In the midst of the novel coronavirus SARS-CoV-2 (COVID-19) pandemic, a new clinical entity named multisystemic inflammatory syndrome in children (MIS-C) has been recognized.1,2 The definition of MIS-C is broad and includes persistent fever, clinical features of Kawasaki disease and toxic shock syndrome, and gastrointestinal disease.3 Many children that have been diagnosed with MIS-C have tested negative for SARS-CoV-2 in nasopharyngeal specimens but typically have antibodies against, or history of exposure to, SARS-CoV-2.4 As MIS-C can mimic other conditions, such as appendicitis and atypical Kawasaki disease, the diagnosis can be elusive without a high index of suspicion.4,5 We present a case of a previously healthy 15-year-old female, admitted to our hospital with multiorgan failure, in the context of severe inflammation, and coronary artery involvement during a surge of COVID-19 cases in Orange County, CA.
A 15-year-old previously healthy and fully immunized Caucasian female presented to the emergency department with a 1-week history of sore throat and fever with decreased oral intake. She had no recent travel, ill contacts, or known SARS-CoV-2 exposures. The patient also reported symptoms of neck stiffness and headache. She was using tampons at the time. She denied chest pain, palpitations, joint pain, joint swelling, or significant weight loss. Family history was only significant for ankylosing spondylitis in the patient’s father and multiple maternal family members with thrombosis and cerebrovascular accidents. The patient was admitted with initial concern for sepsis with systemic inflammatory response. The initial differential diagnosis included COVID-19, MIS-C, Lemierre syndrome, or a rheumatologic illness such as granulomatosis with polyangiitis (formerly Wegner’s granulomatosis).
She was ill-appearing, but initially afebrile, in mild respiratory distress requiring supplemental oxygen. There was no conjunctivitis, cracked lips, or strawberry tongue. It was not possible to examine her pharynx at the time secondary to trismus. Her neck was initially supple with bilateral prominent cervical lymphadenopathy. She was noted to be tachypneic with accessory respiratory muscle use and diffuse bilateral rales. Heart tones were normal, no murmur, rub, or gallop was present. Her abdomen was soft, with no hepatosplenomegaly. Laboratory values are shown in Table 1 and included leukocytosis with a left shift, azotemia, and coagulopathy. C-reactive protein was significantly elevated (203.9 mg/L). B-type natriuretic peptide and troponin were slightly elevated (247 pg/mL and troponin <0.01 ng/mL, respectively). Nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 and streptococcal antigen tests were both negative.
TABLE 1. -
Initial Laboratory Values
|Blood urea nitrogen
|White blood cell count (UA)
|Red blood cell count (UA)
|Erythrocyte sedimentation rate
|B-type natriuretic peptide
WBC indicates white blood cells.
A chest radiograph revealed extensive bilateral pulmonary infiltrates, pulmonary edema, and left-sided pleural effusion (Fig. 1). Hypotension and tachycardia developed, prompting an echocardiogram, which showed low normal left ventricular ejection fraction (57%) and dilatation of the left main (z score +2.4) and left anterior descending coronary arteries (z score +3.3) (Fig. 2).
The patient became febrile and required significant inotropic and respiratory support and was started on empiric intravenous antibiotics (ceftriaxone and clindamycin). The initial differential diagnosis was revised to include toxic shock syndrome, community acquired pneumonia with septic shock, and disseminated intravascular coagulation. The finding of coronary artery dilation heightened the possibility of MIS-C and treatment with high-dose intravenous immunoglobulin and high-dose corticosteroids was considered.
She remained persistently febrile and developed worsening trismus, right-sided neck swelling and pain. Twenty-seven hours after admission, her blood cultures resulted positive for Gram-negative bacilli. The possibility of Fusobacterium necrophorum infection was considered, and the antibiotic regimen was changed to meropenem. This, combined with the evolving neck findings and sepsis picture, pointed to the diagnosis of Lemierre syndrome. Neck and chest CTA revealed nonocclusive thrombus in the right and left internal jugular veins (Fig. 3) with septic emboli in the lungs thus confirming this diagnosis.
She was weaned successfully to room air by the 9th day of hospitalization, and the fever resolved by the 10th day. The acute kidney injury resolved with supportive care. A follow-up echocardiogram done on day 7 of hospitalization revealed normalized coronary artery dimensions and no aneurysms. The patient was discharged home after 10 days of hospitalization on enoxaparin and a 4-week course of amoxicillin-clavulanate.
The SARS-CoV-2 pandemic is an ongoing global health crisis in adults and children.6 One of the more notable features of COVID-19 is that the disease appears to follow a relatively benign course in pediatric patients when compared with the adult population.7 However, in more recent months, there has been an increasing number of children worldwide diagnosed with the new clinical entity MIS-C, which exhibits significant overlap with Kawasaki disease and toxic shock syndrome, and includes gastrointestinal involvement.5,6 The condition occurs in the setting of documented previous SARS-CoV-2 exposure but with negative SARS-CoV-2 PCR testing.8
Similar to our patient’s clinical course, in 1 published series of MIS-C cases, many of those patients presented to the intensive care unit with low blood pressure, poor perfusion, diminished left ventricular systolic function, respiratory distress, coronary artery dilatation, and elevated levels of brain natriuretic peptide and C-Reactive protein after apparent recovery from SARS-CoV-2. Unlike in our patient, however, oropharyngeal involvement was not a common feature in that series.
At this point in the patient’s course, the negative SARS-CoV-2 PCR nasal swab, multisystem pathology, and coronary artery involvement increased the suspicion of MIS-C and prompted discussion of treatment with intravenous immunoglobulin and corticosteroids. The possibility of toxic shock was also considered due to concurrent tampon use. Atypical Kawasaki disease was not considered as likely due to her relatively older age. Thrombocytosis is a classic feature of Kawasaki disease.4 The thrombocytopenia present in our case was more consistent with sepsis, toxic shock syndrome, or MIS-C.9,10 Interestingly, at the time of the patient’s hospital admission, Google Trend® searches for “MIS-C” had peaked. It is important to acknowledge the psychologic effects of the availability heuristic, as this bias may conceal potential risks in the medical decision-making process11. In retrospect, the patient’s acute presenting features, coupled with the rapidly increasing awareness of MIS-C, proved distracting from her true diagnosis of Lemierre syndrome.
Lemierre syndrome, or postanginal septicemia, is characterized by septic thrombophlebitis of the internal jugular vein with metastatic disease following an acute oropharyngeal infection. The Gram-negative obligate anaerobe, F. necrophorum, is the most common bacterium responsible.12 This condition was fairly prevalent in the preantibiotic era; however, since the introduction and widespread use of antibiotics for acute oropharyngeal infections, Lemierre syndrome has been referred to as a “forgotten disease.”13
In this patient, Gram-negative sepsis was suspected early on in the clinical course leading to the initiation of a carbapenem antibiotic, the recommended treatment for Lemierre syndrome.14 The patient was then started on amoxicillin-clavulanate, given there is a significant portion of F. necrophorum that produce β lactamases, conferring penicillin resistance. Due to the existence of several oropharyngeal β-lactamase producing organisms that could inactivate amoxicillin, clavulanate was added.
In retrospect, this case of Lemierre syndrome was classic given the oropharyngeal source of infection, significant lung infection, sepsis, the growth of F. necrophorum, and internal jugular vein thrombi.13 Although suspected on initial presentation, the multisystemic involvement in the setting of the global SARS-CoV-2 pandemic, along with the associated ill-defined yet serious, newly described MIS-C, provided a potentially detrimental distraction from the true diagnosis. This case affirms that pediatricians and subspecialists taking care of acutely ill patients in the era of COVID-19 should continue to remain vigilant when faced with elusive clinical presentations and remember that “not all that glitters is gold.”
1. Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–1608.
2. Feldstein LR, Rose EB, Horwitz SM, et al.; Overcoming COVID-19 Investigators; CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334–346.
3. Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20:453–454.
4. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395:1771–1778.
5. 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.
6. Chiotos K, Bassiri H, Behrens EM, et al. Multisystem inflammatory syndrome in children during the coronavirus 2019 pandemic: a case series. J Pediatric Infect Dis Soc. 2020;9:393–398.
7. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatric. 2020;145:e20200702.
8. Belhadjer Z, Meot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020;142:429–436.
9. Venkata C, Kashyap R, Farmer JC, et al. Thrombocytopenia in adult patients with sepsis: incidence, risk factors, and its association with clinical outcome. J Intensive Care. 2013;1:9.
10. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020;506:145–148.
11. McDermott R. Medical decision making: lessons from psychology. Urol Oncol. 2008;26:665–668.
12. Eilbert W, Singla N. Lemierre’s syndrome. Int J Emerg Med. 2013;6:40.
13. Sinave CP, Hardy GJ, Fardy PW. The Lemierre syndrome: suppurative thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection. Medicine (Baltimore). 1989;68:85–94.
14. Allen BW, Bentley TP. Lemierre syndrome. 2020.Treasure Island, FL: StatPearls;