Abstract
Introduction: Liver iron concentration (LIC), measured by magnetic resonance imaging (MRI), remains the gold standard for assessing total body iron burden in patients with thalassemia. However, MRI is costly, requires specialized infrastructure, and is often inaccessible in low-resource settings.
Iron overload has been linked to cutaneous hyperpigmentation, attributed to dermal iron deposition and iron-induced melanogenesis. These skin changes may reflect systemic iron accumulation. Skin lightness (L* value), measured by a Chromameter, provides an objective, reproducible, and non-invasive method that may serve as a surrogate marker for LIC. This study explores the correlation between skin lightness and MRI-assessed LIC in thalassemia patients, aiming to evaluate its potential as a simple screening tool for iron overload.
Methods: This cross-sectional study enrolled adult thalassemia patients from the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital, Thailand, between January and July 2025. LIC was quantified using T2*-weighted MRI to assess hepatic iron overload. Skin color lightness (L*) was measured using a calibrated Minolta Chromameter (CR-200) at the inner upper arm, lower abdomen, and lower back. The L* value represents skin lightness on a grayscale ranging from 0 (black) to 100 (white). Hemoglobin levels, serum ferritin, and liver function tests were assessed during the same timeframe.
Pearson's correlation was used to assess the relationship between L* values and LIC. Logistic regression identified factors associated with LIC ≥7 mg/g dry weight. Receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of mean L* values and serum ferritin.
Results: Seventy-four adult thalassemia patients were included (mean age 43.8 ± 14.2 years; 40.5% male), 51.4% were transfusion-dependent, and 71.6% had β-thalassemia disease. LIC ≥7 mg/g dry weight was found in 51.4% of patients. Mean skin lightness (L*) values were significantly lower in patients with high LIC at all anatomical sites compared with those in the low LIC group (62.7 ± 3.6 vs 65.5 ± 3.6, p = 0.002). L* showed a significant inverse correlation with LIC (r = -0.404, p < 0.001).
In univariable logistic regression, transfusion dependence (OR 2.69, 95% CI: 1.05–6.89, p = 0.039), elevated alanine transaminase (ALT) levels (OR 1.05, 95% CI: 1.01–1.09, p = 0.013), and lower L* values (OR 0.81, 95% CI: 0.70–0.93, p = 0.004) were significantly associated with LIC ≥7 mg/g dry weight. After adjusting for potential confounders (serum ferritin, transfusion dependency, elevated ALT levels), L* was associated with high LIC with an OR of 0.80 (95% CI: 0.68–0.94, p = 0.007). ROC analysis showed that L* <66 predicted LIC ≥7 mg/g dry weight with 84.2% sensitivity, 55.6% specificity (AUC = 0.699), outperforming ferritin >1,000 ng/mL (sensitivity 57.9%, specificity 72.2%, AUC = 0.651).
Conclusion: Chromameter-assessed skin lightness demonstrated a significant inverse correlation with LIC and moderate predictive accuracy for identifying patients with clinically relevant hepatic iron overload. Given its superior sensitivity to serum ferritin, this method may serve as a non-invasive screening tool for liver hemochromatosis.
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