Corneal confocal microscopy demonstrates minimal evidence of distal neuropathy in children with celiac disease.

Hoda Gad,Adnan Khan,Hatim Abdelrahman,Bara Al-Jarrah,Saras Saraswathi,Georgios Ponirakis,Rayaz A Malik,Anthony K Akobeng,Parul Singh,Mamoun Elawad,Fatma Al-Mudahka,Khalid Hussain,Paraic Mcgrogan,Khaled Abouhazima,Souhaila Al Khodor,Wesam Almasri,Mohamed A Hendaus,Ioannis N Petropoulos,James Wolffsohn

doi:10.1371/journal.pone.0238859

Hoda Gad, Adnan Khan + Show 17 more

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https://doi.org/10.1371/journal.pone.0238859

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Abstract

The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease. This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually. Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002). Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease.

Highlights

Celiac disease (CD) occurs in approximately 0.2–5.5% of children [1]
Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls
Peripheral neuropathy may develop independent of enteropathic symptoms or lack of adherence to a gluten free diet (GFD) [6]

Summary

Introduction

Celiac disease (CD) occurs in approximately 0.2–5.5% of children [1]. CD is classically associated with gastrointestinal (GI) symptoms such as diarrhea, abdominal pain, malabsorption and weight loss. Neurological manifestations including cerebellar ataxia, gluten encephalopathy, sensorineural hearing loss, headache and cognitive decline occur in about 10% of adults with CD [3]. A recent systematic review established that up to 39% of adults with CD may have gluten neuropathy [4]. Found a small fiber neuropathy characterized by burning, tingling and numbness in the hands and feet and diffuse paraesthesiae involving the face, trunk, and lumbosacral region in 40% of adults with CD, mildly abnormal electrophysiology in 90% and a mild-to-severe axonopathy in nerve biopsies [7]. In a study of 13 CD patients, 8 had neuropathic pain, 6 had cerebellar ataxia, 1 had white matter abnormalities on magnetic resonance imaging (MRI) of the brain and 1 had ataxia and cortical myoclonus [8]. A nationwide population-based study of patients with biopsy verified-CD reported an absolute risk of neuropathy of 64 per 100,000 person years in CD patients compared to 15 per 100,000 in matched controls; with an estimated risk of neuropathy being highest in the early years of diagnosis with CD (HR 4.4; 95% CI 2.6–7.4; P < 0.001) [9]

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