Clinical and Histopathological Characteristics of Granuloma Annulare: Significance of Giant Cells and Systemic Inflammatory Markers

<b>Background</b><b>:</b> Granuloma Annulare (GA) is a chronic inflammatory dermatosis with diverse presentations, yet comprehensive data integrating histopathology, long-term prognosis, and systemic inflammatory markers remain limited. This study aimed to analyze these clinicopathological characteristics and identify biomarkers for chronicity and recurrence. <b>Methods:</b> In this retrospective cohort study, we evaluated 34 patients with histopathologically confirmed GA diagnosed between 2013 and 2023. Demographic data, clinical features, comorbidities, treatment outcomes, and laboratory parameters were analyzed. Histopathological findings were re-evaluated to assess pattern types and the presence of specific markers. Statistical correlations between clinical parameters, inflammatory markers, and histopathological features were assessed. <b>Results:</b> The interstitial pattern was the predominant histopathological subtype (64.7%), with universal mucin deposition (100%). A statistically significant positive correlation was observed between lesion duration and the presence of multinucleated giant cells (r = 0.456, <i>p</i> = 0.033), suggesting a time-dependent granuloma maturation. Clinically, generalized GA cases demonstrated significantly longer recovery times compared to localized forms. The overall recurrence rate was 23.5%. A lower BLR was significantly associated with disease recurrence (r = −0.539, <i>p</i> = 0.021). At least one comorbidity was present in 76.5% of the patients. <b>Conclusions:</b> Our findings suggest that giant cell formation serves as a histopathological marker of lesion chronicity, supporting the concept of granuloma remodeling over time. Furthermore, a suppressed BLR may serve as a novel surrogate marker associated with disease recurrence. Given the high burden of comorbidities observed in both localized and generalized forms, GA should be approached as a cutaneous manifestation of underlying systemic dysregulation, suggesting that clinicians should consider routine metabolic screening for these patients.