The natural history of paraquat-associated stomatitis: A four-stage model

Abstract

Background

Paraquat-associated stomatitis (PAS) is a poorly characterized feature of paraquat poisoning and is presented as a binary finding. Despite its diagnostic potential, its evolution and prognostic value remain undefined. This pooled individual-patient analysis aimed to delineate the natural history of PAS and develop a structured, clinically applicable staging system.

Methods

Data from 170 published paraquat poisoning cases were aggregated at the individual-patient level. Variables included exposure-to-symptom interval, lesion morphology, topography, and survival outcome. Temporal and morphological patterns were analyzed using statistical tests to identify predictors of severe mucositis and mortality.

Results

Analysis of 170 cases revealed PAS in 78.8% of patients. Lesion severity and distribution followed a predictable, time-dependent progression. Severe mucositis (WHO Grade 3–4) increased from 13.9% in patients presenting within 6 h to 58.3% in those presenting at 1–3 days (p = 0.027). Anatomically, early presentations (≤6 h) were characterized by focal involvement, predominantly on the tongue (35.8%). With increasing treatment delay, lesions progressed to a multifocal and diffuse pattern, significantly involving the buccal mucosa (Absolute Risk Difference, ARD: 55.6%; p = 0.049) and oropharynx/oesophagus. A strong association existed between severe PAS and systemic complications like acute kidney injury. These patterns formed a four-stage model (Contact-Caustic, Reactive-Inflammatory Spread, Established Ulcerative/Systemic Coupling, Necrotic-Complicative), providing a structured framework for clinical staging and prognosis of PAS.

Conclusion

PAS follows a predictable, time-dependent four-stage evolution—reflecting progressive mucosal and systemic toxicity. This structured model provides a reliable framework for diagnosis, prognostication, and forensic timing of paraquat exposure.