Kawasaki Disease Complicated with Pancreatitis: A Case Report and Literature Review

Kawasaki disease (KD) can be associated with pancreatitis which is unusual. We report a patient diagnosed for pancreatitis before some of common symptoms onset in KD and summarize the main characteristics of the reported 9KD-associated with pancreatitis patients in other’s literatures to improve clinical and diagnosis for KD patients with pancreatitis. After treatment with i.v. immunoglobulins (IVIG) at a dose of 2g/kg aspirin 30 mg/kg/d divided to 3 times, fasting with parenteral nutrition therapy and omeprazole for acid suppression, her abdominal pain was remission and body temperature became normal. Abdominal ultrasound showed edematous pancreatitis had been improved. When pediatric pancreatitis patients have over 5 days fever with rash, bulbar conjunctive injection and plate count increase, KD should be included in the differential diagnosis.


Background
Kawasaki disease is a systematic vasculitis of muscular elastic arteries that can cause coronary injured and is now the most common cause of acquired heart disease in children in development countries. Intravenous immunoglobulin (IVIG) treatment in the acute phase of KD can reduce the prevalence of coronary artery abnormalities [1][2][3]. So early diagnose and treatment is very important for KD. However diagnosis of KD is not so easy sometimes especially for some uncommon symptoms preceding the common symptoms onset in KD.
During the acute febrile phase, KD systemic inflammation can influence tissues including pancreas [4]. Though Amano et al.
found a 22% rate of pathological pancreatitis in 37 KD autopsy cases, clinical symptoms of pancreatitis as a complication of KD is uncommon [4,5]. Now we report a patient diagnosed for pancreatitis before some of the common symptoms onset in KD to improve the knowledge of these patients.

Case presentation
An 8-year-old girl presented to our hospital with an 8 days history of fever (40℃) and 7 days history of abdominal pain and rash.7days before admission, her left neck lymph node became enlarge and painful. 6 days before admission, she had a general abdominal pain and vomiting. There was maculopapular in her limbs and trunk. She also had knee joint pain in that day, but disappeared spontaneously. 2 days before admission, her abdominal CT scan without contrast showed edematous pancreatitis and serum amylase was 20 IU/L. On physical examination, she had dry and red lips, mildly conjunctival injection without exudate, general abdominal pain especially for the right lower quadrant of the abdomen. Heart sounds were normal.
Laboratory examination in our hospital was as follows: blood white cell count 13x10 9 /Lwith87% neutrophils; he-moglobin105g/L; plateletcount, 602x10 9 /L;C-reactiveprotein, The patient was diagnosed with KD complicated with pancreatitis on the day presented to our hospital and treated with i.v. immunoglobulins (IVIG) at a dose of 2 g/kg, aspirin 30 mg/ kg/d divided to 3 times, fasting with parenteral nutrition therapy, omeprazole for acid suppression. After treatment with IVIG, her abdominal pain remission and body temperature became normal. Abdominal ultrasound showed no abnormalities. Laboratory examination was as follows: blood white cell count, 7.3x10 9 /L with 55% neutrophils; hemoglobin 114 g/L; platelet count, 679x10 9 /L; C-reactive protein, 21.5mg/L.

Discussion
Our patient had a fever more than 5 day with bilateral conjunction injection without exudate, maculopapular inherlimbs and trunk, bilateral cervical lymphadenopathy. She also had abdominal pain and edematous pancreatitis. According to the KW diagnostic criteria and the acute pancreatitis diagnostic criteria [6,7], our patient was diagnosed as KD and pancreatitis.
Acute pancreatitis in childhood caused by many factors including: trauma, medicines, bile duct diseases and infections. None of these factors was noted in our patient. And after treatment with IVIG, her abdominal pain remission and edematous pancreatitis had been improved. So we think her pancreatitis is complicated with KD.
From 1987 to now, only 9 cases of KD-associated with pancreatitis has been reported previously [5,[8][9][10][11][12][13]. According to these reported cases, 3 patients had been treated with medicines which can induce acute pancreatitis (Table 1). According to the class of risk by Trivedi and Pitchumoni, steroids belong to the Class I medication associated with acute pancreatitis, while aspirin belongs to the ClassIII [14]. These 3 patients could not be excluded in drug induced acute pancreatitis [5,10]. Excepting these 3 patients, all of common associational or causative factors for pancreatitis were not noted in the KD-associated with pancreatitis patients and our patient.  We summarize the main characteristics of the reported 9 KD-associated with pancreatitis patients and our patient in Table 1.
Though 76% of KD patients are <5 years of age, 70% of KD-associated with pancreatitis patients are greater or equal 5 years of age. And male gender is more predominance. All patients had abdominal pain, but for only one patient were asymptomatic presenting a lipasemia and edematous pancreas with small effusion. All patients have at least fever more than 5 days and erythema of lips or erythema of oral and pharyngeal mucosa, rash and bulbar conjunctive injection are most common clinical findings of classic KD in these patients. Rash and bulbar conjunctive injection were not common in acute pancreatitis.
In the laboratory findings, more than half of these patients have increase plate count which is also not common in acute pancreatitis. So when pancreatitis patients with rash, bulbar conjunctive injection and increase plate count, we should take KD into consideration.
Approximately 10% to 20% of patients with KD are IVIG resistant [6]. In the 10 KD-associated with pancreatitis pa- In conclusions, for pancreatitis patients having over 5 days fever and rash and bulbar conjunctive injection and increase plate count, KD should be included in the differential diagnosis.

Consent for publication
Verbal consent from parents of participants was obtained for this study, which included consent for publication without any identifying participant information.

Availability of data and material
Data generated or analysed during this study are included in this published article. For additional clinical information can be provided by the authors upon request.

Competing interest
All authors declare that they have no conflict of interest.

Funding
This study was partially supported by the fund from Guangzhou Institute of Pediatrics/Guangzhou Women and Children's Medical Center (NO: YIP-2018-005). This study was also partially supported by the fund from the Kawasaki disease cohort study (chiCTR-EOC-17013266) by Guangzhou Women and Children's Medical Center.

Author's contribution
WWL and LZ studied concept and acquisition of data and write the manuscript. XJL studied concept and acquisition of data. PH studied concept, critical revision of manuscript for intellectual content. All authors have agreed to be accountable for all aspects of the work, ensuring that the accuracy or integrity of any part of the work are appropriately investigated and resolved.