Livedo reticularis as a late sign of COVID-19 temporally related multisystem inflammatory syndrome (MIS-C): A case series

Introduction: In children, the dermatologic features appear to occur early with other COVID-19 manifestations. Dermatologists play a key role in the early diagnosis of COVID-19. Multi-system inflammatory syndrome in children (MIS-C) shows a presentation mimicking Kawasaki Disease (KD), with mucocutaneous signs. However, late onset dermatological signs are poorly described. Objectives: to evaluate children with MIS-C during the follow-up and to describe late dermatological signs in these patients. Methods: We followed 14 children (3M;11 F) with MIS-C, with clinical, biochemical, imaging data. Autoantibodies, D-Dimer, CRP, ESR, C3, C4, ferritin, serum amyloid, IgA, IgM, IgG were detected 1-2 months after the resolution of the clinical manifestations of MIS-C. Results: 8/14 children (58%) showed livedo reticularis at the legs, arms, trunk. The livedo was more evident at the legs in all the patients. The livedo started at the remission, after normalization of CRP, ESR, D-Dimer;the sign lasted also for 1-2 months after the discontinuation of steroids and the normalization of haematochemical parameters. 4/8 showed low-title positive autoimmune tests (ANA in 2;ENA anti-Sm in 2;anti-cardiolipin IgG in 1;ASCA in 2). Conclusion: In our series, 8/14 patients showed a livedo reticularis, more marked in the legs, however in some cases with a wide distribution to arms and the trunk. Low-title autoantibodies were transiently positive in 50% of these cases, negative in later detections. Livedo reticularis was a late sign, linked to MIS-C related vasculitis, persisting 1-2 months after the resolution of MIS-C. A different treatment regimen (IVIG plus steroids at 1-2 or 30 mg/Kg/day) did not influence the progress of this clinical manifestation. In 50% of children we documented a transient autoimmune response.

Acute cardiovascular manifestations in children with multisystem inflammatory syndrome associated with COVID-19 infection in a Sicilian case series

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of COVID-19 infection, typically evidenced 4-6 weeks after the infection. The debated pathogenesis is a dysregulation of inflammatory response to SARS-CoV-2 infection ad a cytokine hyperexpression. Persistent fever, respiratory and gastrointestinal symptoms are the most common manifestations, associated with typical clinical signs described in Kawasaki Disease (KD). Furthermore, pleiomorphic cardiac manifestations are described, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, conduction abnormalities and pericardial effusion. These manifestations are a strong link with KD, even if in MIS-C they are more frequently documented. Severe cases can present as Toxyc Shock Syndrome (TSS) with vasodilatory or cardiogenic shock, requiring treatment with plasma expanders, inotropic drugs, diuretics, albumin and -in the more severe patients- extracorporeal membrane oxygenation and mechanical ventilation. KD experience guided the clinicians to treat these children with intravenous immunoglobulin (IVIG), steroids, aspirin (ASA) and, in refractory cases, anti-IL-1 monoclonal antibodies. Objectives: Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. Methods: We describe the short-term outcome in a case series of 12 Sicilian children (4M;8F;age: 1.4-14 years) with MIS-C and a documented recent or actual infection by SARS-CoV-2 who showed cardiac involvement. Results: The cardiac features were: 3 patients showed pericardial effusion;1 coronaritis;6 transient mitral valve regurgitation;1 Brugada pattern, evidenced when he was febrile;2 showed associated mitral and aortic valve regurgitation). 7/8 patients with valve regurgitation showed a significant increase of pro-BNP, normalized during the follow-up. TSS was described in 2 patients, showing a significant increase of troponin, promptly treated with high dose of methylprednisolone, IVIG, vasoactive drugs, albumin and diuretics. 3 patients (21%), after the resolution of the acute phase, showed bradycardia (heart rate < 50/min), persisting for 7-10 days. The bradycardia was not associated with first-degree AVB, or a pathological PR. 6 patients (42%) showed an altered ventricular repolarization phase, in association with an increase of pro-BNP (129-3980 pg/ml). 4/12 (33%) had increased troponin levels (27.3-246 ng/ml) in the acute phase, with the normalization of troponin after IVIG and steroids treatment. Pro-BNP persisted increased for a longer time, besides the clinical improvement and the normalization of blood chemistry parameters. Conclusion: Generally, pro-BNP and troponin levels in MIS-C are higher than in KD, reflecting vasculopathy and cardiomyocytes damage extent. Persistence of increased levels of pro-BNP, in patients with a normalization of inflammatory parameters, suggests a mechanism of myocardial oedema, persisting besides the intensive care approach useful, however, to limit effects on cardiac function and normalize inflammatory parameters. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase and the recovery, even if they do not manifest dyselectroliteemia, coronary lesions, pericardial effusion, myocarditis, shock. This approach can avoid severe arrythmia.