Special Considerations in Pediatric Inflammatory Bowel Disease Pathology
Abstract
:1. Introduction
2. Pediatric Inflammatory Bowel Disease (IBD) Classification
3. Upper Gastrointestinal Tract Involvement in Pediatric Inflammatory Bowel Disease
4. Inflammatory Bowel Disease with Primary Sclerosing Cholangitis (PSC-IBD)
5. Monogenic Inflammatory Bowel Disease (IBD)
5.1. IL-10R/R
5.2. XIAP
5.3. CYBB
5.4. LRBA
5.5. TTC7A
6. Differential Diagnosis
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Class 1 (features incompatible with UC)
|
Class 2 (features rarely found in UC)
|
Class 3 (features uncommon in UC)
|
Monogenic Disorder | Genes | IBD Type Reported | Extraintestinal Associations (in Order of Relative Frequency) |
---|---|---|---|
Agammaglobulinemia | BTK, PIK3CD, PIK3R1 | CD/CD-like, IBD, UC/UC-like | Autoimmunity, infection |
Chronic enteropathy associated with SLCO2A1 gene | SLCO2A1 | IBD, CD/CD-like | Autoimmunity |
Chronic granulomatous disease | CYBA, CYBB, NCF1, NCF2, NCF4 | Granulomatous colitis, IBD, CD/CD-like, UC/UC-like, IBD-U/IC | Autoimmunity, infection, HLH, malignancy |
CHAPLE syndrome | CD55 | ND | Autoimmunity, infection, malignancy |
DOCK8 syndrome | DOCK8 | UC/UC-like, CD/CD-like, IBD | Autoimmunity, infection |
Familial hemophagocytic lymphohistiocytosis 4 | STXBP2 | ND | Autoimmunity, infection, HLH |
Glycogen storage disease type 1B | SLC37A4 | IBD, CD/CD-like | Infection, hematolymphoid involvement, metabolic disease |
Familial GUCY2C diarrhea syndrome | GUCY2C | CD/CD-like, IBD | |
G6PC3 deficiency | G6PC3 | CD/CD-like, IBD | Infection, dysmorphic features |
Haploinsufficiency of A20 | TNFAIP3 | Intestinal BD, CD/CD-like, IBD | Autoimmunity, infection |
Hermansky-Pudlak syndrome | HPS1, HPS4, HPS6 | CD/CD-like, IBD, UC/UC-like | Autoimmunity |
Hoyeraal-Hreidarsson Syndrome | DKC1, RTEL1 | UC/UC-like, CD/CD-like | Dysmorphic features, infection |
IL-10 and IL-10-receptor associated colitis | IL-10, IL-10RA, IL-10RB | IBD, CD/CD-like, IBD-U/IC | Autoimmunity, infection, HLH |
Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) | FOXP3 | IBD, CD/CD-like, UC/UC-like, IBD-U/IC | Autoimmunity, infection |
Immunodysregulation polyendocrinopathy enteropathy X-linked-like syndrome (IPEX-like) | STAT1, STAT3, CTLA4, LRBA, IL21, IL2RA, IL2RB, MALT1 | IBD, CD/CD-like, UC/UC-like, IBD-U | Autoimmunity, infection, malignancy, hematolymphoid involvement |
Kindler syndrome | FERMT1 | UC/UC-like, CD/CD-like | |
Leukocyte adhesion deficiency | ITGB2 | ND | Infection |
Loeys-Dietz syndrome | TGFBR1, TGFBR2 | UC/UC-like, CD/CD-like, IBD | Dysmorphic features, infection |
Mevalonate kinase deficiency | MVK | ND | Autoimmunity |
Nuclear factor-kappa B Essential Modulator deficiency (NEMO) | IKBKG | IBD, CD/CD-like, intestinal BD | Dysmorphic features, infection |
NLRC4-macrophage activating syndrome | NLRC4 | ND | Autoimmunity, infection, HLH |
Niemann-Pick disease type C | NPC1 | CD/CD-like, IBD-U/IC | Metabolic disease |
RIPK1 deficiency | RIPK1 | IBD | Autoimmunity, infection |
Severe combined immunodeficiency | CD3G, DCLRE1C, IL2RG, LIG4, RAG1 | IBD, CD/CD-like | Infection |
Trichohepatoenteric syndrome | SKIV2L, TTC37 | IBD-U/IC, IBD, CD/CD-like | Dysmorphic features, infection |
TTC7A deficiency | TTC7A | IBD, IBD-U/IC, CD/CD-like | Autoimmunity, infection, dysmorphic features, malignancy |
TRIM22 deficiency | TRIM22 | ND | Autoimmunity, infection |
Wiskott-Aldrich syndrome/Wiskott-Aldrich-like syndrome (WAS/WAS-like) | WAS, ARPC1B | IBD, CD/CD-like, UC/UC-like | Autoimmunity, infection |
XIAP deficiency | XIAP | CD/CD-like, IBD, UC/UC-like, IBD-U/IC | Autoimmunity, infection, HLH, hematolymphoid involvement, malignancy |
Pattern | Key Findings | Associated Monogenic Disorders | Other Causes of Pattern |
---|---|---|---|
Chronic active enteritis | Active inflammation (neutrophilic cryptitis and crypt abscesses) Chronic mucosal changes (architectural changes and cellular metaplasia) | IL-10/R; CGD; XIAP; GUCY2C; familial Mediterranean fever; HPS types 1, 4, 6; GSD1; WAS; CVID; TTC7A | Polygenic IBD |
Apoptosis/Epithelial injury pattern | Epithelial injury or apoptosis out of proportion to inflammatory activity | Disorders resulting in B and T cell deficiency/dysregulation; SCID; Omenn syndrome; IPEX; TTC7A; dystrophic epidermolysis bullosa; mevalonate kinase deficiency; disorders of telomere maintenance | GvHD; antimetabolite immunosuppression, especially mycophenolate mofetil; acute GI transplant rejection; viral infection |
Eosinophil-rich pattern | Clusters of eosinophils in the lamina propria and eosinophilic infiltration of surface and crypt epithelium | Omenn syndrome | Non-monogenic IBD; non-IBD etiologies for GI eosinophilia (e.g., allergy, parasitic infection, Langerhans cell histiocytosis) |
Lymphocytic patterns | Lymphocytosis and nodular lymphoid hyperplasia OR Lymphocyte or plasma cell depletion AND Lack of active inflammation and chronic mucosal changes | Lymphocytosis: CVID; IgA deficiency; CTLA4-related disorders; T cell regulatory disorders; IPEX Lymphocyte or plasma cell depletion: CVID; hypogammaglobulinemia; X-linked lymphoproliferative disorder type 1; SCID | Lymphocytosis: celiac disease; post-infectious enteritis (can be secondary to immunodeficiency), medication effect (especially NSAIDs); bacterial overgrowth Lymphoid depletion: medical therapy (e.g., conditioning chemotherapy prior to bone marrow transplant); artifactual due to mucosal edema |
Granulomatous pattern | Non-necrotizing granulomas | CGD; IL-10/R; HPS types 1, 4, 6 | Misidentification of cryptolytic granuloma/germinal center; infectious granulomas (mycobacterial/fungal, usually necrotizing); or very rarely sarcoidosis |
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Andrews, A.R.; Putra, J. Special Considerations in Pediatric Inflammatory Bowel Disease Pathology. Diagnostics 2025, 15, 831. https://doi.org/10.3390/diagnostics15070831
Andrews AR, Putra J. Special Considerations in Pediatric Inflammatory Bowel Disease Pathology. Diagnostics. 2025; 15(7):831. https://doi.org/10.3390/diagnostics15070831
Chicago/Turabian StyleAndrews, Alicia R., and Juan Putra. 2025. "Special Considerations in Pediatric Inflammatory Bowel Disease Pathology" Diagnostics 15, no. 7: 831. https://doi.org/10.3390/diagnostics15070831
APA StyleAndrews, A. R., & Putra, J. (2025). Special Considerations in Pediatric Inflammatory Bowel Disease Pathology. Diagnostics, 15(7), 831. https://doi.org/10.3390/diagnostics15070831