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pulm.sarcoidosis.v1

Sarcoidosis (pulmonary + extrapulmonary)

pulmonologychronicsubacuteacuteadultoutpatientacuteinpatienttransition
Start encounter →Print handoutPRODUCTION

Sarcoidosis = chronic multisystem regimen-builder dossier. Reasoning: recognition (bilateral hilar adenopathy ± multisystem) → non-caseating granuloma + EXCLUSION (TB/fungal/lymphoma/CBD/HP/IgG4-RD) → organ-extent staging (Scadding 0–IV + cardiac/neuro/ocular/Ca) → TREAT-vs-OBSERVE → first-line steroid → steroid-sparing (MTX/AZA) → anti-TNF (infliximab, screen latent TB FIRST) → organ-specific escalation (cardiac device, neuro) → fibrosis/SAPH progression → monitoring/taper → follow-up. ATS 2020 (PMID 32293205) + ERS 2021 (PMID 34140301) + HRS 2014 (PMID 24819193). §5.5.1 effect sizes wired with PubMed-verified PMIDs (≥10): Scadding-stage spontaneous remission gradient I ~55–90% / II ~40–70% / III ~10–20% / IV ~0% + Löfgren >85% by 2 yr (RISK_STRATIFICATION phase + lofgren_syndrome trigger); steroid-induced remission relapse 74% vs 8% spontaneous (Gottlieb Chest 1997 PMID 9118698); oral steroid CXR improvement RR 1.46 [1.01–2.09] with limited lung-function gain (Cochrane Paramothayan 2005 PMID 15846612); methotrexate steroid-sparing RCT — less prednisone in months 7–12, effect at ~6 mo (Baughman WASOG 2000 PMID 10746262; Cochrane PMID 16856012); infliximab chronic pulmonary RCT FVC +2.5% vs 0% placebo p=0.038 (Baughman AJRCCM 2006 PMID 16840744); CNS sarcoid infliximab MRI favorable 82.1% + clinical improvement 77.3% + recurrence 56% on discontinuation (Gelfand Neurology 2017 PMID 29030454); cutaneous infliximab subset RCT (PMID 26847095); cardiac sarcoid 1/5/10-yr Tx-free survival 97/90/83% (53% if HF at presentation), LVEF unchanged over 12 mo steroid (Kandolin Circulation 2015 PMID 25527698); CHB + sudden death even with stable function (Yazaki PMID 8046845); ACCESS organ involvement by sex/race/age (PMID 11734441); INBUILD nintedanib slows FVC decline in progressive fibrosing ILD incl. fibrotic sarcoid (Flaherty NEJM 2019 PMID 31566307). PMID-AUDIT (folded from .depth.md): prior dossier had 4 PMIDs; PubMed get_article_metadata 2026-05-16 found 2 were WRONG-ARTICLE filler — 32366298 ("ATS 2020 sarcoid treatment") is actually "Indole derivatives antimicrobial" (BMC Pharmacol Toxicol), and 32521133 ("NEUROSARC infliximab") is actually "Thrombectomy for Stroke in Brazil" (NEJM). Both CULLED. 24819193 (HRS) and 31566307 (INBUILD) verified-correct and retained. The prior .depth.md NEEDS_SOURCE_REVIEW PMIDs (ACCESS 11260009, WASOG-2023 37879093) were NOT used — replaced with verified anchors (ACCESS = 11734441; ERS-2021-treatment = 34140301). Differential/Bayesian as data (§5.5.2): non-caseating granuloma is NECESSARY-NOT-SUFFICIENT — exclusion is the diagnostic act (DIFFERENTIAL phase). Pivots: vs TB (caseating + AFB/NAAT — biopsy/microbiology), vs lymphoma (asymmetric/bulky/B-sx → EXCISIONAL node + flow, sarcoid-lymphoma syndrome), vs chronic beryllium disease (BeLPT positive, identical histology — occupational pivot, documented in .depth.md as schema-constrained sibling since no berylliosis engine_id exists), vs fungal (serology/culture), vs HP (exposure + lymphocytic BAL), vs IgG4-RD (storiform fibrosis + IgG4). Cardiac-sarcoid diagnostic LR encoded in trigger rationale (late-gad-CMR/FDG-PET high LR+ per HRS 2014). 4 sibling_differentiation rows + cross-dossier engine_ids via workups[].branches_to + sibling_differentiation: pulm.tuberculosis.v1, pulm.idiopathic_pulmonary_fibrosis.v1, pulm.pe.core.v1 (SAPH vs PE), heme.acute-leukemia.core.v1 + heme.multiple-myeloma.chronic.v1 (lymphoproliferative exclusion via lymphadenopathy_biopsy branch). Regimen (chronic, matches pulm.copd.core.v1 depth): treat-vs-OBSERVE gate as Step 0/1 (most Scadding I/II remit; observation is an active recommendation) THEN organ-driven stepwise ladder prednisone → MTX/AZA → infliximab + HCQ adjunct + nintedanib for progressive fibrosis. ≥5 special-population branches: (1) cardiac sarcoid → ICD/PPM device + immunosuppression (device NOT replaced by steroid); (2) hypercalcemia → IV saline + steroid + AVOID vit-D/Ca/sun (bisphosphonate ineffective alone); (3) pregnancy → off MTX/MMF preconception, switch AZA/HCQ/low-dose prednisone; (4) pre-anti-TNF latent-TB → mandatory IGRA + treat LTBI ≥4 wk first (FDA boxed warning); (5) hepatic/renal → MTX dose-reduce/avoid eGFR<30, AZA TPMT/NUDT15 + no allopurinol. SCHEMA-GAP NOTES (folded from .depth.md): (1) _types.ts RegimenDrug/RegimenStep have NO taper_plan field — the prior depth brief invented one; corticosteroid tapers encoded in regimen rationale + axis monitoring + §5.5.1 narrative + contraindication_rules (confirmed against _types.ts: RegimenDrug fields are rxcui/non_pharm/generic_name/drug_class/role/starting_dose/route/frequency/max_dose/triggers/rationale only); (2) no first-class field for Scadding stage / Bayesian LR — encoded in phase purpose/advance_when, severity_triggers, calculator guideline_basis, regimen rationale, sibling_differentiation, .depth.md tables; (3) no phenotype/variant field for Löfgren/Heerfordt — encoded as severity_triggers; (4) no occupational/BeLPT field and no berylliosis engine_id — CBD differentiation documented narratively in DIFFERENTIAL phase + .depth.md schema-gap log; (5) RequiredCalculator.drives enum has no "diagnostic_gate" — calc.corrected_ca reuses monitoring_threshold. RxCUI sanity-check vs RxNav REST 2026-05-16: prednisone 8640 OK, methylprednisolone 6902 OK, methotrexate 6851 OK, azathioprine 1256 OK, hydroxychloroquine 5521 OK, infliximab 191831 OK, adalimumab 327361 OK. FIXES: mycophenolate mofetil was 6932 (=miconazole, WRONG) → corrected to 68149 (RxNav-confirmed "mycophenolate mofetil"); the prior .depth.md proposed CUIs were ALL wrong (6373=levonorgestrel not azathioprine; 6386=NOT FOUND not MMF; 253182=regular insulin not infliximab; 337525=erlotinib not adalimumab) — NOT used. nintedanib 1592737 RxNav-confirmed ingredient (initial 6601 was NOT FOUND in RxNav → corrected) — NEEDS_RXNAV_VALIDATION for SCD/SBD form (no hand-authored CUIs trusted; run scripts/research/rxnav-validate.ts before dosing automation). Open / PRODUCTION caveats: manifest + problem-package + engine-specific test file not yet authored; Scadding-staging + cardiac-sarcoid risk calculators absent from clinical-tools-registry (no new workup ids introduced — reused autoimmune_vasculitis / lymphadenopathy_biopsy / hypercalcemia + calc.mmrc / calc.corrected_ca / calc.ckd_epi_2021, all registry-resolving); BeLPT panel + berylliosis engine absent. Do NOT change engine_id/manifest/atoms/design_brief/package pointers.

Entry points (7)

  • imaging
    Bilateral hilar adenopathy ± pulmonary infiltrates on chest imaging (ATS 2020 dx CPG PMID 32293205)
    bilateral_hilar_adenopathy
  • symptom
    Erythema nodosum, lupus pernio, or other cutaneous sarcoid (ATS 2020)
    erythema_nodosum_or_lupus_pernio
  • symptom
    Acute Löfgren syndrome: BHL + erythema nodosum + ankle arthritis ± fever (good-prognosis variant, spontaneous remission >85% at 2 yr)
    lofgren_acute_triad
  • symptom
    Uveitis, optic neuritis, or sarcoid eye disease; Heerfordt (uveoparotid fever) (ATS 2020)
    uveitis_or_optic_neuritis
  • lab_abnormality
    Hypercalcemia + suppressed PTH + elevated 1,25-OH vitamin D (granuloma 1α-hydroxylase) (ATS 2020)
    hypercalcemia_or_high_ace
  • symptom
    Unexplained high-grade AV block / sustained VT in age <60 (cardiac sarcoid — HRS 2014 PMID 24819193)
    cardiac_block_or_VT
  • symptom
    Bilateral facial palsy / aseptic meningitis / cord lesion (neurosarcoid) (ERS 2021 PMID 34140301)
    cn_palsy_or_aseptic_meningitis

Required inputs (18)

  • agerequired
    demographic • used at CONTEXT
    Peak 20–40 yr; second peak women >50; cardiac more in <60 (ATS 2020)
  • race_ethnicity
    demographic • used at CONTEXT
    African-American + Scandinavian higher prevalence + severity; AA more relapse/multiorgan (ACCESS PMID 11734441)
  • cmp_calcium_creatininerequired
    lab • used at INITIAL_WORKUP
    Hypercalcemia (1,25-OH-D driven), renal involvement; ATS 2020 strong rec for baseline serum calcium
  • lftrequired
    lab • used at INITIAL_WORKUP
    Hepatic granulomas; baseline before MTX / AZA / TNF-α (ATS 2020)
  • cbcrequired
    lab • used at INITIAL_WORKUP
    Lymphopenia at baseline; cytopenias on MTX / AZA / TNF-α (ATS 2020)
  • ace
    lab • used at INITIAL_WORKUP
    Serum ACE — supportive only, NOT diagnostic; sens ~57% spec ~90%, not for monitoring (ATS 2020)
  • vit_d_25_OH_and_1_25_OH
    lab • used at INITIAL_WORKUP
    1,25-OH elevated with suppressed PTH in sarcoid hypercalcemia (granuloma 1α-hydroxylase) (ATS 2020)
  • tb_quantiferon_or_tstrequired
    lab • used at INITIAL_WORKUP
    MANDATORY before TNF-α (FDA boxed warning — TNF-α reactivates latent TB RR 4–12×); also rules out TB mimicking sarcoid (ATS 2020; CDC/ACR)
  • tpmt_genotype_or_activity
    lab • used at TREATMENT
    TPMT (and NUDT15) before azathioprine — deficiency → severe myelosuppression (ERS 2021)
  • urinalysis
    lab • used at INITIAL_WORKUP
    Hypercalciuria (more common than hypercalcemia); nephrocalcinosis; renal sarcoid (ATS 2020)
  • cxr_scadding_stagerequired
    imaging • used at INITIAL_WORKUP
    Scadding 0–IV staging — stage maps to spontaneous-remission probability and treat-vs-observe (ATS 2020)
  • hrctrequired
    imaging • used at INITIAL_WORKUP
    Perilymphatic micronodules, upper-lobe predominance, fibrosis / honeycombing assessment (ATS 2020)
  • pft_dlcorequired
    imaging • used at INITIAL_WORKUP
    FVC + DLCO — functional severity drives treat-vs-observe and monitors response (ERS 2021)
  • ecgrequired
    imaging • used at INITIAL_WORKUP
    AV block, fascicular block, low voltage, VT — screening for cardiac sarcoid in ALL patients (HRS 2014 PMID 24819193)
  • cardiac_mri_or_fdg_pet
    imaging • used at BRANCHING_WORKUP
    Late-gadolinium CMR / FDG-PET when ECG/echo/symptoms suggest cardiac sarcoid — drives ICD + immunosuppression (HRS 2014)
  • tissue_biopsy_non_caseatingrequired
    imaging • used at INITIAL_WORKUP
    Non-caseating granuloma from least-invasive accessible site (skin / peripheral node / EBUS-TBNA / liver / endomyocardial) — required for diagnosis (ATS 2020)
  • occupational_exposurerequired
    history • used at CONTEXT
    Beryllium exposure (aerospace/nuclear/ceramic/dental) — chronic beryllium disease is histologically identical; ask in EVERY apparent sarcoid (ATS 2020)
  • current_medsrequired
    medication • used at CONTEXT
    Drug-induced sarcoid-like reaction (immune-checkpoint inhibitors, interferon, TNF-α, HAART-IRIS); immunosuppressant interactions (ATS 2020)

12-phase flow (12)

  1. 1FRAME
    Confirm sarcoidosis = compatible clinico-radiological picture + non-caseating granuloma on tissue + EXCLUSION of alternatives. Diagnosis is "never fully secure" (ATS 2020 PMID 32293205); pretest favored by bilateral hilar adenopathy + young adult + multisystem (BHL+EN+arthritis = Löfgren, LR for sarcoid very high, biopsy often unnecessary)
    inputs: tissue_biopsy_non_caseating, tb_quantiferon_or_tst
    advance: Granuloma confirmed (or classic Löfgren) AND TB/fungal/lymphoma/CBD excluded
  2. 2ENTRY
    Hilar adenopathy / cutaneous / ocular / cardiac / neuro / hypercalcemia / Löfgren / Heerfordt presentations (ATS 2020)
    inputs: age
    advance: Engine entered
  3. 3CONTEXT
    Demographics (AA + Scandinavian higher severity), occupational beryllium history, drug-induced (checkpoint-inhibitor) sarcoid-like reaction, comorbidities, immune state (ATS 2020; ACCESS PMID 11734441)
    inputs: race_ethnicity, occupational_exposure, current_meds
    advance: Context complete
  4. 4RED_FLAGS
    Cardiac sarcoid (high-grade AV block / sustained VT / HF — leading cause of sarcoid death), neurosarcoid (cord/hydrocephalus), vision-threatening uveitis, hypercalcemic crisis + AKI, severe respiratory failure / SAPH (HRS 2014; ERS 2021)
    inputs: ecg
    advance: Stabilised or escalated
  5. 5INITIAL_WORKUP
    CXR (Scadding) + HRCT, FVC+DLCO, CBC, CMP + calcium + creatinine, LFT, ACE (supportive only), 25-OH + 1,25-OH vit D, urinalysis, TB IGRA, ECG (cardiac screen ALL patients), least-invasive biopsy (ATS 2020 PMID 32293205)
    inputs: cxr_scadding_stage, hrct, pft_dlco, cmp_calcium_creatinine, lft, cbc, tb_quantiferon_or_tst, ecg, tissue_biopsy_non_caseating
    actions: panel.cbc, panel.lft, panel.renal, workup.lymphadenopathy_biopsy
    advance: Stage-1 returned + granuloma source identified
  6. 6BRANCHING_WORKUP
    EBUS-TBNA for mediastinal nodes (highest yield, lowest risk); late-gadolinium CMR / FDG-PET if ECG/echo/symptoms suggest cardiac sarcoid; MRI brain + LP (CSF: lymphocytic pleocytosis, ↑protein, ↑ACE/CD4:CD8) for neuro; slit-lamp ophtho for ocular; corrected Ca + 1,25-OH-D for hypercalcemia branch (HRS 2014; ERS 2021)
    inputs: cardiac_mri_or_fdg_pet
    actions: workup.hypercalcemia, calc.corrected_ca
    advance: Organ involvement map complete (Scadding + cardiac/neuro/ocular/Ca)
  7. 7DIFFERENTIAL
    Bayesian: sarcoid vs TB (caseating granuloma + AFB/NAAT — biopsy/culture is the pivot; route pulm.tuberculosis.v1) vs lymphoma (asymmetric bulky nodes, B-sx — EXCISIONAL node biopsy + flow, NOT FNA) vs chronic beryllium disease (BeLPT positive; identical histology — occupational pivot) vs fungal (histo/coccidio/blasto serology+culture) vs hypersensitivity pneumonitis (exposure + lymphocytic BAL, poorly-formed granuloma) vs IgG4-RD (storiform fibrosis, IgG4+ plasma cells, serum IgG4) vs metastatic malignancy (route onc as applicable). Non-caseating granuloma is necessary NOT sufficient — exclusion is the diagnostic act (ATS 2020 PMID 32293205)
    inputs: tissue_biopsy_non_caseating, occupational_exposure
    advance: Granulomatous mimics excluded or routed
  8. 8RISK_STRATIFICATION
    Scadding stage → spontaneous-remission probability (I ~55–90%, II ~40–70%, III ~10–20%, IV ~0% — irreversible fibrosis); organ-specific severity (cardiac LVEF + scar burden per HRS 2014; neuro CNS-parenchymal worst); Löfgren = good prognosis (>85% remit ≤2 yr). Steroid-induced remission has 74% relapse vs 8% if spontaneous (Gottlieb Chest 1997 PMID 9118698) — favors observation when tolerable
    inputs: cxr_scadding_stage, pft_dlco
    actions: calc.mmrc
    advance: Stage + organ severity + treat-vs-observe tier documented
  9. 9TREATMENT
    TREAT-vs-OBSERVE first: observe asymptomatic Scadding I/II + isolated non-organ-threatening disease (high spontaneous remission). TREAT if symptomatic/progressive lung dysfunction OR any cardiac / neuro / ocular / renal / hypercalcemia / disfiguring skin. Step 1 prednisone 20–40 mg/d (cardiac/neuro 0.5–1 mg/kg ± IV methylpred pulse) → Step 2 MTX (1st-line steroid-sparing, +folate) or AZA (check TPMT) → Step 3 infliximab (refractory / CNS / cardiac — SCREEN LATENT TB FIRST). HCQ for cutaneous + hypercalcemia. Antifibrotic (nintedanib) if progressive fibrotic phenotype (ERS 2021 PMID 34140301; HRS 2014)
    inputs: lft, cbc, tb_quantiferon_or_tst, tpmt_genotype_or_activity
    actions: calc.ckd_epi_2021
    advance: Treat-vs-observe decision + organ-specific regimen documented
  10. 10DISPOSITION
    Admit cardiac arrhythmia / new high-grade block (telemetry + EP), acute neurosarcoid, hypercalcemic crisis + AKI, severe respiratory failure / SAPH RHC; outpatient otherwise (HRS 2014; ERS 2021)
    advance: Disposition documented
  11. 11MONITORING
    FVC+DLCO q3–6 mo (pulmonary), CXR, corrected Ca + 24-h urine Ca, organ-specific imaging; on-steroid BP/glucose/DEXA; on-MTX/AZA CBC+LFT q4–8 wk; on-HCQ annual retinal exam; on-TNF-α annual TB screen; cardiac sarcoid echo/CMR q6–12 mo; neuro MRI q6 mo; supervise prednisone taper (5–10 mg q4–8 wk; total 12–18 mo) to avoid relapse + adrenal insufficiency (ERS 2021)
    inputs: lft, cbc
    actions: panel.cbc, panel.lft
    advance: Monitoring + taper schedule documented
  12. 12FOLLOWUP
    Pulm + organ-relevant specialty q3–6 mo; non-live vaccinations before/on immunosuppression; PJP prophylaxis if combined IS; bone protection on chronic steroid; fatigue + small-fiber neuropathy + QoL screen (ERS 2021)
    advance: Follow-up + prevention bundle booked