Dengue and Plasmodium falciparum Coinfection With Secondary Hemophagocytic Lymphohistiocytosis in a 3-Year-old Boy: A Clinical Conundrum.

Hemophagocytic lymphohistiocytosis (HLH) is a multisystem disease wherein there is an exaggerated immune system activation following a trigger such as infection, malignancy, or autoimmune diseases. Here we report a case of a 3-year-old boy who presented to us with fever, was diagnosed with dengue fever, and treatment started for the same. Clinical response was poor to treatment and high-grade fever persisted. Subsequent evaluation showed Plasmodium falciparum malaria and treatment was initiated with antimalarial drugs. Further clinical deterioration with poor trend of laboratory values over the next few days prompted evaluation for HLH; workup was positive satisfying the HLH-2004 criteria and IV dexamethasone was started. The child gradually improved and was discharged with normal counts on follow-up over the next 3 months. This article emphasizes on the importance of high degree of suspicion, early workup, and initiation of treatment for HLH for a better outcome.

Clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis induced by Leishmania infantum infection.

BACKGROUND: Visceral leishmaniasis (VL) could progress to secondary hemophagocytic lymphohistiocytosis (HLH), which is a rare but life-threatening condition with poor prognosis. So far, the clinical and laboratory characteristics of VL associated HLH have not been well elucidated. METHOD AND FINDINGS: In this study, we retrospectively analyzed the clinical and laboratory profiles between 17 patients with VL associated HLH and 27 patients with VL alone admitted at the Beijing Friendship Hospital, Capital Medical University from May 2016 to March 2021. In addition to the identification of Leishmania infection, hemophagocytosis was identified in bone marrow in the most cases of VL associated HLH (15/17). The patients with VL associated HLH had higher chances of bleeding, hepatomegaly, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, hypofibrinogenemia, elevated secretion of soluble IL-2 receptor or lower NK cell activity compared to patients with VL only. Furthermore, patients with VL associated HLH had higher inflammation status associated with higher levels of Th1 (TNF-α, IFN-γ, IL-1beta, IL-6, IL-8, IL-12p70), Th2 (IL-4) and Th17 cytokines (IL-17, IL-23) in the peripheral blood, and higher parasite load (qPCR and parasite culture). All 27 VL cases were totally recovered after being treated with Sodium Stibogluconate, five of the 17 patients with VL associated HLH died even after timely treatment with anti-parasite and immunosuppressive chemotherapy. CONCLUSION: Without appropriate treatment, visceral leishmaniosis could develop to secondary HLH. The parasite culturing and qPCR detection of bone marrow samples facilitates the diagnosis of VL associated HLH in addition to other findings of HLH. Prompt treatment with anti-Leishmania and immunosuppressive chemotherapy is critical to reduce the mortality of VL associated HLH.

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation. We aimed to describe the clinical and laboratory findings of HLH patients secondary to Visceral leishmaniasis (VL) and their treatment outcome during a 4-year follow-up period compared to primary HLH. METHOD: Forty children with primary HLH confirmed by genetic study and 20 children with HLH secondary to VL confirmed by a blood or bone marrow polymerase chain reaction from 2014 to 2018 in Shiraz, Fars province, Southern Iran, were enrolled. RESULTS: The median age at diagnosis was 11.5 months (range 1-170), and 56.7% were male. Fever and splenomegaly were the most frequent clinical presentations. 93.3% of the subjects had an HScore > 169, which had a good correlation with HLH-2004 criteria (r = 0.371, P = 0.004). Patients with primary HLH experienced more thrombocytopenia (P = 0.012) and higher alanine transaminase (P = 0.016), while patients with VL-associated HLH had higher ferritin (P = 0.034) and erythrocyte sedimentation rate (P = 0.011). Central nervous system (CNS) involvement occurred in 38.3% of patients. The mortality rate was higher in patients with CNS disease (61% vs. 35%, P = 0.051). The 3-yr overall survival rate was 35.9%. (24% in primary HLH and 100% in VL-associated HLH, P < 0.001). In Cox regression analysis, platelet count < 100,000/ µ l (hazard ratio 4.472, 95% confidence interval 1.324-15.107, P = 0.016) correlated with increased mortality in patients with primary HLH. CONCLUSION: VL is a potential source of secondary HLH in regions with high endemicity. Treatment of the underlying disease in VL-associated HLH is sufficient in most cases, with no need to start etoposide-based chemotherapy.

Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?

We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.

A case of pediatric visceral leishmaniasis-related hemophagocytic lymphohistiocytosis diagnosed by mNGS.

BACKGROUND: Visceral leishmaniasis-related hemophagocytic lymphohistiocytosis (VL-HLH) is a secondary hemophagocytic syndrome, which can be life-threatening, caused by leishmania and transmitted by infected sandflies. Rapid and accurate identification of leishmania is crucial for clinical strategies. CASE REPORT: Here, we report an infantile infection in a non-epidemic area of China. The infant was a 9.5-month-old girl with fever, pancytopenia and hepatosplenomegaly, which meet the HLH-2004 standard, and the negative gene results exclude congenital HLH. However, chemotherapy is ineffective and is accompanied by severe infection. Fortunately, she is diagnosed with VL-HLH (visceral leishmaniasis-related hemophagocytic lymphohistiocytosis), as leishmania is detected by next-generation meta-genome sequencing (mNGS) and quickly relieved after treatment with libosomal amphotericin B (L-AMB). CONCLUSION: mNGS can detect leishmania in pediatric HLH, and should be performed as a new detection for VL-HLH, particularly for infants, who may not respond to HLH-2004 regimen.

Síndrome hemofagocítico por Leishmania en paciente con síndrome poliglandular / Hemofagoctic sindrome by Leishmania in patient with poliglandular sindrome

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Toxoplasma-induced hemophagocytic lymphohistiocytosis after haploidentical allogeneic stem cell transplantation.

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune regulation, manifested by fever, pancytopenia, hyperferritiniemia, hypertriglyceridemia, and extensive hemophagocytosis involving the bone marrow and spleen. HLH can occur in adults with an underlying hematopoietic malignancy, or with systemic infections. HLH following hematopoietic stem cell transplantation (HSCT) is unusual, and the diagnosis may be challenging particularly because the diagnostic criteria in the HLH-2004 guidelines overlap with common post-transplant complications such as engraftment syndrome, graft-vs-host disease, and infections. HLH is commonly triggered by viral, bacterial and, less commonly, parasitic infections. Following HSCT, patients with latent Toxoplasma infection may develop systemic disease secondary to reactivation, and rarely this may lead to a HLH physiology, with a very high mortality rate. Herein we describe the successful management of disseminated toxoplasmosis associated with life-threatening HLH using tocilizumab and antimicrobial therapy.

Visceral leishmaniasis presenting as haemophagocytic lymphohistiocytosis.

A 53-year-old man presented with a number of hospital admissions for investigation of fever of unknown origin. He became gradually weaker with significant weight loss, pancytopenia and progressive splenomegaly over a 6-month period of extensive investigation. This was undertaken at different NHS hospitals with involvement of multiple medical specialists. Clinical criteria for haemophagocytic lymphohistiocytosis were met. Following investigation, this was felt likely secondary to a low-grade lymphoma of the spleen, necessitating splenectomy for diagnostic and therapeutic purposes. Ultimately, this risky surgical procedure was avoided when positive L eishmania serology led to successful treatment with amphotericin B.

Fever in a returning traveller: visceral leishmaniasis triggering haemophagocytic lymphohistiocytosis.

We present the case of a 23-year-old student admitted with fever, night sweats and splenomegaly. These non-specific signs and symptoms posed a diagnostic challenge which was further complicated by a history of recent foreign travel. The range of potential diagnoses required a variety of investigations in order to reach the final diagnosis. The incidental finding of an incompetent bicuspid aortic valve and an inflamed gallbladder further clouded the diagnostic process. Despite treatment with broad spectrum antibiotics, the patient continued to deteriorate. Serological testing finally provided a diagnosis of visceral leishmaniasis. The patient subsequently developed haemophagocytic lymphohistiocytosis, a life-threatening immune hyperactivity state that very rarely complicates leishmaniasis infection. With the use of amphotericin B and high-dose steroids, the patient made an excellent recovery.

Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis.

This is the report of a 2-year-old boy who presented with fever, cytopenia, and splenomegaly. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) and treated with HLH-2004 protocol. Repeated bone marrow aspiration showed amastigotes on follow-up. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis to avoid chemotherapy toxicity.

Plasmodium falciparum infection transmitted by transfusion: A cause of hemophagocytic syndrome after bone marrow tranplantation in a non-endemic country.

A 27-year-old man with severe aplastic anemia underwent bone marrow transplantation from his HLA identical brother in July 2016. Conditioning included ATGAM 30 mg/kg for 3 days and Cyclophosphamide 50 mg/kg for 4 days. The patient received several platelet and red blood cell transfusions before and after the conditioning. The patient received broad spectrum antibiotics and caspofungin because persistant febrile neutropenia without bacteriological or mycological documentation. Hemophagocytic syndrome was diagnosed on day +12. Steroids at 1 mg/kg were started on day +12. Fever resolved the same day but resumed 3 days later associated to intravascular hemolysis with no schizocytes on blood smears and negative DAT. Thick blood film smears performed on day +26 revealed Plasmodium falciparum parasites (parasitemia = 20%). Except the level of parasitemia, there were no signs of gravity. Quinine was started on day 26 at a loading dose of 15 mg/kg followed by 8 mg/kg three times a day for 20 doses. Fever vanished after 2 days. Parasitemia cleared in 3 days and remained negative thereafter. Investigations revealed that the patient was transfused by a red cell unit harvested in a voluntary donor native of a malaria endemic country. PCR for P. falciparum performed in this donor in the frame of investigations was positive. The patient is alive with a normal blood count 1 year after BMT.

Childhood Visceral Leishmaniasis: Distinctive Features and Diagnosis of a Re-emerging Disease. An 11-year Experience From a Tertiary Referral Center in Athens, Greece.

BACKGROUND: Visceral leishmaniasis (VL) remains a public health issue in Greece. The aim of this study was to describe the clinical and epidemiologic characteristics of pediatric VL in our region as well as to evaluate the laboratory findings and the diagnostic techniques that are applied. METHODS: We retrospectively reviewed the medical records of all children diagnosed with VL in an 11-year period at a tertiary public hospital in the region of Athens. Demographic features, clinical information and laboratory findings were accessed. RESULTS: A total of 43 cases were recorded during 2005-2015. Median age of the patients was 3.7 years. Pallor (100%), fever (98%), hepatosplenomegaly (55.8%) and appetite loss (32.6%) were the most common presentations of the disease. The predominant laboratory abnormalities were anemia (100%), thrombocytopenia (90.7%), elevated inflammatory markers (86.1%) and decreased albumin/globulin (A/G) ratio (72.1%). Four patients developed secondary hemophagocytic lymphohistiocytosis syndrome, whereas in 3 others abdominal ultrasound showed splenic nodules. Bone marrow aspiration detected Leishmania parasites in 92.7% of cases and the rapid rK39 strip test indicated anti-Leishmania antibodies in 97.1% of children. In addition, all patients in whom indirect immunofluorescent antibody test was implemented had positive results. CONCLUSIONS: VL still affects children in our area. Fever, splenomegaly, anemia and appetite loss are the typical findings in children. Noninvasive techniques (immunofluorescent antibody test, rK39) in combination with bone marrow microscopy are useful in the diagnosis of pediatric VL.

Haemophagocytic lymphohistiocytosis (HLH): a rare but potentially fatal association with Plasmodium vivax malaria.

Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome that is caused by an abnormal activation of the immune system. It can present as the primary syndrome or occur secondary to a variety of conditions such as malignancy, autoimmune diseases and infections. We present a case of a man who developed HLH secondary to Plasmodium vivax infection. He presented with symptoms of fever, chills and myalgias. Physical examination revealed significant hepatosplenomegaly. The presence of pancytopaenia, elevated ferritin levels and haemophagocytosis on bone marrow biopsy confirmed the diagnosis of HLH (based on HLH-2004 criteria). There was a significant improvement after the initiation of intravenous antimalarials. No relapses were documented on follow-up. It is imperative that physicians should promptly recognise and treat this rare condition, as a timely intervention can be lifesaving.