Unilateral Acute Parotitis: A Novel Manifestation of Pediatric Coronavirus Disease

Sushil Sharma; Vikas Mahajan; Ravinder Gupta

doi:10.4103/ipcares.ipcares_163_22

CASE SERIES

Year : 2022 | Volume : 2 | Issue : 4 | Page : 200-203

Unilateral Acute Parotitis: A Novel Manifestation of Pediatric Coronavirus Disease

Sushil Sharma, Vikas Mahajan, Ravinder Gupta
Department of Pediatrics, Acharya Shri Chander College of Medical Sciences and Hospital, Jammu, Jammu and Kashmir, India

Date of Submission	04-Jul-2022
Date of Decision	01-Nov-2022
Date of Acceptance	02-Nov-2022
Date of Web Publication	29-Nov-2022

Correspondence Address:
Dr. Sushil Sharma
Flat Number 602-A, Royal Nest Flats, Adarsh Vihar, Sainik Colony, Jammu, Jammu and Kashmir
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_163_22

Abstract

Background: Severe acute respiratory virus coronavirus-2 infection or coronavirus disease (COVID) is categorized into acute illness and late multiinflammatory syndrome in children (MISC). This has recently been challenged with recognition of presentations with mucocutaneous-enteric symptoms that display considerable overlap between the two. We recognized a similar overlap of manifestations when encountered the three cases of fever associated with unilateral parotitis. Clinical Description: The three patients were of different age groups ranging from 2 months to 7 years of age, all of whom presented with fever, unilateral swelling of face and neck consistent with the region of the parotid gland, and absence of other localizing symptoms or abnormalities on examination. All of them were positive for COVID antibodies, had negative COVID real-time polymerase chain reaction test, did not satisfy the diagnostic criteria of MISC, but had raised inflammatory markers. Since the workup for other common causes of acute parotitis was negative, a clinical diagnosis of post-COVID immune-mediated acute parotitis was kept. Management: All the three patients were managed with systemic steroids (oral or parenteral) and showed complete resolution of symptoms and normalization of laboratory parameters within a few days, a therapeutic response in alignment with an immune-mediated phenomenon. Conclusion: Acute unilateral parotitis with pyrexia may be a hitherto unreported late post-COVID manifestation that is immune mediated and shows an excellent therapeutic response to a short course of steroids.

Keywords: Multi-inflammatory syndrome in children, parotid swelling, steroids

How to cite this article:
Sharma S, Mahajan V, Gupta R. Unilateral Acute Parotitis: A Novel Manifestation of Pediatric Coronavirus Disease. Indian Pediatr Case Rep 2022;2:200-3

How to cite this URL:
Sharma S, Mahajan V, Gupta R. Unilateral Acute Parotitis: A Novel Manifestation of Pediatric Coronavirus Disease. Indian Pediatr Case Rep [serial online] 2022 [cited 2023 Jun 3];2:200-3. Available from: http://www.ipcares.org/text.asp?2022/2/4/200/362236

Facts that have emerged since the onset of the pandemic regarding pediatric severe acute respiratory syndrome coronavirus-2 (SARS COV-2) infections are that children are usually only mildly affected, have low contagiousness, and rarely develop complications.^[1] In most cases, the symptoms resemble other respiratory viral illnesses and tend to subside quickly, with only a minority requiring hospitalization.^[2] A few months into the pandemic, the association of a multisystemic illness similar to Kawasaki disease with SARS COV-2 was recognized, which resulted in high morbidity and sparked apprehension regarding the long-term sequelae.^[3] Multiinflammatory syndrome in children (MISC) has since become a familiar entity, with cases being reported from worldwide.^[4],[5] Mucocutaneous involvement with rash, conjunctivitis, and lymphadenopathy has been reported with acute infection as well as MISC.^[6] Other rarer conditions associated with coronavirus disease (COVID) include acute disseminated encephalomyelitis, Guillain − Barre Syndrome, arthritis, intussusseception, relapses of nephrotic syndrome, etc.

We present three children with febrile illnesses with acute unilateral parotitis. The differential diagnoses for this clinical phenotype would usually include infectious parotitis, sialolithiasis, salivary gland abscess, and neoplasm. The reason for discussing this case series is to highlight the common factors that we noted in these children, all of whom presenting to our institute shortly after the peak of the third wave of COVID in February 2022. This included a positive COVID serology, negative real-time polymerase chain reaction (RT-PCR), raised inflammatory markers, and no other typical clinical manifestations of MISC. Although a few similar cases have been reported from other parts of the world, to the best of our knowledge, there are none from India.^[7],[8],[9]

Case 1

Clinical description

A 7-year-old girl presented to the emergency department with left-sided painless facial swelling near the angle of her jaw for the last 2 days, severe enough to cause partial malocclusion and trismus. This had resulted in difficulties in biting and chewing her food leading to decreased oral intake. There was no history of fever or rash during the current episode and she otherwise appeared well. There was no history of dental pain, swelling at any other site, conjunctival congestion or sudden appearance of facial asymmetry associated with weakness. There was no history of contact with similar patients or any such swelling in the past. There was significant past history of being diagnosed with coronavirus disease-19 on the basis of nasopharyngeal swab for RT-PCR when she had developed fever and upper respiratory tract symptoms 4 weeks before the current illness. The child had become asymptomatic and the RT-PCR had become negative within 7 days. There was a history of fever with upper respiratory symptoms in two other family members, but none of them had undergone COVID RT-PCR at that time and had shown full recovery. There was no similar illness in the past. The child had been immunized including mumps vaccine as part of MMR vaccine, studied in class 2^nd, and had no other contributory history.

On examination, the patient was afebrile and her vitals were stable. Her body mass index was within the normal limits for her age. She had a visible swelling of the left cheek and adjoining preauricular and submandibular areas which measured approximately 7 cm × 5 cm. The swelling was firm, nontender and did not localized increase in temperature, erythema, induration, or fluctuation. The intraoral examination was normal, with no purulent drainage expressible from Stensen's duct, dental caries, or gingivitis. There was no conjunctival congestion, redness of tongue, rashes, or lymphadenopathy. Respiratory, cardiovascular, abdominal, and neurological examinations were noncontributory. On the basis of history and examination, the differential diagnoses considered were mumps, parotid gland abscess, sialolithiasis, and juvenile recurrent parotitis. The absence of prodromal symptoms, being vaccinated, and the nontender and nonerythematous nature of swelling made mumps as unlikely. Similarly, the absence of toxicity and fluctuation precluded suppuration. Juvenile recurrent parotitis has a similar phenotype but has to be recurrent. Investigations were planned keeping these differentials in mind.

Management and outcome

Initial investigations were planned to determine the anatomical origin of the swelling, and laboratory evidence of infection or inflammation. Local soft-tissue ultrasonography demonstrated diffuse asymmetric enlargement and swelling of the left parotid gland without any evidence of an obstructing stone, mass, or abscess. Multiple enlarged lymph nodes were noted in the intraparotid and retroparotid areas. Laboratory values showed normal blood counts, but raised inflammatory markers including raised C-reactive protein (CRP) 33 mg/L and raised erythrocyte sedimentation rate (ESR) 30 mm/1^st h. Serum amylase was also raised at 250 U/L (normal 40–140 U/L). A repeat COVID RT-PCR that was negative ruled out re-infection. SARS-CoV2 immunoglobulin G antibodies were elevated (31 AU/ml; normal <10 AU/ml). Investigations to assess the extent of systemic inflammation due to COVID revealed normal D-Dimer (0.27; normal <0.50 ug/ml) and serum ferritin (45; normal 13–150 ng/ml) levels.

Based on the clinical features of a nonsuppurative swelling of the parotid gland with no other associated symptoms, recent history of COVID, presence of anti-COVID antibodies along with elevated CRP and ESR suggested it to be a post-COVID complication which was probably immune mediated. The absence of other clinical features such as fever, rash, and other systemic involvement and normal levels of D Dimer and serum ferritin excluded the diagnosis of MISC.

The patient had been started on oral amoxycillin at admission but showed no response after 3 days. With the absence of an alternate diagnosis, the possibility of an immune mediated post-COVID parotitis was considered and she was started on oral prednisolone (1 mg/kg/day). She showed rapid resolution of swelling which almost completely disappeared by the 5^th day. A repeat CRP done on the same day was normal (4 mg/l), and the steroids were stopped.

Case 2

Clinical description

A 3.5-year-boy presented with fever and swelling of the right angle of his jaw for 3 days. The fever was mild grade. There was a history of poor appetite for the same duration. There was no history of cough, cold, rashes, loose motions, fast breathing, or swelling at any other site. There was no history of any febrile illness in the recent past, or of having mumps. There was no history of fever in any family member. He was completely immunized as per the schedule.

The patient was febrile (temperature 37.9°C) and had stable vitals. His anthropometric parameters were within the normal range for his age. Mild pallor was observed. The swelling in the right angle of the jaw was approximately 8 cm × 5 cm, firm, nontender, and nonfluctuant. The examination of the oral cavity did not reveal any caries or discharge from stensens duct. There was no rash, lymphadenopathy, redness of the conjunctiva, or tongue. There was no testicular swelling. There were no other pertinent findings on systemic examination.

Management and outcome

As the patient was hemodynamically stable and nontoxic at the time of presentation, a watch and wait policy was adopted and oral paracetamol prescribed, while we awaited the test results. The patient became afebrile on the 2^nd day of admission, but the swelling remained the same size.

His laboratory parameters revealed leucocytosis (17400 × 10⁹/L) which was predominantly lymphocytic. ESR was increased (44 mm) but CRP normal (5 mg/L). Immunoglobulin G antibodies for mumps were negative. The COVID RT-PCR was negative but serology for antiCOVID antibodies was positive (40.75 AU/ml). Ultrasound of the parotid showed a bulky right parotid with patchy hypoechoic areas within the parenchyma suggestive of parotitis. As there were no other clinical features suggestive of MISC including fever, rash, lymphadenopathy, or systemic involvement, the patient was not further evaluated on the lines of MISC. In view of persistence of swelling even after 5 days, the possibility of a parotid swelling secondary to an immune-mediated phenomenon was kept and patient initiated on low dose oral prednisolone (1 mg/kg/day). Like the first case, there was good therapeutic response and almost the complete resolution of the swelling by the 5^th day.

Case 3

Clinical description

A 2-month-old boy presented with fever for 5 days, a swelling on the right side of his face (near the angle of his jaw), irritability, and decreased breastfeeding for 2 days. There was no history of cough, cold, or difficulty in breathing before or during this illness. There was no history of loose motions, vomiting, rash, lethargy, or seizures. He was passing urine normally. There was a history of a brief febrile illness associated with cold and cough, in two family members including his mother a month earlier. They had not been investigated, but had recovered within 5 days. The baby had remained asymptomatic at that time. He was an exclusively breastfed infant. Both the antenatal and perinatal periods had been uneventful. He had received his immunization at 1.5 months.

On examination, the infant was febrile (temperature 38°C), irritable, and had no dehydration or abnormal vital signs. The anterior fontanelle was at level. The swelling present near his right angle of the jaw was around 5 cm × 4 cm in size. It was firm to palpate and there was no fluctuation, tenderness, or erythema. The examination of the oral cavity was normal. There was no abdominal tenderness or any testicular swelling. No abnormality was detected on systemic examination.

Management and outcome

Keeping in view the age of the baby and presence of fever, the patient was initially investigated and treated on the lines of sepsis. On complete blood count, there was leukocytosis (18,700 × 10⁹/L) with normal platelet count (2,50,000 × 10⁹/L). The CRP level was raised at 28 mg/dl (normal 0–6 mg/l). Nonetheless, in view of the pandemic and recent history of fever in the family, he was investigated for COVID. Although the COVID RT-PCR was negative, anti COVID antibodies were significantly raised (58.96 BAU/ml). Further investigations on the lines of MISC revealed raised d-dimer levels at 1260 ng/ml, but serum ferritin (75.78 ng/ml) and pro thrombin index level (INR 100%) were normal. The ultrasound of the right parotid gland revealed enlargement of the gland with few sub-centrimetric lymph nodes underneath, and no obstruction to the drainage. Echocardiography was normal with normal calibre coronaries. The patient had been started on broad-spectrum antibiotics at admission. The possibility of MISC was reviewed considering the fever, positive anti SARS COV 2 antibodies and raised inflammatory markers, but there were insufficient criteria to meet the case definition. Considering post-COVID parotitis, the patient was started on IV methylprednisolone at 2 mg/kg/day. He became afebrile within 48 h and there was complete resolution of the swelling by day 5. Repeat investigations showed a normal TLC (7500 × 10⁹/L) and a normal CRP level (6 mg/l). Steroids were stopped.

Discussion

SARS COV-2 has been characterized into two distinct clinical phenotypes, namely an acute COVID phase in which the case is PCR positive and MISC in which the patient has a association with COVID and are positive for COVID antibodies. The WHO has published a criteria for the diagnosis of MISC, which in addition to fever requires the presence of involvement of two or more organ systems and laboratory evidence of inflammation. This characterization of pediatric COVID into acute and postinfectious entities has recently been challenged as there is the significant overlap between both.^[6] There have been children meeting the criteria for MIS-C in both the acute phase of infection (polymerase chain reaction positive) and postacute or convalescent phase of infection (antibody positive) groups.^[6] Whereas the acute group presented more commonly with respiratory symptoms, the postacute or antibody-positive group presented with muco-enteric symptoms.^[6] Being a pro-inflammatory condition, MISC results in inflammation of various body organs such as the skin, lymph nodes, and heart tissue. The affected tissues show infiltration of T cells, and B cells with the presence of microthrombi, indicative of an ongoing anti-viral immune response and microangiopathic damage, respectively.^[10] However, there is still no clear understanding why certain tissues of the body are more predisposed to viral propagation and whether this depends on the strength of the local immune response.

Shortly, after the peak of the third wave of COVID in February 2022, we encountered these three cases of various ages with fever and unilateral parotid swelling. The fact that all these children were negative for COVID PCR, positive for COVID antibodies, had elevated pro-inflammatory markers, but did not satisfy the MISC criteria [Table 1], suggested post-COVID immune mediated parotitis, rather than an acute infection. There was the absence of a temporally related viral illness in two of the patients preceding the parotid swelling, but it is well known that acute COVID infection can be asymptomatic and hence go unnoticed. The youngest of our patients was only 2 months old at presentation. Only a few cases of parotitis have been reported in young infants, most of which are due to bacterial suppuration.^[11] We ensured that the common causes of acute unilateral parotitis such as mumps and acute suppuration were excluded, before starting the short course of steroids. The excellent therapeutic response (complete resolution of symptoms and normalization of inflammatory biomarkers) that was observed to this brief immunosuppression is another point in favor of an immune-mediated condition.

Table 1: Demographic and clinical features of the three patients of COVID associated parotitis

Click here to view

Recently, there have been a few reports of COVID-associated parotitis in adults^[7] and a case series of 15 patients which had two children aged 10 and 13 years.^[8] Although the direct spread of SARS CoV-2 into the parotid tissue is theoretically possible due to the presence of angiotensin-converting enzyme 2 (the virus receptor) in the parotid tissue, the exact mechanism of parotid enlargement is still not understood.^[12] In one of the case reports, based on the MRIs of parotid gland, it was suggested that there is the presence of adenitis, which might impair the gland functioning and block the main gland duct (Stenon's duct), leading to saliva retention and parotid tissue inflammation.^[13] The ultrasound studies of our patients reveal a similar picture with enlargement of intraparotid lymph nodes as well as parotid gland. This enlargement of the parotid gland has itself been hypothesized due to lymphadenitis being a causal factor. A fundamental difference between previous reports and our case series is that in the former, all the patients were adults who were SARS COV-2 positive at presentation, while our patients were children with negative RT-PCR for SARS COV-2 but positive for anti-COVID antibodies. This suggested that the parotitis in these children was a late manifestation which could be immune in origin, not vastly different in the pathogenesis from MISC.

Each patient was treated individually by separate clinicians in the department before the dots were connected. That is the reason for variation in the spectrum of inflammatory markers and type of immunosuppression used, as there is no existing standard protocol. Another reason for dissemination these clinical details and our hypothesis is to trigger research interest. Studies can be designed to explore this phenomenon further to ascertain the relation of SARS COV 2 with acute parotitis in which a complete inflammatory marker profile, viral panel, and parotid gland magnetic resonance imaging, functioning, and histopathology can be included in the work-up.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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