Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis.

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.

Consequences of hemophagocytic lymphohistiocytosis-like cytokine release syndrome toxicities and concurrent bacteremia.

Serious bacterial infections (SBI) can lead to devastating complications with CD19 CAR T cells and cytokine release syndrome (CRS). Little is known about consequences of and risk factors for SBI with novel CAR T-cell constructs or with CRS complicated by HLH-like toxicities. We report on three patients with B-cell acute lymphoblastic leukemia treated with CD22 CAR T cells who developed SBI and CRS-associated HLH. Serum cytokine profiling revealed sustained elevations well beyond CRS resolution, suggesting ongoing systemic inflammation. Heightened inflammatory states converging with SBI contribute to poor outcomes, and recognition and prevention of extended inflammation may be needed to improve outcomes.

A 58-Year-Old Man With Acute Encephalopathy, Fever, and Multi-Organ Dysfunction.

CASE PRESENTATION: A 58-year-old man with a medical history of type 2 diabetes mellitus and COPD presented with fever, chills, nausea, vomiting, left upper quadrant abdominal pain, and altered mental status for the past week. His mental status rapidly deteriorated and work of breathing increased, which required intubation and mechanical ventilation. The patient's wife reported recent exposure to tick bites after finding several ticks while changing the sheets in their bedroom.

Hemophagocytic syndrome associated with Mycobacterium bovis in a patient with X-SCID: a case report.

BACKGROUND: Mycobacterium bovis could infect patients with immunodeficiency or immunosuppressive conditions via Bacillus Calmette-Guérin (BCG) vaccination. Tuberculosis-related hemophagocytic syndrome (HPS) is reported, but not HPS caused by Mycobacterium bovis in children. CASE PRESENTATION: A 4-month Chinese boy presented fever and cough. The initial laboratory investigation showed the lymphocyte count of 0.97 × 109/L, which decreased gradually. HPS was diagnosed based on the test results that fulfilled the HLH-2004 criteria. In addition, Mycobacterium tuberculosis complex was detected from his peripheral blood via metagenomic next-generation sequencing (mNGS) and M. bovis was identified by polymerase chain reaction-reverse dot blot (PCR-RDB). Thus, the patient was treated with Isoniazid, Rifampin, and Pyrazinamide, but not improved. However, parents refused to accept further therapy, and was discharged on the day 12 of admission. To confirm the pathogenesis, genetic analysis was performed. Mutation in the interleukin-2 receptor subunit gamma gene: Exon 6: c.854G > A; p. Arg285Gln was detected in the patient and the mother, which could underlie X-linked severe combined immunodeficiency. CONCLUSIONS: A boy with X-SCID was diagnosed with M. bovis-associated HPS, emphasizing that X-SCID should be considered when M. bovis is detected in a male infant with low lymphocyte counts.

Desperate times, desperate measures: successful use of chemotherapy in treatment of haemophagocytic lymphohistiocytosis (HLH) due to disseminated histoplasmosis.

We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement.

Incidence and treatment of hemophagocytic lymphohistiocytosis in hospitalized children with Ehrlichia infection.

We report a large cohort of pediatric patients with human monocytic ehrlichiosis (HME), enabling an estimated incidence of secondary hemophagocytic lymphohistiocytosis (HLH) in hospitalized children with HME. Among 49 children with PCR-confirmed Ehrlichia infection, 8 (16%) met current criteria for HLH. Those with HLH had more significant hematologic abnormalities and longer durations from symptom onset to admission and definitive anti-infective therapy. Among these eight, three received chemotherapy plus doxycycline, one of whom died; the other five were treated with doxycycline without chemotherapy, and all survived without HLH recurrence. Our findings demonstrate that antimicrobial therapy alone can successfully resolve Ehrlichia-associated HLH.

Hemophagocytic lymphohistiocytosis is associated with Bartonella henselae infection in a patient with multiple susceptibility genes.

BACKGROUND: Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition, which is often triggered by certain types of infection, cancer and numerous autoimmune diseases; however, of the numerous infectious triggers associated with HLH, the consequences of Bartonella henselae infection have been rarely reported. CASE PRESENTATION: A 48-year-old female presented with a 20-day history of intermittent fever accompanied by systemic rash, fatigue, anorexia and weight loss later she developed shock and unconsciousness. Blood tests showed a reduction of leukocyte, anemia and thrombocytopenia, and pathological results of a bone marrow biopsy confirmed hemophagocytic activity. Metagenomic next-generation sequencing (mNGS) analysis of the lymph node detected the presence of B. henselae. Whole exome sequencing revealed two gene variants, STXBP2 and IRF5, in this adult patient with secondary HLH. Then, she received minocycline and rifampin combination anti-infective therapy. Intravenous immunoglobulin for 5 days followed by a high dose of methylprednisolone were also administered. The patient was successfully discharged from the intensive care unit and remained in good condition after 2 months of follow-up. CONCLUSIONS: mNGS served crucial roles in obtaining an etiological diagnosis, which suggested that screening for B. henselae should be considered in patients with HLH, especially those with a cat at home. In addition, the genetic defects were discovered to not only be present in primary HLH, but also in secondary HLH, even in the elderly.

Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

Hemophagocytic syndrome with severe sepsis caused by Capnocytophaga canimorsus.

Capnocytophaga canimorsus, commonly transmitted by dog bites, can cause severe sepsis, and the mortality rate is very high. We experienced a case of hemophagocytic lymphohistiocytosis (HLH) complicated by severe sepsis caused by C. canimorsus. A 58-year-old man with no remarkable medical history was admitted to another hospital with fever and mild consciousness disorder developed 3 days after being bitten by his dog. The next day, the patient developed disseminated intravascular coagulation and shock and was transferred to our emergency medical center. Blood tests showed hyperferritinemia and cytopenia, and bone marrow aspiration was performed. As a result, we diagnosed severe sepsis and HLH. Once antibiotic and steroid therapy was started, the patient's infection and cytopenia improved. Unfortunately, the patient's fingers and toes required amputation, but his life was saved, and he was discharged from hospital. Because HLH may be hidden in such cases, it may be necessary to measure serum ferritin and perform bone marrow aspiration if hyperferritinemia is suspected.

Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary to Burkholderia cepacia complex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: 'cepacia syndrome' revisited.

X-linked carriers of chronic granulomatous disease (CGD) may become phenotypically affected if substantial skewing from lyonisation occurs. We describe a 73-year-old female carrier with an overt CGD phenotype due to skewed lyonisation, complicated by macrophage activation syndrome (MAS)/haemophagocytic lymphohistiocytosis (HLH) secondary to Burkholderiacepacia complex septicaemia that was successfully treated with a combination of three antibiotics, an antifungal, granulocyte colony stimulating factor, intravenous immune globulin (IVIG) and ciclosporin. Fully phenotypic immunodeficiency is possible in X-linked CGD carriers when skewed lyonisation occurs, rendering such patients to all the same sequelae of CGD such as MAS/HLH. MAS/HLH should be thoroughly excluded when evaluating 'cepacia syndrome' in non-CGD patients.

Acute Respiratory Distress Syndrome Secondary to Histoplasmosis-induced Hemophagocytic Lymphohistiocytosis / Síndrome de distrés respiratorio agudo secundario a linfohistiocitosis hemofagocítica inducida por histoplasmosis

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[Hemophagocytic lymphohistiocytosis with granulomatosis and diffuse T-cell infiltration associated with disseminated Nocardiosis and pulmonary infection due to Streptomyces spp]. / Syndrome d'activation macrophagique associé à une granulomatose et une infiltration lymphocytaire T CD4 diffuse révélant une nocardiose disséminée et une infection pulmonaire à Streptomyces spp.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome frequently secondary to infectious disease, especially in immuno-compromised patients. We report a HLH secondary to disseminated nocardiosis and Streptomyces spp pulmonary infection. CASE REPORT: A 69-years-old women had recent subcutaneous nodules of the forearms and loins associated with peripheral neuropathy and pulmonary nodule of the right upper lobe. Cutaneous biopsy revealed granuloma. Cutaneous lesions worsened and the patient developed a HLH with probable cardiac and neurological involvement, associated with cutaneous granulomatosis and diffuse polyclonal lymphocyte proliferation. Nocardia PCR was positive in cutaneous biopsy. Pulmonary samples revealed Streptomyces in culture and Nocardia in PCR. The evolution under antibiotic treatment was favorable. CONCLUSION: Recent diagnosis of HLH without obvious etiology should lead to etiological investigation, including the search for infections with slow-growing bacteria such as Nocardia or Streptomyces spp.

Haemophagocytic Lymphohistiocytosis in a 16-Year-Old Boy.

Haemophagocytosis encompasses phagocytosis of erythrocytes, leukocytes, platelets and their precursors by macrophages in bone marrow and other tissues. Haemophagocytic lymphohistiocytosis (HLH) usually presents with high fever, pancytopenia, splenomegaly, lymphadenopathy, haemophagocytosis in bone marrow, liver, lymphnodes or CSF. We report coagulase negative Staphylococcus induced HLH in a 16 year old boy presenting with high grade fever, lymphadenopathy, hepatosplenomegaly, pancytopenia with neutropenic sepsis in the department of Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 28th November 2016. He responded to high dose dexamethasone and management of neutropenic sepsis. This might give a guidance in the management of haemophagocytic syndrome at the earliest time to prevent morbidity and mortality.

Hemophagocytic syndrome in patients living with HIV: a retrospective study.

Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n = 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P = 0.01). Ferritin > 5000 ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P = 0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P = 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA.

Tuberculosis-associated hemophagocytic lymphohistiocytosis with subsequent unmasking cryptococcal immune reconstitution inflammatory syndrome (IRIS) in an HIV-negative man.

A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2/kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal. After 5 months of antituberculous treatment, he developed a paralysis of the left arm. A cerebral MRT showed ring-enhanced lesions. Blood cultures and lumbar puncture revealed Cryptococcus neoformans var. grubi. The HIV test was repeatedly negative. Antituberculous treatment was continued for a total of 9 months, and additional treatment with antifungal therapy was established. He recovered fully after 14 months of antifungal treatment.

Fatal case of hemophagocytic lymphohistiocytosis associated with group B streptococcus sepsis: A case report.

RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by an excessive systemic inflammatory response. HLH is classified as primary or secondary, where the latter may occur in association with many infections. However, no case of HLH has been previously associated with group b streptococcus (GBS) sepsis. PATIENT CONCERNS: We present a fatal case of HLH in a 5-year-old girl with GBS sepsis. DIAGNOSIS: The present patient met 5 of the HLH criteria: fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hyperferritinemia. GBS was identified in 2 sets of peripheral blood bacterial cultures. INTERVENTIONS: Empirical antibiotics, inotropes, and immunoglobulins were administered. OUTCOMES: The clinical course of the patient was fulminant and the patient died of septic shock 10 hours after admission to the hospital. LESSONS: We suggest GBS infection can cause HLH and early awareness of HLH associated with GBS infection and proper effective treatment are necessary to reduce mortality.