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derm.urticaria.core.v1PRODUCTION
derm.urticaria.core.v1

Urticaria (acute & chronic spontaneous/inducible)

dermatologyacutesubacutechronicadultpediatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame urticaria as a mast-cell-driven wheal±angioedema disease classified as acute (<6 wk, trigger-driven, self-limited) vs chronic spontaneous (CSU, ≥6 wk, autoimmune/idiopathic) vs chronic inducible (physical-trigger-provoked). The defining pivot is the TRANSIENT individual wheal (<24 h, pruritic, blanching, no residual mark). Anaphylaxis, bradykinin/HAE/ACE-inhibitor angioedema, and urticarial vasculitis are recognised here and routed/escalated, not chronically managed as urticaria.

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urticaria framing + 3-way classification axis set; anaphylaxis/HAE/vasculitis escape routes noted

Patient inputs (17)

Wheals + angioedema, angioedema alone (bradykinin/HAE differential), or wheals alone changes the differential and the danger ceiling; laryngeal angioedema is an airway emergency (EAACI/GA²LEN 2022 PMID 34536239)

Dermographic / cholinergic / cold / delayed-pressure / solar / heat / aquagenic / vibratory provocation defines a chronic inducible subtype and its provocation test + threshold (EAACI/GA²LEN 2022 PMID 34536239)

Acute urticaria is most often post-infectious or drug/food-related; NSAIDs and ACE-inhibitors are the dominant drug exacerbators/mimics to identify (EAACI/GA²LEN 2022 PMID 34536239)

Individual lesion <24 h with no residual mark defines true urticaria; a fixed lesion persisting >24 h with bruising/pigmentation is the urticarial-vasculitis biopsy pivot (EAACI/GA²LEN 2022 PMID 34536239)

The 6-week boundary separates acute (self-limited, trigger-driven) from chronic urticaria (CSU/CIndU — needs the stepwise ladder + autoimmune workup) (EAACI/GA²LEN 2022 PMID 34536239)

ACE-inhibitor angioedema is bradykinin-mediated, antihistamine/epinephrine/steroid-unresponsive — drug withdrawal + HAE-type therapy, NOT the urticaria ladder (EAACI/GA²LEN 2022 PMID 34536239)

Wheals with airway compromise / bronchospasm / hypotension / GI involvement = anaphylaxis — STAT IM epinephrine and route OUT to allergy.anaphylaxis.v1 (EAACI/GA²LEN 2022 PMID 34536239)

Lesions >24 h, painful/burning rather than itchy, bruising/residual pigmentation, ± arthralgia/systemic symptoms → skin biopsy for urticarial vasculitis before treating as CSU (EAACI/GA²LEN 2022 PMID 34536239)

Disease activity + sleep + QoL (UAS7 / UCT / AAS / DLQI — schema-blocked, narrated) drive step-up timing and the response definition at each ladder step (EAACI/GA²LEN 2022 PMID 34536239)

Pediatric weight-band 2nd-gen H1 dosing; in older adults avoid 1st-gen sedating antihistamines (anticholinergic burden) (EAACI/GA²LEN 2022 PMID 34536239)

CSU is associated with autoimmune thyroid disease and other autoimmunity; targeted (not blanket) workup when history/CBC/inflammation suggest it (EAACI/GA²LEN 2022 PMID 34536239)

Limited routine workup in CSU per guideline (CBC + inflammatory markers); eosinophilia/cytopenia flags an alternative diagnosis (EAACI/GA²LEN 2022 PMID 34536239)

ESR/CRP elevation in a "wheal" patient raises urticarial vasculitis / autoinflammatory (Schnitzler) and lowers the biopsy threshold (EAACI/GA²LEN 2022 PMID 34536239)

Recurrent angioedema without wheals + family history → hereditary angioedema (C1-INH) — a non-mast-cell pathway routed OUT, not authored here (EAACI/GA²LEN 2022 PMID 34536239)

Loratadine/cetirizine are the preferred 2nd-gen H1 in pregnancy/lactation; omalizumab data are reassuring; cyclosporine avoided if possible — gates the ladder (EAACI/GA²LEN 2022 PMID 34536239)

Cetirizine/levocetirizine need renal dose reduction in significant CKD; cyclosporine nephrotoxicity surveillance via CKD-EPI 2021 race-free eGFR (EAACI/GA²LEN 2022 PMID 34536239; Inker NEJM 2021)

Cyclosporine + (rarely) high-burden therapy baseline + on-treatment hepatic surveillance (EAACI/GA²LEN 2022 PMID 34536239)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateninganaphylaxis_wheals_plus_systemic
    Wheals (± angioedema) WITH airway/voice change, bronchospasm/wheeze, hypotension/syncope, or GI symptoms — anaphylaxis
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningairway_laryngeal_angioedema
    Tongue / pharyngeal / laryngeal angioedema with voice change, stridor, dysphagia or threatened airway
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebradykinin_acei_or_hae_angioedema
    Recurrent angioedema WITHOUT wheals, on an ACE-inhibitor or with family history, unresponsive to antihistamine/epinephrine/corticosteroid
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_csu_high_uas7_qol_impact
    Chronic spontaneous urticaria with high disease activity (high UAS7) and substantial sleep / quality-of-life impairment despite up-dosed antihistamine
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateurticarial_vasculitis_biopsy
    Individual lesions persisting >24 h, painful/burning rather than itchy, with bruising / residual pigmentation, ± arthralgia/fever/↑ESR-CRP
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesevere_acute_generalized_flare
    Severe acute generalized urticaria with extensive wheals/angioedema not controlled by a 2nd-gen H1 (no systemic anaphylaxis)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildfirst_gen_antihistamine_avoid
    Tendency to use / continue a 1st-generation sedating antihistamine (hydroxyzine, diphenhydramine, chlorphenamine), especially in an older adult
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

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Recommended regimen

Urticaria — EAACI/GA²LEN/EuroGuiDerm/APAAACI 2021/2022 stepwise ladder (CSU/CIndU) + acute rescue
axis: urticaria_stepwise_ladderstep 1 - Step 1 — Standard-dose 2nd-generation H1-antihistamine (first-line, all subtypes)
Selected step "Step 1 — Standard-dose 2nd-generation H1-antihistamine (first-line, all subtypes)" — Acute urticaria and chronic urticaria (CSU/CIndU) — the guideline first-line for every patient; choose one non-sedating 2nd-gen H1 at standard licensed dose
  • cetirizine
    first line
    second_generation_h1_antihistamine
    10 mg • PO • once daily (max: 10 mg/day at standard dose (Step 2 up-dosing separate))
    triggers: acute_or_chronic_urticaria
    EAACI/GA²LEN 2022 (PMID 34536239) STRONG — non-sedating 2nd-gen H1 at standard dose is first-line; cetirizine is among the most evidence-supported and is pregnancy-preferred.
    rxcui 20610
  • levocetirizine
    first line
    second_generation_h1_antihistamine
    5 mg • PO • once daily (max: 5 mg/day at standard dose)
    triggers: acute_or_chronic_urticaria
    EAACI/GA²LEN 2022 (PMID 34536239) — active enantiomer of cetirizine; equivalent first-line standing in the ladder.
    rxcui 356887
  • fexofenadine
    first line
    second_generation_h1_antihistamine
    180 mg • PO • once daily (max: 180 mg/day at standard dose)
    triggers: acute_or_chronic_urticaria, least_sedating_preferred
    EAACI/GA²LEN 2022 (PMID 34536239) — minimally sedating 2nd-gen H1; preferred where sedation/operating-machinery is a concern.
    rxcui 87636
  • loratadine
    first line
    second_generation_h1_antihistamine
    10 mg • PO • once daily (max: 10 mg/day at standard dose)
    triggers: acute_or_chronic_urticaria, pregnancy_preferred
    EAACI/GA²LEN 2022 (PMID 34536239) — long human-pregnancy safety record; loratadine (with cetirizine) is the pregnancy/lactation-preferred 2nd-gen H1.
    rxcui 28889
  • desloratadine
    first line
    second_generation_h1_antihistamine
    5 mg • PO • once daily (max: 5 mg/day at standard dose)
    triggers: acute_or_chronic_urticaria
    EAACI/GA²LEN 2022 (PMID 34536239) — active metabolite of loratadine; equivalent first-line standing.
    rxcui 275635

outpatient playbook — drug actions (4)

  1. 1. cetirizine (standard-dose 2nd-gen H1 — first-line)
    rxcui 20610
    10 mg • PO • once daily
    trigger: Any acute or chronic urticaria (EAACI/GA²LEN 2022 PMID 34536239)
    Non-sedating 2nd-gen H1 at standard dose is guideline first-line for every patient
  2. 2. up-dose the same 2nd-gen H1 (up to 4×)
    rxcui 20610
    up to 40 mg/day (cetirizine example) • PO • once–twice daily
    trigger: Inadequate control after 2–4 wk at standard dose (EAACI/GA²LEN 2022 PMID 34536239)
    Up-dose the SAME agent to ≤4× before adding anything; do not add a 1st-gen antihistamine
  3. 3. add omalizumab (anti-IgE)
    rxcui 302379
    300 mg SC • SC • every 4 weeks
    trigger: Inadequate control on up-dosed H1 after 2–4 wk (EAACI/GA²LEN 2022 PMID 34536239; ASTERIA PMID 25046337)
    STRONG add-on; ~52–66% well-controlled (UAS7≤6) vs ~11–19% placebo at wk 12; assess by 12–16 wk
  4. 4. cyclosporine (omalizumab-refractory, off-label)
    rxcui 3008
    ~3 mg/kg/day • PO • BID
    trigger: Refractory to omalizumab + up-dosed H1 (EAACI/GA²LEN 2022 PMID 34536239; Kulthanan PMID 28916431)
    Off-label; ~73% response by 12 wk at low–moderate dose; BP + creatinine surveillance

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Pruritic, blanching, migratory wheals each resolving <24 h without residual mark (the defining urticaria pivot) (EAACI/GA²LEN 2022 PMID 34536239); Wheals and/or angioedema present ≥6 wk → chronic urticaria (spontaneous vs inducible) classification entry (EAACI/GA²LEN 2022 PMID 34536239); Acute (<6 wk) hives, often after infection / drug / food — self-limited acute urticaria entry (EAACI/GA²LEN 2022 PMID 34536239).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Urticaria (acute & chronic spontaneous/inducible)** (derm.urticaria.core.v1).
Phenotype framing: Terminal differential with named pivots: CSU vs chronic inducible urticaria (reproducible physical-trigger provocation pivot) vs urticarial vasculitis (lesion >24 h + painful + bruising + biopsy pivot) vs hereditary/ACE-inhibitor angioedema (no wheals + no antihistamine response + low C4/C1-INH pivot) vs anaphylaxis (systemic airway/CV/GI involvement pivot) vs mastocytosis/urticaria pigmentosa (Darier sign + tryptase pivot) vs autoinflammatory/Schnitzler syndrome (fever + bone pain + monoclonal IgM pivot) vs drug eruption (new-drug temporal pivot — route derm.drug-eruption.core.v1) vs atopic dermatitis (fixed eczematous, not transient wheals — route derm.atopic-dermatitis.core.v1).
Scope: Frame urticaria as a mast-cell-driven wheal±angioedema disease classified as acute (<6 wk, trigger-driven, self-limited) vs chronic spontaneous (CSU, ≥6 wk, autoimmune/idiopathic) vs chronic inducible (physical-trigger-provoked). The defining pivot is the TRANSIENT individual wheal (<24 h, pruritic, blanching, no residual mark). Anaphylaxis, bradykinin/HAE/ACE-inhibitor angioedema, and urticarial vasculitis are recognised here and routed/escalated, not chronically managed as urticaria.

No severity triggers fired against current inputs.

Plan

Regimen axis: **Urticaria — EAACI/GA²LEN/EuroGuiDerm/APAAACI 2021/2022 stepwise ladder (CSU/CIndU) + acute rescue** — step "Step 1 — Standard-dose 2nd-generation H1-antihistamine (first-line, all subtypes)".
1. cetirizine 10 mg PO once daily (second_generation_h1_antihistamine, first line) — EAACI/GA²LEN 2022 (PMID 34536239) STRONG — non-sedating 2nd-gen H1 at standard dose is first-line; cetirizine is among the most evidence-supported and is pregnancy-preferred.
2. levocetirizine 5 mg PO once daily (second_generation_h1_antihistamine, first line) — EAACI/GA²LEN 2022 (PMID 34536239) — active enantiomer of cetirizine; equivalent first-line standing in the ladder.
3. fexofenadine 180 mg PO once daily (second_generation_h1_antihistamine, first line) — EAACI/GA²LEN 2022 (PMID 34536239) — minimally sedating 2nd-gen H1; preferred where sedation/operating-machinery is a concern.
4. loratadine 10 mg PO once daily (second_generation_h1_antihistamine, first line) — EAACI/GA²LEN 2022 (PMID 34536239) — long human-pregnancy safety record; loratadine (with cetirizine) is the pregnancy/lactation-preferred 2nd-gen H1.
5. desloratadine 5 mg PO once daily (second_generation_h1_antihistamine, first line) — EAACI/GA²LEN 2022 (PMID 34536239) — active metabolite of loratadine; equivalent first-line standing.

Setting playbook (outpatient) — Confirm true urticaria (transient wheal pivot), classify acute vs CSU vs chronic inducible, exclude urticarial vasculitis / bradykinin angioedema, and run the EAACI/GA²LEN stepwise ladder gated on pregnancy/age/renal status (EAACI/GA²LEN 2022 PMID 34536239)
6. cetirizine (standard-dose 2nd-gen H1 — first-line) 10 mg PO once daily — Any acute or chronic urticaria (EAACI/GA²LEN 2022 PMID 34536239) (Non-sedating 2nd-gen H1 at standard dose is guideline first-line for every patient)
7. up-dose the same 2nd-gen H1 (up to 4×) up to 40 mg/day (cetirizine example) PO once–twice daily — Inadequate control after 2–4 wk at standard dose (EAACI/GA²LEN 2022 PMID 34536239) (Up-dose the SAME agent to ≤4× before adding anything; do not add a 1st-gen antihistamine)
8. add omalizumab (anti-IgE) 300 mg SC SC every 4 weeks — Inadequate control on up-dosed H1 after 2–4 wk (EAACI/GA²LEN 2022 PMID 34536239; ASTERIA PMID 25046337) (STRONG add-on; ~52–66% well-controlled (UAS7≤6) vs ~11–19% placebo at wk 12; assess by 12–16 wk)
9. cyclosporine (omalizumab-refractory, off-label) ~3 mg/kg/day PO BID — Refractory to omalizumab + up-dosed H1 (EAACI/GA²LEN 2022 PMID 34536239; Kulthanan PMID 28916431) (Off-label; ~73% response by 12 wk at low–moderate dose; BP + creatinine surveillance)

Non-pharmacologic actions:
- Threshold-guided trigger avoidance for chronic inducible urticaria (EAACI/GA²LEN 2022 PMID 34536239)
- Avoid NSAIDs / ACE-inhibitors where they exacerbate (EAACI/GA²LEN 2022 PMID 34536239)
- Do NOT use 1st-generation sedating antihistamines; do NOT use chronic systemic steroids (EAACI/GA²LEN 2022 PMID 34536239)
- Periodically attempt step-DOWN — most CSU remits over months–years (EAACI/GA²LEN 2022 PMID 34536239)

AVOID / contraindication checks:
- Acei angioedema is bradykinin mediated not antihistamine responsive (EAACI/GA²LEN 2022 PMID 34536239 — stop ACE inhibitor, route HAE/bradykinin pathway, NOT the urticaria ladder)
- Against chronic systemic corticosteroids (EAACI/GA²LEN 2022 PMID 34536239 — short ≤10 d burst for severe acute flare only)
- First generation sedating antihistamines not recommended (EAACI/GA²LEN 2022 PMID 34536239 — sedation + anticholinergic burden, esp. older adults; no advantage over up dosed 2nd gen H1)
- Pregnancy prefer loratadine or cetirizine omalizumab data reassuring avoid cyclosporine if possible (EAACI/GA²LEN 2022 PMID 34536239)
- Cetirizine levocetirizine renal dose reduction in significant ckd (EAACI/GA²LEN 2022 PMID 34536239)
- Cyclosporine nephrotoxicity hypertension monitor bp creatinine limit duration (EAACI/GA²LEN 2022 PMID 34536239; Kulthanan PMID 28916431)
- Anaphylaxis needs IM epinephrine and route out not the urticaria ladder (EAACI/GA²LEN 2022 PMID 34536239)

Monitoring

Regimen monitoring:
- UAS7 UCT AAS DLQI disease control at each step (schema-blocked — narrated; EAACI/GA²LEN 2022 PMID 34536239)
- standard dose H1 response reassessed at 2-4wk then updose (EAACI/GA²LEN 2022 PMID 34536239)
- updosed H1 response reassessed at 2-4wk then add omalizumab (EAACI/GA²LEN 2022 PMID 34536239)
- omalizumab response judged by 12-16wk some respond before wk4 (ASTERIA/GLACIAL PMID 26483177)
- cyclosporine BP plus creatinine surveillance CKD-EPI 2021 (EAACI/GA²LEN 2022 PMID 34536239; Kulthanan PMID 28916431)
- periodic step down attempt when controlled CSU often remits (EAACI/GA²LEN 2022 PMID 34536239)

Setting (outpatient) monitoring:
- Reassess control (UAS7/UCT/AAS/DLQI — narrated) at 2–4 wk per antihistamine step; omalizumab by 12–16 wk (EAACI/GA²LEN 2022 PMID 34536239; PMID 26483177)
- Cyclosporine BP + creatinine (CKD-EPI 2021) on schedule (EAACI/GA²LEN 2022 PMID 34536239; Kulthanan PMID 28916431)

Follow-up plan: Chronic-disease maintenance: most CSU remits over months–years — periodically attempt step-DOWN once controlled; continue the lowest effective step. Trigger avoidance for inducible subtypes + threshold-guided counselling; NSAID/ACE-inhibitor avoidance where they exacerbate. Carry an action plan + epinephrine auto-injector only if there has been true anaphylaxis (not for simple urticaria). Reassess for autoimmune-thyroid association and urticarial vasculitis if the course changes.
- Close-out criterion: step-down attempted when controlled; trigger + return-precaution education documented

Monitoring phase: Disease control re-assessed at each step (UAS7/UCT/AAS/DLQI — narrated): standard-dose H1 response at 2–4 wk → up-dose if uncontrolled; up-dosed H1 response at 2–4 wk → add omalizumab; omalizumab response judged by ~12–16 wk (some respond before week 4); cyclosporine response with BP + creatinine surveillance (CKD-EPI 2021). Re-screen for urticarial vasculitis if lesions become fixed/painful; reassess the diagnosis if no response to an adequately up-dosed antihistamine.

Disposition

Current setting: outpatient — Confirm true urticaria (transient wheal pivot), classify acute vs CSU vs chronic inducible, exclude urticarial vasculitis / bradykinin angioedema, and run the EAACI/GA²LEN stepwise ladder gated on pregnancy/age/renal status (EAACI/GA²LEN 2022 PMID 34536239)

Disposition criteria:
- Continue the lowest effective ladder step + step-down attempts if controlled (EAACI/GA²LEN 2022 PMID 34536239)
- Step up the ladder if a step fails after an adequate 2–4 wk (antihistamine) / 12–16 wk (omalizumab) trial
- ED/airway pathway only for anaphylaxis, laryngeal angioedema, or bradykinin angioedema needing C1-INH/icatibant

Escalation triggers (move to higher acuity):
- Wheals + airway/CV/GI involvement → anaphylaxis: STAT IM epinephrine + route OUT to allergy.anaphylaxis.v1 (EAACI/GA²LEN 2022 PMID 34536239)
- Angioedema without wheals + ACE-inhibitor / family history → stop ACE-inhibitor, C4/C1-INH, bradykinin/HAE pathway (NOT the ladder) (EAACI/GA²LEN 2022 PMID 34536239)
- Fixed lesions >24 h, painful, bruising, systemic symptoms → skin biopsy for urticarial vasculitis (EAACI/GA²LEN 2022 PMID 34536239)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Wheals (± angioedema) WITH airway/voice change, bronchospasm/wheeze, hypotension/syncope, or GI symptoms — anaphylaxis
- [LIFE_THREATENING] Tongue / pharyngeal / laryngeal angioedema with voice change, stridor, dysphagia or threatened airway
- [SEVERE] Recurrent angioedema WITHOUT wheals, on an ACE-inhibitor or with family history, unresponsive to antihistamine/epinephrine/corticosteroid

Citations

- EAACI/GA²LEN/EuroGuiDerm/APAAACI international guideline for the definition, classification, diagnosis, and management of urticaria (Zuberbier et al, Allergy 2022; PMID 34536239, DOI 10.1111/all.15090) + CSU guidelines "what is new" (Zuberbier et al, JACI 2022; PMID 36481045, DOI 10.1016/j.jaci.2022.10.004) + AAAAI/ACAAI JTF practice-parameter update antileukotriene meta-analysis (Rayner et al, JACI 2024; PMID 38852861) + pivotal omalizumab CSU trials (ASTERIA I PMID 25046337; ASTERIA I/II + GLACIAL response analysis PMID 26483177; angioedema pooled PMID 27424128; background-therapy pooled PMID 26054553) + cyclosporine CSU meta-analysis (Kulthanan PMID 28916431) + omalizumab-vs-immunosuppressant network meta-analysis (Lin PMID 36140253) [PMID:34536239](https://pubmed.ncbi.nlm.nih.gov/34536239/)
- Cited evidence (PMID 36481045) [PMID:36481045](https://pubmed.ncbi.nlm.nih.gov/36481045/)
- Cited evidence (PMID 38852861) [PMID:38852861](https://pubmed.ncbi.nlm.nih.gov/38852861/)
- Cited evidence (PMID 25046337) [PMID:25046337](https://pubmed.ncbi.nlm.nih.gov/25046337/)
- Cited evidence (PMID 26483177) [PMID:26483177](https://pubmed.ncbi.nlm.nih.gov/26483177/)

Last reconciled with current guidelines: 2026-05-22.
References
  • EAACI/GA²LEN/EuroGuiDerm/APAAACI international guideline for the definition, classification, diagnosis, and management of urticaria (Zuberbier et al, Allergy 2022; PMID 34536239, DOI 10.1111/all.15090) + CSU guidelines "what is new" (Zuberbier et al, JACI 2022; PMID 36481045, DOI 10.1016/j.jaci.2022.10.004) + AAAAI/ACAAI JTF practice-parameter update antileukotriene meta-analysis (Rayner et al, JACI 2024; PMID 38852861) + pivotal omalizumab CSU trials (ASTERIA I PMID 25046337; ASTERIA I/II + GLACIAL response analysis PMID 26483177; angioedema pooled PMID 27424128; background-therapy pooled PMID 26054553) + cyclosporine CSU meta-analysis (Kulthanan PMID 28916431) + omalizumab-vs-immunosuppressant network meta-analysis (Lin PMID 36140253) — PMID:34536239
  • Cited evidence (PMID 36481045) — PMID:36481045
  • Cited evidence (PMID 38852861) — PMID:38852861
  • Cited evidence (PMID 25046337) — PMID:25046337
  • Cited evidence (PMID 26483177) — PMID:26483177