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Elan Jenkins, Whitney Sherry, Alison G C Smith, Bradley S Rostad, Christina A Rostad, Kaitlin Jones, Preeti Jaggi, Retropharyngeal Edema and Neck Pain in Multisystem Inflammatory Syndrome in Children (MIS-c), Journal of the Pediatric Infectious Diseases Society, Volume 10, Issue 9, September 2021, Pages 922–925, https://doi.org/10.1093/jpids/piab050
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Abstract
We defined the prevalence of neck pain, trismus, or dysphagia (28.4%) and retropharyngeal edema (2.9%) among 137 patients with multisystem inflammatory syndrome in children (MIS-c). Retropharyngeal edema or phlegmon has been documented radiologically in at least 9 children. Symptoms of neck inflammation are common in MIS-c.
Multisystem inflammatory syndrome in children (MIS-c) has been recognized after the high prevalence of COVID-19 within communities [1]. We have observed several patients diagnosed with MIS-c with symptoms of prominent neck pain and/or other otolaryngologic manifestations and have noted that these symptoms do not fall clearly into a designated organ system using the Centers for Disease Control and Prevention (CDC) case definition. We hypothesized that these symptoms are common and sought to define the frequency of neck pain and/or associated symptoms (eg, trismus, drooling, and/or dysphagia) among all MIS-c patients treated at our health care system and to compare the clinical, demographic, and laboratory features between children with these symptoms and those without. Finally, we sought to identify cases of MIS-c with radiographically defined retropharyngeal edema or inflammation in our cohort and previously reported in the medical literature.
METHODS
We identified children diagnosed with MIS-c between March 2020 and January 20, 2021 at Children’s Healthcare of Atlanta, a health care system comprised of 3 freestanding children’s hospitals in metropolitan Atlanta, Georgia. Some patients in March and early April of 2020 were diagnosed retrospectively after the case definition was established. Starting in May 2020, our multidisciplinary team began maintaining a prospectively collected IRB-approved database of patients diagnosed with MIS-c. Cases were identified through daily active surveillance using the CDC case definition [2].
Demographic, clinical, laboratory, treatment, and outcome data were obtained through manual chart abstraction of the electronic medical record. Symptoms of neck pain, dysphagia, drooling, or trismus, as well as any radiologic data of the neck, were recorded. Statistical analysis including descriptive statistics and significance testing of continuous variables with the Wilcoxon rank sum test and categorical variables with the chi-square test of independence or Fisher exact test was performed with R statistical software, version 4.0.2.
In addition, we conducted a medical literature review of previously reported cases describing retropharyngeal edema or abscess with MIS-c using the key words “retropharyngeal” AND “MIS OR multisystem inflammatory syndrome” or “pediatric inflammatory multisystem syndrome” in any publication found published between April 1, 2020 and January 25, 2021.
RESULTS
We identified 137 cases of MIS-c at our institution. There were 39 (28.5%) with neck-related symptoms. Of these, there were 38 patients that had neck pain. Three patients had trismus, and 5 patients had drooling, dysphagia, or difficulty swallowing. Twelve unique patients underwent neck imaging. Neck imaging included computed tomography (CT, n = 8), ultrasound (n = 2), magnetic resonance imaging (MRI, n = 1), and/or plain radiograph (n = 2). Overall, patients with neck pain were more likely to be older (median age 10 years vs 8 years, P = .029) and have undergone lumbar puncture P = .035 (Table 1). Among those with neck imaging by CT and/or MRI, 4 patients had evidence of retropharyngeal edema/inflammation. Representative imaging findings from patients treated at our center are shown in Supplementary Figure 1.
| Demographic and Diagnostic Characteristics . | MIS-c Patients Without Neck Symptomsa (N = 98) . | MIS-c Patients With Neck Symptomsa (N = 39) . |
|---|---|---|
| Age in years, median (IQR)b | 8 (5, 12) | 10 (8, 15) |
| Gender (male), n (%) | 55 (56%) | 25 (64%) |
| Ethnicity: Hispanic or Latino, n (%) | 29 (30%) | 6 (15%) |
| Race: White, n (%) | 37 (38%) | 10 (25%) |
| Race: Black or African-American, n (%) | 51 (53%) | 22 (55%) |
| Length of hospital stay, days, median (IQR) | 6 (4, 8) | 6 (4, 8) |
| Admitted to intensive care unit, n (%) | 61 (62%) | 25 (64%) |
| Myocardial dysfunction on echocardiogram, n (%) | 45 (49%) | 16 (44%) |
| Coronary dilation on echocardiogram, n (%) | 7 (7.5%) | 7 (21%) |
| Elevated troponin. n (%) | 62 (67%) | 28 (74%) |
| Received antibiotics, n (%) | ||
For >3 d | 19 (20%) | 13 (33%) |
For ≤3 d | 78 (80%) | 26 (67%) |
| Received a lumbar puncture, n (%)b | 3 (3.1%) | 5 (14%) |
| Treatments, n (%) | ||
| Received any oxygen supplementation | 51 (52%) | 20 (51%) |
Low-flow nasal cannula | 49 (50%) | 18 (46%) |
High-flow nasal cannula | 33 (34%) | 13 (33%) |
Noninvasive ventilation | 9 (9.2%) | 6 (16%) |
Ventilation or ECMO | 4 (4.1%) | 2 (5.1%) |
| Other immunomodulators (eg, anakinra, tocilizumab) | 5 (5.3%) | 2 (5.3%) |
| Vasoactive medication | 39 (40%) | 19 (50%) |
| Intravenous immunoglobulin | 68 (70%) | 25 (64%) |
| Corticosteroids | 87 (90%) | 31 (79%) |
| Received vasoactive medication, invasive or noninvasive ventilation | 46 (47%) | 21 (54%) |
| Laboratory evaluation at admission, median (IQR) | ||
| White blood cell count (cells/microliter) | 9590 (5920, 13 042) | 9060 (7540, 11 415) |
| Absolute lymphocyte count (cells/microliter) | 1091 (606, 1781) | 778 (578, 1435) |
| Absolute neutrophil count (cells/microliter) | 7225 (3955, 9945) | 6822 (6019, 8970) |
| Platelets (1000 cells/microliter) | 151 (130, 205) | 166 (115, 208) |
| Albumin (g/dL) | 2.85 (2.40, 3.20) | 3.00 (2.60, 3.40) |
| Aspartate transaminase (units/L) | 46 (26, 91) | 43 (24, 82) |
| Alanine transaminase (units/L) | 42 (26, 58) | 43 (21, 76) |
| Ferritin (µg/L) | 493 (264, 1105) | 458 (229, 825) |
| C-reactive protein (mg/L) | 14 (9, 18) | 12 (8, 16) |
| Brain natriuretic peptide (ng/L) | 165 (26, 559) | 73 (48, 357) |
| Prothrombin time (seconds) | 15.50 (14.62, 16.40) | 15.80 (14.85, 16.50) |
| Partial thromboplastin time (seconds) | 36 (32, 40) | 36 (32, 41) |
| International normalized ratio | 1.20 (1.10, 1.30) | 1.20 (1.20, 1.30) |
| d-dimer (ng/mL)b | 1665 (1052, 2433) | 1140 (689, 1614) |
| Demographic and Diagnostic Characteristics . | MIS-c Patients Without Neck Symptomsa (N = 98) . | MIS-c Patients With Neck Symptomsa (N = 39) . |
|---|---|---|
| Age in years, median (IQR)b | 8 (5, 12) | 10 (8, 15) |
| Gender (male), n (%) | 55 (56%) | 25 (64%) |
| Ethnicity: Hispanic or Latino, n (%) | 29 (30%) | 6 (15%) |
| Race: White, n (%) | 37 (38%) | 10 (25%) |
| Race: Black or African-American, n (%) | 51 (53%) | 22 (55%) |
| Length of hospital stay, days, median (IQR) | 6 (4, 8) | 6 (4, 8) |
| Admitted to intensive care unit, n (%) | 61 (62%) | 25 (64%) |
| Myocardial dysfunction on echocardiogram, n (%) | 45 (49%) | 16 (44%) |
| Coronary dilation on echocardiogram, n (%) | 7 (7.5%) | 7 (21%) |
| Elevated troponin. n (%) | 62 (67%) | 28 (74%) |
| Received antibiotics, n (%) | ||
For >3 d | 19 (20%) | 13 (33%) |
For ≤3 d | 78 (80%) | 26 (67%) |
| Received a lumbar puncture, n (%)b | 3 (3.1%) | 5 (14%) |
| Treatments, n (%) | ||
| Received any oxygen supplementation | 51 (52%) | 20 (51%) |
Low-flow nasal cannula | 49 (50%) | 18 (46%) |
High-flow nasal cannula | 33 (34%) | 13 (33%) |
Noninvasive ventilation | 9 (9.2%) | 6 (16%) |
Ventilation or ECMO | 4 (4.1%) | 2 (5.1%) |
| Other immunomodulators (eg, anakinra, tocilizumab) | 5 (5.3%) | 2 (5.3%) |
| Vasoactive medication | 39 (40%) | 19 (50%) |
| Intravenous immunoglobulin | 68 (70%) | 25 (64%) |
| Corticosteroids | 87 (90%) | 31 (79%) |
| Received vasoactive medication, invasive or noninvasive ventilation | 46 (47%) | 21 (54%) |
| Laboratory evaluation at admission, median (IQR) | ||
| White blood cell count (cells/microliter) | 9590 (5920, 13 042) | 9060 (7540, 11 415) |
| Absolute lymphocyte count (cells/microliter) | 1091 (606, 1781) | 778 (578, 1435) |
| Absolute neutrophil count (cells/microliter) | 7225 (3955, 9945) | 6822 (6019, 8970) |
| Platelets (1000 cells/microliter) | 151 (130, 205) | 166 (115, 208) |
| Albumin (g/dL) | 2.85 (2.40, 3.20) | 3.00 (2.60, 3.40) |
| Aspartate transaminase (units/L) | 46 (26, 91) | 43 (24, 82) |
| Alanine transaminase (units/L) | 42 (26, 58) | 43 (21, 76) |
| Ferritin (µg/L) | 493 (264, 1105) | 458 (229, 825) |
| C-reactive protein (mg/L) | 14 (9, 18) | 12 (8, 16) |
| Brain natriuretic peptide (ng/L) | 165 (26, 559) | 73 (48, 357) |
| Prothrombin time (seconds) | 15.50 (14.62, 16.40) | 15.80 (14.85, 16.50) |
| Partial thromboplastin time (seconds) | 36 (32, 40) | 36 (32, 41) |
| International normalized ratio | 1.20 (1.10, 1.30) | 1.20 (1.20, 1.30) |
| d-dimer (ng/mL)b | 1665 (1052, 2433) | 1140 (689, 1614) |
Abbreviations: ECMO, extracorporeal membrane oxygenation; IQR, interquartile range; MIS-c, multisystem inflammatory syndrome in children.
aNeck symptoms: any drooling, dysphagia, trismus, or neck pain.
bDenotes differences are statistically significant; Wilcoxon rank sum test, α = 0.05. Patients with neck pain were older (P = .002) and had a higher d-dimer (P = .004) and were more likely to have undergone lumbar puncture (P = .035).
| Demographic and Diagnostic Characteristics . | MIS-c Patients Without Neck Symptomsa (N = 98) . | MIS-c Patients With Neck Symptomsa (N = 39) . |
|---|---|---|
| Age in years, median (IQR)b | 8 (5, 12) | 10 (8, 15) |
| Gender (male), n (%) | 55 (56%) | 25 (64%) |
| Ethnicity: Hispanic or Latino, n (%) | 29 (30%) | 6 (15%) |
| Race: White, n (%) | 37 (38%) | 10 (25%) |
| Race: Black or African-American, n (%) | 51 (53%) | 22 (55%) |
| Length of hospital stay, days, median (IQR) | 6 (4, 8) | 6 (4, 8) |
| Admitted to intensive care unit, n (%) | 61 (62%) | 25 (64%) |
| Myocardial dysfunction on echocardiogram, n (%) | 45 (49%) | 16 (44%) |
| Coronary dilation on echocardiogram, n (%) | 7 (7.5%) | 7 (21%) |
| Elevated troponin. n (%) | 62 (67%) | 28 (74%) |
| Received antibiotics, n (%) | ||
For >3 d | 19 (20%) | 13 (33%) |
For ≤3 d | 78 (80%) | 26 (67%) |
| Received a lumbar puncture, n (%)b | 3 (3.1%) | 5 (14%) |
| Treatments, n (%) | ||
| Received any oxygen supplementation | 51 (52%) | 20 (51%) |
Low-flow nasal cannula | 49 (50%) | 18 (46%) |
High-flow nasal cannula | 33 (34%) | 13 (33%) |
Noninvasive ventilation | 9 (9.2%) | 6 (16%) |
Ventilation or ECMO | 4 (4.1%) | 2 (5.1%) |
| Other immunomodulators (eg, anakinra, tocilizumab) | 5 (5.3%) | 2 (5.3%) |
| Vasoactive medication | 39 (40%) | 19 (50%) |
| Intravenous immunoglobulin | 68 (70%) | 25 (64%) |
| Corticosteroids | 87 (90%) | 31 (79%) |
| Received vasoactive medication, invasive or noninvasive ventilation | 46 (47%) | 21 (54%) |
| Laboratory evaluation at admission, median (IQR) | ||
| White blood cell count (cells/microliter) | 9590 (5920, 13 042) | 9060 (7540, 11 415) |
| Absolute lymphocyte count (cells/microliter) | 1091 (606, 1781) | 778 (578, 1435) |
| Absolute neutrophil count (cells/microliter) | 7225 (3955, 9945) | 6822 (6019, 8970) |
| Platelets (1000 cells/microliter) | 151 (130, 205) | 166 (115, 208) |
| Albumin (g/dL) | 2.85 (2.40, 3.20) | 3.00 (2.60, 3.40) |
| Aspartate transaminase (units/L) | 46 (26, 91) | 43 (24, 82) |
| Alanine transaminase (units/L) | 42 (26, 58) | 43 (21, 76) |
| Ferritin (µg/L) | 493 (264, 1105) | 458 (229, 825) |
| C-reactive protein (mg/L) | 14 (9, 18) | 12 (8, 16) |
| Brain natriuretic peptide (ng/L) | 165 (26, 559) | 73 (48, 357) |
| Prothrombin time (seconds) | 15.50 (14.62, 16.40) | 15.80 (14.85, 16.50) |
| Partial thromboplastin time (seconds) | 36 (32, 40) | 36 (32, 41) |
| International normalized ratio | 1.20 (1.10, 1.30) | 1.20 (1.20, 1.30) |
| d-dimer (ng/mL)b | 1665 (1052, 2433) | 1140 (689, 1614) |
| Demographic and Diagnostic Characteristics . | MIS-c Patients Without Neck Symptomsa (N = 98) . | MIS-c Patients With Neck Symptomsa (N = 39) . |
|---|---|---|
| Age in years, median (IQR)b | 8 (5, 12) | 10 (8, 15) |
| Gender (male), n (%) | 55 (56%) | 25 (64%) |
| Ethnicity: Hispanic or Latino, n (%) | 29 (30%) | 6 (15%) |
| Race: White, n (%) | 37 (38%) | 10 (25%) |
| Race: Black or African-American, n (%) | 51 (53%) | 22 (55%) |
| Length of hospital stay, days, median (IQR) | 6 (4, 8) | 6 (4, 8) |
| Admitted to intensive care unit, n (%) | 61 (62%) | 25 (64%) |
| Myocardial dysfunction on echocardiogram, n (%) | 45 (49%) | 16 (44%) |
| Coronary dilation on echocardiogram, n (%) | 7 (7.5%) | 7 (21%) |
| Elevated troponin. n (%) | 62 (67%) | 28 (74%) |
| Received antibiotics, n (%) | ||
For >3 d | 19 (20%) | 13 (33%) |
For ≤3 d | 78 (80%) | 26 (67%) |
| Received a lumbar puncture, n (%)b | 3 (3.1%) | 5 (14%) |
| Treatments, n (%) | ||
| Received any oxygen supplementation | 51 (52%) | 20 (51%) |
Low-flow nasal cannula | 49 (50%) | 18 (46%) |
High-flow nasal cannula | 33 (34%) | 13 (33%) |
Noninvasive ventilation | 9 (9.2%) | 6 (16%) |
Ventilation or ECMO | 4 (4.1%) | 2 (5.1%) |
| Other immunomodulators (eg, anakinra, tocilizumab) | 5 (5.3%) | 2 (5.3%) |
| Vasoactive medication | 39 (40%) | 19 (50%) |
| Intravenous immunoglobulin | 68 (70%) | 25 (64%) |
| Corticosteroids | 87 (90%) | 31 (79%) |
| Received vasoactive medication, invasive or noninvasive ventilation | 46 (47%) | 21 (54%) |
| Laboratory evaluation at admission, median (IQR) | ||
| White blood cell count (cells/microliter) | 9590 (5920, 13 042) | 9060 (7540, 11 415) |
| Absolute lymphocyte count (cells/microliter) | 1091 (606, 1781) | 778 (578, 1435) |
| Absolute neutrophil count (cells/microliter) | 7225 (3955, 9945) | 6822 (6019, 8970) |
| Platelets (1000 cells/microliter) | 151 (130, 205) | 166 (115, 208) |
| Albumin (g/dL) | 2.85 (2.40, 3.20) | 3.00 (2.60, 3.40) |
| Aspartate transaminase (units/L) | 46 (26, 91) | 43 (24, 82) |
| Alanine transaminase (units/L) | 42 (26, 58) | 43 (21, 76) |
| Ferritin (µg/L) | 493 (264, 1105) | 458 (229, 825) |
| C-reactive protein (mg/L) | 14 (9, 18) | 12 (8, 16) |
| Brain natriuretic peptide (ng/L) | 165 (26, 559) | 73 (48, 357) |
| Prothrombin time (seconds) | 15.50 (14.62, 16.40) | 15.80 (14.85, 16.50) |
| Partial thromboplastin time (seconds) | 36 (32, 40) | 36 (32, 41) |
| International normalized ratio | 1.20 (1.10, 1.30) | 1.20 (1.20, 1.30) |
| d-dimer (ng/mL)b | 1665 (1052, 2433) | 1140 (689, 1614) |
Abbreviations: ECMO, extracorporeal membrane oxygenation; IQR, interquartile range; MIS-c, multisystem inflammatory syndrome in children.
aNeck symptoms: any drooling, dysphagia, trismus, or neck pain.
bDenotes differences are statistically significant; Wilcoxon rank sum test, α = 0.05. Patients with neck pain were older (P = .002) and had a higher d-dimer (P = .004) and were more likely to have undergone lumbar puncture (P = .035).
In the entire cohort, 8 patients underwent lumbar puncture. Four of those patients had neck pain exclusively, 1 patient had mental status change exclusively, 4 patients had both neck pain and mental status change, and one 4-month-old patient had irritability. Symptoms and findings are summarized in Table 2, which includes data from the 4 patients identified at our center.
| Age . | Symptoms (Cardinal KD-Like Clinical Features) . | Radiographic Findings . | Treatments (All Patients Received Broad Spectrum Antibiotics) . |
|---|---|---|---|
| 17 yr (current cohort, patient 1) | Fever, dysphagia and headache, cardiogenic shock (neck swelling) | Right palatine tonsillitis, mild narrowing of the oropharyngeal airway, no drainable abscess Large prevertebral/retropharyngeal fluid collection. Large right neck phlegmon | Intravenous immunoglobulins, corticosteroids |
| 16 yr (current cohort, patient 2) | Fever, neck pain and dysphagia (conjunctival injection) | Inflammatory cervical adenopathy on the right with retropharyngeal edema | Corticosteroids |
| 15 yr [3] | Headache, sore throat, fever, neck pain and stiffness, vasodilatory shock | Palatine tonsillar enlargement and a retropharyngeal fluid density extending down to C7/T1 | Intravenous immunoglobulins, corticosteroids, anakinra |
| 15 yr (current cohort, patient 3) | Fever, sore throat, neck pain (conjunctival injection) | Retropharyngeal lymphadenitis and prevertebral edema, no drainable abscess. Enlarged adenoids with obstruction of the nasopharyngeal passage | Corticosteroids |
| 13 yr [4] | Fevers, sore throat, posterior pharyngeal edema (cracked lips, neck swelling) | Retropharyngeal abscess | IVIG, corticosteroids |
| 13 yr (current cohort, patient 4) | Fever, headache, neck pain and dysphagia, cardiogenic shock (neck swelling) | Retropharyngeal/prevertebral edema vs fluid collection. Mild mass effect on the nasopharynx and oropharynx | Intravenous immunoglobulins, corticosteroids |
| 12 yr [4] | Fevers, neck pain, fluid responsive shock, trismus, surgical drainage revealed no purulence (neck swelling, rash, cracked lips) | Right-sided retropharyngeal abscess with right cervical adenitis | IVIG, anakinra, remdesivir |
| 4 yr [4] | Fevers, abdominal pain, sore throat, stridor, fluid responsive shock, renal insufficiency (conjunctival injection, rash) | Retropharyngeal effusion | IVIG, corticosteroids |
| 4 yr [5] | Neck swelling, pain and stiffness, facial edema, hypotension (conjunctival injection) | Retropharyngeal fluid collection with soft tissue edema | Intravenous immunoglobulins, corticosteroids |
| Age . | Symptoms (Cardinal KD-Like Clinical Features) . | Radiographic Findings . | Treatments (All Patients Received Broad Spectrum Antibiotics) . |
|---|---|---|---|
| 17 yr (current cohort, patient 1) | Fever, dysphagia and headache, cardiogenic shock (neck swelling) | Right palatine tonsillitis, mild narrowing of the oropharyngeal airway, no drainable abscess Large prevertebral/retropharyngeal fluid collection. Large right neck phlegmon | Intravenous immunoglobulins, corticosteroids |
| 16 yr (current cohort, patient 2) | Fever, neck pain and dysphagia (conjunctival injection) | Inflammatory cervical adenopathy on the right with retropharyngeal edema | Corticosteroids |
| 15 yr [3] | Headache, sore throat, fever, neck pain and stiffness, vasodilatory shock | Palatine tonsillar enlargement and a retropharyngeal fluid density extending down to C7/T1 | Intravenous immunoglobulins, corticosteroids, anakinra |
| 15 yr (current cohort, patient 3) | Fever, sore throat, neck pain (conjunctival injection) | Retropharyngeal lymphadenitis and prevertebral edema, no drainable abscess. Enlarged adenoids with obstruction of the nasopharyngeal passage | Corticosteroids |
| 13 yr [4] | Fevers, sore throat, posterior pharyngeal edema (cracked lips, neck swelling) | Retropharyngeal abscess | IVIG, corticosteroids |
| 13 yr (current cohort, patient 4) | Fever, headache, neck pain and dysphagia, cardiogenic shock (neck swelling) | Retropharyngeal/prevertebral edema vs fluid collection. Mild mass effect on the nasopharynx and oropharynx | Intravenous immunoglobulins, corticosteroids |
| 12 yr [4] | Fevers, neck pain, fluid responsive shock, trismus, surgical drainage revealed no purulence (neck swelling, rash, cracked lips) | Right-sided retropharyngeal abscess with right cervical adenitis | IVIG, anakinra, remdesivir |
| 4 yr [4] | Fevers, abdominal pain, sore throat, stridor, fluid responsive shock, renal insufficiency (conjunctival injection, rash) | Retropharyngeal effusion | IVIG, corticosteroids |
| 4 yr [5] | Neck swelling, pain and stiffness, facial edema, hypotension (conjunctival injection) | Retropharyngeal fluid collection with soft tissue edema | Intravenous immunoglobulins, corticosteroids |
Abbreviations: IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-c, multisystem inflammatory syndrome in children.
| Age . | Symptoms (Cardinal KD-Like Clinical Features) . | Radiographic Findings . | Treatments (All Patients Received Broad Spectrum Antibiotics) . |
|---|---|---|---|
| 17 yr (current cohort, patient 1) | Fever, dysphagia and headache, cardiogenic shock (neck swelling) | Right palatine tonsillitis, mild narrowing of the oropharyngeal airway, no drainable abscess Large prevertebral/retropharyngeal fluid collection. Large right neck phlegmon | Intravenous immunoglobulins, corticosteroids |
| 16 yr (current cohort, patient 2) | Fever, neck pain and dysphagia (conjunctival injection) | Inflammatory cervical adenopathy on the right with retropharyngeal edema | Corticosteroids |
| 15 yr [3] | Headache, sore throat, fever, neck pain and stiffness, vasodilatory shock | Palatine tonsillar enlargement and a retropharyngeal fluid density extending down to C7/T1 | Intravenous immunoglobulins, corticosteroids, anakinra |
| 15 yr (current cohort, patient 3) | Fever, sore throat, neck pain (conjunctival injection) | Retropharyngeal lymphadenitis and prevertebral edema, no drainable abscess. Enlarged adenoids with obstruction of the nasopharyngeal passage | Corticosteroids |
| 13 yr [4] | Fevers, sore throat, posterior pharyngeal edema (cracked lips, neck swelling) | Retropharyngeal abscess | IVIG, corticosteroids |
| 13 yr (current cohort, patient 4) | Fever, headache, neck pain and dysphagia, cardiogenic shock (neck swelling) | Retropharyngeal/prevertebral edema vs fluid collection. Mild mass effect on the nasopharynx and oropharynx | Intravenous immunoglobulins, corticosteroids |
| 12 yr [4] | Fevers, neck pain, fluid responsive shock, trismus, surgical drainage revealed no purulence (neck swelling, rash, cracked lips) | Right-sided retropharyngeal abscess with right cervical adenitis | IVIG, anakinra, remdesivir |
| 4 yr [4] | Fevers, abdominal pain, sore throat, stridor, fluid responsive shock, renal insufficiency (conjunctival injection, rash) | Retropharyngeal effusion | IVIG, corticosteroids |
| 4 yr [5] | Neck swelling, pain and stiffness, facial edema, hypotension (conjunctival injection) | Retropharyngeal fluid collection with soft tissue edema | Intravenous immunoglobulins, corticosteroids |
| Age . | Symptoms (Cardinal KD-Like Clinical Features) . | Radiographic Findings . | Treatments (All Patients Received Broad Spectrum Antibiotics) . |
|---|---|---|---|
| 17 yr (current cohort, patient 1) | Fever, dysphagia and headache, cardiogenic shock (neck swelling) | Right palatine tonsillitis, mild narrowing of the oropharyngeal airway, no drainable abscess Large prevertebral/retropharyngeal fluid collection. Large right neck phlegmon | Intravenous immunoglobulins, corticosteroids |
| 16 yr (current cohort, patient 2) | Fever, neck pain and dysphagia (conjunctival injection) | Inflammatory cervical adenopathy on the right with retropharyngeal edema | Corticosteroids |
| 15 yr [3] | Headache, sore throat, fever, neck pain and stiffness, vasodilatory shock | Palatine tonsillar enlargement and a retropharyngeal fluid density extending down to C7/T1 | Intravenous immunoglobulins, corticosteroids, anakinra |
| 15 yr (current cohort, patient 3) | Fever, sore throat, neck pain (conjunctival injection) | Retropharyngeal lymphadenitis and prevertebral edema, no drainable abscess. Enlarged adenoids with obstruction of the nasopharyngeal passage | Corticosteroids |
| 13 yr [4] | Fevers, sore throat, posterior pharyngeal edema (cracked lips, neck swelling) | Retropharyngeal abscess | IVIG, corticosteroids |
| 13 yr (current cohort, patient 4) | Fever, headache, neck pain and dysphagia, cardiogenic shock (neck swelling) | Retropharyngeal/prevertebral edema vs fluid collection. Mild mass effect on the nasopharynx and oropharynx | Intravenous immunoglobulins, corticosteroids |
| 12 yr [4] | Fevers, neck pain, fluid responsive shock, trismus, surgical drainage revealed no purulence (neck swelling, rash, cracked lips) | Right-sided retropharyngeal abscess with right cervical adenitis | IVIG, anakinra, remdesivir |
| 4 yr [4] | Fevers, abdominal pain, sore throat, stridor, fluid responsive shock, renal insufficiency (conjunctival injection, rash) | Retropharyngeal effusion | IVIG, corticosteroids |
| 4 yr [5] | Neck swelling, pain and stiffness, facial edema, hypotension (conjunctival injection) | Retropharyngeal fluid collection with soft tissue edema | Intravenous immunoglobulins, corticosteroids |
Abbreviations: IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-c, multisystem inflammatory syndrome in children.
Patients treated at our center with retropharyngeal edema were all 13 years of age or older (median age of entire cohort was 8 years of age). Clinical symptoms and treatments for patients with retropharyngeal edema in this cohort and in the medical literature are found in Table 2. Among the 4 patients treated at our center with documented retropharyngeal edema, each received 5 days or more of antibiotic treatment, and 2 received a total of 10 days of antimicrobials. The most commonly used antimicrobials were ampicillin/sulbactam and ceftriaxone.
DISCUSSION
We noted that 28% of patients diagnosed with MIS-c had neck complaints. In addition, to our knowledge, including cases at our center, at least 9 pediatric cases with retropharyngeal edema have now been reported. Furthermore, an adult with multisystem inflammatory syndrome and 2 with acute COVID-19 have also been described to have retropharyngeal edema [6, 7]. All of the patients in this cohort with retropharyngeal edema were treated with antimicrobials in addition to other anti-inflammatory treatment. However, these repeated observations may indicate that MIS-c associated retropharyngeal edema is inflammatory, rather than infectious, in nature and that antibiotic treatment may not be necessary. Retropharyngeal edema has been documented in Kawasaki disease (KD) [8], a distinct inflammatory syndrome that is associated with systemic vasculitis. The exact pathophysiology of retropharyngeal edema in KD is not clear, but one hypothesis is that it may be related to inflammation and vascular permeability in the retropharyngeal space [9, 10]. Suppurative retropharyngeal infections are most common between 2 and 4 years of age, after which time the lymph nodes regress [11]. All of the MIS-c cases with retropharyngeal edema reported were 4 years or older, which is incongruent with the typical epidemiologic distribution of purulent retropharyngeal infection. Among MIS-c patients at our center, a high percentage with neck pain received antimicrobial therapy, but patients with neck pain were not more likely to receive prolonged antimicrobial treatments.
Otolaryngologic manifestations may be under-recognized clinical features of MIS-c that do not fall clearly into the organ system criterion in the current CDC case definition. In a recent UK study, neck pain was similarly documented in 30% of subjects with similar percentages in both inpatient floor patients and those requiring intensive care [12]. Neck pain may also be an important distinguishing feature of MIS-c from other illnesses. In a US study of MIS-c vs other febrile outpatient conditions, neck pain was highly associated with a significantly higher odds ratio of MIS-c than another febrile condition [13].
Limitations of our study include its retrospective nature and variability in the capturing of data during the study period. We retrospectively identified some patients in March and April of 2020 who may have biased case identification and findings, although the first cases of COVID-19 in Georgia were documented in March 2020. In addition, during the study period, clinicians may have had varying levels of recognition of the symptoms associated with MIS-c which may have caused differences in the documentation.
In conclusion, neck symptoms are a relatively frequent manifestation of MIS-c and could be considered a distinct clinical system associated with its diagnosis. Retropharyngeal inflammation has been observed in association with MIS-c.
Notes
Financial support. A.S. received funding through the Emory MSCR program, which is through a NIH TL1/UL1 Grant (TL1TR002382 and UL1TR002378).
Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
