Tracking Immune Activity in Severe Alopecia Areata

Alopecia areata is often approached as a localized autoimmune condition of the hair follicle, yet increasing evidence suggests that disease severity may parallel measurable systemic immune activity. In this context, Sahin and colleagues examined whether readily available hematologic inflammatory signals differ by disease severity and whether they change over time in patients with severe alopecia areata who experience clinical improvement with Janus kinase (JAK) inhibitor therapy.

Rather than focusing on novel biomarkers, the investigators turned to familiar parameters derived from routine blood tests, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammation index (SII). SII integrates platelet counts with NLR, offering a composite snapshot of innate and adaptive immune balance. These indices have been explored across inflammatory dermatologic conditions, but their relationship to alopecia areata severity and treatment response has remained inconsistent.

Study Design at a Glance

This retrospective cohort study evaluated 129 participants treated at a single academic dermatology center between 2015 and 2024. The cohort comprised three equally sized groups: 43 patients with severe alopecia areata, defined by a Severity of Alopecia Tool (SALT) score of 50 or higher and treated with Janus kinase (JAK) inhibitors; 43 patients with mild alopecia areata, characterized by a SALT score of 20 or lower; and 43 age- and sex-matched healthy individuals who served as controls.

All patients in the severe group achieved at least a 50% reduction in SALT score and were included in longitudinal analyses. Most received tofacitinib, with a small minority treated with baricitinib; because of the imbalance, JAK inhibitors were analyzed as a single therapeutic class. Inflammatory markers were assessed at baseline, three months after treatment initiation, and at the time of documented clinical improvement.

Systemic Inflammation Tracks with Disease Severity

At baseline, patients with severe alopecia areata demonstrated significantly higher MLR, NLR, PLR, SII, and erythrocyte sedimentation rate (ESR) compared with both mild cases and healthy individuals (p < 0.05). In contrast, no statistically significant differences were observed between the mild alopecia areata group and controls for any measured inflammatory marker. Red cell distribution width (RDW), mean platelet volume (MPV), and C-reactive protein (CRP) did not differ significantly across groups.

This pattern suggests that systemic inflammatory activation is not a universal feature of alopecia areata but is more closely associated with extensive disease. Importantly, the absence of elevated markers in mild cases underscores the limitations of using these indices as diagnostic tools, while highlighting their potential relevance in assessing inflammatory burden in severe presentations.

Longitudinal Changes with JAK Inhibitor Therapy

Among patients with severe alopecia areata who improved clinically, several inflammatory markers declined over time. NLR and SII showed the most consistent reductions, decreasing significantly across all time points and in pairwise comparisons. PLR also declined, with significant differences observed between baseline and the point of clinical improvement (p < 0.001). MLR and CRP showed more modest but still significant reductions between baseline and clinical response (p = 0.005 and p = 0.033, respectively). ESR and RDW remained largely unchanged.

These findings align with the known mechanism of JAK inhibitors, which interrupt cytokine signaling downstream of IFN-gamma and IL-15, key drivers of immune activation in alopecia areata. While the study was not designed to establish causality or predictive value, the parallel improvement in clinical outcomes and select inflammatory indices is noteworthy.

Conclusions

Taken together, this study reinforces the concept that severe alopecia areata carries a measurable systemic inflammatory signature and that this signature can shift alongside clinical improvement with targeted immunomodulatory therapy. The authors appropriately frame these results as exploratory rather than definitive, given the retrospective design, responder-only cohort, and non-standardized follow-up intervals.

Reference:

Sahin G, Aydin F, Pancar Yuksel E. Systemic Inflammation Marker Alterations in Severe Alopecia Areata Patients Treated with Janus Kinase Inhibitors. J Clin Med. 2026;15(1):396. Published 2026 Jan 5. doi:10.3390/jcm15010396