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Long-term low-dose methotrexate exposure (≥1-2 years, ≥15 mg/week cumulative or PO 7.5-25...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDRF-IATROGENIC-METHOTREXATE-LONGTERM-LYMPHOMA-PREVENTION
TypeRed flag
Statusreviewed 2026-05-19 | pending_clinical_signoff
DiseasesDIS-DLBCL-NOS
SourcesSRC-NCCN-BCELL-2025

Red Flag Origin

DefinitionLong-term low-dose methotrexate exposure (≥1-2 years, ≥15 mg/week cumulative or PO 7.5-25 mg/week chronic) for autoimmune indications including rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease — associated with methotrexate-associated lymphoproliferative disorders (MTX-LPD), most commonly diffuse large B-cell lymphoma (DLBCL) or polymorphic LPD with EBV co-positivity in many cases. Incidence ~1-3% over 5 years of cumulative exposure; Japanese rheumatoid cohorts show higher signal (likely population EBV seroprevalence). Distinctive feature: ~30-60% of MTX-LPD cases regress on MTX withdrawal alone (no chemotherapy needed) — this signature uniquely identifies the iatrogenic etiology. Risk also modestly elevated for solid cancers (skin SCC, melanoma) — separate signal. Prevention-persona RedFlag (§20, v0.3 iatrogenic expansion).
Clinical directioninvestigate
Categoryother

Trigger Logic

{
  "any_of": [
    {
      "finding": "methotrexate_longterm_low_dose_autoimmune",
      "value": true
    },
    {
      "finding": "methotrexate_ge_1y_cumulative",
      "value": true
    },
    {
      "finding": "mtx_lpd_susceptible_cohort",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Prevention-persona RedFlag for long-term low-dose MTX exposure (RA, psoriasis, IBD). Surveillance: low-threshold workup for unexplained lymphadenopathy, B-symptoms, organomegaly, mass — MTX withdrawal + observe 8-12 weeks first (~50% regress); persistent → DLBCL-style workup. Skin examination annually. STUB pending two-Co-Lead signoff per CHARTER §6.1 dev-mode.

Used By

Indications