8-year-old girl with pain in her neck

October 17, 2019

A mildly overweight 8-year-old Hispanic female in rural Colorado is brought to her primary care provider’s office with right neck pain and right-sided neck swelling of a day’s duration. The patient’s mother also stated that her daughter had a maximum temperature (T-max) of 102°F that started that morning. The patient denied any sore throat, rash, headache, rhinorrhea, cough, nasal congestion, abdominal pain, vomiting, or diarrhea. What's the diagnosis?

The case

A mildly overweight 8-year-old Hispanic female in rural Colorado is brought to her primary care provider’s (PCP) office with right neck pain and right-sided neck swelling of a day’s duration. The patient’s mother also stated that her daughter had a maximum temperature (T-max) of 102°F that started that morning. The patient denied any sore throat, rash, headache, rhinorrhea, cough, nasal congestion, abdominal pain, vomiting, or diarrhea.

The patient also denied any swelling of her tongue, hands, or feet. Her mother was concerned that the neck swelling may be related to a recent cat scratch. The patient and her family do not have any cats in the home, but the patient did play with one at a friend’s house in the past week. The mother denied any history of recent travel. No one else in the home had similar symptoms.

Prior to this patient’s presentation, she was in a normal healthy state. She does have a past medical history that includes Kawasaki disease (KD) diagnosed at 3 months of age. She has had regular follow-up with Pediatric Cardiology and there have been no concerns for residual cardiac complications.

On initial exam, the patient was well appearing and was noted to have posterior pharyngeal erythema with asymmetrical tonsils (R 2+, L 1+), and right-sided nonfluctuant anterior cervical/submandibular lymphadenopathy with a supple neck (Figure 1).

As the patient was in school at the time with possible exposure, a rapid group A Streptococcus test was obtained (negative), and culture was sent. The mother was also mildly concerned about the possibility of recurrent KD. She (a medical assistant at the PCP’s clinic) was informed that KD could not be diagnosed in the absence of 5 days of fever. Also, the patient had no other symptoms of KD such as cracked lips, desquamation of hands/feet, or conjunctivitis. The patient was sent home with instructions for supportive care for a presumed viral infection and advised to follow up if her symptoms worsened or did not improve within the next week.

The patient returned to her PCP’s office 3 days later as she had developed worsening right-sided lymphadenitis and continued to have fevers (her last fever was the previous night). Her mother noted that the patient had complained of fatigue the previous night, but otherwise had no new symptoms. Her fevers occurred nightly. The patient’s exam was consistent with the mother’s history of increasing neck swelling, and “2-cm x 3-cm nonfluctuant, mildly tender to palpation, right submandibular prominence” with full range of motion was documented. She remained well appearing.

It was time to supplement the differential diagnosis (Table 1) with further laboratory evaluation (Table 2).

Testing was notable for an elevated C-reactive protein (CRP) count (21.1) and erythrocyte sedimentation rate (ESR, 61), with mild leukocytosis (11.9) and elevated liver enzymes (alkaline phosphatase [ALP], 299; aspartate transaminase [AST], 86; alanine transaminase [ALT], 104). Bartonella henselae polymerase chain reaction (PCR) analysis was sent and later came back negative. A thyroid-stimulating hormone (TSH) test was within normal limits, and blood cultures did not grow any bacteria at 48 hours. The patient’s monospot test was positive, and Epstein-Barr virus (EBV) PCR serology was sent. See Table 2 for additional laboratory information.

At this time, the patient was given the diagnosis of mononucleosis, although some doubt lingered as to whether all the patient’s symptoms could be attributed to mononucleosis-associated EBV or cytomegalovirus (CMV). Abscess/cellulitis was also considered. She had no obvious trauma or puncture wound to the outside of the neck. She also had no dental abnormalities or signs of dental abscess on initial or repeat exam. Given the leukocytosis and elevated inflammatory markers, infection seemed likely. Antibiotics were considered including sulfa-trimethoprim and clindamycin as coverage for Staphylococcus aureus or oral flora lymphadenitis.

The patient was also considered to have ectopic thyroid tissue as in an ectopic thyroiditis. This was less likely as the condition is rare and the patient had a normal TSH. Tuberculosis was also considered as a potential infectious cause of the patient’s symptoms but also seemed less likely as she had no risk factors including travel to an endemic area. A chest x-ray done later was negative, as was a tuberculin skin test. Malignancy was considered a potential cause of the swelling as the patient had a mildly elevated white blood cell (WBC) count and low-grade fevers, but again this was moved to the bottom of the list as she had no other symptoms concerning for malignancy and the duration of symptoms was short. The patient’s elevated liver enzymes were mildly concerning for acute hepatitis but she had no liver enlargement or jaundice on exam. See Table 1 for an expanded differential diagnosis.

With laboratory testing pending, the patient’s condition progressed over the weekend. Her fevers continued nightly, and she developed red eyes (no discharge, no pruritus) and mild cough (for 2 days only) on day 5 of illness. She was seen again in the clinic on day 7 of illness for these new symptoms and persistent fevers. At this time, she had not developed swelling/changes of extremities, joint pains, or any rash that would be consistent with juvenile arthritis. Adenovirus was also considered to be a potential cause of the new onset conjunctivitis. A viral panel (and continued lack of viral symptoms) performed this same day later ruled out viral etiology. Recurrent KD seemed more likely at this time as the patient had fevers for more than 5 days and had developed conjunctivitis. Labs were repeated and notable for decreased leukocytosis and mildly decreased CRP (18). See Table 2.

On day 7 of illness, the patient’s PCP spoke with 2 pediatric Infectious Disease (ID) specialists specifically regarding likelihood of recurrent KD versus other causes of fever, fatigue, and swelling. The PCP was concerned that mononucleosis was not the correct diagnosis. The first pediatric ID specialist did not suspect KD at this point and suggested adding an antibiotic for the lymphadenopathy. The second ID specialist was a fellow, and after discussion with her attending it was decided to have the patient admitted the following morning for imaging of her neck, including an ultrasound to rule out abscess and Kawasaki protocol echocardiogram to rule out KD. Both ID specialists expressed extreme doubt regarding a diagnosis of recurrent KD due to statistical unlikelihood (one quoted a <1% chance).

The patient was seen the next morning in the emergency department (ED) of the tertiary care center where she could be evaluated by the pediatric ID team. She was then admitted with a final diagnosis of recurrent KD after echocardiogram revealed dilated coronary arteries.

Management

The patient’s admission exam at the tertiary care center was notable for prominent tongue papillae, dried/ cracked lips, and limbic sparing conjunctival injections without discharge. An echocardiogram during admission demonstrated mild dilation of the right main coronary artery (z score, 2.73, 3.67 mm), preserved ejection fraction (EF) of 60.7%, and no other cardiac abnormalities.

Rheumatology consult ruled out other causes of recurrent vasculitis such as polyarteritis nodosa and autoinflammatory disorders such as systemic juvenile idiopathic arthritis (Table 1). Previous echo per Kawasaki follow-up had been obtained 9 months prior and showed no vessel dilation. The patient was treated with infliximab followed by intravenous immunoglobulin (IVIG; both KD treatment protocol at this facility), and high-dose aspirin at the tertiary care center.

Discussion

Kawasaki disease is an acute febrile illness with an unknown cause that was first described in Japan by Tomisaku Kawasaki in 1967. Patients typically present with fever, rash, swelling of the hands and feet, conjunctival erythema, swollen lymph nodes in the neck, and inflammation of the mouth, lips, and throat. Kawasaki disease is the leading cause of acquired heart disease among children in developed countries, causing coronary artery dilations and aneurysms. Treatment of KD includes IVIG and aspirin. Kawasaki disease mostly affects young males. The disease is very rare, affecting 9 to 19 per 100,000 in children aged younger than 5 years.1

Kawasaki disease recurrence occurs only in a small percentage of patients with a history of the disease.2 Most sources agree that the recurrence rate of KD is well under 2%.3 Kawasaki disease recurrence is most common in the first 2 years following diagnosis and significantly decreases each year after 2 years from initial diagnosis, with recurrent episodes occurring 83% of the time in the first 3 years after the initial episode.

Other risk factors associated with recurrence are being male and aged younger than 3 years at the initial episode.2 The patient in this case, an 8-year-old female, was nearly statistically safe from the diagnosis, although her mother and her PCP were cautiously suspicious from the onset.

Surprisingly consistent with the data, this patient had mild dilation of the right coronary artery (RCA) and left anterior descending (LAD) coronary artery at age 3 months, which resolved with initial treatment and recurred with her second episode. Yang and colleagues found that “coronary artery complications are more likely to occur in children with recurrent KD if they were present during the first episode.”3 Also, children with longer durations of fever, lower hemoglobin levels, and higher AST levels may be at increased risk for KD.3 See Table 2 regarding elevated AST and decreased hemoglobin.

Patient outcome

The patient responded well to treatment and was discharged home on low-dose aspirin within 48 hours of admission. She had follow-up appointments with ID, Rheumatology, and the PCP clinics. One week after discharge, the patient’s mother noted desquamation of the skin on her daughter’s hands and around her mouth (Figure 2). Repeat echocardiograms were consistent with resolution of dilated coronary arteries within 2 weeks of treatment.

References:

1. Centers for Disease Control and Prevention (CDC). About Kawasaki disease, Available at: https://www.cdc.gov/kawasaki/about.html. Last reviewed October 24, 2018. Accessed September 6, 2019.

2. Sudo D, Nakamura Y. Nationwide surveys show that the incidence of recurrent Kawasaki disease in Japan has hardly changed over the last 30 years. Acta Paediatr. 2017;106(5):796-800.

3. Yang HM, Du ZD, Fu PP. Clinical features of recurrent Kawasaki disease and its risk factors. Eur J Pediatr. 2013;172(12):1641-1647.