Systemic Anti-Inflammatory Effects of Isotretinoin: Evaluation of Red Cell Distribution Width to Lymphocyte and Platelet Ratios as New Hematological Markers and Clinical Outcomes in Acne Vulgaris.

Background: Acne vulgaris is a chronic inflammatory skin disease influenced by systemic immune responses. While isotretinoin is the most effective treatment for severe acne, its effects on hematological markers of inflammation, in particular red cell distribution width (RDW)-to-lymphocyte and RDW-to-platelet ratios, remain unclear.

Methods: This retrospective study analyzed 450 acne patients treated with isotretinoin for at least 24 weeks. Hematological parameters, including complete blood count (CBC) indices, RDW-derived ratios, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), as well as biochemical markers (ALT, AST, ALP) and clinical measures (lesion counts, Global Acne Grading Score [GAGS], Dermatology Life Quality Index [DLQI], SF-36, and Hospital Anxiety and Depression Scale [HADS]) at baseline and weeks 8, 16, and 24.

Results: Isotretinoin treatment was associated with significant reductions in systemic inflammatory markers, including WBC count, NLR, and MLR, while lymphocyte count increased (p < 0.001). The ratios of RDW to lymphocytes and RDW to platelets also decreased over time (p < 0.001). Liver enzymes remained stable. Clinical assessments showed significant improvements in acne severity, quality of life, and mental health scores (p < 0.001). Adverse events were reported in 90.7% of patients, with musculoskeletal symptoms and constipation more common than previously reported.

Conclusion: This study highlights the systemic immunomodulatory effects of isotretinoin, particularly the significant changes in RDW-derived ratios, suggesting their potential as novel inflammatory markers. These findings reinforce the broader effects of isotretinoin beyond sebaceous gland suppression and support its role in the regulation of systemic inflammation.