When celiac disease isn’t the whole story

An adolescent with longstanding diarrhea and severe malabsorption was ultimately diagnosed with celiac disease complicated by an indolent gastrointestinal T-cell lymphoproliferative disorder (ITLPD-GI), highlighting the importance of considering concurrent lymphoproliferative disease when celiac disease does not fully explain clinical findings.

The in-press case study from Gastroenterology was reported by Xueyan Chen, of the Department of Gastroenterology at Peking Union Medical College Hospital in Beijing, China, and colleagues.

Clinical presentation

The patient was an 18-year-old female with a 7-year history of intermittent diarrhea and a 2-year history of intermittent spasms in the hands and feet. Her stools were described as watery, foul-smelling, and oily, occurring up to 6–7 times per day during symptom exacerbations. Symptoms were accompanied by abdominal bloating, nausea, and vomiting.

Over time, the patient developed progressive systemic complications consistent with chronic malabsorption. On examination, she had severe malnutrition with a body mass index of 16.4 kg/m², delayed growth and development, and absent secondary sexual characteristics.

Laboratory testing demonstrated multisystem abnormalities including nutritional anemia, hypoalbuminemia, electrolyte disturbances, and deficiencies in fat-soluble vitamins. Bone metabolism studies showed severe vitamin D deficiency and secondary hyperparathyroidism, and imaging findings were consistent with rickets and osteoporosis.

Additional testing confirmed malabsorption, including an abnormal D-xylose absorption test and positive fecal Sudan staining indicating steatorrhea. Serologic testing showed markedly elevated celiac-associated autoantibodies, including tissue transglutaminase IgA, deamidated gliadin peptide IgA, and endomysial antibodies.

Endoscopic and imaging findings

Upper endoscopy revealed villous blunting and mosaic mucosal changes in the duodenum. Capsule endoscopy demonstrated shortened villi, irregular mucosal texture, nodular changes, and scattered white spots in the small intestine. Colonoscopy showed edematous mucosa in the terminal ileum with mild villous blunting.

Biopsy specimens from the duodenum and terminal ileum demonstrated small-intestinal villous atrophy with lymphocytic infiltration in the epithelium and lamina propria. Immunohistochemistry showed CD3-positive T-cell infiltration and clonal T-cell receptor rearrangement.

Imaging studies also demonstrated intestinal wall thickening and enlarged abdominal lymph nodes, raising concern for lymphoma.

Diagnosis

The patient was diagnosed with celiac disease complicated by indolent T-cell lymphoproliferative disorder (ITLPD) of the gastrointestinal tract.

The investigators noted that the patient’s clinical history and response to dietary therapy supported the diagnosis of celiac disease. After initiation of a gluten-free diet and nutritional support, diarrhea improved significantly and nutritional parameters normalized.

However, the diffuse intestinal lesions and clonal T-cell proliferation raised suspicion for lymphoid malignancy. Histologic findings ultimately supported ITLPD-GI rather than enteropathy-associated T-cell lymphoma (EATL).

Unlike EATL, which typically demonstrates destructive growth, cytologic atypia, and a high Ki-67 index, ITLPD-GI is characterized by indolent behavior, small monomorphic lymphocytes confined to the lamina propria, and a low proliferative index.

Clinical implications

The authors noted that celiac disease may present with both intestinal and extraintestinal manifestations including steatorrhea, growth retardation, osteoporosis, and coagulation abnormalities related to vitamin deficiencies.

They also noted that clonal T-cell proliferation in patients with celiac disease raises concern for two major conditions: EATL, an aggressive complication of refractory celiac disease, or ITLPD-GI, which follows a more indolent course.

"Accurate identification of clonal lymphoproliferation and differentiation between indolent and aggressive forms is crucial for appropriate management and improved long-term prognosis. This requires the integration of multimodal evidence, including clinical assessment, serology, endoscopy, pathological morphology, immunophenotyping, and molecular genetics, as well as long-term follow-up observations of disease behavior," noted the case study authors.

Outcome

The patient was managed with a gluten-free diet and supportive care. No specific treatment for ITLPD-GI was initiated because of its indolent clinical course.

At follow-up, the patient reported normalized bowel habits with one to two formed stools daily. Weight increased from 37 kg to 46 kg, height improved slightly, and secondary sexual characteristics began to develop.

The authors reported no conflicts of interest.