A child with intravenous immunoglobulin–resistant Kawasaki disease who responded to intravenous methyl prednisolone

Case Report A 5 year old boy presented with 6 days history of fever, irritability, and arthralgia. Physical examination revealed a maculopapular rash, conjunctival injection, strawberry tongue and peripheral oedema. There was no cervical lymphadenopathy or BCG induration. Rest of his examination was unremarkable. Initial laboratory results on admission revealed normal blood counts, elevated inflammatory markers, hypoalbuminaemia and sterile pyuria. Echocardiography done on day 6, showed no coronary artery abnormalities or myocarditis.


Introduction
Kawasaki disease (KD) is an acute febrile illness in children with lethal outcome due to associated coronary artery aneurysm 1 . Intravenous immunoglobulin (IVIG) is the standard treatment of KD. IVIG resistance occurs in approximately 15% of patients with KD and carries a poor prognosis 2 . We report a child with IVIG resistant KD who responded to intravenous (IV) methylprednisolone.

Case Report
A 5 year old boy presented with 6 days history of fever, irritability, and arthralgia. Physical examination revealed a maculopapular rash, conjunctival injection, strawberry tongue and peripheral oedema. There was no cervical lymphadenopathy or BCG induration. Rest of his examination was unremarkable. Initial laboratory results on admission revealed normal blood counts, elevated inflammatory markers, hypoalbuminaemia and sterile pyuria. Echocardiography done on day 6, showed no coronary artery abnormalities or myocarditis.
The diagnosis of KD was made based clinically and he was given IVIG 2g/kg with aspirin 100mg/kg/day. There was no clinical improvement with the treatment. The repeat investigations on the 9 th day of the illness revealed neutrophil leucocytosis, anaemia, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) ( Table 1). On the 14 th day of the illness, repeat echocardiography showed dilatation of coronary arteries for which a second dose of IVIG was given. (Table 2) Despite the two doses of IVIG, there was no clinical improvement. Investigations on day 32 showed worsening of the haematological and inflammatory markers. (Table 1) Third echocardiography done on 35 th day of illness revealed worsening of coronary artery dilatation and appearance of another aneurysm (Figure 1).

Figure 1: Dilated coronary arteries and coronary artery aneurysm at LMCA & LADA on day 35
He was started on IV methylprednisolone 30mg/kg, continued for three days, followed by oral prednisolone for 2 weeks.

Discussion
KD, which was previously called mucocutaneous lymph node syndrome, is more common in Asian children 1 . The diagnosis of KD is based entirely on clinical features and basic laboratory investigations. In order to prevent coronary artery involvement, it is essential to establish the diagnosis early in the disease and to commence treatment 2 .
IVIG has been the main treatment modality in KD. IVIG therapy given at 2g/kg during the first 10 days of the disease has reduced the incidence of coronary artery aneurysm from 25% to 5% 2 .
IVIG resistant KD is defined as a persistent or recrudescent fever 36 hours after completion of the initial IVIG infusion 3 . Since patients with IVIG resistance KD are at increased risk of developing coronary artery aneurysms it is recommended to give another dose of IVIG 1 .
There is no consensus on second line therapy for those who failed to respond to two doses of IVIG. Before the availability of IVIG, prednisolone has been used as a first line therapy for KD 2 . Few case series have showed the effectiveness of corticosteroids in halting the progression of coronary artery abnormalities in children with IVIG resistant KD [3][4][5] . A small comparative study showed that intravenous methylprednisolone 30mg/kg for 3 days was superior in terms of suppressing the fever but the incidence of coronary artery aneurysm was similar in both groups 6 . In this child, clinical improvement was noted only after starting IV methylprednisolone therapy and there was no progression of the coronary artery dilatation and aneurysm formation after that. In addition to steroids and IVIG, plasmapheresis, cyclophosphamide, ulinastatin and abciximab are the available treatment options for IVIG resistant KD 10 .