Psoriasis
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Psoriasis
Definition & Epidemiology
Psoriasis is a chronic, immune-mediated inflammatory disorder of the skin characterized by circumscribed, erythematous, dry, scaling plaques covered by silvery-white lamellar scales. It affects approximately 3% of the general population, with equal sex distribution. About one third of patients have a positive family history. Onset shows a bimodal distribution — peaks at age 22.5 years and again at 55 years.
Pathogenesis
Psoriasis involves both innate and adaptive immune systems, resulting in abnormal keratinocyte proliferation. The key cellular and molecular events:
- Antigen-presenting cells are activated, driving differentiation of T_H1 and T_H17 cells
- The T_H17/IL-17 pathway is now recognized as playing the most significant role (previously thought to be primarily T_H1-mediated)
- Key inflammatory mediators: IL-17, IL-23, TNF-α
- The dermal infiltrate consists predominantly of Th1- and Th17-polarized memory T cells, plus neutrophils, macrophages, and increased dendritic cells
- Chemokines recruit both neutrophils (forming Munro abscesses in the epidermis) and lymphocytes (epidermotropism)
- Vascular remodeling: capillary loops in papillary dermis elongate, "kiss" the epidermis, and remodel to resemble postcapillary venules, allowing leukocyte extravasation into papillary tips — the histological "squirting papillae" sign
Genetics: Polygenic inheritance; strongly associated with HLA-Cw6. Genome-wide studies have identified >85 non-MHC loci increasing psoriasis risk. A 2025 GWAS meta-analysis identified new susceptibility alleles impacting disease mechanisms and therapeutic targets (PMID: 40021644).
Clinical Forms
| Type | Features |
|---|---|
| Psoriasis vulgaris (most common) | Persistent erythematous plaques with silvery scales; predilection for elbows, knees, scalp, sacrum, umbilicus |
| Guttate psoriasis | Small droplike (2–10 mm) scaly papules scattered widely; triggered by streptococcal infection |
| Inverse psoriasis | Erythematous, shiny patches in skin folds (groin, axilla, inframammary); scales absent due to friction |
| Pustular psoriasis | Generalized (von Zumbusch) — 2–3 mm pustules with fever, hypocalcemia; palmoplantar (chronic) |
| Erythrodermic psoriasis | Widespread erythrodermia with fine silvery scales; systemic toxicity |
| Nail psoriasis | Pitting, "oil drop" / "oil spot" sign (salmon macule under nail plate), onycholysis, onychodystrophy |
| Palmoplantar psoriasis | Keratotic scaly patches on palms/soles, often with fissures |
Guttate psoriasis:
Plaque psoriasis (psoriasis vulgaris):
Key Clinical Signs
- Auspitz sign: pinpoint bleeding when scales are removed (exposure of dilated capillaries)
- Köbner (isomorphic) phenomenon: new psoriatic lesions at sites of skin trauma
- Auspitz sign and squirting papillae on histology
- Scales are micaceous — peel in layers, looser at periphery, adherent centrally
- Old thick plaques may resemble oyster shells (psoriasis ostracea)
Systemic Associations
- Psoriatic arthritis: 5–30% of patients; in ~20% it precedes skin lesions
- Chronic kidney disease
- Inflammatory bowel disease
- Hepatic disease
- Cardiovascular disease / metabolic syndrome
- Certain malignancies and infections
Treatment
Topical (mild–moderate)
- Corticosteroids (mainstay)
- Vitamin D analogues (calcipotriol/calcitriol)
- Calcineurin inhibitors (tacrolimus, pimecrolimus) — especially for inverse/facial psoriasis
- Keratolytics (salicylic acid, urea) — to reduce hyperkeratosis and scale
Phototherapy (moderate–severe)
- Narrowband UVB (NB-UVB) — 2–3 times/week
- PUVA (psoralen + UVA)
Conventional Systemic
- Methotrexate — folate antagonist; anti-proliferative and anti-inflammatory
- Cyclosporine — calcineurin inhibitor
- Acitretin — retinoid
- Apremilast — PDE4 inhibitor; reduces inflammatory cytokine expression
Biologics (moderate–severe; targeted immunotherapy)
Targets the specific pathogenic cytokines:
| Target | Drug Class | Examples |
|---|---|---|
| TNF-α | Anti-TNF | Etanercept, adalimumab, infliximab |
| IL-12/23 (p40) | Anti-IL-12/23 | Ustekinumab |
| IL-23 (p19) | Anti-IL-23 | Risankizumab, guselkumab, tildrakizumab |
| IL-17A | Anti-IL-17A | Secukinumab, ixekizumab |
| IL-17RA | Anti-IL-17 receptor | Brodalumab |
Small Molecules
- JAK inhibitors (deucravacitinib, tofacitinib) — block JAK-STAT signaling downstream of IL-17/IL-23
- PDE4 inhibitors (apremilast)
- S1PR1 modulators — under evaluation for lymphocyte trafficking regulation
A 2024 systematic review and meta-analysis confirmed efficacy of biologics for generalized pustular psoriasis (PMID: 39469713).
Histology
- Epidermal: acanthosis (epidermal hyperplasia), parakeratosis (retained nuclei in stratum corneum), hypogranulosis, Munro microabscesses (neutrophils in stratum corneum), spongiform pustules of Kogoj (in spinous layer)
- Dermal: elongated, clubbed rete ridges; thinning of suprapapillary plates; dilated, tortuous capillaries in papillary dermis; mixed lymphocytic and neutrophilic infiltrate
Sources: Andrews' Diseases of the Skin, Goldman-Cecil Medicine, Goodman & Gilman's Pharmacological Basis of Therapeutics, Fitzpatrick's Dermatology
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