A 24-year-old Ecuadorian female, previously diagnosed with acute fatty liver (AFL) during pregnancy, developed constitutional symptoms, jaundice, and abdominal pain in a subsequent pregnancy, prompting investigations that suggested a recurrence of AFL. She underwent an elective abortion, which resulted in the resolution of her abdominal pain, and a liver biopsy, which showed granulomatous inflammation and lymphocytic infiltration. She later presented with abdominal distention, productive cough, and persistent constitutional symptoms and jaundice. Extensive laboratory and imaging studies indicated sepsis, acute liver injury, and disseminated intravascular coagulopathy. Her serum Epstein-Barr virus (EBV) level was elevated. Special staining of her previous liver biopsy revealed EBV-positive natural killer (NK) cells. A bone marrow biopsy also revealed EBV-positive NK cells. She was diagnosed with aggressive NK cell leukemia (ANKL) with or without chronic active EBV (CAEBV). Treatment included dexamethasone, atovaquone, bortezomib, and ganciclovir, with plans for a stem cell transplant. However, her course was complicated by infections and multi-organ failure, resulting in her passing. This case highlights the rarity and challenges in managing EBV-associated ANKL, emphasizing the need for early detection and improved treatment options, with stem cell transplantation offering the best prognosis.

Hemophagocytic lymphohistiocytosis (HLH) during pregnancy is a rare and often misdiagnosed disease. The clinical manifestations are non-specific, contributing to a high maternal mortality rate. This case report details the presentation of a 31-year-old pregnant woman with high-grade fever initially treated as an infection-related condition. The diagnostic challenge arose from the rarity of HLH, its variable clinical presentation, and the lack of specificity in clinical and laboratory findings. Despite numerous tests and escalation of therapies, the patient, unfortunately, succumbed to HLH associated with T-cell lymphoma. This case report aims to raise awareness of HLH, emphasizing its challenging definition. Malignancy-associated HLH is not uncommon, and early identification and treatment are paramount to prevent progressive tissue damage, organ failure, and mortality. The atypical presentation of HLH as a clinical manifestation of T-cell lymphoma underscores the need for vigilance in diagnosing this potentially fatal syndrome.

Melioidosis is a rare disease caused by Burkholderia pseudomallei, which has recently acquired prominence in India as an emerging pathogen. It is a gram-negative bacteria found in soil. As delayed diagnosis and treatment are linked to increased mortality, early diagnosis is crucial. We present here a unique instance of melioidosis that was made worse by a rare disorder known as hemophagocytic lymphohistiocytosis (HLH), which necessitates early treatment.

A previously healthy young female of Southeast Asian descent presented with a two-week history of polyarthritis, urticarial rash, sore throat, and 8.6 kg of unintentional weight loss. The initial workup revealed a positive parvovirus B19 polymerase chain reaction with hyperferritinemia. The patient was diagnosed with adult-onset Still\'s disease (AOSD) secondary to parvovirus B19 infection. Bone marrow biopsy also showed evidence of hemophagocytic lymphohistiocytosis. Viral and bacterial infections may trigger AOSD in genetically susceptible hosts either via an unknown mechanism or by direct cytotoxic effect. This case shows an atypical presentation of AOSD, as well as the challenge in diagnosing and treating AOSD complicated by macrophage activation syndrome refractory to standard treatment.

Hemophagocytic lymphohistiocytosis (HLH) is a hyper-inflammatory condition triggered by infections, malignancies, or autoimmune conditions. Brucellosis is a zoonotic disease contracted through exposure to infected animals or consumption of unpasteurized dairy products. The complications of both pathologies may be fatal. This report presents a rare instance of HLH induced by Brucellosis, highlighting the need for increased recognition of this life-threatening association.

Hemophagocytic lymphohistiocytosis (HLH) comprises a broad spectrum of life-threatening cytokine storm syndromes, classified into primary (genetic) or secondary (acquired) HLH. The latter occurs in a variety of medical conditions, including infections, malignancies, autoimmune and autoinflammatory diseases, acquired immunodeficiency, and metabolic disorders. Despite recent advances in the field, the pathogenesis of secondary HLH remains incompletely understood. Considering the heterogeneity of triggering factors and underlying diseases in secondary HLH, a large diversity of animal models has been developed to explore pivotal disease mechanisms. To date, over 20 animal models have been described that each recapitulates certain aspects of secondary HLH. This review provides a comprehensive overview of the existing models, highlighting relevant findings, discussing the involvement of different cell types and cytokines in disease development and progression, and considering points of interest toward future therapeutic strategies.

This is a case of a 75-year-old male with a complicated past medical history who presented initially with weakness, fevers, exertional dyspnea, cough, and confusion. His initial workup revealed elevated aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, and D-dimer. Right upper quadrant (RUQ) ultrasound revealed a partially contracted gallbladder with gallstones, so he underwent laparoscopic cholecystectomy. Due to worsening hyperbilirubinemia and anemia, he later underwent a liver biopsy which showed Epstein-Barr virus (EBV)-positive lymphoid infiltration. He developed anemia, thrombocytopenia, and low fibrinogen. He met the criteria for hemophagocytic lymphohistiocytosis (HLH) with 6/8 HLH-2004 criteria and an H score of 230 with a 96-98% probability of HLH. The patient was promptly treated with steroids, rituximab, and etoposide; however, the patient\'s health continued to deteriorate, and he expired. This case highlights the challenges of early diagnosis of HLH in the elderly patient population due to large differentials, confounding comorbidities, and the rarity of the diagnosis in this age range.

Macrophage activation syndrome (MAS), synonymous with secondary hemophagocytic lymphohistiocytosis (HLH), is a rare and critical complication of rheumatologic disease stemming from the unregulated activation and rapid multiplication of macrophages and T lymphocytes. While it primarily manifests in children diagnosed with systemic juvenile idiopathic arthritis (sJIA), it can arise less frequently in other rheumatologic conditions. Here, we outline the clinical course, treatment, and outcome of MAS diagnosed in an 18-year-old female previously diagnosed with SLE who exhibited a unique clinical presentation.

UNASSIGNED: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication following hematopoietic stem cell transplantation (HSCT). Currently, there is a lack of consensus recommendations for the treatment of post-transplant HLH. This case report emphasizes the successful utilization of ruxolitinib as a salvage therapy for HLH post-HSCT. The aim is to provide valuable insights into the optimal management of this rare and complex complication.
UNASSIGNED: We present a case study of an 11-year-old male patient diagnosed with severe aplastic anemia who received a haploidentical HSCT. On the 86th day post-transplantation, the patient developed recurrent fever, hepatomegaly, hypertriglyceridemia, severe pancytopenia, and elevated levels of inflammatory factors and ferritin. Hemophagocytosis was observed in the bone marrow, and subsequent DNA next-generation sequencing identified adenovirus type C infection, leading to a diagnosis of adenovirus-associated HLH. After unsuccessful treatment attempts with cidofovir, dexamethasone, immunoglobulin, plasmapheresis, and etoposide, ruxolitinib was administered. Remarkably, the patient\'s clinical symptoms rapidly improved, and his test results gradually normalized with ruxolitinib therapy. The adenovirus viral load became undetectable by the 180th day. With continuous remission, ruxolitinib was discontinued on the 137th day post-transplantation, and a 15-month follow-up examination showed no relapse.
UNASSIGNED: We present a case of adenovirus-related secondary HLH (sHLH) post-HSCT, which was effectively treated with ruxolitinib. Our case highlights the potential of ruxolitinib as a therapeutic option for patients with viral infections and sHLH. Nonetheless, the safety and efficacy of this innovative treatment should be evaluated in forthcoming large-scale clinical trials.

High ferritin is an important and sensitive biomarker for hemophagocytic lymphohistiocytosis (HLH), a diverse and deadly group of cytokine storm syndromes. Early action to prevent immunopathology in HLH often includes empiric immunomodulation, which can complicate etiologic work-up and prevent collection of early/pre-treatment research samples. To address this, we instituted an alert system where serum ferritin > 1000ng/mL triggered real-time chart review, assessment of whether the value reflected \"inflammatory hyperferritnemia (IHF)\", and biobanking of remnant samples from consenting IHF patients. We extracted relevant clinical data; periodically measured serum total IL-18, IL-18 binding protein (IL-18BP), and CXCL9; retrospectively classified patients by etiology into infectious, rheumatic, or immune dysregulation; and subjected a subgroup of samples to a 96-analyte biomarker screen. 180 patients were identified, 30.5% of which had IHF. Maximum ferritin levels were significantly higher in patients with IHF than with either hemoglobinopathy or transplant, and highly elevated total IL-18 levels were distinctive to patients with Stills Disease and/or Macrophage Activation Syndrome (MAS). Multi-analyte analysis showed elevation in proteins associated with cytotoxic lymphocytes in all IHF samples when compared to healthy controls and depression of proteins such as ANGPT1 and VEGFR2 in samples from hyperferritinemic sepsis patients relative to non-sepsis controls. This single-center, real-time IFH screen proved feasible and efficient, validated prior observations about the specificity of IL-18, enabled early sample collection from a complex population, suggested a unique vascular biomarker signature in hyperferritinemic sepsis, and expanded our understanding of IHF heterogeneity.