Skin & Subcutaneous Tissue

Psoriasis: outpatient stepwise therapy

Clinical Overview and When to Suspect Psoriasis

— Affects ~3% of US adults; bimodal onset (peaks at 20–30 and 50–60 years)

— Strong genetic component (HLA-Cw6, PSORS1 locus); ~40% have affected first-degree relative

— Symmetric, sharply marginated, erythematous plaques with thick silvery-white scale on extensor surfaces (elbows, knees), scalp, gluteal cleft, umbilicus

— Nail changes: pitting, oil drops, onycholysis, subungual hyperkeratosis

— Patient reports lesions worsen with stress, infection (especially streptococcal pharyngitis → guttate flare), trauma (Koebner phenomenon), or certain drugs

— Joint pain, dactylitis, or enthesitis suggesting psoriatic arthritis (PsA) — present in up to 30%

— Plaque (80–90%) — most common

— Guttate — post-strep, raindrop lesions

— Inverse — flexural, intertriginous

— Pustular — sterile pustules, can be generalized (von Zumbusch = emergency)

— Erythrodermic — >75–90% BSA, systemic instability

— Mild: BSA <3%, no critical sites

— Moderate: BSA 3–10% OR involvement of face/hands/feet/genitals/scalp

— Severe: BSA >10%, PsA, or major QoL impact (DLQI >10)

— PASI (Psoriasis Area Severity Index) used in specialty/clinical trials

Board pearl: Psoriasis is an independent cardiovascular risk factor; severe psoriasis confers MI risk comparable to diabetes — always screen lipids, BP, glucose, and BMI at diagnosis.

Definition: Chronic, immune-mediated inflammatory skin disease driven by IL-23/Th17 axis activation, causing keratinocyte hyperproliferation and characteristic well-demarcated erythematous plaques with silvery scale

When to suspect in the ambulatory clinic:

Classification informs therapy:

Severity grading (drives stepwise therapy):

Step 3 management: Severity assessment plus comorbidity screening (cardiometabolic, depression, PsA) drives whether you stay topical, advance to phototherapy, or refer for systemic/biologic therapy. Do not anchor on BSA alone — genital or palmar disease at 2% BSA is moderate-severe functionally.

Presentation Patterns and Key History

— "Scaly itchy patches that won't go away" on elbows/knees/scalp

— Persistent dandruff unresponsive to OTC shampoos

— "Ringworm" that failed antifungals (think inverse or plaque psoriasis misdiagnosed)

— New rash after sore throat 2–3 weeks prior → guttate psoriasis

— Sudden generalized red painful skin with fever → pustular or erythrodermic — emergency

— Onset, distribution, prior treatments tried (potency of topical steroids used, duration)

— Triggers: streptococcal infection, HIV, stress, alcohol, smoking, drugs (beta-blockers, lithium, antimalarials, IFN-α, rapid systemic steroid taper, TNF inhibitors paradoxically), trauma

— Joint symptoms: morning stiffness >30 min, dactylitis ("sausage digit"), low back pain with inflammatory features, enthesitis (Achilles, plantar fascia)

— Nail involvement, eye symptoms (uveitis), GI symptoms (IBD overlap)

— Quality of life: sleep, work, intimacy, mood — use DLQI or PHQ-9

— Family history of psoriasis, PsA, IBD

— Cardiovascular: HTN, dyslipidemia, MI risk

— Metabolic: obesity, T2DM, NAFLD, metabolic syndrome

— Psychiatric: depression (2× risk), suicidality, alcohol use disorder

— Other autoimmune: IBD (especially Crohn's), uveitis, celiac

— Pregnancy status and intent (alters drug choices drastically)

— Smoking and alcohol (worsen disease, hepatotoxicity risk with methotrexate)

— Vaccination status — critical before starting biologics or systemics

Key distinction: Guttate psoriasis in a child/young adult 2–3 weeks after streptococcal pharyngitis is classic and often self-limited; obtain ASO titer or throat culture. This is distinct from chronic plaque psoriasis and may not require long-term systemic therapy.

Step 3 management: At first visit, document BSA, body sites, DLQI, PsA screen (PEST or PsA screen questionnaire), and cardiometabolic vitals — this single visit drives your entire stepwise algorithm.

Chief complaint clues:

Targeted history must capture:

Comorbidity inventory (Step 3 favorite):

Reproductive/lifestyle screen:

Physical Exam Findings and Functional Assessment

— Sharply demarcated, erythematous, symmetric plaques with silvery-white micaceous scale

— Auspitz sign: pinpoint bleeding when scale is removed (dilated dermal capillaries)

— Koebner phenomenon: new lesions at sites of trauma (scratches, scars, sunburn)

— Predilection: extensor elbows/knees, scalp (often beyond hairline), lumbosacral, umbilicus, gluteal cleft, retroauricular

— Guttate: numerous 2–10 mm "raindrop" papules on trunk/proximal limbs, often post-strep

— Inverse: smooth, glossy, erythematous, non-scaly plaques in axillae, inguinal folds, inframammary — easily mistaken for intertrigo or candidiasis

— Pustular: sterile pustules on erythematous base; generalized pustular psoriasis (von Zumbusch) = fever, leukocytosis, hypocalcemia, hypoalbuminemia → admit

— Erythrodermic: >75% BSA confluent erythema and scaling, risk of high-output failure, hypothermia, sepsis

— Palmoplantar: thick hyperkeratotic plaques with painful fissures, often disabling

— Pitting (most common), oil-drop discoloration, onycholysis, subungual hyperkeratosis, splinter hemorrhages

— Nail involvement → 3× risk of PsA

— DIP joint swelling, dactylitis, Achilles tenderness, plantar fascia tenderness, sacroiliac compression test

— Reduced lumbar flexion (modified Schober) suggests axial PsA

— BP, BMI, waist circumference (metabolic syndrome screen)

— Eye exam if symptoms — uveitis

— Vitals red flags in pustular/erythrodermic: tachycardia, hypotension, hypothermia, fever — these patients are not outpatients

Board pearl: Scale that bleeds when scraped (Auspitz) + extensor symmetric plaques + nail pitting = plaque psoriasis even before biopsy. Biopsy is rarely needed.

Step 3 management: Document BSA using the patient palm rule (1 palm with fingers ≈ 1% BSA) — this is the bedside metric that determines whether the patient stays on topicals or escalates.

Cardinal plaque features:

Subtype-specific findings:

Nail exam (don't skip — predicts PsA):

Musculoskeletal/enthesitis screen:

General/systemic check:

Diagnostic Workup — Initial Evaluation

— Biopsy reserved for atypical cases, suspected pustular variants, or differentiating from CTCL/eczema/tinea

— Histology: parakeratosis, Munro microabscesses, acanthosis with regular elongation of rete ridges, thinning of suprapapillary plates, dilated dermal capillaries

— CBC with differential

— CMP (LFTs, renal function)

— Fasting lipid panel and HbA1c (cardiometabolic comorbidity screen — do regardless of therapy plan)

— Hepatitis B surface antigen, surface antibody, core antibody

— Hepatitis C antibody

— HIV (especially if severe, sudden-onset, or refractory disease — psoriasis can be HIV-associated)

— QuantiFERON-TB Gold or PPD — mandatory before TNF inhibitors, IL-17, IL-23 biologics

— Pregnancy test in reproductive-age women

— Consider ANA if features suggestive of SLE overlap

— Guttate flare → ASO titer, anti-DNase B, throat swab

— Pustular/erythrodermic → CBC, BMP (hypocalcemia, AKI), albumin, CRP, blood cultures if febrile

— PsA suspicion → ESR, CRP, RF, anti-CCP (to exclude RA), uric acid, plain films of hands/feet/SI joints

— Routine plaque psoriasis: none

— Suspected PsA: plain radiographs (look for "pencil-in-cup" deformity, periostitis, ankylosis); MRI for early axial or enthesitis disease

— Lipid panel, fasting glucose/HbA1c every 1–2 years

— Depression screen (PHQ-9) at baseline and periodically

— Discuss alcohol use before methotrexate

Key distinction: A new diagnosis of severe, treatment-refractory, or sudden-onset psoriasis in an adult should prompt HIV testing — HIV can unmask or dramatically worsen psoriasis and changes the therapeutic ladder (avoid broad immunosuppression).

Step 3 management: "Before any biologic, check TB, HBV, HCV, HIV, pregnancy status, and update vaccines" — this is the canonical pre-biologic bundle tested repeatedly.

Diagnosis is clinical in the vast majority of cases — no labs or imaging required to start therapy for typical plaque psoriasis

Baseline labs before systemic/biologic therapy (not for topical-only patients):

Targeted testing by scenario:

Imaging:

Comorbidity-driven workup:

Diagnostic Workup — Advanced and Confirmatory Studies

— Indicated when diagnosis is uncertain, atypical morphology, or to exclude mycosis fungoides, subacute cutaneous lupus, pityriasis rubra pilaris, or seborrheic dermatitis

— Findings: confluent parakeratosis, hypogranulosis, Munro microabscesses (neutrophils in stratum corneum), spongiform pustules of Kogoj, regular acanthosis, dilated tortuous papillary capillaries

— KOH prep and bacterial culture of pustule contents to exclude infection (pustules are sterile in pustular psoriasis)

— Consider IL36RN mutation testing in familial or recurrent generalized pustular psoriasis — affects therapy (spesolimab targets IL-36R)

— Rheumatology referral if PEST score ≥3 or clinical suspicion

— Imaging: plain films first; MRI or ultrasound for early synovitis/enthesitis

— Labs: RF and anti-CCP usually negative (helps distinguish from RA); CRP elevated in ~40%

— CASPAR criteria used for classification

— Update all vaccines before starting biologics: influenza annually, COVID-19 per CDC, pneumococcal (PCV20 or PCV15→PPSV23), Tdap, Shingrix (recombinant — safe with biologics) for ≥50, HPV if indicated

— Live vaccines (MMR, varicella, yellow fever, live zoster, LAIV) must be given ≥4 weeks before biologic initiation and avoided during therapy

— Baseline ophthalmologic exam if uveitis history

— Echo or stress testing only if symptomatic CV disease

— NAFLD screen (RUQ ultrasound or FIB-4) before methotrexate if risk factors

— Methotrexate: CBC, LFTs, Cr, hepatitis serologies, pregnancy test, chest X-ray (if pulmonary risk), FIB-4

— Cyclosporine: BP × 2, BUN/Cr, K, Mg, uric acid, lipids, LFTs

— Apremilast: weight, depression screen

— Acitretin: lipids, LFTs, pregnancy test (teratogen — contraception 3 years post)

Board pearl: Anti-CCP positive with dactylitis and nail pitting → think coexisting RA + psoriasis or reconsider PsA classification. Anti-CCP is typically negative in pure PsA.

Step 3 management: A baseline FIB-4 score replaces routine pre-methotrexate liver biopsy in current guidelines — order it before initiating MTX for moderate-severe psoriasis.

Skin biopsy (4 mm punch):

Pustular psoriasis workup:

Psoriatic arthritis confirmation:

Pre-biologic safety extension:

Comorbidity confirmation:

Drug monitoring baselines:

Risk Stratification and Stepwise Management Logic

— Step 1 — Mild disease (BSA <3%, no critical sites):

— Step 2 — Moderate disease or topical failure (BSA 3–10%, or critical sites):

— Step 3 — Moderate-severe or phototherapy failure:

— Step 4 — Severe, PsA, or systemic failure:

— Genital, facial, palmoplantar, or scalp involvement → treat as moderate-severe regardless of BSA

— PsA present → systemic/biologic, not topical alone

— High DLQI (>10) → escalate

— Failed 8–12 weeks of appropriate topical/photo therapy → escalate

— Comorbid Crohn's/UC → avoid IL-17 inhibitors (can worsen IBD); prefer TNF or IL-23 inhibitors

— Comorbid PsA → TNF, IL-17, or IL-23 inhibitor (all effective)

— Hepatitis B carrier → avoid TNF without prophylaxis; IL-17/23 preferred with monitoring

— Latent TB → treat for ≥1 month before biologic

— Heart failure (NYHA III–IV) → avoid TNF inhibitors

Step 3 management: A "biologic-first" strategy is now acceptable for severe plaque psoriasis or PsA — you do not need to fail methotrexate before initiating a biologic if access permits.

Board pearl: Genital psoriasis at 1% BSA is moderate-severe — quality-of-life impact, not surface area, drives escalation.

The core outpatient algorithm (memorize this ladder):

High-potency topical corticosteroid (TCS) + topical vitamin D analog (calcipotriene) ± emollients

Scalp: clobetasol solution/foam, calcipotriene solution, tar/salicylic acid shampoos

Face/intertriginous: low-potency TCS (hydrocortisone 2.5%) or steroid-sparing topical calcineurin inhibitor (tacrolimus, pimecrolimus) — avoid skin atrophy

Add phototherapy — narrowband UVB (311 nm) 2–3×/week is first-line

PUVA reserved for refractory cases (skin cancer risk)

Continue topicals as adjuncts

Oral systemics: methotrexate, apremilast, cyclosporine (short-term bridge), acitretin (especially pustular/palmoplantar)

Or proceed directly to biologics depending on comorbidities, access, and severity

Biologics: TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab), IL-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab), IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), IL-12/23 (ustekinumab)

Often first-line systemic in severe disease per AAD-NPF 2019/2024 updates

Severity modifiers that bump tier:

Patient-specific drug selection:

Pharmacotherapy — Topicals and Oral Systemics

— Potency matched to site: ultra-high (clobetasol, betamethasone dipropionate) for thick plaques on body/scalp; low-potency (hydrocortisone) for face/folds

— Duration limit: ultra-high potency ≤4 weeks continuous; then taper to weekend pulse or rotate with non-steroid topical

— Adverse effects: atrophy, striae, telangiectasia, tachyphylaxis, HPA suppression (large BSA, occlusion)

— Calcipotriene/calcipotriol and calcitriol — normalize keratinocyte differentiation

— Often combined with TCS (calcipotriene-betamethasone foam/ointment) — synergy plus reduced steroid AEs

— Avoid in face/folds (irritation); hypercalcemia rare unless >100 g/week

— Tazarotene (retinoid) — teratogen, irritation common

— Topical calcineurin inhibitors (tacrolimus, pimecrolimus) — face/genital/inverse psoriasis, off-label but very useful

— Tapinarof (AhR agonist) and roflumilast (PDE4 inhibitor) — newer non-steroidal options, safe in folds/face, no duration limit

— Coal tar, anthralin, salicylic acid (keratolytic) — adjunctive

— Methotrexate 7.5–25 mg PO/SC weekly + folic acid 1 mg daily (or 5 mg weekly off MTX day)

— Apremilast (PDE4 inhibitor) 30 mg BID after titration

— Cyclosporine 2.5–5 mg/kg/day divided BID

— Acitretin (oral retinoid) 10–50 mg/day

— Deucravacitinib (oral TYK2 inhibitor) 6 mg daily — newer, no boxed warning unlike JAK inhibitors

Board pearl: Methotrexate + TMP-SMX is dangerous — both antifolates → severe pancytopenia. This is a tested drug interaction.

Step 3 management: Always co-prescribe folic acid with methotrexate to reduce GI/hepatic/marrow toxicity without losing efficacy.

Topical corticosteroids (cornerstone of mild disease):

Topical vitamin D analogs:

Other topicals:

Oral systemics:

Monitor CBC, LFTs, Cr every 2–3 months; FIB-4 annually

AEs: hepatotoxicity, cytopenias, pneumonitis, teratogen (avoid pregnancy ≥3 months M and F)

Avoid with significant alcohol use, NAFLD, CKD

Oral, no lab monitoring required

AEs: diarrhea, nausea, weight loss, depression/suicidality warning

Good for patients refusing injections or with monitoring barriers

Short-term bridge only (≤1 year) — nephrotoxicity, HTN

Rescue in erythrodermic/pustular flares

Monitor BP, Cr, K, Mg, lipids every 2 weeks initially

Best for pustular and palmoplantar psoriasis

Teratogen — avoid pregnancy for 3 years after discontinuation (re-esterification to etretinate with alcohol)

AEs: cheilitis, xerosis, hyperlipidemia, hepatotoxicity, hyperostosis

Phototherapy and Biologics — Advanced Therapeutics

— Narrowband UVB (311–313 nm) — first-line office or home-based phototherapy

— PUVA (psoralen + UVA) — reserved for refractory disease; higher skin cancer risk (SCC, melanoma), cataracts → eye protection required

— Excimer laser (308 nm) — focal/localized plaques, scalp

— TNF-α inhibitors:

— IL-17 inhibitors:

— IL-23 inhibitors (p19 subunit):

— IL-12/23 inhibitor:

— TB screen (IGRA), HBV/HCV serologies, HIV, pregnancy test

— Update vaccines, especially live vaccines ≥4 weeks before

— Skin cancer history, malignancy history (relative caution)

— Annual TB screening, periodic CBC and LFTs (less stringent than oral systemics)

— Watch for infections, paradoxical reactions (TNF-induced psoriasis)

— Primary non-response → switch class (e.g., TNF → IL-23)

— Secondary loss → check anti-drug antibodies, consider class switch or dose intensification

Key distinction: IL-17 inhibitors are excellent for skin and PsA but contraindicated in IBD; IL-23 inhibitors are safe across IBD, psoriasis, and PsA — pick by comorbidity.

Board pearl: Certolizumab pegol is preferred TNF in pregnancy because it lacks the Fc region and does not cross the placenta significantly.

Phototherapy:

2–3 sessions/week, 20–36 sessions for clearance, then taper

Safe in pregnancy, children, HIV, hepatitis

AEs: erythema, photoaging, modest skin cancer risk (less than PUVA)

Biologics — class overview (subcutaneous unless noted):

Adalimumab 80 mg → 40 mg q2 weeks; etanercept 50 mg weekly; infliximab IV 5 mg/kg at 0/2/6 weeks then q8 weeks; certolizumab (preferred in pregnancy — no Fc, minimal placental transfer)

Effective for PsA and skin

AEs: infection, reactivation TB/HBV, demyelination, worsens HF (avoid NYHA III–IV), drug-induced lupus, paradoxical psoriasis

Secukinumab, ixekizumab, brodalumab (IL-17RA), bimekizumab (IL-17A/F)

Rapid, high efficacy (PASI 90 in many)

Avoid in IBD — can precipitate/worsen Crohn's and UC

AEs: mucocutaneous candidiasis, injection reactions; brodalumab carries suicidality warning

Guselkumab, risankizumab, tildrakizumab

Excellent durability and tolerability; q8–12 week dosing after induction

Safe in IBD; minimal lab monitoring

Ustekinumab (p40) — q12 week dosing, very durable

Pre-biologic checklist (Step 3 ritual):

Monitoring on biologics:

Switching strategy:

Special Populations — Elderly and Renal/Hepatic Impairment

— Increased polypharmacy and drug interactions — beta-blockers, ACEi, lithium, antimalarials may trigger flares

— Skin atrophy from chronic topical steroids → use steroid-sparing topicals (calcipotriene, tapinarof, roflumilast) more readily

— Higher infection risk on biologics — vaccinate aggressively (especially Shingrix, PCV20, RSV, influenza)

— Skin cancer surveillance more important — limit cumulative PUVA exposure

— Falls and arthritis can amplify PsA disability — earlier rheum referral

— Methotrexate: cleared renally — reduce dose if CrCl 30–60, avoid if CrCl <30

— Cyclosporine: intrinsically nephrotoxic — avoid in baseline CKD; if used, monitor Cr every 2 weeks

— Acitretin: primarily hepatic but accumulates in CKD — use cautiously

— Apremilast: dose reduce to 30 mg daily if CrCl <30

— Biologics: generally no renal dose adjustment — TNF, IL-17, IL-23 inhibitors are preferred in CKD

— Avoid NSAIDs for PsA pain in CKD

— Methotrexate: contraindicated in significant hepatic disease; use FIB-4 to risk-stratify (<1.45 low risk, >3.25 advanced fibrosis)

— Acitretin: hepatotoxic — avoid in hepatitis, monitor LFTs and lipids monthly initially

— Cyclosporine: metabolized hepatically — adjust per LFTs

— Hepatitis B: any HBsAg+ patient starting biologic or MTX needs antiviral prophylaxis (entecavir or tenofovir) and hepatology co-management; HBcAb+/HBsAg- patients need monitoring

— Hepatitis C: treat HCV first; biologics generally safe after SVR

— TNF inhibitors contraindicated in NYHA III–IV HF

— Aggressive lipid, BP, glucose control — psoriasis is a CV risk enhancer per ACC/AHA primary prevention guidelines, lowering threshold for statins

— Cyclosporine + statins → rhabdomyolysis risk (especially simvastatin, lovastatin)

— MTX + NSAIDs/PPIs/TMP-SMX → toxicity

— Acitretin + tetracyclines → pseudotumor cerebri

Step 3 management: In an elderly CKD patient with moderate-severe psoriasis, IL-23 or IL-17 biologic is generally safer than methotrexate or cyclosporine — no renal dose adjustment and favorable side-effect profile.

Board pearl: Always check HBV serologies before any systemic immunosuppression; missed HBV reactivation is a common malpractice scenario.

Geriatric considerations:

Renal impairment:

Hepatic impairment:

Cardiovascular comorbidity (overlaps strongly with elderly):

Drug interactions to flag:

Special Populations — Pregnancy, Pediatrics, Other Subgroups

— Disease course variable: ~55% improve, 20% worsen during pregnancy

— Postpartum flare common — plan therapy in advance

— Safe options: emollients, low-potency topical steroids (limited area), narrowband UVB, certolizumab pegol (minimal placental transfer)

— Generally safe biologics (limited data, often continued through 2nd trimester): other TNF inhibitors weighed case-by-case; IL-17, IL-23 inhibitors — limited human data, decision shared

— Contraindicated:

— Cyclosporine: pregnancy category C — used if essential (severe pustular/erythrodermic)

— Impetigo herpetiformis (generalized pustular psoriasis of pregnancy) — emergency; hospitalize, cyclosporine or systemic steroids, monitor fetus

— Topicals avoiding nipple area, NB-UVB, certolizumab compatible

— Methotrexate, acitretin, cyclosporine generally avoided

— Guttate is common pediatric pattern; evaluate for streptococcal trigger (treat strep if positive)

— First-line: emollients, low–mid potency TCS, calcipotriene, calcineurin inhibitors for face/folds

— NB-UVB safe in children

— Approved biologics in pediatrics: etanercept (≥4 yr), ustekinumab (≥6 yr), ixekizumab (≥6 yr), secukinumab (≥6 yr), adalimumab (≥4 yr in some indications)

— Screen for obesity, depression, bullying-related QoL impact

— Methotrexate used; acitretin useful in pustular pediatric psoriasis

— Often severe, refractory; first treat with antiretroviral therapy — frequently resolves

— Avoid broad immunosuppression (MTX, cyclosporine); use NB-UVB, topicals, acitretin, or carefully selected biologics with ID co-management

— Hold biologics typically 1 dosing interval before major surgery; restart when wound healed and no infection

— Topicals continued

Key distinction: Certolizumab is the TNF inhibitor of choice in pregnancy; acitretin is the worst single drug for any reproductive-age woman because of 3-year teratogenic tail.

Step 3 management: A 24-year-old woman with moderate plaque psoriasis planning pregnancy in 6 months → choose NB-UVB or certolizumab, not methotrexate or acitretin.

Pregnancy and lactation:

Methotrexate — abortifacient/teratogen; stop ≥3 months before conception (both sexes)

Acitretin — severe teratogen; avoid pregnancy 3 years after discontinuation

Tazarotene topical — teratogen

PUVA — psoralens teratogenic

Calcipotriene — relatively avoid large surfaces (hypercalcemia risk)

Lactation:

Pediatric psoriasis:

HIV-associated psoriasis:

Perioperative psoriasis:

Complications and Adverse Outcomes

— Psoriatic arthritis (up to 30%): erosive, deforming joint disease; pencil-in-cup deformity, ankylosis, dactylitis, enthesitis, axial disease

— Erythrodermic psoriasis: generalized erythema >75–90% BSA → impaired thermoregulation (hypothermia or hyperthermia), high-output cardiac failure, hypoalbuminemia, dehydration, secondary infection, sepsis

— Generalized pustular psoriasis (von Zumbusch): fever, leukocytosis, hypocalcemia, hypoalbuminemia, AKI, ARDS — emergency admission

— Secondary skin infection (impetiginization), especially with scratching

— Nail destruction with functional impairment

— Increased MI, stroke, CV death (especially severe psoriasis)

— Metabolic syndrome: HTN, dyslipidemia, T2DM, obesity

— NAFLD/NASH — relevant for MTX choice

— Hyperuricemia and gout (high keratinocyte turnover)

— Depression (2× risk), anxiety, alcohol use disorder

— Suicidality — particularly in moderate-severe disease and on brodalumab/apremilast

— Sexual dysfunction (genital involvement)

— Uveitis (more with PsA, HLA-B27+ axial disease)

— Inflammatory bowel disease (Crohn's > UC)

— Celiac disease, lymphoma (small absolute increase)

— TCS: atrophy, striae, telangiectasia, glaucoma if periocular, HPA suppression

— MTX: hepatotoxicity, pancytopenia, pneumonitis, teratogenicity

— Cyclosporine: HTN, nephrotoxicity, hyperkalemia, hypomagnesemia, gingival hyperplasia, hirsutism, malignancy (skin, lymphoma)

— Acitretin: teratogenicity (3-year tail), hyperlipidemia, hepatotoxicity, hyperostosis (DISH), mucocutaneous dryness

— Biologics: serious infections, TB/HBV reactivation, injection reactions, paradoxical psoriasis (TNF), candidiasis (IL-17), depression/suicidality (brodalumab)

— PUVA: SCC, melanoma, cataracts

— Rebound flare with abrupt systemic steroid withdrawal — never treat plaque psoriasis with systemic corticosteroids as primary therapy

Board pearl: Systemic corticosteroids are contraindicated as primary therapy for chronic plaque psoriasis — withdrawal triggers pustular/erythrodermic rebound. This is a classic Step 3 error.

Step 3 management: Suspect generalized pustular psoriasis → admit, fluid resuscitate, correct calcium, IV antibiotics if febrile/septic appearance pending cultures, and initiate spesolimab (anti–IL-36R) or cyclosporine/infliximab for rapid control.

Disease-related complications:

Cardiometabolic complications (the "psoriatic march"):

Psychiatric complications:

Other comorbidities:

Treatment-related complications:

When to Escalate Care — Referral, Inpatient Triage

— Moderate-severe disease (BSA >5–10%, critical sites, DLQI >10)

— Failure of 8–12 weeks of appropriate topical therapy

— Need for phototherapy, oral systemic, or biologic initiation

— Diagnostic uncertainty (atypical morphology, refractory disease, biopsy needed)

— Pediatric psoriasis with significant impact

— PEST score ≥3, dactylitis, enthesitis, inflammatory back pain, joint swelling, or imaging evidence of PsA

— Early referral prevents irreversible erosions

— Cardiology/PCP for CV risk factor management

— Hepatology if HBV/HCV+ or NAFLD and considering MTX

— ID if latent TB + planned biologic

— Behavioral health for depression/suicidality

— Ophthalmology if uveitis symptoms

— Erythrodermic psoriasis with hemodynamic instability, hypothermia, electrolyte disturbance, or sepsis

— Generalized pustular psoriasis (von Zumbusch): fever, AKI, hypocalcemia, leukocytosis, ARDS risk

— Impetigo herpetiformis (pustular in pregnancy)

— Severe secondary infection / suspected sepsis

— Severe medication reaction (DRESS, anaphylaxis from biologic)

— Admit to monitored bed (telemetry if elderly or unstable)

— IV fluids, correct calcium/magnesium/potassium

— Warm environment, emollients, bland wet dressings

— Hold offending drugs (recent steroid taper, lithium, beta-blockers if feasible)

— Cultures (blood, skin, urine) and empiric antibiotics only if signs of infection — pustules themselves are sterile

— Rapid-acting systemic therapy:

— Avoid systemic corticosteroids except as last resort

— Dermatology consult day 1; dietitian for catabolic state; DVT prophylaxis

— Hemodynamically stable, afebrile, electrolytes normalized, oral intake adequate

— Outpatient biologic plan and dermatology follow-up within 1–2 weeks

Step 3 management: In CCS, an erythrodermic psoriasis patient on prednisone taper presenting with fever and confluent erythema → admit, IV fluids, electrolytes, hold steroid taper, dermatology consult, start cyclosporine or infliximab.

Refer to dermatology (outpatient):

Refer to rheumatology:

Co-management referrals:

Inpatient admission criteria (emergencies):

CCS pearl — managing inpatient pustular/erythrodermic psoriasis:

Cyclosporine 3–5 mg/kg/day or infliximab 5 mg/kg — fastest onset

Spesolimab (anti–IL-36R) for generalized pustular flares

Acitretin for ongoing pustular control

Discharge readiness:

Key Differentials — Inflammatory and Papulosquamous Causes

— Flexural distribution (antecubital, popliteal), more pruritic

— Ill-defined, weepy, lichenified plaques without silvery scale

— Personal/family history of atopy (asthma, allergic rhinitis)

— Elevated IgE, eosinophilia

— Responds to topical steroids + emollients but lacks Auspitz sign

— Greasy, yellow scale on scalp, eyebrows, nasolabial folds, chest

— Less well-demarcated, less thick scale

— Associated with Malassezia; responds to antifungals (ketoconazole shampoo)

— Overlap entity sebopsoriasis complicates distinction

— Herald patch → "Christmas tree" distribution on trunk along Langer lines

— Self-limited (6–8 weeks)

— Younger patients, often post-viral

— Differs from guttate psoriasis — pityriasis has collarette scale and centripetal pattern

— Orange-red plaques with islands of sparing, follicular hyperkeratosis, palmoplantar keratoderma

— Can mimic erythrodermic psoriasis; biopsy distinguishes

— Purple, polygonal, pruritic, planar papules (the 6 Ps); Wickham striae

— Oral, genital, scalp (lichen planopilaris) involvement

— Different histology

— Annular plaque with central clearing, advancing scaly border

— KOH prep positive for hyphae

— Often unilateral, asymmetric — unlike symmetric psoriasis

— Patches/plaques in non–sun-exposed areas (bathing-suit distribution)

— Persistent, refractory to standard psoriasis therapy → biopsy

— Atypical lymphocytes with cerebriform nuclei; Pautrier microabscesses

— Annular or papulosquamous lesions in photodistribution

— Anti-Ro/SSA positive

— Drug-induced forms (HCTZ, terbinafine)

— Generalized rash including palms and soles; copper-colored papules

— RPR/VDRL positive — never miss this

Key distinction: Symmetric, sharply marginated, silvery-scaled plaques on extensor surfaces with Auspitz sign and nail pitting = psoriasis. Flexural, pruritic, ill-defined, atopic background = eczema.

Board pearl: A "treatment-resistant psoriasis" patch in bathing-suit distribution in an older adult → biopsy to exclude mycosis fungoides.

Eczema (atopic dermatitis):

Seborrheic dermatitis:

Pityriasis rosea:

Pityriasis rubra pilaris:

Lichen planus:

Tinea corporis:

Mycosis fungoides (cutaneous T-cell lymphoma):

Subacute cutaneous lupus erythematosus:

Secondary syphilis:

Key Differentials — Other Categories and Mimickers

— Drug-induced psoriasiform eruption: beta-blockers, lithium, antimalarials, IFN-α, TNF inhibitors (paradoxical), terbinafine, ACE inhibitors

— Sudden onset or worsening after new medication → review drug list

— Acute generalized exanthematous pustulosis (AGEP): drug-triggered (beta-lactams, macrolides) sterile pustules, resolves on withdrawal; mimics pustular psoriasis but more acute and self-limited

— Keratoderma blennorrhagicum (palms/soles) and circinate balanitis mimic pustular/inverse psoriasis

— Post-GI (Shigella, Salmonella, Campylobacter) or GU (Chlamydia) infection

— HLA-B27 association, "can't see, can't pee, can't climb a tree"

— Tinea cruris vs inverse psoriasis (KOH!), tinea capitis vs scalp psoriasis (hair loss with scale)

— Erythrasma (Corynebacterium) — coral-red Wood's lamp fluorescence in intertriginous areas

— Impetiginized eczema, Staph-driven intertrigo

— Secondary syphilis (always in differential of papulosquamous trunk rash)

— Inverse psoriasis mimics: candidal intertrigo, Hailey-Hailey disease, extramammary Paget's, contact dermatitis

— Pustular psoriasis mimics: AGEP, subcorneal pustular dermatosis (Sneddon-Wilkinson), IgA pemphigus, DRESS with pustules

— Erythroderma differential: drug reaction, atopic dermatitis, CTCL (Sézary syndrome), PRP, paraneoplastic

— Onychomycosis (KOH/culture), trauma, lichen planus, alopecia areata pits (more uniform than psoriatic), Darier disease

— Seborrheic dermatitis, tinea capitis (children — KOH/culture), lichen planopilaris (scarring alopecia)

— KOH prep for any annular or intertriginous lesion

— RPR/VDRL for diffuse trunk/palm-sole rash

— ANA, anti-Ro/SSA for photodistributed annular plaques

— Biopsy for persistent, atypical, or treatment-resistant disease

— Drug timeline review for sudden exacerbation

Key distinction: AGEP vs pustular psoriasis — AGEP onsets within days of new drug, resolves within 2 weeks of withdrawal, lacks chronic plaque psoriasis history; pustular psoriasis is recurrent and usually in a known psoriasis patient.

Step 3 management: A new psoriasiform rash within weeks of starting lithium or a beta-blocker → review the drug timeline and consider switching the offending agent before escalating therapy.

Drug-induced and drug-exacerbated eruptions:

Reactive arthritis (formerly Reiter's):

Cutaneous fungal disease:

Bacterial mimickers:

Inflammatory mimics specific to subtypes:

Nail mimickers:

Scalp mimickers:

Workup hierarchy for ambiguous cases:

Long-Term Plan and Secondary Prevention

— Psoriasis is chronic — frame treatment as disease control, not cure

— Maintain on lowest effective therapy; many biologics allow stable maintenance with q8–12 week dosing

— Monitor for loss of response (anti-drug antibodies, especially infliximab and adalimumab) — consider methotrexate co-administration to reduce immunogenicity or switch agents

— Periodic reassessment: BSA, DLQI, PsA screen every visit

— Cardiovascular risk: check lipids and BP annually; calculate ASCVD risk and treat psoriasis as a risk enhancer — lower statin threshold

— Diabetes: screen with HbA1c every 1–3 years

— NAFLD: FIB-4 annually if on MTX or with metabolic syndrome

— Obesity: weight loss improves disease severity and treatment response; GLP-1 agonists in metabolic syndrome can be additive

— Smoking cessation — strong driver of psoriasis severity; offer counseling/varenicline/NRT

— Alcohol moderation — especially on MTX/acitretin

— Annual PHQ-9; refer for therapy/SSRI if positive

— Address sexual function, intimacy concerns (genital disease)

— Annual influenza

— COVID-19 per CDC

— Pneumococcal (PCV20 or PCV15/PPSV23)

— Shingrix at ≥50 (recombinant, safe with biologics)

— Tdap booster q10 years; RSV if eligible

— Hepatitis A/B if seronegative

— Avoid live vaccines while on biologics or systemic immunosuppression

— Annual full-body skin exam, especially for prior PUVA, cyclosporine, or extensive UVB

— Sun protection counseling (paradoxical — sun helps psoriasis but raises cancer risk)

— Screen for joint symptoms at every visit

— Some evidence that early biologic therapy for skin psoriasis may reduce PsA incidence (e.g., IL-23 inhibitors)

— Review medication list at each visit (avoid lithium, beta-blockers if alternatives exist)

— Treat strep infections promptly (especially guttate-prone patients)

— Skin trauma minimization (Koebner)

Step 3 management: At every psoriasis visit, document BP, BMI, smoking status, depression screen, PsA screen, and review vaccinations — this is the comprehensive longitudinal bundle.

Board pearl: Severe psoriasis is recognized as an ASCVD risk enhancer — use it to justify earlier/more intensive statin therapy per AHA/ACC guidelines.

Long-term therapeutic strategy:

Comorbidity-directed prevention (Step 3 cornerstone):

Mental health:

Vaccinations (ongoing):

Skin cancer surveillance:

PsA prevention/early detection:

Trigger avoidance:

Follow-Up, Monitoring, and Counseling

— Topicals only: 4–8 weeks for initial response, then 3–6 months

— Phototherapy: ongoing 2–3× weekly during induction, then taper; skin exams annually

— Methotrexate: CBC, CMP at 2–4 weeks, then every 2–3 months; FIB-4 annually; chest imaging if pulmonary symptoms

— Cyclosporine: BP and Cr every 2 weeks × 2 months, then monthly; K, Mg, uric acid, lipids periodically; limit to 1 year cumulatively

— Acitretin: LFTs, lipids, pregnancy test monthly × 3 months then quarterly

— Apremilast: weight, mood every 3–6 months; no labs required

— Biologics: TB screen annually; CBC, LFTs every 6–12 months; clinical assessment every 3–6 months

— Deucravacitinib: baseline labs, periodic CBC/LFTs

— Set realistic expectations: clearance possible, cure not; relapse common

— Adherence — topical adherence is poor at baseline; demonstrate application, prescribe correct vehicle (ointment for thick plaques, foam/solution for scalp, cream for folds)

— Trigger education: strep infection treatment, drug awareness, avoid skin trauma, manage stress

— Sun protection despite phototherapy benefit

— Pregnancy planning — review drug safety at every visit for reproductive-age patients

— Vaccination updates — particularly before any biologic switch

— Use DLQI to objectively track impact

— Discuss treatment goals: PASI 75 → PASI 90 → PASI 100 (clear skin) is now an achievable target with modern biologics

— Address cost, insurance prior authorization barriers, copay assistance programs

— Patient support groups (National Psoriasis Foundation)

— NB-UVB home units feasible — reduces office visit burden

— Photo-based follow-up for stable patients

— Important in rural/underserved areas

— New widespread pustules or erythroderma

— New joint pain or dactylitis

— Signs of infection (fever, expanding erythema, purulence) on biologic

— Mood changes, suicidality on apremilast/brodalumab

CCS pearl: After starting methotrexate, the canonical follow-up sequence is labs at 2–4 weeks, then 8–12 weeks, then every 3 months — order CBC, CMP, and document folic acid co-prescription each time.

Step 3 management: Demonstrate topical application in clinic — non-response is more often non-adherence or wrong vehicle than true treatment failure.

Follow-up cadence by therapy:

Counseling at every visit:

Quality-of-life and shared decision-making:

Telemedicine and home phototherapy:

Red flags requiring sooner follow-up:

Ethical, Legal, and Patient Safety Considerations

— Document discussion of infection risk, malignancy concerns, TB/HBV reactivation, infusion reactions, paradoxical reactions, cost, and alternatives

— For acitretin in reproductive-age women: robust counseling on 3-year teratogenic window, dual contraception requirement, mandatory pregnancy testing — analogous to but not identical to iPLEDGE; document thoroughly

— Methotrexate weekly dosing error is a sentinel safety event — once-weekly dosing must be explicitly written, patient educated, pharmacy alerted; daily dosing has caused fatal pancytopenia

— Streptococcal pharyngitis triggering guttate psoriasis — no reporting requirement, but treat per IDSA

— TB conversion on screening before biologic — report per state requirements

— Suspected medication error or adverse event → MedWatch/FDA reporting; document in chart

— Inpatient handoff: psoriasis patients admitted for unrelated illness should have biologics held or continued per ID/infectious-status assessment — explicit handoff to inpatient team

— Post-discharge biologic resumption: delayed restart can trigger flare; coordinate with outpatient derm

— Avoid stopping topicals abruptly without follow-up

— Steroid taper documentation: systemic steroids for unrelated indications can trigger rebound pustular psoriasis — flag to all prescribers in the chart and educate the patient

— Pre-treatment infection screen (TB, HBV, HCV, HIV)

— Vaccination status confirmed and updated

— Allergy and prior reaction documentation

— Pregnancy intent and contraception

— Real-time monitoring for infusion reactions (infliximab)

— Biologics cost $20,000–$80,000/year — assistance programs, biosimilars, prior authorization advocacy

— Skin of color: erythema appears violaceous or hyperpigmented; postinflammatory hyperpigmentation common — counsel and adjust visual severity assessment

— Cultural sensitivity around visible skin disease, religious head coverings affecting scalp therapy adherence

— Pediatric biologic decisions involve assent + parental consent

— Transition to adult care should be planned (transition clinic if available)

— Photograph baseline and follow-up lesions (with consent)

— Record BSA, DLQI, PsA screen — supports medical necessity for prior authorization

Step 3 management: A patient on methotrexate develops mucositis and pancytopenia → stop MTX immediately, give leucovorin rescue, admit, supportive care, and review for inadvertent daily dosing or interacting drug (TMP-SMX, NSAIDs). Report as sentinel event if dosing error confirmed.

Board pearl: Once-weekly methotrexate must be explicitly written and verbally reinforced — daily dosing is a well-known fatal error.

Informed consent for systemics and biologics:

Mandatory reporting and public health:

Transition-of-care risks:

Patient safety bundle for biologics:

Health equity and access:

Capacity and adolescent care:

Documentation pearls:

High-Yield Associations and Rapid-Fire Facts

Board pearl: "Sudden flare after starting lithium for bipolar disorder" + plaques on elbows/knees = drug-induced exacerbation — switch psychiatric agent if feasible before climbing the therapeutic ladder.

Genetics: HLA-Cw6 (PSORS1) — early-onset, guttate, family history

Pathophysiology: IL-23 → Th17 → IL-17 → keratinocyte hyperproliferation

Auspitz sign: pinpoint bleeding when scale removed

Koebner phenomenon: lesions at sites of trauma

Munro microabscess: neutrophils in stratum corneum — histologic hallmark

Guttate trigger: group A streptococcal pharyngitis 2–3 weeks prior

Drugs that trigger/worsen: β-blockers, Lithium, Antimalarials, NSAIDs, Tetracyclines, ACE inhibitors, IFN-α ("BLAst NTACI" mnemonic variations); also rapid systemic steroid withdrawal, TNF inhibitors (paradoxical)

Nail pitting: strongest cutaneous predictor of PsA

Pencil-in-cup deformity: classic PsA radiographic finding

Sausage digit (dactylitis): PsA signature

CASPAR criteria: PsA classification

IBD overlap: Crohn's > UC; avoid IL-17 inhibitors if IBD present

Pregnancy-safe biologic: certolizumab pegol (lacks Fc)

Severe teratogens: methotrexate (3 months off pre-conception), acitretin (3-year tail), tazarotene

Methotrexate fatal interaction: TMP-SMX (antifolate synergy → pancytopenia)

Cyclosporine: rapid rescue agent; nephrotoxicity, HTN; ≤1 year use

Apremilast warning: depression/suicidality, GI side effects, weight loss

Brodalumab boxed warning: suicidality

TNF inhibitor contraindications: NYHA III–IV HF, demyelinating disease, active TB/HBV

IL-17 caution: mucocutaneous candidiasis, IBD worsening

Spesolimab: anti–IL-36R for generalized pustular psoriasis

Deucravacitinib: oral TYK2 inhibitor — newer, no JAK boxed warning

Cardiovascular: severe psoriasis = ASCVD risk enhancer

Metabolic syndrome: check lipids, glucose, BP at diagnosis and annually

PASI 90/100: modern biologic targets

DLQI >10: moderate-severe by quality-of-life criterion

Patient palm = 1% BSA

HIV unmasking: sudden severe psoriasis → check HIV

Erythrodermic and pustular psoriasis: admit, IV fluids, electrolytes, cyclosporine or infliximab, avoid systemic steroids as primary therapy

NB-UVB: safe in pregnancy, children, HIV

Pre-biologic checklist: TB, HBV, HCV, HIV, pregnancy test, update vaccines, no live vaccines on biologic

Methotrexate: weekly dosing, folate co-prescription, FIB-4 monitoring

Acitretin: alcohol forms etretinate (long half-life) — avoid alcohol × 3 years post-treatment in women of reproductive age

Board Question Stem Patterns

"32-year-old man with silvery-scaled plaques on extensor elbows and knees, nail pitting, BSA 3%. Auspitz sign positive."

— Answer: High-potency topical corticosteroid + topical calcipotriene; address CV risk factors

"19-year-old with diffuse small drop-like papules on trunk 2 weeks after pharyngitis."

— Answer: Diagnose guttate psoriasis; treat strep if positive; NB-UVB if extensive; usually self-limited

"Patient on methotrexate develops oral ulcers, fever, pancytopenia after starting TMP-SMX for UTI."

— Answer: Stop MTX, leucovorin rescue, admit, supportive care; drug-drug interaction = antifolate synergy

"28-year-old woman with moderate plaque psoriasis on methotrexate wants to conceive in 6 months."

— Answer: Stop MTX ≥3 months pre-conception; switch to NB-UVB or certolizumab pegol

"Patient with psoriasis tapered off prednisone (given for COPD) now with fever, diffuse sterile pustules, hypocalcemia, hypoalbuminemia."

— Answer: Generalized pustular psoriasis (von Zumbusch); admit, IV fluids, correct electrolytes, cyclosporine or infliximab (or spesolimab); avoid further steroids

"Patient newly started on propranolol or lithium develops worsening psoriasis."

— Answer: Discontinue offending agent if alternatives available

"Patient with psoriasis develops morning stiffness, sausage-shaped 3rd toe, DIP joint swelling."

— Answer: Psoriatic arthritis — rheum referral, plain films, start TNF/IL-17/IL-23 biologic

"Plan to start adalimumab for severe psoriasis. Which test must be performed first?"

— Answer: TB screening (IGRA) plus HBV, HCV, HIV serologies and pregnancy test

"Patient with both Crohn's disease and severe psoriasis."

— Answer: Use IL-23 inhibitor (guselkumab/risankizumab) or TNF inhibitor; avoid IL-17 inhibitors

"Sudden severe refractory psoriasis in a previously healthy 35-year-old."

— Answer: Check HIV; start ART; avoid broad immunosuppression

"95% BSA confluent erythema, hypothermia, hypotension."

— Answer: Admit, IV fluids, warm, correct electrolytes, cyclosporine or infliximab; avoid systemic steroids

"40-year-old with severe psoriasis. LDL 145, BP 138/86."

— Answer: Severe psoriasis = ASCVD risk enhancer → consider statin therapy and intensify lifestyle modification

"Sharply demarcated, smooth, red, non-scaly plaques in axillae and groin not responding to antifungals."

— Answer: Inverse psoriasis; low-potency TCS or topical calcineurin inhibitor

Step 3 management: Pattern-recognize the trigger (drug, infection, withdrawal of steroid) — examiners reward identification of the modifiable precipitant before escalating therapy.

Stem 1 — Classic plaque, initial therapy:

Stem 2 — Guttate after sore throat:

Stem 3 — Methotrexate complication:

Stem 4 — Pregnancy planning:

Stem 5 — Pustular emergency:

Stem 6 — Drug-induced flare:

Stem 7 — PsA recognition:

Stem 8 — Pre-biologic workup:

Stem 9 — IBD overlap:

Stem 10 — HIV unmasking:

Stem 11 — Erythroderma:

Stem 12 — Cardiovascular risk:

Stem 13 — Inverse psoriasis:

One-Line Recap

Psoriasis is a chronic, IL-23/Th17–driven inflammatory skin disease managed by a stepwise outpatient algorithm — topicals for mild disease, phototherapy for moderate, and oral systemics or biologics for severe or PsA-complicated disease — while simultaneously addressing cardiometabolic, psychiatric, and PsA comorbidities and screening rigorously before immunosuppression.

Board pearl: If the stem features a recent steroid taper, new beta-blocker/lithium, or post-strep onset in a psoriasis patient — the answer almost always involves identifying and removing the trigger before escalating immunosuppression.

Step 3 management: Document BSA, DLQI, PsA screen, CV risk factors, vaccination status, and pregnancy intent at every psoriasis visit — this longitudinal bundle is the high-yield ambulatory framework Step 3 rewards.

Severity drives therapy: BSA <3% (mild) → topical steroid + calcipotriene; BSA 3–10% or critical sites → add NB-UVB; severe or PsA → methotrexate/apremilast or biologic (TNF, IL-17, IL-23 inhibitor) — choose by comorbidity (avoid IL-17 in IBD, avoid TNF in HF, use certolizumab in pregnancy)

Always screen before systemics: TB (IGRA), HBV, HCV, HIV, pregnancy test, update vaccines (live vaccines ≥4 weeks before biologic, then avoid), baseline CBC/CMP/lipids/HbA1c; FIB-4 before methotrexate

Never use systemic corticosteroids as primary therapy for plaque psoriasis — withdrawal triggers pustular/erythrodermic rebound; rescue severe flares with cyclosporine, infliximab, or spesolimab instead

Treat the whole patient: psoriasis is an ASCVD risk enhancer — manage lipids, BP, glucose, weight, smoking, alcohol, depression (PHQ-9), and screen for psoriatic arthritis (PEST, dactylitis, nail pitting) at every visit; remember teratogen tails (methotrexate 3 months, acitretin 3 years), the lethal MTX + TMP-SMX interaction, and that sudden severe psoriasis should prompt HIV testing