Immunoglobulin Resistance in Kawasaki Disease

Abstract

Background: The aim of this study was to identify risk factors for immunoglobulin resistance, including clinical symptoms such as arthritis and the pH of intravenous immunoglobulin. Methods: The data of children with Kawasaki disease who had received immunoglobulin were evaluated. Data regarding the brand of immunoglobulin administered were abstracted from the pharmacy records. Results: Eighty consecutive children with Kawasaki disease were evaluated (Mdn age = 28 months, 66% male). The prevalence of immunoglobulin resistance was 30%. Arthritis was a presenting symptom in the acute phase of Kawasaki disease in 8% (6/80, all male) and was seen in significant association with immunoglobulin resistance in comparison to those without arthritis (16.7% vs. 0.2%, p = 0.008). Next, the immunoglobulin brand types were divided into two groups: the relatively high pH group (n = 16), including Carimune (pH 6.6 -0.2), and the low pH group (n = 63), including Gamunex (pH 4-4.5) or Privigen (pH 4.6-5). Overall, no significant difference in immunoglobulin responsiveness was found between the low pH and the high pH groups (73% vs. 56%, p = 0.193), although the low pH group showed a trend toward a larger decrease in erythrocyte sedimentation rate ( p = 0.048), lower steroid use ( p = 0.054), and lower coronary involvement ( p = 0.08) than those in the high pH group. Conclusions: Children presenting with arthritis in the acute phase of Kawasaki disease may be at risk for immunoglobulin resistance.

Arthritis in Kawasaki disease: A poorly recognised manifestation

“…In a remarkable fashion, one patient presented with a biphasic pattern, earlyonset arthritis was followed by late-onset arthritis, as already been reported by Duzova et al 11 It has been suggested that arthritis in KD might lead to a worse outcome 7,10 because it indicates a more intense inflammatory response, 2 accounting for some of the first-line therapy resistance. 5 However, Gong et al did not find any association between the articular involvement and worse prognosis or higher inflammatory response. 2 Curiously, we found higher haemoglobin levels at admission in patients with arthritis, a finding also noted by Gong et al 2 We acknowledge that this may be due to the fact that haemoglobin level is influenced by age, with higher levels in older children.…”

“…It has been suggested that arthritis in KD might lead to a worse outcome because it indicates a more intense inflammatory response, accounting for some of the first‐line therapy resistance . However, Gong et al .…”

“…2,4 Although joint involvement has not been specifically associated with a worst outcome, a body of literature has demonstrated that this subgroup of patients has a more pronounced systemic inflammation and IVIG resistance. 2,5 Arthritis in KD is mainly described in case reports. 2,6,7 It is not a major diagnostic criterion in KD.…”

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

“…Yan et al [44] suggested that clinical features cannot predict IVIG-resistant Kawasaki disease; however, this study found that changes in oral mucosa, cervical lymphadenopathy, swelling of extremities, and polymorphous rash can predict IVIG-resistant Kawasaki disease, whereas conjunctival congestion cannot. Hartas et al [15] showed that patients with Kawasaki disease who also have acute arthritis are at high risk for being IVIG-resistant, but because of the lack of relevant studies, we did not include this factor in our meta-analysis.…”

Preditores clínico-analíticos da doença de Kawasaki refratária à Imunoglobulina endovenosa

“…As guidelines mais recentes 5 recomendam a administração de uma segunda dose de IgEV (pelo seu efeito anti-inflamatório cumulativo) ou a administração de pulsos de corticoide em alta dose (preferencialmente metilprednisolona 20-30 mg/kg, durante três dias, com ou sem um curso subsequente de prednisolona oral). Estes pacientes, pelo fenótipo "hiperinflamatório" subjacente e continuado, apresentam maior risco de desenvolverem aneurismas coronários e complicações, 8,9,18,19 pelo que diversos sistemas de pontuação e preditores têm vindo a ser investigados no sentido de identificar precocemente este grupo de pacientes, permitindo um tratamento adjuvante anti--inflamatório mais agressivo numa fase inicial. O score de Harada, desenvolvido no Japão em 1991, foi primeiro sistema de pontuação criado, inicialmente visando identificar as crianças com maior risco de AAC que seriam selecionadas para a administração de IgEV, nessa altura com disponibilidade limitada.…”