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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 12  |  Issue : 5  |  Page : 235-237

Childhood-onset systemic lupus erythematosus, probably triggered by severe acute respiratory syndrome coronavirus 2 infection, presenting with autoimmune haemolytic anaemia


1 Department of Pediatrics, Baby Memorial Hospital, Kozhikode, Kerala, India
2 Department of Clinical Hematology, Baby Memorial Hospital, Kozhikode, Kerala, India
3 Department of Pathology, Baby Memorial Hospital, Kozhikode, Kerala, India

Date of Submission25-Dec-2021
Date of Decision16-Mar-2022
Date of Acceptance25-Apr-2022
Date of Web Publication31-Oct-2022

Correspondence Address:
Abdul Rauf
Department of Pediatrics, Baby Memorial Hospital, Kozhikode - 673 004, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_123_21

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  Abstract 


Systemic lupus erythematosus (SLE) is a multisystemic and chronic autoimmune disease with varying clinical manifestations. The role of various infectious agents in triggering the disease onset in genetically predisposed patients has been implicated in the pathogenesis of SLE. The severe acute respiratory syndrome coronavirus 2 has been reported to trigger various autoimmune diseases including SLE in few adults. Herein, we report the case of a previously well 12-year-old girl who presented with warm antibody Coombs-positive autoimmune haemolytic anaemia, 3 weeks after testing positive for COVID-19. COVID IgG antibody test was positive. During the hospital stay, she developed multisystem involvement in the form of neurological manifestations and arthritis. She was managed with steroids, intravenous (IV) immunoglobulins and supportive measures. Her anti-nuclear antibody and anti-dsDNA antibodies were positive and complement levels were low, confirming a diagnosis of SLE. Her clinical condition improved rapidly and remained neurologically normal, and serial haemoglobin showed an improving trend. IV steroids were changed to oral form, and hydroxychloroquine was also added. She remained well on 3-week follow-up.

Keywords: Autoimmune haemolytic anaemia, children, COVID-19, severe acute respiratory syndrome coronavirus 2, systemic lupus erythematosus


How to cite this article:
Rauf A, Thekkudan SF, Mampilly N, Vijayan A. Childhood-onset systemic lupus erythematosus, probably triggered by severe acute respiratory syndrome coronavirus 2 infection, presenting with autoimmune haemolytic anaemia. Curr Med Res Pract 2022;12:235-7

How to cite this URL:
Rauf A, Thekkudan SF, Mampilly N, Vijayan A. Childhood-onset systemic lupus erythematosus, probably triggered by severe acute respiratory syndrome coronavirus 2 infection, presenting with autoimmune haemolytic anaemia. Curr Med Res Pract [serial online] 2022 [cited 2022 Nov 27];12:235-7. Available from: http://www.cmrpjournal.org/text.asp?2022/12/5/235/359948




  Introduction Top


Systemic lupus erythematosus (SLE) is a multisystemic and chronic autoimmune disease with varying clinical manifestations.[1] The role of various viruses in triggering the disease in genetically predisposed patients has been implicated in the pathogenesis of SLE. We report the case of a childhood-onset SLE (cSLE), probably triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.


  Case Report Top


A previously well 12-year-old girl tested polymerase chain reaction (PCR) positive for SARS-CoV-2 infection during routine screening and had asymptomatic infection. Three weeks later, she developed progressive fatiguability and was referred to our centre. At the time of admission, she had severe pallor but was haemodynamically stable, and systemic examination was normal. Preliminary investigations revealed features of autoimmune haemolytic anaemia (haemoglobin: 7.0 g/dl, lactate dehydrogenase: 365 U/L, total bilirubin: 2.1 mg/dl and elevated corrected reticulocyte count: 3.5%), polychromasia with nucleated RBCs in peripheral smear and positive direct and indirect Coombs test with monospecific anti-human globulin card test showing anti-IgG and anti-C3d-positive 4+. SARS-CoV-2 PCR test was negative, and IgG antibody was positive. Her C-reactive protein (25 mg/l), erythrocyte sedimentation rate (90 mm/h) and D-dimer (2.9 ng/ml) were elevated. Twelve hours after the admission, she developed acute-onset headache and delirium and had signs of meningeal irritation. She was also noted to have swelling in the left knee joint with tenderness, which had developed over few hours.

She was stabilised with neuroprotective measures, and antibiotics were started. Lumbar puncture was done, and cerebrospinal fluid analysis revealed cells – 5 (all lymphocytes), glucose – 100 mg/dl and protein – 20 mg/dl, which ruled out bacterial meningitis. Considering the clinical presentation of acute involvement of multiple systems with positive SARS-CoV-2 IgG antibody and elevated inflammatory markers, an atypical presentation of multisystem inflammatory syndrome in children (MIS-C), a post-COVID autoimmune process was considered as the first diagnosis. She was managed with IV steroids (dexamethasone 0.15 mg/kg/dose 6th hourly), intravenous immunoglobulin (IVIG, 2 g/kg over 24 h) and aspirin (treatment protocol for MIS-C).[2] Her neurological status improved dramatically within few hours of steroid initiation. She was also given one aliquot/unit of packed red blood cell transfusion. Bone marrow smear showed erythroid hyperplasia with lupus erythematosus (LE) cells [Figure 1]. Her autoimmune workup sent at the time of admission was available by day 3. Her anti-nuclear antibody (ANA) (by immunofluorescence) (3+), dsDNA (3+) and anti-histone antibodies (3+) were strongly positive. Serum complement levels such as C3 – 50 mg/dl (75–135) and C4 – 6 mg/dl (9–36) were low. There was no evidence of glomerulonephritis, and echocardiography was normal. A diagnosis of SLE was made based on the clinical features and immunological markers (2019 European League Against Rheumatism/American College of Rheumatology, score of 16).[3] On review of history, it was confirmed that she was completely asymptomatic and had no features of SLE before the COVID infection. Hence, it was highly probable that cSLE was triggered by SARS-CoV-2. IV steroids were changed to oral formulation (prednisolone) from day 4, and hydroxychloroquine was added. Her serial haemograms showed improvement in Hb levels (9.2 g/dl). Workup for other antibodies like anti-phospholipid antibodies, anticardiolipin and anti-beta2-glycoprotein were negative. She was discharged and followed up after 3 weeks during which she remained asymptomatic and neurologically normal, and Hb showed an improving trend (10.7 g/dl). A plan was made to gradually taper the steroids and consider additional immunomodulation in follow-up, if she develops any organ involvement.
Figure 1: Bone marrow aspirate smear of the child – Bone marrow aspirate smear (×100) with Leishman staining showing a lupus erythematosus cell, a neutrophil/monocyte that has phagocytised the denatured nuclear material of another cell

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  Discussion Top


cSLE is a rare chronic autoimmune multisystem inflammatory disease which has a more severe clinical course than adults.[4] The aetiology of cSLE is multifactorial and includes genetic risk factors, epigenetic mechanisms and environmental triggers. In the past, viruses such as Epstein–Barr virus, parvovirus B19 and cytomegalovirus have been reported to trigger SLE.[5] These viruses may trigger autoimmunity by various mechanisms such as structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self-antigens and activation or apoptosis of B- and T-cells.[6]

There are some reports of presentations or exacerbations of various autoimmune diseases such as rheumatoid arthritis, linked with SARS-CoV-2.[7] Recent studies have found an increased prevalence of autoantibodies such as ANA and lupus anticoagulant in patients with SARS-CoV-2 pneumonia.[8] This may explain the potential of SARS-CoV-2 to trigger autoimmunity, leading to onset of SLE. There are few reports of SLE triggered by COVID in adults and children.[9],[10] It is also notable that LE cells, the tell-tale sign of autoimmune process and a rare finding in present times, were seen in the bone marrow smear of the child.[11]

It is now well established that SARS-COV-2 in children has led to a spike in cases of MIS-C, an autoimmune phenomenon.[12] The present case and the available literature from adult population indicate the possible role of SARS-COV-2 in triggering SLE in genetically susceptible individuals. Further reports and studies are needed to establish the role of SARS-COV-2 as a trigger for cSLE.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgements

Authors acknowledge Dr Mujeeb TM and Dr Surya Antony, DNB Residents, Department of Pediatrics, Baby Memorial Hospital, Calicut, Kerala for their involvement in patient care.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, van Vollenhoven R, et al. Systemic lupus erythematosus. Nat Rev Dis Primers 2016;2:16039. doi: 10.1038/nrdp.2016.39. PMID: 27306639.  Back to cited text no. 1
    
2.
Hennon TR, Penque MD, Abdul-Aziz R, Alibrahim OS, McGreevy MB, Prout AJ, et al. COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) guidelines; a Western New York approach. Prog Pediatr Cardiol. 2020;101232. doi: 10.1016/j.ppedcard. 2020.101232.  Back to cited text no. 2
    
3.
Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol 2019;71:1400-12.  Back to cited text no. 3
    
4.
Tarr T, Dérfalvi B, Győri N, Szántó A, Siminszky Z, Malik A, et al. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus. Lupus 2015;24:796-803.  Back to cited text no. 4
    
5.
Ramos-Casals M. Viruses and lupus: the viral hypothesis. Lupus 2008;17:163-5.  Back to cited text no. 5
    
6.
Getts DR, Chastain EM, Terry RL, Miller SD. Virus infection, antiviral immunity, and autoimmunity. Immunol Rev 2013;255:197-209.  Back to cited text no. 6
    
7.
Saad MA, Alfishawy M, Nassar M, Mohamed M, Esene IN, Elbendary A. COVID-19 and Autoimmune Diseases: A Systematic Review of Reported Cases. Curr Rheumatol Rev 2021;17:193-204.  Back to cited text no. 7
    
8.
Gazzaruso C, Carlo Stella N, Mariani G, Nai C, Coppola A, Naldani D, et al. High prevalence of antinuclear antibodies and lupus anticoagulant in patients hospitalized for SARS-CoV2 pneumonia. Clin Rheumatol 2020;39:2095-7.  Back to cited text no. 8
    
9.
Gracia-Ramos AE, Saavedra-Salinas MÁ. Can the SARS-CoV-2 infection trigger systemic lupus erythematosus? A case-based review. Rheumatol Int 2021;41:799-809.  Back to cited text no. 9
    
10.
Maram KP, Paturi VRR, Alla LS, Bhagavathula MK. COVID-19 triggered systemic lupus erythematosus in a child: a case report. Int J Contemp Pediatr. 2021;8:1304-6  Back to cited text no. 10
    
11.
Sathiavageesan S, Rathnam S. The LE Cell-A Forgotten Entity. Indian J Nephrol 2021;31:71-2.  Back to cited text no. 11
  [Full text]  
12.
Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell 2020;183:968-81.e7.  Back to cited text no. 12
    


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