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derm.prurigo-nodularis.core.v1PRODUCTION
derm.prurigo-nodularis.core.v1

Prurigo nodularis (chronic nodular prurigo)

dermatologychronicadult
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12/12 authored

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

Current phase

Frame

Detailed

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.

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chronic-prurigo framing + always-find-the-driver principle + CTCL/BP escape routes set

Patient inputs (16)

Tense bullae / urticarial plaques (nodular or non-bullous BP) or fixed poikilodermatous patches + lymphadenopathy (CTCL) → biopsy + DIF and route OUT before committing to chronic PN immunosuppression (S2k PMID 36252071)

Symmetric extensor dome-shaped hyperkeratotic excoriated nodules with the "butterfly sign" (mid-back sparing) support PN; plaques/discrete/linear/annular argue a mimic; nodule count gates severity and the IGA-PN response endpoint (S2k PMID 36252071; PRIME PMID 37142763)

PN is almost always SECONDARY — a dermatologic / systemic / neuropathic / psychogenic / drug driver must be sought and treated in parallel; this is the core management axis (S2k PMID 36252071; chronic prurigo review PMID 37717255)

Atopic dermatitis is the commonest dermatologic driver and shares the IL-4/13 axis; atopic background steers driver routing and biologic choice (chronic prurigo review PMID 37717255; PN ± atopy subgroup PMID 41219577)

Worst/Peak-Itch NRS is the defining symptom and the primary patient-reported outcome (WI-NRS/PP-NRS) driving every step-up decision and the biologic response definition (PRIME/PRIME2 PMID 37142763; OLYMPIA 2 PMID 37888917)

Weight loss, night sweats, lymphadenopathy, new/refractory onset in an older adult raise occult lymphoma/CTCL/solid malignancy — lowers the biopsy + age-appropriate-malignancy-workup threshold (S2k PMID 36252071)

Excoriated nodules frequently superinfect (S. aureus — weeping/honey-crust/pustules); infected widespread disease needs anti-staphylococcal therapy + skin care before/with escalation (S2k PMID 36252071)

PN carries a major sleep/anxiety/depression/QoL burden (≈6.5 QALYs lost/patient) incl. excoriation-disorder overlap; gates psychodermatology integration and escalation urgency (Whang JAAD 2021 PMID 34058278)

New/refractory PN in an older adult raises the CTCL/BP biopsy threshold and the occult-malignancy screen; polypharmacy + gabapentinoid sedation/fall caution in the elderly (S2k PMID 36252071)

Iron-deficiency / cytopenia / eosinophilia / lymphoma screen as part of the underlying-itch-driver workup + immunosuppressant baseline (S2k PMID 36252071)

Iron-deficiency pruritus is a treatable systemic driver of PN — part of the itch-driver screen (S2k PMID 36252071)

Cholestatic/hepatic pruritus is a major systemic driver; also methotrexate/cyclosporine hepatic baseline + on-treatment surveillance (S2k PMID 36252071)

Thyroid dysfunction is a screenable systemic itch driver in the PN underlying-disease workup (S2k PMID 36252071)

HIV is an underrecognised systemic driver — HIV-associated PN can be a presenting feature; part of the targeted itch-driver screen (S2k PMID 36252071)

Thalidomide/lenalidomide (REMS), methotrexate, mycophenolate are teratogenic and contraindicated in pregnancy/conception; topical-first, dupilumab data more reassuring — gates the systemic ladder (S2k PMID 36252071)

Uraemic pruritus is a major systemic driver; gabapentin/pregabalin require renal dose reduction; cyclosporine nephrotoxicity surveillance via CKD-EPI 2021 race-free eGFR (S2k PMID 36252071; Inker NEJM 2021)

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

Severity triggers (7)

7 need judgement
  • informationallife_threateningpn_with_red_flag_underlying_disease
    PN with B-symptoms / lymphadenopathy / new or treatment-resistant onset in an older adult, or severe decompensated cholestasis, or features of occult malignancy / new lymphoma / CTCL
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebp_or_ctcl_features_on_presentation_or_biopsy
    Tense bullae / urticarial plaques / marked eosinophilia (nodular or non-bullous bullous pemphigoid) OR fixed poikilodermatous patches / clonal histology (cutaneous T-cell lymphoma) in a "PN" presentation
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_refractory_pn_extreme_qol_sleep_suicidality
    Severe PN with extreme sleep deprivation / quality-of-life collapse / depression or suicidality despite optimised topical ± Step-2 therapy and adequate driver treatment
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatewidespread_excoriated_infected_nodules
    Widespread excoriated nodules with weeping / honey-coloured crust / pustules — S. aureus superinfection ± systemic illness
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateckd_uraemic_driver
    PN driven by chronic kidney disease / dialysis-associated uraemic pruritus
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatepregnancy_systemic_gating
    Pregnant / conceiving patient with PN requiring systemic therapy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatebiologic_refractory_reassess_driver_and_diagnosis
    PN not responding by ~12–16 wk on an adequate first-line biologic trial
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

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TREATMENToptionalDrives dose adjustment
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Recommended regimen

Prurigo nodularis — treat-the-driver + severity-tiered antipruritic ladder (S2k chronic prurigo 2022 / chronic prurigo review 2023)
axis: pn_driver_directed_severity_tiered_ladderstep 1 - Step 1 — Foundational skin care + scratch-cycle interruption + topical anti-inflammatory (all patients, alongside driver therapy)
Selected step "Step 1 — Foundational skin care + scratch-cycle interruption + topical anti-inflammatory (all patients, alongside driver therapy)" — All severities, continuously, in parallel with treating the identified underlying driver — the non-negotiable substrate of every step
  • emollient_and_gentle_skin_care
    first line
    barrier_repair
    S2k chronic prurigo (PMID 36252071) — liberal emollient + gentle non-soap cleansing reduces xerosis-driven itch and the threshold to scratch; the substrate of all antipruritic therapy.
  • scratch_cycle_behavioural_interruption_and_occlusion
    first line
    behavioural_barrier
    S2k (PMID 36252071) + chronic prurigo review (PMID 37717255) — habit-reversal, nail care, and occlusion/bandaging physically break the self-perpetuating itch–scratch cycle; lesions will not heal while scratching continues.
  • clobetasol propionate
    first line
    high_potency_topical_corticosteroid
    0.05% ointment • topical • BID to nodules, ± occlusion; taper with healing (max: limited duration/BSA; avoid prolonged occluded use)
    triggers: localised_hyperkeratotic_nodules
    S2k (PMID 36252071) — high-/super-potent topical corticosteroid (often under occlusion) is first-line topical for hyperkeratotic prurigo nodules; potency matched to thickness, then step down.
    rxcui 21245
  • triamcinolone acetonide
    first line
    intralesional_corticosteroid
    5–10 mg/mL intralesional • intralesional • every 3–4 wk to recalcitrant nodules (max: per-lesion limited; atrophy-aware)
    triggers: few_recalcitrant_thick_nodules
    S2k (PMID 36252071) — intralesional triamcinolone for individual recalcitrant thick nodules unresponsive to topical steroid; limited number per session, atrophy-aware.
    rxcui 10759
  • tacrolimus
    second line
    topical_calcineurin_inhibitor
    0.1% ointment • topical • BID (max: per labeling)
    triggers: steroid_sparing_maintenance, thinner_skin_sites, steroid_atrophy_risk
    S2k (PMID 36252071) — topical calcineurin inhibitor is steroid-sparing for maintenance and thinner-skin sites; transient burning common.
    rxcui 42316
  • capsaicin
    second line
    topical_trpv1_agonist
    0.025–0.1% cream (or high-conc patch in selected) • topical • 4–6×/day to defunctionalise cutaneous nerves (max: localised area; burning limits adherence)
    triggers: localised_neuropathic_component, steroid_sparing
    S2k (PMID 36252071) + chronic prurigo review (PMID 37717255) — topical capsaicin defunctionalises TRPV1+ cutaneous nerve fibres (the remodelled-nerve component of PN); burning limits adherence, requires frequent application.
    rxcui 1992
  • hydroxyzine
    add on
    sedating_antihistamine
    25 mg PO at night • PO • nocte PRN (max: 100 mg/day)
    triggers: nocturnal_itch_sleep_disruption
    S2k (PMID 36252071) — sedating antihistamine is adjunctive for SLEEP only (the nocturnal itch–scratch component), not an effective antipruritic for PN per se; elderly anticholinergic/fall caution.
    rxcui 5553

outpatient playbook — drug actions (4)

  1. 1. emollient + scratch-cycle interruption/occlusion + high-potency / intralesional corticosteroid (alongside driver therapy)
    rxcui 21245
    clobetasol 0.05% ± triamcinolone 5–10 mg/mL IL • topical/intralesional • BID / q3–4 wk
    trigger: All patients, all severities, in parallel with treating the driver (S2k PMID 36252071)
    Skin care + breaking the itch–scratch cycle + potent local anti-inflammatory is the foundational substrate; lesions will not heal while scratching/driver continue
  2. 2. nbUVB / gabapentinoid / antidepressant (neuropathic or psychogenic component, topical-refractory)
    rxcui 25480
    gabapentin 300–3600 mg/day (renal-adjust) • PO / phototherapy • titrated / 2–3×/wk
    trigger: Moderate or topical-refractory PN, neuropathic/psychogenic component (Gupta PMID 30446200; S2k PMID 36252071)
    Targets central sensitisation / neuropathic & psychogenic itch while a biologic is arranged; gabapentinoid renal dose-adjust
  3. 3. dupilumab (IL-4Rα, first-line systemic) or nemolizumab (IL-31RA) — FDA/EMA-approved
    rxcui 1876376
    dupilumab 300 mg q2wk (load 600 mg) • SC • q2wk / nemolizumab q4wk
    trigger: Severe / topical-refractory / high QoL burden with adequate driver treatment (PRIME/PRIME2 PMID 37142763; OLYMPIA 2 PMID 37888917)
    First-line approved systemics — dupilumab pooled wk24 itch 58.8% vs 19.0%; nemolizumab wk16 itch 56.3% vs 20.9% with rapid relief
  4. 4. methotrexate / cyclosporine / azathioprine; thalidomide / naltrexone / aprepitant (selected refractory)
    rxcui 6851
    methotrexate 10–15 mg/wk + folic acid • PO/SC • weekly / per agent
    trigger: Biologic-refractory with adequate driver treatment + re-confirmed diagnosis (chronic prurigo review PMID 37717255)
    Refractory immunosuppressant/immunomodulator/opioid-modulator/NK1 options; teratogen + neuropathy + renal cautions; long-term systemic steroids avoided

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Chronic intense itch (>6 wk) with symmetric firm hyperkeratotic dome-shaped excoriated nodules on extensor limbs/trunk — the defining chronic-nodular-prurigo presentation (S2k chronic prurigo Stander JDDG 2022 PMID 36252071); History of repeated scratching/picking with scratch-associated pruriginous lesions — the self-perpetuating itch–scratch cycle defining chronic prurigo (S2k PMID 36252071); Pre-existing itch driver (atopic dermatitis, CKD, cholestasis, thyroid disease, iron deficiency, HIV, lymphoma, neuropathic, psychogenic, drug) → PN as a SECONDARY itch-scratch sequel (S2k PMID 36252071; chronic prurigo review PMID 37717255).

Objective

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

Assessment

**Prurigo nodularis (chronic nodular prurigo)** (derm.prurigo-nodularis.core.v1).
Phenotype framing: 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).
Scope: 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.

No severity triggers fired against current inputs.

Plan

Regimen axis: **Prurigo nodularis — treat-the-driver + severity-tiered antipruritic ladder (S2k chronic prurigo 2022 / chronic prurigo review 2023)** — step "Step 1 — Foundational skin care + scratch-cycle interruption + topical anti-inflammatory (all patients, alongside driver therapy)".
1. emollient_and_gentle_skin_care (barrier_repair, first line) — S2k chronic prurigo (PMID 36252071) — liberal emollient + gentle non-soap cleansing reduces xerosis-driven itch and the threshold to scratch; the substrate of all antipruritic therapy.
2. scratch_cycle_behavioural_interruption_and_occlusion (behavioural_barrier, first line) — S2k (PMID 36252071) + chronic prurigo review (PMID 37717255) — habit-reversal, nail care, and occlusion/bandaging physically break the self-perpetuating itch–scratch cycle; lesions will not heal while scratching continues.
3. clobetasol propionate 0.05% ointment topical BID to nodules, ± occlusion; taper with healing (high_potency_topical_corticosteroid, first line) — S2k (PMID 36252071) — high-/super-potent topical corticosteroid (often under occlusion) is first-line topical for hyperkeratotic prurigo nodules; potency matched to thickness, then step down.
4. triamcinolone acetonide 5–10 mg/mL intralesional intralesional every 3–4 wk to recalcitrant nodules (intralesional_corticosteroid, first line) — S2k (PMID 36252071) — intralesional triamcinolone for individual recalcitrant thick nodules unresponsive to topical steroid; limited number per session, atrophy-aware.
5. tacrolimus 0.1% ointment topical BID (topical_calcineurin_inhibitor, second line) — S2k (PMID 36252071) — topical calcineurin inhibitor is steroid-sparing for maintenance and thinner-skin sites; transient burning common.
6. capsaicin 0.025–0.1% cream (or high-conc patch in selected) topical 4–6×/day to defunctionalise cutaneous nerves (topical_trpv1_agonist, second line) — S2k (PMID 36252071) + chronic prurigo review (PMID 37717255) — topical capsaicin defunctionalises TRPV1+ cutaneous nerve fibres (the remodelled-nerve component of PN); burning limits adherence, requires frequent application.
7. hydroxyzine 25 mg PO at night PO nocte PRN (sedating_antihistamine, add on) — S2k (PMID 36252071) — sedating antihistamine is adjunctive for SLEEP only (the nocturnal itch–scratch component), not an effective antipruritic for PN per se; elderly anticholinergic/fall caution.

Setting playbook (outpatient) — Confirm PN (exclude CTCL/BP/scabies/HLP mimics), identify + treat the underlying itch driver IN PARALLEL, run the severity-tiered antipruritic ladder to first-line biologic, integrate psychodermatology, and gate systemic agents on pregnancy/age/renal status (S2k chronic prurigo Stander JDDG 2022 PMID 36252071; chronic prurigo review PMID 37717255)
8. emollient + scratch-cycle interruption/occlusion + high-potency / intralesional corticosteroid (alongside driver therapy) clobetasol 0.05% ± triamcinolone 5–10 mg/mL IL topical/intralesional BID / q3–4 wk — All patients, all severities, in parallel with treating the driver (S2k PMID 36252071) (Skin care + breaking the itch–scratch cycle + potent local anti-inflammatory is the foundational substrate; lesions will not heal while scratching/driver continue)
9. nbUVB / gabapentinoid / antidepressant (neuropathic or psychogenic component, topical-refractory) gabapentin 300–3600 mg/day (renal-adjust) PO / phototherapy titrated / 2–3×/wk — Moderate or topical-refractory PN, neuropathic/psychogenic component (Gupta PMID 30446200; S2k PMID 36252071) (Targets central sensitisation / neuropathic & psychogenic itch while a biologic is arranged; gabapentinoid renal dose-adjust)
10. dupilumab (IL-4Rα, first-line systemic) or nemolizumab (IL-31RA) — FDA/EMA-approved dupilumab 300 mg q2wk (load 600 mg) SC q2wk / nemolizumab q4wk — Severe / topical-refractory / high QoL burden with adequate driver treatment (PRIME/PRIME2 PMID 37142763; OLYMPIA 2 PMID 37888917) (First-line approved systemics — dupilumab pooled wk24 itch 58.8% vs 19.0%; nemolizumab wk16 itch 56.3% vs 20.9% with rapid relief)
11. methotrexate / cyclosporine / azathioprine; thalidomide / naltrexone / aprepitant (selected refractory) methotrexate 10–15 mg/wk + folic acid PO/SC weekly / per agent — Biologic-refractory with adequate driver treatment + re-confirmed diagnosis (chronic prurigo review PMID 37717255) (Refractory immunosuppressant/immunomodulator/opioid-modulator/NK1 options; teratogen + neuropathy + renal cautions; long-term systemic steroids avoided)

Non-pharmacologic actions:
- Always treat the identified underlying driver in parallel — route AD to derm.atopic-dermatitis.core.v1; refer systemic driver (nephrology/hepatology/endocrine/ID/haematology) (S2k PMID 36252071)
- Habit-reversal training + nail care + occlusion/bandaging + written scratch-cycle interruption plan (chronic prurigo review PMID 37717255)
- Integrated psychodermatology for excoriation-disorder / depression / anxiety overlap (Whang/Kwatra PMID 34058278)
- nbUVB referral for moderate widespread topical-refractory disease (S2k PMID 36252071)
- Biopsy + DIF for any BP / CTCL features before chronic immunosuppression (S2k PMID 36252071)

AVOID / contraindication checks:
- Thalidomide lenalidomide methotrexate mycophenolate teratogenic contraindicated in pregnancy (S2k PMID 36252071 — REMS/pregnancy prevention programme for thalidomide/lenalidomide; topical first in pregnancy, dupilumab data more reassuring)
- Gabapentinoid renal dose adjust and sedation misuse (S2k PMID 36252071 — gabapentin/pregabalin require renal dose reduction via calc.ckd_epi_2021, esp. with a uraemic driver; sedation/fall/misuse caution, esp. elderly)
- Thalidomide lenalidomide dose dependent peripheral neuropathy (chronic prurigo review PMID 37717255 — cumulative dose limited; baseline + serial neuropathy screening)
- Cyclosporine nephrotoxicity hypertension limit duration (chronic prurigo review PMID 37717255 — BP + creatinine CKD EPI 2021 surveillance; short to intermediate term)
- Avoid long term systemic corticosteroids (S2k PMID 36252071 — rebound + cumulative harm; steroid sparing systemic preferred)
- Sedating antihistamine is for sleep only not an antipruritic for PN (S2k PMID 36252071 — anticholinergic/fall caution in the elderly)
- Must exclude CTCL and bullous pemphigoid before chronic immunosuppression (S2k PMID 36252071 — biopsy + DIF if atypical/refractory; immunosuppressing undiagnosed CTCL is harmful)

Monitoring

Regimen monitoring:
- itch NRS plus nodule count PAS plus sleep QoL at 4-16wk (PRIME/PRIME2 PMID 37142763; OLYMPIA 2 PMID 37888917 — biologic effect by 12–16 wk; nemolizumab rapid itch often by wk4)
- driver specific labs and confirm driver therapy effective (S2k PMID 36252071 — skin will not durably clear while the underlying driver is active)
- gabapentinoid: renal-dose check (CKD-EPI 2021) + sedation/misuse review (Gupta PMID 30446200)
- methotrexate: CBC + LFT periodic + folic acid; azathioprine: TPMT-guided + CBC/LFT (chronic prurigo review PMID 37717255)
- cyclosporine: BP + creatinine (CKD-EPI 2021) on schedule (chronic prurigo review PMID 37717255)
- thalidomide/lenalidomide: serial peripheral-neuropathy screen + pregnancy-prevention programme (chronic prurigo review PMID 37717255)
- dupilumab: conjunctivitis surveillance, no routine labs; nemolizumab: injection-site + long-term tolerability (PRIME/PRIME2 PMID 37142763; OLYMPIA-LTE PMID 41405008)
- sleep mood excoriation surveillance with psychodermatology (Whang/Kwatra PMID 34058278)

Setting (outpatient) monitoring:
- Reassess itch NRS + nodule count/PAS + sleep/QoL at 4–16 wk per agent; confirm driver therapy is effective (S2k PMID 36252071; PRIME/PRIME2 PMID 37142763)
- Drug-class safety on schedule: gabapentinoid renal dose; MTX CBC/LFT; cyclosporine BP/Cr (CKD-EPI 2021); thalidomide neuropathy; dupilumab conjunctivitis (chronic prurigo review PMID 37717255)

Follow-up plan: 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.
- Close-out criterion: scratch-cycle + driver-control + psychodermatology + relapse-and-rediagnosis plan documented

Monitoring phase: 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.

Disposition

Current setting: outpatient — Confirm PN (exclude CTCL/BP/scabies/HLP mimics), identify + treat the underlying itch driver IN PARALLEL, run the severity-tiered antipruritic ladder to first-line biologic, integrate psychodermatology, and gate systemic agents on pregnancy/age/renal status (S2k chronic prurigo Stander JDDG 2022 PMID 36252071; chronic prurigo review PMID 37717255)

Disposition criteria:
- Continue dual-track (driver + skin ladder) outpatient management with derm + driver-specialty follow-up if responding (S2k PMID 36252071)
- Step up the ladder if an adequate trial fails AND the driver is adequately treated (re-confirm diagnosis first)
- Admit only for a red-flag driver needing urgent inpatient workup or widespread infected/erythrodermic disease with systemic illness

Escalation triggers (move to higher acuity):
- B-symptoms / lymphadenopathy / new or treatment-resistant PN in an older adult → urgent biopsy + age-appropriate malignancy/lymphoma workup; route CTCL OUT to derm.cutaneous-t-cell-lymphoma.core.v1 (S2k PMID 36252071)
- Tense bullae / urticarial plaques / eosinophilia → biopsy + DIF; route nodular/non-bullous BP OUT to derm.bullous-pemphigoid.core.v1 (S2k PMID 36252071)
- Severe refractory disease with extreme sleep/QoL impairment or suicidality → escalate to biologic + urgent psychodermatology/psychiatry
- Severe decompensated cholestatic / new aggressive lymphoma driver → urgent driver workup/route + inpatient if unstable

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] PN with B-symptoms / lymphadenopathy / new or treatment-resistant onset in an older adult, or severe decompensated cholestasis, or features of occult malignancy / new lymphoma / CTCL
- [SEVERE] Tense bullae / urticarial plaques / marked eosinophilia (nodular or non-bullous bullous pemphigoid) OR fixed poikilodermatous patches / clonal histology (cutaneous T-cell lymphoma) in a "PN" presentation
- [SEVERE] Severe PN with extreme sleep deprivation / quality-of-life collapse / depression or suicidality despite optimised topical ± Step-2 therapy and adequate driver treatment

Citations

- S2k guideline: diagnosis and treatment of chronic pruritus / chronic prurigo (Stander et al, JDDG 2022; PMID 36252071, DOI 10.1111/ddg.14830 — pursue + treat the underlying disease + symptomatic antipruritic ladder) + chronic prurigo incl. prurigo nodularis: new insights & treatments (Müller, Zeidler, Stander, Am J Clin Dermatol 2023; PMID 37717255, DOI 10.1007/s40257-023-00818-z) + dupilumab LIBERTY-PN PRIME/PRIME2 phase-3 RCTs (Yosipovitch et al, Nat Med 2023; PMID 37142763, DOI 10.1038/s41591-023-02320-9) + pooled (PMID 39006917, DOI 10.1016/j.jdin.2024.03.025) + atopic/non-atopic subgroup (Kim et al, Am J Clin Dermatol 2025; PMID 41219577, DOI 10.1007/s40257-025-00993-1) + nemolizumab OLYMPIA 2 (Kwatra et al, NEJM 2023; PMID 37888917, DOI 10.1056/NEJMoa2301333) + OLYMPIA 1 (JAMA Dermatol 2025; PMID 39602139, DOI 10.1001/jamadermatol.2024.4796) + OLYMPIA-LTE 100-wk (JEADV 2025; PMID 41405008, DOI 10.1111/jdv.70266) + gabapentinoid evidence (Gupta et al, Clin Dermatol 2018; PMID 30446200) + paroxetine RCT (Zylicz et al, J Pain Symptom Manage 2003; PMID 14654262) + PN QoL/economic burden (Whang/Kwatra, JAAD 2021; PMID 34058278) [PMID:36252071](https://pubmed.ncbi.nlm.nih.gov/36252071/)
- Cited evidence (PMID 37717255) [PMID:37717255](https://pubmed.ncbi.nlm.nih.gov/37717255/)
- Cited evidence (PMID 37142763) [PMID:37142763](https://pubmed.ncbi.nlm.nih.gov/37142763/)
- Cited evidence (PMID 39006917) [PMID:39006917](https://pubmed.ncbi.nlm.nih.gov/39006917/)
- Cited evidence (PMID 41219577) [PMID:41219577](https://pubmed.ncbi.nlm.nih.gov/41219577/)

Last reconciled with current guidelines: 2026-05-22.
References
  • S2k guideline: diagnosis and treatment of chronic pruritus / chronic prurigo (Stander et al, JDDG 2022; PMID 36252071, DOI 10.1111/ddg.14830 — pursue + treat the underlying disease + symptomatic antipruritic ladder) + chronic prurigo incl. prurigo nodularis: new insights & treatments (Müller, Zeidler, Stander, Am J Clin Dermatol 2023; PMID 37717255, DOI 10.1007/s40257-023-00818-z) + dupilumab LIBERTY-PN PRIME/PRIME2 phase-3 RCTs (Yosipovitch et al, Nat Med 2023; PMID 37142763, DOI 10.1038/s41591-023-02320-9) + pooled (PMID 39006917, DOI 10.1016/j.jdin.2024.03.025) + atopic/non-atopic subgroup (Kim et al, Am J Clin Dermatol 2025; PMID 41219577, DOI 10.1007/s40257-025-00993-1) + nemolizumab OLYMPIA 2 (Kwatra et al, NEJM 2023; PMID 37888917, DOI 10.1056/NEJMoa2301333) + OLYMPIA 1 (JAMA Dermatol 2025; PMID 39602139, DOI 10.1001/jamadermatol.2024.4796) + OLYMPIA-LTE 100-wk (JEADV 2025; PMID 41405008, DOI 10.1111/jdv.70266) + gabapentinoid evidence (Gupta et al, Clin Dermatol 2018; PMID 30446200) + paroxetine RCT (Zylicz et al, J Pain Symptom Manage 2003; PMID 14654262) + PN QoL/economic burden (Whang/Kwatra, JAAD 2021; PMID 34058278) — PMID:36252071
  • Cited evidence (PMID 37717255) — PMID:37717255
  • Cited evidence (PMID 37142763) — PMID:37142763
  • Cited evidence (PMID 39006917) — PMID:39006917
  • Cited evidence (PMID 41219577) — PMID:41219577