12-phase flow (12)

1. 1FRAME
   Adult chronic/subacute SARD-associated ILD or IPAF — confirm CTD subtype + ILD pattern at rheumatology + pulmonology + thoracic-radiology MDD per ACR/CHEST 2023 + ATS/ERS PPF 2022; scope excludes IPF/UIP without autoimmunity, chronic fibrotic HP, drug-induced ILD, sarcoidosis (encoded as differential-as-data)
   inputs: hrct, autoantibody_panel_ctd
   advance: CTD-ILD/IPAF confirmed at MDD
2. 2ENTRY
   Two converging routes: (a) known CTD (SSc/RA/IIM/Sjögren/MCTD/SLE) + new respiratory symptom / PFT decline / HRCT change; (b) newly discovered ILD + autoimmune features (Raynaud, sicca, mechanic’s hands, Gottron, sclerodactyly, dysphagia, arthritis) → obtain autoantibody panel (ACR/CHEST 2023; Fischer 2015 IPAF)
   inputs: age, sex
   advance: Engine entered
3. 3CONTEXT
   CTD review of systems + autoantibody history, smoking, occupational/environmental antigen exposure (HP/asbestos overlap), FULL medication review (MTX — RA-ILD pneumotoxicity confounder AND drug-ILD; amiodarone/ICI/nitrofurantoin drug-ILD), pregnancy status (CYC/MMF teratogenic — gate teratogenic IS), BP (scleroderma renal-crisis precursor)
   inputs: extrapulmonary_autoimmune_features, current_meds, pregnancy_status, blood_pressure, spo2_room_air, occupational_environmental
   advance: CTD + drug + pregnancy + BP context complete
4. 4RED_FLAGS
   Anti-MDA5 RP-ILD EMERGENCY (Tsuji 2020 PMID 31524333): acute hypoxemic ILD + amyopathic-DM skin signs (Gottron papules, heliotrope, mechanic’s hands, palmar papules) + ferritin↑↑ + MDA5+ → ~50% untreated mortality, time-critical combination immunosuppression. Scleroderma renal crisis: accelerated/malignant HTN + AKI + microangiopathic hemolysis (esp. early dcSSc, RNA-pol-III+, recent glucocorticoid >15 mg/day prednisone-equiv — STEROID IS A PRECIPITANT). Acute exacerbation of CTD-ILD; severe resting hypoxemia (SpO2 ≤88%)
   inputs: spo2_room_air, blood_pressure, ferritin
   actions: ild_acute_exac
   advance: Emergency excluded or RP-ILD/renal-crisis pathway activated
5. 5INITIAL_WORKUP
   HRCT (NSIP-vs-UIP pattern + extent — >20% extensive / Goh limited-vs-extensive in SSc), spirometry + DLCO, autoantibody panel (ANA/ENA/RF/anti-CCP/Scl-70/RNA-pol-III/Jo-1/PL-7/PL-12/MDA5/Ro52), CK/aldolase + ferritin, CBC/BMP/LFT (pre-immunosuppression baseline), ambulatory desaturation, BNP/TTE (PH screen, esp. SSc) per ACR/CHEST 2023
   inputs: hrct, spirometry_dlco, autoantibody_panel_ctd, cbc, bmp_lft
   actions: panel.cbc, panel.lft, panel.renal
   advance: Stage-1 returned
6. 6BRANCHING_WORKUP
   BAL ONLY if infection / alternate dx suspected (esp. before/during immunosuppression — PJP/CMV); surgical lung biopsy STRONGLY recommended against for screening (ACR/CHEST 2023) and rarely needed when CTD + compatible HRCT; nailfold capillaroscopy (SSc); TTE → right heart cath if PH-ILD (SSc). If serology negative + UIP pattern → reconsider IPF / chronic fibrotic HP / drug-ILD (route real sibling engines)
   inputs: tte_for_ph, ck_aldolase
   actions: ild_acute_exac, pulmonary_nodule
   advance: MDD complete (CTD-ILD/IPAF confirmed or routed to sibling engine)
7. 7DIFFERENTIAL
   §5.5.2 differential-as-data — CTD-ILD vs IPF/UIP (older, male, no autoimmunity, definite-UIP HRCT, antifibrotic-only — route pulm.idiopathic_pulmonary_fibrosis.v1) vs chronic fibrotic HP (antigen Hx, mosaic air-trapping, BAL lymphocytosis >30%, IgG precipitins — route pulm.hypersensitivity-pneumonitis.v1) vs drug-induced ILD (temporal MTX/amiodarone/ICI/nitrofurantoin exposure — STOP drug, often reversible) vs sarcoidosis (upper-lobe perilymphatic nodules + hilar adenopathy — route pulm.sarcoidosis.v1) vs IPAF (autoimmune features short of CTD criteria — Fischer 2015 domains). WHICH-CTD-BY-SEROLOGY: Scl-70/RNA-pol-III/centromere → SSc (NSIP>UIP; ILD leading SSc-mortality cause); anti-CCP/RF → RA-ILD (often UIP); Jo-1/PL-7/PL-12/EJ/OJ → anti-synthetase syndrome (NSIP/OP); MDA5 → amyopathic DM RP-ILD emergency; anti-Ro52 amplifies ILD risk/severity across IIM; SSA/SSB → Sjögren (NSIP/LIP); U1-RNP → MCTD; ANA/dsDNA/Sm → SLE. NSIP predominates in most CTDs; RA-ILD is the notable UIP-predominant exception (worse prognosis, antifibrotic-relevant)
   inputs: autoantibody_panel_ctd, hrct, extrapulmonary_autoimmune_features
   advance: CTD subtype + ILD pattern confirmed at MDD or routed to sibling engine
8. 8RISK_STRATIFICATION
   Extent of fibrosis on HRCT (>20% = extensive; Goh staging in SSc: extensive disease + FVC <70% = poor prognosis), FVC/DLCO severity + decline rate, PROGRESSIVE PULMONARY FIBROSIS (ATS/ERS 2022 PPF — ≥2 of 3: worsening symptoms, radiologic progression, physiologic progression within 1 yr, no alternative explanation), anti-MDA5 RP-ILD phenotype (ferritin↑↑, rapid HRCT progression), PH-ILD modifier. SSc-ILD is the leading cause of SSc-related death — drives early treatment
   inputs: spirometry_dlco, hrct, autoantibody_panel_ctd
   actions: calc.mmrc
   advance: Extent + severity + decline-rate + PPF status documented
9. 9TREATMENT
   TREAT THE UNDERLYING CTD + immunosuppression axis — MMF first-line (SLS II PMID 27469583: MMF ≈ oral CYC on FVC, less toxic); CYC (SLS I PMID 16790698) or rituximab (RECITAL PMID 36375479: not superior to IV CYC but equivalent with fewer adverse events) for severe/rapidly progressive; tocilizumab (focuSSced PMID 32866440: FVC%-pred preserved) for early dcSSc-ILD with raised acute-phase reactants. ANTIFIBROTIC ADD-ON — nintedanib for SSc-ILD (SENSCIS PMID 31112379) and for any CTD-ILD meeting PPF criteria (INBUILD PMID 31566307; autoimmune subgroup +104.0 mL/yr PMID 32145830) — add-on, not replacement, for IS. GLUCOCORTICOID background/bridge with SSc RENAL-CRISIS CAUTION (prednisone-equiv >15 mg/day in dcSSc/RNA-pol-III+ is a precipitant). ANTI-MDA5 RP-ILD = combination high-dose GC + tacrolimus + IV CYC ± JAK-inhibitor ± plasmapheresis, time-critical (Tsuji 2020: 89% vs 33% 6-mo survival)
   inputs: autoantibody_panel_ctd, cbc, bmp_lft
   advance: CTD-directed IS + antifibrotic add-on + steroid-caution + RP-ILD pathway documented
10. 10DISPOSITION
    Admit (ICU) for anti-MDA5 RP-ILD, scleroderma renal crisis, or hypoxemic respiratory failure / acute exacerbation; outpatient rheumatology + pulmonology ILD co-clinic otherwise. Transplant referral for progressive disease refractory to IS + antifibrotic (ISHLT principles)
    advance: Disposition documented
11. 11MONITORING
    PFT (FVC/DLCO) q3–6 mo + HRCT + ambulatory desaturation per ACR/CHEST 2023 (PFT/HRCT/ambulatory-desaturation conditionally recommended for monitoring; 6MWD/CXR/bronchoscopy recommended against). Immunosuppression safety: CBC + LFT periodic, infection surveillance, PJP prophylaxis on high-dose/combination IS, CMV monitoring in anti-MDA5 RP-ILD combination IS (Tsuji 2020 — frequent CMV reactivation). SSc: BP + creatinine for renal crisis. Antifibrotic: LFT + GI tolerance (nintedanib). Re-assess PPF criteria each visit
    inputs: spirometry_dlco, bmp_lft, cbc
    advance: Surveillance schedule + PPF re-assessment thresholds documented
12. 12FOLLOWUP
    Rheumatology + pulmonology ILD co-clinic q3–6 mo, PPF re-assessment driving antifibrotic add-on, transplant referral for progressive refractory disease, vaccination, pregnancy planning (switch off teratogenic CYC/MMF pre-conception), comorbidity sweep (PH-ILD, GERD-aspiration in SSc, lung-cancer surveillance), palliative integration for advanced disease (ACR/CHEST 2023)
    advance: Co-clinic + PPF loop + transplant + pregnancy + palliative plan booked