De-identified case · second opinion & research

Nico

Infantile-onset Crohn's disease — very-early-onset IBD (VEO-IBD)

Preschool-age boy (Mexico). Symptoms since ~8 months of age. Colonic, stricturing disease with growth failure; refractory to two anti-TNF agents and, to date, without an identified monogenic cause. This page gathers his history in an organized way so specialists can review it and for anyone researching this disease.

Diagnosis
Infantile Crohn's · Paris A1a/L2/B2/G1
Onset
~8 months of age
Data as of
June 2026

Clinical summary

Boy with infantile-onset Crohn's disease (symptom onset ~8 months; first endoscopy Jan 2023 with an initial diagnosis of unclassified IBD, later reclassified as Crohn's), Paris A1a · L2 (colonic) · B2 (stricturing) · G1 (growth failure), confirmed by endoscopy and biopsy. Initial therapy with corticosteroid + azathioprine + mesalazine without control, and a brief course of tocilizumab (anti-IL-6, Oct–Nov 2023, discontinued for perianal disease + C. difficile). Severe, refractory course: primary non-response to infliximab and adalimumab; vedolizumab discontinued for new-onset transaminase elevation (ALT 128, GGT 229; liver normal 8 months prior). Cyclosporine and methotrexate also discontinued. Steroid-dependent. Recurrent C. difficile infections. On monthly IVIG despite normal IgG. A 935-gene panel (immunodeficiency + skeletal): no actionable monogenic cause; heterozygous VUS in ARHGEF1, CFB, IL6ST, MMP9, NLRP1; ABCG8 risk allele. Non-passable right-colon stricture (inflammatory by imaging).

Timeline

  1. ~8 months of age

    Symptom onset

    Diarrheal stools with fresh blood, up to 8–10 per day.

  2. Jan 2023

    First endoscopy — unclassified IBD

    Initial diagnosis of inflammatory bowel disease, unclassified. Started conventional therapy: prednisolone + azathioprine + mesalazine, without improvement (persistent bleeding and frequent stools).

  3. 2023

    Genetic testing

    Immunodeficiency panel, later expanded to 935 genes (including a skeletal-disorders panel). No actionable monogenic cause; variants of uncertain significance (VUS) and one risk allele in ABCG8.

  4. Oct–Nov 2023

    Tocilizumab (anti-IL-6)

    Three doses (Oct 14, Oct 30, Nov 12). Discontinued when perianal disease appeared along with a Clostridioides difficile relapse.

  5. Jan–Jul 2024

    Infliximab (anti-TNF)

    First dose Jan 13, 2024, then every 15 days until Jul 26, 2024. Perianal disease from 2023 resolved on infliximab; later, inadequate response and a C. difficile relapse.

  6. Aug 2024

    Relapse & admission to a national pediatric institute (Mexico)

    C. difficile relapse. Stool culture: C. difficile + enteropathogenic/enterotoxigenic E. coli. Endoscopy: infantile-onset Crohn's with severe activity; three colonic strictures (ascending, splenic flexure, rectum). Switched from infliximab to adalimumab.

  7. Aug 2024 – Feb 2026

    Adalimumab (anti-TNF)

    Every 3 weeks, with methotrexate and monthly IVIG. Steroid-free from Sep 2024 to Oct 2025.

  8. Jul 2025

    Subclinical activity

    Clinically mild, but elevated calprotectin. Adalimumab reduced.

  9. Oct 2025

    Relapse

    ↑ calprotectin, ↓ albumin and hemoglobin, ↑ ESR; new strictures. Liver panel normal (ALT 13, GGT <10).

  10. Nov 2025

    Hospitalized for C. difficile

    New C. difficile relapse; hospitalized at the institute (metronidazole + vancomycin). Steroid resumed.

  11. Dec 2025

    Anti-TNF failure

    Primary non-response to anti-TNF (infliximab and adalimumab) → candidate for vedolizumab (anti-integrin).

  12. Feb–Apr 2026

    Vedolizumab (anti-integrin)

    Induction: Feb 27, Mar 13 and Apr 10; then every 4 weeks.

  13. Jun 5, 2026

    Last vedolizumab dose

    Final infusion before discontinuation.

  14. Jun 2026

    New liver injury

    Elevated transaminases (ALT 128, GGT 229), active inflammation (ESR 41, leukocytes 16) and iron-deficiency anemia. Liver was normal 8 months earlier.

  15. Jun 2026

    Treatment reorganization

    Vedolizumab and cyclosporine discontinued; family discontinued methotrexate; slow prednisolone taper (steroid-dependent patient).

  16. Jul 2026

    Therapeutic rethink

    Considering an afimkibart program (anti-TL1A, investigational) and other options (ustekinumab, upadacitinib).

Diagnosis & phenotype

A1a

Onset before age 10 (very early / infantile)

L2

Colonic location

B2

Stricturing behavior

G1

Growth failure present

Confirmed by endoscopy + histopathology at a national reference pediatric institute (Mexico). Imaging (MR-enterography): penetrating disease with ulcers, inflammatory-appearing strictures (no fibrofatty proliferation), no fistulae. Perianal disease in 2023 (reason for tocilizumab discontinuation), resolved after starting infliximab (Jan 2024); no longer reported on MR-enterography (Sep 5, 2025).

Treatment

History (discontinued)

DrugClassStatus
Mesalazine + azathioprine 5-ASA + thiopurine Discontinued (2023)
Tocilizumab anti-IL-6 Discontinued (Nov 2023)
Infliximab anti-TNF Discontinued (2024)
Adalimumab anti-TNF Discontinued (Feb 2026)
Vedolizumab anti-integrin (α4β7) Discontinued (Jun 2026)
Cyclosporine calcineurin inhibitor Discontinued (Jun 2026)
Methotrexate immunosuppressant Discontinued (Jun 2026)

Current medications

Under consideration

Laboratory studies

Key markers. The "prior" column is from Oct–Nov 2025 where applicable; the most striking change is the liver (normal in Oct 2025 → elevated in Jun 2026).

ParameterPriorJun 2026
ALT 13 128 ↑
GGT <10 229 ↑
ESR 16 41 ↑
Fecal calprotectin — 1980 ↑
Hemoglobin — 11.1 ↓
Albumin — 3.1 ↓
Platelets 515 589 ↑
Ciclosporin (trough) 54 —
IgG 1040 —

Genetics

935-gene panel (immunodeficiency + skeletal disorders). No actionable monogenic cause.

Negative (classic VEO-IBD genes)

IL10 · IL10RA · IL10RB · LRBA · CTLA4 · XIAP · FOXP3 · chronic granulomatous disease (CYBB/CYBA/NCF)

Heterozygous VUS

  • ARHGEF1
  • CFB
  • IL6ST
  • MMP9
  • NLRP1

+ risk allele in ABCG8 (gallstones).

Pending / to discuss: whole-exome or whole-genome sequencing (WES/WGS) + functional immune studies.

Current diet

Usual intake (not exclusive enteral nutrition). Documented as clinical/nutritional context.

Open questions for specialists

  1. 01 After failing two anti-TNF agents and discontinuing vedolizumab (for liver), what is the optimal maintenance: anti-IL-12/23 (ustekinumab), anti-TL1A (afimkibart) or JAK (upadacitinib)?
  2. 02 Given infantile onset and a negative panel, is whole-exome/genome + functional immune studies warranted? Relevance of the VUS in IL6ST and ARHGEF1?
  3. 03 Origin of the liver injury that appeared in 2026: drug-induced (vedolizumab/methotrexate/cyclosporine) or disease-related?
  4. 04 On monthly IVIG with normal IgG — is there a functional antibody deficiency that justifies it?
  5. 05 Non-passable right-colon stricture: inflammatory or fibrotic? Threshold for dilation/surgery?
  6. 06 Experience with similar cases or pathways into VEO-IBD registries (e.g. NEOPICS, VEO-IBD Consortium)?

Are you a specialist or researcher who can help?

Any guidance, experience with similar cases, or study pathways are welcome.

Contact: arguetagra15@gmail.com