European Journal of Prosthodontics and Restorative Dentistry (2026) 34(2s), 123–135
Keywordschronic lip fissures; cheilitis; risk factors; Nigella sativa; diode laser; CLFI; histopathology; IL-1β; Candida albicans; vitamin deficiency; diagnostic algorithm; oral mucosal disease
AuthorsAbstractBackground:Chronic lip fissures (CLF), characterised by persistent painful splits in the labial vermilion that fail to heal spontaneously within four weeks, represent a clinically significant but undercharacterised condition in oral medicine. Their multifactorial aetiology — encompassing nutritional deficiencies, microbial dysbiosis, atopic predisposition, systemic comorbidities, and parafunctional habits — complicates both diagnosis and management. Standardised severity grading, histopathological characterisation, and evidence-based treatment protocols for CLF are lacking. Objective: To characterise the clinical, morphological, immunological, and microbiological features of CLF by severity grade; identify independent risk factors; and evaluate the efficacy of an integrated treatment protocol incorporating diode laser therapy and cold-pressed Nigella sativa (black seed) oil as adjuncts to standard care. Methods: A prospective controlled clinical trial enrolled 156 patients with confirmed CLF (duration ≥4 weeks), randomised into three parallel groups: Group I (standard treatment, n=52), Group II (standard + diode laser therapy, n=52), and Group III (standard + diode laser + N. sativa oil, n=52). Clinical assessment included a novel Chronic Lip Fissure Index (CLFI), VAS pain scale, and fissure depth measurement. Histopathological evaluation, PCRbased microbiological profiling, and salivary cytokine quantification (IL1β, TNF-α, sIgA) were performed at baseline, 2 weeks, 1 month, and 3 months. Results: Vitamin B2/B6 deficiency (72.4%), lip-licking habit (64.1%), and atopic dermatitis (58.3%) emerged as the most prevalent risk factors, with adjusted ORs of 4.82 (95% CI 2.91–7.98), 3.28 (1.96–5.48), and 3.61 (2.14–6.08), respectively. Histopathological severity correlated significantly with degree of subepithelial fibrosis, vascular changes, and lymphoplasmacytic infiltration (all p<0.001). At 3 months, Group III demonstrated superior outcomes: complete healing rate 96.2% vs 69.2% (Group I) and 84.6% (Group II); IL-1β reduction 79.9% vs 39.8% and 64.9%; recurrence rate 3.8% vs 18.3% and 9.6% (all p<0.001). Conclusion: CLF severity is independently associated with nutritional deficiencies, parafunctional habits, and atopic predisposition, with histopathological severity paralleling clinical grade. The integrated protocol combining diode laser therapy and N. sativa oil with standard care significantly improves clinical, immunological, and microbiological outcomes. A validated diagnostic algorithm and CLFI grading system are proposed.
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