A modern guide to diagnosis, treatment, and living well – by Dr. Theodoros Argyropoulos
Celiac disease is a common, chronic, immune‑mediated enteropathy triggered by gluten (wheat, barley, rye). It affects approximately 1% of the population, often remains undiagnosed, and the cornerstone of therapy is lifelong gluten‑free diet. Diagnosis is primarily based on tTG‑IgA testing and usually endoscopy with biopsies in adults, while many children can be diagnosed without biopsy when antibody levels are very high.
What Celiac Disease Is (and Isn’t)
Celiac disease is an immune‑mediated disorder marked by loss of tolerance to cereal proteins (prolamins: gliadin in wheat, hordein in barley, secalin in rye), collectively known as “gluten.”
Despite its prevalence, it is underdiagnosed because its clinical presentation varies widely: from classic diarrhea and weight loss to “non‑classic” symptoms (bloating, fatigue, headaches) or no symptoms at all.
What Happens in the Gut?
- Cereals (wheat, barley, rye) contain gluten, a protein that is not fully broken down during digestion. Small fragments remain “resistant.”
- In the small intestine, an enzyme called transglutaminase‑2 (TG2) slightly modifies these gluten fragments in people with celiac disease.
- After this modification, the fragments bind more easily to HLA‑DQ2/DQ8 “receptors,” allowing the immune system to mistake gluten for a threat.
The Body’s Response
- T‑lymphocytes are activated. Some act as “alarms” of inflammation, others as “soldiers” attacking tissue.
- The reaction damages the lining of the small intestine: villi (tiny projections that absorb nutrients) shrink/atrophy, reducing absorption of vitamins and minerals.
- The body produces antibodies against TG2 (tTG‑IgA) which appear in the blood and help us diagnose the disease.
Why Is TG2 So Important?
- TG2 is the central switch driving this process.
- A drug under clinical investigation (ZED1227) can block TG2. In trials, when patients took the drug and were intentionally exposed to a small amount of gluten, they developed less intestinal damage and had fewer symptoms.
- It’s not a “pill that lets you eat gluten freely,” but it shows that targeting the right switch reduces the reaction.
A Visual Metaphor
Imagine gluten as a hard stick that doesn’t wear down easily. TG2 is a tool that reshapes it so it fits into the lock (HLA‑DQ2/DQ8). Once it fits, the alarm sounds, defenses gather (immune cells), and in the chaos, the floor is damaged (villi). If we place a stop on the tool (TG2 inhibitor), the alarm doesn’t sound as loudly.
How Common Is Celiac Disease?
- Global prevalence is around 1% (depending on the detection method—antibody testing vs biopsy).
- Rising diagnosis rates in recent decades, likely due to environmental factors and greater clinical awareness.
Who Should Be Tested?
Testing is recommended in:
- First‑degree relatives of patients with celiac disease.
- Individuals with associated conditions: type 1 diabetes, autoimmune thyroiditis, microscopic colitis, IBD, dermatitis herpetiformis, iron‑deficiency anemia, unexplained elevated liver enzymes, etc.
Symptoms: Intestinal and Extra‑intestinal
- Classic intestinal: diarrhea, steatorrhea, abdominal pain/bloating.
- Non‑classic/extra‑intestinal: fatigue, headache, arthralgia, mouth ulcers, anemia, osteopenia/osteoporosis, dermatitis herpetiformis, neurological signs (e.g., ataxia).
Note: many patients are normal weight or overweight at diagnosis — it is incorrect that “everyone loses weight.”
Diagnosis: Step‑by‑Step
1) Serology
- tTG‑IgA: first‑line test, high sensitivity. Beware of IgA deficiency (then use DGP‑IgG or EMA).
- EMA: very specific but more demanding.
- In children <2 years, adding DGP‑IgG increases sensitivity.
2) Endoscopy with Duodenal Biopsies
In adults, this is the standard diagnostic test, with multiple biopsies (duodenal bulb and second portion), assessing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (Marsh–Oberhuber classification).
3) Biopsy‑free Diagnosis (Children)
European pediatric guidelines (ESPGHAN) allow diagnosis without biopsy when tTG‑IgA ≥10× ULN with EMA confirmation and appropriate clinical context. In adults, this is not widely adopted yet, though emerging evidence supports high PPV at very high antibody titers.
4) Genetic Testing (HLA‑DQ2/DQ8)
Useful for excluding the diagnosis in unclear cases or in individuals already avoiding gluten. Absence of DQ2/DQ8 makes celiac disease very unlikely.
Important: All these tests should be performed while the patient is consuming gluten. Stopping gluten prematurely obscures results.
Follow‑Up After Diagnosis
- Dietitian support: consultation with an experienced dietitian is critical for understanding/applying the GFD and ensuring nutritional adequacy.
- Serological monitoring: tTG‑IgA (± DGP) periodically. Antibody drop usually reflects good adherence, but does not always correlate with mucosal healing.
- Repeat endoscopy: not routine for all. Recommended when symptoms persist, serology fails to normalize, or risk is high.
- GIP (Gluten Immunogenic Peptides): detection in urine/stool to identify unintentional exposure (24–48h in urine, up to 7 days in stool). A useful adjunct—best value when tests are repeated.
Treatment Today: Gluten‑Free Diet (GFD)
Lifelong avoidance of wheat‑barley‑rye remains the cornerstone: symptoms improve within 2–4 weeks, antibodies decline over subsequent months. Yet daily life can be challenging:
- Unintentional gluten exposure is very common, even in compliant patients.
- Gluten‑free products are more costly, often higher in fat/sugar and lower in fiber.
- Hyper‑vigilance may reduce quality of life, especially in adolescents.
Practical Tips:
– Choose products labeled “<20 ppm gluten.”
– Avoid cross‑contamination (kitchens, packaging).
– Learn label reading and use safe food lists with your dietitian.
When Symptoms Persist
The most common cause is ongoing gluten intake. If excluded, investigate coexisting disorders (e.g., IBS). A temporary low‑FODMAP diet on a GFD may reduce symptoms in selected patients.
Rarely, disease is refractory: persistent mucosal injury and malabsorption >12 months with strict GFD. Management requires an expert center. Options include budesonide (open‑capsule) and, in type II variants, targeted therapies (e.g., JAK inhibitors) in trials.
Long‑Term Risks & Comorbidities
Patients have a slightly increased risk of overall mortality, mainly due to malignancies and respiratory causes. Lymphoma risk (especially EATL) is increased. Associations exist with IBD, liver disease, osteoporosis/fractures, thyroiditis, etc.
Mucosal healing correlates with improved long‑term outcomes.
Myths & Facts
- “GFD is healthier for everyone.” No—long‑term gluten avoidance in non‑celiac individuals is not proven beneficial and may lead to nutritional imbalance.
- “If antibodies normalize, the gut has healed.” Not always—serology does not reliably reflect mucosal healing in all cases.
- “Celiac disease is only in children.” Incorrect—diagnosis can occur at any age, often in adults with non‑classic features.
Living Well With Celiac Disease: Practical Guide
- Team support (gastroenterologist, dietitian, pharmacist).
- Micronutrient monitoring: iron, ferritin, B12, folate, D, zinc, as appropriate.
- Nutrition & microbiome: focus on whole foods (fruits/vegetables, gluten‑free pseudocereals, potatoes, rice, corn, quinoa, buckwheat), adequate fiber and protein.
- Regular serology (tTG‑IgA ± DGP), with realistic expectations regarding mucosal healing.
- GIP testing if accidental exposure is suspected—as a tool, not a cure.
- Mental well‑being: avoid the “all‑or‑nothing” mindset and social isolation; seek support if anxiety around food becomes overwhelming.
Frequently Asked Questions (FAQ)
1) Can I start a gluten‑free diet “to see if it helps”?
Not before completing the diagnostic process. Early avoidance interferes with tests and may delay diagnosis. Consult your physician first.
2) Is oatmeal allowed?
Only certified gluten‑free oats (because ordinary oats are often cross‑contaminated).
3) My antibodies dropped. Do I need repeat endoscopy?
Not necessarily. Routine re‑biopsy is not recommended for all. It is considered individually—certainly when symptoms persist or red flags appear.
4) Will there be a “celiac pill”?
Research is active (enzymes, TG2 inhibitors, immune tolerance). Currently no approved therapy, but data suggest future treatments may supplement GFD by reducing damage from small gluten exposures.
5) I have celiac disease. Should I test my child?
Yes, especially if they are a first‑degree relative. Screening may be repeated at intervals during childhood depending on risk. Discuss timing with your pediatrician/gastroenterologist.
Conclusion
Celiac disease is not rare, not only in children, and not confined to the intestines. Lifelong gluten avoidance remains the mainstay of treatment, but new monitoring tools and experimental therapies offer hope for safer daily life. Accurate diagnosis, education, and multidisciplinary care are key to living well—without gluten, but with quality and confidence.
This article is based on the recent extensive review “Advances in the pathophysiology, diagnosis, and management of celiac disease” (BMJ, 2025) and current international guidelines. For individualized assessment, please consult your gastroenterologist.
