When did "I don't know" become a diagnosis? A conceptual review on diagnoses of exclusion

Diagnosis of exclusion (DOE) is a term used when a conclusive diagnosis of a condition cannot be reached after exhausting a list of differential diagnoses. A comprehensive search across multiple electronic databases and AI-assisted search platforms was conducted to identify published literature related to DOE. The search identified 29 conditions with a DOE and several articles discussing the concept of DOE. However, no publication reported specific criteria or frameworks to help clinicians reach a DOE. Deliberative, iterative discussions were held with clinical specialists and experts in oral medicine, clinical epidemiology, and probabilistic diagnostics, to discuss the identified publications. Once a consensus was reached, a DOE framework based on probabilistic diagnostics was proposed. This conceptual review proposes a decision-making framework that applies a probabilistic diagnostic approach to reaching a DOE. The proposed framework allows clinicians to establish a diagnostic workup to navigate decision-making thresholds that will guide clinicians in reaching a definitive diagnosis, or alternatively, a DOE with more certainty.