Ten-year Audit of Kawasaki Disease in a District General Hospital

Davison M, Meridis G, Strehle EM. Ten-year Audit of Kawasaki Disease in a District General Hospital. Human Genetics & Embryology 2013, 3(2), 106. Copyright: © 2013 Davison M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The definitive version of this article is available at: http://dx.doi.org/10.4172/2161-0436.1000106 Always use the definitive version when citing. Date deposited: 13 th May 2013


Introduction
Kawasaki disease (KD) or mucocutaneous lymph node syndrome is a rare autoimmune vasculitis a ecting small and medium sized arteries in young children characterized by a fever lasting longer than ve days. e child may also have signs of bilateral conjunctivitis, cervical lymphadenopathy, a polymorphous rash, cracking of the lips and changes in the oral mucosa, and desquamation of the extremities [1]. Having 4 or 5 of these symptoms classes the child as having complete KD; incomplete or atypical KD is characterized by a patient displaying 3 or fewer of these signs accompanying the fever at diagnosis. KD has been shown to be the most common cause of acquired heart disease in children, leading to coronary artery aneurysms [2]. Correct diagnosis is therefore important, though can be di cult as the onset is similar to that of an upper respiratory tract infection, as well as scarlet fever, measles or rubella [1,2]. If the diagnosis is uncertain, it may be con rmed by the appearance of coronary artery aneurysms on echocardiogram or angiography. Irritability is another common symptom in KD, though is not part of the diagnostic criteria.
In the light of recent advances regarding genetic diagnostic techniques, which will be expanded on further in the discussion, the hospital's current diagnostic process and management of KD were assessed.
A 10-year-audit of KD was performed, and the ndings were compared with current literature guidelines on the management. Length of time to diagnosis and variations in treatment were analyzed and their e ects on the outcome for the patients in the acute and chronic phase of KD were reviewed.
Methods e audit was approved by the local trust and the notes of patients with KD over the last 10 years were acquired. e review period was between February 2003 and November 2012. e notes were analyzed in detail and the following factors were reviewed: age at diagnosis, sex, ethnicity, weight, duration and peak of fever, C-reactive protein concentration, length of hospital stay, hemoglobin and platelet levels, coagulation times, urine dipstick results, erythrocyte sedimentation rate, treatment including immunoglobulin and aspirin use, presenting symptoms, complications focusing on any cardiac abnormalities and any other abnormal results. All results obtained from blood tests were cross-referenced with the patient computer database to ensure they were recorded accurately. e computer database also allowed any imaging of the patient such as X-rays, ultrasounds or echocardiograms to be viewed and recorded. e data was then transferred anonymously to a digital form and analyzed.

Results
During the 10-year period 11 patients were identi ed with KD. Seven of the 11 patients were male and the average age was 35 months. e youngest was only 4 months old while the oldest patient diagnosed was 62 months old.
All the patients were found to have a fever lasting between 7 and 28 days. e average length of time the child had a fever was 10 days. All but one of the 11 patients had a highest recorded temperature over 39 degrees centigrade (°C). Nine of these 10 patients experienced spiking temperatures before speci c treatment for KD in the hospital. ree of the patients were diagnosed with incomplete KD, as they did not have 4 or more of the symptoms of diagnostic criteria. All 11 patients developed cervical lymphadenopathy and 10 of the 11 having conjunctivitis and a polymorphous rash. Changes to the lips and oral mucosa were seen in 7 of the 11, with changes to the extremities seen only in6, although this can be a late symptom of the disease.
High C-reactive protein levels (CRP), those greater than 5 mg/l, were seen in 10 of the 11 patients. e only patient who had a normal CRP level did not have his level checked during the initial presentation. e only time he had it recorded was a er discharge at an outpatient appointment, a er the initial diagnosis was missed. e mean CRP level in the children was found to be 126 mg/l. Only 4 patients were found to have a hemoglobin level below11 g/ dl, so quali ed as slightly anemic [1]. e average hemoglobin level was 10.8 g/dl. A high platelet count, above 450×10 9 /l was found in 5 of the patients, with a mean of 460×10 9 /l. All but one of the patients were given a course of immunoglobulin upon diagnosis; the only exception being the child who was not diagnosed initially but later at an outpatient clinic. He was also the only child not to receive high dose aspirin as the clinicians thought it unnecessary as his symptoms had settled, although his fever lasted for 28 days. He was 1 of only 2 children to develop cardiac complications; three le coronary artery aneurysms were found in both of those children. Both were still receiving aspirin therapy at the time of the audit, meaning they had been receiving aspirin for over 2 years.
On average the patients stayed in hospital for 5 days, with all of them having been apyrexial for at least 24 hours before discharge. It took 4 days on average between the child being admitted and the diagnosis being made. Treatment always began immediately upon diagnosis.
Eight of the 11 patients were treated with antibiotics during their time in hospital, all prescribed to treat suspected infections. Once KD had been con rmed antibiotics were stopped. One patient received 5 di erent antibiotics to try and treat a suspected resistant infection. All 11 patients also su ered from irritability during their time in hospital (Table 1).

Discussion
Kawasaki disease has been shown to be an extremely rare condition. On average only one patient was presented to the hospital every year with KD. In the United States in 2009 about 5,500 cases of KD were diagnosed, while approximately 19,000 patients were diagnosed in Japan in 2008 [3,4]. is shows that KD is more common in Asian populations than in Caucasian with the incidence being 30 cases per 100,000 people in the Asian community, while it is in the region of 16 per 100,000 in the Caucasian population [4]. Fever is a common reason for pediatric admissions, with children expecting to su er on average from 8 febrile episodes before 18 months of age [5]. is makes KD even more di cult to diagnose, especially as there is no speci c diagnostic test. A recent study found a possible link between urine proteomics and KD [3]. e proteins Meprin A and lamin C were found to be signi cantly elevated in those children diagnosed with KD. is could o er new ground in the management of KD; children presenting with KD symptoms could be o ered urine testing, possibly leading to quicker and more reliable diagnosis. Our audit found that those who had a fever for a longer period of time su ered more complications. Two of the ve patients with a fever lasting for longer than 8 days developed cardiac complications. No children with a fever under 8 days developed complications.
Early urine testing for these proteins in children with a 5-day, unresponsive temperature may help in improving patient outcomes. All of our patients su ered from this type of fever. Our audit found that the average time of fever before diagnosis to be 9 days, with the child su ering one day of fever a er treatment had begun, much greater than the 5 of the diagnostic criteria.
Little is known about the etiology if KD. Recent studies have suggested a genetic link, although nothing has been proven yet [6]. It has been shown that a sibling of a KD patient is 10-30 times more likely to develop the condition in the future. Parents of KD patients are also twice as likely to have su ered from the disease themselves. ese facts do suggest there to be some link between genetics and KD, though more research is required in this area.
Statistics show that 4% of patients who receive immunoglobulin go on to develop coronary aneurysms [1,6]. Of the 2 patients who developed coronary artery aneurysms1received immunoglobulin therapy while one did not. Treatment with aspirin for 6 weeks in combination with immunoglobulin has been found to be most e ective in preventing cardiac complications [1,7] and all but one of our patients received this. e one child who did not have high dose aspirin or immunoglobulin treatment went on to develop cardiac aneurysms which highlights the importance of adequate treatment as it is well known that this treatment reduces the risk of cardiac aneurysms from 25% to 4% [1,6,7]. e presence of high CRP levels in 10 of the patients also indicates this is an important factor in diagnosing KD. However, this does come with limitations as CRP is very non-speci c and would be raised in a number of acute and chronic conditions [1,2]. e sample size for the audit was small, with only 11 patients being diagnosed over the past 10 years.
is creates di culties in drawing con dent conclusions as the data may be unreliable. All the information was gathered from patient notes so any unrecorded data would be impossible to process.
In summary, a retrospective case note audit was performed and found that delay in diagnosis can be an important factor in cardiac complications.
e data analyzed highlighted the importance of early diagnosis and adequate treatment to protect against cardiac complications. It is hoped that new genetic testing will help clinicians achieve these goals in the near future.