Kapnia AK, Mantzios K, Karanika P, Angelopoulou-Athanatou EV, Tsaklis PV, Flouris AD. Physiological responses of individuals with idiopathic chilblains during cold exposure and rewarming: a nonrandomized clinical trial. Am J Physiol Regul Integr Comp Physiol. 2026 May 1;330(5):R530-R536. doi: 10.1152/ajpregu.00157.2025. Epub 2026 Apr 6. PMID: 41941353.
Abstract
Idiopathic chilblains (IC) is a localized inflammatory disorder affecting acral areas, with unclear pathophysiology and pathogenesis. This study aimed to investigate the vasomotor, autonomic, and inflammatory responses of adults with (HIC+) and without (HIC-) a history of IC during cold exposure and rewarming. Sixteen healthy adults (8 HIC+, 8 HIC-; 10 females, 6 males; aged 19-60 yr) underwent a controlled environmental protocol involving progressive cooling (22-10°C) followed by rewarming (22°C). Skin blood flow (SkBF); finger and toe temperatures (Tf and Tt); mean skin temperature (Tsk); microvascular oxygenation parameters including tissue saturation index (TSI), oxyhemoglobin (O2Hb), and deoxyhemoglobin (HHb); and total blood volume (tHb) were recorded throughout. Serum cortisol, ferritin, vitamin D3, antinuclear antibodies (ANAs), and scleroderma antibody (SCL-70) were also assessed. Compared to HIC- participants, the HIC+ group showed significantly lower SkBF (|d| = 0.43-0.56; P < 0.05) and Tf and Tt (|d| = 0.07-0.75) during cold exposure, along with reduced O2Hb (|d| = 0.33 at 10°C) and increased HHb (|d| = 0.43-0.46 at 14 and 10°C), suggesting impaired oxygen delivery. No between-group differences were observed in TSI. During rewarming, SkBF (47.06 ± 54.94 vs. 22.69 ± 21.48 PU) and HHb levels (5.53 ± 3.64 vs. 3.07 ± 2.84 μM) in the right finger were higher in the HIC+ than the HIC- group (|d| = 0.35-0.54). No significant differences were observed in serum cortisol or thermal perception. No participants developed chilblains or acral symptoms during the 8-wk follow-up. These findings indicate that individuals with a history of IC exhibit heightened cold-induced vasoconstriction and peripheral microvascular hypoxia, which may underlie susceptibility to chilblains and nonfreezing cold injuries.NEW & NOTEWORTHY This is the first study to investigate the vascular and oxygenation responses to cold and rewarming conditions in otherwise healthy adults with a history of idiopathic chilblains. By combining controlled environmental exposure with thermophysiological assessment, the study identifies a hyperconstrictive-hypoxic microvascular phenotype. Future work should explore the role of adrenergic receptor polymorphisms and rewarming kinetics as potential modulators of vascular stress and therapeutic targets for preventing nonfreezing cold injuries.
Keywords: environmental physiology; idiopathic chilblains; microvascular oxygenation; skin blood flow; thermoregulation.
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