Persistent Fever Research Articles

CSFV restricts necroptosis to sustain infection by inducing autophagy/mitophagy-targeted degradation of RIPK3.

CSFV infection in pigs causes persistent high fever, hemorrhagic necrotizing multi-organ inflammation, and high mortality, which seriously threatens the global swine industry. Cell death is an essential immune response of the host against pathogen invasion, and lymphopenia is the most typical clinical feature in the acute phase of CSFV infection, which affects the initial host antiviral immunity. As an "old" virus, CSFV has evolved mechanisms to evade host immune response after a long genetic evolution. Here, we show that necroptosis is a limiting host factor for CSFV infection and that CSFV-induced autophagy can subvert this host defense mechanism to promote its sustained replication. Our findings reveal a complex link between necroptosis and autophagy in the process of cell death, provide evidence supporting the important role for CSFV in counteracting host cell necrosis, and enrich our knowledge of pathogens that may subvert and evade this host defense.

Characteristics and prognostic factors of bacterial meningitis in the intensive care unit: a prospective nationwide cohort study

BackgroundPatients with bacterial meningitis can be severely ill necessitating intensive care unit (ICU) treatment. Here, we describe clinical features and prognostic factors of adults with bacterial meningitis admitted to the ICU in a nationwide prospective cohort study.MethodsWe prospectively assessed clinical features and outcome of adults (age > 16 years) with community-acquired bacterial meningitis included in the MeninGene study between March 1, 2006 and July 1, 2022, that were initially admitted to the ICU. We identified independent predictors for initial ICU admission and for unfavourable outcome (Glasgow Outcome Scale score between 1–4) by multivariable logistic regression.ResultsA total of 2709 episodes of bacterial meningitis were included, of which 1369 (51%) were initially admitted to the ICU. We observed a decrease in proportion of patients being admitted to the ICU during the Covid-19 pandemic in 2020 (decreased to 39%, p = 0.004). Median age of the 1369 patients initially admitted to the ICU was 61 years (IQR 49–69), and the rates of unfavourable outcome (47%) and mortality (22%) were high. During the Covid-19 pandemic, we observed a trend towards an increase in unfavourable outcome. Prognostic factors predictive for initial ICU admission were younger age, immunocompromised state, male sex, factors associated with pneumococcal meningitis, and those indicative of systemic compromise. Independent predictors for unfavourable outcome in the initial ICU cohort were advanced age, admittance to an academic hospital, cranial nerve palsies or seizures on admission, low leukocyte count in blood, high C-reactive protein in blood, low CSF: blood glucose ratio, listerial meningitis, need for mechanical ventilation, circulatory shock and persistent fever. 204 of 1340 episodes (15%) that were initially not admitted to the ICU were secondarily transferred to the ICU. The rates of unfavourable outcome (66%) and mortality (30%) in this group were high.ConclusionsThe majority of patients with community-acquired bacterial meningitis are admitted to the ICU, and the unfavourable outcome and mortality rates of these patients remain high. Patients that are initially admitted to non-ICU wards but secondarily transferred to the ICU also had very high rates of unfavourable outcome.

OP122 Economic Evidence To Support Expanding Use Of Existing Positron Emission Tomography Technology As A Diagnostic Tool For High-Risk Cancer Patients

IntroductionIn Australia, 18F-fluorodeoxyglucose positron emission tomography with low-dose computed tomography (FDG-PET/CT) is currently only funded for cancer staging-related indications. A recent multicenter randomized trial demonstrated that FDG-PET/CT, compared with standard of care computed tomography (CT) imaging, improved antimicrobial management and the outcomes of patients with persistent and recurrent neutropenic fever. There is potential value in expanding the use of FDG-PET/CT as a diagnostic tool for this high-risk population. We conducted an economic evaluation from a healthcare perspective alongside the randomized trial and compared FDG-PET/CT with standard CT up to 6 months after the scans.MethodsCase report forms were used to collect resource utilization data and length of hospitalization. Effectiveness was measured as the number of patients with antimicrobial rationalization and quality-adjusted life-years (QALYs) derived from patient-reported trial-based health-related quality of life. Generalized linear models (GLM) were used to analyze costs and outcomes. Incremental cost-effectiveness ratios (ICERs) for each of the outcomes were calculated and interpreted as the cost per patient with antimicrobial rationalization and cost per QALY gained. To account for sampling, we performed bootstrapping with 1,000 replications using the recycled predictions method.ResultsThe adjusted healthcare costs were lower in the FDG-PET/CT group (mean AUD49,563, 95% confidence interval [CI]: 36,867, 65,133; equivalent to USD34,268, 95% CI: 25,490, 45,033) compared with the standard CT group (mean AUD57,574, 95% CI: 44,837, 73,347; equivalent to USD39,807, 95% CI: 31,000, 50,712). The magnitude of differences in QALYs between the two groups was small (0.001; 95% CI: -0.001, -0.001). When simulated 1,000 times, our analysis showed that across both outcomes FDG-PET/CT was the dominant strategy as it was cheaper and had better outcomes than standard CT in 74 percent of simulations.ConclusionsFDG-PET/CT is cost effective when compared with standard CT for investigating persistent or recurrent neutropenic fever in high-risk patients. Aligning economic evaluations with clinical studies is key to an integrated evidence generation approach for supporting funding for FDG-PET/CT in this patient group.

A rare case of Disseminated Histoplasmosis with Hemophagocytic Lymphohistiocytosis mimicking a flare of Systemic Lupus Erythematosus in a middle-aged man: A Case Report

Abstract Introduction/Objective Disseminated histoplasmosis is a progressive granulomatous disease caused by Histoplasmosis capsulatum which is an intracellular dimorphic fungus endemic to Ohio and Mississippi River valleys in the United States. The progressive spread of the infection to organs is thought to be due to the failure of the activation of the T-cell mediated immune response. Hemophagocytic lymphohistiocytosis is a rare but potentially fatal condition in which histiocytes and lymphocytes build up in and damage organs and other blood cells. Diagnosing Disseminated Histoplasmosis with Hemophagocytic Lymphohistiocytosis in a patient with Systemic Lupus Erythematosus is diagnostically challenging due to the rare presentation. Hence, we are reporting this case to alert physicians to keep a high index of suspicion in such presentations. Methods/Case Report We present a 37-year-old man with a past medical history of Systemic Lupus Erythematosus complicated by Lupus Nephritis on immunosuppressive therapy who presented to the emergency department with hypotension and was admitted for acute kidney injury. Prior to the presentation, he had persistent fever, myalgias, cough, mild shortness of breath, and back pain. CT Chest shows “eggshell” calcification and further parasitology evaluation revealed a diagnosis of histoplasmosis using a blood sample where intracellular Histoplasma organisms were identified. A diagnosis of Hemophagocytic lymphohistiocytosis was made clinically after “Clinical and Testing Criteria” was evaluated. Despite further management, he developed coagulopathy and sepsis which led to his death. Results (if a Case Study enter NA) At autopsy, we found organomegaly of the liver, spleen, and kidneys. Microscopically, these enlarged organs show old fibrotic granulomas and granulomatous inflammation with suspected fungal organisms. Periodic Acid Schiff (Fungus) and Gomori's Methenamine Silver special stain confirm these fungal organisms to be consistent with Histoplasma species (3-5 micron budding yeasts). Conclusion This case report highlights that physicians should be aware of the diagnostic challenge that Disseminated Histoplasmosis with Hemophagocytic Lymphohistiocytosis could pose in patients with Systemic Lupus Erythematosus, especially those on immunosuppression. The clinical presentation could easily mimic a flare of Systemic Lupus Erythematosus, leading to more aggressive immunosuppression. Failure to recognize the infection promptly could lead to grievous complications and sometimes death.

Do Children Less Than 3 Years with Sickle Cell Disease Need to be Routinely Admitted with Fever?

Background Due to functional asplenia, patients with sickle cell disease (SCD) are at increased risk of serious bacterial infection (SBI) with encapsulated organisms. With the advent of prophylactic penicillin, Haemophilus and Pneumococcal vaccination, this risk has decreased, though recommendations for admission in young children are not standardized and based on institutional practice. Historically, our standard at Benioff Children Hospital Oakland (CHO) has been to admit all children with SCD < 3 years with fever due to these historical concerns. We hypothesized that in a well appearing febrile cohort, the risk of complication would be very low (i.e., <3-5%), allowing liberalization of this stringent recommendation. Methods After IRB approval, we conducted a retrospective review of electronic medical records of children with SCD <3 years of age admitted with fever (i.e., ≥38.3ºC) from October 1 st, 2013 to May 30 th 2022 at CHO. We excluded patients who presented with fever and other complications in the emergency department (ED) that would have otherwise required admission including: 1) splenic sequestration; 2) acute chest syndrome (ACS); 3) hypoxia and/or respiratory distress; 4) vaso-occlusive crisis (VOC); 5) hemoglobin (Hb) drop ≥2 g/dL from baseline; 6) severe dehydration; 7) seizures or other neurological concerns; 8) complicated/complex medical history; 9) SARS-CoV-2 infection; 10) age <2 months; 11) soft tissue infection; and 12) UA concerning for infection. Results Sixty-four unique patients with 127 encounters were included with baseline features outlined in Table 1. Ninety-seven encounters were excluded due to presenting signs/symptoms. Rate of bacteremia was 1.6% (2 of 127). Twenty-six of the 127 encounters (20%, 21 unique patients) were deemed complicated, due to: 1) bacteremia (n=2); 2) splenic sequestration (n=6); 3) acute chest syndrome (n=1); 4) worsening anemia requiring transfusion (n=11); 5) pain crisis (n=1); 6) persistent fever (n=4) and 7) norovirus gastroenteritis (n=1). Eighty-five percent were in children 2 years or less. Complicated admissions were statistically longer and had lower hemoglobin and platelets at presentation than uncomplicated admissions (Table 2). There was no difference in age, white blood cell count (WBC) and maximum fever during presentation in the ED (Table 2). Fourteen of 26 complications (54%) occurred in the first two days of admission and the rest thereafter. Conclusions Although the rate of bacteremia was low as expected in children with SCD <3 years of age presenting to the ED with fever and without concerning presenting features, the overall rate of complications during admission for those encounters was much higher than our acceptable a priori threshold. Retrospectively, there were no easily discernible presenting features in this otherwise well-appearing cohort to determine need for admission. Complications often occurred beyond day 2 of admission. The majority of complications occurred in children ≤2 years of age; we therefore will continue to admit all children with SCD and fever ≤ 2 years of age with a low threshold for ongoing admission beyond the 48 hour rule out. Institutional standards must closely monitor for increased adverse events if utilizing more lenient ED discharge criteria in this population.

501. Risk Factors for Persistent Active COVID-19 Among Patients Receiving B-Cell Depleting Therapy versus Non-B-Cell Immunosuppression

Abstract Background Cases of COVID-19 characterized by prolonged replication of SARS-CoV-2 (persistent active COVID [PAC]) have been reported among immunocompromised patients, particularly those receiving B-cell depleting therapy (BCDT); however, the risk has not been quantified. We aimed to identify risk factors associated with PAC, including quantifying the risk associated with receipt of BCDT vs. other types of immunosuppression. Methods We retrospectively identified four groups of immunocompromised patients who tested positive for SARS-CoV-2 between 4/01/2020 and 4/30/2021. These groups included one group of patients who received an anti-CD20 BCDT within 1 year before a positive SARS-CoV-2 PCR and three groups who received non-BCDT which included hematopoietic cell transplant (HCT) recipients, solid organ transplant (SOT) recipients, and patients receiving chemotherapy for hematologic malignancies (HM). Chart review was performed to characterize the clinical course and development of PAC, which was defined as any of the following: (1) initial clinical improvement followed by progression of illness extending beyond 14 days, characterized by persistent fevers or progressive respiratory failure; or (2) persistent symptoms with demonstration of absent seroconversion ≥ 14 days into illness. This distinction may be supported by low crossing thresholds that occurred ≥ 14 days into illness. Logistic models were performed to identify factors associated with development of PAC and other COVID outcomes. Results We identified 67 COVID-positive patients who had received BCDT as well as 30 HM, 118 SOT, and 29 HCT patients. PAC occurred in 15/67 (22%) of patients receiving BCDT vs. 3/177 (1.7%) patients (all SOT recipients) in the non-BCTD group (SOT, HCT, HM) (Odds Ratio, 16.7; 95% confidence interval [CI] 4.7 to 60.0; p=0.00005). 30-day hospitalization and 90-day mortality were similar in BCDT and non-BCDT groups (Table 1, Figure 1) (p > 0.05). Table 1. Risk factors for specific outcomes of COVID-19 Figure 1. Proportion of patients from each cohort of immunocompromised patients who developed persistent active COVID (1A), required hospitalization within 30 days (1B), required mechanical ventilation (1C), required ICU admission (1D), or died within 90 days after diagnosis of COVID-19 (1E) Conclusion Receipt of BCDTs was significantly associated with the development of PAC in comparison to other forms of severe immunosuppression. However, rates of severe outcomes associated with COVID-19 were similar across all groups. More research is necessary to determine effective prevention or treatment strategies for PAC. Disclosures All Authors: No reported disclosures

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

Primary pulmonary T-cell lymphoma mimicking asthma and community-acquired pneumonia: a rare case report

Primary pulmonary T-cell lymphoma (PPTL) is a rare disease. Diagnosing PPTL is challenging due to non-specific clinical symptoms and imaging. A 32-year-old female presented with persistent fever, cough, and dyspnoea. The symptoms were initially treated as asthma and community-acquired pneumonia without improvement. Chest computed tomography (CT) revealed bilateral consolidations with a CT angiogram sign, and flexible bronchoscopy showed infiltrative lesions causing bronchial stenosis. Histopathological examination of the tissue biopsy identified T-cell lymphoma through immunohistochemical staining positive for CD3. This case highlights the importance of considering differential diagnoses such as PPTL in patients with atypical presentations of asthma or non-resolving pneumonia. This case also demonstrates the diagnostic utility of flexible bronchoscopy in identifying airway obstruction due to malignant cells, which can mimic asthma.

Hemophagocytic syndrome and coronary artery aneurysms in a child with Kawasaki disease

Mucocutaneous lymph node syndrome (Kawasaki syndrome/disease) is an acute systemic disease characterized by a predominant lesion of medium and small arteries (arteriitis), the development of destructive proliferative vasculitis. The most serious manifestations of Kawasaki disease are coronaritis and the formation of aneurysms of the coronary arteries, which can be a potential cause of acute coronary syndrome in children. The article presents our own clinical observation of a 7-month-old child with a complete form of Kawasaki disease with the formation of aneurysms of the coronary arteries, complicated by acute coronary and hemophagocytic syndromes. Kawasaki syndrome should be considered in all children with persistent fever ≥ 5 days, and the combination of persistent fever with 2–3 typical features of Kawasaki syndrome should be an absolute indication for echocardiography with mandatory visualization of the coronary arteries.

Clinical characteristics and prognosis in 12 children with SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy

To study the clinical characteristics and prognosis of SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy (ANE) in children. A retrospective analysis was conducted on the medical data of 12 children with SARS-CoV-2 Omicron variant infection-associated ANE who were admitted to the Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital from December 18 to 29, 2022. The children were divided into two groups based on outcomes: death group (7 cases) and survival group (5 cases). The clinical manifestations and auxiliary examination results were compared between the two groups. The median age of the 12 patients was 30 months, with a male-to-female ratio of 1:1. All patients presented with persistent high fever, with a median highest body temperature of 41℃. The median time from fever onset to seizure or consciousness disturbance was 18 hours. The death group had a higher proportion of neurogenic shock, coagulation dysfunction, as well as elevated lactate, D-dimer, interleukin-6, interleukin--8, and interleukin-10 levels compared to the survival group (P<0.05). Children with SARS-CoV-2 Omicron variant infection-associated with ANE commonly present with persistent high fever, rapidly progressing disease, and have a high likelihood of developing consciousness disorders and multiorgan dysfunction within a short period. The occurrence of neurogenic shock, coagulation dysfunction, and significantly elevated cytokine levels suggests an increased risk of mortality.

Intravascular NK/T-cell lymphoma: a case report and literature review.

Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)-positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

Reduced splenic function can mimic artemisinin resistance in severe malaria.

We describe severe post-treatment episodes that complicate Plasmodium falciparum malaria in patients with hyposplenism, characterized by prolonged circulation of red cells containing dead parasites (hearse red cells), persistent or recurrent fever, profound anaemia, and inflammation. Asplenia-related Post-antimalarial Inflammation &amp; Hemolysis (APIH) mimics concomitant infection and parasite resistance to drugs.

La Valentine disease: An outbreak of exanthematic typhus in Marseille, France, in 1810.

Exanthematic typhus was highly frequent in the early 19th century among military troops and prisoners and at hospitals. Based on old reports, we describe an outbreak in a village, in Southern France, in 1810. Twenty-eight cases were identified, over a period of 10 days following the death of the index case, in a soldier. Symptoms included notably persistent constant fever, myalgia and headaches, gastro-intestinal symptoms, prostration and stupor. Three patients suffered delirium and nine died (31.0%). Overall, symptoms persisted for 13-14 days. A total of 16 cases were secondary to contacts with the index case, and 10 cases were in house-hold contacts of secondary cases. Five familial clusters were described. This data suggest that exanthematic typhus outbreaks among civilian populations also occurred outside the context of hospitals, in link with introduction of the disease by prisoners or soldiers.

Abstract 18602: A Rare Case of Ehrlichiosis Induced Myocarditis

Description of Case: A 64-year-old female presented with progressively worsening shortness of breath, headaches, weakness, intermittent confusion, and persistent fevers. Laboratory work-up revealed leukopenia, thrombocytopenia, elevated transaminases, negative viral panel, and elevated CRP. Chest CT revealed ground glass opacities and bilateral interlobular thickening. TTE obtained was normal. She was started on empiric meningitis treatment. She was transferred to the ICU after becoming more hypoxic and hypotensive. Further history revealed recent tick exposure while visiting the eastern North Carolina woods. Doxycycline was started for suspected tick-borne disease on day 2 of her ICU stay. LP was non-revealing. Her course was complicated by development of inferolateral ST segment elevation on EKG. Initial troponin I level was 155.66 ng/mL peaking at 209.24 ng/mL (reference range &lt;= 0.03 ng/mL). Cardiac catheterization revealed no epicardial coronary disease. Repeat TTE showed a decreased LVEF at 25-30% and global hypokinesis. Cardiac MRI revealed evidence of an inflammatory myocardial process, myocardial edema and epicardial fibrosis. The patient had a positive Erhlichia chaffensis IgG antibody titer and Ehrlichia chaffensis DNA polymerase chain reaction was positive. She demonstrated improvement with continuation of doxycycline. Heart failure guideline directed medical therapy was initiated prior to her discharge. Discussion: Ehrlichia infections occur primarily in areas of south and central United States. Transient flu-like symptoms are the most typical manifestations, but more severe complications can occur such as meningoencephalitis, respiratory failure, coagulopathy, myocarditis and death. There are only a few documented cases of myocarditis due to Ehrlichia infections. If not recognized early, myocarditis can be a serious and fatal complication of ehrlichiosis, even in immunocompetent patients. A high level of suspicion for this should be kept in the differential for patients with cardiac manifestations presenting from endemic areas, especially during warmer seasons. Doxycycline therapy should be started promptly for clinical suspicion of Ehrlichia infection.

Abstract 17951: Infective Endocarditis of an Amplatzer PFO Occluder: A Rare and Devastating Complication

Introduction: Patent foramen ovale (PFO) closure is indicated for secondary prevention of ischemic strokes in select patients. PFO closure devices are rarely complicated by infective endocarditis (IE). We present the case of a patient with a closure device infected by Methicillin-sensitive Staphylococcus Aureus (MSSA). Case: A 60-year-old woman with a history of ischemic stroke status post transcatheter PFO closure with a 25 mm Amplatzer occluder eight months prior to presentation was admitted for a two week history of lower back pain, bilateral lower extremity weakness, and urinary incontinence. She denied dental procedures following device implantation. MRI of the spine revealed L3-L4 osteomyelitis with an adjacent epidural abscess which was immediately drained. Blood and intra-operative cultures revealed MSSA. There was no evidence of endocarditis on transthoracic echocardiogram (TTE). Given persistent bacteremia, a transesophageal echocardiogram (TEE) was performed, revealing large, highly mobile vegetations measuring up to 3 cm in length, attached to both the left and right atrial surfaces of the Amplatzer occluder. Urgent surgical removal of the Amplatzer occluder and PFO closure was performed. She received a 4-week course of Cefazolin. Discussion: Despite periprocedural antibiotics and prophylaxis for dental procedures for six months after implantation, IE of PFO occluders can rarely occur days to years after implantation. In patients with PFO occluders and persistent bacteremia or fevers, TEE is the diagnostic modality of choice as TTE are often negative. Management consists of urgent surgical excision and long-term antibiotics.

FREQUENCY OF BONE MARROW INVOLVEMENT IN PYREXIA OF UNKNOWN ORIGIN

The definition of pyrexia of unknown origin (PUO) dates back to 1961; it was described as a persistent fever above 38.3°C (100°F) that evades diagnosis for at least 3 weeks, including 1 week of investigation in hospital.(1) The causes of PUO can be considered in four categories: infective, inflammatory, neoplastic and miscellaneous. The relative prominence of each category has changed over time, with an increasing proportion of patients who remain undiagnosed, which may be up to 51% of cases.(2) In cases where bone involvement is suspected, bone marrow biopsy can serve as a diagnostic tool , for example, myeloproliferative disorders, preleukemias (due to acute myelogenous leukemia), Gaucher’s disease, lymphoma, Erdheim-Chester disease, miliary tuberculosis, disseminated histoplasmosis, multicentric Castleman’s disease, Whipple’s disease, or typhoid/enteric fever.(3) A relationship between pyrexia of unknown origin and utilizing bone marrow biopsy as a diagnostic modality will be an eye opener for the clinicians. It will stress them to incorporate bone marrow biopsy as a part and parcel of the investigations. This study will also help to know the current spectrum of diseases causing PUO in patients in this region.It will help the clinicians in better assessment of the patients and expedite the diagnostic procedure that will ultimately decrease the misery of the patients.

Pediatric Multisystem Inflammatory Syndrome (MIS-C) associated with Covid-19 culminating in multiple complications: A case report

On January 30, 2020, the World Health Organization (WHO) declared a Public Health Emergency of International Concern, due to the novel coronavirus 2019 (definitively named on February 12, 2020 as COVID-19). Initially, Covid-19 infection did not appear to affect the paediatric population, with few reported cases, negligible morbidity, and mortality, and generally asymptomatic. However, subsequently, the English National Health System (NHS) issued an alert about new clinical manifestations of COVID-19 in children, which may be temporarily linked to a previous SARS-CoV-2 infection and determined by history of exposure, serology, or viral detection by RT-PCR, described as a paediatric multisystem inflammatory syndrome temporally associated with SARS-COV-2 (MIS-C). This paper reports the case of a 3-year-old and 6-month-old male patient, neuropathic, microcephalic, epileptic who sought medical attention with persistent fever and abdominal pain. Laboratory tests showed myositis, hepatitis, pancreatitis, positive PCR, elevated D-dimer and serology for covid-19 with non-reactive IgM and reactive IgG, thus meeting the diagnostic criteria for MIS-C. As for its prognosis, MIS-C is a dangerous and potentially fatal disease. The estimated mortality rate for MIS-C is between 0% and 5.3%, which is considered low but much higher than the overall mortality rate for children with COVID-19 (0.09%). Treatment depends on the severity of the disease, the risk of complications, and the possibility of follow-up, with most patients requiring hospitalization.

Systematic analysis of liver failure accompanied with hemophagocytic syndrome in adults

Objective: To retrospectively analyze literature reports and summarize the clinical characteristics of liver failure in patients accompanied with adult hemophagocytic syndrome (HPS). Methods: The Wanfang, CNKI, VIP, PubMed, and Ovid databases were searched for relevant literature on liver failure patients accompanied with adult HPS published from January 1980 to May 2022. The final included literature was systematically reviewed after screening. Results: There were a total of 77 liver failure cases accompanied with adult HPS, with an average age of (41.8 ± 12.5) years. The most common clinical manifestations of these cases were persistent high fever, fatigue, gastrointestinal symptoms, and severe jaundice. The imaging changes were not specific, and the most common was hepatosplenomegaly. Laboratory examination showed a significant increase in serum total bilirubin, lactate dehydrogenase, triglycerides, and soluble interleukin-2 receptor levels, as well as serum ferritin, while there was a decrease in prothrombin activity, natural killer cell activity, and hemocytopenia of two or more lineages in peripheral blood. Myelogram examination showed hemophagocytosis. Adult HPS secondary to infection was more likely to be accompanied with liver failure (55.8%), with an overall case fatality rate of 84.4%. Conclusion: Patients with liver failure accompanied with adult HPS have an extremely high mortality rate and a poor prognosis. Early diagnosis and treatment are the keys to improving the prognosis.

Diagnostics and treatment of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is ahyperferritinemic hyperinflammatory syndrome. Aprimary hereditary form can be distinguished from asecondary acquired form. In adults the secondary form accounts for the vast majority of cases. Infections, malignancies and autoimmune disorders are common triggering factors of secondary HLH. Persistent fever, bicytopenia or pancytopenia and splenomegaly represent major symptoms in HLH and occur in virtually all patients. The diagnosis of HLH is made on the basis of the HLH-2004 criteria. The probability of the presence of HLH can be estimated using the HScore. Patients with HLH require immunosuppressive treatment. Hence, high doses of corticosteroids represent the cornerstone of treatment. Furthermore, immunoglobulins, anakinra, ruxolitinib or etoposide are given depending on the triggering factor. The course and prognosis of HLH are dependent on the early initiation of treatment, the triggering factor and the response to treatment.