| Dimension/system | Missing item | Quantitative evidence | Classification | Strongest source |
|---|---|---:|---|---|
| Hematologic/nutritional | Hypoproteinemia | 18.52% (20/108 adults) | Nutritional consequence of active disease | Pop et al., 2024; DOI: 10.15386/mpr-2776 (pqac-00000001) |
| Hematologic/nutritional | Vitamin B12/folate-deficiency anemia | 9.26% (10/108 adults) | Nutritional consequence; distinct from iron-deficiency anemia | Pop et al., 2024; DOI: 10.15386/mpr-2776 (pqac-00000001) |
| Skeletal/musculoskeletal | Osteopenia, fractures, joint pain | Osteopenia 35–42%; joint pain 20–30% at diagnosis; fracture frequency not quantified | Direct disease-associated manifestations, partly mediated by nutritional deficits | Santonicola et al., 2024; DOI: 10.3390/nu16121814 (pqac-00000007) |
| Endocrine | Hashimoto thyroiditis | 14.81% (16/108 adults) | Associated autoimmune comorbidity | Pop et al., 2024; DOI: 10.15386/mpr-2776 (pqac-00000001) |
| Cardiovascular/thrombotic | Venous or splanchnic thrombosis; atrial fibrillation | No reliable disease-wide frequency retrieved | Association; thrombosis may be promoted by vitamin-K/protein C/S deficiency. Atrial-fibrillation evidence is observational | Pop et al., 2024; DOI: 10.15386/mpr-2776 (pqac-00000003) |
| Renal | Urolithiasis | Frequency not established | Reported disease-associated manifestation; prevalence evidence is insufficient | Lupu et al., 2024; DOI: 10.3389/fimmu.2024.1390755 (pqac-00000002) |
| Respiratory | Asthma | 4.63% (5/108 adults in one tertiary cohort) | Associated comorbidity, not an established direct manifestation | Pop et al., 2024; DOI: 10.15386/mpr-2776 (pqac-00000001) |
| Neurologic | Headache/migraine; epilepsy | Epilepsy 2.78% (3/108 adults); headache/migraine frequency not established | Disease-associated neurologic features; epilepsy estimate is single-center | Lupu et al., 2024, DOI: 10.3389/fimmu.2024.1390755; Pop et al., 2024, DOI: 10.15386/mpr-2776 (pqac-00000001, pqac-00000006) |
| Psychiatric | Depression; anxiety | Depression 9.26%; anxiety 8.33% in a 108-adult cohort | Associated psychiatric comorbidity | Pop et al., 2024; DOI: 10.15386/mpr-2776 (pqac-00000001) |
| Dermatologic | Psoriasis; alopecia areata; atopic dermatitis | Psoriasis 7.41% (8/108 adults); no robust frequency for alopecia or atopic dermatitis | Associated inflammatory or autoimmune comorbidities | Santonicola et al., 2024, DOI: 10.3390/nu16121814; Pop et al., 2024, DOI: 10.15386/mpr-2776 (pqac-00000001, pqac-00000007) |
| Oral | Xerostomia; atrophic glossitis; angular cheilitis | Xerostomia 15% vs 5% of controls; glossitis 6.3% vs 0%; cheilitis not quantified | Disease-associated oral findings, potentially mediated by nutritional deficiency | Santonicola et al., 2024; DOI: 10.3390/nu16121814 (pqac-00000004) |
| Reproductive/obstetric | Miscarriage, stillbirth, fetal-growth restriction, preterm delivery, low birth weight | Stillbirth before diagnosis 0.45% vs 0.29%; FGR 11.7% vs 1.7%; preterm delivery 10.4% vs 6.9%; low birth weight 14.2% vs 6.7% | Adverse outcomes associated mainly with undiagnosed or untreated disease | Santonicola et al., 2024; DOI: 10.3390/nu16121814 (pqac-00000000) |
| ENT/neurologic | Sensorineural hearing loss | No dependable prevalence retrieved | Reported disease-associated manifestation; quantitative evidence is inadequate | Karunaratne & Karunaratne, 2022; DOI: 10.1177/0145561320972604 |
| Immune/infectious | Infection susceptibility | No adequate quantitative evidence retrieved | Insufficient evidence for inclusion as an independent direct feature | Evidence inadequate for a high-confidence source |
| Complicated disease | Refractory celiac disease types I and II | Prevalence 0.31–0.38%; 10-year cumulative incidence 1–4%; five-year survival up to 95% for type I and 58% for type II | Disease subtypes; type II has aberrant clonal IELs and greater lymphoma risk | Villanacci et al., 2020; DOI: 10.32074/1591-951x-157 (pqac-00000012) |
| Interventional trials | ZED1227, oral TG2 inhibitor | Phase 2, 163 participants; dose-dependent preservation of villous-height:crypt-depth ratio and reduced IEL density | Investigational disease-modifying therapy | Massironi et al., 2024; DOI: 10.3748/wjg.v30.i38.4194 (pqac-00000017) |
| Interventional trials | KAN-101, antigen-specific immune tolerance | Phase 2 completed; 55 participants; definitive clinical efficacy not reported in retrieved evidence | Investigational disease-modifying therapy | NCT06001177; earlier NCT04248855 and NCT05574010 (pqac-00000016, pqac-00000019) |
| Interventional trials | Latiglutenase, gluten-degrading enzyme | Multiple completed Phase 2 studies; symptom and histology results have varied | Investigational adjunct for inadvertent gluten exposure | NCT03585478; NCT04243551 (pqac-00000015, pqac-00000020) |
| Interventional trials | Larazotide acetate | Multiple Phase 2 studies completed; Phase 3 registered; confirmatory benefit not established in retrieved evidence | Investigational barrier-directed adjunct | NCT03569007 (pqac-00000019, pqac-00000022) |
| Interventional trials | Nexvax2 peptide immunotherapy | Phase 2 discontinued after interim analysis for lack of significant protection against gluten-induced symptoms | Investigational therapy with negative efficacy signal | NCT03644069 (pqac-00000018, pqac-00000021) |
| Interventional trials | Anti-IL-15 therapy | AMG714 did not prevent mucosal injury versus placebo, although some symptom and IEL signals favored 300 mg | Investigational immunomodulatory therapy | NCT02633020; PRV-015 NCT04424927 (pqac-00000018, pqac-00000021) |


*Table: Compact evidence table of high-confidence clinical, subtype, and therapeutic gaps absent from the curated celiac-disease record. It separates direct manifestations, nutritional effects, associated comorbidities, and investigational treatments.*