Diagonal Earlobe Crease (Frank’s Sign) for Diagnosis of Coronary Artery Disease: A Systematic Review of Diagnostic Test Accuracy Studies

Abstract

Coronary artery disease is a global challenge for healthcare systems. Early diagnosis is a key issue to improve quality of life and reduce morbidity and mortality. Diagonal earlobe crease, a wrinkle extending obliquely across the earlobe, was linked by many authors to various atherosclerotic diseases. This systematic review aimed at summarizing the diagnostic accuracy of diagonal earlobe crease for diagnosis of chronic and acute coronary syndromes in adults. Cochrane’s recommendations for systematic reviews of diagnostic test accuracy studies were followed. The protocol was registered on PROSPERO. Seven electronic databases were searched up to April 2021. The risk of bias and applicability were assessed using the QUADAS-2 tool. Meta-analysis was not performed. Finally, 13 cross-sectional studies evaluating 3951 patients were analyzed, all of which focused on chronic coronary syndromes defined as anatomically significant coronary stenosis. Invasive coronary angiography was used as a reference in most studies, except one which utilized computed tomography angiography. Sensitivity ranged from 26% to 90%, and specificity from 32% to 96%. Positive likelihood ratios varied from 1.11 to 7.03, but most results were below 2. Negative likelihood ratios were from 0.84 to 0.30, but most values exceeded 0.5. Diagnostic accuracy of diagonal earlobe crease for the detection of chronic coronary syndromes is insufficient. It only slightly changes pre-test probability, and its mere presence or absence should not affect the clinical management of the patients. However, for its feasibility and easy interpretation, Frank’s sign could be considered as a part of physical examination.

The Relationship between the Presence of an Earlobe Crease and Overactive Bladder: A Cross-Sectional Case-Controlled Study

“…EC occurs via vascular endothelial dysfunction, which is also associated with the development of coronary vascular disease and other conditions [ 14 , 18 ]. Furthermore, EC associated with atherosclerosis may also be induced by skin aging, collagen degeneration, and telomere shortening [ 19 , 20 , 21 , 22 ]. The EC lesion induced by these consequences ultimately alters the shape of the ear, through the progression of ischemia-induced fibrosis [ 23 ].…”

The importance of inspection in clinical cardiology: Frank's sign

“… 11 Furthermore, a recent systematic review showed that the diagnostic accuracy of diagonal earlobe crease for detecting chronic coronary syndromes is insufficient. 12 Additionally, the Fremantle Diabetes Study assessed the clinical usefulness of FS as a sign of coronary artery disease or retinopathy in type 2 diabetes. 13 This study found that FS was not a significant independent predictor of either coronary artery disease or retinopathy.…”

“…By contrast, an observational study found no significant association between FS and abnormal ankle‐branchial index 11 . Furthermore, a recent systematic review showed that the diagnostic accuracy of diagonal earlobe crease for detecting chronic coronary syndromes is insufficient 12 . Additionally, the Fremantle Diabetes Study assessed the clinical usefulness of FS as a sign of coronary artery disease or retinopathy in type 2 diabetes 13 .…”

Patients with Earlobe Crease May Associate with Lower Concentration of the Age-Suppressing Hormone Klotho

“… 41 In the meantime, there are several systematic reviews disproving such association. 42 , 43 There is also emerging research linking ELC to the mechanical traction secondary to visceral obesity of the face. 44 Furthermore, congenital earlobe creases were notes in neonates with Beckwith-Wiedemann syndrome.…”