Long-term calcineurin-inhibitor exposure ≥5 years — cyclosporine or tacrolimus (prograf,...

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

ID	`RF-IATROGENIC-CALCINEURIN-INHIBITOR-LONGTERM-PREVENTION`
Type	Red flag
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	`DIS-BCC` `DIS-KAPOSI`
Sources	`SRC-IARC-MONO-100B-2012` `SRC-NCCN-SKIN-2025`

Red Flag Origin

Definition	Long-term calcineurin-inhibitor exposure ≥5 years — cyclosporine or tacrolimus (prograf, FK-506) — across transplant, autoimmune (psoriasis, atopic dermatitis, refractory nephrotic syndrome), and ophthalmologic / other indications. IARC Group 1 carcinogen (cyclosporine). Mechanism: direct calcineurin-pathway suppression of T-cell function plus pro-oncogenic effects (TGF-β upregulation, IL-6 induction, impaired DNA repair, anti-apoptotic signaling). Risk profile: cutaneous squamous-cell carcinoma 65-100x background in transplant cohort (calcineurin-inhibitors are a primary driver of this excess), basal-cell carcinoma 10-20x, aggressive SCC variant prone to local recurrence + perineural invasion + nodal metastasis; Kaposi sarcoma in HHV-8-exposed cohort (KSHV reactivation under calcineurin inhibition); cutaneous T-cell lymphoma (less common); lip cancer (cumulative UV co-factor); modest i...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "cyclosporine_continuous_use_ge_5y",
      "value": true
    },
    {
      "finding": "tacrolimus_continuous_use_ge_5y",
      "value": true
    },
    {
      "finding": "calcineurin_inhibitor_use_ge_5y_with_skin_cancer_history",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Prevention-persona RedFlag for long-term ≥5y calcineurin-inhibitor exposure (cyclosporine or tacrolimus). Engine routes to PreventionPlan recommending (1) annual or q6mo whole-body skin exam by dermatologist (q6mo if any prior skin cancer), (2) aggressive sun-protection counseling, (3) HHV-8 awareness in endemic cohorts + KS surveillance (skin, oral, GI), (4) HPV vaccination catch-up if transplant context, (5) shared-decision discussion with transplant team of switch to mTOR inhibitor (sirolimus / everolimus) in patients with cumulative skin- cancer burden — CONVERT + ProSparc evidence: mTOR-switch reduces new SCC. Anchored to DIS-KAPOSI + DIS-BCC. Distinct from broader RF-IATROGENIC-TRANSPLANT-IMMUNOSUPPRESSION-* RFs by drug-class specificity — applies also to non-transplant calcineurin-inhibitor users (psoriasis, atopic dermatitis, nephrotic syndrome). STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode.

Used By

Indications

IND-IATROGENIC-CALCINEURIN-INHIBITOR-LONGTERM-PREVENTION-OBSERVATION - IND-IATROGENIC-CALCINEURIN-INHIBITOR-LONGTERM-PREVENTION-OBSERVATION
IND-IATROGENIC-CALCINEURIN-INHIBITOR-LONGTERM-PREVENTION-SURVEILLANCE - IND-IATROGENIC-CALCINEURIN-INHIBITOR-LONGTERM-PREVENTION-SURVEILLANCE