Psoriasis

Psoriasis is a chronic, immune-mediated, papulosquamous disorder driven by the IL-23/Th17 axis, characterised by well-demarcated erythematous plaques topped with silvery-white scales and a relapsing-remitting course. For NEET PG it is the prototype papulosquamous disease — master the clinical signs (Auspitz, Koebner, Grattage), the histology, nail/joint involvement, and the topical-to-biologic treatment ladder.

Definition & classification

Psoriasis is a genetically determined, T-cell-mediated inflammatory disease of skin, nails and joints with hyperproliferation of keratinocytes and abnormal differentiation. Epidermal turnover time is drastically reduced from the normal ~28–30 days to 3–4 days, producing the characteristic immature, parakeratotic scale.

Clinical types:

Type	Key features	Exam pearls
Chronic plaque (psoriasis vulgaris)	Commonest (~90%); symmetrical plaques on extensors — elbows, knees, scalp, lumbosacral region	"Vulgaris" = ordinary; extensor distribution (contrast with flexural eczema)
Guttate	Multiple small "rain-drop" papules over trunk; follows streptococcal pharyngitis in children/young adults	Best prognosis; check ASO titre
Pustular	Sterile pustules; generalised (von Zumbusch — fever, toxaemia) or localised (palmoplantar)	von Zumbusch precipitated by steroid withdrawal; emergency
Erythrodermic	>90% body surface erythema & scaling; thermoregulatory/fluid loss	Dermatological emergency; high-output failure
Inverse (flexural)	Smooth, shiny, less scaly plaques in axillae, groin, submammary folds	Mistaken for candidiasis/intertrigo
Nail psoriasis	Pitting, oil-drop sign, onycholysis, subungual hyperkeratosis	Strong marker of psoriatic arthritis
Psoriatic arthritis	Seronegative inflammatory arthritis in ~10–30%	RF negative; HLA-B27 link

High-yield: Guttate psoriasis classically follows a streptococcal throat infection by 1–3 weeks and carries the best prognosis. Generalised pustular psoriasis (von Zumbusch type) is frequently precipitated by abrupt withdrawal of systemic corticosteroids — a key reason systemic steroids are avoided in chronic plaque psoriasis.

Etiology & pathophysiology

Psoriasis results from a dysregulated innate and adaptive immune response in genetically susceptible individuals.

Genetics: Strong familial tendency. The major susceptibility locus is PSORS1 on chromosome 6p21, with HLA-Cw6 being the strongest associated allele (linked particularly to early-onset, guttate and more extensive disease).

Immunopathogenesis flow:

Trigger (trauma/infection/drug) → plasmacytoid dendritic cell activation (LL-37/cathelicidin–DNA complexes) → dendritic cells release IL-23 & IL-12 → Th17 and Th1 activation → IL-17, IL-22, TNF-α release → keratinocyte hyperproliferation + neutrophil recruitment → plaque formation.

The IL-23/Th17 axis is the central therapeutic target — explaining the efficacy of IL-17 and IL-23 inhibitor biologics. TNF-α amplifies the loop, which is why anti-TNF agents work.

Provoking/aggravating factors:

• Trauma → Koebner phenomenon (isomorphic response).
• Infection → streptococcal (guttate), HIV (severe/refractory disease).
• Drugs → Beta-blockers, Lithium, Antimalarials (chloroquine), NSAIDs, KAL/ACE inhibitors, terbinafine, interferon; abrupt systemic steroid withdrawal. Mnemonic: "BLANK" drugs worsen psoriasis.
• Smoking & alcohol, obesity, stress.
• Hypocalcaemia precipitates pustular flares.

High-yield: HLA-Cw6 is the most strongly associated HLA allele; PSORS1 is the principal genetic locus. Lithium, beta-blockers and antimalarials are the classic drug aggravators tested in MCQs.

Clinical features

The lesion is a sharply demarcated, erythematous, indurated plaque with adherent silvery-white (micaceous) scales, typically over extensor surfaces, scalp and lumbosacral area, often symmetrical.

Diagnostic clinical signs (very high-yield):

1. Grattage test (method of Brocq): gentle scraping of the plaque produces silvery scales (candle-grease / signe de la tache de bougie).
2. Auspitz sign: on removing the scales, pinpoint bleeding points appear — due to thinned suprapapillary epidermis over dilated, tortuous dermal papillary capillaries. (Note: Auspitz sign is absent in inverse and pustular psoriasis.)
3. Koebner (isomorphic) phenomenon: new lesions appear along sites of trauma/scratch — also seen in lichen planus, vitiligo, viral warts.

Mnemonic for Koebner-positive conditions: "PLANT" — Psoriasis, Lichen planus, All Nail-trauma related, T (vitiligo, viral warts).

Scalp: thick adherent scaling with relative sparing of hair (non-scarring). Genital/inverse: glazed erythematous plaques.

Nail changes (seen in up to 50%; predictor of arthritis):

Nail sign	Anatomical basis
Pitting	Parakeratosis of proximal nail matrix
Oil-drop / salmon patch	Psoriasis of nail bed seen through plate
Onycholysis	Distal separation of plate from bed
Subungual hyperkeratosis	Nail bed hyperproliferation
Splinter haemorrhages	Dilated bed capillaries

High-yield: Pitting is the most common nail change; oil-drop sign is the most specific. Nail disease is a strong clinical predictor of psoriatic arthritis.

Psoriatic arthritis (Moll & Wright classification, 5 patterns):

1. Asymmetrical oligoarthritis (commonest).
2. Symmetrical polyarthritis (RA-like, but RF negative).
3. Distal interphalangeal (DIP)–predominant (classic, associated with nail disease).
4. Arthritis mutilans ("pencil-in-cup" deformity, telescoping fingers) — most destructive.
5. Spondylitis/sacroiliitis (HLA-B27 linked).

Look for dactylitis ("sausage digit") and enthesitis (e.g. Achilles). It is a seronegative spondyloarthropathy — RF and anti-CCP negative.

Diagnosis & investigation of choice

Psoriasis is primarily a clinical diagnosis. When atypical, skin biopsy is the investigation of choice.

Histopathology (classic features):

• Parakeratosis (retained nuclei in stratum corneum).
• Munro microabscesses — neutrophil collections in the parakeratotic stratum corneum (hallmark).
• Spongiform pustules of Kogoj — neutrophils in the stratum spinosum (characteristic of pustular psoriasis).
• Regular elongation of rete ridges (psoriasiform/acanthotic) with thinning of suprapapillary plates (basis of Auspitz sign).
• Loss of stratum granulosum, dilated tortuous dermal papillary capillaries, Munro–Sabouraud mononuclear infiltrate.

High-yield: Munro microabscess (neutrophils in stratum corneum) and spongiform pustule of Kogoj (neutrophils in stratum spinosum) are the pathognomonic histological clues. Suprapapillary plate thinning + dilated papillary vessels = the Auspitz sign substrate.

Severity scoring — PASI (Psoriasis Area and Severity Index):

• Body divided into 4 regions: head, upper limbs, trunk, lower limbs.
• Each scored for erythema, induration (thickness), and desquamation (scaling) on a 0–4 scale, weighted by area of involvement.
• PASI range = 0 to 72. A PASI 75 response (≥75% reduction from baseline) is the conventional endpoint for treatment efficacy in trials.
• BSA (Body Surface Area) and DLQI (Dermatology Life Quality Index) are used alongside; severe disease ≈ BSA >10% or PASI >10 or DLQI >10 ("rule of tens").

Management / drug of choice

Treatment is stepwise, escalating with severity and refractoriness.

Treatment ladder flow:

Topicals (mild/limited) → Phototherapy (moderate) → Systemic agents (severe/extensive) → Biologics (refractory/severe with comorbidity).

1. Topical therapy (first line, limited disease <5–10% BSA):

Agent	Notes
Topical corticosteroids	Mainstay for rapid control; potent steroids for plaques
Vitamin D3 analogues (calcipotriol, calcitriol)	First-line maintenance; often combined with steroid (e.g. calcipotriol + betamethasone)
Coal tar	Antiproliferative; Goeckerman regimen (tar + UVB)
Dithranol (anthralin)	Ingram regimen; stains skin/clothes
Topical retinoid (tazarotene)	Normalises differentiation
Calcineurin inhibitors (tacrolimus)	Useful for face & flexures (steroid-sparing)
Salicylic acid	Keratolytic adjunct to remove scale

2. Phototherapy (moderate/extensive):

• Narrowband UVB (311–313 nm) — the preferred phototherapy.
• PUVA (Psoralen + UVA): more effective but higher long-term risk of squamous cell carcinoma and photoageing.

3. Conventional systemic agents (severe/extensive/arthritis):

• Methotrexate — drug of choice for severe psoriasis and psoriatic arthritis; folate antagonist; monitor LFTs/CBC; cumulative-dose hepatotoxicity (consider Fibroscan/liver biopsy); teratogenic. Give folic acid supplementation.
• Cyclosporine — fast acting; best for rapid control / erythrodermic flares; limited to short courses due to nephrotoxicity & hypertension.
• Acitretin (oral retinoid) — drug of choice for pustular and erythrodermic psoriasis; highly teratogenic (avoid pregnancy for ≥3 years; no alcohol — converts to etretinate); mucocutaneous dryness, hyperlipidaemia.
• Apremilast — oral PDE-4 inhibitor; modest efficacy, good safety.

4. Biologics (moderate-to-severe, refractory):

Target	Agents
TNF-α	Etanercept, infliximab, adalimumab
IL-12/23 (p40)	Ustekinumab
IL-17	Secukinumab, ixekizumab, brodalumab
IL-23 (p19)	Guselkumab, risankizumab, tildrakizumab

High-yield: Methotrexate is the systemic drug of choice for severe plaque psoriasis and psoriatic arthritis. Acitretin is preferred for pustular & erythrodermic types. Cyclosporine gives the fastest control for acute flares. Systemic corticosteroids are avoided (rebound and risk of pustular conversion on withdrawal).

High-yield: Screen for latent tuberculosis (Mantoux/IGRA + CXR) before starting TNF-α inhibitors and other biologics — reactivation is a key safety concern.

Complications

• Erythroderma — fluid/electrolyte loss, hypothermia, high-output cardiac failure, sepsis.
• Generalised pustular psoriasis (von Zumbusch) — fever, leucocytosis, hypocalcaemia, life-threatening.
• Psoriatic arthritis — joint destruction, arthritis mutilans.
• Psoriatic comorbidities / "psoriatic march": chronic systemic inflammation → metabolic syndrome, obesity, type 2 diabetes, dyslipidaemia, NAFLD, and increased cardiovascular morbidity (MI/stroke). Also higher rates of uveitis, IBD (Crohn's), depression.
• Treatment-related: MTX hepatotoxicity & myelosuppression; cyclosporine nephrotoxicity/HTN; PUVA-related skin malignancy; retinoid teratogenicity.

High-yield: Severe psoriasis is an independent cardiovascular risk factor ("psoriatic march"). Always screen and manage metabolic syndrome.

Key differentials

Condition	Distinguishing features
Seborrhoeic dermatitis	Greasy yellow scales, nasolabial folds/scalp; less well-defined; overlap = "sebopsoriasis"
Lichen planus	Violaceous, flat-topped, pruritic papules; Wickham striae; Koebner positive; oral lacy lesions
Pityriasis rosea	Herald patch → "Christmas-tree" trunk distribution; collarette scale; self-limiting
Tinea corporis	Annular, active scaly edge with central clearing; KOH positive for hyphae
Discoid eczema (nummular)	Coin-shaped, exudative, intensely itchy, ill-defined
Secondary syphilis	Copper-coloured palmoplantar papulosquamous lesions; serology positive
Mycosis fungoides	Persistent patches/plaques; biopsy shows atypical lymphocytes (Pautrier microabscess)
Pityriasis rubra pilaris	Orange-red plaques with islands of sparing, follicular plugging, palmoplantar keratoderma

High-yield: Central clearing + KOH-positive scale = tinea (not psoriasis). Wickham striae + pruritus point to lichen planus. Islands of sparing suggest pityriasis rubra pilaris.

Recently asked / exam angle

• Auspitz sign mechanism — pinpoint bleeding from thinned suprapapillary epidermis over dilated papillary capillaries; remember it is absent in pustular and inverse psoriasis.
• Munro microabscess vs Kogoj pustule location (stratum corneum vs stratum spinosum).
• Drug that worsens psoriasis — lithium / beta-blocker / chloroquine / NSAID (single-best-answer).
• Guttate psoriasis — preceding streptococcal infection; image-based question with rain-drop lesions on trunk.
• Nail signs — oil-drop sign as most specific; pitting as most common; link to arthritis.
• Drug of choice matching: MTX (plaque/arthritis), acitretin (pustular/erythrodermic), cyclosporine (rapid control).
• HLA association — HLA-Cw6 (skin), HLA-B27 (psoriatic spondylitis).
• von Zumbusch triggered by steroid withdrawal; why systemic steroids are contraindicated.
• PASI maximum score = 72; PASI 75 as response endpoint.
• Biologic targets — IL-17 (secukinumab), IL-23 (guselkumab), TNF-α (etanercept); pre-treatment TB screening.
• Arthritis mutilans — "pencil-in-cup" radiographic deformity and telescoping digits.

Rapid revision

1. Psoriasis = T-cell/Th17-mediated; epidermal turnover falls from ~28 days to 3–4 days.
2. HLA-Cw6 strongest allele; PSORS1 main locus; central axis = IL-23/Th17 → IL-17.
3. Auspitz sign = pinpoint bleeding after scale removal; absent in pustular/inverse types.
4. Koebner phenomenon = lesions at trauma sites (also LP, vitiligo, warts).
5. Grattage test yields candle-grease silvery scales.
6. Munro microabscess (stratum corneum) and Kogoj pustule (stratum spinosum) are histologic hallmarks; parakeratosis + rete ridge elongation.
7. Guttate follows streptococcal sore throat; best prognosis; check ASO.
8. von Zumbusch generalised pustular psoriasis follows systemic steroid withdrawal — emergency.
9. Nail: pitting (commonest), oil-drop (most specific), onycholysis, subungual hyperkeratosis — predict arthritis.
10. Psoriatic arthritis = seronegative; arthritis mutilans → pencil-in-cup deformity; HLA-B27 for spondylitis.
11. Drugs worsening psoriasis (BLANK): Beta-blockers, Lithium, Antimalarials, NSAIDs, K/ACE inhibitors.
12. Methotrexate = DOC severe plaque/arthritis; acitretin for pustular/erythrodermic; cyclosporine for rapid control; NBUVB preferred phototherapy; screen TB before biologics; PASI max = 72.