Multisystem inflammatory syndrome in neonate with skin lesions—A rare case report

Sanmithra P K Arunakumar; Raghunadan B G Krishnamurthy Rao; Lakshmipathy S Rajagopaliah; Sujatha Ramabhatta

doi:10.4103/mgmj.mgmj_107_22

CASE REPORT

Year : 2022 | Volume : 9 | Issue : 3 | Page : 431-434

Multisystem inflammatory syndrome in neonate with skin lesions—A rare case report

Sanmithra P K Arunakumar, Raghunadan B G Krishnamurthy Rao, Lakshmipathy S Rajagopaliah, Sujatha Ramabhatta
Department of Pediatrics, K C General Hospital, Bengaluru, Karnataka, India

Date of Submission	12-Jul-2022
Date of Acceptance	04-Aug-2022
Date of Web Publication	29-Sep-2022

Correspondence Address:
Dr. Raghunadan B G Krishnamurthy Rao
Department of Pediatrics, K C General Hospital, Bengaluru 560003, Karnataka
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mgmj.mgmj_107_22

Abstract

Multisystem inflammatory syndrome in children is a serious condition that occurs due to postinfectious immune-mediated hyperinflammatory reaction seen in children, which develops after 4–6 weeks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection; it is rare in neonates. We present here a case of a term newborn with fever, respiratory distress, and necrotic skin lesion that gradually progressed to multisystem dysfunction. Reverse transcription polymerase chain reaction for SARS-CoV-2 was negative for both mother and the baby. SARS-CoV-2 IgG titer was negative in the mother but was found to be positive in the newborn. The diagnosis of multisystem inflammatory syndrome in neonate was made and was successfully treated with intravenous immunoglobulin and corticosteroids.

Keywords: Intravenous immunoglobulin, necrotic skin lesions, neonatal multisystem inflammatory syndrome, severe acute respiratory syndrome coronavirus-2

How to cite this article:
Arunakumar SP, Rao RB, Rajagopaliah LS, Ramabhatta S. Multisystem inflammatory syndrome in neonate with skin lesions—A rare case report. MGM J Med Sci 2022;9:431-4

How to cite this URL:
Arunakumar SP, Rao RB, Rajagopaliah LS, Ramabhatta S. Multisystem inflammatory syndrome in neonate with skin lesions—A rare case report. MGM J Med Sci [serial online] 2022 [cited 2022 Dec 7];9:431-4. Available from: http://www.mgmjms.com/text.asp?2022/9/3/431/357481

Introduction

COVID-19 has become a public health crisis globally with a huge recent second wave in India. As of July 31, 2021, the total cases in India stood at 31.7 million with 424,777 deaths.^[1] Early studies showed that children were spared severe COVID-19. However, several case reports of multisystem inflammatory syndrome in children (MIS-C) have been narrated. There are documented clinical features such as acute respiratory distress syndrome, temperature instability, gastrointestinal and cardiovascular dysfunction, hypotension or shock, abnormal liver enzymes, and skin lesions in MIS-C.^[2]

The hypothetical pathogenesis of MIS-C states that it is thought to be due to immune dysregulation following the exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which may cause a similar hyperinflammatory syndrome in neonates due to transplacental transfer of antibodies. One case series from Kolhapur, India, has demonstrated the multisystem inflammatory syndrome in neonate (MIS-N) in the first week of life.^[3]

We present a rare case of MIS-N with features primarily of acute kidney injury and encephalopathy in the first week of postnatal life.

Case report

A term female neonate weighing 2.72 kg was delivered by lower segment caesarean section for failed induction of labor to an asymptomatic primigravida mother and presented with yellowish discoloration of the body (up to thighs) at 24 h of life. The diagnosis of pathological jaundice was made and phototherapy was initiated. As per the protocol, the mother was screened for SARS-CoV-2 by reverse transcription polymerase chain reaction (RTPCR) before delivery, and the result was negative.

On day 5 of life, the neonate was brought with complaints of hurried breathing. She was lethargic, febrile (101°F), dehydrated with tachypnea (respiratory rate [RR]: 70/min), subcostal retractions, and bilateral crepitation. The right lower abdomen noted a necrotic skin lesion of size 10 × 5 mm with surrounding erythema and indurated base [Figure 1]. Another similar lesion of size 5 × 3 mm was noted on the lateral border of the right foot. With sepsis imminent, intravenous piperacillin/tazobactam and appropriate fluid and electrolyte management were started. The newborn developed stridor a few hours later. Intravenous dexamethasone and adrenaline nebulization were initiated. Investigations revealed high C-reactive protein (88.6 mg/L; normal = 0–5 mg/L), elevated blood urea nitrogen (BUN) (84 mg/dL), and serum creatinine (1.8 mg/dL) with hypernatremia (serum sodium = 156 mg/dL and serum chloride = 123 mmol/L). No abnormality was detected on chest x-ray. Complete blood count (CBC) revealed leukocytosis (25,700 cells/mm³) and severe thrombocytopenia (30,000 cells/mm³). Multifocal clonic seizures developed, which responded to intravenous phenobarbitone. Suspecting late-onset neonatal sepsis with acute kidney injury and the possibility of meningitis, antibiotics were upgraded to intravenous vancomycin and meropenem (renal correction doses). Urine output and glomerular filtration rate (GFR) were monitored.

Figure 1: Skin lesion at presentation

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The neurological condition and renal parameters worsened further (BUN = 199 mg/dL and serum creatinine = 2.3 mg/dL; GFR = 10 mL/min/1.73 m²). On day 6 of life, the condition aggravated with increasing generalized edema, shock, and features suggestive of disseminated intravascular coagulation requiring vasopressor support. Nonpurulent conjunctivitis of the eyes was noticed. Respiratory distress worsened requiring continuous positive airway pressure (CPAP) support. Repeat chest x-ray showed a homogenous patch in the right upper lobe. No pleural effusion or cardiac abnormality was noted. Platelets were transfused.

RTPCR for SARS-CoV-2 was negative. The mother’s rapid antibody test (AbChek Antibody Rapid Test Kit) was negative. The newborn’s rapid antibody test for SARS-CoV-2 revealed positivity for immunoglobulin G (IgG). Inflammatory markers and coagulation profiles were sent for investigation. D-dimer was elevated (5.2 mg/L; normal = 0–0.5 mg/L) along with lactate dehydrogenase and serum ferritin (770 U/L and 1218 ng/mL, respectively). The blood culture remained sterile after 72 h of incubation.

Because of multisystem involvement, positive IgG to SARS-CoV-2 elevated D-dimer and inflammatory markers and in the absence of other possible explanations, the diagnosis of MIS-N was considered. Intravenous immunoglobulin (IVIG) was started on day 7 at the dosage of 2 g/kg over 24 h. Intravenous dexamethasone was continued and oral aspirin (3 mg/kg every 24 h) was started.

After a few hours of starting IVIG, there was a dramatic improvement. On day 8 of life, respiratory distress improved, and CPAP support was weaned off. Edema reduced. CBC, renal functions, and serum electrolytes started to normalize by day 9. Clinical stability was noted, and the newborn was off vasopressor by day 11. Skin lesions started to heal. Improvement in central nervous system functions was also observed, and anticonvulsant dosage was tapered. Ultrasonography of the abdomen and pelvis revealed a normal study. 2D echocardiography revealed minimal pericardial effusion with structurally normal cardia and normal biventricular function. Orogastric tube feeding was initiated on day 8, and gradually direct breastfeeding was achieved on day 14. Cerebrospinal fluid analysis was within normal limits, and cerebrospinal fluid culture remained sterile after 72 h of incubation.

Repeat inflammatory markers showed a decreasing trend. Intravenous antibiotics were administered for a total of 14 days. No focal or diffuse cerebral lesions were noted in magnetic resonance imaging brain. Oral phenobarbitone was tapered and stopped after 10 days. Dexamethasone dosage was tapered and stopped on day 18. Repeat 2D echocardiography recorded structurally normal cardia and normal biventricular function. The newborn was successfully discharged on day 19 of life in a stable condition with oral aspirin for 6 weeks and direct breastfeeding.

Discussion

The MIS-C following the exposure to SARS-CoV-2 is uncommon with the deadly presentation. The case series from Kolhapur has described fever/temperature instability, cardiac, hematologic/thrombosis, respiratory, gastrointestinal, neurological, cutaneous, and renal manifestations as various presentations of MIS-N.^[3] The current guidelines of treatment are IVIG and steroids with excellent response. Some clinicians have also used anakinra (recombinant interleukin-1β antagonist) for the treatment.^[2]

Several authors have described the skin manifestations of COVID-19. Though these lesions occur in older age children and the adult population, neonatal skin manifestations are yet to be fully understood. The skin lesion over the right lower abdomen as described in the report might indicate lesions similar to the lesions over the buttocks described in a case report by Kappanayil et al.^[4] and acro-ischemia in the older population as described by Calvão et al.^[5]

The diagnosis of MIS-N was confirmed by the presence of anti-SARS-CoV-2 IgG antibodies in the newborn and a dramatic response to immunoglobulin therapy. In our case, the mother was asymptomatic throughout her pregnancy. We believe the mother might have previously been exposed to SARS-CoV-2 somewhere in the late second or third trimester before the mandated RTPCR testing. Hence, we believe that our case of MIS-N, which presented between the days 5 and 7 of postnatal life, is due to the in-utero exposure to SARS-CoV-2, resulting in multiple organ injuries. Vivanti et al. have demonstrated the vertical transmission of SARS-CoV-2 in a neonate born to a mother infected in the third trimester and presenting with neurological symptoms.^[6] Possible vertical transmission of the virus in the second trimester and the development of neonatal MIS are mentioned in a case report by Shaiba et al.^[7] Flannery et al. have demonstrated that only SARS-CoV-2 IgG antibodies were transferred across the placenta in 86.75% of seropositive pregnant mothers, and cord blood IgG concentrations were associated with maternal antibody concentrations. They further stated that transfer rates were directly associated with time progressed from maternal infection to delivery and are not associated with the acuteness of maternal infection.^[8]

Conclusion

With this case report, we focus on the gravity of the ever-increasing arena of newer neonatal clinical manifestations related to SARS-CoV-2 infection, which demands our increased clinical suspicion for earlier diagnosis and treatment. There is a need for further research into the vertical transmission of SARS-CoV-2 to the fetus and MIS-N and the sensitivity and specificity of rapid antibody test kits. In India, pregnant women have become more vulnerable to SARS-CoV-2 exposure because of lockdown relaxations and the ever-mutating virus. Hence, protecting the maternal–fetal pair from newer variants of SARS-CoV-2 through a suitable vaccination approach and COVID-appropriate behaviors is the dire need of the hour.

Ethical consideration

The approval/clearance for research protocol titled: “Multisystem inflammatory syndrome in neonate with skin lesions—A rare case report” has been obtained from the Institutional Ethics Committee of K.C. General Hospital, Malleshwaram, Bengaluru, Karnataka, India vide letter dated May 31, 2022.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Declaration of patient consent

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

References

1.	MyGov. IndiaFightsCorona COVID-19. New Delhi: Ministry of Electronics & Information Technology, Government of India; 2021. Available from: https://www.mygov.in/covid-19. [Last accessed on 2021 Jul 31].
2.	Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: Review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel) 2020;7:69.
3.	Pawar R, Gavade V, Patil N, Mali V, Girwalkar A, Tarkasband V, et al. Neonatal multisystem inflammatory syndrome (MIS-N) associated with prenatal maternal SARS-CoV-2: A case series. Children (Basel) 2021;8:572.
4.	Kappanayil M, Balan S, Alawani S, Mohanty S, Leeladharan SP, Gangadharan S, et al. Multisystem inflammatory syndrome in a neonate, temporally associated with prenatal exposure to SARS-CoV-2: A case report. Lancet Child Adolesc Health 2021;5:304-8.
5.	Calvão J, Relvas M, Pinho A, Brinca A, Cardoso JC Acro-ischaemia and COVID-19 infection: Clinical and histopathological features. J Eur Acad Dermatol Venereol 2020;34:e653-754.
6.	Vivanti AJ, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do Cao J, et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun 2020;11:3572.
7.	Shaiba LA, Hadid A, Altirkawi KA, Bakheet HM, Alherz AM, Hussain SA, et al. Case report: Neonatal multi-system inflammatory syndrome associated with SARS-CoV-2 exposure in two cases from Saudi Arabia. Front Pediatr 2021;9:652857.
8.	Flannery DD, Gouma S, Dhudasia MB, Mukhopadhyay S, Pfeifer MR, Woodford EC, et al. Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios. JAMA Pediatr 2021;175:594-600.