Treatment of Celiac Disease in Refractory Coeliac Disease Type 1: Persistence or Recurrence of Symptoms After Strict Gluten-Free Diet

A subset of patients with celiac disease continue to experience symptoms and villous atrophy despite maintaining a strict gluten-free diet for at least 12 months. When other causes are excluded and the intraepithelial lymphocyte immunophenotype remains normal, this presentation is classified as refractory coeliac disease type 1 (RCD-I) — a distinct clinical situation that requires a specific management approach.

Clinical Scenario

RCD type 1 is defined by the persistence or recurrence of symptoms and villous atrophy after at least 12 months on a strict gluten-free diet, with no other identifiable cause. The intraepithelial lymphocyte (IEL) immunophenotype is normal — polyclonal or oligoclonal — which distinguishes RCD-I from the more aggressive type 2 form and directly informs the treatment strategy.

Treatment Approach

Management of RCD-I extends beyond dietary measures. The protocol involves adding immunosuppressive therapy from the thiopurine class to a steroid regimen, targeting sustained remission. Criteria for re-evaluation and potential discontinuation are also defined within the full protocol.

Full sequencing, agent selection, and re-evaluation criteria available in the structured protocol below.
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References

DOI: 10.1002/ueg2.70195

RCD is defined by the persistence or recurrence of symptoms and villous atrophy after at least 12 months on a strict GFD, in the absence of other causes.

RCD‑I: The immunophenotype of IELs is normal.

Conventional immunosuppressant, such as azathioprine, may be added in selected cases. When used, azathioprine should be re‑evaluated for possible discontinuation after 2–3 years of clinical, histological and immunophenotypic stability.

In RCD‑1, the addition of thiopurines, such as, azathioprine or 6‑mercaptopurine to steroids was effective in inducing a clinical response in some cases.

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