ORAL MANIFESTATIONS OF AMYLOIDOSIS AS AN EARLY INDICATOR OF THE DISEASE - A LITERATURE REVIEW
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5531Keywords:
Amyloidosis, Oral Manifestations, Oral Cavity Symptoms, Oral Health, Oral Cavity MucosaAbstract
Introduction and Purpose: Amyloidosis is a rare group of diseases characterized by the irreversible extracellular deposition of insoluble amyloid fibrils in various organs and tissues. Treatment should begin as early as possible, immediately following diagnosis. Therefore, clinicians should be aware of the disease’s characteristic features, including those visible in the oral cavity- which will be the focus of this article. While systemic manifestations are often emphasized, changes in the oral cavity can serve as early- and sometimes the first- indicators of the disease.
The aim of this article is to present the most relevant and recent scientific reports from the past ten years regarding oral manifestations of amyloidosis, highlight their diagnostic value, and emphasize the role of the dental professionals in the multidisciplinary approach to early detection and patient care.
Description of the State of Knowledge: Recent literature highlights a broad range of oral manifestations in amyloidosis, including macroglossia, nodular lesions, hemorrhagic changes, and chronic ulcers- some of which may appear without systemic symptoms. Histopathological biopsy with Congo red staining remains the gold standard for confirming amyloid deposits. Case reports increasingly show that oral findings can prompt systemic evaluation, leading to earlier diagnosis and management. This underscores the importance of dental professionals in recognizing subtle signs and initiating appropriate referrals.
Conclusions: Oral signs of amyloidosis can be the first clue to a systemic disease. Recognizing the type and location of lesions helps assess whether the disease is localized or systemic. Early diagnosis may improve outcomes- and in some cases, even save the patient’s life.
References
Maloney, B., Fisher, V., & Healy, C. M. (2025). Localized amyloidosis of the oral cavity: A rare clinical entity. Clinical Case Reports, 13(5), e70413. https://doi.org/10.1002/ccr3.70413
Muchtar, E., Dispenzieri, A., Magen, H., Grogan, M., Mauermann, M., McPhail, E. D., Kurtin, P. J., Leung, N., Buadi, F. K., Dingli, D., Kumar, S. K., & Gertz, M. A. (2021). Systemic amyloidosis from A (AA) to T (ATTR): A review. Journal of Internal Medicine, 289(3), 268–292. https://doi.org/10.1111/joim.13169
Aldinc, E., Campbell, C., Gustafsson, F., Beveridge, A., Macey, R., Marr, L., Summers, C., & Zhang, D. (2023). Musculoskeletal manifestations associated with transthyretin-mediated (ATTR) amyloidosis: A systematic review. BMC Musculoskeletal Disorders, 24(1), 751. https://doi.org/10.1186/s12891-023-06853-5
Hänselmann, A., Berliner, D., Bauersachs, J., & Bavendiek, U. (2022). Cardiac amyloidosis-interdisciplinary approach to diagnosis and therapy. Herz, 47(4), 324–331. https://doi.org/10.1007/s00059-022-05122-w
Dongiglio, F., Monda, E., Palmiero, G., Verrillo, F., Rubino, M., Diana, G., Cirillo, A., Fusco, A., Vetrano, E., Lioncino, M., Caiazza, M., Cerciello, G., Capodicasa, L., Chiosi, F., Simonelli, V., De Rimini, M. L., Natale, F., Di Santo, A., Moscarella, E., Calabrò, P., ... Limongelli, G. (2023). Pathophysiology, functional assessment and prognostic implications of nutritional disorders in systemic amyloidosis. Journal of Clinical Medicine, 12(2), 528. https://doi.org/10.3390/jcm12020528
Bustamante, J. G., & Zaidi, S. R. H. (2023). Amyloidosis. In StatPearls. StatPearls Publishing.
Laptseva, N., Benz, D. C., Schwotzer, R., & Flammer, A. J. (2024). Cardiac amyloidosis. Swiss Medical Weekly, 154, 4186. https://doi.org/10.57187/s.4186
Karam, C., Mauermann, M. L., Gonzalez-Duarte, A., Kaku, M. C., Ajroud-Driss, S., Brannagan, T. H., III, & Polydefkis, M. (2024). Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: Recommendations from a panel of experts. Muscle & Nerve, 69(3), 273–287. https://doi.org/10.1002/mus.28026
Tavares, T. S., da Costa, A. A. S., Araújo, A. L. D., de Souza, L. L., Pascoaloti, M. I. M., Bernardes, V. F., Aguiar, M. C. F., Vargas, P. A., Fonseca, F. P., Pontes, H. A. R., Lopes, M. A., Santos-Silva, A. R., da Silva, T. A., & Caldeira, P. C. (2024). Oral manifestations of amyloidosis and the diagnostic applicability of oral tissue biopsy. Journal of Oral Pathology & Medicine, 53(1), 61–69. https://doi.org/10.1111/jop.13504
Pontes, F. S., Ferreira, G. B., Fonseca, F. P., Ribeiro, T. F., Caldeira, P. C., Tavares, T. S., Bentes, A. P., Lopes, M. A., Silva, T. A., Lemos, J. G., & Pontes, H. A. (2023). Oral amyloidosis: An update. Medicina Oral, Patología Oral y Cirugía Bucal, 28(4), e341–e346. https://doi.org/10.4317/medoral.25761
Liu, W., Jiang, C., Shen, X., Wu, Y., & Wei, J. (2025). A scientometric study on research characteristics and trends of amyloidosis involving the oral cavity. Journal of Dental Sciences, 20(2), 1257–1261. https://doi.org/10.1016/j.jds.2024.12.010
Chiu, A., Dasari, S., Nasr, S. H., Dispenzieri, A., Dao, L. N., Dalland, J. C., Howard, M. T., Larson, D. P., Rech, K. L., Theis, J. D., Vrana, J. A., & McPhail, E. D. (2024). Salivary gland amyloidosis: Proteomic identification and clinicopathologic characterization of 57 cases. Human Pathology, 151, 105628. https://doi.org/10.1016/j.humpath.2024.105628
Galvez-Cardenas, K. M., & Varela, D. C. (2020). Uvula amyloidosis. The New England Journal of Medicine, 383(6), 577. https://doi.org/10.1056/NEJMicm1915258
Bezerra, H. K. F., de França, T. R. T., Prado, J. D., Saint-Gerons, R. S., de Amorim Carvalho, E. J., & da Cruz Perez, D. E. (2022). Oral localized amyloidosis. Head and Neck Pathology, 16(3), 818–822. https://doi.org/10.1007/s12105-022-01436-7
Chebil, R. B., Nour, M., Eya, M., Sanda, M., Badreddine, S., Lamia, O., & Nabiha, D. (2024). Oral manifestations of undiscovered systemic amyloidosis: A series of seven cases. The Pan African Medical Journal, 49, 89. https://doi.org/10.11604/pamj.2024.49.89.20032
John, S., Subba, P., Aramugam, A., Gupta, S., & Khanna, R. (2025). A serious warning: A case report on localized amyloidosis of the oral cavity. Indian Journal of Pathology & Microbiology, 68(1), 212–215. https://doi.org/10.4103/ijpm.ijpm_720_23
Takumi, K., Staziaki, P. V., Hito, R., Nadgir, R. N., Berk, J. L., Andreu-Arasa, V. C., Chavez, W., & Sakai, O. (2020). Amyloidosis in the head and neck: CT findings with clinicopathological correlation. European Journal of Radiology, 128, 109034. https://doi.org/10.1016/j.ejrad.2020.109034
Maturana-Ramírez, A., Ortega, A. V., Labbé, F. C., de Moraes, Ê., & Aitken-Saavedra, J. P. (2018). Macroglossia, the first manifestation of systemic amyloidosis associated with multiple myeloma: Case report. Journal of Stomatology, Oral and Maxillofacial Surgery, 119(6), 514–517. https://doi.org/10.1016/j.jormas.2018.06.009
Zhang, Y., Wu, Y., Yao, L., Feng, X., Luo, X., & Chen, Q. (2023). Multiple myeloma initially manifesting as a solitary deep ulcer on the tongue: A case study and literature review. European Journal of Dermatology, 33(6), 618–623. https://doi.org/10.1684/ejd.2023.4628
Xavier, S. D., Bussoloti, I. F., & Müller, H. (2005). Macroglossia secondary to systemic amyloidosis: Case report and literature review. Ear, Nose, & Throat Journal, 84(6), 358–361.
Ensign, W. G. (1952). Macroglossia as a manifestation of primary systemic amyloidosis: Report of a case. Journal of the American Medical Association, 149(2), 136–138. https://doi.org/10.1001/jama.1952.72930190001009
Dawoud, B. E. S., & Ariyaratnam, S. (2016). Amyloidosis presenting as macroglossia and restricted tongue movement. Dental Update, 43(7), 641–647. https://doi.org/10.12968/denu.2016.43.7.641
Oruba, Z., Kaczmarzyk, T., Urbańczyk, K., Jurczyszyn, A., Fornagiel, S., Gałązka, K., Bednarczyk, A., & Chomyszyn-Gajewska, M. (2018). Intraoral manifestation of systemic AL amyloidosis with unique microscopic presentation of intracellular amyloid deposition in striated muscles. Polish Journal of Pathology, 69(2), 200–204. https://doi.org/10.5114/pjp.2018.76705
Lee, A. Q., & Aronowitz, P. (2021). Scalloped tongue in primary amyloidosis. Journal of General Internal Medicine, 36(8), 2456–2457. https://doi.org/10.1007/s11606-021-06890-7
Xue, N., Kuang, W., Zhang, X., Ruan, M., Wang, J., & Zeng, X. (2023). Amyloidosis initially only manifesting as oral mucosal hemorrhagic lesions: A case series report. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 136(4), e133–e138. https://doi.org/10.1016/j.oooo.2023.07.017
Gonzalez-Ramos, J., Garrido-Gutiérrez, C., González-Silva, Y., Yébenes-Gregorio, L., Beato-Merino, M., Vidaurrázaga-Arcaya, C., & Herranz-Pinto, P. (2017). Relapsing bullous amyloidosis of the oral mucosa and acquired cutis laxa in a patient with multiple myeloma: A rare triple association. Clinical and Experimental Dermatology, 42(4), 410–412. https://doi.org/10.1111/ced.13084
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