Marked pleural effusion after i.v. immunoglobulin therapy for Kawasaki disease.

Abstract

Kawasaki disease (KD) is an acute, febrile, systemic vasculitis and is sometimes complicated by multiple organ dysfunction syndrome. Pleural effusion (PE) is a rare complication of KD1-3 and develops during the acute phase of KD. Herein we report on a boy who developed marked PE that appeared after i.v. immunoglobulin (IVIG) therapy. A previously healthy Japanese boy aged 1 year 3 months had fever, changes in mucosa of the oropharynx, bilateral bulbar conjunctival injection, induration of the extremities, and a rash, all of which fulfilled the diagnostic criteria for KD.4 Chest radiograph, echocardiography, and electrocardiogram were normal. Complete blood count (CBC), blood chemistry, and coagulation study were compatible with KD. He was treated with 2 g/kg IVIG and oral flurbiprofen at a dose of 4 mg/kg per day on day 4 of the illness. Fever subsided on the next day. His clinical symptoms of KD immediately disappeared. Approximately 48 h after completion of IVIG, follow-up laboratory examination indicated thrombocytopenia (platelets, 75 × 109/L), accompanied by abnormal coagulation tests (activated partial thromboplastin time [APTT], 32.7 s; international normalized ratio of prothrombin time [PT-INR], 0.95; fibrin/fibrinogen degradation products [FDP], 35.9 μg/mL; fibrinogen, 151 mg/dL). Chest radiograph showed PE in the right thorax. He was referred to the present hospital on day 8 of illness. There was mild dyspnea and low oxygen saturation (96% at room air). CBC still showed thrombocytopenia (white blood cells, 9.1 × 109/L; red blood cells, 4.46 × 1012/L; platelets, 78 × 109/L). Blood chemistry was normal, except for mild elevation of transaminases (aspartate aminotransferase, 69 IU/L; alanine transaminase, 55 IU/L). Coagulation study was abnormal: APTT, 35.1 s; PT-INR, 1.09; D-dimer, 78.7 μg/mL; FDP, 135.8 μg/mL; fibrinogen, 139 mg/dL; and thrombin–anti-thrombin complex, 4.8 ng/L. An increase in fibrin/fibrinogen degradation products combined with thrombocytopenia fulfilled the criteria of disseminated intravascular coagulopathy (DIC). Chest radiograph and computed tomography showed bilateral PE, predominantly in the right thorax (Fig. 1). Ultrasonography showed no coronary dilatation and no pericardial effusion. In the right thorax, thoracentesis was performed on day 9 of illness. A total of 130 mL pleural fluid was drained. Pleural fluid was exudative with a pleural fluid/serum protein ratio of 0.53. Various causes of PE were excluded as follows. CBC, and blood and urine laboratory studies excluded hemophagocytic syndrome and glomerulonephritis. Pathogen-specific serological tests for mycoplasma were negative. Culture of the PE was negative. Immunological tests excluded autoimmune disease. Laboratory data normalized without specific treatment on day 18 of illness. The patient was discharged from hospital on day 22 of illness. Follow up after 1 year showed no evidence of coronary dilatation, myocardial infarction, or ischemia on echocardiography and electrocardiogram. In the present case there appeared to be a causal relationship between IVIG therapy for KD and marked PE for the following reasons. First, marked PE occurred shortly after IVIG, and at that time, acute symptoms of KD had already improved. Second, PE is a rare complication of IVIG.5 Third, IVIG is known to induce hematological side-effects, such as thrombotic phenomenon and hyperviscosity.5 Because DIC simultaneously occurred with marked PE in the recovery phase, we speculate that PE and DIC independently occurred as severe side-effects of IVIG. Mechanisms of adverse reactions to IVIG are largely unknown. Plasma-derived vasoactive or hemodynamically active factors in IVIG can cause some adverse effects.5 Similar to the present case, Lee et al.3 noted simultaneous occurrence of DIC and PE. We speculate that IVIG might have caused DIC and PE in the present case. Because IVIG is frequently used as standard therapy for KD, marked PE should be recognized as one of the serious side-effects of IVIG. The authors declare no conflict of interest. K.K., M.H., and T.T. were involved with all stages of management of the patient; T.N. and K.S. edited and assisted with writing the manuscript. All authors read and approved the final manuscript.