Juvenile Autoimmune Myasthenia Gravis due to Thymoma Following Coronavirus Disease 2019 Infection in a Child

Vykuntaraju K Gowda¹ https://orcid.org/0000-0001-7244-0492, Varsha Reddy², Dhananjaya KVN³, Usha Amirtham⁴

^1,2Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India

³Department of Radiodiagnosis & Imaging, Kasturba Medical College, Mangaluru, Karnataka, India

⁴Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Corresponding Author: Vykuntaraju K Gowda, Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India, Phone: +91 9535212556, e-mail: drknvraju08@gmail.com

Received on: 14 August 2022; Accepted on: 05 September 2023; Published on: 15 April 2023

ABSTRACT

Introduction: The acquired myasthenia gravis (MG) is an autoimmune neuromuscular junction (NMJ) disorder. Thymomas and thymic carcinomas are extremely rare in children. We are reporting a rare case of MG following the coronavirus disease 2019 (COVID-19) infection.

Case description: A 10-year-old girl presented with difficulty in getting up from sitting, swallowing, and drooping of eyelids. Weakness was more in the evening. On examination, bilateral ptosis had a power of 2/5 in the proximal and 3/5 in the distal group of muscle. There was a history of COVID-19 infection 45 days ago. Investigations revealed a decremental response in repetitive nerve stimulation. The neostigmine challenge test noted improvement in ptosis and weakness. Computed tomography (CT) showed a large thymic lesion. Antibody to the acetylcholine receptor (AChR) and COVID-19 spike protein was positive. Treated with oral pyridostigmine, steroids, and thymectomy, and showed significant improvement in power. Histopathology of the excised mediastinal mass revealed type B2 thymoma.

Conclusion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can precipitate MG in the underlying thymoma.

How to cite this article: Gowda VK, Reddy V, V N DK, et al. Juvenile Autoimmune Myasthenia Gravis due to Thymoma Following Coronavirus Disease 2019 Infection in a Child. Pediatr Inf Dis 2023;5(1):20-22.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patient’s parents/legal guardians for publication of the case report details and related images

Keywords: Acetylcholine receptor antibodies, Coronavirus disease 2019 infection, Gravis, Myasthenia, Thymoma.

INTRODUCTION

Acquired MG is an autoimmune disorder of the NMJ.¹ It is caused by autoantibodies directed toward the skeletal muscle AChR or muscle-specific receptor tyrosine kinase antibodies.² The thymus gland plays a role in the origin of the anti-AChR antibodies.³ Thymomas and thymic carcinomas are extremely rare in children, and only a few studies have been published to date.⁴ There are two reports of COVID-19 infection-related exacerbation of the preexisting MG.⁵^,⁶ There are no reports of MG secondary to COVID-19 in children; hence we are reporting this case.

CASE DESCRIPTION

A 10-year-old girl presented with difficulty in walking, getting up from lying posture and sitting, falls while climbing stairs, and difficulty chewing and swallowing and drooping of both eyelids. Weakness was more in the evening. There was a history of COVID-19 infection 45 days ago. On examination, the child was conscious and oriented, and bilateral symmetric ptosis was present (Fig. 1A). The tone was decreased in all four limbs, with the power of 2/5 in the proximal muscles, and 3/5 in the distal group of muscles, deep tendon reflexes were intact, and flexor plantar response. Investigations revealed serum creatinine phosphokinase was 120 units/L (normal—20–200), and thyroid stimulating hormone was 2.03 mU/L (normal—0.4–5). The nerve conduction velocity of all four limbs was normal. Repetitive nerve stimulation testing (RNST) showed a decremental response in the right median and ulnar nerves (Fig. 2). On the neostigmine challenge test, timed fatigable weakness showed improvement in ptosis and weakness (Figs 1B and C). Contrast-enhanced CT of the thorax showed a large thymic lesion (Fig. 3). Antibody to AChR was positive—36.6 pmol/mL (normal <0.25). Anti-muscle specific kinase antibody—negative. COVID-19 spike protein antibodies were positive >250 U/mL. The child was diagnosed to have juvenile MG. The child was treated with oral pyridostigmine and showed significant improvement in activity after starting treatment. Oral prednisolone started at 1 mg/kg/day. Histopathology of the excised mediastinal mass revealed a neoplasm composed of polygonal neoplastic cells with large nuclei and prominent nucleoli arranged in aggregates admixed with numerous lymphocytes. Immunohistochemistry showed positivity for cytokeratin (CK) and p63 and negativity for cluster of differentiation 5 and C117 (Fig. 4), suggestive of type B2 thymoma.

Figs 1A to C: Clinical photo (A) Showing bilateral ptosis, and narrow palpebral fissure before (B) and after (C) Neostigmine challenge test

Fig. 2: Repetitive nerve stimulation testing (RNST) of the right median nerve showing decremental response in the lower panel

Figs 3A to F: (A) Frontal radiograph of chest showing enlarged mediastinal soft tissue (arrow). (B to F) Plain and contrast-enhanced CT of the chest with reformatted coronal and sagittal sections showing soft tissue mass lesion in the anterior mediastinum with mild post-contrast enhancement (arrow). It is seen in prevascular and para-aortic regions with maintained fat planes. The small non-enhancing hypodense area seen in the prevascular region adjacent to the left main pulmonary artery suggests necrosis (curved arrow)

Figs 4A to F: Immunomorphology of the mediastinal mass. Histopathology of lesions shows (A) Hematoxylin and eosin (H and E) ×20 neoplasm with serum lakes, (B) H and E ×100, and (C) H and E ×400 neoplastic cells admixed with lymphocytes, (D) IHC—CK neoplastic cells are positive for CK, (E) IHC—p63, (F) Neoplastic cells are positive for P63.

DISCUSSION

Here, we report a 10-year-old girl presenting with MG following COVID-19 infection with underlying thymoma. Various neurological manifestations of SARS-CoV-2 described are meningoencephalitis, acute disseminated encephalomyelitis, encephalopathy, posterior reversible encephalopathy syndrome, hyposmia/ageusia, ophthalmoparesis, facial paresis, Guillain-Barré syndrome, neuropathy, myalgia, myositis, and rhabdomyolysis.

We diagnosed juvenile MG based on classical clinical features of fatigable weakness, improvement in symptoms following the neostigmine challenge test, decremental response in repetitive nerve stimulation, and positive antibodies to AChRs. We diagnosed as following COVID-19 infection as a child with COVID-19 infection with reverse transcription polymerase chain reaction positive 45 days prior to weakness and positive antibodies for COVID-19 spike protein antibodies during this presentation.

There are only a few recent reports of MG following infections.⁷^,⁸ The molecular mimicry between the AChR and SARS-CoV-2 proteins might be the reason for MG following SARS-CoV-2 infections.⁹ CT scan of the chest shows a large lesion with both cystic and solid components suggestive of a long-standing lesion. In our child’s classical COVID-19 symptoms and the SARS-CoV-2 antibodies, we assume a COVID-19 infection triggered the MG in underlying asymptomatic thymoma in this child.

CONCLUSION

This is the first case of post-SARS-CoV-2 infection-triggered MG in a child. Thymoma should be considered in children with MG following SARS-CoV-2 infection, as they may require surgical excision.

ORCID

Vykuntaraju K Gowda https://orcid.org/0000-0001-7244-0492

REFERENCES

1. Drachman DB. Myasthenia gravis. N Engl J Med 1994;330(25):1797–1810. DOI: 10.1056/NEJM199406233302507

2. Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001;7(3):365–368. DOI: 10.1038/85520

3. Roxanis I, Micklem K, Willcox N. True epithelial hyperplasia in the thymus of early-onset myasthenia gravis: implications for immunopathogenesis. J Neuroimmunol 2001;112(1–2):163–173. DOI: 10.1016/s0165-5728(00)00415-x

4. Stachowicz-Stencel T, Bien E, Balcerska A, et al. Thymic carcinoma in children: a report from the polish pediatric rare tumors study. Pediatr Blood Cancer 2010;54(7):916–920. DOI: 10.1002/pbc.22482

5. Ramaswamy SB, Govindarajan R. COVID-19 in refractory myasthenia gravis- a case report of successful outcome. J Neuromuscul Dis 2020;7(3):361–364. DOI: 10.3233/JND-200520

6. Anand P, Slama MCC, Kaku M, et al. COVID-19 in patients with myasthenia gravis. Muscle Nerve 2020;62(2):254–258. DOI: 10.1002/mus.26918

7. Saha A, Batra P, Vilhekar KY, et al. Post-varicella myasthenia gravis. Singapore Med J 2007;48(6):e177–e180. PMID: 17538742. PMID: 17538742.

8. Felice KJ, DiMario FJ, Conway SR. Postinfectious myasthenia gravis: report of two children. J Child Neurol 2005;20(5):441–444. DOI: 10.1177/08830738050200051501

9. Schwimmbeck PL, Dyrberg T, Drachman DB, et al. Molecular mimicry and myasthenia gravis. J Clin Invest 1989;84(4):1174–1180. DOI: 10.1172/JCI114282

________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.