against the cytokines responsible for the hyperactive response are now widely used in in the treatment of MAS Specifically, IL1-R antagonists, like anakinra (Kineret), can lead to rapid clinical improvement in children and are now used alone or in conjunction with corticosteroids as first-line therapy In addition, adjunctive therapy with IVIG may be used, especially if there is concern for infection Additional medications that may be used include the calcineurin inhibitors Notably, a new medication that blocks interferon gamma, emapalumab, was recently approved to treat refractory FHL and may have use in the treatment of MAS HLH and MAS are severe life-threatening immune dysregulatory syndromes that may progress rapidly when untreated As such, prompt consideration for these pathologic processes with early decision to admit to the hospital is essential to the successful care of these patients As the process evolves, affected children may develop sepsis-like physiology with cytokine storm and ultimately cardiopulmonary collapse Thus, they often require hemodynamic and respiratory support in addition to the treatment for potential infectious complications related to both treatment with immunosuppressive medications and underlying illnesses KAWASAKI DISEASE CLINICAL PEARLS AND PITFALLS Fever, often exceeding 40°C, is the most consistent manifestation of the disease Extreme irritability is commonly observed Initiation of IVIG within the first 10 days of the illness shortens disease duration and minimizes complications Some children present with a clinical picture that does not fulfill the classic clinical criteria (incomplete KD) The majority of complications are cardiac in nature so close monitoring of the cardiac system is imperative Infants ≤6 months should have laboratory studies if febrile for days or longer, even if there are no other clinical manifestations of KD present Current Evidence KD is an acute, self-limited vasculitis that occurs in children of all ages It is an idiopathic vasculitis of medium-sized vessels that has surpassed acute rheumatic fever to become the leading cause of acquired heart disease in children in the developed world KD is 50% more common in boys than in girls, and it usually affects children younger than years of age The highest incidence occurs in children who live in East Asia (e.g., Japan, Korea, and Taiwan) or are of Asian ancestry living elsewhere in the world It is more common in winter and early spring in North America The disease may be more difficult to diagnose in infants and adolescents, and it is more likely to cause chronic sequelae in these age groups Characteristically, children with KD have fever, conjunctivitis, rash, mucosal inflammation, lymphadenopathy, and extremity changes The major morbidity of KD, however, occurs in the heart Coronary artery aneurysms (CAA) or ectasia develop in approximately 15% to 25% of untreated children and may lead to myocardial infarction, sudden death, arrhythmias, depressed myocardial contractility and heart failure, and chronic coronary artery insufficiency IVIG decreases the incidence of coronary artery aneurysms by three- to fivefold if given within 10 days of disease onset A recent prospective study from the Netherlands showed that male gender, delay of treatment (>10 days), and IVIG retreatment were independent risk factors for coronary artery aneurysm development Management of children with suspected KD, therefore, requires accurate and expeditious diagnosis and close monitoring of the cardiovascular system In KD, as in other forms of vasculitis, blood vessel damage appears to result from an aberrant immune response leading to endothelial cell injury and vessel wall damage A direct cell-mediated attack on endothelial cells, either because they are infected with an as-yet unidentified infectious agent, or simply as innocent bystanders, may underlie the vascular injury The reason that KD preferentially involves coronary arteries is unknown The pathologic changes of the coronary arteries seen in KD have been classified by Fujiwara and Hamashima into four stages, depending on the duration of illness at the time of examination ( Table 101.15 ) Many lines of evidence point toward a role of infections in the causation of KD The fact that the disease often occurs in epidemics, that boys are more susceptible than girls, and that household contacts of children with KD are at increased risk for developing the disease in Japan, all point to a transmissible agent Nonetheless, although many putative etiologies have been proposed during the past four decades, suggestions that certain viruses (EBV, human coronavirus, parvovirus, HIV-2) or bacterial toxins (streptococcal erythrogenic toxin, staphylococcal toxic shock toxin) account for the majority of cases have not been substantiated Increased incidence in Asian populations suggests a genetic component Many researchers now believe that KD represents a final common pathway of immunemediated vascular inflammation in genetically susceptible children triggered by any of a variety of common infections TABLE 101.15 Pathology of Kawasaki Disease a Stage I—Disease duration 50 days Scar formation, calcification in coronary arteries Stenosis and recanalization of coronary vessel lumen Myocardial fibrosis without acute inflammation a Duration of each stage may be decreased by prompt treatment with IVIG IVIG, intravenous immunoglobulin Goals of Treatment Early recognition of the symptoms of KD is essential to effective and timely therapy Although no definitive test for KD exists, recognition of the constellation of signs and symptoms is instrumental in making the diagnosis The goals of treatment are to reduce the amount of ectasia and aneurysms that occur among the coronary arteries which can be accomplished by the initiation of IVIG therapy within the first 10 days of the illness Clinical Considerations Clinical Recognition KD is a clinical syndrome diagnosed on the basis of fever and four of the five signs of mucocutaneous inflammation ( Table 101.16 ) These diagnostic criteria should be regarded as imperfect, with