Six patients with Kawasaki disease showing retropharyngeal low‐density areas on computed tomography

Abstract

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology characterized by fever, skin rash, cervical lymphadenopathy, conjunctivitis, and changes in the mouth and extremities, which predominantly affects young children.1 The diagnosis of KD is made according to the Japanese diagnostic guideline on the clinical findings.2 The acute phase symptoms are self-limiting, whereas formation of coronary artery aneurysms could cause acute myocardial infarction in the future. Although several authors have reported cases of KD mimicking retropharyngeal abscess (RPA) and suggested difficulty in differential diagnosis from infectious RPA, each described a single or two cases and often lacked laboratory findings.3–12 We present here six Japanese patients with KD showing retropharyngeal low-density area (LDA) on computed tomography (CT) and their laboratory findings. We retrospectively reviewed the medical records of 54 KD patients (mean age, 40.5 months old) who were admitted to Kitami Red Cross Hospital from June 2003 to May 2008. The diagnosis of KD was made according to the Japanese diagnostic guidelines.2 Group A streptococcus and primary Epstein–Barr virus infection were ruled out on throat culture and serological test, respectively. Six patients were initially suspected as having RPA from their clinical findings accompanied by retropharyngeal LDA on CT, and were included in the study. The clinical and laboratory features are summarized in Table 1. Age at onset ranged from 30 to 98 months (mean, 54.7 months). There was no sex difference. Bilateral or unilateral neck swelling with or without pain was observed in all of the patients. Neck stiffness, trismus and drooling were also observed. These symptoms appeared by the second illness day (first illness day was defined as the first day of fever). The other symptoms relating to KD such as skin rash, oral manifestations, conjunctival injection, and erythema or edema of the palms and soles developed by the seventh illness day. Injection of bacille Calmette–Guerin site was observed in only one patient (patient 2). In addition to retropharyngeal LDA, CT demonstrated cervical and deep neck lymphadenopathy in all of the patients. Ring enhancement around the LDA was not observed on enhanced CT (Fig. 1). Enhanced computed tomography of the neck in patient 3. Arrowheads, low-density area without ring enhancement in the retropharyngeal space. Leukocytosis and elevated serum levels of C-reactive protein (CRP) were observed in all patients. Transient hyponatremia (<135 mEq/L) and hypoalbuminemia (<30 g/L), and elevation of serum alanine aminotransferase levels (ALT; >35 IU/L) were observed in five, four, and four patients, respectively (Table 1). All the patients were initially treated with antibiotics such as sulbactam/ampicillin, sulbactam/cefoperazone, clindamycin, or a combination of them but were not responsive. Following the diagnosis of KD, all patients received high dose-intravenous gammaglobulin (HD-IVGG) therapy (2 g/kg). Patients 1 and 4 poorly responded to the first course of HD-IVGG and required a second course of HD-IVGG. Patient 4 had pericardial effusion in the acute stage of the disease. Patient 1 had mild dilatation of the left coronary arteries but no aneurysms. LDA on CT disappeared following HD-IVGG therapy. Six of the 54 KD patients had both RPA-like manifestation and retropharyngeal LDA on CT. Because CT was not performed in all of the KD patients, the prevalence of RPA-like lesions may be underestimated. During the same period, five patients were admitted to Kitami Red Cross Hospital because of presumably infectious RPA. Thus, KD is a major cause of RPA-like lesions at least in prevalent races or countries. To our knowledge 11 cases of KD mimicking RPA have been reported in the English-language literature.3–12 Although no sex difference was observed in the present series, there was a male preponderance (13 : 4) when combined with the previous reports. Similar to the present patients, in most of the previously reported KD patients, KD with retropharyngeal LDA was initially indistinguishable from retropharyngeal cellulitis or early stage RPA and accompanied by deep neck lymphadenopathy, as observed in the present patients on CT.3–12 Although five of them underwent surgical drainage or needle aspiration, no suppurative fluid or bacteria was detected.3–6 In the present patients, retropharyngeal LDA disappeared following HD-IVGG therapy rather than antibiotic therapy, and thus likely reflected local inflammation and edema as suggested by Langley et al.7 Some features of KD such as edematous extremities, pericardial effusion, and hyponatremia are associated with overexpression of pro-inflammatory cytokines and resultant vascular leakage possibly mediated by vascular endothelial growth factor and hypoalbuminemia.13,14 Consistent with this, four and five of the present six patients had hypoalbuminemia and hyponatremia, respectively. Because the retropharyngeal space consists of loose connective tissue, local edema could preferentially develop in the space under the generalized inflammatory condition, when deep neck lymphadenopathy is present. In addition to hypoalbuminemia and hyponatremia, four of the present patients had transient elevation of serum levels of ALT. Elevation of serum ALT levels is observed in up to 40% of KD cases and could be used for differential diagnosis of KD from bacterial infection but needs careful interpretation particularly after long-term administration of antibiotics.1 Hyponatremia, hypoalbuminemia, and liver dysfunction are often observed in KD and are useful for the differential diagnosis from bacterial infection.15 Indeed, none of the present patients with presumably infectious RPA had these findings, although leukocytosis and high serum levels of CRP are commonly observed (data not shown). In three of the previously reported cases KD was diagnosed on the 10th illness day or later when the coronary aneurysms had formed.3,6,7 A Japanese nationwide survey of KD demonstrated that coronary lesions are also detected in some incomplete or atypical cases fulfilling three or fewer items of the criteria.2 Furthermore, hyponatremia, hypoalbuminemia, and liver dysfunction as observed in the present patients are risk factors for giant coronary aneurysms and predictive factors for IVGG unresponsiveness.14 Thus, echocardiography is recommended to avoid delay in diagnosis in cases of RPA-like lesions refractory to antibiotics, particularly accompanied by these laboratory abnormalities, even if the diagnostic criteria are not fulfilled. In conclusion, KD should be suspected in any cases of RPA-like lesions refractory to antibiotics, particularly accompanied by liver dysfunction, hypoalbuminemia, or hyponatremia at an early stage of the disease. Retropharyngeal LDA without ring enhancement on enhanced CT in KD possibly reflects local edema and is not an indication for invasive procedures such as needle aspiration and surgical drainage.