Hoagland Sign as an Aid for Antimicrobial Stewardship—A Case Report

Hoagland sign is an early and transient bilateral painless upper eyelid edema observed in patients with Epstein-Barr virus (EBV)-related infectious mononucleosis. This sign can predate the appearance of exudative pharyngitis and cervical lymphadenopathy. Usually, this sign disappears by first week of infection. Here, we describe the occurrence of late onset Hoagland sign in a 14-year old boy who presented to us on 10th day of fever. Hoagland sign appeared after 10 days from symptom onset in our patient. Despite persistence of fever, the presence of Hoagland sign which appeared prior to confirmation of EBV infection was a helpful indicator for stopping antibiotics. In view of tonsillar hypertrophy with potential airway compromise and biochemical parameters suggestive of possible secondary hemophagocytic lymphohistiocytosis, he was initiated on steroids with which defervescence and prompt resolution of symptoms occurred. EBV can present as acute undifferentiated febrile syndrome which might result in inappropriate use of antibiotics. This case highlights the importance of using clinical clues like Hoagland sign to optimize antimicrobial stewardship.

ADULT SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS – A CASE SERIES

Hemophagocytic lymphohistiocytosis is a hyper-inammatory condition that is either Familial (Primary) or Secondary to autoimmune diseases , infection, malignancy or other triggers.It is a cytokine storm syndrome where there inefcient antigen removal that leads to sustained cytokine release.It is a rare phenomenon occuring in adults that has got a specic trigger which is less documented and have a good response to steroids where as Familial form is a childhood disease due to genetic defects, both of which are life threatening and may need Allogenic bone marrow transplant. Macrophage activation syndrome is also a subtype of this entity that occurs in the treatment phase of SLE and Still's disease.We describe here 8 cases of secondary HLH, their primary triggers and treatment response.

A Fatal Case of Severe Acute Organophosphorus Pesticide Poisoning Complicated with Secondary Hemophagocytic Lympho-Histiocytosis, Severe Lower Intestinal Hemorrhage and Intestinal Mucormycosis

A man in his 50’s, under influence of alcohol, accidentally ingested a pesticide, and was referred for further management and admitted to our hospital. An empty can of Curacron® was found at the site in his farm where he took the alleged pesticide. This raised the suspicion of organophosphorus pesticide poisoning and he was managed at two medical centres before getting admitted to our hospital. His hospital course was complicated with multiorgan dysfunction, shock, respiratory failure and intermediate syndrome. On day five he developed secondary hemophagocytic lymphohistiocytosis (sHLH) and had hematochezia on day six. Colonoscopy revealed multiple circumferential ulcerations in descending and sigmoid colon with luminal narrowing. Biopsy of colonic tissue showed evidence of intestinal Mucormycosis. The clinical presentation of organophosphorus pesticide poisoning in this patient was complicated with multiple issues and included sHLH, chemical gastroenteritis, hemorrhagic ulcers and intestinal zygomycosis. The organophosphorus pesticide ingested by the patient was a 50% emulsifiable concentrate of profenofos along with vegetable oil, soyabean oil and polyglycol ether alkyl aryl sulphate calcium salt 5.25% w/w as an emulsifier/spreading agent. The management of the patient is discussed. Due to the possibility of the emulsifier adhering to the gastrointestinal tract and causing mucosal injury, it is necessary to identify the drug composition and ingredients of the pesticide as soon as possible when managing organophosphorus poisoning.

Hemophagocytic lymphohistiocytosis: a rare and life-threatening diagnosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome of excessive activation of immune system. It frequently affects infants from birth to 18 months of age, but is also observed in children and adults of all ages. HLH can occur as a familial or sporadic disorder, and it is triggered by a variety of events, Infection being the most common trigger both in familial and in sporadic cases. Prompt treatment is very critical in cases of HLH, but the greatest barrier is often delay in diagnosis due to the rarity of this syndrome, variable clinical presentation, and lack of specificity of the clinical and laboratory findings. The key clinical features of HLH are high persistent fever, hepatosplenomegaly, blood cytopenia, elevated aminotransferase and ferritin levels, and coagulopathy. A diagnosis of HLH is mostly under-recognized, and is associated with high mortality, especially in adults; thus, prompt diagnosis and treatment are essential. We here present a rare case of HLH in an adult which was non-familial and infection being the trigger causing secondary hemophagocytic lymphohistiocytosis.

Clinical Value of 18F-FDG PET/CT Scan and Cytokine Profiles in Secondary Hemophagocytic Lymphohistiocytosis in Idiopathic Inflammatory Myopathy Patients: A Pilot Study

BackgroundSecondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal complication in idiopathic inflammatory myopathy (IIM) patients. The clinical value of radiological manifestations and serum cytokines remain unknown in this systemic crisis. This study aims to investigate the clinical value of PET/CT scan and cytokine profiles in predicting and understanding sHLH in IIM patients.MethodsAdult IIM patients who were admitted to the four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from January 1, 2017 to December 31, 2020 were reviewed. PET/CT scan, cytokine profiles, and other factors of patients who met the inclusion and exclusion criteria were collected and analyzed.ResultsSixty-nine out of 352 IIM patients were finally enrolled into the study. Ten patients developed sHLH and 70.0% of them died within 6 months. After false discovery rate (FDR) correction and multivariate logistic regression analysis, increased serum interferon (IFN)-γ level (p = 0.017), higher spleen mean standard uptake value (SUVmean, p = 0.035), and positivity of anti-MDA5 antibody (p = 0.049) were found to be significantly correlated with development of sHLH in IIM patients. The combination of serum IFN-γ, spleen SUVmean, and anti-MDA5 antibody found a balanced and satisfying predictor with a cutoff value of 0.047 and AUC of 0.946. A moderate correlation was identified between ferritin and spleen SUVmean (p = 0.001, r = 0.380) as well as serum IFN-γ(p = 0.001, r = 0.398). Before FDR correction, higher bilateral lung SUVmean (p = 0.034) and higher colon/rectum SUVmean (p = 0.013) were also observed in IIM patients who developed sHLH. By narrowing down to IIM patients with sHLH, anti-MDA5-antibody-positive DM patients tended to suffer from unfavorable outcome (p = 0.004) in Kaplan–Meier survival analysis.ConclusionIncreased serum level of IFN-γ, elevated splenic FDG uptake, and positivity of anti-MDA5 antibody were significantly correlated with development of sHLH in IIM patients. Lung and lower digestive tract might also be affected due to systemic immune activation in IIM patients with sHLH. In addition, splenic FDG uptake, in combination with serum IFN-γand anti-MDA5 antibody, was found valuable in predicting development of sHLH in IIM patients. Among IIM patients with sHLH, anti-MDA5-antibody-positive DM patients showed higher tendency for unfavorable outcome.

Outcomes with Hematopoietic Stem Cell Transplantation in Secondary Hemophagocytic Lymphohistiocytosis: A Systematic Review and Meta-Analysis

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by the hyper-stimulation of the immune system. HLH has a poor prognosis with up to a 100% mortality without an adequate therapy. Contrary to primary HLH, an efficient management approach has yet to be established for secondary HLH in adults. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of hematopoietic stem cell transplantation (HSCT) in this context. Methods Following the preferred reporting items for systemic reviews and Mata-analysis (PRISMA) guidelines, a comprehensive literature search was performed on 4 databases (PubMed, Cochrane Register of Controlled Trials, Embase and Clinicaltrials.gov) using MeSH terms and keywords for "Lymphohistiocytosis, Hemophagocytic" AND "Hematopoietic stem cell transplantation" AND "Therapeutics" AND "Treatment Outcome" from the date of inception to June 2021. Our search produced 2346 results and duplicates were removed. After excluding irrelevant and review articles during primary and secondary screening, seven original studies reporting HSCT as the treatment for secondary HLH in pediatric and adult patient population were included. The methodological quality of the included studies was evaluated using NIH quality assessment tool. Inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). Results: A total of 136 patients from 7 studies were included. The median age of the patients was 32 (0.5-77) years and 57.4% (62/108) were males as reported by 4 studies. (Table 1) Allogeneic HSCT was used as a treatment modality for 100% (n=136) of the patients. The median time from diagnosis to HSCT was 4.9 (0.1-24) months as reported by 3 studies and median follow-up time was 22 (3-192) months as reported by 4 studies. The pooled overall response rate (ORR) after HSCT was 80% (95% CI 0.66-0.91, I 2 =21%, n=59) with pooled complete response (CR) of 54.5% (95% CI 0.19-0.87, I 2 =86%, n=59) and pooled partial response (PR) of 22.4% (95% CI 0.04-47, I 2 =72%, n=59). At a median follow-up of 30 (3-120) months, the pooled overall survival (OS) was 78.8% (95% CI 0.67-0.89, I 2 =41%, n=136). The pooled relapse rate (RR) was 12.2% (95 CI 0.045-0.22, I 2 =0%, n=61). The pooled incidence of acute graft versus host disease (GVHD) grade I/II and grade III/IV was 37.5% (95% CI 0.24-0.51, I 2 =0%, n=48) and 19.8% (95% CI 0.09-0.32, I 2 =0%, n=50) respectively, while pooled incidence of chronic GVHD was 26% (95% CI 0.13-0.41, I 2 =25%, n=50). Conclusion: HSCT shows excellent response rates and survival in patients with secondary HLH with an acceptable safety profile and should be considered. However, it is imperative that large prospective studies should be done to consolidate these findings. Figure 1 Figure 1. Disclosures McGuirk: Novartis: Research Funding; Gamida Cell: Research Funding; Astelllas Pharma: Research Funding; EcoR1 Capital: Consultancy; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding.