CELIAC DISEASE AS A MASKING CONDITION — THE ROLE OF EXTRAINTESTINAL SYMPTOMS IN DELAYED DIAGNOSIS

Patryk Twardy; Weronika Wagner; Jakub Białożyt; Anna Dębniak; Maciej Gutarowicz; Patryk Modelewski; Kaja Nieradka; Krystyna Klahs; Michał Armatys; Maciej Muraszko-Kuźma

doi:10.31435/ijitss.2(50).2026.5564

Authors

Patryk Twardy Clinical Provincial Hospital of Saint Jadwiga the Queen in Rzeszów, Poland https://orcid.org/0009-0009-5510-3545
Weronika Wagner Clinical Provincial Hospital of Saint Jadwiga the Queen in Rzeszów, Poland https://orcid.org/0009-0001-0269-0418
Jakub Białożyt University Clinical Hospital No. 2 PUM in Szczecin, Poland https://orcid.org/0009-0000-2721-6694
Anna Dębniak University Clinical Hospital No. 2 PUM in Szczecin, Poland https://orcid.org/0009-0009-8511-3912
Maciej Gutarowicz Independent Public Provincial Hospital in Szczecin, Poland https://orcid.org/0009-0003-5139-3756
Patryk Modelewski University Clinical Hospital No. 2 PUM in Szczecin, Poland https://orcid.org/0009-0009-0682-4901
Kaja Nieradka Clinical Provincial Hospital of Saint Jadwiga the Queen in Rzeszów, Poland https://orcid.org/0009-0009-4373-3726
Krystyna Klahs Independent Public Specialist Health Care Facility in Lębork, Poland https://orcid.org/0009-0001-7747-6854
Michał Armatys UNO-MED Medical Center, Tarnów, Poland https://orcid.org/0009-0003-9647-8091
Maciej Muraszko-Kuźma District Hospital in Limanowa of the Name of Divine Mercy, Poland https://orcid.org/0009-0003-4812-1493

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5564

Keywords:

Celiac Disease, Extraintestinal Manifestations, Delayed Diagnosis, Atypical Celiac Disease, Gluten-Related Disorders

Abstract

Background: Celiac disease is a chronic autoimmune enteropathy caused by gluten in genetically predisposed people. It affects about 1% of the population. It was once seen mainly in children, but adult diagnoses are rising. Symptoms stem from immune reactions and nutrient deficiencies from gluten intake. Proper diagnostic tests allow quick diagnosis and treatment with a gluten-free diet (Durazzo et al., 2022).

Aim: This study intends to present the current state of knowledge regarding celiac disease, with particular emphasis on its extraintestinal manifestations. Their occurrence frequently represents a diagnostic challenge for physicians and may lead to inappropriate treatment management. This review intends to increase physicians’ clinical awareness and encourage the use of appropriate, targeted diagnostic investigations.

Conclusions: The conducted literature analysis shows that celiac disease remains undiagnosed in a significant proportion of patients presenting with extraintestinal symptoms. Because gastrointestinal manifestations predominated in the past, physicians’ diagnostic vigilance has diminished. Extraintestinal symptoms currently constitute a major diagnostic challenge and are increasingly observed, complicating and delaying accurate diagnosis. Untreated celiac disease may lead to serious complications that could be prevented through proper interpretation of these manifestations. Therefore, it is the key for physicians — particularly those working in primary care — to recognize these disease manifestations and quickly initiate treatment with a gluten-free diet, which markedly improves the prognosis of patients with celiac disease.

References

Aboulaghras, S., Piancatelli, D., Taghzouti, K., Balahbib, A., Alshahrani, M. M., Al Awadh, A. A., Goh, K. W., Ming, L. C., Bouyahya, A., & Oumhani, K. (2023). Meta-analysis and systematic review of HLA-DQ2/DQ8 in adults with celiac disease. International Journal of Molecular Sciences, 24(2), 1188. https://doi.org/10.3390/ijms24021188

Al-Toma, A., Zingone, F., Branchi, F., Schiepatti, A., Malamut, G., Canova, C., Rosato, I., Ocagli, H., Trott, N., Elli, L., Popp, A., Gianfrani, C., Auricchio, R., Neefjes-Borst, A., Sanders, D. S., Cellier, C., Mulder, C. J., Bouma, G., Lundin, K. E. A., Sollid, L. M., & Schumann, M. (2025). European Society for the Study of Coeliac Disease 2025 updated guidelines. United European Gastroenterology Journal, 13(10), 1855–1886. https://doi.org/10.1002/ueg2.70119

Ashok, T., Patni, N., Fatima, M., Lamis, A., & Siddiqui, S. W. (2022). Celiac disease and autoimmune thyroid disease. Cureus, 14(6), e26243. https://doi.org/10.7759/cureus.26243

Berry, N., Basha, J., Varma, N., Varma, S., Prasad, K. K., Vaiphei, K., Dhaka, N., Sinha, S. K., & Kochhar, R. (2018). Anemia in celiac disease is multifactorial in etiology. JGH Open, 2(5), 196–200. https://doi.org/10.1002/jgh3.12073

Casella, E. (2025). Delay in the diagnosis of celiac disease today. Medical Research Archives, 13(7). https://doi.org/10.18103/mra.v13i7.6645

Dev, K., Rahul, F., Makheja, K., Kumar, J., Ahuja, V., Ekta, F., Dholia, S., Khan, S., & Talpur, A. S. (2021). Frequency of cutaneous disorders in patients with celiac disease. Cureus, 13(9), e18148. https://doi.org/10.7759/cureus.18148

Durazzo, M., Ferro, A., Brascugli, I., Mattivi, S., Fagoonee, S., & Pellicano, R. (2022). Extra-intestinal manifestations of celiac disease. Journal of Clinical Medicine, 11(1), 258. https://doi.org/10.3390/jcm11010258

Fanaeian, M. M., Alibeik, N., Ganji, A., Fakheri, H., Ekhlasi, G., & Shahbazkhani, B. (2021). Prevalence of migraine in adults with celiac disease. PLOS ONE, 16(11), e0259502. https://doi.org/10.1371/journal.pone.0259502

Flores Monar, G. V., Islam, H., Puttagunta, S. M., Islam, R., Kundu, S., Jha, S. B., Rivera, A. P., & Sange, I. (2022). Association between type 1 diabetes mellitus and celiac disease. Cureus, 14(3), e22912. https://doi.org/10.7759/cureus.22912

Hadjivassiliou, M., Croall, I. D., Zis, P., Sarrigiannis, P. G., Sanders, D. S., Aeschlimann, P., Grünewald, R. A., Armitage, P. A., Connolly, D., Aeschlimann, D., & Hoggard, N. (2019). Neurologic deficits in celiac disease. Clinical Gastroenterology and Hepatology, 17(13), 2678–2686. https://doi.org/10.1016/j.cgh.2019.03.014

Heikkilä, K., Pearce, J., Mäki, M., & Kaukinen, K. (2015). Celiac disease and bone fractures. The Journal of Clinical Endocrinology & Metabolism, 100(1), 25–34. https://doi.org/10.1210/jc.2014-1858

Husby, S., Koletzko, S., Korponay-Szabó, I., Kurppa, K., Mearin, M. L., Ribes-Koninckx, C., Shamir, R., Troncone, R., Auricchio, R., Castillejo, G., Christensen, R., Dolinšek, J., Gillett, P., Hróbjartsson, A., Koltai, T., Mäki, M., Nielsen, S. M., Popp, A., Størdal, K., Werkstetter, K., & Wessels, M. (2020). ESPGHAN guidelines for diagnosing coeliac disease. Journal of Pediatric Gastroenterology and Nutrition, 70(1), 141–156. https://doi.org/10.1097/MPG.0000000000002497

Jericho, H., Sansotta, N., & Guandalini, S. (2017). Extraintestinal manifestations of celiac disease. Journal of Pediatric Gastroenterology and Nutrition, 65(1), 75–79. https://doi.org/10.1097/MPG.0000000000001420

Kowalski, M. K., Domżał-Magrowska, D., & Małecka-Wojciesko, E. (2025). Celiac disease—Narrative review. Foods, 14(6), 959. https://doi.org/10.3390/foods14060959

Krawczyk, A., Kretek, A., Pluta, D., Kowalczyk, K., Czech, I., Radosz, P., & Madej, P. (2022). Gluten-free diet—Remedy or risk? Ginekologia Polska, 93(5), 422–426. https://doi.org/10.5603/GP.a2021.0223

Kreutz, J. M., Adriaanse, M. P. M., van der Ploeg, E. M. C., & Vreugdenhil, A. C. E. (2020). Nutrient deficiencies in celiac disease. Nutrients, 12(2), 500. https://doi.org/10.3390/nu12020500

Kvamme, J. M., Sørbye, S., Florholmen, J., & Halstensen, T. S. (2022). Population-based screening for celiac disease. Scientific Reports, 12, 12647. https://doi.org/10.1038/s41598-022-16705-2

Laurikka, P., Nurminen, S., Kivelä, L., & Kurppa, K. (2018). Early detection of extraintestinal manifestations. Nutrients, 10(8), 1015. https://doi.org/10.3390/nu10081015

Li, L., Fu, L., Zhang, L., & Feng, Y. (2022). Genetic interaction between psoriasis and celiac disease. Scientific Reports, 12, 21508. https://doi.org/10.1038/s41598-022-25217-y

Lungaro, L., Manza, F., Costanzini, A., Barbalinardo, M., Gentili, D., Caputo, F., Guarino, M., Zoli, G., Volta, U., De Giorgio, R., & Caio, G. (2023). Osteoporosis and celiac disease. Nutrients, 15(5), 1089. https://doi.org/10.3390/nu15051089

Mearns, E. S., Taylor, A., Thomas Craig, K. J., Puglielli, S., Leffler, D. A., Sanders, D. S., Lebwohl, B., & Hadjivassiliou, M. (2019). Neurological manifestations in celiac disease. Nutrients, 11(2), 380. https://doi.org/10.3390/nu11020380

Paez, M. A., Gramelspacher, A. M., Sinacore, J., Winterfield, L., & Venu, M. (2017). Delay in diagnosis of celiac disease. The American Journal of Medicine, 130(11), 1318–1323. https://doi.org/10.1016/j.amjmed.2017.05.027

Patt, Y. S., Lahat, A., David, P., Patt, C., Eyade, R., & Sharif, K. (2023). Immunopathological landscape of celiac disease. International Journal of Molecular Sciences, 24(20), 15482. https://doi.org/10.3390/ijms242015482

Repo, M., Hannula, M., Taavela, J., Hyttinen, J., Isola, J., Hiltunen, P., Popp, A., Kaukinen, K., Kurppa, K., & Lindfors, K. (2021). Iron transporter proteins in celiac disease. Nutrients, 13(3), 776. https://doi.org/10.3390/nu13030776

Reunala, T., Salmi, T. T., Hervonen, K., Kaukinen, K., & Collin, P. (2018). Dermatitis herpetiformis. Nutrients, 10(5), 602. https://doi.org/10.3390/nu10050602

Rubio-Tapia, A., Hill, I. D., Semrad, C., Kelly, C. P., Greer, K. B., Limketkai, B. N., & Lebwohl, B. (2023). ACG guidelines. The American Journal of Gastroenterology, 118(1), 59–76. https://doi.org/10.14309/ajg.0000000000002075

Seidita, A., Mansueto, P., Compagnoni, S., Castellucci, D., Soresi, M., Chiarello, G., Cavallo, G., De Carlo, G., Nigro, A., Chiavetta, M., Mandreucci, F., Giuliano, A., Disclafani, R., & Carroccio, A. (2022). Anemia in celiac disease. Journal of Personalized Medicine, 12(10), 1582. https://doi.org/10.3390/jpm12101582

Singh, P., Arora, S., Lal, S., Strand, T. A., & Makharia, G. K. (2016). Celiac disease in infertility. Journal of Clinical Gastroenterology, 50(1), 33–39. https://doi.org/10.1097/MCG.0000000000000285

Tan, I. L., Coutinho de Almeida, R., Modderman, R., Stachurska, A., Dekens, J., Barisani, D., Meijer, C. R., Roca, M., Martinez-Ojinaga, E., Shamir, R., Auricchio, R., Korponay-Szabó, I. R., Castillejo, G., Szajewska, H., Koletzko, S., Zhernakova, A., Kumar, V., Li, Y., Visschedijk, M. C., Weersma, R. K., & Withoff, S. (2021). Circulating miRNAs in celiac disease. Frontiers in Immunology, 12, 734763. https://doi.org/10.3389/fimmu.2021.734763

Therrien, A., Kelly, C. P., & Silvester, J. A. (2020). Extraintestinal manifestations of celiac disease. Journal of Clinical Gastroenterology, 54(1), 8–21. https://doi.org/10.1097/MCG.0000000000001267

Wieser, H., Ciacci, C., Soldaini, C., Gizzi, C., Pellegrini, L., & Santonicola, A. (2025). Fertility in celiac disease. Nutrients, 17(9), 1575. https://doi.org/10.3390/nu17091575