|
| Infliximab |
5mg/kg IV |
It binds to and inhibits TNF α, thereby preventing the release of pro- inflammatory cytokines and interleukins. |
Infections, hepatomegaly, bradycardia, anemia, neutropenia, leukopenia |
18 of the 20 patients were treated successfully with infliximab, 2 required additional plasma exchange therapy. |
[77] |
| In phase III RCT, it did not appear to reduce treatment, although it was helpful in reducing fever duration, few markers of inflammation and left anterior descending coronary artery Z scores [tr6]. |
[78] |
|
| Etanercept |
0.4-0.8 mg/kg/week for three weeks. |
Soluble receptor blockade of TNF α receptors. |
Headache, sinus infections, psoriasis, hepatitis B, allergic reactions. |
Fifteen patients successfully completed the study. No serious adverse effects were noted. Though etanercept did not significantly improve the treatment outcome, but there was no case of prolonged or recurring fever requiring second dose of IVIG. None of the children developed coronary artery dilation or other abnormalities. |
[80] |
|
| Steroids Methylprednisolone |
Reduces inflammation by preventing the migration of leukocytes and decreasing capillary permeability. |
30 mg/kg IV infused over 2 hrs for 3 days |
Sinus bradycardia, hypothermia, hypertension, hypokalemia |
Incidence of coronary artery abnormalities was significantly lower in IVIG plus steroids group compared to IVIG and aspirin alone (CI 0.12-0.28, p<0.0001). |
[69] |
| Meta-analysis of 9 clinical studies showed that IVMP and steroids combined treatment reduced the risk of coronary artery abnormalities significantly (OR 0.3, 95% CI 0.20-0.46). |
[72] |
|
| Dexamethasone |
|
0.3mg/kg/day for 3 days |
|
Patients receiving combined IVIG and dexamethasone treatment had shorter febrile period and hospital stay (p<0.001). Even the risk of coronary artery abnormalities was lower in this group, but it was not statistically significant (p=0.03). |
[76] |
|
| Methotrexate |
Inhibits the enzymes dihydrofolate reductase and thymidylate synthase, which play a role in folate synthesis. Might also reduce the release of IL-1 and IL-6 and leukotrienes. |
10 mg/BSA weekly PO |
Stomatitis, alopecia, bone marrow suppression, hepatotoxicity |
Patients treated with methotrexate following IVIG had lower duration of fever (p=0.023), lower CRP (p<0.001) with no adverse effects. |
[93] |
| Case reports showing resolution of symptoms of KD with no adverse effects. |
[92,94,95] |
|
| Cyclosporine |
Inhibits the assembly and release of IL-2, also inhibits the activation of T lymphocytes, thereby suppressing immune activation. |
4 mg/kg/day IV or PO |
Hyperkalemia, hypertension, hirsutism, infections, tremors and renal susceptibility |
Out of 28 patients of refractory KD, 18 (64.3%) became afebrile within 3 days of cyclosporine treatment, while 6 (21.4%) failed to respond even after 5 days of treatment. |
[79] |
|
| Cyclophosphamide |
Inhibits DNA synthesis and prevents cell division by cross linking DNA strands |
2 mg/kg/day IV |
Hemorrhagic cystitis, alopecia, diarrhea, mucositis, bone marrow suppression |
2 patients out of the 5 who developed refractory KD were treated with additional cyclophosphamide in addition to IVIG and reported no progression of coronary aneurysms and no adverse effects. |
[82] |
|
| Plasma exchange |
Centrifugation of blood, followed by discarding of filtered plasma containing the inflammatory cytokines and its replacement with another colloid such as donor plasma or albumin. |
- |
Transfusion allergic reactions, paresthesia, hypocalcemia, hypotension, bleeding. |
Six patients unresponsive to IVIG and infliximab were treated with plasma exchange therapy and they reported complete resolution of symptoms. Even the patients who had coronary artery lesions, later reported suppression or reversal of abnormalities. |
[74] |
| 9 children with IVIG resistant KD were treated with plasma exchange and showed good response. Although three patients developed CAA, there was a resolution of these lesions by the end of a year. |
[54] |
