12-phase flow (12)

1. 1FRAME
   Frame as the COMMONEST autoimmune subepidermal blistering disease of the ELDERLY — anti-hemidesmosome (BP180/BP230) autoimmunity, chronic-relapsing, managed on a severity-tiered ladder with TOPICAL clobetasol as the survival-superior mainstay. The non-bullous prodrome (itch ± urticarial/eczematous, no blisters) is the diagnostic trap. Drug-induced BP (gliptin/checkpoint/diuretic) is reconciled here. Infection/sepsis from eroded skin is the leading cause of death and is escalated/routed.
   advance: chronic autoimmune-bullous framing set; non-bullous-prodrome + drug-induced + infection escape routes noted
2. 2ENTRY
   Recognise the elderly patient with tense bullae on erythematous/urticarial base + intense pruritus, OR the non-bullous prodrome (months of itch ± urticarial/eczematous lesions, no blisters), OR a new gliptin/checkpoint-inhibitor/loop-diuretic preceding the eruption; capture itch severity up front (cardinal + earliest symptom).
   inputs: pruritus_severity
   actions: workup.chronic_pruritus
   advance: entry trigger present; itch severity recorded
3. 3CONTEXT
   Build diagnosis context: tense (BP) vs flaccid/Nikolsky+ (pemphigus) blister morphology, the non-bullous-phase features that explain prior misdiagnosis, age/frailty/dementia and neurologic comorbidity (independent BP associations + application-capacity determinants), and a rigorous DRUG RECONCILIATION for DPP-4 inhibitors (esp. vildagliptin), immune-checkpoint inhibitors, and loop diuretics/spironolactone (drug-induced BP — withdrawal is disease-modifying).
   inputs: blister_morphology_tense_vs_flaccid, non_bullous_phase_features, drug_reconciliation_dpp4i_checkpoint_diuretic, age, neurologic_comorbidity
   actions: workup.chronic_pruritus
   advance: BP clinically supported; culprit drug identified/withdrawn if present; frailty + neurologic context established
4. 4RED_FLAGS
   Extensive BP with secondary infection / sepsis (denuded eroded skin → bacteraemia — the LEADING cause of death) or erythroderma → admit + infection/sepsis pathway. Severe/scarring mucosal involvement (esp. ocular) → reassess for mucous-membrane pemphigoid + emergent ophthalmology/ENT. Checkpoint-inhibitor-induced BP in an oncology patient → oncology coordination. Steroid-related decompensation in the frail elderly. Unrecognised non-bullous prodrome = diagnostic-delay flag → biopsy + serology now.
   inputs: secondary_infection_or_sepsis_signs, mucosal_involvement_extent
   actions: panel.cbc, panel.inflammation
   advance: infection/sepsis, erythroderma, severe-mucosal, checkpoint-induced, and diagnostic-delay flags screened and escalated/routed if present
5. 5INITIAL_WORKUP
   The autoimmune-bullous diagnostic set: PERILESIONAL skin biopsy for DIF (linear C3 ± IgG along the basement-membrane zone — GOLD STANDARD) + a separate LESIONAL H&E (subepidermal split with an eosinophil-rich infiltrate); serum anti-BP180-NC16A (± anti-BP230) ELISA (confirms dx + activity baseline); CBC for eosinophilia; pre-immunosuppressant safety labs (LFT, creatinine, latent-TB + HBV/HCV) if escalation likely. Biopsy two sites — DIF perilesional, H&E lesional.
   inputs: perilesional_skin_dif, anti_bp180_nc16a_elisa, cbc_eosinophilia, infection_screen_tb_hbv_hcv
   actions: panel.cbc, panel.lft, panel.renal
   advance: perilesional DIF + lesional H&E sent; anti-BP180/BP230 ELISA drawn; pre-systemic safety labs if escalation likely
6. 6BRANCHING_WORKUP
   Autoimmune-bullous decision tree on DIF + salt-split + serology: linear BMZ DIF + epidermal-roof IIF on salt-split skin + anti-BP180-NC16A → BP; intercellular IgG/C3 DIF + anti-Dsg1/3 → pemphigus (route derm.pemphigus.core.v1); linear BMZ DIF but DERMAL-floor salt-split binding → epidermolysis bullosa acquisita / anti-p200 pemphigoid; granular IgA dermal-papillae DIF + intense grouped itch + celiac → dermatitis herpetiformis; linear IgA BMZ → linear IgA bullous dermatosis; predominant/scarring mucosal disease → mucous-membrane pemphigoid (ophthalmology/ENT). DIF-negative full-thickness necrosis + drug latency → SJS/TEN-spectrum (route derm.sjs-ten.core.v1).
   inputs: mucosal_involvement_extent, iif_salt_split_skin
   actions: workup.chronic_pruritus
   advance: DIF pattern + salt-split localisation + serology assign BP OR an alternative bullous diagnosis is assigned + routed
7. 7DIFFERENTIAL
   Terminal autoimmune/blistering differential with named pivots: BP vs pemphigus vulgaris (intraepidermal, flaccid, mucosal, Nikolsky+, intercellular DIF, anti-Dsg pivot) vs mucous-membrane pemphigoid (predominant/scarring mucosa, ocular/oral pivot) vs epidermolysis bullosa acquisita (trauma-site, dermal-floor salt-split pivot) vs dermatitis herpetiformis (grouped intensely itchy, granular IgA, celiac pivot) vs linear IgA bullous dermatosis (linear IgA pivot) vs bullous drug eruption / SJS-TEN (drug latency, DIF-negative necrosis pivot — route derm.sjs-ten.core.v1) vs bullous arthropod/contact/diabetic bullae (distribution/exposure pivot) vs urticaria (non-bullous-phase mimic — route derm.urticaria.core.v1) vs scabies/eczema (non-bullous mimic — route derm.atopic-dermatitis.core.v1). Drug-induced BP is a within-BP modifier, not an alternative.
   advance: single best bullous diagnosis selected; drug-induced status flagged; mimics routed
8. 8RISK_STRATIFICATION
   Severity = blister count + BSA + mucosal + infection + frailty (BLISTER strata: 3–9 mild, 10–30 moderate, >30 severe; BPDAI used clinically — schema-blocked, captured narratively). Localised/moderate → high-potency topical clobetasol ± doxycycline; extensive/refractory → systemic prednisone + steroid-sparing immunosuppressant; refractory → rituximab/omalizumab/dupilumab/IVIG. Frailty/dementia + extensive disease still favours topical-clobetasol-first (survival benefit) where application is feasible.
   inputs: body_surface_area_and_blister_count, pruritus_severity
   advance: mild/moderate/extensive/refractory tier + escalation decision assigned
9. 9TREATMENT
   Severity-tiered EADV 2022 ladder. WITHDRAW any culprit drug (gliptin/checkpoint/loop-diuretic) first — often improves disease. Localised/moderate: high-potency TOPICAL clobetasol propionate whole-body (Joly NEJM 2002 — survival-superior + fewer severe complications vs oral steroids; FIRST LINE) ± doxycycline (BLISTER — non-inferior short-term control, safer long-term; preferred when oral steroids contraindicated). Extensive/refractory: oral prednisone 0.5 mg/kg/day with taper + a steroid-sparing immunosuppressant (azathioprine [check TPMT], MMF, methotrexate). Refractory: rituximab / omalizumab / dupilumab / IVIG. AVOID prolonged high-dose systemic steroids in the frail elderly (mortality — prefer topical clobetasol / doxycycline). Frailty/pregnancy/TPMT/renal-hepatic gate agent choice; gestational pemphigoid is a distinct entity (note).
   inputs: frailty_dementia_caregiver_capacity, pregnancy_status, tpmt_activity, creatinine
   advance: culprit withdrawn if present; severity-appropriate ladder step started; agent gated on frailty/pregnancy/TPMT/renal-hepatic
10. 10DISPOSITION
    Mostly outpatient/derm-clinic. Admission for: extensive BP with secondary infection/sepsis or erythroderma (thermoregulatory/fluid/septic risk), severe disease in a frail elderly patient unable to apply whole-body topical therapy at home, or steroid-related decompensation. Checkpoint-inhibitor-induced BP → coordinate with oncology re: immunotherapy hold. Severe/scarring mucosal disease → MMP pathway + ophthalmology/ENT. Systemic-therapy initiation/monitoring via dermatology; route complications OUT by engine.
    inputs: secondary_infection_or_sepsis_signs, frailty_dementia_caregiver_capacity
    advance: disposition documented; admission only for infection/erythroderma/application-incapacity/decompensation; derm follow-up arranged
11. 11MONITORING
    Disease: itch + new-blister count + BSA + anti-BP180-NC16A titre at follow-up — the ELISA titre tracks disease activity and rising titre predicts relapse (Schmidt 2000). Drug safety: systemic steroid → glucose/BP/bone/infection; azathioprine/MMF/methotrexate → CBC + LFT (and TPMT-guided azathioprine dosing); doxycycline → photosensitivity/GI; rituximab → infusion reactions, hypogammaglobulinaemia, infection (PML — rare). Infection vigilance throughout (leading cause of death). Taper systemic therapy to the lowest effective dose/topical maintenance.
    inputs: anti_bp180_nc16a_elisa, glucose_hba1c
    actions: panel.cbc, panel.lft
    advance: activity reassessed (itch/blisters/anti-BP180 titre); drug-class safety labs on schedule; infection surveillance ongoing
12. 12FOLLOWUP
    Chronic relapsing-remitting maintenance: taper to lowest effective therapy (ideally topical/intermittent), relapse-recognition education (itch/new blisters), anti-BP180 titre trend for relapse prediction, periodic steroid/immunosuppressant safety surveillance, infection precautions, and — for drug-induced BP — a permanent culprit-avoidance flag (and an alternative-antidiabetic plan if gliptin-induced). Dermatology continuity for any systemic agent; reassess the diagnosis (repeat biopsy/serology) if the course is atypical or treatment-refractory.
    inputs: drug_reconciliation_dpp4i_checkpoint_diuretic, pruritus_severity
    actions: workup.chronic_pruritus
    advance: taper plan + relapse education + titre surveillance + culprit-avoidance flag + safety monitoring documented