Hidden Celiac Disease: How One Patient Was Missed by Standard Blood Tests

Celiac.com 02/18/2026 - This study describes a patient whose illness looked like severe malabsorption, but standard blood tests for celiac disease were negative. The report shows how doctors worked through many possible causes, why the diagnosis remained difficult, and how a strict gluten-free diet still led to major improvement. The case is important because it highlights a form of celiac disease that can be missed if clinicians rely on blood testing alone.

Background: What “Seronegative” Celiac Disease Means

In typical celiac disease, the immune system reacts to gluten and causes injury to the lining of the small intestine. Many people with celiac disease develop measurable antibodies in the blood that help confirm the diagnosis. However, some patients can have celiac disease even when these blood tests are negative. This is often called “seronegative celiac disease,” meaning that standard celiac antibody tests do not show the expected markers.

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Because blood tests are widely used as a first step, seronegative cases can be overlooked or delayed. In these situations, doctors may need to rely more heavily on symptoms, small-intestine biopsy findings, careful exclusion of other diseases, and the patient’s response to a gluten-free diet.

Patient Presentation: Years of Symptoms and Severe Mineral Problems

The patient in this case was a forty-one-year-old woman with a long history of intermittent watery diarrhea and recurring low mineral and protein levels in her blood. Over several years, she repeatedly developed low potassium, low calcium, low magnesium, low vitamin D, and low albumin. She later presented with abdominal pain, vomiting, diarrhea, and profound weakness.

On examination, she appeared undernourished and pale. A striking physical finding was a very enlarged spleen that could be felt well below the rib margin, consistent with massive splenomegaly. She also had muscle spasms consistent with low calcium. Despite her low albumin level, her liver-related blood tests did not suggest that the liver itself was failing to make proteins, which supported the idea that she was not absorbing nutrients properly.

Testing and Early Clues: Anemia, Malabsorption, and Negative Celiac Blood Tests

Laboratory testing showed anemia consistent with iron deficiency and inflammation. In addition, repeated testing confirmed persistent disturbances in minerals and acid-base balance, including episodes of metabolic acidosis. These abnormalities fit with a picture of chronic intestinal disease causing poor absorption and ongoing losses.

Importantly, standard blood testing for celiac disease was negative. The authors note that the patient was not avoiding gluten at the time of the blood testing, which helps rule out the possibility that the tests were negative simply because she had already stopped eating gluten.

Imaging Findings: Massive Spleen Enlargement and Intestinal Changes

Cross-sectional imaging of the abdomen supported the finding of massive spleen enlargement, with the spleen measuring up to about twenty-five centimeters. Imaging also suggested intestinal involvement, including diffuse thickening of the small bowel, enlarged lymph nodes in the mesentery, and a small amount of abdominal fluid. These findings raised concern for several serious conditions, including chronic infection, inflammatory bowel disease, and certain cancers of the immune system.

Because an enlarged spleen can occur in blood cancers or conditions associated with abnormal blood flow through the liver, the team considered a broad set of possibilities and pursued extensive evaluation.

Ruling Out Other Causes: Infection, Autoimmune Disease, Inflammatory Bowel Disease, and Cancer

A major part of this case involved excluding other explanations for the patient’s symptoms, abnormal blood results, and imaging findings. Infectious causes were investigated with a broad workup and were reported as negative. Tuberculosis was considered and evaluated with multiple tests and did not appear to be the cause. Stool studies and other testing did not identify a clear infectious explanation.

The team also evaluated for inflammatory bowel disease. Colonoscopy with biopsies and an inflammatory marker test from stool were normal, which argued against inflammatory bowel disease. Autoimmune disorders that can mimic celiac disease were also considered, and an autoimmune blood panel was negative.

Other specific causes of malabsorption and small-intestine injury were evaluated. Whipple disease was excluded by special testing of small-intestine biopsy tissue. Parasitic infection was considered, and the biopsy showed no parasites.

Because the spleen was massively enlarged and imaging raised concern for disorders of the lymphatic system, the team also evaluated for lymphoma and other blood cancers. They performed specialized analysis of biopsy tissue and blood to look for abnormal immune-cell populations, and later performed a bone marrow biopsy. These evaluations did not show evidence of malignancy.

Small-Intestine Biopsy: Findings Suggestive of Early Celiac-Type Injury

A key part of the evaluation came from small-intestine biopsies. The biopsy description included preserved villous structure but with an increase in immune cells within the lining of the intestine. The report describes these findings as consistent with “Marsh type one to two” changes, which can fit with early celiac disease or gluten-related intestinal injury, especially when combined with symptoms of malabsorption.

Because many other causes of similar biopsy changes were investigated and did not fit, the biopsy findings became more meaningful in the overall diagnostic picture, even though the blood tests for celiac disease were negative.

Treatment: Replacing Deficiencies and Starting a Gluten-Free Diet

During hospitalization, the patient required aggressive replacement of minerals, initially through intravenous therapy and later with high-dose oral supplements. She received active vitamin D therapy, sodium bicarbonate to help correct acid-base imbalance, and vitamin supplementation including thiamine and a multivitamin.

Crucially, the team also started a strict gluten-free diet and arranged dietary counseling. Although she continued to experience recurring low potassium and metabolic acidosis for a time, her diarrhea improved substantially after dietary changes.

By discharge, her overall condition had improved and her mineral levels were stabilized with ongoing oral therapy. She was discharged with supplements for potassium, calcium, magnesium, and bicarbonate, along with medication to slow diarrhea and strict instructions to avoid gluten.

Follow-Up and Outcome: Marked Symptom Improvement With Gluten Avoidance

After discharge, follow-up took place by telephone several weeks later. The patient reported near-complete resolution of diarrhea and continued adherence to the gluten-free diet. This strong clinical response supported the idea that gluten exposure was driving her illness, even though the usual blood tests did not confirm celiac disease.

The authors summarize that the combination of long-standing diarrhea, signs of malabsorption, biopsy changes consistent with gluten-related intestinal injury, negative celiac blood tests, and clear improvement on a gluten-free diet made seronegative celiac disease the most plausible explanation after other causes had been excluded.

Why This Study Matters for People With Celiac Disease

This case highlights a practical and important message: a negative celiac blood test does not always rule out celiac disease. For people who have chronic diarrhea, unexplained nutrient deficiencies, persistent low minerals, weight loss or undernourishment, or other signs of malabsorption, additional evaluation may be needed even when blood tests are negative.

For the celiac community, the report underscores that celiac disease can appear in unusual ways, including severe metabolic imbalance and an enlarged spleen, which can look like other serious illnesses. It also shows how delayed recognition can lead to years of suffering and repeated medical crises.

Most importantly, the patient improved significantly once gluten was removed from the diet. For people with suspected celiac disease or gluten-related illness, this case supports the need for thorough evaluation and careful clinical judgment, particularly when symptoms and nutritional problems strongly suggest malabsorption. Earlier identification of seronegative celiac disease could help prevent complications, correct deficiencies, and greatly improve quality of life.

Read more at: cureus.com