onset in infancy (SAVI), and another by additive loss-of-function mutations in proteasome genes causing the proteasome-associated autoinflammatory syndromes (PRAAS) (also, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures [CANDLE]), presented with chronically elevated interferon (IFN) signatures, suggesting a pathogenic role for type-I IFN in autoinflammatory diseases (2, 3). Type-I IFN was first discovered as a soluble antiviral factor over 50 years ago, and a role in sterile inflammation was proposed in patients with systemic lupus erythematosus (4). However, the discovery of genetic mutations that cause the autoinflammatory type-I interferonopathies CANDLE (2, 5), SAVI (3, 6-8), and Aicardi-Goutières syndrome (AGS) (9, 10) have shed light on pathomechanisms that drive chronic IFN signaling, and recent studies blocking IFN signaling validate a critical role for type-I IFNs (11). AGS-causing loss-of-function mutations in nucleases impair self-nucleic acid homeostasis, SAVI-causing

A retrospective chart review was conducted to detect patients with sarcoidosis seen by pediatric rheumatology service from the period of 1992 to 2013 at Children's hospital of New Orleans. Twenty-seven patients were identified. The average duration of symptoms before diagnosis was 5 (range 1-120) months. Five patients had onset before the age of 5 years and were diagnosed with early-onset sarcoidosis. The most common manifestations at presentation were constitutional symptoms (62 %) followed by ocular (38 %). During the course of illness, 19/27 (70 %) had multiorgan involvement. Common manifestations included uveitis/iritis (77 %), fever (50 %), hilar adenopathy (42 %), arthritis (31 %), peripheral lympadenopathy (31 %), hepatosplenomegaly (31 %), parenchymal lung disease (27 %), and skin rash (19 %). Unusual manifestations included granulomatous bone marrow disease (3 cases), hypertension (2), abdominal aortic aneurysm (large vessel vasculitis; 1), granulomatous hepatitis (1), nephrocalcinosis (1), membranous nephropathy (1), refractory granulomatous interstitial nephritis with recurrence in transplanted kidney (1), CNS involvement (2), parotid gland enlargement (1), and sensorineural hearing loss (1). Biopsy specimen was obtained in 21/27 (77 %) patients, and demonstration of noncaseating granuloma associated with negative stains for mycobacteria and fungi was seen in 18 patients. Elevated angiotensin-converting enzyme level was seen in 74 % of patients. Treatment with oral prednisone was initiated in symptomatic patients with significant clinical improvement. Low-dose methotrexate (MTX) 10-15 mg/m(2)/week orally, as steroid-sparing agent, was administered in 14 patients. Other immunomodulators included cyclophosphamide (2 patients), etanercept (2), infliximab (2), mycophenolate mofetil (1), and tacrolimus (1). Childhood sarcoidosis is prevalent in Louisiana. Most of the affected children present with a multisystem disease associated with manifestations similar to those of adult patients. Low-dose MTX seems to be effective, steroid sparing, and safe adjunct to treat sarcoidosis with multiorgan involvement. Early-onset disease is less common and associated with increased morbidity, flares, and poor prognosis.

During the SARS-CoV-2-associated infection (COVID-19), pandemic initial reports suggested relative sparing of children inversely related to their age. Children and neonates have a decreased incidence of SARS-CoV-2 infection, and if infected they manifested a less severe phenotype, in part due to enhanced innate immune response. However, a multisystem inflammatory syndrome in children (MIS-C) or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 emerged involving coronary artery aneurysms, cardiac dysfunction, and multiorgan inflammatory manifestations. MIS-C has many similarities to Kawasaki disease and other inflammatory conditions and may fit within a spectrum of inflammatory conditions based on immunological results. More recently neonates born to mothers with SARS-CoV-2 infection during pregnancy demonstrated evidence of a multisystem inflammatory syndrome with raised inflammatory markers and multiorgan, especially cardiac dysfunction that has been described as multisystem inflammatory syndrome in neonates (MIS-N). However, there is a variation in definitions and management algorithms for MIS-C and MIS-N. Further understanding of baseline immunological responses to allow stratification of patient groups and accurate diagnosis will aid prognostication, and inform optimal immunomodulatory therapies. Impact Multisystem inflammatory system in children and neonates (MIS-C and MIS-N) post COVID require an internationally recognized consensus definition and international datasets to improve management and plan future clinical trials. This review incorporates the latest review of pathophysiology, clinical information, and management of MIS-C and MIS-N. Further understanding of the pathophysiology of MIS-C and MIS-N will allow future targeted therapies to prevent and limit clinical sequelae.

No abstract

Kawasaki Disease, a systemic vasculitis of unknown origin with specific predilection for the coronary arteries, is the most common cause of childhood-acquired heart disease in western countries. Despite its world-wide incidence, the pathophysiology of this enigmatic disease is still under investigation. Diagnosis is made on a clinical basis, with supportive laboratory evidence and imaging. Once identified, timely initiation of treatment is imperative in order to quell the inflammatory response and decrease the incidence of long-term sequelae, specifically coronary artery aneurysms. Finally, longitudinal follow-up should be implemented based on risk stratification and individualized to each patient.