Secondary Hemophagocytic Syndrome Research Articles

Observation of severe pediatric inflammatory multisystem syndrome associated with COVID-19

One of the rare manifestations of COVID-19 is pediatric inflammatory multisystem syndrome, most often in publications it is found out how pediatric inflammatory multisystem syndrome in children (РIMS). The progression of the inflammatory response in РIMS may be a consequence of the development of secondary hemophagocytic syndrome, a significant part of which is refractory fever, an increase in ferritin, AST and ALT, cytopenia, an increase in interleukin 6, severe hepatic and neurological dysfunction. The case with this group of representatives of other multiple organ failure manifestations in the detection of acute distress syndrome and acute heart failure, in the detection of the development of myocarditis.
 A feature of the described clinical detection is the dynamic observation of a severe pediatric multisystem inflammatory syndrome associated with COVID-19, complicated by myocarditis with acute heart failure, left ventricular dysfunction and secondary hemophagocytic syndrome, in an 11-year-old girl with underlying obesity. The child is taking triple therapy with glucocorticosteroids in combination with intravenous immunoglobulin and cyclosporine A, with an expected effect on the ongoing treatment. Possible features of observation are noted: 1) a very early start of РIMS during the acute phase of СOVID-19; 2) transient dyslipidemia at the onset of РIMS with an increase in cholesterol, mainly due to the low-density lipoprotein fraction, and spontaneous regression without lipid-lowering drugs; 3) MRI signs of myocarditis in a month after the onset of the disease, despite the normalization of echocardiography and pro-BNP.

Pulmonary proteinosis and secondary hemophagocytic syndrome in a patient with lysinuric protein intolerance.

Pulmonary proteinosis and secondary hemophagocytic syndrome in a patient with lysinuric protein intolerance.

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusions: Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.

Hemophagocytosis in peripheral blood culture preceding hemophagocytosis in bone marrow biopsy in secondary hemophagocytic syndrome

Hemophagocytosis in peripheral blood culture preceding hemophagocytosis in bone marrow biopsy in secondary hemophagocytic syndrome

Etoposide treatment in secondary hemophagocytic syndrome: impact on healthcare-associated infections and survival

BackgroundEtoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use.Results168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI.ConclusionsIn patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.

Renal involvement as a unique manifestation of hemophagocytic syndrome.

Renal-limited hemophagocytic syndrome (HPS) is a rare clinical setting characterized by abnormal activation of the immune system. Fever associated with pancytopenia, hepatosplenomegaly with liver dysfunction, and hypofibrinogenemia are usually observed in HPS. From a histological level, the presence of non-malignant macrophages infiltrating bone marrow and organs represents the hallmark of this condition. Non-malignant macrophages are associated with phagocytizing activities involving other blood cells. While primary HPS is usually associated with inherited dysregulation of the immune system, secondary HPS usually occurs in the context of infection or is linked to a neoplastic process. Clinical presentation varies and can potentially lead to life-threatening settings. While renal involvement has frequently been reported, however, detailed descriptions of the kidney manifestations of HPS are lacking. More critically, the diagnosis of HPS is rarely supported by renal biopsy specimens. We report four rare cases of biopsy-proven renal-limited HPS in patients presenting with acute kidney injury (AKI). The available evidence on this topic is critically discussed in light of the possible emergence of an autonomous entity characterized by an isolated kidney involvement.

A retrospective analysis of EBV-DNA status with the prognosis of lymphoma.

Epstein–Barr virus (EBV) infection is proved to be associated with clinicopathology of lymphoma. However, little is known about the relationship between EBV‐DNA status after treatment and prognosis. In this study, real‐time polymerase chain reaction (PCR) was used for quantitative detection of EBV‐DNA load in peripheral blood of all 26,527 patients with lymphoma, and the clinical characteristics and prognosis of 202 patients were retrospectively analysed, including 100 patients with positive EBV‐DNA and 102 randomly selected patients with negative EBV‐DNA. We found that the average rate of EBV‐DNA positivity in lymphomas was 0.376%, and EBV‐DNA‐positive patients presented higher risk with elevated lactate dehydrogenase (LDH) and β2‐MG level, B symptoms, secondary hemophagocytic syndrome and lower objective response rate compared to EBV‐DNA‐negative patients. Multivariate analysis revealed EBV‐DNA‐positive patients had inferior progression‐free survival (PFS) and overall survival (OS) and EBV‐DNA level before treatment was related to PFS but not OS of T/NK cell lymphoma. In T/NK cell lymphoma, EBV‐DNA converting negative after treatment was correlated with better PFS but not OS, and second‐line therapy could induce more EBV‐DNA‐negative conversion compared to CHOP‐based therapy. In all, EBV‐DNA positivity before treatment can be a biomarker representing the tumour burden and an independent prognostic factor. EBV‐DNA‐negative conversion after treatment is a good prognostic factor for T/NK cell lymphomas.

ПЕРВЫЙ ОПЫТ ПРИМЕНЕНИЯ ЭКСТРАКОРПОРАЛЬНОЙ МЕМБРАННОЙ ОКСИГЕНАЦИИ У ДЕВОЧКИ С ДЕТСКИМ МУЛЬТИСИСТЕМНЫМ ВОCПАЛИТЕЛЬНЫМ СИНДРОМОМ, АССОЦИИРОВАННЫМ С COVID-19

Pediatric inflammatory multisystem syndrome (PIMS) associated with the new coronavirus infection is the most severe late complication of the COVID-19 infection in children. We present the Russia’s first clinical observation of a 9 years old girl with PIMS with successful use of extracorporeal membrane oxygenation (ECMO) in treatment. The disease was characterized by rapid progression of myocardial dysfunction, shock, multiple organ failure, secondary hemophagocytic syndrome, and resistance to therapy. Intensive therapy, including glucocorticosteroids, tocilizumab, intravenous immunoglobulin, antiplatelet agents and anticoagulants, respiratory and cardiotonic support, ECMO, renal replacement therapy and antimicrobials have allowed the child to stabilize and recover.

Hemophagocytic syndrome associated with leishmaniasis: case report

Secondary hemophagocytic syndrome (sHLH) is a hyperinflammatory reaction which manifests with fever, cytopenia and organ damage. possible causes of sHLH include leishmaniasis. The article describes a clinical case of sHLH in patient with visceral leishmaniasis. A female 30 years old developed hectic daily fever up to 40 °C, pancytopenia, cytolytic syndrome, hyperferritin- and hypertriglyceridemia, immunoglobulin G to capsid antigens of the Epstein-Barr virus, enlarged liver and spleen a one and a half month after returning from Spain. based on the HLH-2004 and H-Score criteria, a sHLH was diagnosed, presumably associated with the Epstein-Barr virus. Immunosuppressive treatment with dexamethasone, cyclosporin-A and etoposide was started under the HLH-2004 program. Apyrexia, reduction of splenomegaly and resolution of cytolysis were achieved. The fever resumed 20 days after the start of chemotherapy, the spleen enlarged again, and therefore a diagnostic splenectomy was performed. Morphological analysis of the removed spleen revealed leishmania. After amphotericin-B therapy, the patient recovered. Chemotherapy of sHLH led to a temporary improvement for a period sufficient to verify the diagnosis and conducting of successful treatment.

Analysis of Prognostic Risk Factors and Establishment of Prognostic Scoring System for Secondary Adult Hemophagocytic Syndrome.

Introduction: The objective of this paper is to identify the prognostic risk factors of secondary adult hemophagocytic syndrome (HLH) in hospitalized patients and establish a simple and convenient prognostic scoring system. Method:We reviewed 162 adult patients secondary with HLH treated in Zhejiang Cancer Hospital and the First Affiliated Hospital of Medical College of Zhejiang University from January 2014 to December 2018 were enrolled to form the test group; from January 2019 to February 2021, 162 adult patients in the hospitals constituted the validation group. The HLH prognosis scoring system was constructed according to the risk factors, and the patients were divided into three risk groups: low risk, medium risk, and high risk. The scoring system was verified by Kaplan–Meier method and log rank test survival analysis. The discrimination ability was evaluated according to the receiver operating characteristic (ROC) curve. Results: Univariate and multivariate analysis showed that the independent risk factors for the prognosis of HLH were male sex, activated partial prothrombin time (APTT) greater than 36 s, lactate dehydrogenase (LDH) greater than 1000 U/L, and C-reactive protein (CRP) greater than 100 mg/L. The area under the ROC curve was 0.754 (95% Cl: 0.678–0.829). The patients were divided into a low-risk group (0–1), a medium-risk group (2–4), and a high-risk group (5–6). The 5-year overall survival (OS) rate were 87.5%, 41.8% and 12.8%, respectively (p < 0.001). The area under ROC curve was 0.736 (95% Cl: 0.660–0.813) in the validation group, and the 2-year OS of patients in low-risk, medium-risk and high-risk groups were 88.0%, 45.1% and 16.7%, respectively (p < 0.001). Conclusion:The new prognostic scoring system can accurately predict the prognosis of secondary adult HLH and can further provide basis for the accurate treatment of secondary adult HLH.

Лечение вторичного гемофагоцитарного синдрома у пациентов с системным ювенильным идиопатическим артритом. Результаты когортного ретроспективного исследования

Secondary hemophagocytic syndrome (SHS) is a life-threatening complication of systemic juvenile idiopathic arthritis (SJIA, syn.: systemic-onset juvenile idiopathic arthritis). Timely treatment of SHS can improve outcomes and reduce mortality rates. There has been little evidence worldwide on the effectiveness of therapy for SHS in patients with SJIA, including the use of genetically engineered biopharmaceutical drugs (GEBDs). Objective. To evaluate the efficacy of different treatment regimens for SHS in patients with SJIA. Patients and methods. This study included 100 patients with SJIA complicated by SHS who were examined and treated at the rheumatology department of the National Medical Research Center for Children’s Health (Moscow) from August 2010 to May 2021. All patients met the criteria for SJIA and SHS diagnosis. The efficacy of different therapy regimens for SHS was assessed according to treatment response criteria and achievement of the clinically inactive status of SHS. The Kaplan-Meier survival analysis was used to investigate the proportion and duration of the period prior to SHS recurrence (relapse-free interval) after the end of therapy, including the use of GEBDs for the treatment of SJIA. The proportion of relapse-free survival cases and the duration of relapse-free interval were assessed within 36 months in 79 of 100 patients (89/114 (78%) SHS cases). Results. Medical records of 100 patients with 114 cases of SHS were retrospectively studied. In 84/114 (73%) cases, SHS developed in patients not receiving GEBDs (“biologically naïve”), and in 30/114 (26%) cases, SHS developed against the background of GEBD therapy (“biologically non-naïve”). Combination therapy, which included intravenous (dexamethasone 17.9 [10; 20] mg/m2/day or methylprednisolone 12.1 [5; 20] mg/kg/day) and oral (prednisolone 0.9 [0.5; 2] mg/kg/day) glucocorticosteroids (GCs), as well as cyclosporine (CsA) at a dose of 4.5 [2; 7] mg/kg/day and normal human immunoglobulin (syn. intravenous immunoglobulin; IVIG) at a dose of 1.5 [0.3; 2] g/kg. In 24/114 (21%) cases, GEBDs were prescribed for the treatment of SHS: in 11 (10%) – tocilizumab, in 8 (7%) – canakinumab, and in 5 (4%) – rituximab. Hemophagocytic syndrome resolved in 111/114 (97%) cases, lethal outcome was registered in 3/114 (3%) cases. Conclusion. Response to treatment and inactive SHS status achievement in the shortest possible time were recorded when using a treatment regimen that included intravenous and oral administration of GCs, as well as CsA and IVIG, regardless of the background use of GEBDs for the treatment of SJIA. In “biologically naïve” patients, response to treatment developed faster, and the proportion and duration of relapse-free interval were significantly greater than in “biologically non-naïve” patients. Key words: secondary hemophagocytic syndrome, systemic juvenile idiopathic arthritis, treatment, genetically engineered biopharmaceutical drugs

A Comparison Study of Anti-CLL1 CART Cells Equipped with Different Co-Stimulatory Domains in the Treatment of Children with Refractory/Relapsed Acute Myeloid Leukemia

Background: It's well established that conventional chemotherapy doesn't benefit children with refractory/relapsed acute myeloid leukemia (R/R-AML). Though multiple attempts, i.e., novel target agents, and intensive chemotherapy, have been translated into clinics, few have been proved to be successful. Chimeric antigen receptor (CAR) T cell therapy is increasingly becoming a curative candidate for refractory hematological malignancies. Recently, anti-CLL1 CAR T-cells have been reported to effectively treat children with R/R-AML by several groups even though with a small sample size. However, the impact of co-stimulatory domain (CD28/CD27 versus 4-1BB) on the efficacy of CAR T-cells could not be neglected, which is not investigated so far. Thus, we here compare the impact of different costimulatory molecules on the safety and efficacy of anti-CLL1 CAR T-cells in treating children with R/R-AML.Methods: Seven R/R-AML children treated with anti-CLL1-based CAR T-cells were enrolled into this preliminary comparison study. The baseline characteristics, time of CAR T-cells generation, in vivo persistence of CAR T-cells, cytokine release profiling, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), secondary hemophagocytic lymphohistiocytosis (sHLH) or macrophage activation syndrome (MAS), and other adverse events, the length of hospitalization, remission status, and the follow-up data were collected for analysis.Results: Among these seven patients, four received CD28/CD27 based CAR T-cells, and three received 4-1BB based CAR T-cells therapy. The CD28/CD27 group consisted of two boys and two girls, with the median age of 7.5 (range; 5 to 11), while the 4-1BB group consisted of two boys and one girl, with the median age of 12 (range; 8 to 12). Generation of CD28/CD27 equipped CAR T-cells (median, 14 days) were faster than that of 4-1BB ones (median, 21 days). All patients experienced grade 1 to 3 CRS and were well managed with one patient experiencing grade 1-2 ICANS but without any sHLH or MAS. The maximum durations were 156 days for CD28/CD27, ranging from 0 to 156 days and 274 days for 4-1BB, ranging from 16 to 274 days) respect. For hospitalization, CD28/CD27 group experienced subtle longer hospital stays (median, 23 days; range, 14 to 30 days) than 4-1BB group (median, 21 days; range, 18 to 54 days). The overall response rates were 67 % and 75 % in 4-1BB group and CD28/CD27 group respectively. Three of four patients in CD28/CD27 group achieved morphological remission with MRD negativity, while two of three patients in 4-1BB group achieved morphological CR, with one as being MRD negativity. Of all the seven cases, only one patient proceeded to hematopoietic stem cell transplant (HSCT) and died of GVHD seven months after HSCT, however, another four patients who achieved CR could not received HSCT due to poor economic status. Of the remaining six patients, two non-respondent died of disease progression, one patient relapsed and subsequently died, and the other three remained alive and being followed up.Conclusion: Though the enrollment was too small for us to draw a conclusion, we have noticed a similar efficacy/safety index between 4-1BB and CD28/CD27 equipped anti-CLL1-based CAR T-cells in treating children with R/R-AML. In sum, the relatively high efficacy and low grade and manageable side effects were also validated in this study. DisclosuresNo relevant conflicts of interest to declare.

Macrophage activation syndrome in COVID-19

The novel coronavirus epidemic is characterized by high rates of morbidity and relatively high mortality. Laboratory test results in patients include leukopenia, an increase in liver function tests and ferritin levels reaching hundreds, and sometimes thousands of units. These data remind us about the macrophage activation syndrome (MAC). Secondary hemophagocytic lymphohistiocytosis syndrome, MAC, which pathogenesis is based on a defect in the mechanisms of T-cell cytotoxicity and decreased level of natural killer cells associated with the defect in the perforin-encoding gene as well as hyperproduction of a number of cytokines – interleukin (IL)-1â, tumor necrosis factor-á, etc. by T-lymphocytes and histiocytes, indirectly leading to the activation of macrophages and production of proinflammatory cytokines, in particular IL-6 hyperproduction. MAC is one of "hyperferritinemic syndromes". These disorders have similar clinical and laboratory manifestations, and they also respond to similar treatments, suggesting that hyperferritinemia may be involved in the overall pathogenesis and is characterized by elevated ferritin level and cytokine storm. Despite the fact that data on the immune and inflammatory status in patients with COVID-19 have only started to appear, it is already clear that hyperinflammation and coagulopathy affect the disease severity and increase the risk of death in patients infected with SARS-CoV-2. Hence, understanding the pathogenesis of the novel coronavirus infection can help in its early diagnostics and treatment.

Organ Lesions in Adults with Secondary Hemophagocytic Syndrome

Background. Secondary hemophagocytic syndrome (SHPS) is a reaction of systemic hyperinflammation triggered by infectious, tumor, or autoimmune processes. With no immunosuppressive (modulating) therapy most patients die from multiple organ failure. Aim. To describe organ lesions characteristic of SHPS patients. Materials &amp; Methods. The retrospective study included patients treated from June 2009 to June 2019. SHPS was diagnosed using HLH-2004 criteria and H-Score. The analysis focused on the incidence and character of lesions in lungs, central nervous system, liver, skin, and cardiovascular system. All patients with persistent fever received anti-infective treatment with broad-spectrum antibiotics in line with local hospital practice. Patients with collagenosis and tumors, which caused SHPS, received standard immunosuppressive and antitumor therapy, respectively. Results. The analysis covered the data of 91 patients (41 man and 50 women), median age was 58 years (range 2-90 years). SHPS was caused by hematological malignancies (n = 52; 57 %), infections (n = 11; 12 %), autoimmune diseases (n = 5; 6 %), and allogeneic hematopoietic stem cell transplantation (n = 13; 14 %). In 10 (11 %) patients no cause was identified. Immunosuppressive therapy was administered to 71 (78 %) patients. Overall survival was 27 % (median 15 days) with median follow-up for alive of 540 days (range from 7 days to 10 years). Clinically significant organ lesions were identified in 76 (83 %) patients. Most commonly SHPS was reported together with polyserositis, respiratory and hepatic disorders, and neurological symptoms from focal deficit to seizure status. Less often skin lesions (from macular rash to epidermolysis bullosa) and such cardiovascular disorders as arrhythmia and/or arterial hypotension were observed. The effective SHPS therapy resulted in restoration of organ functions. Conclusion. SHPS can cause respiratory disorders, polyserositis, different neurological disorders, cytopenia in patients with unexplained fever and cytolytic and/or cholestatic syndrome. Primary organ lesions as well as clinical and laboratory manifestations of SHPS may vary in different patients.

БОЛЕЗНЬ КАВАСАКИ И МУЛЬТИСИСТЕМНЫЙ ВОСПАЛИТЕЛЬНЫЙ СИНДРОМ ПРИ ИНФЕКЦИИ COVID-19 У ДЕТЕЙ

During the COVD-19 pandemic, some pediatric patients in many countries around the world experienced a syndrome resembling a severe Kawasaki disease (KD), often accompanied by shock. Due to the incomplete signs of the classic KD in the era before the present pandemic, in many publications from European countries and the United States, this condition was called «multisystem inflammatory syndrome in children – MIS-C» or «hyperinflammatory shock» or «Kawasaki-like syndrome». This syndrome with a new coronavirus infection is characterized by refractory fever, frequent gastrointestinal symptoms, heart damage (including coronary dilation in some patients, and acute left ventricular failure in the majority), increased ESR and CRP levels, neutrophilia, extremely high troponin levels, increased ferritin, AST, ALT, lactate dehydrogenase, creatine phosphate kinase, interleukin-6 and interleukin-10, coagulopathy with an increase in D-dimer and fibrinogen, thrombocytopenia, sometimes procalcitonin increase. The manifestations of a cytokine storm may meet the criteria for secondary hemophagocytic syndrome. The mechanism of myocardial damage remains unclear. Treatment with high-dose intravenous immunoglobulin is effective, and in the presence of signs of hemophagocytic syndrome, dexamethasone or methylprednisolone. Further research is needed to understand the pathogenesis, resemblance and differences of this syndrome with classic KD, understanding of heart injuiry and early recognition for the need of urgent care.

Secondary hemophagocytic syndrome in adult patients. Study of 91 patients

Background. Secondary hemophagocytic lymphohystiocytosis (sHLH) is a hyperinflammatory reaction provoked by some trigger (cancer, autoimmune or infection). The majority of affected patients are at high risk of fatal multiple organ failure without getting immunsupressive treatment.Objective. Clinical and laboratory profile of sHLH patients.Materials and methods. Retrospective study included clinical, instrumental and lab data from the 91 patients followed between June 2009 and June 2019. Diagnosis sHLH had been based on HLH-2004 and H-Score criteria. The analyzed parameters had been fever chart, liver and spleen enlargement, changes in the bone marrow; values levels of glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, bilirubin, triglycerides, total ferritin with percentage of glycosylation. All patients with rheumatic disorders or malignancies had received either immunosuppressive or cytotoxic therapy. Febrile patients received anti-infective treatment according to the local routine protocols.Results. The data from 91 patients (41 male and 50 female) had been analyzed. Median age was 58 (2–90) years. The sHLH trigger-diseases spectrum included leukemia/lymphoma (n = 52), infection diseases (n = 11), autoimmune disorders (n = 5), allogenic bone marrow transplantation (n = 13), unidentified (n = 10). A fever with an unknown origin and refractory to antibacterial treatment had been observed in 87 (96 %) patients. Morphological hemophagocytic evidences in the bone marrow had been found in 83 %. Breath shortening, liver failure, neurologic disturbances, systemic effusions, rash, heart failure had been registered in 83 % patients. Detected splenomegaly presented in 56 %. Laboratory changes, median were as following: serum glutamic-pyruvic transaminase (alanine aminotransferase, SGPT) – 92 (39.2–1060.8) IU/L; serum glutamic oxaloacetic transaminase (aspartate aminotransferase, SGOT) – 105 (40–4177) IU/L; alkaline phosphatase – 225 (120.9–989) IU/L; bilirubin – 50.5 (22–559) µmol/L; triglycerides – 3.2 (1.95–8.6) mmol/L; total ferritin – 10000 (597–255000) ng/mL with glycosylation percentage – 20.45 (0–37.8) %. 71 patients received various of HLH-directed therapy courses. The overall survival rate was 27 %, median follow-up – 540 days.Conclusion. The main clinical and instrumental findings in sHLH are fever, refractory to anti-infective treatment, elevation of transaminases, serum alkaline phosphatase, triglycerides, total ferritine with low glycosylated fraction. Early diagnosing and immunesupression are the main factors of survival.

Case Report: Malakoplakia Developing in the Graft Colon Post Intestinal Transplant

Abstract Casestudy Malakoplakia is a rare chronic granulomatous disease thought to be caused by a macrophage bactericidal defect and most commonly affecting the genitourinary tract. Most cases are associated with chronic infections or immunosuppression, with most transplant related cases observed after renal transplantation. Results A male in his thirties developed short gut syndrome secondary to injuries and subsequently underwent a small and large bowel transplant and was treated with immunosuppressive medications. He developed multiple episodes of acute rejection and multiple infectious foci, including a peri-rectal fluid accumulation growing Escherichia Coli, bacteremia with Klebisella oxytica, and Epstein Barr Virus viremia. Functional imaging revealed increased activity in mesenteric lymph nodes and in the peri-rectal fluid accumulation. On endoscopy, a rectal ulcer associated with mucosal protuberance was noted and tissue was obtained for pathologic diagnosis. Histologic examination revealed mucosal infiltration by numerous macrophages with abundant granular cytoplasm. Michaelis-Gutmann bodies (considered pathognomonic for malakoplakia) were identified showing PAS and Von- Kossa positivity. Acid fast stain was negative. These findings supported the diagnosis of malakoplakia. Other differential diagnoses were considered, including post-transplant lymphoproliferative disorder, neoplasia, infection with mycobacterial or fungal species, and secondary hemophagocytic lymphohistiocytosis syndrome. These were excluded based on the characteristic histologic findings. Given the diagnosis, treatment with oral antibiotics was attempted. Follow up biopsies revealed disease persistence and the patient was transitioned to a prolonged course of intravenous antibiotics and bethanechol, with eventual histologic response. Unfortunately, due to stenosis and adhesions that developed secondary to the episodes of acute rejection, the patient eventually underwent graft explanation. Conclusion Our case highlights the risk factor milieu encountered in intestinal transplant patients and the prolonged treatment often required to treat malakoplakia. Additionally, malakoplakia constitutes an unusual consideration in intestinal transplant patients and prompt diagnosis is required to direct proper management of these patients.

Challenges of Pediatric Multisystem Inflammatory Syndrome Associated with Covid-19 - A Series of Clinical Cases

Background According to the first SARS-CoV-2 pandemic data, signs and symptoms were less frequently reported among pediatric patients versus adults. Later in April, was described as the multisystem inflammatory syndrome in children (MIS-C) associated with COVID -19. The clinical presentation of MIS-C includes fever, simultaneous involvement of two or more organ systems, altered inflammation parameters and laboratory or epidemiological evidence of SARS-CoV-2 infection. MIS-C features some similar clinical aspects with Kawasaki disease, toxic shock syndrome, and secondary hemophagocytic lymph histiocytosis syndrome / macrophage activation syndrome. This review describes the clinical features of 7 cases of MIS-C treated in the Republic of Moldova.

The Lazarus effect of very high-dose intravenous anakinra in severe non-familial CNS-HLH.

The interleukin (IL)-1 receptor antagonist, anakinra, is recognised to be effective in secondary haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS).1 Mostly used subcutaneously, intravenous anakinra has been described for the cytokine storm characteristic of secondary HLH or MAS and variably for neurological involvement in HLH, but not specifically for refractory CNS-HLH1,2 (appendix p 5). Here, we describe a child with life-threatening secondary HLH on high-dose intravenous anakinra infusion, whose disease course was complicated by CNS-HLH that responded to a steep escalation of the anakinra dose.

COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate

ContextPreliminary data on coexistence of secondary hemophagocytic lymphohistiocytosis syndrome (HLH) and disseminated intravascular coagulation (DIC) in critically ill children with novel coronavirus disease (COVID-19) are emerging. Herein, we summarize the available literature and fill-in the gaps in this regard.Evidence AcquisitionWe have performed a literature search for articles in PubMed, EMBASE and Google Scholar databases till May 12, 2020, with following keywords: “COVID-19”, “SARS-CoV-2”, “HLH”, “HScore”, “coagulopathy”, “D-dimer”, “cytokine storm”, “children” and “pediatrics” with interposition of Boolean operator “AND”.ResultsChildren presenting with moderate-severe COVID-19 and Kawasaki disease shock-like syndrome exhibit peripheral blood picture analogous to HLH. HScore, a validated tool to diagnose HLH, has been suggested to screen severe COVID-19 patients for cytokine storm. However, HScore faces certain limitations in this scenario. It may be more pragmatic to use ‘high D-dimer’ (> 3 µg/mL) instead of ‘low fibrinogen’ to facilitate early detection of cytokine storm. COVID-19 associated coagulopathy resembles hypercoagulable form of DIC with bleeding being rarely reported. Although the International Society on Thrombosis and Haemostasis (ISTH) interim guidance recommends low molecular weight heparin in all hospitalized patients, data is lacking in population below 14 years of age. However, in the presence of life-threatening thromboembolic event or symptomatic acro-ischemia, unfractionated heparin (UFH) should be used with caution.ConclusionsHScore can be used as a complement to clinical decision for initiating immunosuppression. Children with moderate-to-severe COVID-19, especially those with documented thrombocytopenia or chilblains, should be regularly monitored for coagulopathy.