normalises keratinocyte differentiation, ↓hyperproliferation	Teratogenic — contraindicated in pregnancy
Calcineurin inhibitors (tacrolimus, pimecrolimus) ^[17]	Inhibit calcineurin → ↓T-cell activation and IL-2 production	As steroid-sparing agents ^[17]; useful for facial and flexural psoriasis where steroid atrophy risk is high; S/E: initial burning and stinging; caution with sun exposure/phototherapy (↑risk of skin cancer with chronic use) ^[17]

4.3 Phototherapy (Moderate Disease — Second Line)

Phototherapy: narrow band-UVB (311nm), excimer laser (308nm) ^[15].

Narrowband ultraviolet B (UVB): used for psoriasis, atopic eczema, vitiligo, chronic urticaria ^[17].

MoA: UVB photons are absorbed by DNA in epidermal cells → formation of thymine dimers → (1) induces apoptosis of pathogenic T cells in the skin, (2) suppresses local immune response, (3) ↓keratinocyte proliferation. Narrowband (311 nm) is preferred over broadband because it targets the therapeutic wavelength more precisely with fewer side effects.
Protocol: Typically 2–3× per week, gradual dose escalation based on skin type (Fitzpatrick); course of 20–30 treatments
Efficacy: ~70% of patients achieve clearance or near-clearance
Side effects: Erythema (sunburn), skin aging, theoretical ↑risk of skin cancer with long-term cumulative exposure (lower than PUVA)
Contraindications: Photosensitising conditions (SLE, xeroderma pigmentosum), photosensitising drugs, history of melanoma

Psoralen-ultraviolet A (PUVA) ^[17]:

MoA: Psoralen: prodrug of natural photosensitiser → only activated in skin exposed to UVA → cross-link DNA strands when activated ^[17]. This inhibits DNA replication → antiproliferative + immunosuppressive. Psoralen intercalates between DNA base pairs and forms covalent cross-links upon UVA activation.
More complex + associated with ↑adverse effects → generally reserved for poor responders ^[17]
Side effects: Nausea (oral psoralen), phototoxic burns, ↑risk of skin cancer (squamous cell carcinoma especially, with cumulative dose > 200 treatments), cataracts (UV-blocking glasses required for 24h post-treatment), premature photoaging
Contraindications: Pregnancy (psoralen teratogenic), severe hepatic/renal impairment, history of melanoma, photosensitivity disorders, children < 12 years

If UV available → first-line: UVB phototherapy (NB or BB) alone; UVB phototherapy + acitretin; then PUVA; then UVB + MTX ^[13]

4.4 Systemic Therapy (Moderate-to-Severe Disease — Third Line)

MoA: Methotrexate ("metha" = relating to methyl; "trexate" = folate antagonist) → inhibits dihydrofolate reductase → ↓tetrahydrofolate → ↓purine/pyrimidine synthesis → ↓DNA synthesis → antiproliferative effect on rapidly dividing cells (keratinocytes AND lymphocytes). At low doses (as used in psoriasis/PsA), the primary mechanism is actually anti-inflammatory: ↑extracellular adenosine → broad immunosuppression.
Dose: Weekly (NOT daily) — typically 7.5–25 mg once weekly, oral or subcutaneous
Preferred in psoriatic arthritis — to co-treat skin psoriasis ^[4]
Efficacy: ~60–70% achieve PASI 75

Side effects ^[11]:

Hepatotoxicity — dose-dependent fibrosis/cirrhosis; monitor LFT; avoid alcohol; fibroscan at baseline and periodically
Bone marrow suppression — pancytopenia; monitor CBC; co-prescribe folic acid 5 mg (on non-MTX days) to reduce haematological toxicity
Interstitial pneumonitis — acute hypersensitivity reaction (not dose-related); present with cough, dyspnoea, fever; CXR shows bilateral infiltrates
Nephrotoxicity — rare at psoriasis doses
Teratogenicity — Category X; both men and women must use contraception during and for 3 months (men) / 1 ovulatory cycle (women) after cessation
GI upset, stomatitis, alopecia

Contraindications: Pregnancy/breastfeeding, active infection, significant hepatic impairment, pre-existing cytopenias, significant renal impairment (↓clearance → ↑toxicity), active peptic ulcer, heavy alcohol use

Alcohol: ↑risk of development, worsening, mortality of psoriasis + associated with ↓effectiveness of Tx (especially may be dangerous in potentiating toxicity of methotrexate) ^[4]

MoA: Cyclosporine ("cyclo" = cyclic peptide; "sporine" = derived from fungus Tolypocladium inflatum) → binds cyclophilin → inhibits calcineurin → blocks NFAT nuclear translocation → ↓IL-2 transcription → ↓T-cell activation and proliferation. Rapid onset (2–4 weeks), making it useful for acute flares.
Dose: 2.5–5 mg/kg/day orally
Also active against skin psoriasis ^[4]
Efficacy: Very effective; ~70–80% achieve PASI 75; fast onset

Side effects:

Nephrotoxicity — the major dose-limiting toxicity; dose-dependent vasoconstriction of renal afferent arterioles → ↓GFR; monitor creatinine closely
Hypertension — renal vasoconstriction + sodium retention; monitor BP at every visit
Hyperlipidaemia
Hypertrichosis, gingival hyperplasia
↑Risk of infections and malignancy (especially skin cancers and lymphoma with prolonged use)
Tremor, paraesthesia, headache

Contraindications: Renal impairment, uncontrolled hypertension, concurrent PUVA or other immunosuppressants, malignancy, active infection

Duration: Should ideally be limited to 1–2 years due to cumulative nephrotoxicity

Avoid HCQ [hydroxychloroquine]: may exacerbate psoriasis ^[12]

Retinoids, e.g., acitretin (Neotigason) ^[4]:

MoA: ↑differentiation, ↓hyperkeratosis, anti-inflammatory effects ^[4]. Acitretin binds nuclear retinoic acid receptors (RAR) → normalises keratinocyte differentiation and proliferation; also has immunomodulatory effects.
Use: severe psoriasis, including pustular and erythrodermic forms, often in combination with phototherapy ^[4]
Dose: 25–50 mg daily orally
Efficacy: Moderate as monotherapy (~40% PASI 75); excellent when combined with UVB or PUVA (synergistic)

Side effects ^[4]:

Dry skin/mucous membranes, cheilitis (almost universal), alopecia
Deranged LFT or hepatotoxicity
↑Triglycerides (retinoids ↑VLDL synthesis)
Skeletal abnormalities with long-term use (hyperostosis, calcification of ligaments)
Teratogenicity — Category X; extremely long half-life of the active metabolite etretinate → women must avoid pregnancy for 3 years after stopping acitretin (the longest wash-out period of any dermatological drug)
Alcohol converts acitretin to etretinate (even longer half-life) → women must absolutely avoid alcohol during and after treatment

Contraindications: Pregnancy (current or planned within 3 years), breastfeeding, severe hepatic/renal impairment, pre-existing hyperlipidaemia

Acitretin — The 3-Year Rule

Women of childbearing age on acitretin must use contraception for 3 years after stopping the drug. This is because acitretin can be converted to etretinate (especially with alcohol), which has a half-life of ~120 days and is stored in adipose tissue. No other dermatological drug has such a prolonged teratogenic risk window. This is a favourite exam question.

Apremilast (PDE-4 inhibitor) ^[15]:

MoA: Apremilast ("a" = anti; "premilast" from PDE4) → inhibits phosphodiesterase 4 (PDE4) → prevents breakdown of cAMP → ↑intracellular cAMP → activates protein kinase A → suppresses NF-κB → ↓production of pro-inflammatory cytokines (TNF-α, IL-17, IL-23, IFN-γ) and ↑anti-inflammatory IL-10.
Dose: 30 mg BD orally (after titration)
Efficacy: Moderate (~30–40% PASI 75); inferior to biologics but oral and well-tolerated
Side effects: GI (diarrhoea, nausea — common early, usually self-limiting), weight loss, headache, depression/mood changes
Contraindications: Pregnancy; caution in patients with depression/suicidal ideation
Advantage: No immunosuppression → no need for TB screening or hepatitis screening; does not require laboratory monitoring

4.5 Biologic Therapy (Severe / Refractory Disease)

Biologics represent the most targeted therapies available and have revolutionised psoriasis management. They target specific cytokines in the IL-23/IL-17 axis.

Biologic categories for psoriasis ^[4]^[15]:

Agent	Structure	Dose/Route	Key Points
Adalimumab	Fully human monoclonal antibody	SC every 2 weeks	Most widely used anti-TNF; also treats PsA, IBD
Infliximab	Chimeric monoclonal antibody	IV infusion at weeks 0, 2, 6, then Q8w	Fastest onset of all biologics; useful for severe/erythrodermic psoriasis; infusion reactions possible
Etanercept	Soluble TNF receptor fusion protein	SC once/twice weekly	Least potent anti-TNF for psoriasis; better for PsA

MoA: TNF-α is a master pro-inflammatory cytokine that amplifies the entire psoriatic cascade (activates NF-κB in keratinocytes, promotes dendritic cell maturation, induces endothelial adhesion molecules). Blocking TNF-α interrupts this amplification loop.
Efficacy: ~60–70% achieve PASI 75 (adalimumab, infliximab); ~40–50% (etanercept)

Side effects:

Anti-TNF has more side effects, TB reactivation ^[9] — TNF-α is essential for granuloma maintenance → blocking it allows dormant M. tuberculosis to reactivate
↑Risk of serious infections (bacterial, fungal, viral)
HBV reactivation
Demyelinating diseases (rare; contraindicated in MS)
Worsening heart failure (contraindicated in NYHA III/IV)
Paradoxical psoriasis — some patients develop NEW psoriasiform lesions on anti-TNF therapy; mechanism unclear but involves ↑IFN-α from plasmacytoid dendritic cells
Injection site reactions, infusion reactions (infliximab)
Possible modest ↑risk of lymphoma (debated)

Contraindications: Active TB or untreated latent TB, active serious infection, HBV without antiviral prophylaxis, demyelinating disease (MS), severe heart failure (NYHA III/IV), malignancy (relative)

Ustekinumab ^[4]^[13]:

MoA: Ustekinumab ("ust" = u-stekinumab) → monoclonal antibody against the p40 subunit shared by IL-12 and IL-23. IL-12 drives Th1 differentiation; IL-23 drives Th17 differentiation. Blocking p40 interrupts both pathways simultaneously.
Dose: 45 mg (< 100 kg) or 90 mg (≥ 100 kg) SC at weeks 0, 4, then Q12w
Efficacy: ~70% PASI 75
Advantage: Very convenient dosing (every 12 weeks); good safety profile
Side effects: Upper respiratory tract infections, headache, fatigue; generally well-tolerated
Contraindications: Active TB, serious infections

Anti-IL-17 (secukinumab, ixekizumab) ^[4]^[15]:

Agent	Target	Notes
Secukinumab	IL-17A	300 mg SC weekly × 5, then Q4w
Ixekizumab	IL-17A	160 mg SC week 0, then 80 mg Q2w × 12w, then Q4w
Brodalumab	IL-17 receptor A	Blocks IL-17A, IL-17F, IL-17E simultaneously
Bimekizumab	IL-17A + IL-17F	Dual neutralisation; highest PASI 90 response rates

MoA: IL-17A is the key effector cytokine driving keratinocyte hyperproliferation and neutrophil recruitment. Blocking IL-17A is the most direct way to interrupt the effector phase of psoriasis.
Efficacy: Highest among all biologics — ~80–90% achieve PASI 75; ~60–70% achieve PASI 90
Side effects:
- Candidiasis (oral, mucocutaneous) — IL-17 is critical for mucosal immunity against Candida; blocking it removes this defence. Usually mild and treatable.
- Neutropenia (usually mild)
- ↑Risk of IBD flare/new-onset IBD — IL-17 has protective roles in the gut; blocking it may unmask or exacerbate IBD. Avoid in patients with active IBD.
Contraindications: Active IBD (Crohn's disease), active serious infections

IL-23 inhibitors ^[15]:

Agent	Target
Guselkumab	IL-23 p19 subunit
Risankizumab	IL-23 p19 subunit
Tildrakizumab	IL-23 p19 subunit

MoA: Unlike ustekinumab (which blocks both IL-12 and IL-23 via p40), these agents specifically target the p19 subunit unique to IL-23. This selectively blocks Th17 pathway without affecting Th1 pathway (which depends on IL-12 alone). This is more targeted and preserves broader immune surveillance.
Efficacy: Excellent — ~85–90% PASI 75; high sustained response; some patients achieve drug-free remission after withdrawal
Side effects: Very favourable safety profile; upper respiratory infections, injection site reactions; minimal immunosuppression
Advantage: Long dosing intervals (e.g., risankizumab Q12w after loading); increasingly used as first-line biologic

Deucravacitinib (TYK2 inhibitor) ^[15]:

MoA: Deucravacitinib ("deucra" = allosteric; "vacitinib" = JAK/TYK inhibitor) → selectively inhibits TYK2 (Tyrosine Kinase 2) by binding to its regulatory pseudokinase domain (allosteric inhibition). TYK2 mediates signalling downstream of IL-23, IL-12, and type I interferons. By selectively inhibiting TYK2 (rather than JAK1/2/3), it avoids the broader immunosuppressive effects seen with pan-JAK inhibitors (tofacitinib, baricitinib).
Dose: 6 mg QD orally
Efficacy: ~55–60% PASI 75; superior to apremilast
Side effects: Nasopharyngitis, upper respiratory infections, herpes simplex, acne; better safety profile than JAK inhibitors
Advantage: Oral; does not require laboratory monitoring for haematological parameters (unlike JAK inhibitors)
Contraindications: Pregnancy; avoid in active serious infections

Subtype	Specific Management Considerations
Chronic plaque	Stepwise: topical → phototherapy → systemic → biologic (standard algorithm above)
Guttate	Throat swab/ASO; treat streptococcal infection with antibiotics (penicillin V); often self-limiting; NB-UVB if persistent; tonsillectomy reserved for patients with clear relationship of flares with tonsillitis ^[4]
Pustular (generalised — von Zumbusch)	Medical emergency; acitretin for pustular forms ^[4]; cyclosporine (rapid onset); infliximab; supportive (fluid/electrolytes/temperature); NEVER systemic steroids ^[5]
Erythrodermic	Medical emergency; admit; supportive care (fluid replacement, electrolyte correction, temperature management, nutritional support); cyclosporine or infliximab (rapid-acting); close monitoring of vitals (temp, haemodynamics) ^[4]
Inverse (flexural)	Low-potency topical steroids (face/flexures); calcineurin inhibitors (tacrolimus/pimecrolimus) as steroid-sparing; vitamin D analogues
Scalp	Tar-based shampoo; potent topical steroid scalp lotions/solutions (betamethasone valerate 0.1% scalp lotion); calcipotriol scalp solution
Nail	Topical steroids (under occlusion); calcipotriol; difficult to treat topically (poor penetration); systemic therapy often needed; biologics effective
Palmoplantar	Very potent topical steroids (thick skin → low absorption); acitretin; PUVA (topical psoralen "soak" PUVA); biologics if refractory

Management of PsA — addressed briefly as it overlaps with dermatological management ^[4]^[12]:

Severity	Treatment
Mild arthritis	NSAIDs / local steroid injection ^[4]^[12]
Active arthritis (≥ 3 tender/swollen joints)	Early use of DMARDs ^[4]^[12]: Methotrexate preferred (co-treats skin); sulfasalazine (preferred in non-psoriatic SpA); leflunomide; cyclosporine
Refractory to conventional DMARDs	Anti-TNF-α ^[4]; anti-IL-17 (secukinumab, ixekizumab — dual skin + joint efficacy); anti-IL-23 (guselkumab); JAK inhibitors (tofacitinib, upadacitinib)
Enthesitis	NSAIDs (1st line) ± local steroid injections (except Achilles tendon due to ↑risk of tendon rupture); TNF-α inhibitor if refractory (conventional DMARDs not effective for extra-articular manifestations) ^[4]
Dactylitis	NSAIDs (1st line), anti-TNFα (if refractory) ^[4]
Axial symptoms	As in axial SpA (conventional DMARDs not effective) ^[4]; NSAIDs → anti-TNF / anti-IL-17

Note risk of psoriasis flare upon tapering oral steroids → CAUTIOUS with starting oral steroids ^[4] — even as bridging therapy in PsA, oral corticosteroids carry the risk of skin psoriasis flare on tapering.

Avoid HCQ: may exacerbate psoriasis ^[12] — hydroxychloroquine is a standard DMARD for RA but is contraindicated in PsA because antimalarials exacerbate psoriasis.

Drug	Key Contraindications in Psoriasis Context
Systemic corticosteroids	Absolutely contraindicated — rebound flare → pustular/erythrodermic psoriasis ^[5]
Hydroxychloroquine	May exacerbate psoriasis ^[12]
Lithium	Relative contraindication → exacerbated by lithium ^[18]
β-blockers	Can trigger or worsen psoriasis (↓cAMP)
Methotrexate	Pregnancy, hepatic impairment, heavy alcohol, renal impairment, cytopenias
Cyclosporine	Renal impairment, uncontrolled HTN, concurrent PUVA, malignancy
Acitretin	Pregnancy (avoid conception for 3 years post-cessation), hyperlipidaemia
Anti-TNF	Active TB, serious infection, NYHA III/IV HF, demyelinating disease
Anti-IL-17	Active IBD (Crohn's disease)

Drugs to AVOID in Psoriasis Patients — Exam Favourite

Contraindications in psoriasis patients ^[5]:

Systemic corticosteroids — rebound flare → pustular/erythrodermic emergency
Hydroxychloroquine / Antimalarials — exacerbates psoriasis
Lithium — exacerbates psoriasis (relative C/I; if essential for bipolar disorder, monitor skin closely)
β-blockers — can trigger/worsen psoriasis
NSAIDs — can exacerbate (though paradoxically used for PsA pain); use with caution

Mnemonic: "CLASH" — Corticosteroids (systemic), Lithium, Antimalarials, (Some) NSAIDs, Hydroxychloroquine

Figure 12 from AAD Guidelines ^[13]:

Topical therapy → if inadequate:

If UV available:

First line: UVB Phototherapy (NB or BB) alone; UVB Phototherapy + Acitretin

Then: PUVA; UVB Phototherapy + MTX

If UV NOT available:

First line (alphabetical): Acitretin, Adalimumab, Alefacept, Cyclosporine, Etanercept, Infliximab, Methotrexate, Ustekinumab

Second line: Acitretin + Biologic; CSA + Biologic; MTX + Biologic; UVB + Biologic; CSA + MTX

Treatment of psoriasis ^[15]:

Step	Modalities	Key Agents
1. Topical Treatments	Corticosteroids, vitamin D3 analogues, coal tar, calcineurin inhibitors ^[15]	Betamethasone 0.1%, calcipotriol, Dermovate (palms/soles)
2. Phototherapy	Narrow band-UVB (311 nm), excimer laser (308 nm) ^[15]	NB-UVB 2–3×/week; PUVA for refractory
3. Systemic Therapy	Apremilast (PDE-4 inhibitor), methotrexate, cyclosporine, retinoids, biologics (TNF-α inhibitor, IL-12/-23 inhibitor, IL-17 inhibitors, IL-23 inhibitors), Deucravacitinib (TYK2 inhibitor) ^[15]	Step-up based on severity and response

High Yield Summary

Treatment ladder: Topical → Phototherapy → Conventional systemics → Biologics/small molecules
Rule of Tens for systemic therapy: BSA > 10%, PASI > 10, or DLQI > 10
Topical mainstays: Potent corticosteroid (betamethasone 0.1%) + vitamin D analogue (calcipotriol); choose potency by body site (genital 42% absorption vs sole 0.14%)
Phototherapy: NB-UVB first-line; PUVA reserved for refractory (↑skin cancer risk with cumulative doses)
Conventional systemics: MTX (preferred for PsA), cyclosporine (rapid onset, nephrotoxic), acitretin (pustular/erythrodermic; 3-year teratogenicity window)
Biologics: Anti-IL-23 (guselkumab, risankizumab) and anti-IL-17 (secukinumab, ixekizumab) are most effective; anti-TNF carries TB reactivation risk; ustekinumab (anti-IL-12/23 p40) convenient Q12w dosing
Newer agents: Deucravacitinib (oral TYK2 inhibitor), apremilast (oral PDE4 inhibitor)
NEVER: Systemic corticosteroids (rebound pustular/erythrodermic), hydroxychloroquine (exacerbates), lithium (exacerbates)
Anti-IL-17 contraindication: Active IBD (Crohn's) — IL-17 protects gut
Anti-TNF contraindication: Active TB, NYHA III/IV HF, demyelinating disease — always screen with CXR + QuantiFERON before starting
PsA management: NSAIDs → MTX (preferred) → anti-TNF or anti-IL-17; avoid oral steroids (psoriasis flare on taper); avoid HCQ (exacerbates psoriasis)
Emergencies (pustular/erythrodermic): Admit, supportive care, cyclosporine or infliximab (rapid onset); acitretin for pustular

Active Recall - Psoriasis Management

References

^[4] Senior notes: Ryan Ho Rheumatology.pdf (p66, p107–108, p123–124) ^[5] Senior notes: Block A - Dermatology PBL 1.pdf (p17) ^[9] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf (p35, p39, p41) ^[11] Senior notes: Adrian Lui Pediatrics Notes.pdf (p456) ^[12] Senior notes: Maksim Medicine Notes.pdf (Section 13.6 Spondyloarthritides — PsA management, p324–326) ^[13] Lecture slides: GC 090. Treatments for skin diseases.pdf (p110, p117–118) ^[15] Lecture slides: Derm General Clerkship 2026 Part1.pdf (p30) ^[16] Senior notes: Block A - I have an itchy rash (eczema, urticaria, tinea infection and psoriasis).pdf (p1) ^[17] Senior notes: Ryan Ho Fundamentals.pdf (p419–420) ^[18] Senior notes: Ryan Ho Psychiatry.pdf (p53)

Complications of Psoriasis

Psoriasis is far more than "just a skin disease." The systemic inflammatory state that drives cutaneous manifestations also produces a wide range of complications affecting joints, cardiovascular system, metabolism, mental health, and — in severe subtypes — can threaten life directly.

Psoriasis is a chronic inflammatory reaction → so many complications ^[9]

The complications can be conceptually organised into:

Complications of the disease itself (direct and systemic)
Complications of specific severe subtypes (erythrodermic, pustular)
Complications of treatment

1. Complications of the Disease Itself

Psoriatic arthritis (30%) ^[2] — this is the most important comorbidity of psoriasis.

Pathophysiology: The same IL-23/IL-17/TNF-α axis that drives skin inflammation also targets the entheses (sites where tendons/ligaments insert into bone), synovium, and bone. The shared inflammatory milieu means that skin and joint disease often flare in parallel, though not always.
Pattern: 5 subtypes (Moll and Wright classification — mnemonic "DRAMA") ^[12]:
- DIPJ predominant — associated with nail changes
- RA-like symmetric polyarthritis
- AS-like predominant spondyloarthritis (axial)
- Arthritis Mutilans — destructive, telescoping digits (rarest, most severe)
- Asymmetric oligoarthritis (≤ 4 joints — most common subtype)
Dactylitis ("sausage digits"): uniform swelling of an entire digit due to flexor tenosynovitis — virtually pathognomonic for PsA
Enthesitis: inflammation at tendon insertions (Achilles, plantar fascia) — a hallmark of seronegative spondyloarthropathy
Nail involvement: More common in patients with psoriatic arthritis and may be one of the strongest clinical predictor for concomitant psoriatic arthritis ^[3] — the nail matrix and the DIP joint share a common entheseal complex, so disease at one site predicts disease at the other
Ocular: Anterior uveitis ^[12] — presents with red, painful eye and photophobia; can lead to visual impairment if untreated
Consequence if untreated: Progressive joint erosion and ankylosis; "pencil-in-cup" deformity; functional disability; arthritis mutilans (opera-glass hand)

Why Does Nail Psoriasis Predict Joint Disease?

The DIP joint and the nail matrix are anatomically continuous through a shared entheseal structure called the "functional entheseal unit." The extensor tendon inserts into the distal phalanx and is intimately connected to the nail matrix. Inflammation at this enthesis therefore affects both the nail (causing pitting, onycholysis) and the DIP joint (causing dactylitis, erosion) simultaneously. This is why nail disease in psoriasis is the strongest predictor for developing psoriatic arthritis.

Psoriasis can also affect arteries → stiffness, increased risk of CV disease ^[5]

Increased risk of cardiovascular diseases in patients with severe psoriasis ^[15]:

Three-fold increased risk for myocardial infarction ^[15]
4 year reduction in life expectancy ^[15]

This is one of the most clinically significant complications and is increasingly recognised as a major driver of morbidity and mortality in psoriasis.

Pathophysiology — "The Psoriatic March":

The mechanism linking psoriasis to cardiovascular disease is systemic inflammation driving accelerated atherosclerosis. The steps are:

Chronic cutaneous inflammation → systemic release of pro-inflammatory cytokines (TNF-α, IL-6, IL-17)
Systemic cytokines → insulin resistance (TNF-α inhibits insulin receptor substrate phosphorylation) → metabolic syndrome
Insulin resistance → endothelial dysfunction (↓nitric oxide bioavailability, ↑endothelin-1)
Endothelial dysfunction → ↑vascular adhesion molecules → monocyte recruitment → foam cell formation → atherosclerotic plaque
Plaque progression → major adverse cardiovascular events (MI, stroke, CV death)

Psoriasis vessels are more stiff ^[9]

Key epidemiological data ^[9]:

For a 30-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.29 and 3.10, respectively ^[9]
For a 60-year-old patient with mild or severe psoriasis, the adjusted RR is 1.08 and 1.36, respectively ^[9]
The overall risk among inpatients admitted at least once was increased by 50% compared with the general population (SMR 1.52) ^[9]

The key insight is that the CV risk is disproportionately elevated in younger patients with severe psoriasis — at age 30, severe psoriasis triples MI risk, while at age 60 (when traditional risk factors dominate), the incremental risk from psoriasis is smaller. This means aggressive CV risk factor management should begin early in severe psoriasis patients.

Certain systemic disorders such as diabetes, heart insufficiency, and obesity occur significantly more often in patients with psoriasis than in control subjects ^[9]

Component	Prevalence in Psoriasis	Mechanism
Obesity	34% vs 18% in general population ^[9]	Bidirectional: obesity amplifies psoriasis (adipokines: TNF-α, IL-6, leptin, resistin promote Th17) and psoriasis promotes weight gain (inflammation → insulin resistance → dyslipidaemia → visceral adiposity). Adipose tissue is an active endocrine/immune organ.
Type 2 diabetes mellitus	~2× risk	TNF-α induces insulin resistance by serine phosphorylation of IRS-1 → impaired insulin signalling
Dyslipidaemia	↑TG, ↓HDL	Systemic inflammation → ↑hepatic VLDL production; compounded by acitretin (if used)
Hypertension	~1.5× risk	Endothelial dysfunction; ↑endothelin-1; sympathetic activation from chronic systemic inflammation

Prevalence: Up to 2× higher in psoriasis patients
Mechanism: Shared insulin resistance + TNF-α-mediated hepatic steatosis; compounded by alcohol use and methotrexate hepatotoxicity
Clinical relevance: NAFLD limits the use of methotrexate; requires monitoring with fibroscan

5.5% of patients had suicidal ideation, and 9.7% wished they were dead ^[9]

Depression: affects up to 30% of psoriasis patients — driven by biopsychosocial factors:
- Biological: systemic TNF-α and IL-6 cross the blood-brain barrier and modulate serotonin metabolism (↑indoleamine 2,3-dioxygenase activity → ↓tryptophan → ↓serotonin)
- Psychological: disfigurement, embarrassment, perceived stigma, helplessness from chronic incurable disease
- Social: isolation, impaired intimate relationships, occupational limitations
Anxiety: similarly elevated; anticipatory anxiety about flares
Alcohol and substance misuse: self-medication; alcohol further worsens psoriasis and potentiates methotrexate toxicity — creating a vicious cycle
Patients with severe psoriasis demonstrated an increased overall mortality risk (HR 1.5) ^[9] — this mortality excess is partially driven by CV disease but also by depression, suicide, and substance misuse

Exam Point — Impact on Quality of Life

Psoriasis has one of the highest impacts on quality of life of any medical condition — comparable to cancer, heart disease, and diabetes. The DLQI (Dermatology Life Quality Index) is used to quantify this, and a DLQI > 10 alone can justify systemic therapy escalation under the Rule of Tens. Always ask about psychosocial impact and screen for depression.

Interestingly, one "complication" of psoriasis is actually protective:

Rarely impetiginised in psoriasis ^[15] Increased production of skin-derived antimicrobial peptides ^[15] Protection against secondary infection due to antimicrobial peptide production ^[5]

Psoriatic keratinocytes overproduce antimicrobial peptides (AMPs) — especially cathelicidin (LL-37), human β-defensins, and S100A7 (psoriasin). These AMPs are part of the innate immune response driven by IL-17A stimulation of keratinocytes. As a result, psoriatic plaques are remarkably resistant to secondary bacterial infection — in stark contrast to eczematous skin, which is highly susceptible to S. aureus colonisation and infection (due to defective barrier + downregulated AMPs in Th2-dominant inflammation).

Comorbidity	Notes
Ocular: Blepharitis, conjunctivitis, uveitis, xerosis, corneal lesions ^[3]	Anterior uveitis particularly associated with PsA and HLA-B27
COPD ^[3]	Shared smoking aetiology + systemic inflammation
Chronic kidney disease ^[3]	Chronic inflammatory state → glomerular injury; also drug-related (cyclosporine, NSAIDs)
Malignancy (e.g., lymphoma) ^[3]	Chronic immune stimulation + immunosuppressive treatments (cyclosporine, PUVA with cumulative dose)
NAFLD / Liver cirrhosis ^[3]	Insulin resistance, alcohol, methotrexate
Inflammatory bowel disease	Shared IL-23R genetic variants; gut-skin axis
Folate consumption	Rapid cell turnover in psoriasis → increased folate utilisation ^[14]; can contribute to macrocytosis (though rarely enough to cause frank megaloblastic anaemia)

2. Complications of Severe Subtypes

Erythrodermic psoriasis represents generalised failure of the skin's normal barrier and homeostatic functions. It is a medical emergency.

High risk of complications related to loss of adequate protection ^[3]:

Complication	Mechanism	Consequence
Hypothermia ^[3]^[4]^[8]	Loss of thermoregulation ^[4]: massive cutaneous vasodilation → ↑radiative and convective heat loss from the skin; loss of the insulating stratum corneum barrier	Core temperature drops → cardiac arrhythmias, impaired metabolic function; must be managed in warm, humid environment
High-output cardiac failure ^[3]^[4]^[8]	↑Shunting of blood through skin via peripheral vasodilation ^[4]: the massively inflamed skin acts as a giant arteriovenous shunt → ↑venous return → ↑cardiac output demand. If the heart cannot meet this demand (especially in elderly or those with pre-existing cardiac disease), high-output HF develops.	Dyspnoea, peripheral oedema, elevated JVP; manage with fluid balance and treat underlying skin disease
Hypoalbuminaemia ^[3]^[4]^[8]	Profuse exfoliation of skin leading to oedema and wasting ^[4]: keratinocytes contain protein, and massive exfoliation → significant protein loss through the skin; additionally, systemic inflammation → negative acute phase response → ↓hepatic albumin synthesis	Peripheral oedema (↓oncotic pressure), poor wound healing, malnutrition
Electrolyte abnormalities secondary to fluid loss ^[3]^[4]	Profuse fluid loss → fluid/electrolyte imbalance ^[4]: disrupted stratum corneum → ↑transepidermal water loss (TEWL) by up to 10–20× normal → dehydration + loss of Na⁺, K⁺, Ca²⁺	Hyponatraemia, hypokalaemia, hypocalcaemia; ECG changes; requires IV fluid and electrolyte replacement
Infection and sepsis ^[3]^[4]^[8]	↑Risk of sepsis, e.g., S. aureus sepsis, widespread HSV superinfection ^[4]: despite psoriatic AMP production, the massive barrier disruption in erythroderma overwhelms this defence; billions of organisms can colonise and invade through cracked, fissured skin	Systemic sepsis (S. aureus most common); requires blood cultures + empirical antibiotics if febrile

Erythroderma: mortality up to 4–64%, prognosis generally depends on underlying conditions ^[4]

Good prognosis: psoriasis, atopic dermatitis, drug allergy (improve within weeks/months after Tx) ^[4]

Poor prognosis: Sézary syndrome, paraneoplastic erythroderma ^[4]

Most severe variant = von Zumbusch type of generalised pustular psoriasis ^[3]:

Associated with fever, malaise, diarrhoea, leukocytosis and hypocalcaemia ^[3]
Sepsis, hepatic or respiratory abnormalities are potential complications ^[3]

Complication	Mechanism
Sepsis	Widespread pustulation + epidermal disruption → entry point for bacteria; compounded by leukocyte dysfunction during acute flare
Hepatic abnormalities	Reactive hepatitis from systemic inflammation; cholestasis
Respiratory abnormalities	Neutrophilic infiltration of lungs → sterile pneumonitis; ARDS in severe cases
Hypocalcaemia	Mechanism not fully understood; likely multifactorial — albumin loss (↓total calcium), massive calcium sequestration in inflamed skin, ↑calcitriol consumption by proliferating keratinocytes
Acute kidney injury	Prerenal (dehydration from fluid loss) + sepsis-related intrinsic renal injury

Pustular psoriasis and erythrodermic psoriasis are rare causes of mortality ^[3] — while rare, these subtypes can kill. The advent of effective biologics (infliximab, cyclosporine) has significantly reduced mortality.

Treatment itself carries significant iatrogenic risks, which must be weighed against disease severity:

Treatment	Complication	Mechanism	Monitoring
Topical corticosteroids (chronic/potent)	Skin atrophy, striae, telangiectasia, purpura	Corticosteroids inhibit collagen synthesis and fibroblast proliferation → dermal thinning; visible after 2–3 weeks with very potent steroids	Clinical assessment; limit duration; use steroid-sparing agents
Topical corticosteroids (abrupt cessation)	Rebound pustular psoriasis ^[4]^[17]	Withdrawal of anti-inflammatory suppression → unopposed IL-17/TNF-α surge → explosive flare; same mechanism as systemic steroid rebound	Always taper; never stop abruptly
Methotrexate	Hepatotoxicity, bone marrow suppression, interstitial pneumonitis	Folate antagonism → ↓DNA synthesis in rapidly dividing cells (haematopoietic cells, hepatocytes); cumulative hepatic fibrosis; idiosyncratic pneumonitis	CBC/LFT Q2–4w initially, then Q3m; fibroscan; folic acid supplementation
Cyclosporine	Nephrotoxicity, hypertension	Calcineurin inhibition → vasoconstriction of renal afferent arterioles → ↓GFR; Na⁺ retention → HTN	Creatinine and BP at every visit; limit duration to 1–2 years
Acitretin	Teratogenicity (3-year risk), hyperlipidaemia, hepatotoxicity	Retinoid → disrupts embryonic morphogenesis; ↑hepatic VLDL synthesis	Lipid profile; LFT; strict contraception for 3 years post-cessation
PUVA (cumulative)	Skin cancer (SCC especially), cataracts, photoaging	Psoralen-UVA crosslinks DNA → mutagenesis with cumulative exposure ( > 200 treatments); UV damage to lens	Limit lifetime treatments; UV-blocking glasses for 24h post-treatment; skin cancer surveillance
Anti-TNF-α	TB reactivation, serious infections, HBV reactivation, demyelination	TNF-α maintains granulomas → blocking it → reactivation of latent TB; broad immunosuppression → ↑infection risk	CXR + QuantiFERON pre-treatment; HBV serology; clinical monitoring
Anti-IL-17	Candidiasis, IBD exacerbation	IL-17 is critical for mucosal defence against Candida and intestinal barrier integrity	Monitor for oral thrush; avoid in active Crohn's disease

Scenario	Complication
Guttate → Chronic plaque	~33% of guttate psoriasis progresses to chronic plaque psoriasis; the remainder resolves spontaneously
Stable plaque → Erythrodermic	Triggered by: systemic steroid withdrawal, infection, phototoxic reactions, drug triggers; results in skin failure as above
Stable plaque → Generalised pustular	Triggered by: systemic steroid withdrawal, pregnancy (impetigo herpetiformis), infection; life-threatening
Chronic psoriasis → Treatment-resistant disease	May indicate HIV coinfection (paradoxically severe psoriasis despite immunosuppression); always test HIV in refractory cases

High Yield Summary

Psoriatic arthritis (~30%): 5 subtypes (DRAMA); nail involvement is the strongest predictor; dactylitis and enthesitis are hallmarks; can cause destructive arthritis mutilans if untreated
Cardiovascular disease: Three-fold increased MI risk in severe psoriasis; 4-year reduction in life expectancy; "psoriatic march" — systemic inflammation → insulin resistance → endothelial dysfunction → atherosclerosis; risk disproportionately elevated in YOUNG patients with severe disease
Metabolic syndrome: Obesity (34% vs 18%), T2DM, dyslipidaemia, HTN — all significantly more common; shared inflammatory pathways
Depression/Suicidality: 5.5% suicidal ideation, 9.7% wish they were dead; biopsychosocial aetiology; always screen
Erythrodermic psoriasis = "skin failure": hypothermia, high-output HF, hypoalbuminaemia, electrolyte imbalance, sepsis; mortality up to 64% if untreated
Generalised pustular psoriasis: fever, leukocytosis, hypocalcaemia; sepsis, hepatic/respiratory complications; medical emergency
Infection resistance: Psoriatic plaques rarely get secondarily infected (unlike eczema) due to ↑antimicrobial peptide production (LL-37, β-defensins)
Treatment complications: MTX hepatotoxicity (potentiated by alcohol); cyclosporine nephrotoxicity; PUVA → SCC with cumulative dose; anti-TNF → TB reactivation; anti-IL-17 → candidiasis and IBD flare; steroid withdrawal → rebound pustular psoriasis
Disease progression: Guttate → 33% progress to chronic plaque; stable plaque → erythrodermic or pustular if triggered by steroid withdrawal, infection, or drug triggers

Active Recall - Complications of Psoriasis

References

^[2] Senior notes: Maksim Medicine Notes.pdf (Section 4.3 Psoriasis, p69) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1791–1795) ^[4] Senior notes: Ryan Ho Rheumatology.pdf (p120–124) ^[5] Senior notes: Block A - Dermatology PBL 1.pdf (p17) ^[8] Senior notes: Maksim Medicine Notes.pdf (Erythroderma section, p77) ^[9] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf (p36–37) ^[12] Senior notes: Maksim Medicine Notes.pdf (Section 13.6 Spondyloarthritides — PsA, p324–326) ^[14] Senior notes: Block A - Pallor_ diagnosis of anaemia; nutritional anaemia; anaemia of systemic diseases.pdf (p19) ^[15] Lecture slides: Derm General Clerkship 2026 Part1.pdf (p29) ^[17] Senior notes: Ryan Ho Fundamentals.pdf (p419–420)

High Yield Summary

Definition: Chronic immune-mediated inflammatory skin disease with keratinocyte hyperproliferation → well-demarcated erythematous plaques with silvery scale
Epidemiology: 2% Caucasians, ~0.3–0.6% HK; M=F; bimodal onset (Type 1 early + FHx, Type 2 late + metabolic syndrome)
Genetics: 40% FHx+; HLA-Cw6 (PSORS1) accounts for ~50% heritability; IL12B, IL23A implicated
Pathophysiology: Dendritic cell → IL-12/IL-23 → Th1/Th17 → IL-17A → keratinocyte hyperproliferation + neutrophil recruitment → vicious cycle
Triggers: Strep → guttate; drugs (antimalarials, β-blockers, lithium, NSAIDs); steroid withdrawal → pustular/erythrodermic flare; HIV; trauma (Koebner); stress; smoking; alcohol; obesity
NEVER give systemic steroids → rebound flare (pustular/erythrodermic)
Clinical signs: Auspitz sign, Koebner phenomenon, nail changes (pitting, onycholysis, oil-drop sign), distribution (extensors > flexors)
Key subtypes: Plaque (MC), Guttate (Strep-associated), Pustular (steroid withdrawal), Erythrodermic (emergency), Inverse (flexural)
Psoriasis is systemic: ↑CV risk (psoriatic march), psoriatic arthritis (~30%), metabolic syndrome, depression, NAFLD
Contrast with eczema: well-demarcated vs ill-defined, extensors vs flexors, silvery scale vs weeping/crusting

High Yield Summary

Plaque psoriasis DDx: Think "scaly red plaque" — seborrhoeic dermatitis (greasy, nasolabial, no nails), eczema (ill-defined, flexors), tinea (annular, KOH+), lichen planus (purple, flat-topped, Wickham's striae), mycosis fungoides (refractory, biopsy essential), subacute cutaneous lupus (photosensitive, anti-Ro+)
Guttate DDx triad: guttate psoriasis (Strep Hx, silvery) vs pityriasis rosea (herald patch, collarette) vs secondary syphilis (palms/soles, VDRL+)
Pustular DDx: GPP vs AGEP — both emergencies; GPP = steroid withdrawal/psoriasis flare, lakes of pus, extremities; AGEP = drug-induced, discrete pustules, abdomen, resolves with drug withdrawal
Erythroderma DDx: 5 causes — pre-existing dermatosis exacerbation, drug eruption, malignancy (CTCL/Sézary), infection, idiopathic; always biopsy from 2+ sites
Key investigations to differentiate: KOH scraping (tinea), fungal culture (onychomycosis), VDRL (syphilis), skin biopsy (mycosis fungoides, erythroderma), patch testing (contact dermatitis), throat swab/ASO (guttate vs pityriasis rosea)
Never forget: Look at scalp, nails, post-auricular, umbilicus for hidden psoriatic plaques — they may clinch the diagnosis

High Yield Summary

Psoriasis is a clinical diagnosis — no blood test confirms it. Key clinical features: well-demarcated plaques, silvery scale, extensor distribution, Auspitz sign, Koebner phenomenon, nail changes
Always examine hidden sites: scalp (beyond hairline), nails, post-auricular, gluteal cleft, umbilicus
Skin biopsy when in doubt: look for parakeratosis + hypogranulosis, regular acanthosis, Munro's microabscesses, dilated papillary capillaries
Guttate psoriasis: check throat swab + ASO for GAS
Severe/refractory psoriasis: check HIV
CASPAR criteria for PsA: entry = inflammatory musculoskeletal disease; then ≥ 3 points from psoriasis (current +2, Hx +1, FHx +1), nail lesions (+1), dactylitis (+1), RF negative (+1), juxta-articular new bone (+1)
PsA radiology: pencil-in-cup deformity = simultaneous erosion + new bone formation (cf. RA = erosion only, OA = osteophytes only)
Pre-biologic workup: CXR + QuantiFERON (TB screening), Hep B/C serology — anti-TNF carries risk of TB reactivation
Severity thresholds (Rule of Tens): BSA > 10 OR PASI > 10 OR DLQI > 10 → moderate-to-severe → systemic therapy indication
Comorbidity screening: metabolic syndrome, CV risk, depression (5.5% suicidal ideation), NAFLD

High Yield Summary

Treatment ladder: Topical → Phototherapy → Conventional systemics → Biologics/small molecules
Rule of Tens for systemic therapy: BSA > 10%, PASI > 10, or DLQI > 10
Topical mainstays: Potent corticosteroid (betamethasone 0.1%) + vitamin D analogue (calcipotriol); choose potency by body site (genital 42% absorption vs sole 0.14%)
Phototherapy: NB-UVB first-line; PUVA reserved for refractory (↑skin cancer risk with cumulative doses)
Conventional systemics: MTX (preferred for PsA), cyclosporine (rapid onset, nephrotoxic), acitretin (pustular/erythrodermic; 3-year teratogenicity window)
Biologics: Anti-IL-23 (guselkumab, risankizumab) and anti-IL-17 (secukinumab, ixekizumab) are most effective; anti-TNF carries TB reactivation risk; ustekinumab (anti-IL-12/23 p40) convenient Q12w dosing
Newer agents: Deucravacitinib (oral TYK2 inhibitor), apremilast (oral PDE4 inhibitor)
NEVER: Systemic corticosteroids (rebound pustular/erythrodermic), hydroxychloroquine (exacerbates), lithium (exacerbates)
Anti-IL-17 contraindication: Active IBD (Crohn's) — IL-17 protects gut
Anti-TNF contraindication: Active TB, NYHA III/IV HF, demyelinating disease — always screen with CXR + QuantiFERON before starting
PsA management: NSAIDs → MTX (preferred) → anti-TNF or anti-IL-17; avoid oral steroids (psoriasis flare on taper); avoid HCQ (exacerbates psoriasis)
Emergencies (pustular/erythrodermic): Admit, supportive care, cyclosporine or infliximab (rapid onset); acitretin for pustular

High Yield Summary

Psoriatic arthritis (~30%): 5 subtypes (DRAMA); nail involvement is the strongest predictor; dactylitis and enthesitis are hallmarks; can cause destructive arthritis mutilans if untreated
Cardiovascular disease: Three-fold increased MI risk in severe psoriasis; 4-year reduction in life expectancy; "psoriatic march" — systemic inflammation → insulin resistance → endothelial dysfunction → atherosclerosis; risk disproportionately elevated in YOUNG patients with severe disease
Metabolic syndrome: Obesity (34% vs 18%), T2DM, dyslipidaemia, HTN — all significantly more common; shared inflammatory pathways
Depression/Suicidality: 5.5% suicidal ideation, 9.7% wish they were dead; biopsychosocial aetiology; always screen
Erythrodermic psoriasis = "skin failure": hypothermia, high-output HF, hypoalbuminaemia, electrolyte imbalance, sepsis; mortality up to 64% if untreated
Generalised pustular psoriasis: fever, leukocytosis, hypocalcaemia; sepsis, hepatic/respiratory complications; medical emergency
Infection resistance: Psoriatic plaques rarely get secondarily infected (unlike eczema) due to ↑antimicrobial peptide production (LL-37, β-defensins)
Treatment complications: MTX hepatotoxicity (potentiated by alcohol); cyclosporine nephrotoxicity; PUVA → SCC with cumulative dose; anti-TNF → TB reactivation; anti-IL-17 → candidiasis and IBD flare; steroid withdrawal → rebound pustular psoriasis
Disease progression: Guttate → 33% progress to chronic plaque; stable plaque → erythrodermic or pustular if triggered by steroid withdrawal, infection, or drug triggers

Psoriasis

1. Definition

2. Epidemiology

2.1 Prevalence and Geographic Variation

2.2 Demographics

2.3 Risk Factors

3. Anatomy and Skin Function Relevant to Psoriasis

3.1 Normal Skin Architecture

3.2 Dermal Vasculature

3.3 Skin Immune System

4. Aetiology and Pathophysiology

4.1 Genetics

4.2 Environmental Triggers

4.3 Pathophysiology — The Immune Loop

4.4 Histopathological Correlates

5. Classification / Types of Psoriasis

5.1 Clinical Subtypes

5.2 Special Populations

6. Clinical Features

6.1 Symptoms (with Pathophysiological Basis)

6.2 Signs (with Pathophysiological Basis)

6.2.1 Skin Signs

6.2.2 Nail Signs (~50–90% lifetime prevalence)

6.2.3 Specific Subtypes — Morphological Signs

6.2.4 Associated Systemic Signs / Comorbidities (The "Psoriatic March")

6.3 Distribution Summary

7. Key Clinical Examination Findings — Summary Table

8. Severity Assessment

Active Recall - Psoriasis (Definition, Epidemiology, Aetiology, Pathophysiology, Clinical Features)

References

1. Framework for the Differential Diagnosis

2. Differential Diagnosis by Psoriasis Subtype

2.1 Plaque Psoriasis — Differentials

2.2 Guttate Psoriasis — Differentials

2.3 Pustular Psoriasis — Differentials

2.4 Erythrodermic Psoriasis — Differentials

2.5 Inverse (Flexural) Psoriasis — Differentials

2.6 Nail Psoriasis — Differentials

2.7 Psoriatic Arthritis — Differentials (Rheumatological Context)

3. Systematic Approach to Narrowing the Differential

4. Summary Differential Diagnosis Table — "At a Glance"

Active Recall - Psoriasis Differential Diagnosis

1. Diagnostic Criteria — Psoriasis (Cutaneous)

1.1 Clinical Diagnostic Features

1.2 Diagnostic Criteria for Psoriatic Arthritis — CASPAR Criteria

2. Diagnostic Algorithm

3. Investigation Modalities — Detailed Breakdown

3.1 Investigations for Diagnosis

3.1.1 Physical Examination (The Primary Diagnostic Tool)

3.1.2 Skin Biopsy (Punch Biopsy)

3.1.3 Investigations to Exclude Mimics

3.2 Severity Assessment Tools

3.3 Investigations for Comorbidity Screening

3.4 Investigations for Psoriatic Arthritis

3.5 Pre-Treatment Investigations (Before Systemic Therapy)

4. Summary — Investigation Purposes at Each Stage

Active Recall - Psoriasis Diagnosis and Investigations

1. Principles of Management

2. Management Algorithm

3. Indications for Systemic Therapy

4. Treatment Modalities — Detailed Breakdown

4.1 General Measures (All Patients)

4.2 Topical Therapy (Mild Disease — First Line)

4.2.1 Topical Corticosteroids

4.2.2 Vitamin D Analogues

4.2.3 Other Topical Agents

4.3 Phototherapy (Moderate Disease — Second Line)

4.3.1 Narrowband UVB (NB-UVB)

4.3.2 PUVA (Psoralen + UVA)

4.4 Systemic Therapy (Moderate-to-Severe Disease — Third Line)

4.4.1 Methotrexate (MTX)

4.4.2 Cyclosporine (Ciclosporin)

4.4.3 Retinoids — Acitretin

4.4.4 Apremilast (PDE4 Inhibitor)

4.5 Biologic Therapy (Severe / Refractory Disease)

4.5.1 Anti-TNF-α Agents

4.5.2 Anti-IL-12/23 (Ustekinumab)

4.5.3 Anti-IL-17 Agents

4.5.4 Anti-IL-23 Agents (Selective p19 Inhibitors)

4.5.5 TYK2 Inhibitor — Deucravacitinib