Celiac Disease Masquerading as Fever of Unknown Origin

A 33-year-old woman experienced a month-long fever reaching 39°C (approximately 102°F), accompanied by muscle aches. Notably, she had no abdominal pain, diarrhea, or weight loss. After clinicians ruled out infection, cancer, and other potential causes, the diagnosis emerged from her small intestine: celiac disease.

The case, published in October 2026 in Oxford Medical Case Reports, describes celiac disease disguised as a fever of unknown origin. The authors, physicians in Marrakesh, Guelmim and Agadir in Morocco, titled their report “Pyrexia as the primary paradox.”

A Fever with No Obvious Source

The patient had no significant medical history and reported no recent travel, sick contacts, or new medications. On examination, she was pale and thin, with a tachycardia of 130 beats per minute and hypotension of 95/55 mm Hg.

Laboratory results revealed two critical findings: severe iron-deficiency anemia with a hemoglobin of 8.0 g/dL and a ferritin level of 7 ng/mL, indicating depleted iron stores. C-reactive protein, an inflammation marker, was markedly elevated at 140 mg/L. Physical examination showed no swollen lymph nodes, hepatosplenomegaly, or neurological abnormalities.

Physicians pursued a comprehensive differential for prolonged fever. Blood and urine cultures were negative, as were tests for HIV, hepatitis B, hepatitis C, and tuberculosis. An echocardiogram ruled out cardiac valve infection. Antinuclear antibody and antineutrophil cytoplasmic antibody tests were negative. Muscle enzyme levels were normal, electromyography showed no myopathy, blood protein analysis was unremarkable, and CT scans of the chest, abdomen, and pelvis identified no tumor or abscess.

An Antibody Test Points to the Gut

The pivotal finding was a celiac disease blood test. Her anti-tissue transglutaminase IgA antibody level, a standard screening marker, was 37 U/mL, well above the laboratory’s normal cutoff of less than 4.

Upper endoscopy revealed flattened folds in the duodenum, the first portion of the small intestine. Biopsy confirmed partial blunting of the villi responsible for nutrient absorption, along with increased intraepithelial lymphocytes, consistent with celiac disease at modified Marsh stage IIIa.

Celiac disease is an autoimmune disorder triggered by gluten, a protein found in wheat, barley, and rye, causing immune-mediated damage to the small intestine. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) estimates that approximately 1% of the global population has the condition, including about 2 million individuals in the United States.

Impaired iron absorption due to intestinal damage explains the patient’s anemia. Unexplained iron deficiency is a recognized indicator to consider celiac testing.

A Gluten-Free Diet and a Declining Fever

Treatment included acetaminophen for fever and aches, intravenous iron supplementation, and initiation of a gluten-free diet. Upon discharge on day 10, the patient was fever-free and her C-reactive protein had decreased to 75 mg/L.

At the three-month follow-up, her fevers and systemic symptoms had resolved, and she had gained weight. Hemoglobin rose to 10.2 g/dL, and C-reactive protein returned to normal at 5 mg/L. She continued the gluten-free diet and oral iron therapy.

The clinical improvement after gluten elimination supports the diagnosis, though a single case cannot confirm that celiac disease alone accounts for all symptoms. The authors proposed a possible mechanism: gluten-triggered inflammation releases immune signaling molecules such as interleukin-6 and tumor necrosis factor alpha, which may elevate the brain’s temperature set point. This hypothesis is drawn from prior research; cytokine levels were not measured in this patient, so the mechanism remains unproven.

Rare, Not Unprecedented, and Easy to Overlook

Fever is not a typical feature of celiac disease. The authors characterized it as an exceptionally rare presentation documented only in isolated case reports, and this is not the first instance. A 2013 case report described a 16-year-old girl whose celiac disease also presented as a fever of unknown origin.

Fever of unknown origin remains a classic diagnostic challenge: a persistent fever unexplained after initial thorough evaluation. Infections, malignancies, and inflammatory diseases account for many cases, and gastrointestinal disorders are rarely the first consideration when the gut appears quiescent.

The authors recommend that clinicians consider celiac testing in adults with prolonged, unexplained fever, particularly when iron-deficiency anemia is present. The blood test is inexpensive and widely available.

Celiac disease can manifest systemically beyond the gut. NIDDK lists additional symptoms including fatigue, joint or bone pain, and an itchy, blistering skin rash known as dermatitis herpetiformis.

For patients, a key practical takeaway applies: NIDDK advises against initiating a gluten-free diet before testing, as eliminating gluten first can obscure the diagnosis. Anyone who suspects celiac disease should consult a clinician before making dietary changes.

Key Questions Answered

What happened in this case?

A 33-year-old woman in Morocco endured a month of fevers and muscle aches without digestive symptoms. After extensive evaluation, she received a diagnosis of celiac disease.

How did doctors identify the celiac disease?

A blood test revealed elevated anti-tissue transglutaminase IgA antibodies, and small intestinal biopsy confirmed the diagnosis.

Can celiac disease cause fever?

It is unusual, but such cases have been reported. The authors suggest that gluten-induced inflammation may raise body temperature, though this mechanism remains unproven.

How was the woman treated?

She received intravenous iron and began a gluten-free diet. Her fever resolved, and her inflammation marker normalized within three months.

Should someone stop eating gluten before testing?

No. Testing is most accurate while gluten remains in the diet. Individuals who suspect celiac disease should speak with a clinician before making any dietary changes.

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