The Histological Basis of Frank’s Sign

Stoyanov, George S; Dzhenkov, Deyan; Petkova, Lilyana; Sapundzhiev, Nikolay; Georgiev, Svetoslav

doi:10.1007/s12105-020-01205-4

Cited by 22 publications

(23 citation statements)

References 17 publications

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“…In agreement with previous studies, we have found an association between the Frank’s sign and age, with it being more prevalent in patients over 70 years. A possible explanation for this is that ELC reflects the ageing processes of skin and arteries [ 12 , 14 ]. We also found an association of ELC with classical vascular risk factors involved in atherosclerotic disease, especially with hypertension, and diabetes, as well as the presence of non-stenotic carotid plaques.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent histopathological study in 45 consecutive adult patients referred for autopsy, Stoyanov GS et al analysed samples from both earlobes as well as cardiac samples from all four cardiac compartments. They found a significant correlation between the morphological changes of the myocardium and the presence of the earlobe creases with arterial myoelastofibrosis, Wallerian-like degeneration in peripheral nerves, and deep tissue fibrosis found in the base of the crease [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of the Frank’s sign by aetiopathogenic stroke subtype: A prospective analysis

et al. 2021

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Background and purpose The Frank’s sign is a diagonal earlobe crease running from the tragus to the edge of the auricle at an angle of 45°. Many studies have associated this sign with coronary artery disease and some with cerebrovascular disease. The objective of this study was to analyse the prevalence of the Frank’s sign in patients suffering from acute stroke with a particular focus on its prevalence in each of the five aetiopathogenic stroke subtypes. Special interest is given to embolic stroke of undetermined source (ESUS), correlating the sign with clinical and radiological markers that support an underlying causal profile in this subgroup. Methods Cross-sectional descriptive study including 124 patients admitted consecutively to a stroke unit after suffering an acute stroke. The Frank’s sign was evaluated by the same blinded member of the research team from photographs taken of the patients. The stroke subtype was classified following SSS-TOAST criteria and the aetiological study was performed following the ESO guidelines. Results The Frank’s sign was present in 75 patients and was more prevalent in patients with an ischaemic stroke in comparison with haemorrhagic stroke (63.9 vs. 37.5, p<0.05). A similar prevalence was found in the different ischaemic stroke subtypes. The Frank’s sign was significantly associated with age, particularly in patients older than 70 who had vascular risk factors. Atherosclerotic plaques found in carotid ultrasonography were significantly more frequent in patients with the Frank’s sign (63.6%, p<0.05). Analysing the ESUS, we also found an association with age and a higher prevalence of the Frank’s sign in patients with vascular risk factors and a tendency to a high prevalence of atherosclerosis markers. Conclusion The Frank’s sign is prevalent in all aetiopathogenic ischaemic stroke subtypes, including ESUS, where it could be helpful in suspecting the underlying cardioembolic or atherothrombotic origin and guiding the investigation of atherosclerosis in patients with ESUS and the Frank’s sign.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prevalence of the Frank’s sign by aetiopathogenic stroke subtype: A prospective analysis

et al. 2021

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“…Autopsy studies involving biopsies of ear lobes in patients with DELC found thickening of arterial walls and tears in the elastin (21) and that both earlobe and myocardium are supplied by end arteries without collateral circulation (22) . More recently Stoyanov (23) found that patients with DELC had diffuse fibrosis of an arterial vessel located at the base of the ear lobe crease and that this was associated with corresponding changes to myocardial tissue. As with our study, Stoyanov et al also found that this correlation was independent of age.…”

Section: Pathophysiologymentioning

confidence: 99%

Why we should be looking for ear lobe creases. A systematic review and meta-analysis of diagonal ear lobe crease and coronary artery disease.

Curtis

Walford

2020

Preprint

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Objectives The association between diagonal ear lobe crease (DELC) and cardiovascular disease was first suggested in 1973 although some studies have attributed this to confounding cardiovascular factors. This review looked to see if there is a significant association between DELC and angiography-confirmed coronary artery disease (CAD) independent of other risk factors. Design Systematic review and meta-analysis of selected studies using the PRISMA checklist. Setting 12 different hospitals with angiography in eight countries. Participants 4960 adult patients undergoing coronary angiography. Main Outcome Measures • Presence/absence of diagonal ear lobe crease • Diagnostic Odds Ratio • Sensitivity/Specificity Results 12 studies were included in the meta-analysis. Findings from our study suggest: • Patients with DELC have a 4x increased likelihood of having CAD (OR 4.61 P<0.00001). • The relationship between DELC and CAD was independent of age and all other conventional cardiovascular risk factors. • Bilateral DELC has a stronger association with CAD than unilateral DELC. • Presence of DELC has insufficient sensitivity / specificity to be used as a diagnostic test for cardiovascular disease but instead should be used as a risk marker. Conclusions We found that DELC is associated with CAD independently of other known cardiovascular risk factors including age. Histology studies indicate that atherosclerosis is causing DELC and patients with DELC appear to have an increased risk of CAD. It has insufficient sensitivity or specificity to be used as a diagnostic test but should be used as a valuable risk marker to be aware of whilst examining ears.

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“…It could be used in primary care or emergency departments if its diagnostic accuracy is sufficient to support decision-making. In 2020, Stoyanov et al published research investigating earlobes along with cardiac samples in the autopsy study [7]. Histopathological examination of DELC-positive earlobes showed myoelastofibrosis in the arterial vessel located at the base of the earlobe, fibrosis, and Wallerian-like degeneration with eosinophilic inclusions in the peripheral nerves.…”

Section: Introductionmentioning

confidence: 99%

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

Więckowski

Gallina

Surdacki

et al. 2021

JCM

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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.

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The Histological Basis of Frank’s Sign

Cited by 22 publications

References 17 publications

Prevalence of the Frank’s sign by aetiopathogenic stroke subtype: A prospective analysis

Prevalence of the Frank’s sign by aetiopathogenic stroke subtype: A prospective analysis

Why we should be looking for ear lobe creases. A systematic review and meta-analysis of diagonal ear lobe crease and coronary artery disease.

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

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