12-phase flow (12)

1. 1FRAME
   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.
   advance: urticaria framing + 3-way classification axis set; anaphylaxis/HAE/vasculitis escape routes noted
2. 2ENTRY
   Recognise transient pruritic blanching wheals ± angioedema; record individual-wheal duration (<24 h pivot) and the 6-week acute-vs-chronic boundary up front — both drive the entire downstream path.
   inputs: individual_wheal_duration, symptom_duration_6wk_threshold
   actions: workup.urticaria_angioedema
   advance: true-urticaria morphology confirmed; acute vs chronic assigned
3. 3CONTEXT
   Build the classification + trigger context: wheals-only vs wheals+angioedema vs angioedema-only; physical-inducible trigger inventory (dermographism/cholinergic/cold/delayed-pressure/solar/heat/aquagenic/vibratory); recent infection/drug/food; NSAID and ACE-inhibitor exposure; autoimmune history. CSU needs only a limited routine workup — broad allergy testing is NOT indicated to diagnose urticaria.
   inputs: angioedema_presence_and_distribution, physical_inducible_trigger_inventory, recent_infection_drug_food_trigger
   actions: workup.urticaria_angioedema
   advance: subtype (acute / CSU / CIndU) + trigger context established
4. 4RED_FLAGS
   Anaphylaxis (wheals + airway/voice change/wheeze/hypotension/GI) → STAT IM epinephrine, route OUT to allergy.anaphylaxis.v1 (workup.anaphylaxis). Isolated recurrent angioedema WITHOUT wheals + ACE-inhibitor or family history → bradykinin/HAE pathway: C4/C1-INH, stop ACE-inhibitor — does NOT respond to antihistamine/epinephrine/corticosteroid. Urticarial vasculitis (individual lesions >24 h, painful/burning, bruising/post-inflammatory pigmentation, ± systemic) → skin biopsy. These are recognised here, NOT managed as urticaria.
   inputs: anaphylaxis_systemic_features, ace_inhibitor_use, urticarial_vasculitis_features, family_history_recurrent_angioedema
   actions: workup.anaphylaxis, workup.urticaria_angioedema
   advance: anaphylaxis / bradykinin-HAE-ACEi / urticarial-vasculitis screened and escalated/routed if present
5. 5INITIAL_WORKUP
   Urticaria is a clinical diagnosis — no test confirms it. Routine CSU workup is deliberately LIMITED: CBC + ESR/CRP (and stop there unless history/exam directs otherwise). Extended targeted workup only as indicated: autoimmune-thyroid screen when suggested; provocation/threshold testing for a suspected inducible subtype; skin biopsy for urticarial-vasculitis features; C4/C1-INH if angioedema without wheals. Blanket food/allergy panels are NOT recommended.
   inputs: cbc_with_differential, inflammatory_markers_esr_crp, autoimmune_thyroid_association
   actions: panel.cbc, panel.inflammation
   advance: limited routine workup done; targeted tests sent only as clinically indicated
6. 6BRANCHING_WORKUP
   Decision tree off the wheal pivot: transient wheal + itch + blanching → urticaria, classify acute vs CSU vs CIndU (subtype-specific provocation/threshold test for CIndU); fixed lesion >24 h + burning + bruising + ↑ESR/CRP → biopsy for urticarial vasculitis; angioedema without wheals + ACE-inhibitor/family history → C4/C1-INH (HAE/ACEi pathway, route OUT); wheals + systemic involvement → anaphylaxis (route OUT); fixed eczematous chronic plaques (not transient wheals) → atopic dermatitis (route derm.atopic-dermatitis.core.v1); urticarial eruption temporally tied to a new drug → drug-eruption (route derm.drug-eruption.core.v1).
   inputs: urticarial_vasculitis_features, physical_inducible_trigger_inventory
   actions: workup.urticaria_angioedema, workup.chronic_pruritus
   advance: subtype assigned OR an alternative diagnosis assigned + routed by engine_id
7. 7DIFFERENTIAL
   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).
   advance: single best diagnosis selected; vasculitis/HAE/anaphylaxis actively excluded
8. 8RISK_STRATIFICATION
   Activity + control + QoL = severity (UAS7 / UCT / AAS for angioedema / DLQI — schema-blocked as TS calculators, captured narratively). Mild well-controlled acute → standard-dose 2nd-gen H1 ± short rescue; persistent/poorly-controlled chronic → up-dosed H1 then omalizumab; severe high-UAS7 with sleep/QoL impact or refractory → omalizumab/cyclosporine. Anaphylaxis / airway angioedema / bradykinin-HAE override the ladder entirely.
   inputs: disease_activity_quality_of_life_burden
   advance: activity/control tier + escalation decision assigned
9. 9TREATMENT
   Acute severe flare: short oral corticosteroid burst (≤10 d) as RESCUE only + a 2nd-gen H1; IM epinephrine if anaphylaxis. Chronic (CSU/CIndU) — the guideline stepwise ladder: Step 1 standard-dose 2nd-generation H1-antihistamine → Step 2 up-dose the SAME 2nd-gen H1 up to 4× standard → Step 3 add omalizumab → Step 4 cyclosporine (omalizumab-refractory). First-generation sedating antihistamines are NOT recommended (anticholinergic/sedation, no efficacy advantage). Chronic systemic corticosteroids are recommended AGAINST. Comorbidity gating: ACE-inhibitor angioedema → stop drug + HAE pathway (NOT the ladder); pregnancy → loratadine/cetirizine preferred, avoid cyclosporine if possible, omalizumab data reassuring; renal → cetirizine/levocetirizine dose-reduce, cyclosporine eGFR + BP surveillance.
   inputs: pregnancy_lactation_status, age, renal_function_egfr, liver_function_baseline
   advance: correct ladder step (or acute rescue) started; agent gated on pregnancy/age/renal; 1st-gen-avoid + against-chronic-steroid rules applied
10. 10DISPOSITION
    Acute uncomplicated urticaria → outpatient with a 2nd-gen H1 and return precautions for angioedema/anaphylaxis. CSU/CIndU → outpatient dermatology/allergy ladder management. ED only for: anaphylaxis, laryngeal/airway angioedema, bradykinin-mediated angioedema needing C1-INH/icatibant, or a severe acute generalized flare needing parenteral rescue. Route anaphylaxis/HAE OUT by engine_id.
    inputs: anaphylaxis_systemic_features, angioedema_presence_and_distribution
    advance: disposition documented; ED/airway pathway only for anaphylaxis/airway/bradykinin angioedema
11. 11MONITORING
    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.
    inputs: disease_activity_quality_of_life_burden, renal_function_egfr
    actions: panel.cbc
    advance: control re-assessed at the step-appropriate interval; cyclosporine BP/Cr on schedule
12. 12FOLLOWUP
    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.
    inputs: physical_inducible_trigger_inventory, disease_activity_quality_of_life_burden
    actions: workup.chronic_pruritus
    advance: step-down attempted when controlled; trigger + return-precaution education documented