12-phase flow (12)

1. 1FRAME
   Frame as the NOT-TO-MISS indolent cutaneous lymphoma that classically masquerades as "treatment-resistant eczema/psoriasis" for years. The dermatology engine owns RECOGNITION → repeat steroid-washed skin biopsy with immunophenotype + TCR clonality → ISCL/EORTC TNMB staging incl. blood (Sézary) → stage-directed therapy (skin-directed first for early disease), and ROUTES advanced/systemic/transplant care by engine_id to hematology-oncology shared-care (heme.cutaneous-lymphoma-systemic.core.v1). This is the engine derm.atopic-dermatitis / derm.psoriasis / derm.vitiligo route to when an "eczema/psoriasis" resists adequate therapy or is atypical. Early IA disease has near-normal life expectancy; advanced/Sézary prognosis is grim — the failure mode is years of immunosuppressing an undiagnosed lymphoma (ISCL/EORTC PMID 17540844; Agar PMID 20855822).
   advance: derm-scope set; resistant-eczema recognition + systemic/heme-onc route noted by engine_id
2. 2ENTRY
   Recognise the resistant-"eczema/psoriasis" adult, the fixed bathing-trunk poikilodermatous patch/plaque eruption, a new cutaneous tumour/ulcer in long-standing disease, erythroderma with intractable pruritus, or an established CTCL in surveillance; capture duration + treatment-resistance history up front (the strongest recognition signal — diagnostic delay is the dominant harm).
   inputs: duration_and_treatment_resistance_history
   actions: workup.chronic_pruritus
   advance: entry trigger present; duration + treatment-resistance history recorded
3. 3CONTEXT
   Build the recognition context: fixed non-sun-exposed "bathing-trunk" distribution, poikiloderma, varied/asymmetric morphology, intractable pruritus + QoL burden, and immunosuppression/transplant status (aggressive-course modifier). Reframe years of "eczema/psoriasis that never truly clears on adequate therapy" as CTCL until biopsy says otherwise — the core message of this engine.
   inputs: lesion_distribution_and_morphology, pruritus_severity_and_qol, immunosuppression_or_transplant
   actions: workup.chronic_pruritus
   advance: MF-favouring morphology/distribution + treatment-resistance context established; CTCL actively considered
4. 4RED_FLAGS
   Do NOT keep immunosuppressing undiagnosed disease. Screen: erythroderma + skin-failure (thermoregulatory/fluid compromise, exfoliation) → admit + systemic + infection management; Staphylococcus aureus superinfection / sepsis (leading cause of death in advanced disease) → urgent anti-staphylococcal therapy; large-cell transformation (rapidly growing/ulcerated tumour, accelerated progression) → urgent heme-onc + re-biopsy + restage; lymphadenopathy / visceral disease → nodal biopsy + stage-directed imaging + heme-onc routing.
   inputs: erythroderma_and_skin_failure_signs, secondary_infection_sepsis_signs, large_cell_transformation_signs, lymphadenopathy_and_visceral_signs
   actions: panel.cbc, panel.inflammation, workup.le_edema
   advance: erythroderma/skin-failure, sepsis, transformation, and nodal/visceral red flags screened and escalated/routed if present
5. 5INITIAL_WORKUP
   DIAGNOSIS: serial skin biopsies from the most indurated/representative lesions AFTER holding topical/systemic corticosteroids and phototherapy ≥2 wk (steroids blunt the epidermotropic infiltrate and lower yield — repeat biopsy over time if non-diagnostic). Synoptic histopathology: atypical epidermotropic cerebriform lymphocytes, Pautrier microabscess, lining-up along the basal layer; immunohistochemistry (loss of CD7/CD26, aberrant CD4:CD8, CD30 for transformation/brentuximab); T-cell-receptor gene rearrangement (clonality). Blood: CBC + flow cytometry / Sézary-cell count (B0/B1/B2), LDH, LFT. The ISCL early-MF diagnostic algorithm integrates clinical + histopathologic + molecular + immunopathologic points (ISCL/EORTC PMID 17540844).
   inputs: skin_biopsy_immunophenotype_tcr_clonality, cbc_with_differential_and_sezary_flow, lft
   actions: panel.cbc, panel.lft, panel.inflammation
   advance: steroid-washed serial biopsy with immunophenotype + TCR clonality obtained; blood Sézary class + LDH/LFT determined
6. 6BRANCHING_WORKUP
   Diagnosis/staging branch: ISCL early-MF algorithm positive → MF confirmed → ISCL/EORTC T-class (T1 patch/plaque <10% BSA, T2 ≥10%, each a=patch-only vs b=plaque; T3 tumour; T4 erythroderma) + N (nodes) + M (visceral) + B (blood B0/B1/B2). Erythroderma + B2 = Sézary syndrome. Stage-directed imaging: none for limited early patch disease; CT/PET-CT + LDH for tumour-stage / erythrodermic / lymphadenopathic / B2 disease; nodal/visceral biopsy as indicated. CD30 immunostain + subtype (folliculotropic, large-cell-transformed) gate brentuximab vedotin candidacy and prognosis, carried to heme-onc. Hold steroids before any repeat biopsy.
   inputs: prior_topical_steroid_phototherapy_exposure, staging_imaging_by_stage, cd30_expression_and_subtype
   actions: workup.le_edema, panel.inflammation
   advance: ISCL/EORTC TNMB stage assigned (incl. blood class); Sézary identified if erythroderma+B2; CD30/subtype + stage-directed imaging obtained as indicated
7. 7DIFFERENTIAL
   Terminal eczematous/erythrodermic differential with named pivots: MF vs atopic dermatitis (route derm.atopic-dermatitis.core.v1 — the canonical misdiagnosis; pivot: fixed non-sun-exposed bathing-trunk distribution + poikiloderma + treatment-resistance + atypical clonal epidermotropic biopsy) vs psoriasis (route derm.psoriasis.core.v1 — sharp salmon plaque/silver scale/nail pits pivot) vs nummular eczema (coin lesions, responds to steroids pivot) vs tinea corporis (route derm.tinea-dermatophytosis.core.v1 — KOH+ annular advancing scale pivot) vs drug eruption (temporal drug link pivot) vs large-plaque parapsoriasis (an MF precursor / early form — low re-biopsy threshold pivot) vs erythroderma causes (Sézary vs drug vs erythrodermic psoriasis vs erythrodermic AD — peripheral-blood clonality + Sézary-cell count/B-class + CD4:CD8 pivot) vs CD30+ lymphoproliferative disorders — lymphomatoid papulosis / primary-cutaneous ALCL (waxing-waning self-healing papulonodules vs MF pivot) vs allergic contact dermatitis (geometric margin + patch-test pivot). When an adult "eczema/psoriasis" resists adequate therapy or is atypical, re-biopsy for MF — recognition delay is the dominant harm.
   advance: single best diagnosis selected, or repeat steroid-washed biopsy performed because CTCL cannot be confidently excluded in resistant adult disease
8. 8RISK_STRATIFICATION
   ISCL/EORTC clinical staging (schema-blocked as a TS calculator — captured narratively): IA (T1 patch/plaque <10% BSA) → near-normal life expectancy; IB/IIA (T2 / limited nodal) early; IIB (T3 tumour); III (T4 erythroderma); IVA (B2/node) ; IVB (visceral). Independent adverse prognostic factors (Agar n=1,502): advanced skin/clinical stage, increased age, male sex, elevated LDH, large-cell transformation, folliculotropic MF, and blood clone without Sézary cells (B0b); patches-only (T1a/T2a) better than plaque (T1b/T2b); poikilodermatous/hypopigmented MF favourable. Stage + B-class drive skin-directed-vs-systemic choice, imaging, surveillance cadence, and heme-onc routing. Skin tumour burden tracked by mSWAT (modified Severity-Weighted Assessment Tool — schema-blocked, narrative).
   inputs: ldh, skin_biopsy_immunophenotype_tcr_clonality
   actions: panel.inflammation
   advance: ISCL/EORTC stage + blood class assigned; adverse prognostic factors enumerated; mSWAT baseline captured narratively
9. 9TREATMENT
   STAGE-DIRECTED — skin-directed first for early disease (most early-stage patients have a normal life expectancy; goal is disease/symptom control + QoL, NOT cure, and avoiding overtreatment). Early (IA–IIA): topical corticosteroid, topical mechlorethamine (chlormethine nitrogen-mustard gel), topical bexarotene, phototherapy (nbUVB / PUVA — non-pharm), localized radiotherapy (non-pharm). Refractory-early / extensive skin: + interferon (pegylated IFN-α — non-PEG recombinant interferons withdrawn), oral bexarotene (retinoid — hypertriglyceridaemia/central-hypothyroidism pre-treat & monitor), low-dose methotrexate, total-skin electron-beam therapy (non-pharm). Advanced (IIB tumour / III erythroderma / IVA–B) & Sézary: brentuximab vedotin (CD30+, ALCANZA), mogamulizumab (anti-CCR4, MAVORIC — esp. Sézary/blood), HDAC inhibitors romidepsin/vorinostat, extracorporeal photopheresis (Sézary — non-pharm), systemic chemotherapy gemcitabine / liposomal doxorubicin for aggressive disease, allogeneic SCT (non-pharm) for selected advanced disease — ROUTED to heme.cutaneous-lymphoma-systemic.core.v1 by engine_id with shared-care. Aggressive skin/itch care + S. aureus infection surveillance throughout (leading cause of death in advanced). Gate on pregnancy (skin-directed only; defer retinoid/chemo/systemics — teratogenic), immunosuppression (aggressive course), and CD30 status (brentuximab).
   inputs: pregnancy_status, creatinine
   advance: stage-directed skin-directed plan set for early disease; refractory/advanced steps defined; advanced/Sézary/transplant routed to heme-onc with carryover; infection surveillance + comorbidity/pregnancy gating documented
10. 10DISPOSITION
    Almost entirely outpatient/derm-clinic for early disease (skin-directed therapy, phototherapy, surveillance). Admission only for: erythrodermic MF/Sézary with skin failure (thermoregulatory/fluid compromise) or secondary S. aureus sepsis, or aggressive transformed/advanced disease needing inpatient systemic therapy. Multidisciplinary cutaneous-lymphoma / heme-onc referral for advanced (≥IIB), erythrodermic/Sézary, transformed, or systemic-indicated disease; transplant evaluation routed for selected advanced disease.
    inputs: erythroderma_and_skin_failure_signs, secondary_infection_sepsis_signs
    advance: disposition documented; admission only for skin-failure/sepsis/aggressive disease; MDT/heme-onc referral for advanced/Sézary/transformed; systemic/transplant delegated by engine_id
11. 11MONITORING
    Disease: stage-based response by mSWAT skin score + photographs at each visit, blood Sézary-cell tracking (CBC/flow) for B1/B2 disease, LDH trend, and surveillance for large-cell transformation (re-biopsy on any clinical change — a major adverse prognostic shift). Drug safety: oral bexarotene → fasting lipids + TSH/free-T4 at baseline, ~2–4 wk, then periodically (anticipatory fenofibrate + levothyroxine); methotrexate → CBC/LFT periodic + folic acid; interferon → CBC/LFT + depression/flu-like surveillance; routed systemics (brentuximab peripheral neuropathy, mogamulizumab MAVORIC-class skin/infusion/autoimmune events) co-monitored. Infection vigilance throughout — Staphylococcus aureus is the leading cause of death in advanced disease.
    inputs: lipid_panel_and_tsh, creatinine
    actions: panel.cbc, panel.lft, panel.inflammation
    advance: mSWAT + blood-Sézary + LDH response tracked at the stage-appropriate interval; bexarotene lipid/TSH + drug-class safety on schedule; transformation/infection surveillance defined
12. 12FOLLOWUP
    Lifelong dermatology continuity (incurable but often chronic-indolent in early stages): stage-stratified skin exams, mSWAT + blood-Sézary surveillance, intensive skin-barrier + antipruritic + emollient care and S. aureus decolonisation/surveillance (leading cause of death in advanced), patient education on the indolent-but-monitored course and QoL-weighted goals (avoid overtreatment of early disease — most have a normal life expectancy), bexarotene metabolic-monitoring continuity, and re-biopsy + re-stage + heme-onc re-route on transformation/progression/erythroderma/Sézary conversion. Reconcile any systemic-therapy cutaneous toxicity and resume skin-directed control after routed systemic therapy.
    inputs: pruritus_severity_and_qol, large_cell_transformation_signs
    actions: workup.chronic_pruritus
    advance: lifelong stage-stratified surveillance + mSWAT/blood tracking + skin/infection care + QoL-weighted education + transformation re-entry path documented