Kawasaki disease (KD) is a systemic vasculitis that affects medium-sized arteries with a predilection for involvement of the coronary arteries. The diagnosis of complete KD relies on fever for at least 5 days in the presence of 4 of 5 other clinical criteria (changes in extremities, polymorphous exanthema, bilateral bulbar conjunctival injection without exudates, changes in lips and oral cavity, and cervical lymphadenopathy [>1.5 cm in diameter]). In incomplete KD, patients have persistent fever but fewer than 4 of the 5 characteristics (1). Gastrointestinal signs or symptoms are not part of the diagnostic criteria for KD; however, many patients with KD have abdominal complaints and/or liver function abnormalities as part of their presentation (2). On occasion, gastrointestinal symptoms may be the presenting chief complaint. The present study identifies the spectrum of presentation, demographic/laboratory features, and clinical outcomes of patients with KD who were initially referred for gastroenterology consultation.
We reviewed all cases of KD admitted to Children's Hospital Colorado from January 2009 through February 2011. All patients with KD were diagnosed by a pediatric infectious disease specialist. Patients were defined as patients with KD who presented primarily with prominent gastrointestinal symptoms, resulting in gastrointestinal service consultation before their diagnosis of KD. A retrospective chart review was conducted to collect demographic, clinical, laboratory, and outcome data. All of the patients were independently reviewed by the authors who concurred with the ultimate diagnosis of KD. Day of illness was defined using the first day of fever as day of illness 1. Intravenous immunoglobulin (IVIG) resistance was defined as persistent or recrudescent fever >36 hours after the completion of the IVIG infusion. Incomplete KD was defined using published criteria (1). Coronary artery abnormalities were defined as coronary arteries with a z score of >2.5.
Seven of 118 (6%) patients with KD, who were admitted and initially referred to gastroenterology were identified. Demographic, clinical, laboratory, and outcome data of the 7 identified patients are presented in Table 1. All 7 patients were male with a median age of 9.7 years (range 4.9–14). The median duration of hospitalization was 4 days (range 2–9). All 7 patients had marked abdominal pain at presentation, 5 of 7 (70%) had vomiting, 4 of 7 (57%) had diarrhea, and jaundice was evident in 3 of 7 (43%) patients. All 7 (100%) patients had fever for >5 days and rash. Nonpurulent conjunctivitis, mucocutaneous manifestations, and extremities changes were detected in 6 of 7 (86%), 5 of 7 (71%), and 3 of 7 (43%) patients, respectively. None of the patients had cervical lymphadenopathy. Four of the 7 patients (57%) were diagnosed as having incomplete KD. Hepatomegaly was detected in 4 (57%) of the 7 patients, but none had splenomegaly.
One or more abnormalities in liver studies were found in 6 of 7 (86%) patients. All 6 patients had elevated γ-glutamyl transpeptidase and alanine aminotransferase. Aspartate aminotransferase was elevated in 3 of 7 (43%) patients, and total bilirubin was elevated in 4 of 7 (57%) patients. Six (86%) of the 7 patients had abnormal abdominal imaging, by ultrasound or computed tomography scan (Table 1). Gastroenterology consultation was obtained at median day 5 of illness, and infectious disease consultation was obtained at median day 6 of illness. Pediatric surgery consultation was obtained in 3 patients. Two of the patients (29%) had IVIG resistance requiring additional therapy. Coronary artery abnormalities (dilation) were detected in 1 patient (14.3%). The pediatric gastroenterologists’ initial diagnoses of the 7 patients are shown in Table 2.
Although vomiting and diarrhea occur commonly in patients with KD, severe abdominal pain, jaundice, and cholangitis are unusual presenting complaints (3). This case series highlights the spectrum of gastrointestinal signs and symptoms in children with KD.
Various presentations of KD with primary gastrointestinal complaints have been reported in the literature. Zulian et al (4) presented a case series of 10 patients with KD (4.5% of their cohort) who presented with signs and symptoms of an acute surgical abdomen. Nine of the 10 patients underwent surgical intervention before the diagnosis of KD was evident. Mesenteric vasculitis with possible thrombosis was postulated to be the pathogenetic mechanism for some of these patients. Hepatitis, cholangitis, jaundice, or significantly elevated transaminases have been reported previously by several authors (2,5–7). Patients with KD presenting with intestinal obstruction and gastrointestinal hemorrhage have also been reported (8–10). In most of these patients, the initial diagnostic impression was a gastrointestinal disorder.
The mechanism of gastrointestinal involvement in KD is not clear. One proposed hypothesis is that the vasculitis of the gastrointestinal vessels may be the etiology of gastrointestinal signs and symptoms. Systemic vasculitis has been documented in many organs and sites in 37 autopsied patients with KD including the salivary glands, intestine, liver, biliary tract, and pancreas (11). Other theories postulate that the gastrointestinal tract may be the primary site of entry of an etiologic agent of KD (12) or that an infectious respiratory agent may spread through the bloodstream to target tissues including the gastrointestinal tract (12). Another theory is that the gastrointestinal symptoms are caused by a toxin produced by the KD agent that may or may not enter via the gastrointestinal tract (13).
It is interesting that patients in this series with gastrointestinal presentation were male, older, and had lower inflammatory markers and peripheral blood eosinophilia. The significance of these findings in not known. Although peripheral blood eosinophilia has been previously reported in patients with KD, the mechanism is unknown (14).
The initial diagnoses made by the gastroeneterologists for our patients were hepatitis (4 patients), acute cholecystitis (1 patient), acute cholangitis (1 patient), and enterocolitis (1 patient). The 6 patients with initial diagnoses of hepatitis/cholectystitis/cholangitis presented with abdominal pain, fever, elevated liver transaminases, elevated γ-glutamyl transpeptidase, and dilated gallbladders on abdominal imaging. Four of them had hepatomegaly and 3 had jaundice on examination, a picture consistent with acute hepatitis/hepatobiliary disease. The patient who was initially diagnosed with enterocolitis had a normal liver panel and colonic wall edema on abdominal imaging (gallbladder was normal); however, these diagnoses did not explain the concomitant rash, conjunctivitis, or mucosal changes found in these patients. Persistence of fever and elevated inflammatory markers prompted consultation of infectious disease and consideration of KD. Two of the 7 patients experienced shock and were admitted to the pediatric intensive care unit. Neither patient has any focus of staph or strep infection. These 2 patients show dramatic improvement after IVIG administration. One had a left main coronary artery z score of 3.57.
Four of the 7 patients were diagnosed as having incomplete KD. Absence of some of the usual clinical criteria used to make the diagnosis of KD may have contributed to the initial diagnostic confusion. Evaluation of patients with possible incomplete KD is sometimes difficult. An algorithm has been published by the American Heart Association to guide evaluation of these patients (1). A high index of suspicion and consultation with a physician experienced in KD evaluation is useful in establishing the diagnosis in such cases.
In conclusion, gastrointestinal signs and symptoms occasionally occur as the predominant clinical presentation in patients with acute KD. Gastroenterologists need to be aware of such presentations to facilitate timely diagnosis and institution of appropriate therapy. Unexplained gastrointestinal symptoms in the presence of fever and rash and at least 1 or 2 of the major clinical signs of KD (especially nonexudative conjunctivitis, mucocutaneous changes) should prompt consideration of KD in the differential diagnosis.
The authors acknowledge Dr Michael Narkewicz for reviewing this article.
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