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pulm.ctd-ild.v1PRODUCTION
pulm.ctd-ild.v1

Connective-tissue-disease-associated ILD (CTD-ILD / IPAF)

pulmonologychronicsubacuteadult
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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)

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CTD-ILD/IPAF confirmed at MDD

Patient inputs (18)

CTD subtype distribution + immunosuppression/transplant candidacy (ACR/CHEST 2023)

CTD epidemiology (female-predominant SSc/SLE/Sjögren); pregnancy status gates teratogenic IS (ACR/CHEST 2023)

CYC + MMF are teratogenic/contraindicated in pregnancy — switch to pregnancy-compatible IS pre-conception (DailyMed MMF/CYC labels)

Resting + ambulatory hypoxemia drives severity, O2, and RP-ILD recognition (ACR/CHEST 2023)

Accelerated/malignant HTN is the scleroderma renal crisis pivot — steroid is a precipitant (SSc subtype caution)

MTX-pneumotoxicity confounder in RA-ILD; amiodarone/ICI/nitrofurantoin drug-ILD differential; IS drug-interaction screen (ACR/CHEST 2023)

Raynaud, sicca, mechanic’s hands, Gottron/heliotrope, sclerodactyly, dysphagia, arthritis — clinical domain for which-CTD + IPAF (Fischer 2015)

ANA/ENA/RF/anti-CCP/Scl-70/RNA-pol-III/Jo-1/PL-7/PL-12/MDA5/Ro52 set which-CTD + IPAF serologic domain (ACR/CHEST 2023; Fischer 2015)

Pre-immunosuppression baseline; cytopenia screen (SLE); CYC/MMF myelosuppression (DailyMed labels)

Renal crisis (SSc) creatinine + nintedanib/MMF/CYC hepatic-renal baseline + serial (DailyMed labels)

NSIP-vs-UIP pattern + extent (>20% extensive; Goh staging in SSc) is the central radiologic axis (ACR/CHEST 2023)

FVC + DLCO baseline + decline rate drive severity and PPF determination (ATS/ERS 2022 PPF)

Screen SSc PH-ILD (TRV, RV function); PH is a strong poor-prognosis modifier (ACR/CHEST 2023)

Antigen/asbestos exposure for HP/asbestosis differential when serology negative (ATS/JRS/ALAT 2020 HP)

Myopathy screen for IIM/anti-synthetase; anti-MDA5 DM is often amyopathic (normal CK) — do not exclude on normal CK

Markedly elevated ferritin is a poor-prognosis marker in anti-MDA5 RP-ILD (Tsuji 2020 PMID 31524333)

SSc PH-ILD screen / cardiac involvement vs ILD-driven dyspnea (ACR/CHEST 2023)

ACR/CHEST 2023 conditionally recommends ambulatory desaturation for MONITORING (not screening) of CTD-ILD

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Severity triggers (8)

8 need judgement
  • informationallife_threateninganti_mda5_rp_ild_emergency
    Anti-MDA5-positive rapidly progressive ILD — acute hypoxemic ILD + amyopathic-DM skin signs (Gottron papules, heliotrope, mechanic’s hands, palmar/periungual papules) + ferritin↑↑ + MDA5+; ~50% untreated mortality, time-critical
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningscleroderma_renal_crisis
    Scleroderma renal crisis — accelerated/malignant HTN + AKI ± microangiopathic hemolytic anemia, especially early diffuse cutaneous SSc / RNA-pol-III+ / recent glucocorticoid >15 mg/day prednisone-equiv
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningdifferential_acute_deterioration_ctd_ild
    Acute deterioration on CTD-ILD background — RP-ILD/acute exacerbation vs mimic? §5.5.2: infection (PJP/CMV/viral/bacterial — high index on immunosuppression) vs PE (CTPA — D-dimer NON-discriminating in established ILD) vs cardiogenic edema (BNP↑↑, echo) vs scleroderma renal crisis (BP/creatinine in SSc) vs drug-induced ILD (recent culprit) vs anti-MDA5 RP-ILD (MDA5+, ferritin↑↑) vs idiopathic acute exacerbation (diagnosis of exclusion)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereacute_exacerbation_ctd_ild
    Acute exacerbation of CTD-ILD — acute worsening dyspnea + new bilateral GGO/consolidation NOT fully explained by infection, PE, or cardiogenic edema, on a CTD-ILD background
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereprogressive_pulmonary_fibrosis_ctd_ild
    Progressive pulmonary fibrosis on a CTD-ILD background — ≥2 of 3 (worsening respiratory symptoms, radiologic progression, physiologic FVC/DLCO decline) within 1 yr, no alternative explanation, despite appropriate management (ATS/ERS 2022 PPF)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_hypoxemia_resting
    Resting SpO2 ≤88% on room air in CTD-ILD
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatessc_ild_extensive_disease
    SSc-ILD with extensive disease on HRCT (>20% fibrosis, or Goh "indeterminate" extent with FVC <70%) — poor-prognosis Goh stage; SSc-ILD is the leading cause of SSc-related death
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatedifferential_ctd_ild_vs_mimics
    ILD with possible autoimmunity — is it CTD-ILD/IPAF or a mimic? §5.5.2 pivots with test characteristics. WHICH-CTD-BY-SEROLOGY: Scl-70/RNA-pol-III/centromere → SSc (NSIP>UIP; RNA-pol-III+ raises renal-crisis + cancer risk); anti-CCP/RF → RA-ILD (often UIP — worse prognosis, antifibrotic-relevant); Jo-1/PL-7/PL-12/EJ/OJ → anti-synthetase syndrome (NSIP/OP, mechanic’s hands); MDA5 → amyopathic DM RP-ILD EMERGENCY (ferritin↑↑); anti-Ro52 amplifies ILD risk/severity across IIM; SSA/SSB → Sjögren (NSIP/LIP, cysts); U1-RNP → MCTD; ANA/dsDNA/Sm → SLE. PATTERN: NSIP predominates in most CTDs; RA-ILD is the UIP-predominant exception. MIMICS: IPF/UIP (older, male, NO autoimmune serology/features, definite-UIP HRCT → pulm.idiopathic_pulmonary_fibrosis.v1); chronic fibrotic HP (antigen Hx + mosaic air-trapping + BAL lymphocytosis >30% + IgG precipitins → pulm.hypersensitivity-pneumonitis.v1); drug-induced ILD (temporal MTX/amiodarone/ICI/nitrofurantoin — STOP drug, often reversible); sarcoidosis (upper-lobe perilymphatic nodules + hilar adenopathy → pulm.sarcoidosis.v1); SLE pneumonitis / systemic lupus flare overlap (→ rheum.sle-flare.core.v1); IPAF (autoimmune features short of CTD criteria — Fischer 2015 clinical/serologic/morphologic domains)
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

CTD-ILD treat-the-CTD immunosuppression + antifibrotic add-on — ACR/CHEST 2023 + ATS/ERS PPF 2022
axis: ctd_ild_immunosuppression
Selected axis "CTD-ILD treat-the-CTD immunosuppression + antifibrotic add-on — ACR/CHEST 2023 + ATS/ERS PPF 2022" by default fallback (first axis)
  • mycophenolate mofetil
    first line
    antimetabolite_immunosuppressant
    500 mg PO BID, titrate to target 1500 mg PO BID as tolerated • PO • BID (max: 3000 mg/day)
    triggers: confirmed_CTD_ILD, SSc_ILD, IIM_ILD, Sjogren_ILD, MCTD_ILD, IPAF_treatment_indicated
    SLS II (Tashkin Lancet Respir Med 2016 PMID 27469583): MMF 24 mo ≈ oral CYC 12 mo on %FVC (no significant between-group difference p=0.24) with markedly less toxicity (leucopenia 4 vs 30; fewer deaths 5/69 vs 11/73) → MMF preferred first-line for most CTD-ILD. Teratogenic — contraindicated in pregnancy (REMS); reliable contraception required
    rxcui 68149
  • cyclophosphamide
    second line
    alkylating_immunosuppressant
    IV 500–750 mg/m2 q4 weekly (or oral ≤2 mg/kg/day per SLS I); pulse preferred for toxicity • IV • q4 weeks (induction course)
    triggers: severe_or_rapidly_progressive_CTD_ILD, MMF_failure_or_intolerance, anti_MDA5_RP_ILD_combination_component
    SLS I (Tashkin NEJM 2006 PMID 16790698): oral CYC vs placebo improved 12-mo FVC%-pred by +2.53% (95% CI 0.28–4.79; P<0.03). Reserve for severe/rapidly progressive disease or as combination component in anti-MDA5 RP-ILD (Tsuji 2020 PMID 31524333). Teratogenic, gonadotoxic, hemorrhagic cystitis (mesna + hydration), myelosuppression — contraindicated in pregnancy
    rxcui 3002
  • rituximab
    second line
    anti_CD20_monoclonal
    1000 mg IV at weeks 0 and 2 (RECITAL regimen) • IV • weeks 0 and 2, repeat per B-cell/clinical course
    triggers: severe_or_progressive_CTD_ILD, CYC_intolerance_or_cumulative_dose_concern, refractory_anti_synthetase_or_RA_ILD
    RECITAL (Maher Lancet Respir Med 2023 PMID 36375479): rituximab NOT superior to IV CYC (24-wk FVC difference −40 mL, 95% CI −153 to 74, p=0.49) but EQUIVALENT efficacy with fewer adverse events (445 vs 646) and lower corticosteroid exposure → viable alternative to IV CYC for severe CTD-ILD requiring IV therapy. Screen HBV; infusion reactions; infection/hypogammaglobulinaemia risk
    rxcui 121191
  • tocilizumab
    add on
    anti_IL6_receptor_monoclonal
    162 mg SC weekly • SC • weekly
    triggers: early_diffuse_cutaneous_SSc_ILD, elevated_acute_phase_reactants_CRP_IL6
    focuSSced (Khanna Lancet Respir Med 2020 PMID 32866440): primary skin (mRSS) endpoint NOT met (p=0.10), but secondary FVC%-predicted favoured tocilizumab (LSM difference 4.2, 95% CI 2.0–6.4, nominal p=0.0002) → preserves lung function in early dcSSc-ILD with elevated acute-phase reactants. GI-perforation risk (caution with diverticulitis/steroids/NSAIDs); infection; LFT/lipid/neutrophil monitoring
    rxcui 612865
  • nintedanib
    add on
    antifibrotic_intracellular_TKI
    150 mg PO BID (100 mg BID if Child-Pugh A / poor tolerance) • PO • BID WITH FOOD (max: 300 mg/day)
    triggers: SSc_ILD, CTD_ILD_meeting_progressive_pulmonary_fibrosis_criteria, continued_decline_despite_immunosuppression
    SENSCIS (Distler NEJM 2019 PMID 31112379): SSc-ILD adjusted annual FVC −52.4 vs −93.3 mL/yr (Δ 41.0 mL/yr; 95% CI 2.9–79.0; P=0.04). INBUILD (Flaherty NEJM 2019 PMID 31566307) PF-ILD −80.8 vs −187.8 mL/yr; autoimmune-ILD subgroup +104.0 mL/yr (Wells 2020 PMID 32145830). ADD-ON to immunosuppression (not a replacement) for SSc-ILD or any CTD-ILD meeting ATS/ERS 2022 PPF criteria. Diarrhoea (loperamide + dose-reduce 150→100 BID); hepatotoxicity; bleeding/ATE risk — caution on full anticoagulation; CYP3A4/P-gp substrate
    rxcui 1592737
  • prednisone
    comorbidity specific
    systemic_corticosteroid
    lowest effective dose; KEEP <15 mg/day prednisone-equiv in SSc (renal-crisis precipitant) • PO • once daily
    triggers: inflammatory_CTD_ILD_non_SSc, IIM_ILD_induction, anti_synthetase_or_organising_pneumonia_pattern
    Background/bridge anti-inflammatory for inflammatory CTD-ILD (IIM, anti-synthetase, NSIP with inflammation, SLE/MCTD/Sjögren). SSc CAUTION: moderate-high dose glucocorticoid (prednisone-equiv >15 mg/day), especially in early diffuse cutaneous SSc / RNA-pol-III+, is a SCLERODERMA RENAL CRISIS precipitant — use lowest effective dose, monitor BP + creatinine closely, and prefer steroid-sparing immunosuppression in SSc
    rxcui 8640
  • methylprednisolone
    rescue
    systemic_corticosteroid
    500–1000 mg IV daily ×3 (pulse) then high-dose oral taper — anti-MDA5 RP-ILD / severe acute IIM-ILD • IV • pulse ×3 then transition to oral with slow taper over months
    triggers: anti_MDA5_RP_ILD, severe_acute_IIM_ILD, acute_exacerbation_CTD_ILD_non_SSc
    High-dose pulse glucocorticoid is a component of the anti-MDA5 RP-ILD combination regimen (Tsuji 2020 PMID 31524333 — high-dose GC + tacrolimus + IV CYC). Taper over months guided by ferritin/HRCT/PFT response (encoded here in rationale/monitoring — `taper_plan` is not a _types.ts field). AVOID high-dose pulse as first move in SSc-dominant disease (renal-crisis risk)
    rxcui 6902
  • tacrolimus (anti-MDA5 RP-ILD combination component)
    rescue
    calcineurin_inhibitor_immunosuppressant
    PO titrated to trough 5–10 ng/mL, as part of up-front combination with high-dose GC + IV CYC • PO • BID titrated to trough
    triggers: anti_MDA5_positive_rapidly_progressive_ILD, amyopathic_DM_with_acute_hypoxemia
    Special-pop: anti-MDA5 RP-ILD EMERGENCY branch — Tsuji 2020 (PMID 31524333) up-front combination (high-dose GC + tacrolimus + IV CYC, ± plasmapheresis if worsening) gave 6-mo survival 89% vs 33% for step-up therapy (P<0.0001). TIME-CRITICAL: combination must start early (IV CYC given ~20 days earlier than step-up). Intensive opportunistic-infection surveillance (frequent CMV reactivation reported); PJP prophylaxis
    rxcui 42316
  • mycophenolate mofetil (SSc steroid-sparing — renal-crisis caution)
    comorbidity specific
    antimetabolite_immunosuppressant
    500 mg BID → target 1500 mg BID; minimise concurrent glucocorticoid • PO • BID
    triggers: systemic_sclerosis_ILD, RNA_pol_III_positive, early_diffuse_cutaneous_SSc
    Special-pop: SSc branch — SSc-ILD is the leading cause of SSc-related death; MMF is the preferred steroid-sparing first-line (SLS II PMID 27469583). Because moderate-high glucocorticoid precipitates scleroderma renal crisis (esp. early dcSSc / RNA-pol-III+), build the regimen around steroid-sparing IS ± nintedanib add-on and keep any glucocorticoid <15 mg/day prednisone-equiv with BP/creatinine surveillance
    rxcui 68149
  • RA-ILD methotrexate-pneumotoxicity disambiguation + MTX withdrawal
    comorbidity specific
    medication_reconciliation
    hold/withdraw MTX; distinguish MTX pneumonitis from RA-ILD progression (temporal relation, BAL, HRCT pattern); RA-ILD is often UIP • n/a • at presentation and on any respiratory change in RA on MTX
    triggers: rheumatoid_arthritis_on_methotrexate_with_new_ILD, acute_subacute_pneumonitis_on_MTX
    Special-pop: RA-ILD branch — methotrexate pneumotoxicity is a key confounder; new respiratory disease in RA-on-MTX requires disambiguating drug-induced pneumonitis (often reversible on withdrawal) from progressive RA-ILD. RA-ILD is the notable UIP-predominant CTD-ILD (worse prognosis) → if UIP/PPF, antifibrotic add-on (nintedanib INBUILD PMID 31566307) is relevant alongside RA-directed therapy
  • pregnancy — switch off teratogenic immunosuppression
    contraindication substitute
    medication_safety
    discontinue MMF and cyclophosphamide pre-conception; switch to pregnancy-compatible IS (e.g., azathioprine or a calcineurin inhibitor) with rheumatology co-management • n/a • pre-conception planning and throughout pregnancy
    triggers: pregnancy, planning_conception, reproductive_potential_without_reliable_contraception
    Special-pop: pregnancy branch — mycophenolate mofetil and cyclophosphamide are TERATOGENIC and CONTRAINDICATED in pregnancy (MMF REMS; CYC fetotoxic/gonadotoxic). Plan ahead: stop teratogenic agents before conception, bridge with a pregnancy-compatible immunosuppressant, and co-manage CTD activity with rheumatology/MFM
  • nintedanib 100 mg BID (hepatic impairment — Child-Pugh A; AVOID Child-Pugh B/C)
    contraindication substitute
    antifibrotic_intracellular_TKI
    100 mg PO BID (reduced) • PO • BID with food
    triggers: Child_Pugh_A_hepatic_impairment, antifibrotic_indicated_with_hepatic_impairment
    Special-pop: hepatic/renal-dosing branch — nintedanib Child-Pugh A reduce to 100 mg BID; NOT recommended Child-Pugh B/C (DailyMed label). MMF/CYC require renal-function-aware dosing and intensified CBC/LFT surveillance; choose the best-tolerated combination with tighter monitoring when hepatic/renal impairment coexists
    rxcui 1592737

outpatient playbook — drug actions (3)

  1. 1. mycophenolate mofetil
    rxcui 68149
    500 mg BID → target 1500 mg BID • PO • BID
    trigger: Confirmed CTD-ILD/IPAF requiring treatment
    First-line — SLS II (PMID 27469583) MMF ≈ oral CYC efficacy, less toxic; teratogenic — confirm contraception/pregnancy status
  2. 2. nintedanib (antifibrotic add-on)
    rxcui 1592737
    150 mg BID (100 mg BID Child-Pugh A) • PO • BID with food
    trigger: SSc-ILD or CTD-ILD meeting ATS/ERS 2022 PPF criteria
    SENSCIS PMID 31112379 / INBUILD PMID 31566307 — add-on to IS, slows FVC decline; not a replacement for immunosuppression
  3. 3. rituximab OR IV cyclophosphamide (severe/progressive)
    rxcui 121191
    RTX 1000 mg IV wk 0 + wk 2 (RECITAL); or IV CYC 500–750 mg/m2 q4w • IV • per induction course
    trigger: Severe / rapidly progressive disease or MMF failure
    RECITAL PMID 36375479 — RTX equivalent to IV CYC with fewer adverse events; SLS I PMID 16790698 — CYC vs placebo positive

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Known CTD (SSc/RA/IIM/Sjögren/MCTD/SLE) + new dyspnea / cough / PFT decline / HRCT change (ACR/CHEST 2023); HRCT ILD pattern (NSIP > UIP; RA-ILD often UIP) in a patient with autoimmune features (ACR/CHEST 2023); Progressive exertional dyspnea + dry cough with extrapulmonary autoimmune features (ACR/CHEST 2023).

Objective

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

Assessment

**Connective-tissue-disease-associated ILD (CTD-ILD / IPAF)** (pulm.ctd-ild.v1).
Phenotype framing: §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)
Scope: 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)

No severity triggers fired against current inputs.

Plan

Regimen axis: **CTD-ILD treat-the-CTD immunosuppression + antifibrotic add-on — ACR/CHEST 2023 + ATS/ERS PPF 2022**.
1. mycophenolate mofetil 500 mg PO BID, titrate to target 1500 mg PO BID as tolerated PO BID (antimetabolite_immunosuppressant, first line) — SLS II (Tashkin Lancet Respir Med 2016 PMID 27469583): MMF 24 mo ≈ oral CYC 12 mo on %FVC (no significant between-group difference p=0.24) with markedly less toxicity (leucopenia 4 vs 30; fewer deaths 5/69 vs 11/73) → MMF preferred first-line for most CTD-ILD. Teratogenic — contraindicated in pregnancy (REMS); reliable contraception required
2. cyclophosphamide IV 500–750 mg/m2 q4 weekly (or oral ≤2 mg/kg/day per SLS I); pulse preferred for toxicity IV q4 weeks (induction course) (alkylating_immunosuppressant, second line) — SLS I (Tashkin NEJM 2006 PMID 16790698): oral CYC vs placebo improved 12-mo FVC%-pred by +2.53% (95% CI 0.28–4.79; P<0.03). Reserve for severe/rapidly progressive disease or as combination component in anti-MDA5 RP-ILD (Tsuji 2020 PMID 31524333). Teratogenic, gonadotoxic, hemorrhagic cystitis (mesna + hydration), myelosuppression — contraindicated in pregnancy
3. rituximab 1000 mg IV at weeks 0 and 2 (RECITAL regimen) IV weeks 0 and 2, repeat per B-cell/clinical course (anti_CD20_monoclonal, second line) — RECITAL (Maher Lancet Respir Med 2023 PMID 36375479): rituximab NOT superior to IV CYC (24-wk FVC difference −40 mL, 95% CI −153 to 74, p=0.49) but EQUIVALENT efficacy with fewer adverse events (445 vs 646) and lower corticosteroid exposure → viable alternative to IV CYC for severe CTD-ILD requiring IV therapy. Screen HBV; infusion reactions; infection/hypogammaglobulinaemia risk
4. tocilizumab 162 mg SC weekly SC weekly (anti_IL6_receptor_monoclonal, add on) — focuSSced (Khanna Lancet Respir Med 2020 PMID 32866440): primary skin (mRSS) endpoint NOT met (p=0.10), but secondary FVC%-predicted favoured tocilizumab (LSM difference 4.2, 95% CI 2.0–6.4, nominal p=0.0002) → preserves lung function in early dcSSc-ILD with elevated acute-phase reactants. GI-perforation risk (caution with diverticulitis/steroids/NSAIDs); infection; LFT/lipid/neutrophil monitoring
5. nintedanib 150 mg PO BID (100 mg BID if Child-Pugh A / poor tolerance) PO BID WITH FOOD (antifibrotic_intracellular_TKI, add on) — SENSCIS (Distler NEJM 2019 PMID 31112379): SSc-ILD adjusted annual FVC −52.4 vs −93.3 mL/yr (Δ 41.0 mL/yr; 95% CI 2.9–79.0; P=0.04). INBUILD (Flaherty NEJM 2019 PMID 31566307) PF-ILD −80.8 vs −187.8 mL/yr; autoimmune-ILD subgroup +104.0 mL/yr (Wells 2020 PMID 32145830). ADD-ON to immunosuppression (not a replacement) for SSc-ILD or any CTD-ILD meeting ATS/ERS 2022 PPF criteria. Diarrhoea (loperamide + dose-reduce 150→100 BID); hepatotoxicity; bleeding/ATE risk — caution on full anticoagulation; CYP3A4/P-gp substrate
6. prednisone lowest effective dose; KEEP <15 mg/day prednisone-equiv in SSc (renal-crisis precipitant) PO once daily (systemic_corticosteroid, comorbidity specific) — Background/bridge anti-inflammatory for inflammatory CTD-ILD (IIM, anti-synthetase, NSIP with inflammation, SLE/MCTD/Sjögren). SSc CAUTION: moderate-high dose glucocorticoid (prednisone-equiv >15 mg/day), especially in early diffuse cutaneous SSc / RNA-pol-III+, is a SCLERODERMA RENAL CRISIS precipitant — use lowest effective dose, monitor BP + creatinine closely, and prefer steroid-sparing immunosuppression in SSc
7. methylprednisolone 500–1000 mg IV daily ×3 (pulse) then high-dose oral taper — anti-MDA5 RP-ILD / severe acute IIM-ILD IV pulse ×3 then transition to oral with slow taper over months (systemic_corticosteroid, rescue) — High-dose pulse glucocorticoid is a component of the anti-MDA5 RP-ILD combination regimen (Tsuji 2020 PMID 31524333 — high-dose GC + tacrolimus + IV CYC). Taper over months guided by ferritin/HRCT/PFT response (encoded here in rationale/monitoring — `taper_plan` is not a _types.ts field). AVOID high-dose pulse as first move in SSc-dominant disease (renal-crisis risk)
8. tacrolimus (anti-MDA5 RP-ILD combination component) PO titrated to trough 5–10 ng/mL, as part of up-front combination with high-dose GC + IV CYC PO BID titrated to trough (calcineurin_inhibitor_immunosuppressant, rescue) — Special-pop: anti-MDA5 RP-ILD EMERGENCY branch — Tsuji 2020 (PMID 31524333) up-front combination (high-dose GC + tacrolimus + IV CYC, ± plasmapheresis if worsening) gave 6-mo survival 89% vs 33% for step-up therapy (P<0.0001). TIME-CRITICAL: combination must start early (IV CYC given ~20 days earlier than step-up). Intensive opportunistic-infection surveillance (frequent CMV reactivation reported); PJP prophylaxis
9. mycophenolate mofetil (SSc steroid-sparing — renal-crisis caution) 500 mg BID → target 1500 mg BID; minimise concurrent glucocorticoid PO BID (antimetabolite_immunosuppressant, comorbidity specific) — Special-pop: SSc branch — SSc-ILD is the leading cause of SSc-related death; MMF is the preferred steroid-sparing first-line (SLS II PMID 27469583). Because moderate-high glucocorticoid precipitates scleroderma renal crisis (esp. early dcSSc / RNA-pol-III+), build the regimen around steroid-sparing IS ± nintedanib add-on and keep any glucocorticoid <15 mg/day prednisone-equiv with BP/creatinine surveillance
10. RA-ILD methotrexate-pneumotoxicity disambiguation + MTX withdrawal hold/withdraw MTX; distinguish MTX pneumonitis from RA-ILD progression (temporal relation, BAL, HRCT pattern); RA-ILD is often UIP n/a at presentation and on any respiratory change in RA on MTX (medication_reconciliation, comorbidity specific) — Special-pop: RA-ILD branch — methotrexate pneumotoxicity is a key confounder; new respiratory disease in RA-on-MTX requires disambiguating drug-induced pneumonitis (often reversible on withdrawal) from progressive RA-ILD. RA-ILD is the notable UIP-predominant CTD-ILD (worse prognosis) → if UIP/PPF, antifibrotic add-on (nintedanib INBUILD PMID 31566307) is relevant alongside RA-directed therapy
11. pregnancy — switch off teratogenic immunosuppression discontinue MMF and cyclophosphamide pre-conception; switch to pregnancy-compatible IS (e.g., azathioprine or a calcineurin inhibitor) with rheumatology co-management n/a pre-conception planning and throughout pregnancy (medication_safety, contraindication substitute) — Special-pop: pregnancy branch — mycophenolate mofetil and cyclophosphamide are TERATOGENIC and CONTRAINDICATED in pregnancy (MMF REMS; CYC fetotoxic/gonadotoxic). Plan ahead: stop teratogenic agents before conception, bridge with a pregnancy-compatible immunosuppressant, and co-manage CTD activity with rheumatology/MFM
12. nintedanib 100 mg BID (hepatic impairment — Child-Pugh A; AVOID Child-Pugh B/C) 100 mg PO BID (reduced) PO BID with food (antifibrotic_intracellular_TKI, contraindication substitute) — Special-pop: hepatic/renal-dosing branch — nintedanib Child-Pugh A reduce to 100 mg BID; NOT recommended Child-Pugh B/C (DailyMed label). MMF/CYC require renal-function-aware dosing and intensified CBC/LFT surveillance; choose the best-tolerated combination with tighter monitoring when hepatic/renal impairment coexists

Setting playbook (outpatient) — Confirm CTD-ILD/IPAF at rheum+pulm+radiology MDD, classify CTD subtype + ILD pattern, initiate + monitor immunosuppression (MMF first-line) ± antifibrotic add-on, surveil for progression/PPF, integrate transplant + palliative as needed (ACR/CHEST 2023)
13. mycophenolate mofetil 500 mg BID → target 1500 mg BID PO BID — Confirmed CTD-ILD/IPAF requiring treatment (First-line — SLS II (PMID 27469583) MMF ≈ oral CYC efficacy, less toxic; teratogenic — confirm contraception/pregnancy status)
14. nintedanib (antifibrotic add-on) 150 mg BID (100 mg BID Child-Pugh A) PO BID with food — SSc-ILD or CTD-ILD meeting ATS/ERS 2022 PPF criteria (SENSCIS PMID 31112379 / INBUILD PMID 31566307 — add-on to IS, slows FVC decline; not a replacement for immunosuppression)
15. rituximab OR IV cyclophosphamide (severe/progressive) RTX 1000 mg IV wk 0 + wk 2 (RECITAL); or IV CYC 500–750 mg/m2 q4w IV per induction course — Severe / rapidly progressive disease or MMF failure (RECITAL PMID 36375479 — RTX equivalent to IV CYC with fewer adverse events; SLS I PMID 16790698 — CYC vs placebo positive)

Non-pharmacologic actions:
- Rheumatology + pulmonology ILD co-clinic establishment (ACR/CHEST 2023)
- Vaccination (influenza, pneumococcal, COVID, RSV) before/during immunosuppression
- Smoking cessation; GERD-aspiration management in SSc
- Lung transplant referral for progressive disease refractory to IS + antifibrotic (ISHLT principles)
- Pregnancy planning — switch off teratogenic MMF/CYC pre-conception
- Palliative care integration for advanced/refractory disease

AVOID / contraindication checks:
- Mycophenolate mofetil teratogenic contraindicated in pregnancy REMS reliable contraception (DailyMed MMF label)
- Cyclophosphamide teratogenic gonadotoxic hemorrhagic cystitis mesna hydration myelosuppression (DailyMed cyclophosphamide label)
- SSc renal crisis glucocorticoid precipitant keep prednisone equiv lt 15mg day monitor BP creatinine (ACR/CHEST 2023; SSc renal crisis literature)
- Anti MDA5 RP ILD time critical combination IS do not step up (Tsuji Arthritis Rheumatol 2020 PMID 31524333 — 89% vs 33% 6 mo survival)
- Nintedanib hepatotoxicity LFT baseline then monthly x3 then periodic (DailyMed nintedanib label)
- Nintedanib not recommended Child Pugh B C reduce to 100 BID Child Pugh A (DailyMed nintedanib label)
- Nintedanib bleeding and arterial thromboembolic risk caution on full anticoagulation (DailyMed nintedanib label)
- Rituximab screen HBV before therapy infusion reactions hypogammaglobulinaemia (DailyMed rituximab label)
- Tocilizumab GI perforation risk caution diverticulitis steroids NSAIDs infection LFT (DailyMed tocilizumab label)
- PJP prophylaxis and opportunistic infection surveillance on high dose or combination IS (ACR/CHEST 2023; Tsuji 2020 CMV reactivation)
- Antifibrotic is add on not replacement for immunosuppression in CTD ILD (ATS/ERS 2022 PPF; SENSCIS PMID 31112379)
- Immunosuppression is first line in CTD ILD NOT IPF style antifibrotic only (contrast PANTHER IPF harm — CTD ILD differs fundamentally)

Monitoring

Regimen monitoring:
- FVC and DLCO q3-6m progression and PPF reassessment (ACR/CHEST 2023; ATS/ERS 2022 PPF)
- HRCT and ambulatory desaturation for monitoring per ACR CHEST 2023 (PMID 38973729)
- CBC and LFT periodic on MMF CYC nintedanib (DailyMed labels)
- opportunistic infection surveillance PJP prophylaxis on high dose or combination IS (ACR/CHEST 2023)
- CMV monitoring in anti MDA5 RP ILD combination IS (Tsuji 2020 PMID 31524333 — frequent CMV reactivation)
- SSc BP and creatinine for scleroderma renal crisis especially on any glucocorticoid
- ferritin and HRCT trend to guide anti MDA5 RP ILD steroid taper (Tsuji 2020 PMID 31524333)
- GI tolerance and LFT on nintedanib add on (DailyMed nintedanib label)
- pregnancy status and contraception review before and during MMF CYC (DailyMed MMF/CYC labels)
- PH ILD screen TTE in SSc and lung cancer GERD aspiration comorbidity sweep (ACR/CHEST 2023)

Setting (outpatient) monitoring:
- FVC/DLCO q3–6 mo, HRCT + ambulatory desaturation per ACR/CHEST 2023
- CBC/LFT periodic on MMF/CYC/nintedanib (DailyMed)
- SSc BP + creatinine for renal crisis on any glucocorticoid
- PPF re-assessment each visit (ATS/ERS 2022 PMID 35486072)

Follow-up plan: 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)
- Close-out criterion: Co-clinic + PPF loop + transplant + pregnancy + palliative plan booked

Monitoring phase: 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

Disposition

Current setting: outpatient — Confirm CTD-ILD/IPAF at rheum+pulm+radiology MDD, classify CTD subtype + ILD pattern, initiate + monitor immunosuppression (MMF first-line) ± antifibrotic add-on, surveil for progression/PPF, integrate transplant + palliative as needed (ACR/CHEST 2023)

Disposition criteria:
- Continue IS ± antifibrotic + surveillance if stable (ACR/CHEST 2023)
- Expedite transplant clinic if progressive refractory disease

Escalation triggers (move to higher acuity):
- Anti-MDA5 RP-ILD features (acute hypoxemia + amyopathic-DM signs + ferritin↑↑) → ED/inpatient time-critical combination IS (Tsuji 2020 PMID 31524333)
- Scleroderma renal crisis (accelerated HTN + AKI) → ED/inpatient (ACE-inhibitor; hold high-dose steroid)
- Rapid FVC decline / PPF despite IS → expedite antifibrotic add-on + transplant evaluation

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Anti-MDA5-positive rapidly progressive ILD — acute hypoxemic ILD + amyopathic-DM skin signs (Gottron papules, heliotrope, mechanic’s hands, palmar/periungual papules) + ferritin↑↑ + MDA5+; ~50% untreated mortality, time-critical
- [LIFE_THREATENING] Scleroderma renal crisis — accelerated/malignant HTN + AKI ± microangiopathic hemolytic anemia, especially early diffuse cutaneous SSc / RNA-pol-III+ / recent glucocorticoid >15 mg/day prednisone-equiv
- [LIFE_THREATENING] Acute deterioration on CTD-ILD background — RP-ILD/acute exacerbation vs mimic? §5.5.2: infection (PJP/CMV/viral/bacterial — high index on immunosuppression) vs PE (CTPA — D-dimer NON-discriminating in established ILD) vs cardiogenic edema (BNP↑↑, echo) vs scleroderma renal crisis (BP/creatinine in SSc) vs drug-induced ILD (recent culprit) vs anti-MDA5 RP-ILD (MDA5+, ferritin↑↑) vs idiopathic acute exacerbation (diagnosis of exclusion)

Citations

- 2023 ACR/CHEST Guideline for Screening & Monitoring of ILD in people with SARDs; ATS/ERS/JRS/ALAT 2022 IPF update + Progressive Pulmonary Fibrosis Guideline [PMID:38973729](https://pubmed.ncbi.nlm.nih.gov/38973729/)
- Cited evidence (PMID 38973714) [PMID:38973714](https://pubmed.ncbi.nlm.nih.gov/38973714/)
- Cited evidence (PMID 35486072) [PMID:35486072](https://pubmed.ncbi.nlm.nih.gov/35486072/)
- Cited evidence (PMID 16790698) [PMID:16790698](https://pubmed.ncbi.nlm.nih.gov/16790698/)
- Cited evidence (PMID 27469583) [PMID:27469583](https://pubmed.ncbi.nlm.nih.gov/27469583/)

Last reconciled with current guidelines: 2026-05-16.
References
  • 2023 ACR/CHEST Guideline for Screening & Monitoring of ILD in people with SARDs; ATS/ERS/JRS/ALAT 2022 IPF update + Progressive Pulmonary Fibrosis Guideline — PMID:38973729
  • Cited evidence (PMID 38973714) — PMID:38973714
  • Cited evidence (PMID 35486072) — PMID:35486072
  • Cited evidence (PMID 16790698) — PMID:16790698
  • Cited evidence (PMID 27469583) — PMID:27469583