Most people with celiac disease improve on a gluten-free diet and never develop a serious complication. The complications that matter are the ones that appear when the disease is severe, when it goes untreated, or when it does not respond to the diet, and they explain why persistent symptoms on treatment are taken seriously.
Celiac crisis
Celiac crisis is a life-threatening complication in which patients with severe diarrhea have dehydration, electrolyte imbalances, renal failure and finally shock. It represents the extreme of untreated malabsorption rather than a new disease, and it develops most often in those with severe, extensive small-bowel involvement.
Refractory celiac disease
Refractory celiac disease (RCD) occurs when the symptoms and the intestinal damage persist despite adherence to a gluten-free diet, once gluten exposure and other causes have been excluded. It is divided by the phenotype of the intraepithelial lymphocytes (IELs):
- Type I RCD is characterised by phenotypically normal IELs and has a better prognosis.
- Type II RCD features phenotypically aberrant IELs. It behaves as an in situ aggressive T-cell lymphoma and carries a high rate of progression to enteropathy-associated T-cell lymphoma.
Enteropathy-associated T-cell lymphoma
Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal lymphoma that is strongly associated with celiac disease; the risk is highest in patients with type II refractory disease. Because it is a complication of the same process, unexplained worsening — or a fever, weight loss or recurrence of severe symptoms in a patient who had been stable — prompts investigation.
Malignancy and mortality overall
Population studies show only a modest increase in overall risk. In a large cohort, people with celiac disease had a hazard ratio of 1.29 for any malignancy and 1.31 for mortality compared with the general population, with the excess concentrated in the year after diagnosis; the increased risk that persisted beyond that year was mainly for lymphoproliferative disease. The clinically important point is not that celiac disease is a cancer-prone state, but that a small excess of intestinal and lymphoid malignancy is real and is the reason refractory and non-responsive disease is investigated rather than observed.