Effects of methylprednisolone pulse on cytokine levels in Kawasaki disease patients unresponsive to intravenous immunoglobulin

Abstract

This study aimed to determine the effects of intravenous methylprednisolone pulse (IVMP) therapy on cytokine levels in patients with acute Kawasaki disease (KD) unresponsive to initial intravenous immunoglobulin (IVIG) therapy. Fifteen KD patients unresponsive to initial IVIG, 2 g/kg/day, were randomized to receive IVMP (n = 7), 30 mg/kg/day for 3 days or additional IVIG (n = 8), 2 g/kg/day, and plasma cytokine levels were compared. The fraction of febrile patients was significantly lower in the IVMP group than in the additional IVIG group on day 2 (0/7 vs. 3/8, p = 0.03), but not on day 4 and later (3/7 vs. 4/8, p = 1.00) because of recurrent fever. The prevalence of coronary lesions was similar between the two groups (2/7 vs. 2/8, p = 1.00). The ratios of plasma levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 to those at enrollment (defined as day 1) were significantly lower in the IVMP group on day 4 (0.50 +/- 0.27 vs. 1.01 +/- 0.46, 0.53 +/- 0.39 vs. 0.93 +/- 0.44, p = 0.02 and 0.045, respectively), but not on day 7 (0.54 +/- 0.34 vs. 0.88 +/- 0.39, 0.76 +/- 0.39 vs. 0.61 +/- 0.17, p = 0.07 and 0.83, respectively). The ratios of interleukin-2 receptor, interleukin-6, and vascular endothelial cell growth factor to those at enrollment did not differ significantly between the two groups. In conclusion, for KD patients unresponsive to initial IVIG, IVMP suppresses cytokine levels faster, but subsequently similarly, compared with additional IVIG.

Kawasaki disease refractory to standard treatments that responds to a combination of pulsed methylprednisolone and plasma exchange: Cytokine profiling and literature review

“…Takahara et al [14] reported that levels of IL-6 in PE fluid decreased after PE, while sTNF-aR type 1 and type 2 remained at a high level. However, a randomized trial to compare IVMP with additional IVIG for refractory KD by Miura et al [9] revealed IVMP reduced TNF-a more profoundly than IVIG. Thus, the combination of IVMP and PE might decrease the levels of IL-6 and TNF-a.…”

Progress in pediatric vasculitis

“…Four trials examined high-dose methylprednisolone 'pulses' (IVMP) in combination with IVIG, either as primary combination therapy [50,51 ] or as adjunctive treatment after inadequate IVIG response [52,53]. The first was a randomized, double-blind, placebo-controlled trial [50] of a dose of 30 mg/kg methylprednisolone (101 individuals) or placebo (98 individuals), followed by IVIG 2 g/kg and standard aspirin therapy.…”

Kawasaki Disease, Others Heart Injuries, Not Only Coronary Arteritis

“…The most utilized treatment is the application of Intravenous gammaglobulin (GGIV) at a dose of 2 per kg in a sole dose for a 12-infusion; this is the most accepted treatment and has allowed to the reduction of prevalence of aneurysms to <5% and a mortality of 2% to 0.3%, although the GGIV scheme is at a dosage of 400 mg × kg × day for 5 days, plus aspirin at 80 to 100 mg × kg × day. According to response, the GGIV dose can be repeated, or corticoids can be added, especially in refractory cases (Cha, 2008;Chung, 2009;Falcini, 2006;Hung, 2009;Miura, 2008;Newbauer, 2004;Ogata, 2009;Okada, 2009;Sano, 2010;Tremoulet, 2008).…”

“…Concerning recommendation for treatment of KD during the past 3 years, it as been mentioned that the greatest effectiveness in cases of relapse or resistance is obtained on utilizing pulses of methylprednisolone in addition to GG. In cases of recurrence of fever or resistance to GGIV, this combination has even been recommended as initial therapy (Cha, 2008;Chung, 2009;Miura, 2008;Ogata, 2009;Okada, 2009;Sha, 2008). Cardiovascular sequelae of KD in the adult in Japan.…”