12-phase flow (12)

1. 1FRAME
   Frame PN as the NODULAR subtype of chronic prurigo: a chronic neuroimmune-fibrotic itch–scratch disease (IL-31 / IL-4·IL-13 + cutaneous nerve remodelling), almost always SECONDARY to an identifiable itch driver. The two governing principles: (1) ALWAYS pursue + treat the underlying driver in parallel with the skin; (2) the not-to-miss is nodular CTCL / nodular bullous pemphigoid masquerading as PN — biopsy threshold. Managed almost entirely outpatient.
   advance: chronic-prurigo framing + always-find-the-driver principle + CTCL/BP escape routes set
2. 2ENTRY
   Recognise chronic intense itch (>6 wk) with symmetric hyperkeratotic excoriated nodules and a documented itch–scratch cycle; capture itch-severity NRS up front (the primary PRO driving the entire ladder).
   inputs: itch_severity_nrs
   actions: workup.chronic_pruritus
   advance: chronic-prurigo-nodular entry recognised; itch NRS recorded
3. 3CONTEXT
   Build the diagnosis + driver context: symmetric extensor dome-shaped hyperkeratotic excoriated nodules with mid-back-sparing "butterfly sign", nodule count/distribution, atopic diathesis, and the structured UNDERLYING-ITCH-DRIVER screen (dermatologic / systemic / neuropathic / psychogenic / drug). The driver search is the core management axis, not an afterthought.
   inputs: nodule_count_distribution_morphology, underlying_itch_driver_screen, atopic_diathesis
   actions: workup.chronic_pruritus
   advance: PN morphology supported; underlying-driver inventory established
4. 4RED_FLAGS
   Screen the not-to-miss + complications: B-symptoms / lymphadenopathy / new or treatment-resistant PN in an older adult → occult lymphoma/CTCL/solid malignancy (lower biopsy + age-appropriate-malignancy-workup threshold); tense bullae/urticarial plaques → nodular/non-bullous bullous pemphigoid; widespread excoriated weeping/honey-crusted nodules → S. aureus superinfection. Severe cholestasis / new lymphoma are red-flag drivers needing urgent workup/route.
   inputs: systemic_symptom_and_malignancy_screen, secondary_infection_signs
   actions: panel.cbc, panel.inflammation
   advance: malignancy/CTCL/BP red flags + superinfection screened and escalated/routed if present
5. 5INITIAL_WORKUP
   The itch-driver screen IS the workup: CBC + differential, ferritin/iron studies, renal function (panel.renal — uraemic), LFT/cholestasis (panel.lft — hepatic), TSH (panel.thyroid), HIV serology, ± age-appropriate malignancy / lymphoma evaluation. PN is a clinical diagnosis; targeted labs identify the treatable driver, not PN itself.
   inputs: cbc_with_differential, ferritin_iron_studies, lft_cholestasis_panel, tsh_thyroid_function, hiv_serology
   actions: panel.cbc, panel.lft, panel.renal, panel.thyroid
   advance: itch-driver labs sent; treatable systemic driver identified or excluded
6. 6BRANCHING_WORKUP
   Driver-and-mimic decision tree: eczematous flexural + atopy → atopic-dermatitis driver (route derm.atopic-dermatitis.core.v1); burrows/web-space/contacts → nodular scabies (route derm.scabies.core.v1); violaceous polygonal hypertrophic plaques → hypertrophic lichen planus (route derm.lichen-planus.core.v1); fixed poikilodermatous patches / lymphadenopathy / atypical → SKIN BIOPSY for CTCL (route derm.cutaneous-t-cell-lymphoma.core.v1); tense bullae/urticarial plaques or eosinophilia → biopsy + DIF for nodular/non-bullous bullous pemphigoid (route derm.bullous-pemphigoid.core.v1); CKD/diabetes + central-keratotic plugged papules → perforating dermatosis. Biopsy + DIF lowered-threshold whenever BP/CTCL features.
   inputs: bullous_or_lymphoma_features
   actions: workup.chronic_pruritus
   advance: PN confirmed + driver assigned, OR a mimic assigned + routed by engine_id; CTCL/BP excluded or biopsied
7. 7DIFFERENTIAL
   Terminal differential with named pivots: PN vs lichen simplex chronicus (lichenified plaques vs discrete nodules pivot) vs hypertrophic lichen planus (violaceous polygonal pruritic plaque + Wickham pivot — route derm.lichen-planus.core.v1) vs nodular scabies (burrow + contact itch + scraping pivot — route derm.scabies.core.v1) vs perforating dermatosis (central keratotic plug + CKD/diabetes pivot) vs nodular/non-bullous bullous pemphigoid (tense bulla / DIF linear C3-IgG pivot — route derm.bullous-pemphigoid.core.v1) vs nodular CTCL (fixed poikilodermatous / clonal biopsy pivot — route derm.cutaneous-t-cell-lymphoma.core.v1) vs multiple keratoacanthomas (rapid crateriform pivot) vs neurotic excoriations / excoriation disorder (no primary nodule, psychocutaneous pivot) vs actinic prurigo (photodistributed + cheilitis pivot).
   advance: single best diagnosis + the identified driver assigned; CTCL/BP actively excluded
8. 8RISK_STRATIFICATION
   Severity = itch NRS × nodule count/extent × sleep/QoL/psychiatric burden (WI-NRS/PP-NRS, IGA-PN stage, PAS, DLQI — schema-blocked as TS calculators, captured narratively). Mild localised → topical-only; moderate widespread or topical-refractory → phototherapy/gabapentinoid/antidepressant ± step to systemic; severe / topical-refractory / extreme sleep-QoL-suicidality burden → first-line systemic biologic + psychodermatology. Red-flag underlying disease (lymphoma/CTCL, severe cholestasis, occult malignancy) overrides the cosmetic ladder → urgent workup/route.
   inputs: sleep_psychiatric_qol_burden, itch_severity_nrs
   advance: mild/moderate/severe tier + escalation + driver-urgency decision assigned
9. 9TREATMENT
   TWO PARALLEL TRACKS, always: (A) TREAT THE IDENTIFIED DRIVER (dermatologic — route AD; systemic — uraemic/cholestatic/thyroid/iron/HIV-directed; neuropathic — gabapentinoid; psychogenic — psychodermatology) and (B) the severity-tiered skin ladder. Step 1: emollient + gentle skin care + scratch-cycle behavioural interruption + occlusion/bandaging (non-pharm) + high-potency / intralesional corticosteroid + topical calcineurin + topical capsaicin; sedating antihistamine for sleep only. Step 2: nbUVB phototherapy (non-pharm); gabapentin/pregabalin (neuropathic itch); antidepressant (mirtazapine / SSRI / doxepin) for refractory or psychogenic component. Step 3 (first-line systemic): dupilumab (IL-4Rα — PRIME/PRIME2, FDA/EMA-approved) or nemolizumab (IL-31RA — OLYMPIA, FDA-approved). Step 4 (refractory): methotrexate / cyclosporine / azathioprine; thalidomide-lenalidomide (teratogen/neuropathy — REMS); opioid modulators (naltrexone) / aprepitant (NK1) selected. Long-term systemic corticosteroids avoided. Gating: pregnancy → avoid thalidomide/lenalidomide/MTX/MMF; renal → gabapentinoid renal dose + cyclosporine eGFR surveillance.
   inputs: pregnancy_status, age, renal_function_egfr
   advance: driver treatment started in parallel + appropriate skin-ladder step started; agent gated on pregnancy/age/renal
10. 10DISPOSITION
    Almost entirely outpatient dermatology + driver-specialty co-management (nephrology/hepatology/haematology/psychiatry as indicated). Inpatient only for: a red-flag driver needing urgent inpatient workup (new aggressive lymphoma/CTCL, severe decompensated cholestasis), or widespread infected/erythrodermic disease with systemic illness. Route CTCL/BP/AD/scabies OUT by engine_id; route the systemic driver to its specialty.
    inputs: systemic_symptom_and_malignancy_screen
    advance: disposition documented; outpatient derm + driver-specialty follow-up arranged; admission only for red-flag driver / severe superinfection
11. 11MONITORING
    Disease: itch NRS + nodule count/healing (PAS) + sleep/QoL at 4–16 wk to judge step response — biologic effect typically by 12–16 wk (nemolizumab rapid itch often by wk 4). Driver-specific: re-check the driver labs and confirm driver therapy is taking effect (the skin will not clear if the driver is untreated). Drug safety: gabapentinoid renal dosing + sedation/misuse; immunosuppressant labs (MTX CBC/LFT; cyclosporine BP/Cr CKD-EPI 2021; thalidomide neuropathy screen); dupilumab conjunctivitis; nemolizumab injection-site. Reassess diagnosis (biopsy for CTCL/BP) if refractory despite a biologic.
    inputs: itch_severity_nrs, renal_function_egfr
    actions: panel.cbc, panel.lft
    advance: objective itch/nodule response assessed at the agent-appropriate interval; driver-specific + drug-class safety labs on schedule
12. 12FOLLOWUP
    Chronic-disease maintenance: durable scratch-cycle interruption (habit-reversal, occlusion, nail care, written plan), continued driver control (the disease relapses if the driver recurs), proactive emollient/skin-care habit, sleep + mental-health surveillance with integrated psychodermatology for excoriation/depression/anxiety, gabapentinoid renal-dose continuity, biologic interval/step-down once durably controlled, and re-evaluation of the diagnosis (CTCL/BP) if the course remains atypical. Dermatology continuity for any systemic agent.
    inputs: underlying_itch_driver_screen, sleep_psychiatric_qol_burden
    actions: workup.chronic_pruritus
    advance: scratch-cycle + driver-control + psychodermatology + relapse-and-rediagnosis plan documented