The platelet-to-lymphocyte ratio (PLR) has emerged as an informative marker revealing shifts in platelet and lymphocyte counts due to acute inflammatory and prothrombotic states. PLR has been extensively examined in neoplastic diseases accompanied by immune suppression and thrombosis, which can be predicted by combined blood cell counts and their ratios. Several large observational studies have demonstrated the value of shifts in PLR in evaluating the severity of systemic inflammation and predicting infections and other comorbidities, in inflammatory rheumatic diseases. The value of PLR as an inflammatory marker increases when its fluctuations are interpreted along with other complementary hematologic indices, particularly the neutrophil-to-lymphocyte ratio (NLR), which provides additional information about the disease activity, presence of neutrophilic inflammation, infectious complications, and severe organ damage in systemic lupus erythematosus. PLR and NLR have high predictive value in rheumatic diseases with predominantly neutrophilic inflammation (e.g., Behçet disease and familial Mediterranean fever). High PLR, along with elevated platelet count, is potentially useful in diagnosing some systemic vasculitides, particularly giant-cell arteritis. A few longitudinal studies on rheumatic diseases have demonstrated a decrease in PLR in response to anti-inflammatory therapies. The main limitations of PLR studies are preanalytical faults, inadequate standardization of laboratory measurements, and inappropriate subject selection. Nonetheless, accumulating evidence suggests that PLR can provide valuable information to clinicians who encounter multisystem manifestations of rheumatic diseases, which are reflected in shifts in platelet, lymphocyte, neutrophil, or monocyte counts. Interpretation of PLR combined with complementary hematologic indices is advisable to more accurately diagnose inflammatory rheumatic diseases and predict related comorbidities.

Scientific hypotheses are essential for progress in rapidly developing academic disciplines. Proposing new ideas and hypotheses require thorough analyses of evidence-based data and predictions of the implications. One of the main concerns relates to the ethical implications of the generated hypotheses. The authors may need to outline potential benefits and limitations of their suggestions and target widely visible publication outlets to ignite discussion by experts and start testing the hypotheses. Not many publication outlets are currently welcoming hypotheses and unconventional ideas that may open gates to criticism and conservative remarks. A few scholarly journals guide the authors on how to structure hypotheses. Reflecting on general and specific issues around the subject matter is often recommended for drafting a well-structured hypothesis article. An analysis of influential hypotheses, presented in this article, particularly Strachan's hygiene hypothesis with global implications in the field of immunology and allergy, points to the need for properly interpreting and testing new suggestions. Envisaging the ethical implications of the hypotheses should be considered both by authors and journal editors during the writing and publishing process.