Kawasaki disease (KD) is a generalized, acute infantile vasculitis of medium- and small-sized arteries. The vascular inflammation occurs mostly in the coronary vessels and less frequently in the other vessels. KD affects children younger than five years of age; however, some studies have shown that KD may occur in adolescence and adulthood. People of Asian origin are highly affected with the disease especially those from Japan and neighboring countries. Males show a slight predominance over females. The usual symptoms of KD are high fever, conjunctivitis, oral mucosal changes, cheilitis, cervical lymph nodes, rash, and reddening of the palms and soles with subsequent desquamation.
Since the first description of the disease by the Japanese doctor, Tomisaku Kawasaki, in 1967 and his report for the English literature in 1974, thousands of cases have been reported worldwide. The highest prevalence is found in Japan and among the Japanese in Hawaii, followed by the United States. On average, the incidence rate of KD among Asian population is estimated to be 46 cases per 100,000.
The disease generally resolves spontaneously within several days, however, coronary aneurysms may develop in about 25% of untreated patients. The peak mortality happens 15-45 days after the onset of fever and the mortality rate is estimated to be 2%. Clinical examination is the basic method for diagnosis KD and sometimes it is associated with echocardiography or coronary angiography to detect the coronary aneurysms.
Al-Mosawi et al. (2006) assessed the criteria of diagnosis of Kawasaki disease (KD), cardiac status, and the management. All the criteria for KD diagnosis, including duration of fever, presence of conjunctivitis, cervical lymphadenopathy, oral cavity changes or appearance of skin rashes, were reviewed. Also, the heart status was reviewed. Thirty-four children were corresponding with the diagnosis of KD, of which 30 cases were Bahraini. The median age at presentation was 31 months, and five children were above five years. All patients presented with fever which lasted between two and 30 days. The other criteria of KD were presented in the patients as followings: 76.4% had cervical lymphadenopathy, 85.3% had conjunctivitis, 73.5% had polymorphic rashes, 82.3% had oral changes, 82.3% had erythema of palms and soles, and 14.7% developed peeling of hands, soles and peripheral regions during hospitalization. Two cases showed atypical presentation with prolonged fever. The first case was a 6-year-old girl who had fever for more than two weeks, cervical lymphadenopathy, conjunctivitis, myocarditis, and gall bladder hydrops. The second case was a 21-month-old girl who presented with fever, rash, erythema of palms and soles, peeling, and significant coronary artery dilatation (CAD). Sixteen patients (47%) had abnormalities on echocardiography, of which 15 cases showed CAD without aneurysm and the other case had myocarditis. All patients except two received aspirin therapy until CAD resolved completely.
Majeed and Olson (1978) reported the first two cases of Kawasaki disease in Kuwait.
Majeed et al. (1990) undertook a prospective study of 41 pediatric cases of Kawasaki disease in Kuwait seen over a period of 12-years. The cases presented throughout the year, although the incidence of presentation was found to increase in the winter and spring. In all clinical and epidemiological features, the Kuwaiti cases were similar to those reported from Japan and the USA. However, the male:female ratio (2.2:1) was found to be relatively higher to those reported in other populations. No deaths were reported.
Jawad et al. (1997) reported five infants and pre-school children that fulfill four of the five criteria for Kawasaki disease. The subjects presented at Al-Amiri Hospital consisted of three girls and two boys aged between 5 months and 3 years. Two subjects demonstrated atypical presentations; one subject mimicked infectious mononucleosis and another subject suffered from severe abdominal pain and was found afterwards to experience hydrops of the gall bladder. All patients underwent treatment during the first 10 days of diagnosis, however, echocardiographic modifications were found in three subjects. Jawad et al. (1997) suggested the existence of a causative infectious agent in Kuwait due to the occurrence of many cases in a short period of time.
The incidence of coronary artery aneurysms (CAA) in Kawasaki disease (KD) was assessed through a study conducted by Abushaban et al. (1999). Clinical and echocardiographic results were reviewed for 135 children aged between 3 months and 13 years for a period of nine years. The male to female ratio was found to be 1.54:1 and all subjects received intravenous Gamma-globulin (IVGG) throughout the acute phase. The echocardiogram was found to be normal in 106 subjects and follow-up studies of 6 months to one year continued to be normal. It was found that 10 subjects suffered from CAA throughout the acute phase and out of those eight subjects underwent a follow-up of 3 months to 1.5 years and revealed a full regression of CAA. Abushaban et al. (1999) concluded that subjects included in this study experienced less severe coronary artery modifications due to KD revealing the possibility of the positive effect of the early administration of IVGG.
Bourusly and Jawad (2005) reported five Kuwaiti children suffering from Kawasaki disease (KD) during the period between October 2000 and January 2001. All affected children (three females and two males) belonged to the same extended family sharing the same household. The age of onset of the diseases was at 4.5, 7.1, 5, 3.5, and 4.6 years, respectively. The first four cases including three females and one male were hospitalized and diagnosed with scarlet fever in October 2000, while the fifth case (a male) was hospitalized due to fever three months later. The duration of fever on admission was found to be 6, 7, and 8 days for the females and 4 and 1 day/s for the males. All subjects demonstrated four vital additional criteria for the diagnosis of KD and therefore underwent several laboratory tests including CBC, ESR, ECG, LFT, ASOT, and throat swab culture for Beta-hemolytic Streptococcus group A. Case 1 (female) demonstrated signs of meningeal irritation and the highest ESR value, while case 4 (male) showed severe genital erythema and peeling that diminished after commencing IVIG treatment. All subjects tested positive for Beta-hemolytic Streptococcus group A, negative for ASOT, and the levels of platelet counts were elevated in all subjects except case 5 (male) who experienced a relapse seven months later. Following the relapse, case 5 was treated with IVIG; however his baseline echocardiograph revealed dilatation of the left descending coronary artery without any aneurysm leading to a daily treatment of salicylates. Bourusly and Jawad (2005) proposed a co-primary infection as a result of many cases arising at the same time or within the same period of the onset of the first case. In addition, genetic susceptibility to KD was proposed due to the relapse of KD in the same subject or the belated advancement of KD in members of the same family prior to the exposure of the first index case. [Bourusly M, Jawad N. Kawasaki disease in a Kuwaiti family. Kuwait Med J. 2005, 37 (2):110-2.]
Husain and Hoque (2006) reported an 11 year old boy who experienced meningoencephalitis and was found later on to suffer from incomplete Kawasaki disease. During the subacute phase of sickness, the patient experienced prolonged fever while lacking an infection, a rash, oral mucosal alterations, and finger and perianal peeling correlated with thrombocytosis, based on these symptoms the subject was diagnosed as having meningoencephalitis and incomplete Kawasaki disease, therefore, he underwent intravenous immunoglobulin and aspirin treatment. He became afebrile, improved through treatment, and was discharged following 12 days of admission; however, during the discharge the patient experienced peeling of the fingertips and toes while the platelet count, erythrocyte and echocardiograms were found to be normal.
Bhatnagar et al. (2003) conducted a retrospective study on patients diagnosed with Kawasaki disease admitted to a hospital in Oman, during the period of 1995 to 2002, to study this disease's clinical profile and outcome, and document its recognition. Data was collected from the records of all children diagnosed according to the standard diagnostic criteria of this disease. Data analysis was done according to the patients' age, sex, seasonal variation, duration of hospital stay, duration of fever, clinical manifestation, response to treatment which was standard for all patients (single infusion of IVIG and aspirin during the acute phase with the dose being reduced after resolution of fever), and analysis of their laboratory investigations. Those with cardiac involvement and echocardiographic abnormalities were followed up for a period of at least a year, while those with coronary artery abnormalities were followed up for a long period with a pediatric cardiologist and were continued on low dose Aspirin until the normalization of the echocardiography studies. A total of 40 patients (21 males and 19 females) were diagnosed with this disease, but one patient's clinical details were not available as was treated in the UK. The mean age at diagnosis was 29 months with most of the patients (61.5%) in the age group 6-30 months. The incidence of Kawasaki disease showed seasonal variation with most of the cases presenting in March (17.5%) and October (15%), and most of the cases occurred in 1998 (eight cases) and 1999 (10 cases). The patients had a mean duration of hospital stay of 8.5 days and the mean duration of fever was 9.4 days. As regarding treatment, 37 patients received high dose aspirin and IVIG single infusion over a 12 hour period (three required a second dose as there was no response to the first dose); 26 (70%) of these patients took one day, seven (18.9%) took two days, one (2.7%) took three days, while three (8.1%) took four days post-infusion for the fever to subside. The other regimen of IVIG was given to two patients in the year 1995, which was 400 mg/kg/day for four days, and fever settled within six and eight days, respectively. The characteristic clinical features of Kawasaki disease were documented in the following frequencies: oral lesions (100%), non-purulant conjunctivitis (74.3%), polymorphus rash (71.8%), non-tender cervical lymphadenopathy (69.2%), peripheral extremity edema (61.5%), and desquamation (53.8%). In addition, all patients were noticed to be irritable on admission and during the febrile period, 33.3% had joint symptoms, 20.5% had gastrointestinal symptoms, and two cases had signs of meningism. As regarding the laboratory investigations, 56.4% had normochromic normocytic anemia, 46.2% had leukocytosis, 12.8% had thrombocytosis which increased to 28.6% during the next week, ESR and CPR were elevated >30 in 91.7% and >10 mg/l in 92.3%, respectively. Three patients had lymphocytic leukocytosis in CSF, but culture was negative. Two patients had normal abdominal ultrasound. Ten out of 40 patients had abnormal echo studies, with 12.5% (5/10) having coronary artery involvement with residua of coronary artery dilatation with or without stenosis, while the rest had cardiac involvement (myocarditis in four, mitral valvulitis in three, and pericardial effusion in three) with complete resolution.
Venugopalan et al. (2003) reported a case of Kawasaki disease which was resistant to immunoglobulin G therapy. A three year old boy was admitted with history of fever and irritability for three days, followed by development of generalized skin rash, oral mucosal and conjunctival congestion along with cervical lymphadenopathy. Investigations revealed low hemoglobin (Hb) of 9 grams/dl, white cell count of 12.8 with ANC of 11.7, platelets of 313, and ESR of 90 mm/hr. As his condition was diagnosed to be Kawasaki disease, he was given a single infusion of intravenous immunoglobulin G (IVIG) and started on high dose of aspirin, but he developed heart failure post infusion for which he was managed in an intensive care unit and needed intravenous inotropes. Echo Doppler studies showed reversed motion of the interventricular septum with mild dilatation of the left atrium and ventricle which ejection fraction was 61%. The patient was then transferred to the authors' care as his condition was not improving. He continued to be irritable, febrile, tachycardic (146/min) with blood pressure of 110/68, had bilateral non-exudative conjunctivitis and red tongue and lips with peeling of its corners, enlarged right anterior cervical lymph nodes, swelling of the dorsum of his hands and feet with muscular tenderness, extensive peeling of skin at the groin, and fading maculopapular rash over the upper chest. Cardiovascular examination revealed cardiomegaly with gallop rythum and a grade 2/6 short parasternal systolic murmur, and there was a palpable liver of 5 cm below the costal margin. Investigation after a week from the onset of his illness, showed dropping of his hemoglobin to 7.3 g/dl, platelets dropped to 440, ESR was 96 mm/hr, and CRP increased to 462 mg/l, slight elevation of bilirubin of 24 micromol/l (mostly conjugated), raised serum immunoglobulin G (IgG) of 15.8 g/l but normal IgA and IgM, positive antinuclear antibodies (ANA) 1:160 and elevated IgG fraction of anticardiolipin antibodies (ACA) but with normal antineutrophil cytoplasm antibodies and autoantibody profile. Echocardiographic studies showed improvement of septal motion, left ventricular ejection fraction of 68%, and normal proximal coronary arteries, and no hydrops of the gallbladder was detected by abdominal ultrasound. Despite being given a second course of IVIG in four divided doses daily for four days along with the high dose aspirin and stopping of the anti-failure drugs, his condition continued to deteriorate with spikes of fever, poor appetite and loss of weight. His hemoglobin persisted on 7.23 g/dl after two weeks, platelets increased to 1060, ESR increased to 140 mm/hr and CRP dropped to 124 mg/l, and he developed coronary artery aneurysms as shown by an echocardiograph. As his condition was resistant to the IVIG therapy as shown by his persistent symptoms and inflammation, he was given prednisolone 2mg/kg/day and the aspirin was reduced to 4 mg/kg/day, which improved his clinical (fever and irritability subsided, with improvement of his appetite) and biochemical (Hb increased to 12.2 g/dl, platelets dropped to 450, ESR and CRP dropped to 8 mm/hr and 6 mg/l, respectively, with normalization of ANA and ACA levels) profile. He remained well under regular follow up on low aspirin dose and the prednisolone was tapered over two weeks but the aneurysms persisted at the same size without thrombus formation and no myocardial ischemia was evident on ECG.
Elamin (1993) reported the presence of two siblings in Khartoum with Kawasaki disease.
Tabarki et al. (2001) reported a 4-year-old female who was hospitalized due to having acute encephalopathy, however, five days after hospitalization she demonstrated classical traits of Kawasaki disease and fell into a coma. During a one year follow-up, the patient suffered from severe mental retardation, diffuse brain atrophy, and poor neurologic outcome in spite of the early treatment with immunoglobulin.
Shelleh et al. (2000) reported a rare occurrence of KD in an adult. The patient was a Yemeni adult male, who presented with all diagnostic criteria for KD. In addition, his case was complicated by the rare feature of tricuspid regurgitation, and tricuspid valve endocarditis. During follow-up, two years after the diagnosis, he was found to have a right bundle branch block.