A Case of a Relapsing Remitting Macrophage Activating Syndrome After Covid-19 Vaccine In a Teenager with UNC13D Heterozygous Variant of Uncertain Significance

Introduction: Macrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case Presentation: A 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron;however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. Discussion(s): MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023 Elsevier Inc.

Reactivation of Parvovirus B19 Infection: An Uncommon Trigger of Macrophage Activation Syndrome in Adult-Onset Still's Disease.

A 40-year-old woman presented with four weeks of intermittent high-grade fever, cough, and joint pain, and two weeks of a generalized rash. She was found to have adult-onset Still's disease (AOSD) and rapidly developed macrophage activation syndrome (MAS) on the second day of admission. Among infectious etiologies, Epstein-Barr virus and members of the herpes virus family are common triggers of MAS. However, our patient was found to have reactivation/recurrence of parvovirus B19 infection as the cause; this is an uncommon trigger reported infrequently in the medical literature. Despite intensive treatment, the patient passed away.

Incidence and Clinical Outcomes of Newonset Autoimmune Connective Tissue Diseases after Covid-19 Infection- a Systematic Literature Review

Background/Aims Cases of new autoimmune and autoinflammatory conditions have been reported among COVID-19 survivors. A literature review on newonset autoimmune connective tissue diseases (ACTDs) following infection with COVID-19 is lacking.This systematic literature review aimed to evaluate the potential association between COVID-19 infection and the development of new-onset ACTDs in adults. Methods Articles published until September 2022, investigating the association between COVID-19 infection and new-onset ACTDs were included. The ''population'' searched was patients with disease terms for autoimmune connective tissue diseases, including (but not limited to) systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), any idiopathic inflammatory myositis (IIM), antisynthetase syndrome, mixed CTD and undifferentiated CTD (and related MeSH terms), with ''intervention'' as COVID-19 and related terms. For terms for COVID-19, a dedicated search strategy developed by the National Institute for Clinical Excellence was used.Medline, Embase, and Cochrane databases were searched, restricted to English-language articles only. Eligible articles were: case reports and series (of any sample size), observational studies, qualitative studies and randomised controlled trials. Patients developing ACTDs without prior COVID-19 or reporting flares of existing ACTDs were excluded. Information was extracted on patient demographics, new ACTDs' onset time, clinical characteristics, COVID-19 and ACTD treatment, and COVID-19 and ACTDs outcomes. The protocol was registered in PROSPERO (CRD42022358750). Results After deduplication, 2239 articles were identified. After screening title and , 2196 papers were excluded, with 43 proceeding to fulltext screening. Ultimately, 28 articles (all single case reports) were included. Of the 28 included patients, 64.3% were female. The mean age was 51.1 years (range 20-89 years). The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including 4 cases of dermatomyositis);7 (25%) SLE;4 (14.3%) anti-synthetase syndrome;4 (14.3%) SSc;2 (7.1%) other ACTD (one diagnosed with lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) were diagnosed with lupus nephritis. The average onset time from COVID-19 infection to ACTD diagnosis was 23.7days. A third of the patients were admitted to critical care, one for ACTD treatment for SLE with haemophagocytic lymphohistiocytosis (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. The majority (80%) of patients went into remission of ACTD following treatment, while two (10%) patients died- one due to macrophage activation syndrome associated with anti-synthetase syndrome and two from unreported causes. Conclusion Our results suggest a potential association between COVID-19 infection and new-onset ACTDs, predominantly in young females, reflective of wider CTD epidemiology. The aetiology and mechanisms by which ACTDs arise following COVID-19 infection remain unknown and require more robust epidemiological data.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

Evaluation of the effects of anakinra treatment on clinic and laboratory results in patients with COVID-19.

OBJECTIVE: Some anti-cytokine treatments are being used to control the hyperinflammatory condition defined as cytokine storm that develops during COVID-19 infection. In this study, we aim to investigate the effects of anakinra, an IL-1 antagonist, on the clinical status and laboratory values of hospitalized patients with the COVID-19 infection. The aim of the study was to investigate the effects of anakinra, an IL-1 antagonist, on the clinical and laboratory results of hospitalized patients with COVID-19 infection. METHODS: This study was planned as a retrospective study. The age, gender, and current comorbidities of a total of 66 patients who were treated with anakinra for COVID-19 infection from November 2020 to January 2021 were analyzed. The amount of oxygen demand (L/s), the type of oxygen supplementation, oxygen saturation, radiological findings, WBC count, lymphocyte count, neutrophil count, C-reactive protein, LDH, ferritin, fibrinogen, D-dimer levels were monitored before the treatment, and after the anakinra treatment, newly gathered results were compared. Patients' hospitalization period, oxygen need, and their clinical status at discharge were evaluated. The effects of early anakinra treatment (9 days before and after the onset of symptoms) on the prognosis were evaluated. SPSS version 21.0 provided by IBM Company in the USA, Chicago, IL was used for statistical analysis and p<0.05 was considered significant. RESULTS: Sixty-six patients were included in the study. There was no significant gender difference in the prognosis of the patients. There was a significant difference in the statistical deterioration in patients with comorbidities (p=0.004). Patients who started the anakinra treatment at an early stage developed less need for intensive care and low mortality ratios (p=0.019). There were significant improvements on the levels of WBC (p=0.045), neutrophils (p=0.016), lymphocyte (p=0.001), LDH (p=0.005), ferritin (p=0.02), and fibrinogen (p=0.01) after the administration of anakinra therapy. CONCLUSION: We found that earlier and appropriate use of anakinra therapy in COVID-19 patients with the signs of macrophage activation syndrome reduces the need for oxygen support in patients and contributes to improvement in laboratory results and radiological findings, and most importantly reduces the need for intensive care.

Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease.

Background: Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. Case 1: An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. Case 2: A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Conclusions: Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.

Cytokine Storm Syndromes in Pediatric Patients.

Cytokine storm syndromes (CSS) represent a diverse group of disorders characterized by severe overactivation of the immune system. In the majority of patients, CSS arise from a combination of host factors, including genetic risk and predisposing conditions, and acute triggers such as infections. CSS present differently in adults than in children, who are more likely to present with monogenic forms of these disorders. Individual CSS are rare, but in aggregate represent an important cause of severe illness in both children and adults. We present 3 rare, illustrative cases of CSS in pediatric patients that describe the spectrum of CSS.

Solid organ graft-versus-host disease in a recipient of a COVID-19 positive liver graft

A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors

Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?

Introduction: Failure to maintain the inflammatory and anti-inflammatory balance during COVID-19 treatment may result in a severe clinical course. In our study, we aimed to determine the relationship between the meteorin-like protein (metrnl), which plays a role in the anti-inflammatory balance, and the clinical course. Material(s) and Method(s): Between October 2021 and December 2021, 160 patients who were hospitalized in our hospital and whose delta variant COVID-19 infection was confirmed and 80 healthy controls, were enrolled in the study. Patients were divided into two groups according to the severity degree of COVID-19 (Group 1: Moderate COVID-19, Group 2: Severe COVID-19 MAS). Result(s): When comparing the metrnl levels of the groups, it was observed that the metrnl level was statistically significantly lower in Group 2 patients (p< 0.001). While no statistically significant difference was observed between the healthy control group and Group 1, it was observed that the metrnl level of Group 2 patients was statistically significantly lower than the healthy control group (p= 0.77, <0.001 respectively). In the ROC curve analysis of Metrnl level performed in Group 1 and 2 patients, the cut-off value was taken as 17.54 ng/mL, its sensitivity was observed as 80% and the specificity was observed as 60% in predicting the development of severe COVID-19 in patients whose levels were below this value. Conclusion(s): The low level of metrnl, which is thought to play a key role in anti-inflammatory balance, contributes to the development of macrophage activation syndrome, which leads to the severe clinical course in COVID-19 patients.Copyright © 2023 Bilimsel Tip Yayinevi. All rights reserved.

Anti-inflammatory therapy in patients with severe COVID-19 pneumonia: A single-center observational study Hyperinflammation treatment in COVID-19

Aim: In our study, the effects of methylprednisolone and anakinra drugs in the treatment of hyperinflammation in severe COVID-19 patients were investigated. Material(s) and Method(s): In this single-center retrospective study, severe COVID-19 patients followed up with signs of hyperinflammation were examined. The patients were examined in the Sequential Treatment Group receiving high-dose methylprednisolone followed by Anakinra, and the concomitant treatment group receiving both at the same time. Inflammatory parameters, imaging findings, and way of leaving the intensive care unit of the patients were compared. Result(s): A total of 87 patients were included in the present study. In both treatment groups, an increase in lymphocyte levels and a decrease in CRP, lactate dehydrogenase (LDH) and ferritin levels were detected at the end of treatment values compared to the initial treatment values. (p<0.001 and p<0.001). Also, LDH values after the treatment were significantly lower in the concomitant treatment group than in the sequential treatment group (p=0.049). In the present study, 53 of the patients were discharged with good recovery and 34 died. The mortality rate was 31% in the concomitant treatment group and 43% in the sequential treatment group. In terms of mortality, numerical findings in favor of the concurrent treatment group were determined. Discussion(s): In addition to the studies in the literature, it was found that the concomitant use of Methylprednisolone and Anakinra can be an effective treatment option that reduces mortality and improves inflammatory parameters.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Kawasaki Disease in Children and Pediatric Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 During the Pandemic (Clinical Lecture).

The article presents modern data about Kawasaki disease, which is a genetically determined systemic vasculitis with damage to the coronary arteries and multisystem manifestations. The etiology is not fully understood, but there is considered a possible role of viruses in the initiation of the aggravated immune response with possible development of macrophage activation syndromes and shock, which can lead to death. There are difficulties in diagnosing Kawasaki disease due to a variety of symptoms that are typical for a lot of infectious and autoimmune diseases (scarlet fever, measles, yersiniosis, systemic juvenile idiopathic arthritis). Early diagnosis and treatment (in the first 10 days of illness) using high doses of intravenous immunoglobulin and aspirin are associated with a low risk of development of coronary aneurysms and other complications. The authors also presented the data on the characteristics of severe Kawasaki-like diseases, which were recorded in several countries of Europe and America at the peak of the COVID-19 pandemic, and diagnostic criteria for the pediatric multisystem inflammatory syndrome associated with SARS-CoV-2, proposed by the Royal College of Pediatrics and Children Health (UK).Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Kawasaki Disease in Children and Pediatric Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 During the Pandemic (Clinical Lecture).

The article presents modern data about Kawasaki disease, which is a genetically determined systemic vasculitis with damage to the coronary arteries and multisystem manifestations. The etiology is not fully understood, but there is considered a possible role of viruses in the initiation of the aggravated immune response with possible development of macrophage activation syndromes and shock, which can lead to death. There are difficulties in diagnosing Kawasaki disease due to a variety of symptoms that are typical for a lot of infectious and autoimmune diseases (scarlet fever, measles, yersiniosis, systemic juvenile idiopathic arthritis). Early diagnosis and treatment (in the first 10 days of illness) using high doses of intravenous immunoglobulin and aspirin are associated with a low risk of development of coronary aneurysms and other complications. The authors also presented the data on the characteristics of severe Kawasaki-like diseases, which were recorded in several countries of Europe and America at the peak of the COVID-19 pandemic, and diagnostic criteria for the pediatric multisystem inflammatory syndrome associated with SARS-CoV-2, proposed by the Royal College of Pediatrics and Children Health (UK).Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Assessment and management of the SARS-CoV-2 infection: A secondary center experience: Approach to COVID-19 infection

Aim: The aim of the study was to evaluate the management and outcomes of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a secondary hospital. Material(s) and Method(s): This study included 699 hospitalized patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 on chest computed tomography (CT). Demographics, comorbidities, initial laboratory tests on admission, treatment modalities, complications and outcomes were evaluated retrospectively. Result(s): The mean age was 57.0+/-15.6 (range:16-94 years), and male to female ratio was 1.24;58.7% of the patients had at least one underlying comorbidity, the most common was hypertension;18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3% had increased lactate dehydrogenase, and 58.5% had increased D-dimer. Chest CT revealed moderate and severe stages in 57.9% of the patients. Hydroxychloroquine was given to 37.2% and favipiravir to 67.1% of the patients. No significant difference was observed between treatment groups in terms of mortality (P=0.487);5.8% of the patients were transferred to the ICU, 75.6% of whom needed non-invasive and 36.5% invasive mechanical ventilation. The overall case-fatality rate was 0.9. Discussion(s): Older age, male gender, low lymphocyte count, CT findings, including bilateral involvement and severe stage were significantly associated with poor prognosis and mortality.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Case report: Virus-induced hemophagocytic lymphohistiocytosis in a patient with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive inborn error of immunity (IEI), which is accompanied by immune dysregulation. Hypoparathyroidism, adrenocortical failure and candidiasis are its typical manifestations. Here we report about recurrent COVID-19 in a 3-year-old boy with APECED, who developed retinopathy with macular atrophy and autoimmune hepatitis after the first episode of SARS-CoV-2 infection. Primary Epstein-Barr virus infection and a new episode of SARS-CoV-2 infection with COVID pneumonia triggered the development of severe hyperinflammation with signs of hemophagocytic lymphohistiocytosis (HLH): progressive cytopenia (thrombocytopenia, anemia, lymphopenia), hypoproteinemia, hypoalbuminemia, high levels of liver enzymes, hyperferritinemia, increased triglycerides levels; and coagulopathy with a low level of fibrinogen. Treatment with corticosteroids and intravenous immunoglobulins did not lead to a significant improvement. The progression of HLH and COVID-pneumonia resulted in a fatal outcome. The rarity and varied presentation of the HLH symptoms led to diagnostic difficulties and diagnosis delay. HLH should be suspected in a patient with immune dysregulation and impaired viral response. Treatment of infection-HLH is a major challenge due to the difficulties in balancing immunosuppression and management of underlying/triggering infection.

A case of systemic lupus erythematosus presenting with intestinal lymphangiectasia-associated protein-losing enteropathy accompanying hyperinflammation.

Systemic lupus erythematosus (SLE) has the potential to affect virtually every organ; however, gastrointestinal system manifestations are relatively rare compared to other autoimmune diseases such as systemic sclerosis and inflammatory bowel disease. A 29-year-old female patient attended to the emergency room with abdominal distention, acute onset abdominal pain and constipation. She had watery chronic diarrhea (4-5 times/d) and weight loss (6 kg, 12%) for 4 months. While there was increased intestinal wall thickness, air-liquid levels were shown on abdomen computed tomography scan. The patient underwent abdominal surgery due to diagnosis of ileus. Ileocecal resection was performed and pathologic evaluation revealed intestinal lymphangiectasia. Autoimmune serology was performed with the following resulats: anti-nuclear antibody 1/3200 with homogenous pattern, anti-DNA antibody and anti-Sm/ribonucleoprotein antibodies were positive in addition to low complement levels (C3: 0.28 [0.9-1.8 g/L], C4: 0.06 [0.1-0.4 g/L]) indicating diagnosis of SLE. Development of intestinal involvement in SLE (lupus enteritis) is mainly grouped into 3 headings such as mesenteric vasculitis, pseudo-obstruction, and protein-losing enteropathy. Although the pathogenesis of intestinal lymphangiectasia remains unknown, it has been reported that immune complex-mediated visceral vasculitis may result in bowel wall and mucosal edema. To our knowledge this is the first case report accompanying hyperinflammatory response in addition to intestinal lymphangiectasia in SLE. On the other hand, clinicians should be alert for other reasons for hyperinflammatory syndromes rather than COVID-19, even during the pandemic.

Clinical and Laboratory Evaluations of Patients Diagnosed as Having Multisystem Inflammatory Syndrome Associated with Coronavirus Disease 2019 in Children: A Single Center Experience from Konya

Objective Multisystem inflammatory syndrome in children (MIS-C), characterized by fever, inflammation, and multiorgan dysfunction, was newly defined after severe acute respiratory syndrome coronavirus 2 infection. The clinical spectrum of MIS-C can be classified as mild, moderate, and severe. We aimed to evaluate demographics, clinical presentations, laboratory findings, and treatment modalities of patients with MIS-C according to clinical severity. Methods We performed a retrospective study of patients who were diagnosed as having MIS-C between September 2020 and October 2021 in the Necmettin Erbakan University Meram Faculty of Medicine, Türkiye. Results A total of 48 patients (24 females and 24 males) with a median age at diagnosis of 10.3 years (range: 42 months-17 years) were enrolled, the most common clinical severity of MIS-C was moderate. The common presentations of patients were fever (97%), nonpurulent conjunctivitis (89.6%), rashes (81.3%), fatigue (81.3%), strawberry tongue (79.2%), and myalgia (68.8%). The most common laboratory findings were lymphopenia (81.2%), thrombocytopenia (54.1%), elevated D-dimer levels (89.5%), C-reactive protein (CRP;100%), procalcitonin (97%), erythrocyte sedimentation rate (87.5%), ferritin (95.8%), interleukin 6 (IL-6) (86.1%), and probrain natriuretic peptide (pro-BNP) (97%). High levels of CRP, procalcitonin, pro-BNP, and urea were associated with the severity of MIS-C (p < 0.05). Fifteen of the patients were found to have pulmonary involvement. Ascites were the most common finding on abdominal ultrasonography (11 patients) and were not seen in a mild form of the disease. During the study period, two patients died. Conclusion It is important to make patient-based decisions and apply a stepwise approach in treating patients with MIS-C due to the increased risk of complications and mortality. © 2022. Thieme. All rights reserved.

Multisystem inflammatory syndrome associated with COVID-19 in children: Risk factors of severe life-threatening course of the disease

Background/Purpose: Multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19 infection is a life-threatening condition, required intensive care. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. Method(s): The retrospective study included 166 children (99 male, 67 female), aged from 4 months to 17 years (median 8.2 years), who met the WHO criteria for MIS-C. The criterion of severity was the fact of the ICU admission. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To assess the factors associated with the severe course of MIS-C, patients were divided into two groups: those who were hospitalized in the ICU (n = 84;50.6%), and those who did not (n = 82;49.4%). Patients with a more severe course of MIS-C were significantly older. They had a high frequency of signs such as rash, edema, hepatomegaly, splenomegaly, neurological and respiratory symptoms. Hypotension/shock and myocardial damage were much more common in patients hospitalized in the ICU. Among the laboratory changes there were significant differences in the levels of hemoglobin, leukocytes and platelets, CRP, creatinine, troponin and D-dimer. The presence of macrophage activation syndrome was higher in patients, admitted in the ICU. Children, required intensive care required high dose corticosteroids and IVIG more often (table 1). FIGURE: 1) The first symptoms of progeria in infancy: scleroderma-like changes in the skin of the lower extremities and stiffness of knee joints at the age of 2 months. 2) Girl at the age of 3 years 5 months. Almost total alopecia with the absence of eyebrows and eyelashes. Pronounced venous pattern in the forehead, nasal bridge and nasolabial triangle. Conclusion(s): MIS-C is potentially a severe life-threatening condition, in which more than half (50.6%) of patients needed the ICU admission. The main factors determining the severity of MIS-C were: cardiovascular, resiratory and central nervous system disorders. It has been found that factors such as hepatomegaly, splenomegaly, D-dimer >2568 ng/ml, troponin >10 pg/ml, make it possible to identify a group of patients with high risk of severe MIS-C who may potentially need hospitalization in the ICU.

Kawasaki disease following SARS-CoV-2 infection: Stronger inflammation with no increase in cardiac complications.

Background: Herein we investigate the difference between Kawasaki disease (KD) with and without a recent history of SARS-CoV-2 infection. Methods: We compared the clinical characteristics of patients with KD during the SARS-CoV-2 pandemic in a single children's hospital in Korea. Fifty-two patients were enrolled and divided into group 1 (with a history of COVID-19, n = 26) and group 2 (without a history of COVID-19, n = 26) according to whether or not they contracted COVID-19 within the 8 weeks before hospitalization. Data, including clinical features and laboratory results, were analyzed and compared between groups. Results: The median age of patients was significantly higher in group 1 than in group 2 (53 months [IQR, 24-81] vs. 15 months [IQR, 6-33], p = 0.001). The incidence of cervical lymphadenopathy was significantly higher (p = 0.017), while that of BCGitis was significantly lower in group 1 (p = 0.023), and patients had a significantly longer hospital stay (5 days [IQR, 3-8] vs. 3 days [IQR, 3-4], p = 0.008). In group 1, platelet count was significantly lower (p = 0.006), and hemoglobin and ferritin levels were significantly higher (p = 0.013 and p = 0.001, respectively) on the first admission day. Following treatment with intravenous immunoglobulin (IVIG), the platelet count was significantly lower (p = 0.015), and the percentage of neutrophils and neutrophil-to-lymphocyte ratio were significantly higher in group 1 (p = 0.037 and p = 0.012). Although there was no statistical difference, patients requiring infliximab treatment due to prolonged fever was only in group 1. The incidence of cardiovascular complications did not differ between the groups. Conclusions: Post-COVID KD showed a stronger inflammatory response than KD-alone, with no differences in cardiac complications.

First report of a patient meeting criteria for both multisystem inflammatory syndrome in children and adult onset Still's disease.

BACKGROUND: COVID-19 is associated with a postinfectious hyperinflammatory disorder, multisystem inflammatory syndrome in children (MIS-C), that shares characteristics with still's disease, known as systemic juvenile idiopathic arthritis (SJIA) in children younger than 16, and adult onset Still's disease (AOSD) in children 16 and older. Both MIS-C and SJIA/AOSD can be complicated by macrophage activation syndrome (MAS), a potentially fatal condition of cytokine storm. CASE PRESENTATION: We present a 16 year-old male who developed quotidian fever, headache, conjunctival injection, sore throat, nausea and vomiting, diarrhea, rash, and symmetrical polyarticular arthralgia/arthritis 4 weeks after exposure to SARS-CoV-2 and 2 weeks after his first vaccination against COVID-19. Our patient's laboratory results were significant for elevated inflammatory markers and acute phase reactants. He met criteria for diagnosis with both MIS-C and AOSD. After receiving first-line treatment for both diseases, IVIG and methylprednisolone, our patient improved. CONCLUSION: MAS is a life-threatening rheumatological emergency, and physicians must be able to identify diseases, like MIS-C and AOSD, that may be complicated by MAS. Our patient's distinguishing feature on presentation was symmetrical polyarticular arthralgia/arthritis, which has not been associated with MIS-C. Simultaneously, AOSD-which is associated with polyarticular arthralgia/arthritis-is only now being recognized as a possible post-infectious entity in the aftermath of COVID-19 infection. In patients like our own, who meet criteria for both MIS-C and AOSD, administering first line treatment for both diseases may be best practice.