107 - KAWASAKI DISEASE COMPLICATING WITH MACROPHAGE ACTIVATION SYNDROME: THE IMPORTANCE OF A PROMPT DIAGNOSIS AND TREATMENT. THREE CASES REPORT.

KD is an acute vasculitis affecting children mainly under 5 years of age, leading to CAA   in 25% of  untreated patients . Macrophage  Activation Syndrome ( MAS) is a secondary  hemophagocytic lymphohistiocytosis ( HLH) that can complicate the  acute, subacute, and chronic phases of KD.  We reviewed retrospectively  three  cases of children affected by KD complicating with MAS hospitalized in two Pediatric Unit of two Hospitals of Emilia Romagna, a northern region of Italy.

Case 1: a previously healthy 23-month-old girl with full clinical criteria of KD and a haemorrhagic rash due to  MAS occurred during  the acute phase of KD, responded promptly to  a high dose of Immune Globulin intravenous ( IVIG )  and  3 pulses of high doses of methylprednisolone ( MPD) with  improvement of clinical signs and laboratory tests without  development of coronary artery alterations (CAA)  at any phase of illness.

Case 2: a previously healthy 10-month-old girl with incomplete KD presenting with persistent fever and maculopapular rash, IVIG- non responder, complicating in the subacute phase with MAS manifesting  persistent fever, hypertransaminasemia, hyperferritinemia and hypofibrinogenemia  after two high doses of IVIG and boluses of MPD; she responded to addiction of IL-1 blocker , anakinra. She  did not present CAA alterations at any phase of illness. 

 Case 3: a previously healthy 26-month-old boy with  incomplete KD ( fever, maculopapular rash, cheilitis and hyperemic conjunctivitis) with gallbladder hydrops and IVIG-non responder to 2 doses and  boluses of high doses of MPD . In subacute phase he complicated with  MAS and responded to anakinra iv. During subacute phase he developed transient aneurysms  that regressed during the chronic  phase.    

These  cases demonstrate that prompt diagnosis and aggressive  immunomodulatory treatment can limit the most  severe complications of MAS; high doses of  IVIG and MPD  may result in a favourable outcome or may need more aggressive adjunctive  treatment.

  Anakinra,  cyclosporine, monoclonal antibodies, or plasmapheresis can be used as adjunctive treatment in case of unrensponsive MAS in KD. 

  Notably, MAS, present during the subacute phase of case 2 and 3 , promptly responded to IL-1 blocker  without use of cyclosporine . Our experience confirms  that IL-1 blocker can be considered first – line treatment after non response to IVIG  and MPD  in KD complicating with MAS, avoiding the over- treatment   with cytotoxic drugs.