What it is:A chronic, T-lymphocyte-driven systemic inflammatory disease, not just a skin rash. The immune system misfires and tells keratinocytes to multiply way too fast, which is why lesions are thick, scaly, and keep coming back.
The core problem:Genetic susceptibility plus a trigger (infection, skin trauma, stress, certain drugs) sets off an abnormal T-cell response. That response drives keratinocytes to proliferate roughly 10 times fasterthan normal skin turnover, producing the classic thick, silvery, well-demarcated plaques.
What you do about it:Match therapy intensity to severity (BSA/PASI), start with topicals for limited disease, and escalate to phototherapy, systemic nonbiologics, or biologics as disease gets more extensive or comorbidities (especially psoriatic arthritis) enter the picture.
Treat psoriasis like the systemic inflammatory disease it is, not a cosmetic skin problem. That's why comorbidity screening (arthritis, depression, cardiometabolic disease) matters just as much as picking the right cream, and why the biologics all target the same handful of cytokines (TNF-α, IL-12/23, IL-17, IL-23) instead of anything applied to skin.
Every treatment decision starts with "how much skin, how bad." Two measurements do the talking.
| Measure | What it captures | Cutoffs |
|---|---|---|
| BSA(body surface area) | How much skin is involved. One patient's palm ≈ 1% BSA, a quick bedside trick. | Mild ≤5% · Moderate-severe >5–10% · Severe ≥10% |
| PASI(Psoriasis Area and Severity Index) | Combines BSA with erythema, induration, and scaling into one score. | Moderate ≥8 (higher cutoffs used in biologic trials) · Severe ≥10 |
| DLQI(Dermatology Life Quality Index) | How much it affects the patient's actual life. | Severe if ≥10, regardless of BSA |
A patient can have small BSA but still be "severe"if the DLQI is high, think palms, soles, face, or genitals. A tiny plaque on the palm can be more disabling than a large one on the back. Severity isn't just a ruler measurement, it's disease burden.
The 2011 European classification simplifies this into two buckets for treatment purposes: mild(topical therapy is enough) versus moderate-to-severe(needs phototherapy or systemic therapy). That two-bucket split is what the treatment algorithm below is built around.
Skip memorizing the biologic names and learn this pathway instead. Every systemic agent on the market blocks one specific step in it.
Genetic predisposition plus an unknown precipitating factor (skin injury, infection, certain drugs, smoking, alcohol, obesity, psychological stress) triggers an abnormal T-lymphocyte response. The psoriasis susceptibility locus 1 (PSORS1)on chromosome 6p accounts for up to 50% of disease heritability. HLA-Cw6and TNF-αare major susceptibility genes, alongside IL-23.
| Step | What happens | Drug class that blocks it |
|---|---|---|
| 1 | Dermal dendritic cells activate Th1 and Th17 lymphocytes | (upstream, not directly druggable) |
| 2 | IL-23 drives and sustains the Th17 population | IL-23 inhibitors(guselkumab, tildrakizumab, risankizumab) |
| 3 | Th17 cells and other sources release IL-17A, which binds keratinocyte receptors | IL-17A inhibitors(secukinumab, ixekizumab, brodalumab) |
| 4 | TNF-α, interferon-gamma, and IL-1 amplify epidermal hyperplasia and dermal inflammation | TNF inhibitors(adalimumab, etanercept, infliximab, certolizumab) |
| 5 | Keratinocytes proliferate abnormally fast and fail to differentiate properly | Topical vitamin D analogs, retinoids, anthralin (direct antiproliferative action) |
Notice that ustekinumab hits step 2 from a different angle, it blocks the shared p40 subunit of both IL-12 and IL-23, which is why it's classed as "IL-12/23" rather than pure IL-23. The newer, more selective agents (guselkumab, tildrakizumab, risankizumab) only block the p19 subunit unique to IL-23, sparing IL-12. That's a common exam distinction: p40 = old and broader, p19 = new and IL-23-specific.
Classic plaque psoriasis (psoriasis vulgaris) is what you'll see most: erythematous to red-violet plaques, at least 0.5 cm, well-demarcated, topped with silvery flaking scale.They favor extensor surfaces (knees, elbows) but can generalize over large BSA.
| Feature | Detail |
|---|---|
| Pruritus | Can be severe. Frequent scratching causes excoriations; itch is often what drives patients to seek treatment, not the plaques themselves. |
| Psychosocial | Lesions can be physically debilitating or socially isolating, this is why DLQI matters as much as BSA. |
| Comorbidities | Psoriatic arthritis, depression, anxiety, hypertension, obesity, diabetes, Crohn's disease, alcoholism. |
Lithium, NSAIDs, antimalarials, beta-blockers, fluoxetine, and abrupt corticosteroid withdrawalcan all exacerbate preexisting psoriasis. Worth a double-take any time a psoriasis patient starts one of these for an unrelated reason, or flares after stopping a steroid taper too fast.
Psoriatic arthritis develops in about 30% of plaque psoriasis patients.Most often it's polyarticular peripheral arthritis, but presentations vary (peripheral, axial, mono- or polyarticular). Ask about joint pain and stiffness at every visit, it changes the treatment algorithm toward systemic/biologic therapy even if skin involvement alone would call for topicals.
Diagnosis is clinical, based on the physical exam findings of characteristic lesions. Skin biopsy is not diagnosticof psoriasis, it's used to rule other things out, not to confirm psoriasis in.
Once diagnosed, severity is staged using the BSA/PASI/DLQI framework above, which is what actually determines which rung of the treatment algorithm a patient starts on.
Goals:minimize or eliminate lesions, control pruritus, reduce flare frequency, treat comorbidities, identify and manage trigger factors, avoid treatment-related toxicity, keep it cost-effective, counsel (stress reduction matters), and preserve quality of life.
Topical agents→ if inadequate, add phototherapyOR add a systemic agent→ continue moisturizers throughout → once controlled, step down to the lowest potency/dose that maintains control.
Start a systemic agent (commonly methotrexate)± topical or phototherapy; strongly consider a biologicupfront if comorbidities exist (especially psoriatic arthritis) → if inadequate, escalate to a more potent systemic or biologic agent(occasionally rotating two systemics) ± topical → if still inadequate, add a biologic if not already used± other agents → once controlled, step down to the lowest maintaining dose.
Both algorithms end the same way: once controlled, step down to the lowest potency or dose that maintains control, not stop abruptly. This is the same logic as tapering topical steroids to avoid rebound flares.
Anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive. Recommended first-line for limited psoriasis, alone or combined with nonsteroidal topicals. Potency is enhanced by vehicle choice and occlusion.
| Potency | Representative agents |
|---|---|
| Class 1: Superpotent | Clobetasol propionate 0.05%, betamethasone dipropionate 0.05% ointment, halobetasol 0.05% |
| Class 2: Potent | Fluocinonide 0.05%, desoximetasone 0.25%, betamethasone dipropionate cream/gel |
| Class 3: Upper mid-strength | Mometasone furoate 0.1% ointment, triamcinolone acetonide 0.5% |
| Class 4: Mid-strength | Mometasone furoate 0.1% cream, triamcinolone acetonide 0.1% ointment |
| Class 5: Lower mid-strength | Fluticasone propionate 0.05%, hydrocortisone valerate 0.2%, triamcinolone 0.1% cream |
| Class 6: Mild | Desonide, alclometasone dipropionate |
| Class 7: Least potent | Hydrocortisone 0.5–2.5% |
Lower-potencyagents for infants and thin-skin areas (face, intertriginous folds). Mid-to-high potencyis initial therapy for other adult body areas. Reserve superpotent (Class 1)agents for very thick or recalcitrant plaques like palms and soles, and cap them at 2–4 weeksto avoid skin atrophy, HPA-axis suppression, or (rarely) Cushing syndrome.
Vehicle matters:ointments are the most occlusive and potent (best dermal penetration) but greasy; creams/lotions are preferred for daytime use. Cutaneous adverse effects: atrophy, acne, contact dermatitis, striae, telangiectasias, hypopigmentation.
Calcipotriene (Dovonex) and calcitriol (Vectical)are vitamin D3 analogs. They bind vitamin D receptors to inhibit keratinocyte proliferation, enhance differentiation, and inhibit T-lymphocyte activity, striking directly at the overgrowth mechanism. First-line monotherapy or combined with a topical steroid for mild disease; applied BID. Adverse effects are local irritation: burning, pruritus, peeling, erythema.
Tazarotene (Tazorac)is a topical retinoid that normalizes keratinocyte differentiation and clears inflammatory infiltrate. Applied once daily, usually at night; combining with a topical steroid boosts efficacy and cuts irritation. Dose-dependent burning and stinging are common; reduce by using cream form, lower concentration, alternate-day dosing, or short-contact application. Contraindicated in pregnancyand in women of childbearing potential without effective contraception, all retinoids are teratogenic.
Anthralindirectly suppresses keratinocyte proliferation. Short-contact anthralin therapy (SCAT) is preferred: apply only to thick plaques for ≤2 hours then wipe off, protecting surrounding skin with zinc oxide or stiff paste. SCAT concentrations run 1–4%; continuous therapy uses 0.05–0.4%. Use cautiously (if at all) on the face and skin folds, risk of severe irritation and allergic contact dermatitis.
Coal taris keratolytic with possible antiproliferative/anti-inflammatory effects, but used infrequently now due to modest efficacy, slow onset, unpleasant odor, and clothing staining. Low teratogenicity risk makes it an option in pregnancy.
Salicylic acidis keratolytic, useful in shampoos/bath oils for scalp disease, and boosts corticosteroid penetration. Watch for systemic absorption/toxicity with use over >20% BSA or in renal impairment. Not for use in children; okay for limited/localized disease in pregnancy.
Pimecrolimus 1% (Elidel)is a calcineurin inhibitor useful under occlusion and for moderate-to-severe inverse psoriasis(intertriginous areas). Good alternative for face/fold lesions since it skips the steroid atrophy problem and is less irritating than calcipotriene.
UVB(broadband or narrowband, NB-UVB) is given alone, or combined with a topical photosensitizer for enhanced efficacy: crude coal tar (Goeckerman regimen) or anthralin (Ingram regimen).
UVAis typically paired with an oral psoralen photosensitizer, this combination is called PUVA(psoralen + UVA).
Patients need eye protection during and for 24 hours aftertreatment. Oral psoralens taken with food or milk minimize nausea/vomiting. Long-term PUVA causes photoaging and cataracts, and carries a dose-related carcinogenesis risk, don't combine it with cyclosporine (increased cutaneous malignancy risk).
General phototherapy adverse effects: erythema, pruritus, xerosis, hyperpigmentation, blistering.
| Drug | Dose | Key notes |
|---|---|---|
| Retinoid | ||
| Acitretin (Soriatane) | 25 mg/day (low-dose, not for monotherapy) or 50 mg/day; take with meals | teratogenicavoid pregnancy for ≥2 yrs after; no blood donation ≥1 yr after |
| Calcineurin inhibitor | ||
| Cyclosporine | Induction 2.5–5 mg/kg/day divided BID; maintenance 1.25–3 mg/kg/day; taper by 1 mg/kg/day weekly when stopping | Short courses (<12 wk) preferred over continuous to limit nephrotoxicity |
| Antimetabolite | ||
| Methotrexate | Start 7.5–15 mg once weekly, ↑ 2.5 mg q2–4wk to max 25 mg/wk (PO, SC, or IM) | teratogenic/abortifacient; pair with folic acid 1–5 mg daily |
| JAK inhibitor | ||
| Tofacitinib (Xeljanz) | 5 mg PO BID or 11 mg XR once daily; 5 mg once daily if mod-severe renal or mod hepatic impairment | Approved for psoriatic arthritis, not plaque psoriasis; don't combine with biologic DMARDs or potent immunosuppressants |
| PDE4 inhibitor | ||
| Apremilast (Otezla) | Titrate day 1–5 (10 mg → 30 mg BID), then 30 mg BID maintenance | Reduce dose in severe renal impairment; most common effects: diarrhea, nausea, headache |
Relative potency ranking from the handbook: cyclosporine > methotrexate ≥ acitretinwhen used as monotherapy for plaque clearance.
Reserved for moderate-to-severe disease when other systemics are inadequate or contraindicated, or when comorbidities (like psoriatic arthritis) push you there sooner. Cost is the main reason they aren't first-line.
| Drug | Dosing | Notes |
|---|---|---|
| Adalimumab(Humira) | PsA: 40 mg SC q2wk. Plaque psoriasis: 80 mg SC load, then 40 mg SC q2wk starting 1 wk later | Monoclonal TNF-α antibody, rapid control |
| Etanercept(Enbrel) | PsA: 50 mg SC weekly. Plaque psoriasis: 50 mg SC twice weekly ×3 mo, then 50 mg weekly | Fusion protein, fully humanized (unlike chimeric infliximab); approved down to age 4 |
| Infliximab(Remicade) | 5 mg/kg IV at weeks 0, 2, 6, then q8wk | Chimeric antibody; can pair with methotrexate for PsA |
| Certolizumab pegol(Cimzia) | 400 mg SC (2×200 mg) q2wk; if <90 kg: 400 mg at wks 0/2/4 then 200 mg q2wk | PEGylated antigen-binding fragment, no Fc region |
Common adverse effects across the class:infections (URI, sinusitis), injection site reactions, headache, rash. Screen for latent TB before starting any TNF inhibitor.
| Drug | Target | Dosing |
|---|---|---|
| Ustekinumab(Stelara) | IL-12/23 (shared p40 subunit) | ≤100 kg: 45 mg SC at wk 0, 4, then q12wk. >100 kg: 90 mg SC same schedule |
| Guselkumab(Tremfya) | IL-23 (p19 subunit) | 100 mg SC at wk 0, 4, then q8wk |
| Tildrakizumab(Ilumya) | IL-23 (p19 subunit) | 100 mg SC at wk 0, 4, then q12wk; healthcare provider administration only |
| Risankizumab(Skyrizi) | IL-23 (p19 subunit) | 150 mg (two 75 mg SC injections) at wk 0, 4, then q12wk |
Guselkumab is q8wkmaintenance while tildrakizumab and risankizumab are q12wk, despite all three targeting the same p19 subunit of IL-23. Easy to mix up on an exam, tie guselkumab's shorter interval to it being the first-in-class p19 agent with a slightly different dosing trial design.
Ustekinumabadverse effects: URI, headache, fatigue; serious risks shared with other biologics (TB, fungal/viral infection, malignancy), plus a reported association with reversible posterior leukoencephalopathy syndrome (RPLS).
Secukinumab, ixekizumab, and brodalumab all block IL-17A signaling to keratinocytes, comparable efficacy, similar adverse effect profile (nasopharyngitis, URIs, injection site reactions).
| Drug | Structure | Dosing |
|---|---|---|
| Secukinumab(Cosentyx) | Fully human IgG1κ, binds IL-17A directly | 300 mg SC at wk 0, 1, 2, 3, 4, then q4wk |
| Ixekizumab(Taltz) | Humanized IgG4, neutralizes IL-17A | 160 mg SC load, then 80 mg q2wk through wk 12, then 80 mg q4wk |
| Brodalumab(Siliq) | Fully human IgG2, binds the receptor(IL-17RA), not the cytokine | 210 mg SC at wk 0, 1, 2, then q2wk |
Brodalumab is the odd one out: it blocks the IL-17 receptor A, which sits downstream of multiple IL-17 subtypes (not just IL-17A), giving it a theoretically broader block than secukinumab or ixekizumab. Also, neutralizing anti-ixekizumab antibodiescan develop over time and are linked to reduced drug levels and loss of efficacy, worth knowing when a patient who was doing well starts flaring on a stable dose.
Mycophenolate mofetilinhibits DNA/RNA synthesis and has antiproliferative lymphocyte effects; used off-label for some moderate-to-severe cases. Hydroxyureainhibits S-phase DNA synthesis, occasionally used off-label for recalcitrant severe disease, though biologics are usually the better option today.
Tazarotene, acitretin, and methotrexate are all contraindicated in pregnancy(retinoids are teratogenic; methotrexate is a teratogen and abortifacient). Salicylic acid is acceptable only for limited, localized disease. Coal tar carries low teratogenic risk if needed.
When psoriatic arthritis is present, treatment choice shifts toward agents with joint-disease evidence: most biologics (TNF inhibitors, ustekinumab, IL-17A and IL-23 inhibitors) and the JAK inhibitor tofacitiniball carry PsA indications, so a patient with both skin and joint disease often gets one drug covering both rather than two separate regimens.
| Parameter | When | Watching for |
|---|---|---|
| BSA / PASI / DLQI | Every visit | Treatment response, need to step up or down |
| TB screening | Before starting any biologic | Reactivation of latent TB, all biologics carry this risk |
| CBC, LFTs | Baseline and periodically on methotrexate | Macrocytic anemia, hepatotoxicity |
| Pulmonary symptoms | Ongoing, on methotrexate | Pulmonary toxicity, a less common but serious effect |
| Renal function, BP, magnesium, potassium | Baseline and during cyclosporine therapy | Nephrotoxicity, hypertension, electrolyte disturbance |
| Lipids, triglycerides | Baseline and on acitretin | Hypertriglyceridemia |
| Skin exam | Ongoing, especially with cyclosporine or extensive PUVA history | Skin cancer risk, which rises with treatment duration and prior PUVA |
| Infection signs | Every visit, on any biologic | Serious infection, a class-wide risk |
| Joint symptoms | Every visit | New or progressing psoriatic arthritis |
| Time to response | 2–8 weeks minimum before judging failure | Sustained, pharmacologically specific benefit takes weeks; corticosteroids act faster but that's not the whole picture |