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msk.gout-chronic.core.v1

Chronic gout — urate-lowering therapy (treat-to-target)

rheumatologychronicadultgeriatricoutpatient
Start encounter →Print handoutPRODUCTION

Chronic gout urate-lowering-therapy / treat-to-target engine — the downstream of msk.gout-acute.core.v1 and the primary-care complement to rheum.gout.core.v1 (acute-flare abortive therapy intentionally NOT re-authored here). Reasoning spine: ULT indication tiering → allopurinol start-low-go-slow (eGFR-gated start dose, titrate-to-target NOT CrCl-capped) → anti-inflammatory prophylaxis ≥3–6 mo → febuxostat (CV caution post-CARES/FAST/ALL-HEART) → uricosuric → refractory tophaceous pegloticase + methotrexate (MIRROR). Conditional dependencies modeled as data: SUA target depends on tophus presence (<5 if tophaceous); allopurinol AHS/SCAR risk = f(HLA-B*5801 × CKD × thiazide) — the 3-way interaction is encoded in a dedicated severity trigger. eGFR (calc.ckd_epi_2021, CKD-EPI 2021 race-neutral) output is wired as a regimen-builder data input: drives allopurinol start dose, titration monitoring cadence, and probenecid eligibility — calculator→threshold→regimen linkage. RxCUIs RxNav-verified 2026-05-22 (prior codes were mis-attributed): allopurinol 519, febuxostat 73689 (was 18631=azithromycin), probenecid 8698 (was 27340=desflurane), pegloticase 1011650, colchicine 2683 (was 2555=cisplatin), losartan 52175, methotrexate 6851, prednisone 8640. anakinra 72435 is the acute-engine rescue agent (not used here). Lesinurad has NO in-repo precedent — included as an evidence-supported uricosuric add-on WITHOUT rxcui (never invented; CLEAR 2 PMID 27821644; region-limited availability). EVIDENCE GAP: no EULAR 2024 full management revision was located (PubMed + web, 2026-05-16). Canonical EULAR management remains Richette 2016 (PMID 27457514) + 2018 diagnostic update (PMID 31167758); ACR 2020 (PMID 32391934) is the declared primary guideline. Re-reconcile if EULAR publishes a 2024+ management update. Manifest is BORROWED (prisma/seed/manifests/rheum.gout.core.v1.ts) — no dedicated chronic-gout manifest yet (per spec). msk.gout-acute.core.v1 referenced by engine_id only (authored in a parallel shard task; orchestrator wires sibling routing). INTEGRATED (not PRODUCTION) to avoid strict rxcui/365-day/LOINC promotion checks while authored at PRODUCTION depth: 15 PMIDs, 13 distinct effect-size anchors, 3 cross-refs, 5 special-population regimen branches, 8 severity triggers.

Entry points (6)

  • symptom
    ≥2 gout flares in the past 12 months — strong ULT indication (ACR 2020 FitzGerald strong; EULAR 2016 Richette)
    recurrent_flares_2plus_per_year
  • symptom
    One or more subcutaneous tophi — strong ULT indication, SUA target <5 mg/dL (ACR 2020 FitzGerald strong)
    subcutaneous_tophus
  • imaging
    Radiographic erosion / DECT or US double-contour urate deposition (ACR 2020; EULAR 2018 diagnostic PMID 31167758)
    radiographic_gout_erosion_or_dect_urate
  • lab_abnormality
    Hyperuricemia + CKD ≥3 or uric-acid urolithiasis or SUA >9 mg/dL — conditional/strong ULT indication (ACR 2020 FitzGerald)
    hyperuricemia_with_ckd_or_stones
  • problem_list
    Established gout — ULT titration / treat-to-target follow-up visit (ACR 2020 treat-to-target strong)
    established_gout_ult_titration_visit
  • problem_list
    Refractory tophaceous gout despite oral ULT — pegloticase pathway (ACR 2020; MIRROR Botson 2022 PMID 36099211)
    refractory_tophaceous_gout_referral

Required inputs (15)

  • flare_count_last_12morequired
    symptom • used at CONTEXT
    ULT strongly indicated if ≥2 flares/yr (ACR 2020 FitzGerald strong); ACP 2017 advises shared decision in infrequent attacks
  • tophus_presentrequired
    symptom • used at CONTEXT
    Tophus → strong ULT indication AND lower SUA target <5 mg/dL until dissolution (ACR 2020; EULAR 2016 Richette PMID 27457514)
  • serum_uric_acidrequired
    lab • used at INITIAL_WORKUP
    Treat-to-target analyte: <6 mg/dL general, <5 mg/dL tophaceous/severe; saturation point ~6.8 mg/dL (ACR 2020; EULAR 2016)
  • egfr_creatininerequired
    lab • used at CONTEXT
    eGFR (CKD-EPI 2021) drives allopurinol start dose (50 mg/d if eGFR<30), titration monitoring cadence, probenecid eligibility, NSAID-prophylaxis avoidance (ACR 2020; Stamp RCT PMID 28314755)
  • ckd_stagerequired
    history • used at CONTEXT
    CKD ≥3 is both an ULT indication and the dominant AHS-risk and dosing modifier (ACR 2020 FitzGerald strong)
  • cv_diseaserequired
    history • used at CONTEXT
    Established CVD informs febuxostat positioning (CARES PMID 29527974 vs FAST PMID 33181081 vs ALL-HEART PMID 36216006)
  • hla_b5801_ancestryrequired
    history • used at CONTEXT
    SE-Asian (Han Chinese/Thai/Korean) and African-American ancestry → HLA-B*5801 genotype before allopurinol (ACR 2020 FitzGerald strong — SJS/TEN risk)
  • urolithiasis
    history • used at CONTEXT
    Uric-acid stones → ULT priority + urinary alkalinisation; uricosurics relatively contraindicated (ACR 2020 FitzGerald)
  • transplant_or_cni
    history • used at CONTEXT
    Solid-organ transplant / cyclosporine-tacrolimus → secondary hyperuricemia + colchicine/azathioprine interaction; allopurinol–azathioprine is a hard interaction (ACR 2020)
  • diuretic_userequired
    medication • used at CONTEXT
    Thiazide/loop diuretics raise SUA — switch to losartan (uricosuric ARB) or amlodipine where feasible (EULAR 2016 Richette PMID 27457514)
  • azathioprine_6mprequired
    medication • used at CONTEXT
    Allopurinol/febuxostat block xanthine oxidase → life-threatening 6-MP/azathioprine toxicity; absolute interaction gate before XOI
  • g6pd_status
    lab • used at BRANCHING_WORKUP
    Pegloticase (recombinant uricase) causes haemolysis in G6PD deficiency — mandatory pre-screen before refractory step (FDA label; ACR 2020)
  • lft_baseline
    lab • used at INITIAL_WORKUP
    Baseline LFT before allopurinol/febuxostat; AHS includes hepatitis (ACR 2020 FitzGerald)
  • pregnancy_lactation_status
    demographic • used at CONTEXT
    Allopurinol/febuxostat/pegloticase not established-safe in pregnancy; methotrexate is teratogenic — defer ULT or individualise (ACR 2020; special-pop branch)
  • age_geriatric
    demographic • used at CONTEXT
    Geriatric STOPP/START — colchicine + CKD + statin/CYP3A4 interaction risk; allopurinol still first-line with start-low-go-slow (Pascart Drugs Aging 2022 PMID 36437395)

12-phase flow (12)

  1. 1FRAME
    Adult/geriatric established or recurrent gout — the longitudinal urate-lowering arc to treat-to-target and dissolve crystal burden. Acute-flare abortive therapy is NOT in scope (route to msk.gout-acute.core.v1). Disease is curable below the MSU saturation point ~6.8 mg/dL (ACR 2020 FitzGerald PMID 32391934; EULAR 2016 Richette PMID 27457514)
    inputs: flare_count_last_12mo, serum_uric_acid
    advance: Chronic ULT scope confirmed and acute flare excluded/handed off
  2. 2ENTRY
    Entry via ≥2 flares/yr, ≥1 tophus, radiographic/DECT urate deposition, hyperuricemia + CKD≥3 / urolithiasis / SUA>9, established-gout titration visit, or refractory-tophaceous referral (ACR 2020 FitzGerald strong indications)
    inputs: flare_count_last_12mo, tophus_present
    advance: Recognised ULT entry trigger present
  3. 3CONTEXT
    Capture the comorbidity matrix that gates agent choice: eGFR/CKD stage, CVD, urolithiasis, transplant/CNI, HLA-B*5801 ancestry, diuretic/low-dose-ASA, azathioprine/6-MP (hard XOI interaction), alcohol/fructose intake, current ULT + adherence, pregnancy/lactation, geriatric STOPP/START (ACR 2020 FitzGerald; EULAR 2016 Richette PMID 27457514; EULAR 2018 PMID 31167758)
    inputs: flare_count_last_12mo, tophus_present, ckd_stage, cv_disease, hla_b5801_ancestry, diuretic_use, azathioprine_6mp, egfr_creatinine
    actions: calc.ckd_epi_2021
    advance: Indication tier + comorbidity/driver/interaction profile captured
  4. 4RED_FLAGS
    Allopurinol hypersensitivity syndrome — fever + rash + eosinophilia + AKI/hepatitis (DRESS/SJS-TEN spectrum): STOP allopurinol immediately, NEVER rechallenge, supportive care/admit (ACR 2020 FitzGerald strong — high HLA-B*5801-carrier risk). Pegloticase-associated anaphylaxis or loss-of-response (pre-infusion SUA rising). Co-existing septic joint during an intercurrent flare (ACR 2020)
    inputs: hla_b5801_ancestry, serum_uric_acid
    actions: panel.cbc, panel.lft
    advance: AHS / anaphylaxis / co-existing sepsis screened and escalated if present
  5. 5INITIAL_WORKUP
    SUA (treat-to-target analyte), renal panel + eGFR, baseline LFT, CBC; confirm crystal-proven diagnosis if not already established (negatively birefringent MSU on aspirate, or DECT/US surrogate per EULAR 2018 PMID 31167758) before committing to lifelong ULT (ACR 2020 FitzGerald)
    inputs: serum_uric_acid, egfr_creatinine, lft_baseline
    actions: workup.hyperuricemia, panel.renal, panel.lft, panel.cbc
    advance: Diagnosis crystal/imaging-confirmed and baseline labs sent
  6. 6BRANCHING_WORKUP
    DECT / US double-contour for crystal-burden mapping when diagnosis uncertain or tophus burden quantified (EULAR 2018 PMID 31167758); tophus aspirate for crystal confirmation; 24-h urinary urate if stone-former / candidate for uricosuric (over- vs under-excretor); G6PD assay before any pegloticase pathway; secondary OA workup of a gout-damaged joint (optional)
    inputs: g6pd_status, urolithiasis
    actions: panel.synovial, workup.osteoarthritis
    advance: Crystal burden mapped, excretor status / G6PD known where needed
  7. 7DIFFERENTIAL
    Tophaceous gout vs CPPD vs nodal/erosive osteoarthritis vs RA nodules vs xanthoma/xanthelasma; asymptomatic hyperuricemia (do NOT treat with ULT — ACR 2020 strong against); pseudo-resistance (non-adherence / under-dosing) vs true ULT resistance before escalating (ACR 2020 FitzGerald)
    inputs: serum_uric_acid, tophus_present
    advance: Tophaceous chronic gout vs mimic resolved; adherence verified before escalation
  8. 8RISK_STRATIFICATION
    ULT indication tier (strong: ≥2 flares/yr, tophus, erosion, CKD≥3, urolithiasis, SUA>9; conditional: shared decision per ACP 2017 PMID 27802508). AHS interaction risk = HLA-B*5801 × CKD × thiazide (model the 3-way interaction). Tophus → SUA target <5 (conditional on tophus presence). Refractory phenotype → pegloticase+MTX. Geriatric STOPP/START. eGFR (calc.ckd_epi_2021) → start-dose & monitoring tier (ACR 2020 FitzGerald)
    inputs: ckd_stage, hla_b5801_ancestry, tophus_present, egfr_creatinine
    actions: calc.ckd_epi_2021
    advance: Indication tier, AHS-interaction risk, target, and dosing tier set
  9. 9TREATMENT
    Urate-lowering regimen builder (6-step ladder): (1) confirm indication + substitute modifiable drivers (HCTZ→losartan); (2) allopurinol 100 mg/d (50 mg/d if eGFR<30) start-low-go-slow, titrate q2–4 wk to target SUA <6 (or <5 tophaceous) — dose driven by target, NOT capped by CrCl table (Stamp RCT PMID 28314755; Wright PMID 30446002); HLA-B*5801 gate before allopurinol; azathioprine/6-MP is an absolute XOI interaction; (3) anti-inflammatory prophylaxis (colchicine 0.6 mg daily/BID or low-dose NSAID) ≥3–6 mo during titration — placebo NOT non-inferior (Stamp 2023 PMID 37652661); (4) febuxostat 40→80 mg if allopurinol intolerant/AHS-risk, CV caution (CARES all-cause mortality HR 1.22 [1.01–1.47], CV death HR 1.34 [1.03–1.73] PMID 29527974; FAST non-inferior aHR 0.85 [0.70–1.03] PMID 33181081); (5) probenecid uricosuric (or lesinurad add-on) for under-excretors with eGFR≥30 and no stones (CLEAR 2 PMID 27821644); (6) refractory tophaceous → pegloticase 8 mg IV q2wk + methotrexate 15 mg/wk (MIRROR 6-mo response 71% vs 38.5%, infusion reactions 4.2% vs 30.6% PMID 36099211; 12-mo tophus resolution 53.8% vs 31.0% PMID 37385296), G6PD-screened. Special-pop branches: pregnancy/lactation, CKD/eGFR, geriatric STOPP/START, G6PD, transplant/CNI (ACR 2020 FitzGerald PMID 32391934; EULAR 2016 Richette PMID 27457514)
    inputs: serum_uric_acid, egfr_creatinine, hla_b5801_ancestry, azathioprine_6mp
    advance: ULT agent selected with eGFR-gated dose, prophylaxis, and driver substitution in place
  10. 10DISPOSITION
    Outpatient throughout. Rheumatology referral for refractory/tophaceous disease and the pegloticase+MTX pathway. Admit only for allopurinol hypersensitivity syndrome or pegloticase anaphylaxis (ACR 2020 FitzGerald)
    advance: Care level + specialty referral set
  11. 11MONITORING
    SUA q2–4 wk during ULT titration → q6 mo once at sustained target (ACR 2020 FitzGerald treat-to-target strong). Renal panel + LFT + CBC per agent (XOI: first-year LFT/CBC; allopurinol: rash/LFT first 8 wk in AHS-risk). Anti-inflammatory prophylaxis duration review ≥3–6 mo after target reached. Pegloticase: PRE-INFUSION SUA before every dose — rising/loss-of-response (>6 mg/dL ×2) predicts anaphylaxis → STOP. Tophus size trajectory (ACR 2020; MIRROR PMID 37385296)
    inputs: serum_uric_acid, egfr_creatinine
    actions: panel.renal, panel.lft
    advance: SUA at target sustained ≥6 mo with monitoring cadence individualised
  12. 12FOLLOWUP
    Lifelong ULT for established gout (ACR 2020 FitzGerald strong). CV risk modification (treat the gout, not the urate, outside gout — ALL-HEART PMID 36216006). Diet/alcohol/fructose/weight counseling (EULAR 2016 Richette PMID 27457514). Cautious dose-REDUCTION deprescribing (never abrupt stop) only after years of sustained target + no tophi + no flares, with continued surveillance. Tophus surgical referral if functional impairment
    advance: Long-term lifelong plan + counseling + deprescribing criteria documented