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Does celiac disease influence survival in lymphoproliferative malignancy?

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Abstract

Celiac disease (CD) is associated with both lymphoproliferative malignancy (LPM) and increased death from LPM. Research suggests that co-existing autoimmune disease may influence survival in LPM. Through Cox regression we examined overall and cause-specific mortality in 316 individuals with CD+LPM versus 689 individuals with LPM only. CD was defined as having villous atrophy according to biopsy reports at any of Sweden’s 28 pathology departments, and LPM as having a relevant disease code in the Swedish Cancer Register. During follow-up, there were 551 deaths (CD: n = 200; non-CD: n = 351). Individuals with CD+LPM were at an increased risk of death compared with LPM-only individuals [adjusted hazard ratio (aHR) = 1.23; 95 % confidence interval (CI) = 1.02–1.48]. However, this excess risk was only seen in the first year after LPM diagnosis (aHR = 1.76), with HRs decreasing to 1.09 in years 2–5 after LPM diagnosis and to 0.90 thereafter. Individuals with CD and non-Hodgkin lymphoma (NHL) were at a higher risk of any death as compared with NHL-only individuals (aHR = 1.23; 95 % CI = 0.97–1.56). This excess risk was due to a higher proportion of T cell lymphoma in CD patients. Stratifying for T- and B cell status, the HR for death in individuals with CD+NHL was 0.77 (95 % CI = 0.46–1.31). In conclusion, we found no evidence that co-existing CD influences survival in individuals with LPM. The increased mortality in the first year after LPM diagnosis is related to the predominance of T-NHL in CD individuals. Individuals with CD+LPM should be informed that their prognosis is similar to that of individuals with LPM only. However, this study had low statistical power to rule our excess mortality in patients with CD and certain LPM subtypes.

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Abbreviations

CD:

Celiac disease

CI:

Confidence interval

HR:

Hazard ratio

VA:

Villous atrophy

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Acknowledgments

JFL: Örebro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, the Swedish Research Council—Medicine (522-2A09-195), the Swedish Celiac Society, the Fulbright commission. BL: The American Scandinavian Foundation, the Celiac Sprue Association, and the National Center for Research Resources, a component of the National Institutes of Health (KL2 RR024157). JAM: The National Institutes of Health – DK071003 and DK057892.

Conflict of interest

JAM: Grant support: Alba Therapeutics (> $50,000); Advisory board: Alvine Pharmaceuticals, Inc. (< $10,000), Nexpep (< $10,000), Consultant (none above 10,000 USD): Ironwood, Inc., Flamentera, Actogenix, Ferring Research Institute Inc., Bayer Healthcare Pharmaceuticals, Vysera Biomedical, 2G Pharma, Inc., ImmunosanT, Inc. and Shire US Inc. The other authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

    Jonas F. Ludvigsson, Anders Ekbom & Fredrik Granath

  2. Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden

    Jonas F. Ludvigsson

  3. Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA

    Alberto Rubio-Tapia & Joseph A. Murray

  4. Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Benjamin Lebwohl & Peter H. R. Green

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  1. Jonas F. Ludvigsson
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  2. Benjamin Lebwohl
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  3. Alberto Rubio-Tapia
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  4. Joseph A. Murray
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Correspondence to Jonas F. Ludvigsson.

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Ethics approval: This project (2006/633-31/4) was approved by the Research Ethics Committee of the Karolinska Institute, Sweden on June 14th, 2006.

Appendix

Appendix

See Tables 4, 5.

Table 4 All-cause mortality in relation to time since diagnosis of non-Hodgkin lymphoma (NHL) in individuals with and without celiac disease (CD)
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Table 5 All-cause mortality in relation to time since diagnosis of lymphoproliferative malignancy (LPM) in individuals with and without celiac disease (CD)
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Ludvigsson, J.F., Lebwohl, B., Rubio-Tapia, A. et al. Does celiac disease influence survival in lymphoproliferative malignancy?. Eur J Epidemiol 28, 475–483 (2013). https://doi.org/10.1007/s10654-013-9789-8

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