Cocamidopropyl betaine: another possible oral healthcare chemical associated with plasma cell lesions of the oral cavity

by Jill Meyer-Lippert November 18, 2025

Jay Saepoo, DDS, MS, Nidhi Handoo, BDS, MS, Sherry Timmons, DDS, PhD, Emily Lanzel, DDS, MS, Kittiphoj Tikkhanarak, DDS, and John William Hellstein, DDS, MS

Objective.

To examine the apparent increase in plasma cell lesions of the oral cavity over the course of the past two decades and to propose a possible explanation and therapeutic approach for a subset of these cases.

Study Design.

Data from cases evaluated at the University of Iowa Surgical Oral Pathology Laboratory (UI-SOP) between July 2003 and May 2024 were retrospectively reviewed to analyze demographics, clinical presentations, and trends in the incidence of these lesions. Additionally, a subset of clinical cases seen at the Oral Pathology Clinic from 2023 to 2024 was examined to explore a potential association with the use of cocamidopropyl betaine (CAPB)-containing toothpaste.

Results.

A total of 61 cases were retrieved from UI-SOP archive and analyzed. An increase in the histopathologic diagnoses of oral plasma cell lesions was observed. The clinical case series would seem to indicate CAPB as a possible additional chemical associated with plasma cell gingivitis.

Conclusions.

Eliminating the CAPB-containing toothpaste appeared to be a predictable reason for resolution of the gingival/mucosal phenotype in multiple patients. Further collection of cases in a controlled prospective manner may be helpful in confirming the association. (Oral Surg Oral Med Oral Pathol Oral Radiol 2025;140:218 226)

Plasma cell gingivitis cases are recognized as clinical lesions that are flat to slightly raised, erythematous, and diffuse, but confined to the attached gingival surfaces. Plasma cell mucositis has been a term utilized when such lesions extend beyond the attached gingival surfaces. Plasma cell gingivitis has been described for many decades and has generally been associated with sensitivity reactions to various oral healthcare products or food flavoring agents.1-5 Histologically, these lesions exhibit a dense chronic inflammatory infiltrate predominated by plasma cells within the underlying connective tissue. Occasionally, further investigation is required to determine whether the plasma cell infiltrate represents a monoclonal plasma cell neoplasm. In plasma cell gingivitis/mucositis cases, standard immunohistochemical analysis typically reveals a bitypic polyclonal proliferation of plasma cells. Treatment of plasma cell gingivitis primarily involves the identification and elimination of potential allergens. However, when an allergen cannot be identified, treatment with topical or systemic steroids has shown variable success.

In recent years, an increasing number of plasma cell lesions have been identified in our surgical oral pathology service and among clinical patients seen in the Oral Pathology Clinic. This trend has also been observed by other oral pathologists, as noted on the Bulletin Board for Oral Pathology listserv, (https:// emmer.com/bbop/) where discussions highlighted an apparent rise in these lesions being submitted to biopsy services. For that reason, there has been a desire to try and explain this apparent increase and seek out a possible explanation. Historically, one of the most likely reasons for plasma cell gingivitis/mucositis cases were sensitivity reactions associated with chemicals such as cinnamon flavoring and herbal ingredients within the patient’s toothpaste.1,5 As a result, clinicians were often advised to recommend switching to children’s bubblegum-flavored toothpaste, which typically lacks cinnamon flavoring and herbal additives though they still usually contain sodium lauryl sulfate (SLS). This approach was effective in managing many cases. Despite this, the apparent increase in biopsy submissions and clinical diagnoses of plasma cell lesions persisted. Notably, cinnamon flavoring agents and herbal ingredients have not become significantly more prevalent in North American toothpastes, suggesting that additional, as-yet-unidentified factors may be contributing to the rising incidence of these lesions.

Statement of Clinical Relevance.

This study suggests that the recent rise in plasma cell lesions of the oral cavity may be linked to the use of cocamidopropyl betaine (CAPB)-containing toothpaste and proposes eliminating CAPB as a simple, effective therapeutic approach to improve patient outcomes.