Kawasaki Disease-Associated Pancreatitis in an Adolescent: A Case Report and Literature Review

TL;DR

A 13-year-old boy with unexplained abdominal pain and elevated pancreatic enzymes was later diagnosed with Kawasaki disease, highlighting the need for awareness of this rare and atypical presentation.

Contribution

This case report and literature review emphasize the atypical presentation of Kawasaki disease with pancreatitis in older children and adolescents.

Findings

Pancreatitis can precede mucocutaneous symptoms in Kawasaki disease.

Delayed diagnosis is common due to the absence of classic KD features.

Older children and adolescents may present with unexplained abdominal pain and elevated pancreatic enzymes.

Abstract

Background: Pancreatic involvement in Kawasaki disease (KD) is rare. Case presentation: A 13-year-old adolescent presented with severe epigastric pain, elevated pancreatic enzyme levels, and conjunctival injection, but he lacked a fever and the other classic features of KD. The patient was initially diagnosed with acute pancreatitis and treated conservatively. As his abdominal pain improved, mucocutaneous findings emerged, leading to a diagnosis of complete KD. A literature review was conducted to summarize reported cases of KD-associated pancreatitis. This review highlights the older age of affected patients, the variability in the timing of pancreatitis onset, and a tendency toward delayed diagnosis. Conclusions: Pancreatic involvement, including pancreatitis, can occur before typical mucocutaneous features and should be considered in older children and adolescents presenting with unexplained abdominal pain and pancreatic enzyme elevation. Increased awareness of this atypical presentation may help reduce diagnostic delay and support timely management.

Full text

1. Introduction

Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that primarily affects medium-sized arteries. Gastrointestinal manifestations, including abdominal pain, vomiting, hepatic dysfunction, and gallbladder hydrops, are relatively common [1]. However, pancreatic involvement is exceedingly rare. Importantly, when pancreatitis occurs as an initial manifestation before the development of classic mucocutaneous features, the diagnosis of KD can be particularly challenging and may be delayed. To date, only a limited number of cases of KD-associated pancreatitis have been reported, and the diagnostic approach and optimal management are not well established. Here, we report the case of an adolescent with KD, whose initial presentation was acute pancreatitis without classic KD manifestations. This case highlights the diagnostic challenge posed when pancreatitis is the initial manifestation of KD and underscores the importance of considering KD in children and adolescents presenting with unexplained pancreatic involvement.

2. Case Presentation

A 13-year-old Japanese boy was referred to our hospital with epigastric pain lasting for 1 day. Nine days before admission, he had developed fever and headache. Conjunctival injection appeared thereafter, and new-onset epigastric pain appeared one day before admission. He had no significant past or family history and no known allergies. He had normal growth and development and had received all routine childhood vaccinations.

On admission, he had a heart rate of 80 beats/min, blood pressure of 130/80 mmHg, temperature of 37.2 °C, and oxygen saturation of 99% on ambient air. Physical examination revealed marked epigastric tenderness without muscular defense or rebound tenderness. The patient was afebrile but showed conjunctival injection, without other mucocutaneous features of KD. Laboratory tests showed leukocytosis (15.1 × 10^3^/μL) with neutrophilia (89.2%) and elevated C-reactive protein levels (3.8 mg/dL). Serum amylase (334 U/L), pancreatic amylase (61 U/L), lipase (77 U/L), aspartate aminotransferase (46 U/L), and alanine transaminase (56 U/L) levels were elevated. Fasting, continuous intravenous fluid replacement, antibiotics, and analgesics were initiated for suspected acute pancreatitis. Intermittent epigastric pain persisted, and fever developed on the third day of hospitalization; however, no other gastrointestinal symptoms were observed. There was no evidence of gallstones, biliary dilatation, or any pancreatic abnormalities on imaging, including ultrasound and magnetic resonance imaging (MRI). Rapid antigen tests for COVID-19, influenza virus, human metapneumovirus, respiratory syncytial virus, group A Streptococcus, and adenovirus were negative. Polymerase chain reaction (PCR) tests for measles and rubella showed negative results. Serological testing indicated no previous infection with Epstein–Barr virus (EBV) or past infection with cytomegalovirus (CMV). An interferon-gamma release assay (IGRA) was negative. Serum IgG4 levels were within the normal range.

After ulinastatin (UTI) was initiated, the abdominal pain resolved, and the serum total amylase, pancreatic amylase, and lipase levels decreased from their peak values of 334 IU/L, 95 IU/L, and 126 IU/L, respectively. However, fever and conjunctival injection persisted, and a rash subsequently appeared on the trunk and limbs. Echocardiography demonstrated dilation of the proximal right coronary artery (4.3 mm, Z-score 2.7) and the left anterior descending artery (4.0 mm, Z-score 2.9), fulfilling the criteria for coronary artery aneurysm. Upon re-interviewing the patient and his family, cervical lymphadenopathy was reported to have occurred prior to admission, although it was not present at the time of hospitalization. He was diagnosed with complete KD on hospital day 9 (illness day 18 from the onset of fever) after persistent fever since hospital day 3, the appearance of clinical features, and the detection of coronary artery aneurysms. Despite the initial intravenous immunoglobulin (IVIG), aspirin, UTI, and cyclosporin A (CsA), he remained febrile and required infliximab (IFX), additional IVIG, and methylprednisolone pulse therapy. He subsequently received tapering corticosteroid therapy as maintenance treatment. No re-elevation of pancreatic enzymes or relapse of pancreatitis was observed during follow-up, and the coronary artery aneurysms remained stable.

3. Discussion

KD rarely presents with pancreatic involvement, with only a limited number of previously reported cases [2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Our adolescent patient presented with severe epigastric pain, marked elevation of pancreatic enzymes, and conjunctival injection at admission, but he lacked fever and other classic KD features. These atypical findings initially led to a diagnosis of acute pancreatitis and delayed the recognition of KD, illustrating a key diagnostic challenge.

A narrative literature review was conducted to identify previously reported cases of KD associated with pancreatitis. We searched the PubMed database for English-language articles published up to September 2025 using the search terms “Kawasaki disease” and “pancreatitis.” In addition, the reference lists of relevant articles were manually reviewed to identify additional reports not indexed in PubMed.

Previous reports have indicated that the timing of pancreatic involvement in KD varies. Although abdominal pain is the most frequent symptom of acute pancreatitis, some patients are asymptomatic and identified only through elevated levels of pancreatic enzymes. Our review found that 9 of the 17 reported cases (53%) experienced abdominal pain before KD was clinically diagnosed, and IVIG was initiated between illness days 7 and 22, with a median of day 9 [3,8,9,11,12,13]. Because timely IVIG administration is crucial for reducing the risk of coronary artery aneurysms, such diagnostic delays may have important clinical implications [16]. Notably, pancreatitis-associated KD tended to occur in older children and adolescents, with 12 out of 17 patients (71%) being ≥5 years old, older than the typical peak age of KD. When abdominal pain precedes mucocutaneous manifestations, clinicians may prioritize abdominal emergencies or primary pancreatitis, contributing to diagnostic delays, particularly in older children and adolescents in whom KD is less commonly suspected. Among patients whose abdominal pain developed before KD was clinically diagnosed, the number of KD symptoms present at the time of pain onset ranged widely (1–5 symptoms), with no specific mucocutaneous sign appearing earlier than the others. This heterogeneity in the early clinical presentation of KD-associated pancreatitis likely further contributes to diagnostic difficulty. The clinical characteristics, laboratory findings, and treatment responses of the previously reported 16 cases, together with those of our patient, are summarized in Table 1.

Acute pancreatitis in children can be caused by a wide variety of factors, including congenital or anatomical abnormalities, infections, drugs, trauma, systemic inflammatory diseases, metabolic disorders, and nutritional factors [17]. In the present case, the patient presented with characteristic epigastric pain suggestive of acute pancreatitis. However, pancreatic enzyme elevation was mild, and imaging findings were unremarkable; therefore, the International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) diagnostic criteria for acute pancreatitis were not strictly met [18]. In contrast, at the time of diagnosis, the 2015 Japanese clinical guidelines for acute pancreatitis did not specify a strict threshold for pancreatic enzyme elevation; therefore, acute pancreatitis was clinically suspected in this case [19].

Abdominal MRI revealed no evidence of gallstones, biliary dilatation, or triglycerides. There was no history of medication or trauma, and serological tests for common viral infections (including EBV, CMV, and mycoplasma) were negative. Although other inflammatory or systemic diseases can cause pancreatitis, no clinical features or laboratory findings indicated the presence of these conditions.

Conjunctival injection was observed at admission; however, the absence of a persistent fever and other mucocutaneous manifestations made the diagnosis of KD challenging at presentation. The patient gradually developed the characteristic features of KD and was diagnosed with complete KD according to the Japanese diagnostic guidelines [20]. Although he presented with mucocutaneous findings, fever, and coronary involvement, there were no signs of circulatory dysfunction or coagulopathy, and SARS-CoV-2 antigen testing was negative with no known exposure to COVID-19. These distinctions did not fulfill the World Health Organization (WHO) criteria for multisystem inflammatory syndrome (MIS-C). The presence of conjunctival injection at the time of abdominal pain further supported the idea that pancreatic involvement may have been an early manifestation of KD. Taken together, these findings suggested that the pancreatic involvement was most consistent with KD-associated pancreatitis.

However, the pathophysiology of pancreatic involvement in KD has not been fully elucidated. Several pathological studies suggest that pancreatic involvement may reflect the same immune-mediated vasculitic process underlying KD rather than representing a purely incidental finding. Amano et al. reported that autopsies of patients with KD who died before the introduction of IVIG therapy revealed pancreatitis in 22% of cases and inflammation of the pancreatic duct in 53% of cases [21]. Rowley et al. reported a distinctive pattern of IgA plasma cell infiltration in both vascular and non-vascular tissues in acute fatal KD, including the coronary arteries, pancreatic ducts, and kidneys [22]. Moreover, CD8 + T lymphocytes and macrophages have been identified in the pancreatic islets, displaying an inflammatory pattern similar to that observed in coronary artery aneurysms [23]. These findings support the hypothesis that pancreatic inflammation in KD is primarily immune-mediated and may share a common vasculitic mechanism with coronary artery lesions. Nevertheless, important uncertainties remain, including whether pancreatic involvement represents a primary target of vasculitis or a secondary manifestation of systemic inflammation, as well as its true clinical significance. Because pancreatic involvement may be asymptomatic or overshadowed by other systemic features, it may also be underrecognized in routine clinical practice.

The therapeutic strategies for KD-associated pancreatitis are not well established. In previously reported cases, pancreatic involvement was generally managed conservatively with supportive care, including fasting and intravenous fluid therapy. Regarding KD, initial treatment commonly consisted of IVIG. Among the 15 reported cases, including ours, 13 were treated with IVIG; however, IVIG resistance occurred in 4 patients [6,8,24,25]. Because these observations are based on a small number of published cases and are subject to publication bias, they should be interpreted with caution. In the present case, UTI, a protease inhibitor used for acute pancreatitis and listed as an off-label option in the Japanese KD guidelines, improved the pancreatic symptoms [20]. However, UTI did not prevent the subsequent emergence of classic KD manifestations. This suggests that UTI improved pancreatic injury but did not control the underlying systemic vasculitis. In our case, corticosteroid therapy was introduced after refractoriness to IVIG, IFX, and CsA, with subsequent clinical improvement. Taken together, these findings suggest that pancreatitis as an atypical presentation of KD may be associated with IVIG resistance, and this raises the hypothesis that methylprednisolone pulse therapy may be considered in selected patients with KD and pancreatic involvement.

4. Conclusions

Pancreatic involvement, including pancreatitis, may precede typical features of KD and contribute to diagnostic delay, especially in older children and adolescents. Awareness of this atypical presentation may facilitate earlier recognition of KD in patients with unexplained pancreatitis.