TY - JOUR
T1 - Resolution of a steroid-resistant, hypereosinophilic immune diathesis with mepolizumab and concomitant amelioration of a mixed thrombotic microangiopathy
AU - Mulvey, J. Justin
AU - Magro, Cynthia
AU - Chadburn, Amy
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/3
Y1 - 2018/3
N2 - The anaphylatoxins produced by an unbridled complement cascade in atypical hemolytic uremic syndrome (aHUS) can alter the leukocyte environment in tissues and peripheral blood, causing clinically significant eosinophilia. While the membrane attack complex and C5a anaphlatoxin can be suppressed with anti-C5 biologics, the production of C3a is still capable of driving a destructive hypereosinophilic syndrome in spite of anticomplement therapy. The side-effects of glucocorticoids in treating hypereosinophilic syndrome limit their therapeutic index in long-term treatment and this behooves the use of alternative strategies. While use of the anti-IL-5 antibody, mepolizumab, has been reported for treatment of primary hypereosinophilic syndromes off-label, its usage in the setting of complement-driven thrombotic microangiopathy has not been attempted. We report mepolizumab's rapid resolution of a glucocorticoid-resistant hypereosinophilic syndrome that caused multi-organ dysfunction in a patient with a complex immune diathesis. The patient's long standing TTP/aHUS disease activity, shown to have direct correlation with his eosinophil count, improved with anti-IL-5 therapy, suggesting a reciprocal enhancement between the conditions.
AB - The anaphylatoxins produced by an unbridled complement cascade in atypical hemolytic uremic syndrome (aHUS) can alter the leukocyte environment in tissues and peripheral blood, causing clinically significant eosinophilia. While the membrane attack complex and C5a anaphlatoxin can be suppressed with anti-C5 biologics, the production of C3a is still capable of driving a destructive hypereosinophilic syndrome in spite of anticomplement therapy. The side-effects of glucocorticoids in treating hypereosinophilic syndrome limit their therapeutic index in long-term treatment and this behooves the use of alternative strategies. While use of the anti-IL-5 antibody, mepolizumab, has been reported for treatment of primary hypereosinophilic syndromes off-label, its usage in the setting of complement-driven thrombotic microangiopathy has not been attempted. We report mepolizumab's rapid resolution of a glucocorticoid-resistant hypereosinophilic syndrome that caused multi-organ dysfunction in a patient with a complex immune diathesis. The patient's long standing TTP/aHUS disease activity, shown to have direct correlation with his eosinophil count, improved with anti-IL-5 therapy, suggesting a reciprocal enhancement between the conditions.
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U2 - 10.1016/j.bcmd.2017.04.008
DO - 10.1016/j.bcmd.2017.04.008
M3 - Article
C2 - 28648630
AN - SCOPUS:85021244397
SN - 1079-9796
VL - 69
SP - 38
EP - 42
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
ER -