Hydrocele in a case of atypical Kawasaki disease: case report and review of diagnostic criteria

Kawasaki disease is a self-limiting vasculitic syndrome that predominantly affects medium and small-sized arteries and can be complicated by the development of coronary artery aneurysms (CAA) in 25% of untreated patients, which fall to 4% with treatment [1]. It is the leading cause of acquired paediatric heart disease worldwide, and can lead to myocardial infarction and late coronary artery stenosis [1]. It tends to affect previously healthy infants and children. Accurate diagnosis of incomplete and atypical Kawasaki Disease is important, because these patients are at risk of coronary artery lesions seen in typical Kawasaki Disease [2].

Classic Kawasaki Disease as defined by the American Heart Association (AHA) is associated with fever of at least 4-day duration and clinical features such as conjunctivitis, rash, adenopathy, mucositis and oedema of extremities [3], but there have also been increasing numbers of case reports of unusual clinical presentations of Kawasaki Disease, such as gallbladder hydrops and acute cholestatic hepatitis [4].

In this case report, we describe a patient with acute testicular hydrocele who was subsequently diagnosed to have incomplete Kawasaki Disease. We wish to highlight the importance of considering a diagnosis of Kawasaki Disease in a child with prolonged fever and unexplainable symptoms suggestive of inflammation, especially unexpected presentations such as a testicular hydrocele, as timely diagnosis is essential to reduce treatment delay.

The current understanding of Kawasaki Disease pathophysiology is limited due to several factors – low availability of human tissues of disease, failure to identify specific etiological triggers, and incomplete understanding of underlying molecular and cellular mechanisms [7]. In a post-mortem study of patients with Kawasaki Disease, 73% of patients were identified to have renal artery involvement and acute kidney injury involving glomerulonephritis with intracapillary changes and deposition of immune complex composed of IgA and complement component 3 [8]. These findings are comparable to findings of other inflammatory human diseases like IgA vasculitis and IgA nephropathy [8]. This suggests that the disease is largely associated with inflammation.

Because of the wide range of clinical presentations, epidemiological surveys were used to develop clinical diagnostic criteria for the disease. Epidemiological surveys from Japan were used to produce a set of diagnostic criteria [1, 9], and this is also reflected in the latest AHA 2017 scientific statement by McCrindle et al. [3]:

(a) Fever of at least 5 days duration, with at least 4 out of the 5 criteria listed below, in the absence of another known disease process to explain the illness

Patients with fewer than 4-out-of-5 of the principal symptoms can be diagnosed with Kawasaki Disease when coronary aneurysm or dilatation is diagnosed by echocardiography or coronary angiography [3]. However, diagnosis remains a challenge, as the defined criterion for Kawasaki Disease does not identify all children with the illness [3]. Many children with Kawasaki Disease exhibit other reported signs not part of the clinical diagnostic criteria, including irritability and inflammation at the site of a previous BCG immunization [10]. Some other less common but associated clinical findings include arthritis, aseptic meningitis, pneumonitis, uveitis, gastroenteritis, meatitis, dysuria and otitis [11]. Rarer abnormalities include gallbladder hydrops [4], gastrointestinal ischemia, jaundice, petechial rash, febrile convulsions, encephalopathy, ataxia, syndrome of inappropriate antidiuretic hormone secretion and macrophage activation syndrome [11, 12]. Due to its wide range of clinical presentations, Kawasaki Disease may manifest as a diagnostic dilemma [13]. It was especially difficult in our case, as the raised inflammatory markers (CRP, ESR) may be attributed to the culture proven urinary tract infection. Additionally, prolonged fever may occur with micro-abscesses in the kidney, and rash is a common finding in viral infections. However, the development of an acute hydrocele, along with clinical evidence of systemic inflammation, prompted the evaluation of atypical Kawasaki Disease, of which the AHA criteria was subsequently fulfilled. This clearly highlights that there is still merit in consideration of Kawasaki Disease, despite having already identified underlying infections that have been adequately and appropriately treated. Therefore, we recommend that for any child with prolonged unexplained fever, especially with other clinical signs suggestive of inflammation, Kawasaki Disease should be considered, even if an infective process or cause of the fever has already been identified, so as to avoid significant delays in diagnosis and delayed intravenous immunoglobulin administration.

The diagnosis of atypical Kawasaki Disease in our case is confirmed by 2DE. The Japanese Ministry of Health (JMH) criterion for Kawasaki Disease coronary involvement is defined on the basis of absolute dimension of internal diameter of coronary artery [14]. The American Heart Association (AHA) 2017 guidelines is adapted from McCrindle et al. [3] and Manlhiot et al’s [15] proposition of a classification scheme based on z score for severity of coronary artery abnormalities. JMH defines aneurysm in children less than 5 years old to have internal diameters (ID) of > 3 mm, with updated JMH guidelines in 2008 defining small aneurysms as ID < 4 mm, medium aneurysms as ID 4-8 mm, and large aneurysms as ID > 8 mm [16]. AHA 2017 revised criteria lists “no involvement of coronary artery” as Z score < 2, “dilation only” as Z score 2 to < 2.5, “small aneurysm” as Z score > =2.5 to < 5, “medium aneurysm” as Z score > =5 to < 10, and “large or giant aneurysm” as Z score > =10 [16]. Other 2DE findings of KD include coronary artery ectasia, dilatation and aneurysm, lack of tapering of coronary arteries, myocardial dysfunction, pericardial effusion, aortic root dilatation and valvular regurgitation [16]. In our case, although the 2DE shows ID ranging from mean of 2.24 to 2.70 mm which does not fulfil JMH criteria, the Z-score of + 2.9 in the LAD is in keeping with AHA 2017 definition of small aneurysm.

There have been previous reports on hydroceles with cases of patients with Kawasaki Disease [17‐19]. Kabani et al. described three patients with atypical Kawasaki Disease and communicating hydrocele [18], and Sacco et al. described an additional case of hydrocele that developed at onset of typical Kawasaki Disease [19]. A hydrocele can be produced by excessive fluid production within the scrotal sac, defective absorption of fluid, interference with lymphatic drainage of the testicle and scrotum, or by a direct connection with the peritoneal cavity. The majority of hydroceles present at birth, and are due to the presence of a patent processus vaginalis, which usually close spontaneously by 12 months [20]. The mechanism of sudden processus vaginalis opening in acute Kawasaki Disease remains unknown [17], although it is postulated that the inflammatory process of Kawasaki Disease can contribute to this process. This is supported by case reports of hydroceles developing in testicular infections [21], with Chesney et al. describing a small hydrocele secondary to Haemophilus influenza type B [22]. Jibiki et al. have nicely summarized case reports into a table, demonstrating the association of Kawasaki Disease with acute scrotum [17]. This suggests that although the incidence of acute scrotum in patients with Kawasaki Disease is unknown, careful observation may identify additional patients with Kawasaki Disease [17].

In a 2014 study by Xu et al. [23] that studied the trend of C-reactive protein (CRP) in paediatric patients with urinary tract infections pre- and post- antibiotic treatment after 24 h, the pre- and post- treatment CRP levels were 68.17 +/− 39.42 and 26.13 +/− 14.15 mg/L respectively. The significant difference in CRP before and after treatment in the study (P < 0.05) [23] shows that CRP can be used for observing pathogenesis and curative effect. In our patient, CRP downtrended at a slower rate from 294.4 mg/L on day 4 to 90.2 mg/L on day 9, suggesting the possibility of a separate ongoing inflammatory process.

The child in our case only had 1 additional compatible clinical criterion (rash) in addition to fever of more than 5 days duration. However, in view of the presentation of an acute hydrocele, further investigations were conducted to evaluate for Kawasaki Disease. This eventually led to the diagnosis of incomplete Kawasaki Disease, hence facilitating the timely administration of intravenous immunoglobulin prior to day 10 of fever.

Although there are well recognized clinical features associated with classic Kawasaki Disease, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete Kawasaki Disease. Timely diagnosis of Kawasaki Disease can reduce cardiovascular morbidity, thus it is important to consider this diagnosis in a child with prolonged fever and unexplainable inflammatory symptoms. We recommend that for any child with prolonged unexplained fever, Kawasaki Disease should be considered, even if an infective process or cause of the fever has already been identified. Acute hydrocele can also be a clinical feature of Kawasaki Disease, and is possibly related to the underlying systemic inflammatory processes, thus clinicians dealing with diagnostic dilemmas involving inflammatory processes should always consider Kawasaki Disease as a potential differential diagnosis.