Consider Misdiagnosis in Refractory Kawasaki

NEW YORK — Although the majority of children with Kawasaki disease responds well to intravenous immunoglobulin therapy, 10%–15% of these patients are refractory to the first course of IVIG, and 50% of those continue to manifest fever after the second IVIG dose.

At a meeting sponsored by New York University, Dr. Philip J. Kahn described current treatment options for the child with refractory Kawasaki disease.

“Kawasaki disease is the No. 1 cause of acquired heart disease in children in developed countries. In 2000, over 4,000 hospitalizations in the United States were attributed to Kawasaki disease,” said Dr. Kahn, a pediatric rheumatologist at the NYU Langone Medical Center. “In the United States, all patients diagnosed with Kawasaki disease are treated, primarily because the children appear very ill, and they face a 20% risk of aneurysm if left untreated.”

Fortunately, IVIG reduces the risk of aneurysm to less than 5%, according to Dr. Kahn.

He recommended 2 g/kg over 8-12 hours, although the dose may be divided over 2 days.

Clinicians may also follow a protocol of 400 mg/kg per day for 4 days, especially when myocarditis is present.

Aspirin does not appear to lower the risk of aneurysm, said Dr. Kahn.

Because of the risk of aneurysm, failure to respond to IVIG is a serious concern. Patients who continue to have recrudescent or persistent fever 48 hours after the first IVIG dose should receive a second IVIG dose, according to Dr. Kahn.

If fever persists after the second dose, rethink your diagnosis, said Dr. Kahn.

Consideration should be given to other possible etiologies, such as infection (for example, streptococcus, staphylococcus, Epstein-Barr virus, adenovirus, measles, Rocky Mountain spotted fever, or leptospirosis), drug reaction (for example, to antibiotics, anticonvulsants, or antifungals), autoimmune disease (such as systemic juvenile idiopathic arthritis or polyarteritis nodosa), or acrodynia (for example, a mercury hypersensitivity reaction).

If the child is still thought to have Kawasaki disease, other treatment options are available. Steroids can shorten the duration of fever and hospital stays. A recent report found fewer coronary lesions in high-risk Kawasaki disease patients who were given pulse methylprednisolone with IVIG than in those given IVIG alone (Eur. J. Pediatr. 2009;168:181–5.)

Because tumor necrosis factor–alpha is elevated during the acute phase of Kawasaki disease and high levels are found in patients who develop aneurysms, studies have investigated the use of infliximab, an anti-TNF-alpha agent.

Indeed, fever ceased within 24 hours in 11 of 12 Kawasaki disease patients who were refractory to IVIG and were treated with infliximab (5 mg/kg), and the treatment was found to be safe and well tolerated (J. Pediatr. 2008;153:833–8.)

Other medications that have been used to treat IVIG-refractory Kawasaki disease include the protease inhibitor ulinastatin (combined with aspirin), the platelet GPIIb/IIIa inhibitor abciximab, and pentoxifylline, which acts by inhibiting the synthesis of TNF.

Immunosuppressants have sometimes been used to treat the vasculitis that is associated with Kawasaki disease, and in Japan some patients have undergone plasmapheresis.

Interestingly, the incidence of Kawasaki disease in children who are aged younger than 5 years is much higher in Japan (112 per 100,000) than in the United States, where it is higher in children of Asian descent (32.5 per 100,000) than in children of non-Asian descent (9.1 per 100,000), according to Dr. Kahn. Unlike the United States, where all children diagnosed with Kawasaki disease receive treatment, in Japan the clinicians utilize scoring systems to identify patients who are at high risk for aneurysm development, and they treat only those selected patients.

Some medications discussed in this review are not approved for use in Kawasaki disease.

Disclosures: Dr. Kahn had no financial disclosures to report.

Giant fusiform aneurysms of the left coronary artery and left anterior descending artery are visible in a child with Kawasaki.

Source © 2008 Elsevier Inc.

NEW YORK — Although the majority of children with Kawasaki disease responds well to intravenous immunoglobulin therapy, 10%–15% of these patients are refractory to the first course of IVIG, and 50% of those continue to manifest fever after the second IVIG dose.

At a meeting sponsored by New York University, Dr. Philip J. Kahn described current treatment options for the child with refractory Kawasaki disease.

“Kawasaki disease is the No. 1 cause of acquired heart disease in children in developed countries. In 2000, over 4,000 hospitalizations in the United States were attributed to Kawasaki disease,” said Dr. Kahn, a pediatric rheumatologist at the NYU Langone Medical Center. “In the United States, all patients diagnosed with Kawasaki disease are treated, primarily because the children appear very ill, and they face a 20% risk of aneurysm if left untreated.”

Fortunately, IVIG reduces the risk of aneurysm to less than 5%, according to Dr. Kahn.

He recommended 2 g/kg over 8-12 hours, although the dose may be divided over 2 days.

Clinicians may also follow a protocol of 400 mg/kg per day for 4 days, especially when myocarditis is present.

Aspirin does not appear to lower the risk of aneurysm, said Dr. Kahn.

Because of the risk of aneurysm, failure to respond to IVIG is a serious concern. Patients who continue to have recrudescent or persistent fever 48 hours after the first IVIG dose should receive a second IVIG dose, according to Dr. Kahn.

If fever persists after the second dose, rethink your diagnosis, said Dr. Kahn.

Consideration should be given to other possible etiologies, such as infection (for example, streptococcus, staphylococcus, Epstein-Barr virus, adenovirus, measles, Rocky Mountain spotted fever, or leptospirosis), drug reaction (for example, to antibiotics, anticonvulsants, or antifungals), autoimmune disease (such as systemic juvenile idiopathic arthritis or polyarteritis nodosa), or acrodynia (for example, a mercury hypersensitivity reaction).

If the child is still thought to have Kawasaki disease, other treatment options are available. Steroids can shorten the duration of fever and hospital stays. A recent report found fewer coronary lesions in high-risk Kawasaki disease patients who were given pulse methylprednisolone with IVIG than in those given IVIG alone (Eur. J. Pediatr. 2009;168:181–5.)

Because tumor necrosis factor–alpha is elevated during the acute phase of Kawasaki disease and high levels are found in patients who develop aneurysms, studies have investigated the use of infliximab, an anti-TNF-alpha agent.

Indeed, fever ceased within 24 hours in 11 of 12 Kawasaki disease patients who were refractory to IVIG and were treated with infliximab (5 mg/kg), and the treatment was found to be safe and well tolerated (J. Pediatr. 2008;153:833–8.)

Other medications that have been used to treat IVIG-refractory Kawasaki disease include the protease inhibitor ulinastatin (combined with aspirin), the platelet GPIIb/IIIa inhibitor abciximab, and pentoxifylline, which acts by inhibiting the synthesis of TNF.

Immunosuppressants have sometimes been used to treat the vasculitis that is associated with Kawasaki disease, and in Japan some patients have undergone plasmapheresis.

Interestingly, the incidence of Kawasaki disease in children who are aged younger than 5 years is much higher in Japan (112 per 100,000) than in the United States, where it is higher in children of Asian descent (32.5 per 100,000) than in children of non-Asian descent (9.1 per 100,000), according to Dr. Kahn. Unlike the United States, where all children diagnosed with Kawasaki disease receive treatment, in Japan the clinicians utilize scoring systems to identify patients who are at high risk for aneurysm development, and they treat only those selected patients.

Some medications discussed in this review are not approved for use in Kawasaki disease.

Disclosures: Dr. Kahn had no financial disclosures to report.

Giant fusiform aneurysms of the left coronary artery and left anterior descending artery are visible in a child with Kawasaki.

Source © 2008 Elsevier Inc.

NEW YORK — Although the majority of children with Kawasaki disease responds well to intravenous immunoglobulin therapy, 10%–15% of these patients are refractory to the first course of IVIG, and 50% of those continue to manifest fever after the second IVIG dose.

At a meeting sponsored by New York University, Dr. Philip J. Kahn described current treatment options for the child with refractory Kawasaki disease.

“Kawasaki disease is the No. 1 cause of acquired heart disease in children in developed countries. In 2000, over 4,000 hospitalizations in the United States were attributed to Kawasaki disease,” said Dr. Kahn, a pediatric rheumatologist at the NYU Langone Medical Center. “In the United States, all patients diagnosed with Kawasaki disease are treated, primarily because the children appear very ill, and they face a 20% risk of aneurysm if left untreated.”

Fortunately, IVIG reduces the risk of aneurysm to less than 5%, according to Dr. Kahn.

He recommended 2 g/kg over 8-12 hours, although the dose may be divided over 2 days.

Clinicians may also follow a protocol of 400 mg/kg per day for 4 days, especially when myocarditis is present.

Aspirin does not appear to lower the risk of aneurysm, said Dr. Kahn.

Because of the risk of aneurysm, failure to respond to IVIG is a serious concern. Patients who continue to have recrudescent or persistent fever 48 hours after the first IVIG dose should receive a second IVIG dose, according to Dr. Kahn.

If fever persists after the second dose, rethink your diagnosis, said Dr. Kahn.

Consideration should be given to other possible etiologies, such as infection (for example, streptococcus, staphylococcus, Epstein-Barr virus, adenovirus, measles, Rocky Mountain spotted fever, or leptospirosis), drug reaction (for example, to antibiotics, anticonvulsants, or antifungals), autoimmune disease (such as systemic juvenile idiopathic arthritis or polyarteritis nodosa), or acrodynia (for example, a mercury hypersensitivity reaction).

If the child is still thought to have Kawasaki disease, other treatment options are available. Steroids can shorten the duration of fever and hospital stays. A recent report found fewer coronary lesions in high-risk Kawasaki disease patients who were given pulse methylprednisolone with IVIG than in those given IVIG alone (Eur. J. Pediatr. 2009;168:181–5.)

Because tumor necrosis factor–alpha is elevated during the acute phase of Kawasaki disease and high levels are found in patients who develop aneurysms, studies have investigated the use of infliximab, an anti-TNF-alpha agent.

Indeed, fever ceased within 24 hours in 11 of 12 Kawasaki disease patients who were refractory to IVIG and were treated with infliximab (5 mg/kg), and the treatment was found to be safe and well tolerated (J. Pediatr. 2008;153:833–8.)

Other medications that have been used to treat IVIG-refractory Kawasaki disease include the protease inhibitor ulinastatin (combined with aspirin), the platelet GPIIb/IIIa inhibitor abciximab, and pentoxifylline, which acts by inhibiting the synthesis of TNF.

Immunosuppressants have sometimes been used to treat the vasculitis that is associated with Kawasaki disease, and in Japan some patients have undergone plasmapheresis.

Interestingly, the incidence of Kawasaki disease in children who are aged younger than 5 years is much higher in Japan (112 per 100,000) than in the United States, where it is higher in children of Asian descent (32.5 per 100,000) than in children of non-Asian descent (9.1 per 100,000), according to Dr. Kahn. Unlike the United States, where all children diagnosed with Kawasaki disease receive treatment, in Japan the clinicians utilize scoring systems to identify patients who are at high risk for aneurysm development, and they treat only those selected patients.

Some medications discussed in this review are not approved for use in Kawasaki disease.

Disclosures: Dr. Kahn had no financial disclosures to report.

Giant fusiform aneurysms of the left coronary artery and left anterior descending artery are visible in a child with Kawasaki.

Source © 2008 Elsevier Inc.