CHF may rarely complicate the acute phase of KD When this is because of myocarditis, routine treatment with IVIG generally results in rapid clinical improvement Although IVIG therapy involves infusing large volumes of isotonic solution—2 g/kg of 5% IVIG delivers 40 mL/kg over to 12 hours—improvements in myocardial contractility compensate for the volume load, and treatment rarely leads to circulatory deterioration By the second week of illness, and especially in children with coronary artery dilatation, ischemia or infarction must be excluded as causes of new myocardial dysfunction Kawasaki Shock Syndrome An uncommon complication (7% in one study from a single institution), Kawasaki shock syndrome has been recognized as a complication that can occur during the acute phase of the illness, unrelated to IVIG infusion It is defined as systolic hypotension for age, or signs of poor perfusion It was noted that the patients who developed shock syndrome were more likely to be female, to have laboratory findings consistent with greater inflammation (higher CRP levels), more severe laboratory abnormalities (e.g., lower platelet counts, hyponatremia, hypoalbuminemia, and consumptive coagulopathy), and to have impaired cardiac function All cases required fluid resuscitation and about half required inotropic support These patients seem to have greater incidences of coronary artery abnormalities and IVIG resistance Other Complications Arthritis occurs in approximately one-third of children with KD Because it is rare in many of the conditions that may mimic KD, the presence of synovitis adds supportive evidence for the diagnosis in ambiguous cases The arthritis tends to involve the small joints of the extremities during the acute phase of illness and the large joints during the second and third weeks The arthritis of KD is always nondeforming and self-limited, generally resolving within 30 days Anti-inflammatory medications such as ibuprofen are usually effective in relieving symptoms until spontaneous resolution occurs Refractory Kawasaki Disease KD may recur in 1% to 2% of children within 12 months of diagnosis, and an additional 5% to 10% of children treated with IVIG and aspirin may respond poorly to IVIG treatment during the initial bout of illness In fact, patients who fail to respond completely to IVIG pose the greatest therapeutic dilemma Prolonged fever itself correlates with increased risk of developing coronary artery abnormalities, and fever lasting for more than 14 days identifies a group of children at risk for developing giant coronary artery aneurysms (internal diameter >8 mm), the group that is most susceptible to infarction and sudden death In cases of persistent, recurrent, or recrudescent KD, there are multiple options, including retreatment with a second dose of IVIG, g/kg over to 12 hours The risk of additional IVIG seems to be minimal, and several studies show a dose response to IVIG in KD A persistent fever may be a reaction to treatment with IVIG and therefore children are not usually retreated until at least 36 hours after the initial IVIG infusion It is, however, extremely important to confirm the diagnosis; it must be remembered that failure to respond to IVIG might indicate that the child has a different source of fever, such as a bacterial or viral infection, or a chronic inflammatory disease Approximately two-thirds of children with KD who fail to respond to an initial dose of IVIG improve with a second course A small number seem to be resistant to IVIG, and they should be treated with intravenous pulsed-dose methylprednisolone (30 mg/kg/day) for days Infliximab may be an alternative to a second infusion of IVIG or corticosteroids for IVIG-resistant patients Patients who fail to respond to this regimen may be candidates for cyclosporine, cytotoxic agents, or other monoclonal antibody therapy LYME DISEASE Please see Chapter 94 Infectious Disease Emergencies Suggested Readings and Key References Juvenile Rheumatoid Arthritis Adams A, Lehman TJ Update on the pathogenesis and treatment of systemic onset juvenile rheumatoid arthritis Curr Opin Rheumatol 2005;17:612–616 Cassidy JT, Petty RE Juvenile rheumatoid arthritis In: Textbook of Pediatric Rheumatology 3rd ed Philadelphia, PA: WB Saunders; 1995 Cunnane G, Doran M, Bresnihan B Infections and biological therapy in rheumatoid arthritis Best Pract Res Clin Rheumatol 2003;17:345–363 Duffy CM, Colbert RA, Laxer RM, et al Nomenclature and classification in chronic childhood arthritis Time for a change? Arthritis Rheum 2005;52:382–385 Hashkes PJ, Laxer RM Update on the medical treatment of juvenile idiopathic arthritis Curr Rheumatol Rep 2006;8:450–458 Ilowite NT Current treatment of juvenile rheumatoid arthritis Pediatrics 2002;109:109–115 Ilowite NT Update on biologics in juvenile idiopathic arthritis Curr Opin Rheumatol 2008;20:613–618 Kelly A, Ramanan AV Recognition and management of macrophage activation syndrome in juvenile arthritis Curr Opin Rheumatol 2007;19:477–481 Murray K, Thompson SD, Glass DN Pathogenesis of juvenile chronic arthritis: genetic and environmental factors Arch Dis Child 1997;77:530–534 Schneider R, Passo MH Juvenile rheumatoid arthritis Rheum Dis Clin North Am 2002;28:503–530 Systemic Lupus Erythematosus Aggarwal A, Srivastava P Childhood onset systemic lupus erythematosus: how is it different from adult SLE? Int J Rheum Dis 2015;18(2):182–191 Hiraki LT, Benseler SM, Tyrrell PN, et al Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study J Pediatr 2008;152:550–556 Lehman T Systemic lupus erythematosus in children In: Klein-Gitelman M, Tepas E, eds UpToDate Waltham, MA Accessed on July 2, 2014 Malattia C, Martini A Paediatric-onset systemic lupus erythematosus Best Pract Res Clin Rheumatol 2013;27:351–362 Petri M, Orbai A, Alarcon GS, et al Derivation and validation of systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus Arthritis Rheum 2012;64(8):2677–2686 Silverman E, Eddy A Systemic lupus erythematosus In: Cassidy JT, Petty RE, Laxer RM, et al., eds Textbook of Pediatric Rheumatology 6th ed Philadelphia, PA: Saunders Elsevier; 2011:315–343 Tedeschi S, Johnson S, Dimitrios B, et al Developing and refining new candidate criteria for systemic lupus erythematous classification: an international collaboration Arthritis Care Res 2018;70(4):571–581 Dermatomyositis Bohan A, Peter JB Polymyositis and dermatomyositis N Engl J Med 1975;292:344– 347, 403–407 Pachman LM Juvenile dermatomyositis: immunogenetics, pathophysiology, and disease expression Rheum Dis Clin North Am 2002;28:579–602 Tse S, Lubelsky S, Gordon M, et al The arthritis of inflammatory childhood myositis syndromes J Rheumatol 2001;28:192–197 HLH/MAS Behrens EM, Beukelman T, Paessler M, et al Occult macrophage activation syndrome inpatients with systemic juvenile idiopathic arthritis J Rheumatol 2007;34(5):1133– 1138 Cooper N, Rao K, Goulden N, et al The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis Bone Marrow Transplant 2008;42(Suppl 2):S47–S50 Henter JI, Samuelsson-Horne A, Aricò M, et al Histocyte Society Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation Blood 2002;100(7):2367–2373 Janka G Hemophagocytic lymphohistiocytosis: when the immune system runs amok Klin Padiatr 2009;221(5):278–285 Janka GE Familial and acquired hemophagocytic lymphohistiocytosis Eur J Pediatr 2007;166(2):95–109 Loh NK, Lucas M, Fernandez S, et al Successful treatment of macrophage activation syndrome complicating adult Still disease with anakinra Intern Med J 2012;42(12):1358–1362 Marsh RA, Vaughn G, Kim MO, et al Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation Blood 2010;116(26):5824–5831 Miettunen PM, Narendran A, Jayanthan A, et al Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients Rheumatology (Oxford) 2011;50(2):417–419 Nagafuji K, Nonami A, Kumano T, et al Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis Haematologica 2007;92(7):978–981 Ravelli A, Grom AA, Behrens EM, et al Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment Genes Immun 2012;13(4): 289–298 Risma K, Jordan MB Hemophagocytic lymphohistiocytosis: updates and evolving concepts Curr Opin Pediatr 2012;24(1):9–15 Vasculitis/Polyarteritis Nodosa Dedeoglu F, Sundel RP Vasculitis in children Pediatr Clin North Am 2005;52:547– 575 Fink CW Vasculitis Pediatr Clin North Am 1986;33:1203–1219 Gunal N, Kara N, Cakar N, et al Cardiac involvement in childhood polyarteritis nodosa Int J Cardiol 1997;60:257–262 Sundel R, Szer I Vasculitis in childhood Rheum Dis Clin North Am 2002;28:625–654 Ting TV, Hashkes PJ Update on childhood vasculitides Curr Opin Rheumatol 2004;16:560–565 Kawasaki Disease American Academy of Pediatrics Kawasaki disease In: Pickering LK, Baker CJ, Kimberlin DW, et al., eds Red Book: 2012 Report of the Committee on Infectious Diseases 29th ed Elk Grove Village, IL: American Academy of Pediatrics; 2012:454–460 Dimitriades VR, Brown AG, Gedalia A Kawasaki disease: pathophysiology, clinical manifestations and management Curr Rheumatol Rep 2014;16:423 Dionne A, Burns J, Dahdah N, et al Treatment intensification in patients with Kawasaki disease and coronary aneurysm at diagnosis Pediatrics 2019;143(6):e20183341 Hedrich CM, Schnabel A, Hospach T Kawasaki Disease Front Pediatr 2018;6:198 Kanegaye JT, Wilder MS, Molkara D, et al Recognition of a Kawasaki disease shock syndrome Pediatrics 2009;123:e783 ... Opin Rheumatol 2005;17:612–616 Cassidy JT, Petty RE Juvenile rheumatoid arthritis In: Textbook of Pediatric Rheumatology 3rd ed Philadelphia, PA: WB Saunders; 1995 Cunnane G, Doran M, Bresnihan... Curr Rheumatol Rep 2006;8:450–458 Ilowite NT Current treatment of juvenile rheumatoid arthritis Pediatrics 2002;109:109–115 Ilowite NT Update on biologics in juvenile idiopathic arthritis Curr... Benseler SM, Tyrrell PN, et al Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study J Pediatr 2008;152:550–556 Lehman T