| Phenotype | Leading causal hypotheses | Strongest human evidence | Key competing/non-causal explanations | Timing/reversibility | Verdict | Single most efficient resolving study |
|---|---|---|---|---|---|---|
| Dental Enamel Defects (developmental enamel hypoplasia in permanent dentition) | Ameloblast-directed IgA autoimmunity and food-antigen cross-reactivity; calcium/vitamin-D deficiency during amelogenesis; systemic inflammation; genetic susceptibility | Enamel-directed antibodies occur in celiac cohorts, but direct causal experiments are mainly animal-based; observational studies show symmetric chronological defects, while one controlled study found no significant association | Developmental illness, nutritional deficiency unrelated to celiac disease, fluorosis, genetic enamel disorders, regional ascertainment and diagnostic variation | Arises only while enamel is forming; established defects are irreversible. Early diagnosis/GFD may prevent defects in teeth not yet mineralized | CONTESTED | Prospective birth cohort measuring nutrient status and enamel-specific antibodies before and during permanent-tooth mineralization, with standardized dental imaging and treated-versus-untreated exposure analysis |
| Recurrent Aphthous Stomatitis | Hematinic deficiency from malabsorption; gluten-driven mucosal immune inflammation; cytokine-mediated injury; direct oral autoimmunity | RAS is enriched in case-control cohorts; in a small biopsy-confirmed series, four adherent patients improved within six months of GFD, but no mechanism-specific intervention exists | Idiopathic RAS; iron, folate or B12 deficiency from other causes; Behçet disease, Crohn disease, infection, immunodeficiency and medication effects | May precede gastrointestinal symptoms or be the sole presentation; recurrent lesions can improve on GFD, but persistence is possible and individual ulcers heal independently | UNKNOWN | Randomized gluten-withdrawal/gluten-challenge study in newly diagnosed celiac patients with RAS, stratified by corrected versus uncorrected hematinic deficiencies and using blinded ulcer counts |
| Arthritis (celiac-associated arthropathy) | Gluten-driven systemic immune activation; increased permeability and gut–joint trafficking; microbiome-mediated inflammation; nutrient deficiency and altered bone–muscle physiology | A carefully investigated 2023 case had sterile, non-erosive inflammatory polyarthritis resolving within three weeks of GFD; observational ultrasound studies report more synovitis with gluten exposure, but controlled mechanistic evidence is absent | Rheumatoid, psoriatic, reactive or spondyloarthritis; infection; crystal disease; vitamin-D deficiency; coincident autoimmunity; nonspecific arthralgia and referral bias | Can precede celiac diagnosis and occur without gastrointestinal symptoms; some cases remit rapidly on GFD, whereas persistence suggests another rheumatic disorder | UNKNOWN | Prospective inception cohort with rheumatologist-confirmed synovitis, synovial-fluid profiling and blinded ultrasound before GFD and during controlled gluten challenge after remission |
| Female infertility (and adverse pregnancy outcomes attributed to celiac disease) | Anti-TG2 binding inhibits endometrial angiogenesis and trophoblast invasion and promotes apoptosis; placental TG2 inhibition; malabsorption-related iron, folate, B12 or zinc deficiency; systemic inflammation | Patient antibodies bind human syncytiotrophoblast and damage primary trophoblasts in vitro; epidemiologic studies show excess infertility and adverse outcomes concentrated in undiagnosed/untreated disease, with risks attenuated after diagnosis/GFD | Age, BMI, smoking and socioeconomic confounding; thyroid or other autoimmunity; endometriosis/PCOS; shared HLA susceptibility; infertility-clinic selection and surveillance bias | Infertility or miscarriage may precede celiac diagnosis; risks generally diminish after diagnosis and GFD, although robust prospective fertility-treatment trials are lacking | CONTESTED | Multicenter prospective preconception cohort measuring anti-TG2, nutrients and placental/endometrial function before and after GFD, with antibody-negative celiac and nutrient-matched controls |
| Constipation (as a presenting bowel habit despite enteropathy) | Inflammation-mediated enteric neuromuscular and hormonal dysregulation; autonomic dysfunction; dysbiosis; impaired absorption; low-fiber, ultra-processed GFD after diagnosis | In 12 newly diagnosed patients, four weeks of GFD shortened small-bowel and colonic transit and increased contractility; dietitian-led fiber-quality intervention improved hard stools in treated children | IBS-C, pelvic-floor dysfunction, hypothyroidism, medications, ordinary chronic constipation and low-fiber dietary substitution; small studies lack healthy controls | May present before diagnosis; motility can improve within weeks, but constipation may persist despite mucosal treatment and can also arise from the GFD itself | CONTESTED | Larger controlled longitudinal study combining colonic transit, anorectal manometry, mucosal inflammation, microbiome and quantified fiber intake before and after GFD |
| Elevated Hepatic Transaminases (celiac hepatitis and its gluten-free-diet reversibility) | Increased intestinal permeability permits microbial products and antigens to activate hepatic innate immunity; circulating cytokines; anti-TG2 deposition or activity inhibition; malnutrition-related injury | Classic adult cohort: 67/158 had elevated enzymes and 60/67 normalized after one year of GFD; gluten challenge has reproduced abnormalities. Permeability correlates with AST, but the precise mediator is unproven | Viral or autoimmune hepatitis, MASLD/steatosis, alcohol, medication toxicity, Wilson disease, hemochromatosis and false-positive celiac serology in chronic liver disease | Often present at diagnosis and usually normalize within 6–12 months; persistence requires adherence review and investigation for another liver disease, though some pediatric abnormalities persist beyond one year | CONTESTED | Prospective GFD intervention with serial permeability, portal microbial-product, cytokine and anti-TG2 measurements, paired liver assessment, rigorous adherence monitoring and prespecified exclusion of competing liver diseases |


*Table: Concise synthesis of the six phenotype-specific mechanistic verdicts, reversibility constraints, major alternatives, and highest-yield resolving studies, based on the gathered human and translational evidence (pqac-00000005, pqac-00000014, pqac-00000021, pqac-00000027, pqac-00000035, pqac-00000041, pqac-00000045).*