Kawasaki disease



Kawasaki disease


Ranon Mann, Adam Friedman and Adam Wulkan


Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


image


Kawasaki disease (KD), seen primarily in infants and children, is an acute febrile multiorgan vasculitic process well known for its mucocutaneous and nodal involvement. Although KD was described in Japan nearly 50 years ago, its pathogenesis has yet to be clarified. Increasing evidence supports an infectious etiology.



Management strategies


The primary goal when treating a patient with KD is the prevention of cardiac complications, including coronary artery disease, aneurysm formation, myocardial infarction, and even sudden death. The mainstay of therapy has for years been the use of high-dose salicylates (e.g., aspirin) and intravenous γ-globulin (IVIG) in order to manage the acute, intense, inflammatory characteristics of this condition and to prevent the aforementioned cardiovascular sequelae.


In the acute inflammatory phase, aspirin, a potent inhibitor of prostaglandin synthesis, is initially dosed at 80–100 mg/kg/day orally, divided four times per day for 2 weeks. After the patient is afebrile for 48 hours, the dose is reduced to 3–5 mg/kg orally daily and continued for 6 to 8 weeks until the erythrocyte sedimentation rate (ESR) and platelet count normalize. Multiple trials have failed to elucidate the benefit of high-dose aspirin therapy with regards to outcomes; therefore, current evidence is insufficient to support the use of salicylates as an integral component of first-line therapy in KD.


IVIG is a known first-line therapy in the treatment of KD. IVIG, which can lead to rapid defervescence, is able to neutralize circulating myelin antibodies and to downregulate proinflammatory cytokines, including interferon-γ (INF-γ). The pediatric dosing, which is equivalent to the adult dosing, is 400 mg/kg/day intravenously over 2 hours as a single daily infusion for 4 consecutive days, or alternatively (and apparently more efficaciously) a single dose of 2 g/kg intravenously infused over 12 hours. Failure of IVIG therapy has been linked to a gene polymorphism in the plasma platelet-activating factor acetylhydrolase. No specific regimen has been assigned for these non-responding cases.



Specific investigations










Kawasaki disease: an overview.

Pinna GS, Kafetzis D, Tselkas O, Skevaki CL. Curr Opin Infect Dis 2008; 21: 263–70.


Echocardiography, stress imaging, angiography, MRI, and ultrafast computed tomography (CT) scans have been useful in the diagnosis of coronary aneurysms, occlusions, and stenosis. Echocardiography is recommended both at the time of diagnosis and after 2 to 6 weeks. It has recently been demonstrated that multi-detector CT is preferable to transthoracic echocardiography or MRI. CT can detect calcification and estimate soft plaques, offer rapid data collection and simple interpretation of images, all of which serve as an advantage over other diagnostic modalities. Conversely, MRI cannot offer rapid capture of images, thus prolonging the time under anesthesia and its associated risks. Transthoracic echocardiography can only image the proximal arteries and therefore cannot reliably detect stenosis.



The diagnosis and treatment of Kawasaki disease.

Royle J, Burgner D, Curtis NJ. Pediatr Child Health 2005; 41: 87–93.


These guidelines highlight the difficulties in the diagnosis of KD. A meta-analysis of recent data offers insight that may assist in the early recognition of this important pediatric disease. The clinical features of KD are common to many other childhood illnesses, and therefore the diagnostic criteria are not highly sensitive. Blood serologies and chemistries may be helpful, but none is diagnostic and most have a low specificity. The echocardiogram should not be used as a diagnostic test. A normal echo does not exclude KD, as coronary lesions generally occur in the convalescent phase and may develop as late as 6 to 8 weeks after the onset of fever. Because there is no specific diagnostic test for KD, increased awareness of the epidemiology and the spectrum of clinical presentation is essential for early recognition and optimal management.



First-line therapies












image Immunoglobulin A
image Aspirin (acetylsalicylic acid) B






Kawasaki disease: an update on diagnosis and treatment.

Kuo HC, Yang KD, Chang WC, Ger LP, Hsieh KS. Pediatr Neonatol 2012; 53: 4–11.


This review provides an update on the various treatment modalities available for KD, including methylprednisolone, TNF-α antagonists, statins, plasma exchange, and cytotoxic agents. It concludes that high-dose aspirin does not appear to decrease the incidence of coronary artery lesions, although further studies are required.


Treating KD refractory to IVIG is a therapeutic challenge. Recent studies have shown associations of age, platelet count, ESR, hemoglobin, C-reactive protein (CRP), eosinophil count, LDH, albumin, and alanine aminotransferase (ALT) with failure of primary treatment with IVIG. Because IVIG failure has an increased risk of coronary artery lesions, it is essential to treat such patients with a second dose of IVIG, intravenous methylprednisolone, or a TNF-α inhibitor.



Resistance to intravenous immunoglobulin in children with Kawasaki disease.

Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, et al. J Pediatr 2008; 153: 117–21.


IVIG treatment for the acute stage of KD has shown to be effective and safe. However, it is known that 10–20% of patients are resistant to initial therapy (2 g/kg IV). These patients are at increased risk for the development of coronary artery abnormalities. Using demographic and laboratory information on IVIG-resistant cases, this retrospective study attempted to develop a scoring system to help identify future resistant cases among patients in San Diego County. This would perhaps indicate the need for secondary therapies early in the treatment of these patients. Unfortunately, the diversity of the patient population did not allow for the development of an accurate and clinically useful scoring system.

Related posts:

Cat scratch disease Hemangiomas Drug eruptions Herpes genitalis Necrolytic migratory erythema Nevoid basal cell carcinoma syndrome

Stay updated, free articles. Join our Telegram channel
Tags:
Aug 7, 2016 | Posted by in Dermatology | Comments Off on Kawasaki disease

Full access? Get Clinical Tree
Get Clinical Tree app for offline access