Ruxolitinib in IVIG-resistant kawasaki disease-associated macrophage activation syndrome complicated by a giant coronary artery aneurysm: a case report and narrative literature review

Background Kawasaki disease (KD)-associated macrophage activation syndrome (KD-MAS) is a life-threatening complication with limited treatment options. Ruxolitinib, a JAK1/2 inhibitor, has shown efficacy in refractory systemic juvenile idiopathic arthritis-associated MAS (sJIA-MAS) and hemophagocytic lymphohistiocytosis (HLH). Its use in KD-MAS has been described in one previous case treated with ruxolitinib plus corticosteroids; use in a patient who also developed a giant coronary artery aneurysm has not been reported. A 3-month-old male infant with IVIG-resistant KD developed persistent fever despite two courses of IVIG, the first given before referral, and methylprednisolone pulse therapy. KD-MAS was diagnosed on the basis of bicytopenia, hyperferritinemia, elevated soluble CD25, hypofibrinogenemia, and hemophagocytes in the bone marrow. Ruxolitinib was initiated early. Body temperature normalized within 72 h, with rapid improvement in inflammatory markers. Coronary dilation was documented on illness day 22. By illness day 24, the left anterior descending artery (LAD) met giant-aneurysm criteria ( Z -score: 10.93; later peak 11.9), whereas the proximal right coronary artery remained a medium aneurysm (peak Z -score: 5.73). After a third course of IVIG and long-term antithrombotic therapy with aspirin plus low-molecular-weight heparin, the aneurysms regressed over 16 months of follow-up. Clinical and laboratory improvement temporally followed the addition of ruxolitinib, although the contribution of ruxolitinib cannot be separated from concomitant IVIG and glucocorticoid therapy. Discussion A narrative literature review identified ten relevant studies. Reported KD-MAS treatment is predominantly IVIG plus glucocorticoids, with cyclosporine A and biologics reserved for refractory cases. This case is the second published report of ruxolitinib in KD-MAS, and the first to document a giant coronary artery aneurysm with 16-month coronary follow-up. Conclusion KD-MAS should be suspected in IVIG-resistant KD with persistent fever and cytopenias. Addition of ruxolitinib was temporally associated with rapid clinical and inflammatory-marker improvement; however, its independent therapeutic contribution cannot be determined because of concurrent IVIG and glucocorticoid therapy. Systemic inflammatory improvement did not prevent coronary progression, so intensive coronary surveillance must continue.