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Letters to the Editor

Acute Appendicitis in Multisystem Inflammatory Syndrome in Children With COVID-19

Lishman, Juanita FCPaed; Kohler, Charles MBChB, MRCS; de Vos, Corne FCPaedSurg; van der Zalm, Marieke M. PhD; Itana, Justina MBChB; Redfern, Andrew FCPaed; Smit, Liezl FCPaed; Rabie, Helena PhD

Author Information
The Pediatric Infectious Disease Journal: December 2020 - Volume 39 - Issue 12 - p e472-e473
doi: 10.1097/INF.0000000000002900
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To the Editors:

South Africa has the highest number of COVID-19 cases in Africa to date with Cape Town as the initial epicenter. Up to 20 August 2020, 78 children with positive polymerase chain reaction (PCR) severe acute respiratory syndrome (SARS)-CoV-2 were admitted to Tygerberg Hospital in Cape Town. We present 4 of these children, 5- to 12-years-old age (2 males) with appendicitis and confirmed SARS-CoV-2 on PCR of respiratory specimens (Table 1). Three children were initially diagnosed with acute appendicitis and treated surgically and multisystem inflammatory syndrome in children (MIS-c) was diagnosed in all three after appendectomies. The fourth child was admitted with clinical appendicitis and tested for SARS-CoV-2 due to hospital policy but was managed non-surgically and did not have MIS-c.

TABLE 1. - Clinical and Laboratory Characteristics of Children With Appendicitis and Positive SARS-CoV-2 on Respiratory Specimen
Case 1 2 3 4
Age 8 5 12 8
Sex F F M M
SARS-CoV-2 PCR Positive Positive Positive Positive
Diagnosis MIS-C MIS-C MIS-C
Complicated acute appendicitis Complicated acute appendicitis Uncomplicated acute appendicitis Uncomplicated acute appendicitis
Signs and symptoms
 Duration of symptoms prior to surgery 1 1 3 N/A
 Fever + + + +
 Abdominal pain + + + +
 Vomiting + +
 Diarrhea +
 Rash + + +
 Conjunctival injection + + +
 Shock + + +
Surgery
 Findings at surgery Perforated appendix with pus in 4 quadrants. Perforated appendix. Pus in pelvis and lower abdomen. Hyperemia N/A
No pus or signs of abscess formation. Mesenteric lymph node
 Histology Not available Acute appendicitis with perforation and peritonitis. Acute appendicitis with peritonitis. N/A
Acute lymphadenitis with microabscess formation.
Laboratory findings
 CRP (peak) 500 mg/L 238 mg/L 112 mg/L 14 mg/L
 Ferritin (peak) 1361 ug/L 611 ug/L 544 ug/L 106 ug/L
 D-Dimer (peak) >17.6 mg/L 17.6 mg/L 5.7 mg/L
 Pro-BNP (peak) 3158 ng/L - 282 ng/L
 Troponin T (peak) 8 ng/L - 21 ng/L
 Creatine kinase 1144 U/L - 1096 U/L
 Lymphocytes (nadir) 0.37 × 109/L 0.86 × 109/L 0.72 × 109/L
 Urea (initial) 19.7 mmol/L 4.6 mmol/L 3.3 mmol/L 6.8 mmol/L
 Creatinine (initial) 146 umol/L 25 umol/L 54 umol/L 53 umol/L
 Albumin (nadir) 23 g/L 22 g/L 31 g/L
 Blood culture Neg Neg Neg Neg
Management
 Intensive care + (4 d) + (1 d) High care
 Inotropic support + + +
 IVIG + + +
 Steroid pulse + + +
 Aspirin + + +
 Antibiotics + + + +
 Respiratory support Ventilated for 2 days followed by 2 days high flow oxygen. Nasal prong oxygen
 Duration of hospitalization (d) 10 11 7 4
Imaging
 Echocardiogram findings Normal left ventricular function (ejection fraction = 70%). Both coronary arteries echobright, within normal size. Dilated coronary arteries. Ejection fraction 62%. Mild impairment of left ventricular systolic function (ejection fraction 52%), coronary arteries not dilated. -

Similar to a recent case series from London, we highlight that children with COVID-19 may present with clinical features suggestive of appendicitis or atypical appendicitis as part of MIS-c.1,2 Cases 1 and 2 were included in a recent report on MIS-c in Cape Town, and all children were diagnosed with appendicitis during a time where an increase in these case was identified in our center.2 However, unlike children from London, all children with MIS-c and appendicitis were PCR positive for SARS-CoV-2. Moreover, children in the London series were diagnosed with terminal ileitis and none required surgery.1 In our series of MIS-c, 3 of the children had surgically confirmed appendicitis (Table 1): 2 with complicated appendicitis with perforation and intra-abdominal pus and the third was confirmed histologically.

The possible relationship of viral entry through angiotensin-converting enzyme 2 receptors, abundantly present in the terminal ileum, and its relationship with terminal ileitis has been well documented.3 What is not clear, is whether appendicitis may occur as a complication of SARS-CoV-2 through similar proposed mechanisms related to the inflammation associated with viral entry or reactive lymphoid hyperplasia causing luminal obstruction. Acute appendicitis is known to be associated with Kawasaki disease, of which MIS-c shares many common clinical and pathologic features, possibly related to appendicular artery vasculitis.4 In Kawasaki disease, abdominal features may represent more severe disease.5 No fecoliths were found in any of the children requiring appendectomy, possibly supporting inflammation or vasculitis as pathologic mechanism.

Where surgical emergencies are not managed in conjunction with pediatricians, surgeons should familiarize themselves with the features of MIS-c to facilitate early identification and referral of possible cases. The importance includes the impact on diagnosis of appendicitis, postoperative recovery, and the management of multisystem involvement, which differentiates this entity from the regular course of isolated acute appendicitis. Our experience suggests that, as with Kawasaki disease, pediatricians that diagnose MIS-c should be vigilant and continue to carefully evaluate children for surgical complications, including appendicitis and perforation, particularly if abdominal pain is part of the presenting complaint. Access to sophisticated imaging to differentiating appendicitis from terminal ileitis may be limited in some settings, but if there is doubt the most sophisticated available imaging should be sought.

Our experience further highlights the suspected association between acute appendicitis, COVID-19, and MIS-c. This should always be considered particularly in children with clinical appendicitis who are PCR positive for SARS-CoV-2 at the time of presentation.

ACKNOWLEDGMENTS

We would like to acknowledge leadership of The Department of Paediatrics and Child Health and Tygerberg Hospital and Desmond Tutu TB Centre of Stellenbosch University in the COVID-19 response.

REFERENCES

1. Tullie L, Ford K, Bisharat M, et al. Gastrointestinal features in children with COVID-19: an observation of varied presentation in eight children. Lancet Child Adolesc Health. 2020;4:e19–e20.
2. Webb K, Abraham DR, Faleye A, et al. Multisystem inflammatory syndrome in children in South Africa. Lancet Child Adolesc Health. 2020. S2352-4642(20)30272-8. doi: 10.1016/S2352-4642(20)30272-8 Online ahead of print.
3. Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24:422.
4. Garnett GM, Kimball S, Melish ME, et al. Appendicitis as the presenting manifestation of Kawasaki disease. Pediatr Surg Int. 2014;30:549–552.
5. Fabi M, Corinaldesi E, Pierantoni L, et al. Gastrointestinal presentation of Kawasaki disease: a red flag for severe disease?. PLoS One. 2018;13:e0202658.
Keywords:

COVID-19; MIS-c; appendicitis

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