Kawasaki syndrome (KS) is the most relevant cause of heart disease in children living in developed countries. Intravenous immunoglobulin (IVIG) has a preventive function in the formation of coronary artery abnormalities and a poor strictly-curative action in established coronary damage. More than two decades ago, the Harada score was set to assess which children with KS should be subject to administration of IVIG, evaluating retrospectively a large cohort of patients with regard to age, sex and laboratory data. Nowadays, high dose IVIG is administered to all children with a confirmed diagnosis of KS, but a tool for predicting non-responsiveness to the initial infusion of IVIG has not been found. The prediction of IVIG resistance is a crucial issue, as recognising these high-risk patients should consent the administration of an intensified initial treatment in combination with IVIG in order to prevent coronary injuries. Few reports have focused on factors, referring to both clinical parameters and laboratory data at the onset of KS, in order to predict which patients might be IVIG non-responsive. We have analysed three different risk scores which were formulated to predict IVIG resistance in Japanese children with typical KS, but their application in non-Japanese patients or in those with incomplete and atypical patterns of the disease has been studied in a fragmentary way. Overall, our analysis showed that early and definite ascertainment of likely IVIG non-responders who require additional therapies reducing the development of coronary artery involvement in children with KS is still a challenge.

An overwhelming activation of cytotoxic T cells and well-differentiated macrophages leading to systemic overload of inflammatory mediators characterizes the so-called macrophage activation syndrome (MAS); this potentially life-threatening clinical entity may derive from several genetic defects involved in granule-mediated cytotoxicity but has been largely observed in patients with juvenile idiopathic arthritis, many rheumatologic diseases, infections, and malignancies. The occurrence of MAS in the natural history or as the revealing clue of monogenic autoinflammatory disorders (AIDs), rare conditions caused by disrupted innate immunity pathways with overblown release of proinflammatory cytokines, has been only reported in few isolated patients with cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome since 2001. All these patients displayed various clinical, laboratory, and histopathologic features of MAS and have often required intensive care support. Only one patient has died due to MAS. Defective cytotoxic cell function was documented in a minority of patients. Corticosteroids were the first-line treatment, but anakinra was clinically effective in three refractory cases. Even if MAS and AIDs share multiple clinical features as well as heterogeneous pathogenetic scenes and a potential response to anti-interleukin-1 targeted therapies, MAS requires a prompt specific recognition in the course of AIDs due to its profound severity and high mortality rate.

Paroxysmal crises of fever and systemic inflammation herald familial Mediterranean fever (FMF), considered as the archetype of all inherited systemic autoinflammatory diseases. Inflammatory bouts are characterized by short-term and self-limited abdominal, thoracic, and/or articular symptoms which subside spontaneously. Erysipelas-like findings, orchitis, and different patterns of myalgia may appear in a minority of patients. In recent years, many non-classical manifestations have been reported in the clinical context of FMF, such as vasculitides and thrombotic manifestations, neurologic and sensory organ abnormalities, gastrointestinal diseases, and even macrophage activation syndrome. As FMF left unrecognized and untreated is ominously complicated by the occurrence of AA-amyloidosis, it is highly desirable that diagnosis of this autoinflammatory disorder with its multiple clinical faces can be contemplated at whatever age and brought forward.

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Raynaud's phenomenon (RP) is a vasospastic disorder characterized by recurrent self-limited episodes of skin pallor, cyanosis, and hyperemia caused by paroxysmal spasms in the small arteries of the fingers and toes and can occur in any age group. Hands, feet, nose, ears, and nipples can be affected. The diagnosis is made clinically, assessing varying degrees of ischemia in the involved areas of skin, but this transient ischemia may also herald the onset of connective tissue disease. Investigation is recommended when RP starts in childhood to exclude an underlying autoimmune condition and close follow-up for its development. Management of RP in children includes conservative and pharmacologic treatments.