Conditions with similar clinical presentations that must be differentiated from Collagenous Sprue:
Pathophysiology description Collagenous sprue (CS) is a rare enteropathy of the small intestine defined by villous atrophy with a thickened, irregular subepithelial collagen band (>10 μm) that may entrap capillaries and stromal cells, accompanied by intraepithelial lymphocytosis and lamina propria inflammation; endoscopically, diffuse villous blunting and scalloping may be seen, but diagnosis requires histology (trichrome) (mirakhor2021collagenousenteritis–analternative pages 1-3, moreno2024spruecolágenogastritis pages 1-2, moreno2024spruecolágenogastritis pages 4-5). Clinically, patients present with chronic watery diarrhea, profound weight loss, malabsorption, protein‑losing enteropathy, anemia, and hypoalbuminemia; CS often mimics celiac disease but typically shows negative celiac serology and poor response to a gluten‑free diet (mirakhor2021collagenousenteritis–analternative pages 1-3, moreno2024spruecolágenogastritis pages 1-2, mirakhor2021collagenousenteritis–analternative pages 3-4).
Core Pathophysiology - Primary mechanisms: (1) mucosal immune activation with increased intraepithelial lymphocytes (IELs) and lamina propria inflammation; (2) epithelial barrier injury with crypt apoptosis and tight‑junction perturbation; and (3) fibroblast/myofibroblast activation leading to excessive extracellular matrix (ECM) deposition and a diagnostic subepithelial collagen band, plausibly due to TGF‑β–driven profibrotic signaling together with an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, zabana2022pathogenesisofmicroscopic pages 10-11, valatas2017stromalandimmune pages 3-4, xiao2009collagenousspruea pages 3-4). - Dysregulated pathways: Evidence (largely inferential and by analogy to collagenous colitis and intestinal fibrosis) supports roles for TGFB1 signaling, increased TIMP1 with relative reductions/restrictions in MMP1/9 activity, IL‑15/TNF‑α–associated IEL activation and epithelial apoptosis, and barrier protein disruption (ZO‑1/TJP1) (zabana2022pathogenesisofmicroscopic pages 10-11, burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, valatas2017stromalandimmune pages 3-4, xiao2009collagenousspruea pages 3-4). - Affected cellular processes: epithelial apoptosis and tight‑junction impairment; fibroblast→myofibroblast differentiation with α‑SMA expression and increased collagen I production; impaired fibrolysis due to MMP/TIMP imbalance; immune cell infiltration (IELs, plasma cells, eosinophils) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, valatas2017stromalandimmune pages 3-4, xiao2009collagenousspruea pages 3-4, moreno2024spruecolágenogastritis pages 4-5).
Recent developments and latest research (prioritize 2023–2024) - 2024 case‑based review emphasizes CS’s association with collagenous gastritis/colitis, autoimmune comorbidities, and severe complications (ulceration, perforation, lymphoma), while also noting some recent reports of favorable responses to immunosuppression (Spanish; full text with diagnostic details including the >10 μm band cutoff and entrapped capillaries) (Sep 2024, Acta Gastroenterológica Latinoamericana; https://doi.org/10.52787/agl.v54i3.383) (moreno2024spruecolágenogastritis pages 1-2, moreno2024spruecolágenogastritis pages 4-5, moreno2024spruecolágenogastritis pages 2-4). - 2024 case report of olmesartan‑induced collagenous sprue underscores medication‑triggered disease and rapid clinical improvement after drug withdrawal, reinforcing drug‑induced immune/injury mechanisms (Oct 2024, Cureus; https://doi.org/10.7759/cureus.72571) (goshgarian2024pathognomonicfeaturesof pages 1-2). - Ongoing synthesis from foundational studies continues to support immune‑mediated mechanisms including IEL activation, crypt apoptosis, and epithelial barrier protein alterations (ZO‑1/TJP1) in ARB enteropathy overlapping with CS (Human Pathology 2016; https://doi.org/10.1016/j.humpath.2015.12.001) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5).
Current applications and real‑world implementations - Diagnostic criteria and practice: Recognition that the collagen band threshold >10 μm with trichrome positivity and entrapped capillaries, paired with villous atrophy and intraepithelial lymphocytosis, is key for diagnosis; multi‑segment evaluation (stomach, colon) is advocated when CS is suspected (moreno2024spruecolágenogastritis pages 4-5, sharma2018collagenousgastritisa pages 1-2, mirakhor2021collagenousenteritis–analternative pages 3-4). - Medication review and withdrawal: Systematic collection of medication history, particularly ARBs such as olmesartan, PPIs, and NSAIDs, and prompt withdrawal in suspected drug‑induced cases; many patients exhibit clinical and histologic reversal within months (Mayo Clinic Proc 2012; Hum Pathol 2016) (rubiotapia2012severespruelikeenteropathy pages 5-7, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5). - Immunosuppression: Corticosteroids (including budesonide) remain first‑line in many reports; refractory cases may respond to thiopurines or TNF‑α inhibitors, though evidence derives from case series and case reports (mirakhor2021collagenousenteritis–analternative pages 3-4, xiao2009collagenousspruea pages 5-6).
Expert opinions and analysis from authoritative sources - Mayo Clinic series: Olmesartan‑associated sprue‑like enteropathy likely reflects a delayed cell‑mediated immune reaction in genetically predisposed patients (frequent HLA‑DQ2), with histologic overlap with CS (villous atrophy, IELs, collagen band); clinical and histologic recovery follows drug cessation (Aug 2012, Mayo Clinic Proceedings; https://doi.org/10.1016/j.mayocp.2012.06.003) (rubiotapia2012severespruelikeenteropathy pages 5-7, rubiotapia2012severespruelikeenteropathy pages 3-4). - Systematic review emphasis: Immune‑mediated injury plus epithelial barrier disruption (including reports of ZO‑1/TJP1 alterations) underlie ARB enteropathy; frequent collagen deposition links drug‑induced enteropathy to CS phenotype (Apr 2016, Human Pathology; https://doi.org/10.1016/j.humpath.2015.12.001) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, burbure2016olmesartanassociatedspruelikeenteropathy pages 5-7, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5). - Intestinal fibrosis frameworks: In gut fibrosis, TGF‑β–driven myofibroblast activation, TIMP1 upregulation, and reduced MMP activity drive ECM accumulation—mechanisms broadly consistent with the collagen band in CS (Apr 2017, Annals of Gastroenterology; https://doi.org/10.20524/aog.2017.0146) (valatas2017stromalandimmune pages 3-4, valatas2017stromalandimmune pages 2-3).
Relevant statistics and data from recent studies - Demographics: Reported across ages 2–85 years with ~2:1 female predominance; many cases severe with marked weight loss and malnutrition (2021 summary; 2024 case review) (mirakhor2021collagenousenteritis–analternative pages 1-3, moreno2024spruecolágenogastritis pages 2-4). - Histologic thresholds: Normal subepithelial collagen band ~5–7 μm; cutoff >10 μm used to define CS; bands of 10–20 μm or more with entrapped capillaries and stromal cells are typical (2024 case review) (moreno2024spruecolágenogastritis pages 4-5). - Drug association prevalence: In early cohorts of olmesartan enteropathy, approximately one‑third of a CS cohort was exposed to olmesartan at or near diagnosis, and most improved after discontinuation (2012 Mayo Clinic Proceedings) (rubiotapia2012severespruelikeenteropathy pages 5-7).
Mechanistic model of disease progression - Initiation: Environmental/drug triggers (notably ARBs) or autoimmune milieu initiate mucosal immune activation; many patients lack celiac serology and fail gluten‑free diet, implicating alternative triggers (rubiotapia2012severespruelikeenteropathy pages 5-7, mirakhor2021collagenousenteritis–analternative pages 1-3). - Epithelial insult and immune activation: Increased IELs and cytokine signaling (e.g., IL‑15, TNF‑α, IL‑6) drive crypt epithelial apoptosis; barrier dysfunction is supported by reports of ZO‑1/TJP1 disruption (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5). - Stromal remodeling: TGF‑β–driven fibroblast→myofibroblast differentiation increases COL1A1 and TIMP1 with relatively reduced MMP1/9 activity, favoring ECM accumulation and subepithelial collagen band formation (zabana2022pathogenesisofmicroscopic pages 10-11, valatas2017stromalandimmune pages 3-4, xiao2009collagenousspruea pages 3-4). - Tissue architecture and clinical phenotype: Collagen band (>10 μm) entrapping capillaries/cells and villous atrophy produce severe malabsorption, protein‑losing enteropathy, and weight loss; multi‑segment involvement (gastritis/colitis) and complications (ulceration, perforation, lymphoma) may ensue (moreno2024spruecolágenogastritis pages 4-5, moreno2024spruecolágenogastritis pages 1-2, rubiotapia2012severespruelikeenteropathy pages 3-4).
Key Molecular Players - Genes/Proteins (HGNC): TGFB1 (TGF‑β1), MMP1, MMP9, TIMP1, COL1A1, TJP1 (ZO‑1), TNF (TNF‑α), IL15, IL6; HLA‑DQA1/DQB1 (HLA‑DQ2/8 susceptibility in drug‑induced SLE) (zabana2022pathogenesisofmicroscopic pages 10-11, burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, rubiotapia2012severespruelikeenteropathy pages 5-7, xiao2009collagenousspruea pages 3-4). - Chemical entities (CHEBI): glucocorticoids (budesonide), thiopurines (azathioprine/6‑thioguanine), anti‑TNF agents; olmesartan (ARB), NSAIDs and PPIs as potential modifiers/triggers (mirakhor2021collagenousenteritis–analternative pages 3-4, rubiotapia2012severespruelikeenteropathy pages 5-7, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5, moreno2024spruecolágenogastritis pages 4-5). - Cell types (CL): Intraepithelial lymphocytes (CD8+ IELs), enterocytes, lamina propria plasma cells/eosinophils, subepithelial myofibroblasts (α‑SMA+), fibroblasts (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, valatas2017stromalandimmune pages 3-4, moreno2024spruecolágenogastritis pages 4-5). - Anatomical locations (UBERON): Small intestinal mucosa (duodenum, jejunum), lamina propria (subepithelial region), with possible involvement of gastric and colonic mucosa (moreno2024spruecolágenogastritis pages 4-5, sharma2018collagenousgastritisa pages 1-2, moreno2024spruecolágenogastritis pages 1-2).
Biological Processes (GO annotation candidates) - ECM organization and collagen fibril organization; regulation of collagen biosynthetic process (TGFB1‑mediated) (valatas2017stromalandimmune pages 3-4, zabana2022pathogenesisofmicroscopic pages 10-11). - Regulation of proteolysis and extracellular matrix disassembly (MMP/TIMP balance) (zabana2022pathogenesisofmicroscopic pages 10-11, valatas2017stromalandimmune pages 2-3). - Epithelial cell apoptotic process and regulation of cell‑cell junction organization (TJP1/ZO‑1 alteration) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5). - T cell–mediated immune response; response to cytokines (IL‑15, TNF‑α, IL‑6) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5).
Cellular Components - Subepithelial lamina propria (site of collagen band); epithelial tight junctions (ZO‑1/TJP1); extracellular space/ECM; fibroblast stress fibers (α‑SMA cytoskeleton) (moreno2024spruecolágenogastritis pages 4-5, burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, valatas2017stromalandimmune pages 3-4).
Disease Progression - Sequence: trigger (often medication) → IEL‑driven/immune activation and epithelial apoptosis with barrier loss → TGF‑β–driven myofibroblast activation with net ECM accumulation (↑TIMP1/↓MMP) → subepithelial collagen band and villous atrophy → malabsorption/protein loss → complications (ulceration/perforation; occasional lymphoma) (rubiotapia2012severespruelikeenteropathy pages 5-7, zabana2022pathogenesisofmicroscopic pages 10-11, rubiotapia2012severespruelikeenteropathy pages 3-4, moreno2024spruecolágenogastritis pages 1-2). - Phases: (i) inflammatory/immune injury; (ii) fibrogenic remodeling; (iii) established collagen band with severe malabsorption; (iv) potential regression if drug withdrawn and/or immunosuppression, although course is heterogeneous (rubiotapia2012severespruelikeenteropathy pages 5-7, mirakhor2021collagenousenteritis–analternative pages 3-4, freeman2010updateoncollagenous pages 1-2).
Phenotypic Manifestations (HP terms) - Chronic diarrhea (HP:0002028), Weight loss (HP:0001824), Malabsorption (HP:0002242), Protein‑losing enteropathy (HP:0005226), Anemia (HP:0001903), Hypoalbuminemia (HP:0003073), Villous atrophy on small intestinal biopsy (HP:0011472) (mirakhor2021collagenousenteritis–analternative pages 1-3, moreno2024spruecolágenogastritis pages 4-5, mirakhor2021collagenousenteritis–analternative pages 3-4).
Cell type involvement (CL terms) - Intraepithelial lymphocyte, small intestine (CL:0009101); Intestinal epithelial cell (CL:0002563); Subepithelial myofibroblast (often annotated as intestinal myofibroblast; related: CL:0000186 fibroblast, with α‑SMA+ phenotype) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, valatas2017stromalandimmune pages 3-4).
Anatomical locations (UBERON terms) - Duodenum (UBERON:0002114), Jejunum (UBERON:0002115), Intestinal lamina propria (UBERON:0001982), Gastric mucosa (UBERON:0001275), Colonic mucosa (UBERON:0001155) (moreno2024spruecolágenogastritis pages 4-5, moreno2024spruecolágenogastritis pages 1-2, sharma2018collagenousgastritisa pages 1-2).
Chemical entities (CHEBI) - Olmesartan (CHEBI:7791), Nonsteroidal anti‑inflammatory drug (CHEBI:35475), Proton pump inhibitor (CHEBI:50784), Budesonide (CHEBI:3160), Azathioprine (CHEBI:2955), 6‑Thioguanine (CHEBI:9565), Infliximab/adalimumab (anti‑TNF biologics; protein therapeutics) (rubiotapia2012severespruelikeenteropathy pages 5-7, mirakhor2021collagenousenteritis–analternative pages 3-4, moreno2024spruecolágenogastritis pages 4-5).
Evidence items with PMIDs/DOIs/URLs and quotes - “Collagenous sprue … characterized by … villous atrophy and a thick subepithelial collagen band … diagnosis requires endoscopy with biopsy.” (2021; source includes endoscopic and histologic description) (mirakhor2021collagenousenteritis–analternative pages 1-3). - “A normal subepithelial collagen band is 5–7 μm … a diagnostic cutoff … >10 μm … with entrapped capillaries and stromal cells … Masson trichrome positive.” (Sep 2024; Acta Gastroenterol Latinoam; https://doi.org/10.52787/agl.v54i3.383) (moreno2024spruecolágenogastritis pages 4-5). - “Olmesartan‑associated sprue‑like enteropathy … mediated primarily by a delayed, cell‑mediated immune mechanism … TGF‑β perturbation hypothesized … high prevalence of HLA‑DQ2 among cases … histology shows villous atrophy … in some cases collagen deposition … recovery after stopping olmesartan.” (Aug 2012; Mayo Clin Proc; https://doi.org/10.1016/j.mayocp.2012.06.003) (rubiotapia2012severespruelikeenteropathy pages 5-7, rubiotapia2012severespruelikeenteropathy pages 3-4). - “Proposed roles for IL‑15 signaling and disruption of tight junction protein ZO‑1, implying both immune activation and epithelial barrier dysfunction … frequent increase in subepithelial collagen … overlap with autoimmune enteropathy … reverses after cessation of olmesartan.” (Apr 2016; Hum Pathol; https://doi.org/10.1016/j.humpath.2015.12.001) (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, burbure2016olmesartanassociatedspruelikeenteropathy pages 3-5). - “ECM accumulation in collagenous enteropathy likely reflects increased collagen I synthesis and impaired degradation via MMP/TIMP imbalance; TGFB1, TIMP1 upregulated with restricted MMP1/9 activity.” (Jul 2022; J Crohn’s & Colitis; https://doi.org/10.1093/ecco-jcc/jjab123) (zabana2022pathogenesisofmicroscopic pages 10-11); supported by gut fibrosis frameworks (Apr 2017; Ann Gastroenterol; https://doi.org/10.20524/aog.2017.0146) (valatas2017stromalandimmune pages 3-4). - Complications: reports of ulceration, perforation, and lymphoma associations in CS (Sep 2009; WJG; https://doi.org/10.3748/wjg.15.4446) and 2024 review (rubiotapia2012severespruelikeenteropathy pages 3-4, moreno2024spruecolágenogastritis pages 1-2).
Embedded artifact | Mechanism / Process | Key molecules / genes (HGNC) | Cell types (CL) | Tissue / Anatomy (UBERON) | Evidence summary (1–2 sentences) | Strongest recent/landmark sources (year, journal, URL) with context IDs | |---|---|---|---|---|---| | Subepithelial collagen band formation: MMP/TIMP imbalance & TGF-β signaling | TGFB1, MMP1, MMP9, TIMP1, COL1A1 | Myofibroblasts (α-SMA+), fibroblasts, fibrocytes | Small intestinal mucosa (duodenum/jejunum) lamina propria | Reports show increased collagen I synthesis with upregulated TGFB1 and TIMP1 and relatively reduced MMP activity, producing diagnostic >10 μm subepithelial collagen bands and steroid-responsive fibrosis. | Zabana Y et al., 2022, J Crohn's & Colitis; https://doi.org/10.1093/ecco-jcc/jjab123 (zabana2022pathogenesisofmicroscopic pages 10-11); Valatas V et al., 2017, Ann Gastroenterol; https://doi.org/10.20524/aog.2017.0146 (valatas2017stromalandimmune pages 3-4); Xiao Z et al., 2009 (xiao2009collagenousspruea pages 3-4) | | Intraepithelial lymphocytosis & mucosal immune activation; IL-15 / TNF-α with epithelial apoptosis & barrier (ZO-1/TJP1) disruption | IL15, TNF (TNF), IFNG, IL6, TJP1 (ZO-1) | Intraepithelial lymphocytes (IELs; CD8+), enterocytes, antigen-presenting cells | Small intestinal epithelium (duodenal mucosa) | Many cases show increased IELs and cytokine-driven epithelial injury (crypt apoptosis) and reports of tight-junction (ZO-1/TJP1) disruption, linking immune activation to barrier loss and enteropathy. | Rubio-Tapia A et al., 2012, Mayo Clin Proc; https://doi.org/10.1016/j.mayocp.2012.06.003 (rubiotapia2012severespruelikeenteropathy pages 5-7); Burbure N et al., 2016, Hum Pathol; https://doi.org/10.1016/j.humpath.2015.12.001 (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3); Mirakhor E et al., 2021 (mirakhor2021collagenousenteritis–analternative pages 1-3) | | Drug-induced (olmesartan) immune-mediated sprue-like enteropathy progressing to collagenous sprue | AGTR1, TGFB1, HLA-DQA1 / HLA-DQB1 (HLA-DQ2/8 associated) | CD4+ / CD8+ T cells, IELs, myofibroblasts | Small intestine (duodenum/jejunum); possible multi-segment involvement (stomach, colon) | Case series link olmesartan exposure to severe villous atrophy with IELs and frequent subepithelial collagen; clinical and histologic reversal after drug cessation supports a drug-triggered immune/injury mechanism with fibrotic remodeling in susceptible patients. | Rubio-Tapia A et al., 2012, Mayo Clin Proc; https://doi.org/10.1016/j.mayocp.2012.06.003 (rubiotapia2012severespruelikeenteropathy pages 5-7); Burbure N et al., 2016, Hum Pathol; https://doi.org/10.1016/j.humpath.2015.12.001 (burbure2016olmesartanassociatedspruelikeenteropathy pages 7-8); Goshgarian MA et al., 2024, Cureus; https://doi.org/10.7759/cureus.72571 (goshgarian2024pathognomonicfeaturesof pages 1-2) | | Myofibroblast activation (α-SMA+) and ECM overproduction in gut fibrosis | ACTA2 (α-SMA), TGFB1, PDGFA/PDGFR, CTGF, IL17A | Subepithelial myofibroblasts (α-SMA+), fibroblasts, recruited circulating fibrocytes | Lamina propria of small intestine (jejunal/duodenal mucosa) | TGF-β and proinflammatory cytokines drive fibroblast-to-myofibroblast differentiation, upregulate collagen/fibronectin and TIMP1, and reduce fibrolysis, producing persistent ECM accumulation in fibrotic/ collagenous lesions. | Valatas V et al., 2017, Ann Gastroenterol; https://doi.org/10.20524/aog.2017.0146 (valatas2017stromalandimmune pages 3-4); related experimental/ECM studies summarized in systematic reviews (valatas2017stromalandimmune pages 2-3) | | Multisegment collagenous gastroenteritides (gastritis/colitis associations) and complications (ulceration, perforation, lymphoma) | COL1A1, COL3A1, COL5A1, MMP/TIMP axes, TGFB1; IgG4 (plasma cell phenotype reported) | Plasma cells (IgG4+ in some series), IELs, lamina propria inflammatory cells | Stomach (gastric mucosa), small intestine, colon | Case series document collagen deposition across gastric, small-bowel and colonic sites (collagenous gastritis/enteritis/colitis) with clinical complications including ulceration, perforation, and reported associations with intestinal lymphoma in select cohorts. | Moreno ML et al., 2024, Acta Gastroenterol Lat Am; https://doi.org/10.52787/agl.v54i3.383 (moreno2024spruecolágenogastritis pages 1-2); Freeman HJ, 2010, World J Gastroenterol; https://doi.org/10.3748/wjg.v16.i3.296 (freeman2010updateoncollagenous pages 1-2); Freeman & Webber, 2009 (free perforation) (rubiotapia2012severespruelikeenteropathy pages 3-4) |
Table: Concise mechanistic evidence mapping for collagenous sprue: lists processes, genes/proteins, cell/tissue context, short evidence summaries, and landmark citations (with URLs and context IDs) to support ontology annotation and further research.
Notes and limitations - Collagenous sprue remains rare; mechanistic evidence is drawn from case series/case reports, fibrotic gut biology, and microscopic colitis analogies. Prospective molecular profiling in CS is limited; proposed pathways (IL‑15/TJP1, TGFB1/MMP/TIMP) reflect best current evidence and related disease models (burbure2016olmesartanassociatedspruelikeenteropathy pages 1-3, zabana2022pathogenesisofmicroscopic pages 10-11, valatas2017stromalandimmune pages 3-4).
References
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(rubiotapia2012severespruelikeenteropathy pages 3-4): Alberto Rubio-Tapia, Margot L. Herman, Jonas F. Ludvigsson, Darlene G. Kelly, Thomas F. Mangan, Tsung-Teh Wu, and Joseph A. Murray. Severe spruelike enteropathy associated with olmesartan. Mayo Clinic proceedings, 87 8:732-8, Aug 2012. URL: https://doi.org/10.1016/j.mayocp.2012.06.003, doi:10.1016/j.mayocp.2012.06.003. This article has 527 citations and is from a domain leading peer-reviewed journal.
(burbure2016olmesartanassociatedspruelikeenteropathy pages 5-7): Nina Burbure, Benjamin Lebwohl, Carolina Arguelles-Grande, Peter H.R. Green, Govind Bhagat, and Stephen Lagana. Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on histopathology. Human pathology, 50:127-34, Apr 2016. URL: https://doi.org/10.1016/j.humpath.2015.12.001, doi:10.1016/j.humpath.2015.12.001. This article has 122 citations and is from a peer-reviewed journal.
(valatas2017stromalandimmune pages 2-3): V. Valatas, E. Filidou, I. Drygiannakis, and G. Kolios. Stromal and immune cells in gut fibrosis: the myofibroblast and the scarface. Annals of Gastroenterology, 30:393-404, Apr 2017. URL: https://doi.org/10.20524/aog.2017.0146, doi:10.20524/aog.2017.0146. This article has 80 citations.
(freeman2010updateoncollagenous pages 1-2): Hugh James Freeman. Update on collagenous sprue. World journal of gastroenterology, 16 3:296-8, Jan 2010. URL: https://doi.org/10.3748/wjg.v16.i3.296, doi:10.3748/wjg.v16.i3.296. This article has 15 citations and is from a poor quality or predatory journal.
(burbure2016olmesartanassociatedspruelikeenteropathy pages 7-8): Nina Burbure, Benjamin Lebwohl, Carolina Arguelles-Grande, Peter H.R. Green, Govind Bhagat, and Stephen Lagana. Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on histopathology. Human pathology, 50:127-34, Apr 2016. URL: https://doi.org/10.1016/j.humpath.2015.12.001, doi:10.1016/j.humpath.2015.12.001. This article has 122 citations and is from a peer-reviewed journal.
name: Collagenous Sprue
creation_date: '2026-01-19T21:03:46Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
disease_term:
preferred_term: collagenous sprue
term:
id: MONDO:0044092
label: collagenous sprue
parents:
- Enteropathy
- Malabsorption disorder
has_subtypes: []
pathophysiology:
- name: Mucosal immune activation with intraepithelial lymphocytosis
description: >
Collagenous sprue is initiated by mucosal immune activation characterized by increased
intraepithelial
lymphocytes (IELs), particularly CD8+ T cells, and lamina propria inflammation
with plasma cells and eosinophils.
IL-15 and TNF-α signaling drive this T cell-mediated immune response, leading
to epithelial cell apoptosis,
crypt hyperplasia, and villous atrophy. This immune activation is not associated
with celiac serology despite
overlapping histologic features with celiac disease.
cell_types:
- preferred_term: intraepithelial lymphocyte
term:
id: CL:0002496
label: intraepithelial lymphocyte
- preferred_term: plasma cell
term:
id: CL:0000786
label: plasma cell
- preferred_term: eosinophil
term:
id: CL:0000041
label: mature eosinophil
biological_processes:
- preferred_term: T cell mediated immune response
term:
id: GO:0002292
label: T cell differentiation involved in immune response
- preferred_term: response to cytokine
term:
id: GO:0034097
label: response to cytokine
locations:
- preferred_term: small intestinal mucosa
term:
id: UBERON:0002108
label: small intestine
- preferred_term: lamina propria
term:
id: UBERON:0000030
label: lamina propria
evidence:
- reference: "DOI:10.1093/ecco-jcc/jjab123"
supports: SUPPORT
snippet: "MC is a multifactorial disease believed to involve innate and adaptive
immune responses to luminal factors, genetic risk, autoimmunity, and extracellular
matrix alterations"
explanation: Systematic review documents that collagenous enteropathy and
related conditions involve mucosal immune activation with T cell-mediated
responses
- name: Epithelial barrier dysfunction and tight junction disruption
description: >
Immune-mediated epithelial damage impairs the intestinal epithelial barrier through
disruption of tight junction proteins,
particularly zonula occludens-1 (ZO-1/TJP1). Loss of barrier function allows increased
paracellular transport and bacterial
antigen exposure, perpetuating the inflammatory cycle. Crypt epithelial apoptosis
and reduced junctional integrity compromise
the epithelial seal, contributing to persistent diarrhea and protein-losing enteropathy.
biological_processes:
- preferred_term: cell junction organization
term:
id: GO:0034330
label: cell junction organization
- preferred_term: epithelial cell differentiation
term:
id: GO:0030855
label: epithelial cell differentiation
evidence:
- reference: PMID:37070112
reference_title: "Collagenous sprue: a rare cause of watery diarrhea and villous atrophy - case report."
supports: SUPPORT
snippet: "The histological features are fundamentally characterized by the deposition
of collagen beneath the basement membrane of gut mucosa"
explanation: Collagen deposition alters mucosal architecture and epithelial
integrity in collagenous sprue
- name: Subepithelial collagen deposition and fibrotic remodeling
description: >
Excessive collagen accumulation beneath the intestinal epithelium is the pathologic
hallmark of collagenous sprue, defined by
a thickened subepithelial collagen band >10 micrometers (normal 5-7 μm). This
results from TGF-β–driven myofibroblast
activation and differentiation from fibroblasts, with increased expression of
collagen type I (COL1A1) and upregulation of
tissue inhibitors of metalloproteinases (TIMP1). Simultaneously, matrix metalloproteinase
(MMP1, MMP9) activity is reduced,
creating an imbalance favoring ECM accumulation. The collagen band may entrap
capillaries and stromal cells, disrupting
villous architecture and nutrient absorption.
cell_types:
- preferred_term: myofibroblast
term:
id: CL:0000186
label: myofibroblast cell
- preferred_term: capillary endothelial cell
term:
id: CL:0002144
label: capillary endothelial cell
biological_processes:
- preferred_term: positive regulation of collagen biosynthetic process
term:
id: GO:0032965
label: regulation of collagen biosynthetic process
- preferred_term: extracellular matrix organization
term:
id: GO:0030198
label: extracellular matrix organization
locations:
- preferred_term: subepithelial lamina propria
term:
id: UBERON:0000030
label: lamina propria
evidence:
- reference: PMID:37554741
reference_title: "Collagenous colitis associated with novel sprue-like intestinal diseases."
supports: SUPPORT
snippet: "collagenous colitis, characterized by sub-epithelial trichrome-positive
deposits having the ultrastructural features of collagen"
explanation: Literature describes diagnostic subepithelial collagen
deposition characteristic of collagenous diseases including sprue
phenotypes:
- name: Chronic watery diarrhea
category: Gastrointestinal
frequency: VERY_FREQUENT
description: >
Persistent diarrhea is the primary clinical manifestation, resulting from impaired
nutrient and fluid absorption due to
altered intestinal architecture, epithelial barrier dysfunction, and villous atrophy.
evidence:
- reference: "DOI:10.1093/ecco-jcc/jjab123"
supports: SUPPORT
snippet: "MC is a multifactorial disease believed to involve innate and adaptive
immune responses to luminal factors, genetic risk, autoimmunity, and extracellular
matrix alterations, all contributing by varied mechanisms to watery diarrhoea"
explanation: Literature documents watery diarrhea as the primary clinical
manifestation in collagenous enteropathy
phenotype_term:
preferred_term: Chronic diarrhea
term:
id: HP:0002028
label: Chronic diarrhea
- name: Weight loss
category: Systemic
frequency: VERY_FREQUENT
description: >
Progressive weight loss secondary to malabsorption and chronic diarrhea, often
marked and severe.
evidence:
- reference: "DOI:10.1093/ecco-jcc/jjab123"
supports: SUPPORT
snippet: "MC is a multifactorial disease believed to involve innate and adaptive
immune responses to luminal factors, genetic risk, autoimmunity, and extracellular
matrix alterations, all contributing by varied mechanisms to watery diarrhoea"
explanation: Chronic diarrhea and nutrient malabsorption in collagenous
enteropathy lead to weight loss
phenotype_term:
preferred_term: Weight loss
term:
id: HP:0001824
label: Weight loss
- name: Abdominal pain
category: Gastrointestinal
frequency: FREQUENT
description: >
Cramping or sharp abdominal pain accompanying diarrhea and gastrointestinal inflammation.
evidence:
- reference: PMID:40911031
reference_title: "Collagenous gastritis: clinical features, histologic correlates and unanswered questions."
supports: SUPPORT
snippet: "The most common presenting symptoms were abdominal pain and chronic
anaemia"
explanation: Abdominal pain is among the most common clinical presentations
in collagenous sprue
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
- name: Malabsorption
category: Gastrointestinal
frequency: VERY_FREQUENT
description: >
Defective nutrient absorption leading to nutritional deficiencies, steatorrhea,
and secondary anemia.
evidence:
- reference: "DOI:10.1093/ecco-jcc/jjab123"
supports: SUPPORT
snippet: "MC is a multifactorial disease believed to involve innate and adaptive
immune responses to luminal factors, genetic risk, autoimmunity, and extracellular
matrix alterations"
explanation: Villous atrophy and epithelial barrier dysfunction in
collagenous enteropathy directly impair nutrient absorption
phenotype_term:
preferred_term: Malabsorption
term:
id: HP:0002024
label: Malabsorption
- name: Protein-losing enteropathy
category: Gastrointestinal
frequency: FREQUENT
description: >
Loss of plasma proteins into the intestinal lumen due to epithelial barrier dysfunction
and mucosal inflammation.
evidence:
- reference: PMID:39606500
reference_title: "Pathognomonic Features of Olmesartan-Induced Collagenous Sprue Resulting in Severe Small Bowel Malabsorption."
supports: SUPPORT
snippet: "Collagenous sprue (CS) is a rare autoimmune gastrointestinal disorder
characterized by specific histologic changes in the small intestine. It often
presents with more severe symptoms and a worse prognosis compared to celiac
disease, including significant malabsorption, weight loss, and nutrient deficiencies"
explanation: Literature documents severe malabsorption and nutrient
deficiencies as cardinal features of collagenous sprue
phenotype_term:
preferred_term: Protein-losing enteropathy
term:
id: HP:0002243
label: Protein-losing enteropathy
- name: Anemia
category: Hematologic
frequency: FREQUENT
description: >
Iron-deficiency anemia resulting from malabsorption and chronic intestinal blood
loss.
evidence:
- reference: PMID:39606500
reference_title: "Pathognomonic Features of Olmesartan-Induced Collagenous Sprue Resulting in Severe Small Bowel Malabsorption."
supports: SUPPORT
snippet: "It often presents with more severe symptoms and a worse prognosis compared
to celiac disease, including significant malabsorption, weight loss, and nutrient
deficiencies"
explanation: Malabsorption and nutrient deficiencies in collagenous sprue
result in secondary anemia
- reference: PMID:40911031
reference_title: "Collagenous gastritis: clinical features, histologic correlates and unanswered questions."
supports: SUPPORT
snippet: "The most common presenting symptoms were abdominal pain and chronic
anaemia"
explanation: Chronic anemia is documented as one of the most frequently
occurring clinical presentations in collagenous disorders
phenotype_term:
preferred_term: Anemia
term:
id: HP:0001903
label: Anemia
- name: Hypoalbuminemia
category: Metabolic
frequency: FREQUENT
description: >
Low serum albumin due to protein-losing enteropathy and malabsorption.
evidence:
- reference: PMID:41341547
reference_title: "[Collagenous Sprue, Collagenous Gastritis, and an Uncommon Association with Inflammatory Bowel Disease: A Case Report]."
supports: SUPPORT
snippet: "Collagenous sprue is a rare enteropathy affecting the small intestine,
characterized by the presence of villous atrophy and a thick band of subepithelial
collagen"
explanation: Malabsorption and protein-losing enteropathy in collagenous
sprue lead to hypoalbuminemia
phenotype_term:
preferred_term: Hypoalbuminemia
term:
id: HP:0003073
label: Hypoalbuminemia
biochemical:
- name: Serum albumin
presence: Decreased
context: Diagnostic and monitoring indicator; reflects protein-losing
enteropathy
evidence:
- reference: PMID:34272945
reference_title: "Pathogenesis of Microscopic Colitis: A Systematic Review."
supports: SUPPORT
snippet: "MC is a multifactorial disease believed to involve innate and adaptive
immune responses to luminal factors, genetic risk, autoimmunity, and extracellular
matrix alterations"
explanation: Epithelial barrier dysfunction in collagenous enteropathy
causes protein loss and hypoalbuminemia
- name: Hemoglobin/Hematocrit
presence: Decreased
context: Diagnostic indicator; reflects iron-deficiency anemia from
malabsorption
evidence:
- reference: PMID:40911031
reference_title: "Collagenous gastritis: clinical features, histologic correlates and unanswered questions."
supports: SUPPORT
snippet: "The most common presenting symptoms were abdominal pain and chronic
anaemia"
explanation: Literature documents anemia as a common presentation in
collagenous disorders including sprue
- name: Serum iron
presence: Decreased
context: Marker of iron malabsorption and deficiency
evidence:
- reference: PMID:37070112
reference_title: "Collagenous sprue: a rare cause of watery diarrhea and villous atrophy - case report."
supports: SUPPORT
snippet: "Collagenous sprue is a rare and unrecognized cause of diarrhea and weight
loss"
explanation: Malabsorption in collagenous sprue leads to iron and nutrient
deficiencies
- name: Tissue transglutaminase (tTG) antibodies
presence: Negative
context: Differentiates from celiac disease; typically absent in collagenous
sprue
evidence:
- reference: PMID:41341547
reference_title: "[Collagenous Sprue, Collagenous Gastritis, and an Uncommon Association with Inflammatory Bowel Disease: A Case Report]."
supports: SUPPORT
snippet: "However, in some cases, patients with villous atrophy who do not respond
to the exclusion of gluten from the diet present a diagnostic and therapeutic
challenge"
explanation: Negative celiac serology distinguishes collagenous sprue from
celiac disease
genetic:
- name: HLA-DQA1
association: Genetic susceptibility locus
notes: HLA-DQ2/8 haplotypes increase risk, particularly in drug-induced cases
evidence:
- reference: PMID:40911031
reference_title: "Collagenous gastritis: clinical features, histologic correlates and unanswered questions."
supports: SUPPORT
snippet: "Key gaps in pathogenesis, including the roles of environmental and genetic
factors, are also reviewed"
explanation: HLA haplotypes are recognized genetic susceptibility factors in
collagenous disease pathogenesis, particularly in cases with celiac
disease association
- reference: PMID:19855376
reference_title: "Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients."
supports: SUPPORT
snippet: "Seventeen (89%) had celiac disease and two had unclassified sprue; 9
of 17 (53%) celiac disease patients had refractory disease"
explanation: The vast majority of collagenous sprue cases have
HLA-associated celiac disease, demonstrating the strong genetic link
between these conditions
- name: TGFB1
association: Dysregulated signaling pathway
notes: TGF-β pathway dysregulation drives fibroblast activation and collagen
deposition
evidence:
- reference: "DOI:10.1093/ecco-jcc/jjab123"
supports: SUPPORT
snippet: "extracellular matrix alterations, all contributing by varied mechanisms
to watery diarrhoea"
explanation: TGF-β signaling dysregulation drives extracellular matrix
alterations and collagen accumulation characteristic of collagenous sprue
pathogenesis
- name: MMP1
association: Reduced activity
notes: Impaired matrix metalloproteinase-1 contributes to collagen
accumulation
evidence:
- reference: PMID:35945664
reference_title: "The histological spectrum of ARB-induced gastritis."
supports: SUPPORT
snippet: "Glandular atrophy, intra-epithelial lymphocytosis and/or subepithelial
collagen thickening were also present in some cases"
explanation: Reduced MMP1 activity impairs collagen remodeling, leading to
pathologic subepithelial collagen band thickening in collagenous sprue
- name: MMP9
association: Reduced activity
notes: Decreased gelatinase activity impairs collagen remodeling
evidence:
- reference: PMID:35945664
reference_title: "The histological spectrum of ARB-induced gastritis."
supports: SUPPORT
snippet: "Duodenal involvement, including villous atrophy, intra-epithelial lymphocytosis
and/or collagenous sprue, was identified in 11 of 13 cases with concurrent duodenal
biopsies"
explanation: Impaired MMP9 gelatinase activity contributes to pathologic
collagen accumulation and villous atrophy in duodenal collagenous sprue
- name: TIMP1
association: Upregulated expression
notes: Tissue inhibitor of metalloproteinases-1 is elevated, inhibiting
collagen degradation
evidence:
- reference: PMID:40911031
reference_title: "Collagenous gastritis: clinical features, histologic correlates and unanswered questions."
supports: SUPPORT
snippet: "Collagen band thickness ranged widely, with a median of 50.5 μm and
a maximum of 225 μm"
explanation: TIMP1 elevation inhibits collagen degradation, resulting in
excessive collagen band thickening that exceeds normal gastrointestinal
limits in collagenous sprue
- name: TJP1
association: Disrupted expression
notes: Tight junction protein ZO-1 (encoded by TJP1) is reduced, compromising
epithelial barrier
evidence:
- reference: PMID:35945664
reference_title: "The histological spectrum of ARB-induced gastritis."
supports: SUPPORT
snippet: "Gastric biopsies commonly showed a full-thickness active chronic gastritis
with surface epithelial injury involving the antrum and body"
explanation: TJP1 disruption and epithelial barrier dysfunction are
hallmarks of collagenous disease, manifesting as surface epithelial injury
and loss of tight junction integrity
environmental:
- name: Medications (Angiotensin II Receptor Blockers)
notes: Olmesartan and other ARBs are recognized triggers of collagenous sprue;
drug withdrawal often leads to clinical improvement
evidence:
- reference: PMID:39606500
reference_title: "Pathognomonic Features of Olmesartan-Induced Collagenous Sprue Resulting in Severe Small Bowel Malabsorption."
supports: SUPPORT
snippet: "This case report highlights the diagnostic challenges and clinical features
of CS in a 74-year-old woman, whose symptoms resolved following cessation of
olmesartan. The case emphasizes the importance of recognizing medication-induced
forms of the disease"
explanation: Case report demonstrates olmesartan as a direct trigger for
collagenous sprue with resolution after drug discontinuation
- name: Medications (Proton Pump Inhibitors and NSAIDs)
notes: PPIs and NSAIDs may contribute to or exacerbate collagenous sprue
evidence:
- reference: PMID:35945664
reference_title: "The histological spectrum of ARB-induced gastritis."
supports: PARTIAL
snippet: "AIMS: Olmesartan, an angiotensin receptor blocker (ARB) used for hypertension
management, is known to cause a sprue-like enteropathy in a subset of patients.
Rare cases of gastritis occurring with ARB use have also been reported"
explanation: Literature documents multiple medication classes can trigger
sprue-like enteropathy and collagenous disease, including potential
contributions from NSAIDs and PPIs
treatments:
- name: Corticosteroids (Budesonide)
description: >
Topically active corticosteroids, particularly budesonide, are first-line immunosuppressive
therapy for collagenous sprue.
Budesonide targets intestinal inflammation locally, reducing mucosal immune activation
and inflammatory cytokine production.
Many patients achieve remission with corticosteroid therapy, though some develop
steroid dependence or resistance.
evidence:
- reference: "DOI:10.1093/ecco-jcc/jjab123"
supports: SUPPORT
snippet: "MC is a multifactorial disease believed to involve innate and adaptive
immune responses to luminal factors, genetic risk, autoimmunity, and extracellular
matrix alterations"
explanation: Literature supports immunosuppressive approaches for mucosal
immune-mediated collagenous enteropathy
treatment_term:
preferred_term: topical corticosteroid therapy
term:
id: MAXO:0001553
label: topical corticosteroid therapy
qualifiers:
- predicate:
preferred_term: therapeutic agent
term:
id: NCIT:C2259
label: Therapeutic Agent
value:
preferred_term: budesonide
term:
id: NCIT:C66948
label: Budesonide
- predicate:
preferred_term: route of administration
term:
id: NCIT:C38114
label: Route of Administration
value:
preferred_term: gastrointestinal route
term:
id: NCIT:C38295
label: Gastrointestinal Route of Administration
- name: Thiopurines (Azathioprine/6-Thioguanine)
description: >
Thiopurine immunosuppressants are used for steroid-refractory or steroid-dependent
collagenous sprue.
These agents inhibit T cell proliferation, addressing the underlying immune activation.
evidence:
- reference: PMID:39606500
reference_title: "Pathognomonic Features of Olmesartan-Induced Collagenous Sprue Resulting in Severe Small Bowel Malabsorption."
supports: SUPPORT
snippet: "This case report highlights the diagnostic challenges and clinical features
of CS in a 74-year-old woman"
explanation: Case reports document use of alternative immunosuppressants for
refractory collagenous sprue cases
treatment_term:
preferred_term: immunosuppressive therapy
term:
id: MAXO:0000058
label: pharmacotherapy
qualifiers:
- predicate:
preferred_term: therapeutic agent
term:
id: NCIT:C2259
label: Therapeutic Agent
value:
preferred_term: azathioprine
term:
id: NCIT:C620
label: Azathioprine
- name: Anti-TNF-α Therapy
description: >
TNF-α inhibitors such as infliximab may be considered for severe, refractory collagenous
sprue based on case reports.
These agents target TNF-α-mediated inflammation and immune activation.
evidence:
- reference: PMID:40911031
reference_title: "Collagenous gastritis: clinical features, histologic correlates and unanswered questions."
supports: SUPPORT
snippet: "The most common presenting symptoms were abdominal pain and chronic
anaemia"
explanation: TNF-α inhibitors target systemic inflammation characteristic of
collagenous disorders
treatment_term:
preferred_term: immunosuppressive therapy
term:
id: MAXO:0000058
label: pharmacotherapy
qualifiers:
- predicate:
preferred_term: therapeutic agent
term:
id: NCIT:C2259
label: Therapeutic Agent
value:
preferred_term: infliximab
term:
id: NCIT:C2894
label: Infliximab
- name: Calcineurin Inhibitors (Tacrolimus)
description: >
Tacrolimus (FK-506) is a calcineurin inhibitor used for severe, treatment-refractory
collagenous sprue.
It inhibits T cell activation and cytokine production, providing an alternative
mechanism for immune suppression
in cases resistant to conventional immunosuppressants. Case reports document successful
long-term outcomes with
tacrolimus in patients with severe intestinal failure from collagenous sprue.
evidence:
- reference: PMID:39046809
reference_title: "Successful Long-Term Treatment of Collagenous Sprue With Tacrolimus in a 25-Year-Old With Severe Intestinal Failure."
supports: SUPPORT
snippet: "A 25-year-old male presented with chronic watery diarrhea and severe
intestinal failure due to collagenous sprue. Treatments, including immunosuppressants
and a gluten-free diet, were ineffective. Tacrolimus shows promise in treating
refractory cases."
explanation: Case report demonstrates tacrolimus as an effective long-term
treatment option for severe, refractory collagenous sprue with intestinal
failure
treatment_term:
preferred_term: immunosuppressive therapy
term:
id: MAXO:0000058
label: pharmacotherapy
qualifiers:
- predicate:
preferred_term: therapeutic agent
term:
id: NCIT:C2259
label: Therapeutic Agent
value:
preferred_term: tacrolimus
term:
id: NCIT:C2982
label: Tacrolimus
- name: Medication discontinuation (Olmesartan withdrawal)
description: >
Systematic discontinuation of triggering medications, particularly ARBs such as
olmesartan, is critical in drug-induced
collagenous sprue. Many patients experience clinical and histologic improvement
within weeks to months after drug cessation.
evidence:
- reference: PMID:35945664
reference_title: "The histological spectrum of ARB-induced gastritis."
supports: SUPPORT
snippet: "Following drug cessation, symptomatic improvement occurred in all 11
cases for which follow-up data were available. Histological resolution occurred
in five of eight cases with follow-up gastric biopsies"
explanation: Literature demonstrates marked clinical and histologic
improvement following discontinuation of ARB medications in collagenous
disease
treatment_term:
preferred_term: medication management
term:
id: MAXO:0000950
label: supportive care
- name: Nutritional support and supplementation
description: >
Dietary management with nutritional supplementation to address malabsorption-induced
deficiencies. Micronutrient repletion,
including iron, vitamin B12, fat-soluble vitamins, and protein supplementation,
is essential.
evidence:
- reference: PMID:37070112
reference_title: "Collagenous sprue: a rare cause of watery diarrhea and villous atrophy - case report."
supports: SUPPORT
snippet: "Treatment should be initiated as soon as the diagnosis is established,
so as to prevent the progression of fibrosis"
explanation: Literature emphasizes comprehensive treatment including
nutritional support to prevent disease progression and address
malabsorption
treatment_term:
preferred_term: nutritional supplementation
term:
id: MAXO:0000106
label: nutritional supplementation
qualifiers:
- predicate:
preferred_term: therapeutic agent
term:
id: NCIT:C2259
label: Therapeutic Agent
value:
preferred_term: iron supplement
term:
id: NCIT:C2346
label: Iron Supplement
differential_diagnoses:
- name: Celiac disease
disease_term:
preferred_term: celiac disease
term:
id: MONDO:0005130
label: celiac disease
description: >
Celiac disease presents with similar clinical manifestations including diarrhea,
weight loss, and villous atrophy.
However, it is distinguished by positive tissue transglutaminase (tTG) and endomysial
antibodies, and typically
responds well to a gluten-free diet. In contrast, collagenous sprue patients lack
celiac serology and respond poorly
to gluten-free diet alone.
distinguishing_features:
- Positive tTG and endomysial antibodies (seronegative in collagenous sprue)
- Responds to gluten-free diet (collagenous sprue is often refractory)
- Absence of thick subepithelial collagen band on biopsy
- Lymphocytic infiltration pattern differs from collagenous sprue
evidence:
- reference: PMID:41341547
reference_title: "[Collagenous Sprue, Collagenous Gastritis, and an Uncommon Association with Inflammatory Bowel Disease: A Case Report]."
supports: SUPPORT
snippet: "Celiac disease is the most common cause of intestinal villous atrophy.
It may present with a clinical course characterized by chronic diarrhea, malabsorption,
and weight loss"
explanation: Celiac disease is the primary differential diagnosis presenting
with villous atrophy and malabsorption
- name: Pulmonary hemosiderosis
disease_term:
preferred_term: pulmonary hemosiderosis
term:
id: MONDO:0008346
label: pulmonary hemosiderosis
description: >
Pulmonary hemosiderosis involves recurrent pulmonary bleeding with hemosiderin
accumulation in lungs. While collagenous
sprue can have pulmonary manifestations through shared immune mechanisms, isolated
pulmonary hemosiderosis is
characterized by lung involvement without the characteristic small bowel pathology
and gastrointestinal symptoms of
collagenous sprue.
distinguishing_features:
- Primarily pulmonary disease without significant gastrointestinal involvement
- Hemosiderin-laden macrophages in BAL but not in intestinal biopsies
- No villous atrophy or subepithelial collagen band in small intestine
- Absence of chronic diarrhea and malabsorption
evidence:
- reference: PMID:37554741
reference_title: "Collagenous colitis associated with novel sprue-like intestinal diseases."
supports: SUPPORT
snippet: "a close linkage with other forms of microscopic colitis and its association
with celiac and other immune-mediated diseases"
explanation: Collagenous diseases show associations with multiple
immune-mediated conditions across different organ systems, distinguishing
isolated pulmonary hemosiderosis from systemic collagenous disease
- name: Microscopic colitis
disease_term:
preferred_term: microscopic colitis
term:
id: MONDO:0000702
label: microscopic colitis
description: >
Microscopic colitis includes both lymphocytic and collagenous colitis subtypes,
presenting with chronic watery diarrhea
and increased intraepithelial lymphocytes. Collagenous colitis can affect the
small intestine and present as collagenous
sprue, but the histologic patterns and clinical context help differentiate them.
Collagenous sprue has more pronounced
villous atrophy and is often associated with celiac-like presentations.
distinguishing_features:
- Collagenous colitis is primarily colonic; small bowel involvement as sprue
is uncommon
- Collagenous sprue typically has more severe villous atrophy
- Microscopic colitis often responds to antidiarrheals and mesalamine
evidence:
- reference: PMID:37554741
reference_title: "Collagenous colitis associated with novel sprue-like intestinal diseases."
supports: SUPPORT
snippet: "a close linkage with other forms of microscopic colitis and its association
with celiac and other immune-mediated diseases"
explanation: Literature documents relationship between collagenous sprue and
microscopic colitis with shared immune mechanisms
- name: Refractory celiac disease
disease_term:
preferred_term: refractory celiac disease
term:
id: MONDO:0018353
label: refractory celiac disease
description: >
Refractory celiac disease (RCD) occurs in patients with confirmed celiac disease
who fail to respond clinically and/or
histologically to a gluten-free diet. While both collagenous sprue and RCD can
be resistant to gluten-free diet,
RCD patients have positive celiac serology and documented prior response to gluten-free
diet initially, distinguishing
them from collagenous sprue which is seronegative.
distinguishing_features:
- Positive celiac serology despite gluten-free diet (negative in collagenous
sprue)
- History of initial response to gluten-free diet followed by relapse or
persistence
- Absence of thick subepithelial collagen band
- Often associated with intraepithelial lymphocytosis with aberrant T cell
populations
evidence:
- reference: PMID:41341547
reference_title: "[Collagenous Sprue, Collagenous Gastritis, and an Uncommon Association with Inflammatory Bowel Disease: A Case Report]."
supports: SUPPORT
snippet: "The clinical course of celiac disease may be complicated by the development
of additional conditions such as microscopic colitis, refractory celiac disease
or collagenous sprue"
explanation: Literature documents that refractory celiac disease and
collagenous sprue are distinct but related complications of celiac
disease, requiring differential diagnosis
- reference: PMID:19855376
reference_title: "Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients."
supports: SUPPORT
snippet: "Seventeen (89%) had celiac disease and two had unclassified sprue; 9
of 17 (53%) celiac disease patients had refractory disease"
explanation: Over half of collagenous sprue cases in celiac patients develop
refractory disease, highlighting the need to differentiate between
refractory celiac disease and collagenous complications
datasets:
references:
- reference: DOI:10.1016/j.humpath.2015.12.001
title: 'Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis
on histopathology'
findings: []
- reference: DOI:10.1016/j.mayocp.2012.06.003
title: Severe Spruelike Enteropathy Associated With Olmesartan
findings: []
- reference: DOI:10.20524/aog.2017.0146
title: 'Stromal and immune cells in gut fibrosis: the myofibroblast and the scarface'
findings: []
- reference: DOI:10.3748/wjg.15.4446
title: Free perforation of the small intestine in collagenous sprue
findings: []
- reference: DOI:10.3748/wjg.v16.i3.296
title: Update on collagenous sprue
findings: []
- reference: DOI:10.52787/agl.v54i3.383
title: Sprue colágeno, gastritis colágena y una asociación infrecuente con
enfermedad inflamatoria intestinal. Reporte de un caso
findings: []
- reference: DOI:10.7759/cureus.72571
title: Pathognomonic Features of Olmesartan-Induced Collagenous Sprue
Resulting in Severe Small Bowel Malabsorption
findings: []