|Year : 2016 | Volume
| Issue : 3 | Page : 149-152
Clinical profile and outcome of kawasaki disease in children in himalayan region of North India
Vijay Yadav1, Parveen Bhardwaj1, Minoo Sharma2
1 Department of Pediatrics, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
2 Department of Physiology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
|Date of Web Publication||11-Aug-2016|
Department of Pediatrics, Indira Gandhi Medical College, Shimla - 171 001, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Background: Kawasaki disease (KD) is an important cause of acquired heart disease with significant morbidity if not diagnosed and managed appropriately. It is usually under-diagnosed due to lack of knowledge regarding this entity among pediatricians and dermatologists. In this retrospective, tertiary care teaching institute based study clinical profile and outcome of KD in children from Himalayan region of north India was appraised.
Methods: Clinical details of all the cases diagnosed as KD over 3 years from January 2011 to December 2013 were collected from inpatient files and outpatient follow-up clinical records.
Results: Twelve children were diagnosed to have KD out of which seven had classical KD and five had incomplete KD. Mean age at presentation was 2.45 years and male to female ratio was 1.4:1. All children were treated with intravenous immunoglobulin and aspirin. Two out of 12 children had residual coronary artery disease at 6 weeks, 3 and 6 months of follow-up echocardiography.
Conclusions: KD remains an important differential diagnosis for fever, rash, and lymphadenopathy in children <5 years.
Keywords: Coronary artery ectasia, intravenous immunoglobulin, Kawasaki disease, vasculitis
|How to cite this article:|
Yadav V, Bhardwaj P, Sharma M. Clinical profile and outcome of kawasaki disease in children in himalayan region of North India. Indian J Rheumatol 2016;11:149-52
| Introduction|| |
Kawasaki disease (KD), formerly known as mucocutaneous lymph node syndrome and infantile polyarteritis nodosa is an acute febrile illness of childhood seen worldwide in all populations, with the highest incidence occurring in children of Asian background. KD is a vasculitis with a predilection for the coronary arteries, and approximately 20-25% of untreated patients experience coronary artery abnormalities, including aneurysms. KD is the leading cause of acquired heart disease in children in most developed countries, including the USA and Japan.  KD is a disease of young children with 80% of the patients being under the age of 5 years. The condition is uncommon in infants below 3 months of age, but has been known to occur even in neonates while the peak age of onset of KD in Japan is 6-11 months, it is somewhat higher in the United States (viz. 18-24 months). ,, In last decade, more and more cases are being reported from different parts of India ,,, but a large number of cases are still being missed due to ignorance among physicians about this disease.
| Subjects and Methods|| |
Clinical details of all the cases diagnosed as KD over 3 years from January 2011 to December 2013 were collected from inpatient files and outpatient follow-up clinical records. The criteria for diagnosis of classic KD included: Fever for at least 5 days and four of the following and lack of another known disease: (i) Bilateral nonexudative conjunctival congestion, (ii) changes of the mucous membrane of upper respiratory tract like congested pharynx, congested fissured lips, strawberry tongue, (iii) polymorphous rash, (iv) changes of the extremities; peripheral edema, and (v) unilateral lymphadenopathy.  When the patient had a persistent fever but fewer than four out the five characteristics the diagnosis of atypical or incomplete KD was made.  We recorded the details of clinical symptoms, signs, and details of various investigations such as complete blood counts, differential counts, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), antistreptolysin titers, liver functions tests, kidney functions, electrolytes, throat swab, electrocardiography, chest X-rays, cerebrospinal fluid (CSF) examination, urine routine and microscopy and urine and blood cultures. Echocardiography was done in all patients, and the findings were looked for left ventricular (LV) dysfunction, mitral regurgitation (MR), pericardial effusion, perivascular brightness, lack of tapering, and aneurysm or ectasia of the coronary artery. They were followed up as per AHA guidelines. 
| Results|| |
A total of 12 children were diagnosed to have KD during 3 years. The ages ranged from 2 months to 7 years, and the mean age was 2.45 years. There were 7 males and 5 females and the male to female ratio was 1.4:1. Nine children were diagnosed within 10 days of illness, and the rest were after 10 days as they reported to us late. The most common symptom was fever noted in all patients followed by rash (50%), swelling of hand and feet in 33.3%, redness of eyes and irritability in 25%. Other symptoms present were abdominal pain, diarrhea, vomiting, seizures, and arthalgia as shown in [Table 1]. The most common sign was edema in hand and feet present in 83.3% followed by cervical lymphadenopathy and conjunctival congestion which were noted in 75% of patients. Lip changes (erythema, dryness, fissuring, peeling, cracking, and edema) were seen in 67%. Polymorphous rash (58.3%), strawberry tongue (58.3%), hepatomegaly (16.6%), congestive cardiac failure (8.3%), and icterus (8.3%) were the other findings noted as shown in [Table 1].
Leukocytosis and thrombocytosis were seen in ten patients (83.3%) each. ESR was elevated in all patients, and one patient had ESR more than 100. Increased CRP was also noted in all patients. Echocardiography (ECG) changes (prolonged PR interval, nonspecific ST-T wave changes) were seen in two patients. Echocardiography findings seen were pericardial effusion (25%), coronary ectasia (16.6%), poor LV ejection fraction (8.3%) and MR (8.3%). Anemia (50%), hypoalbuminemia (33.3%), elevated liver enzymes (16.6%), sterile pyuria (16.6%), and aseptic meningitis (8.3%) were the other laboratory finding as shown in [Table 2].
On the basis of clinical criteria, the classical KD was seen in seven patients; incomplete Kawasaki was seen in five patients. All the patients were treated with single dose intravenous immunoglobulin (IVIG) (2 g/kg), and aspirin was given 70-80 mg/kg/day every 6 h for 2 weeks of illness, thereafter 3-5 mg/kg/day as a single dose. One patient received the second dose of IVIG as his fever and irritability persisted after first dose of IVIG, and he responded well after the second dose. After 6 weeks follow-up, echocardiography was done in all patients, ten patients had normal ECHO finding, so their aspirin was stopped.
While two patients were continued on low dose of aspirin as their follow-up echos done at 3 rd and 6 th month revealed persistent coronary artery ectasia.
| Discussion|| |
KD was first reported by a Japanese pediatrician, Tomisaku Kawasaki, in 1967.  It is a self-limiting childhood illness, occurring predominantly in age <5 years and more common in males (M:F 1.5:1) , which is similar to our findings. The annual incidence of KD in children below 5 years of age is 60-150/100,000. ,, The true incidence in India is not known because it is usually misdiagnosed as viral illness and is hence less reported. It is the most common cause of vacuities in the pediatric population. The etiology is unknown, although many suspect an infectious etiology. Even though the initiating event has not yet been identified, the immune system is known to be involved during the acute stage of KD.  In the absence of treatment, KD can be divided into three clinical phases. The acute febrile phase is characterized by fever and the other acute signs of illness and usually lasts 1-2 weeks. The subacute phase is associated with desquamation, thrombocytosis, the development of coronary aneurysms, and the highest risk of sudden death in patients in whom aneurysms have developed, and generally lasts about 2 weeks. The convalescent phase begins when all clinical signs of illness have disappeared and continues until the ESR returns to normal, typically about 6-8 weeks after the onset of illness.  We diagnosed ten patients in acute phase while the remaining two were diagnosed in subacute phase. In our series, we had seven patients of classical KD and five patients of incomplete KD. Incomplete KD is more common in children younger than 1 year, in whom the rate of coronary artery aneurysms is paradoxically higher if not treated. Therefore, establishing the diagnosis and initiating treatment are essential. We noted coronary artery abnormalities in two male children in form of ectasia of left coronary artery they both were younger than 1 year, and they reported to us late and received IVIG after 10 days of illness. We had five patients of incomplete KD out of which one presented with seizures, CSF picture was suggestive of aseptic meningitis, and brain magnetic resonance imaging was normal. Cardiovascular manifestations can be prominent in the acute phase of the illness and are the leading cause of morbidity and mortality. Coronary artery abnormalities develop in 20-25% of children with untreated KD. Abnormalities may include diffuse ectasia or coronary aneurysms. Aneurysms usually become apparent one to 3 weeks after the onset of fever; their appearance more than 5 weeks after the onset of illness is uncommon. 
Fever, rash, and nonexudative conjunctivitis were the most common clinical features as noted by various authors as shown in [Table 3]. In our case series, we had seen rash in 50% cases which are less as compared to other series the reasons for this may be that some of our cases reported late, parents were not aware of rash and had atypical presentations.
|Table 3: Comparison of clinical features of various case series with present case series |
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Leukocytosis, high ESR, raised CRP and thrombocytosis were the prominent laboratory findings noted by various case series as shown in [Table 4].
|Table 4: Comparison of laboratory parameters of various case series with present case series |
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Immunoglobulin intravenous (IGIV) is the current standard of therapy, IGIV quickly normalizes the inflammatory proteins of the acute phase, except the ESR, and also improve the myocardial function.  IVIG reduces the prevalence of coronary disease from 20% to 25% in children treated with aspirin alone to 2-4% in those treated with IVIG and aspirin within the first 10 days of illness. IVIG-resistant KD occurs in approximately 15% of patients and is defined by persistent or recrudescent fever 36 h after completion of the initial IVIG infusion. Patients with IVIG resistance are at increased risk for coronary artery abnormalities. Typically, another dose of IVIG at 2 g/kg is administered to patients with IVIG resistance.  We had one child of IVIG-resistant KD, who responded well to the second dose of IVIG. Aspirin is administered in patients with KD for its anti-inflammatory and antithrombotic effects. , During the acute phase of illness, aspirin is administered at 70-80 mg/kg/day given every 6 h. Around the 14 th day of illness, when fever has resolved, aspirin is reduced to antithrombotic doses of 3-5 mg/kg/day as a single daily dose which is then continued for the next few weeks. Aspirin should be discontinued at 6-8 weeks of illness if the echocardiography is normal at this period. If echocardiography done at 6-8 weeks reveals coronary artery aneurysm, low-dose aspirin should not be discontinued. Other therapies that have been used to date include intravenous methylprednisolone and less often, cyclophosphamide, and plasmapheresis. A tumor necrosis factor inhibitor, infliximab, has also been given for the treatment of IVIG-resistant disease, usually if a second dose of IVIG or corticosteroids are ineffective.  KD was associated with a mortality rate of 1-2% in the pre-IVIG era. With improved recognition and appropriate therapy of the disease in the acute phase, this has dropped to 0.08%. Deaths are most common 2-12 weeks after the onset of the illness and are usually secondary to the coronary aneurysms. , In this case series, we have found that a child having high acute phase reactants, age <1 year and those presenting late had high cardiac morbidities.
The limitations of this study were that it was a retrospective study, included only 12 patients and we might have missed few cases of incomplete and atypical KD.
| Conclusions|| |
KD is under-diagnosed due to lack of awareness among the treating physician and the disease may be misdiagnosed as a viral exanthema in some cases. Incomplete KD may be sometimes difficult to diagnose. Male gender and age <1 year are the known risk factors for coronary aneurysm. As undiagnosed and untreated KD can lead to coronary artery aneurysm or ectasia so prompt recognition and treatment may reduce long-term morbidity and mortality.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]