amphotericin-b and Lymphohistiocytosis--Hemophagocytic

Hemophagocytic lymphohistiocytosis (HLH) secondary to

Topics: Amphotericin B; Antifungal Agents; Histoplasmosis; HIV Infections; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal complication of visceral leishmaniasis (VL). To provide a basis for early and correct diagnosis and to improve prognosis in the future, we describe a case series of VL-associated HLH in adults in our center in the past decade after review of all reported cases of adult VL-associated HLH in English through May 2022. In our case series, a total of 111 patients were diagnosed with VL. Among these patients, only six cases were diagnosed with VL-associated HLH. All patients tested positive for serology. Leishmania was detected for the first time by bone marrow aspiration (BMA) in three of the six patients and in the other three patients after three or four BMAs. It took more than 1 month from onset to diagnosis of VL for all the six cases, and the longest time was 6 months. Five of the six patients recovered after receiving sodium stibogluconate. VL-associated HLH is rare but potentially life-threatening in adults and predisposes to early delays in diagnosis. However, diagnostic techniques are not complicated or difficult, so it is more important to consider that it is not recognized by physicians. Although guidelines recommend liposomal amphotericin B as the most effective therapy, our experience suggests that sodium stibogluconate can be an alternative option when liposomal amphotericin B is unavailable or unaffordable.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic

We present the case of a 7-year-old boy who fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). Prompt visualization of his bone marrow confirmed the diagnosis of visceral leishmaniasis (VL). He responded well to treatment with liposomal amphotericin-B. The patient had a false-negative enzyme-linked immunosorbent assay for Leishmania infantum and a false-positive immunoglobulin M test for Epstein Barr virus (EBV). Because age at presentation is similar in children with VL and familial HLH for whom EBV is the usual trigger, ruling out VL is extremely important because nonspecific serologic tests for EBV can lead to the inappropriate diagnosis of EBV-driven primary HLH and to the administration of unnecessary immunochemotherapy.

Topics: Amphotericin B; Antifungal Agents; Child; Humans; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Prognosis

Hemophagocytic lymphohistiocytosis is a potentially fatal disorder resulting from excessive activation and non-malignant proliferation of T lymphocytes and macrophages. Neoplasms, autoimmune disorders and systemic infections can cause secondary hemophagocytic syndrome. The association of hemophagocytic syndrome and visceral leishmaniasis is rarely found in childhood. We report a case of an infant affected by hemophagocytic lymphohistiocytosis secondary to visceral leishamniasis and describe all cases of hemophagocytic syndrome associated with visceral leishamniasis in childhood reported in literature, focusing on clinical manifestation, diagnosis and treatment.

Topics: Amphotericin B; Antiprotozoal Agents; Humans; Infant; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male

The clinical features of leishmaniasis overlap with that of hemophagocytic lymphohistiocytosis (HLH) and the diagnosis of visceral leishmaniasis (VL) related HLH can be challenging.. To review information available on disease course, treatment, adjunctive therapy used and the outcomes of VL related HLH.. We describe an illustrative case and review all reported cases of VL associated HLH in the English literature till March 2007.. VL associated HLH is rare, with 56 cases reported in the English literature. Clinical features lack discriminating value to recognize VL as the inciting etiology. Bone marrow aspiration (BMA) establishes the diagnosis in 78% of cases but is often negative at onset of the syndrome due to the pauci-microbial nature of the disease and patchy involvement. Repeated marrow aspiration, liver biopsy, blood cultures and serology may be required to establish the diagnosis. Liposomal amphotericin is the drug of choice. IVIG may be considered when there is an inadequate response to anti-leishmanial therapy in severe and refractory disease.. VL related HLH is often under-recognized because of overlapping clinical features and negative marrow evaluation at onset, leading to high mortality rates.

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Immunoglobulins, Intravenous; Infant; Leishmaniasis, Visceral; Liposomes; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged

Topics: Adolescent; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Doxorubicin; Etoposide; Histoplasmosis; Humans; Immunocompetence; Lymphohistiocytosis, Hemophagocytic; Male; Mass Spectrometry; Methylprednisolone; Treatment Outcome

Visceral leishmaniasis (VL) is an endemic in Southern Europe. However, details regarding disease burden, clinical presentations, laboratory markers, management and outcome in children are scarce.. Medical records of children (<14 years) admitted with VL to 10 pediatric units in Andalusia (2004-2019) were retrospectively reviewed. VL diagnosis was based on clinical presentation, serology, microscopy and molecular methods. Diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was established using the hemophagocytic lymphohistiocytosis-2004 criteria.. A total of 127 patients were identified. Median age was 14.5 months; the main clinical presentations were fever and splenomegaly (95.3% each). Cytopenias were the most common laboratory abnormalities. Diagnostics as well as treatment regimens varied over time and the participating centers. Liposomal amphotericin B was prescribed in 97.6%; relapses as well as adverse events were rarely observed (3.1% each). Thirty-seven patients, diagnosed with sHLH required longer hospital admission (P = 0.001), an increased number of platelet (P < 0.006) and red blood cell (P = 0.0001) transfusions and pediatric intensive care unit admission (P = 0.007). Monocytopenia (P = 0.011) and high C-reactive protein levels (P = 0.031), variables not included in the hemophagocytic lymphohistiocytosis-2004 criteria, were associated with sHLH. One patient deceased in the context of the Leishmania infection.. We report data on the largest pediatric VL cohort from Europe, commonly associated with sHLH. Raised C-reactive protein levels and monocytopenia appear to be associated with sHLH. The latter may help to identify these patients and to guide decisions regarding need of additional supportive clinical care and immunomodulatory therapies. The observed high rate of heterogeneity in terms of diagnosis and management warrants the establishment of appropriate guidelines.

Topics: Amphotericin B; Antiprotozoal Agents; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Laboratories; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Retrospective Studies; Spain

Visceral leishmaniasis (VL) is a neglected tropical disease with more than 30,000 cases annually reported worldwide. In Brazil, about 3,700 cases are annually reported. The VL clinical presentation is variable, from asymptomatic to severe cases with a high risk of death. We reported three cases of VL with clinical sign similarities but distinct development. All cases had bone marrow hemophagocytosis and hemophagocytic lymphohistiocytosis (HLH) criteria. HLH is a rare condition that may have secondary causes, including infectious and parasitic diseases, like VL. The delayed recognition of the secondary HLH (sHLH) association to VL may cause unfavorable outcomes and death.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Brazil; Fatal Outcome; Female; Humans; Immunoglobulins; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Methylprednisolone; Neglected Diseases; Treatment Outcome; Young Adult

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.. 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).. 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.

Topics: Amphotericin B; Antiprotozoal Agents; Female; High-Throughput Nucleotide Sequencing; Humans; Infant; Leishmania; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic

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.

Topics: Abdominal Pain; Adult; Amphotericin B; Antifungal Agents; Biopsy; Bone Marrow; Dexamethasone; Diagnosis, Differential; Drug Therapy, Combination; Encephalitis, Viral; Etoposide; Female; Fever; Histoplasma; Histoplasmosis; Humans; Invasive Fungal Infections; Lymphohistiocytosis, Hemophagocytic; Meningitis; Nausea; Treatment Outcome

Mucormycosis is an aggressive, angioinvasive fungal infection with a predilection for the rhino-orbital cavity, predominantly in immunocompromised patients such as patients with uncontrolled diabetes. Prognosis is very poor, with a survival rate of 40% to 50%; therefore, early detection and initiation of treatment is paramount. Presenting symptoms are vague and mucormycosis is rare, so recognition, awareness, and knowledge of this infection are key to timely intervention and enhanced patient survival.

Topics: Adult; Amphotericin B; Antifungal Agents; Debridement; Dexamethasone; Diagnosis, Differential; Fluconazole; Humans; Immunocompromised Host; Immunosuppressive Agents; Interleukin 1 Receptor Antagonist Protein; Lymphohistiocytosis, Hemophagocytic; Male; Mucormycosis; Paranasal Sinuses; Prognosis; Sinusitis; Therapeutic Irrigation; Tomography, X-Ray Computed

A 62-year old British Caucasian woman normally resident in Spain presented with fever and pancytopaenia after returning to the UK. Her symptoms persisted despite broad-spectrum antibiotics, and she gradually became confused, hypotensive and progressively more pancytopaenic. Imaging demonstrated hepatosplenomegaly, and a bone marrow aspirate confirmed a diagnosis of haemophagocytic lymphohistiocytosis (HLH). Bone marrow polymerase chain reaction (PCR) and blood serology were both positive for Leishmania donovani, consistent with visceral leishmaniasis (VL). Following treatment with dexamethasone and amphotericin, she improved clinically and biochemically, and was able to return to Spain. Fever in the returning traveller is a common acute medical presentation. Although HLH and VL are rare diagnoses, both carry a very high mortality rate if undiagnosed and untreated.

Topics: Amphotericin B; England; Female; Fever; Humans; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Spain; Travel

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

Topics: Amphotericin B; Antiprotozoal Agents; Diagnosis, Differential; Fever of Unknown Origin; Humans; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Pancytopenia; Splenomegaly; Treatment Outcome; Weight Loss

Topics: Adolescent; Amphotericin B; Antigens, Fungal; Antiviral Agents; Biopsy; Bone Marrow; Cytomegalovirus; Cytomegalovirus Infections; Female; Fever of Unknown Origin; Graft Rejection; Histoplasma; Histoplasmosis; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lymphohistiocytosis, Hemophagocytic; Mycophenolic Acid; Renal Dialysis; Treatment Outcome; Viral Load

We describe a Venezuelan visitor to Japan who was diagnosed with hemophagocytic lymphohistiocytosis (HLH). The patient was also diagnosed with human immunodeficiency virus (HIV) and Epstein-Barr virus infection by the Western blot and polymerase chain reaction (PCR) tests, respectively. The cause of HLH was considered to be these two infections at first; however, the patient did not recover with antiretroviral/anti-herpes virus therapy. Thereafter, diagnosis of disseminated histoplasmosis was confirmed with an antigen detection test, culture, and PCR test of blood, urine, and bone marrow, and the patient improved gradually after the initiation of liposomal amphotericin B. This case highlights the importance of ruling out endemic mycosis as a cause of HLH even if other probable causes exist in patients from endemic areas.

Topics: Amphotericin B; Antiviral Agents; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Histoplasma; Histoplasmosis; HIV; HIV Infections; Humans; Japan; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Travel; Venezuela

A 27-year-old man presented with high-grade intermittent fever for 4 months, generalised fatigue for 2 months, intermittent gum bleeds for 1 month and loss of weight of 15 kg. He appeared cachectic with generalised wasting, had pallor and features of reticuloendothelial system proliferation. His liver span was 17 cm. He had massive splenomegaly. His cardiovascular, respiratory and neurological examination were normal. He was diagnosed to have visceral leishmaniasis (VL) based on bone marrow (BM) examination that showed Leishmania donovani (LD) bodies and was treated with liposomal amphotericin (LA). During the course of therapy, he developed bleeding from various mucosal and venepuncture sites. His further evaluation, which included a repeat BM aspirate, showed haemophagocytes. Final diagnosis made was VL with secondary haemophagocytic lymphohistiocytosis. He was continued on LA with intravenous hydrocortisone. He developed refractory distributive shock with multiorgan dysfunction and succumbed to his illness.

Topics: Administration, Intravenous; Adult; Amphotericin B; Bone Marrow Examination; Fever; Humans; Hydrocortisone; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male

Histoplasmosis is an endemic mycosis with global distribution, primarily reported in immunocompromised individuals. A 29-year old immunocompetent male presented with fever, hepatosplenomegaly and pancytopenia. His peripheral blood showed features suggestive of intravascular hemolysis and echocardiography showed features suggestive of pulmonary arterial hypertension. Bone marrow showed yeast with morphology suggestive of

Topics: Adult; Amphotericin B; Antifungal Agents; Fever; Heart Failure; Hemolysis; Hepatomegaly; Histoplasmosis; Humans; Immunocompetence; Itraconazole; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia; Splenomegaly

A 4-month-old male infant presented acutely unwell with fever. He was initially treated for sepsis but failed to improve with IV broad spectrum antibiotics. Haemophagocytic lymphohistiocytosis (HLH) was diagnosed due to his fever, pancytopenia, splenomegaly, hypertriglyceridaemia, hypofibrinogenaemia and significant hyperferritinaemia. An array of differentials for HLH including both immunological and infectious causes were considered and excluded. He had travelled to Madrid, and hence visceral leishmaniasis (VL) was suspected, but was not confirmed on the initial bone marrow aspirate (BMA) microscopy or culture. He improved with empirical treatment with dexamethasone and liposomal amphotericin B. VL was later confirmed on BMA PCR. He made a good recovery and remained well at 12 month follow-up. Non-endemic countries need rapid and sensitive VL diagnostics. A thorough travel history and high clinical index of suspicion are necessary to avoid the pitfall of treatment with intense immunosuppression recommended in treatment guidelines for HLH.

Topics: Amphotericin B; Antiprotozoal Agents; Dexamethasone; Fever; Glucocorticoids; Humans; Infant; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Polymerase Chain Reaction; Spain; Travel; United Kingdom

In this case report, we describe a rare manifestation of amphotericin B (AMB) toxicity. A case of fever, hepato-splenomegaly and pancytopenia was diagnosed, based on serological test and demographic profile, as visceral leishmaniasis complicated with secondary haemophagocytic lymphohistiocytosis. He was managed with conventional AMB. Subsequently, patient was showing subjective and objective improvement. Suddenly after receiving 450 mg of cumulative dose of AMB, patient developed hearing loss. On evaluation, he was found to have bilateral mixed hearing loss. Patient was investigated for the causes of hearing loss. When nothing could be attributed as an aetiology, AMB was stopped (after 500 mg cumulative dose). After missing the dose of AMB, patient had a dramatic improvement in his sense of hearing, which was confirmed objectively by audiometry before and after the event.

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Ototoxicity

A 46-year-old Dominican man, known to have HIV, presented with constitutional symptoms of two week's duration. The patient was found to have cytopenias, significantly elevated ferritin level and lymphadenopathy. Biopsies and laboratory studies met the criteria for hemophagocytic lymphohistiocytosis (HLH). A concomitant diagnosis of histoplasmosis was confirmed as the trigger for HLH and treatment resulted in clinical improvement and resolution of symptoms.

Topics: Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Histoplasmosis; HIV Seropositivity; Humans; Itraconazole; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Treatment Outcome

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.

Topics: Amphotericin B; Antiprotozoal Agents; Fever; Humans; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Travel-Related Illness; Young Adult

Leishmaniasis is endemic in many countries worldwide, with a prevalence of 12 million people infected, and an estimated annual incidence of 500 000 visceral leishmaniasis cases. In Europe visceral leishmaniasis is considered endemic mainly in the Mediterranean countries and cases in non-endemic European countries north of the Alps have primarily been reported in returning travellers. The incubation period is typically described between 6 weeks to 6 months. The cases presented highlight the occurrence of longer incubation periods and illustrate the individual variability for progression from infection to disease.. We report the cases of 18-months-old twin girls living at the German-Swiss border, who developed visceral leishmaniasis 7 and 15 months after travelling to Tuscany. They presented with fever of unknown origin and pancytopenia. Both had splenomegaly and in the first case haemophagocytic lymphohistiocytosis or leukaemia was initially included in the differential diagnosis. Diagnosis of visceral leishmaniasis was confirmed by presence of intracytoplasmic localised leishmania parasites on bone marrow aspirate and/or positive leishmania serology. Both girls responded well to treatment with liposomal amphotericin B. The mother and two older siblings remained uninfected, while the father was diagnosed to be an asymptomatic carrier.. Visceral leishmaniasis is an important differential diagnosis for fever of unknown origin and pancytopenia in young children living in countries with endemic disease and highlights the importance of obtaining a detailed travel history. Hemophagocytic lymphohistiocytosis and acute leukaemia present with similar symptoms and consequently are important differential diagnoses. Factors determining progression from infection to disease are not fully understood but younger age seems to be an important risk factor. Screening of siblings from affected individuals therefore may be warranted.

Topics: Amphotericin B; Antiprotozoal Agents; Diagnosis, Differential; Diseases in Twins; Endemic Diseases; Female; Fever; Humans; Infant; Italy; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia; Splenomegaly; Travel

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Fever; Humans; Itraconazole; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia; Splenomegaly

Topics: Adolescent; Amphotericin B; Antiparasitic Agents; Bone Marrow; Dexamethasone; Glucocorticoids; Humans; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male

Haemophagocytic lymphohistiocytosis is an uncommon syndrome that results from an uncontrolled activation of macrophages and lymphocytes resulting in the compromise of multiple organs that is potentially fatal without timely treatment. It can be hereditary or a secondary result of infectious processes, neoplasms or autoimmune conditions. We present the case of a patient with HIV/AIDS who developed hemophagocytic lymphohistiocytosis as well as disseminated intravascular coagulation associated with histoplasmosis and who was successfully treated with amphotericin B, steroids and transitory dialytic support.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Disseminated Intravascular Coagulation; Histoplasmosis; Humans; Lymphohistiocytosis, Hemophagocytic

Topics: Adolescent; Amphotericin B; Antifungal Agents; Bone Marrow; Diagnosis, Differential; Fever of Unknown Origin; Fungemia; Histoplasma; Histoplasmosis; Humans; Infusions, Intravenous; Kidney Transplantation; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia; Transplant Recipients

Visceral leishmaniasis (VL) is re-emerging in endemic areas. The epidemiological, clinical, laboratory, and treatment outcome characteristics in a large cohort of VL patients is described herein.. The cases of 67 VL patients (57% male, mean age 56 years) treated in two Greek hospitals over the last 7 years were identified and evaluated retrospectively.. Forty-six percent of patients reported contact with animals. Seventeen patients (25%) were immunocompromised, and 22% were co-infected with another pathogen. Sixty-four percent of patients had fever, 57% had weakness, 37% had sweats, 21% had weight loss, and 13% had a dry cough, while 6% developed haemophagocytic syndrome. The median duration of symptoms was 28 days. Fifty-eight percent of patients had splenomegaly, 49% had hepatomegaly, and 36% had lymphadenopathy. The diagnosis was established by positive PCR in peripheral blood (73%) and/or bone marrow specimens (34%). Sixty-one patients (91%) received liposomal amphotericin (L-AMB). Six patients (10%) did not respond or relapsed but were eventually cured after a second cycle of L-AMB. During a 6-month follow-up, the overall mortality was 9%, although none of these deaths was attributed to VL.. VL is still a common disease in endemic areas, affecting immunocompetent and immunocompromised patients. Its diagnosis is challenging, and molecular techniques are valuable and helpful tools to achieve this. Treatment with L-AMB is safe and very effective.

Topics: Adolescent; Adult; Amphotericin B; Animals; Antiprotozoal Agents; Bone Marrow; Coinfection; Communicable Diseases, Emerging; Female; Fever; Greece; Hepatomegaly; Hospitals; Humans; Immunocompromised Host; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Splenomegaly; Treatment Outcome; Young Adult

Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immunocompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue.. Hemofagositik lenfohistiositoz (HLH) uzamış ateş, sitopeni, hepatosplenomegali semptomları ile seyreden, active olmuş, morfolojik olarak benign makrofaj ve doğal öldürücü hücreler ile sitotosik T lenfosit fonksiyon bozukluğu sonucu gelişen hiperenflamatuvar bir durumdur. İki aylık düşmeyen ateş yakınması ile başvuran hasta HLH tanısı aldı ve hastanın genetik incelemesinde UNC13D (c.175G>C; p.Ala59Pro) geninde yeni tanımlanan bir mutasyon saptandı. Hastaya deksamatazon, etopozit ve intratekal metotreksat tedavileri başlandı. Tedavinin 2. haftasında, üç doz etopozit aldıktan sonra, yumuşak damakta plak lezyonu fark edildi ve bu nekrotik lezyon debride edildi. Debridman materyalinin patolojik incelemesinin PAS, Grocott boyamasında aspergilloz enfeksiyonu ile uyumlu olarak çok sayıda septalı hif görüldü. Etopozid tedavisi sonlandırılarak altı hafta boyunca amphotericin B tedavisi verildi. HLH 2004 tedavi protokolü oral siklosporin ile sekiz haftaya tamamlandı. HLH tedavisi sırasında yumuşak damak perforasyonuna neden olacak kadar ağır aspergilloz enfeksiyonu geçiren bir olgu bildirilmemiştir. İmmünyetmezlikli hastada mantar enfeksiyonları nazal septum perforasyonuna neden olabilmektedir ve tedavi nekrotik dokunun debridmanı ve antifungal tedavi ile sağlanabilmektedir.

Topics: Amino Acid Substitution; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Combined Modality Therapy; Cyclosporine; Debridement; Dexamethasone; Drug Therapy, Combination; Etoposide; Female; Humans; Immunocompromised Host; Infant; Lymphohistiocytosis, Hemophagocytic; Membrane Proteins; Methotrexate; Mutation, Missense; Nasal Septal Perforation; Opportunistic Infections; Palate, Soft; Point Mutation; Stomatitis

A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.

Topics: Adult; Amphotericin B; Antifungal Agents; Cyclosporine; Dexamethasone; Face; Fasciitis, Necrotizing; Humans; Immune Tolerance; Lymphohistiocytosis, Hemophagocytic; Male; Mycoses; Paecilomyces; Pseudomonas aeruginosa; Pseudomonas Infections; Skin Ulcer; Surgical Stomas; Tracheotomy; Treatment Outcome

To describe characteristics of visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis (HLH) with focus on diagnostic clues and pitfalls, including the frequency of central nervous system (CNS) involvement, and to determine the efficacy of liposomal amphotericin B (L-AmB).. We retrospectively analyzed clinical and laboratory features, diagnostic procedures, and treatment of 13 patients with HLH with imported visceral leishmaniasis, reported to the German HLH reference center (1999-2012).. The spectrum of presentations was indistinguishable from patients with hereditary HLH or with acquired HLH because of infections with other pathogens. In 8 patients, disease onset occurred before the age of 2 years, coinciding with the typical age of manifestation of primary HLH. Two patients had mild nonspecific CNS findings. Misleading antiviral IgM (n = 6) and autoantibodies (n = 2) led to inaccurate interpretation of the etiology of HLH, sometimes with inappropriate therapeutic consequences. False negative results for Leishmania were obtained by initial bone marrow microscopy in 6/13, serology in 1/12, bone marrow culture in 2/5, and polymerase chain reaction of peripheral blood in 1/3 patients, and all bone marrow samples tested were Leishmania-positive by polymerase chain reaction (n = 7). L-AmB was administered to 12 patients, 5 of whom had no prior HLH-directed immunosuppressive therapy; sodium stibogluconate was administered to 1 patient. Persistent remission was achieved in 11 cases. Two patients required repeated or prolonged L-AmB therapy.. Awareness of diagnostic pitfalls may save patients from unnecessary toxic treatment. CNS involvement is rare. L-AmB shows efficacy in visceral leishmaniasis-associated HLH.

Topics: Amphotericin B; Antibodies, Protozoan; Antiprotozoal Agents; Autoantibodies; Bone Marrow; Child; Child, Preschool; DNA, Protozoan; Female; Humans; Infant; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Polymerase Chain Reaction; Retrospective Studies; Treatment Outcome

Zygomycosis is an opportunistic infection generally found in immunocompromised individuals. Herein we present a pediatric patient with primary cutaneous mucormycosis that developed at a site of trauma. Diagnosis and treatment are discussed.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Catheters, Indwelling; Child; Dermis; Female; Humans; Immunocompromised Host; Lymphohistiocytosis, Hemophagocytic; Myelodysplastic Syndromes; Opportunistic Infections; Remission Induction; Zygomycosis

Hemophagocytic lymphohistiocytosis (HLH) associated with visceral leishmaniasis (VL) is a very rare phenomenon. We report the first known North American case in a 21 month old boy. He was initially diagnosed with Epstein Barr virus (EBV) triggered HLH and treated with the international treatment protocol, HLH-2004. Stem cell transplant was planned due to repeated reactivations of disease, but his pretransplant bone marrow revealed an unexpected protozoan-Leishmania donovani. Treatment with liposomal amphotericin B led to resolution of all manifestations of HLH. We discuss how the clinical and laboratory features of both entities can closely mimic each other and are extremely difficult to differentiate. This case also raises the question of whether to screen all children with suspected HLH for Leishmania in a non endemic area.

Topics: Amphotericin B; Antiprotozoal Agents; Humans; Infant; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Treatment Outcome

Pancytopenia, fever and splenomegaly are frequent causes for referrals to paediatric haematology departments, on the suspicion of acute leukaemia. We report two cases of Danish children with the tropical disease visceral leishmaniasis (VL) contracted on short vacations in Southern Europe. One of the patients developed secondary haemophagocytic lymphohistocytosis (HLH). Both children were successfully treated with liposomal amphotericin B. In Denmark, VL is a rare but important differential diagnosis to acute leukaemia and HLH, and should be ruled out after journeys to endemic areas, including Southern Europe.

Topics: Amphotericin B; Antiprotozoal Agents; Child, Preschool; Female; France; Herpesvirus 4, Human; Humans; Italy; Leishmania infantum; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Treatment Outcome

Infantile visceral leishmaniasis associated hemophagocytic lymphohistiocytosis (HLH) is a rare clinicopathological entity, difficult to diagnose and fatal if untreated. The diagnosis should be considered in young infants with fever and splenomegaly. We report two cases of HLH caused by visceral leishmaniasis. In the first case, a 3-month-old boy was admitted with fever and pancytopenia, leading to the diagnosis of HLH based on complete clinical and biological features including hemophagocytosis on bone marrow smears. Investigations for an underlying genetic, metabolic disease and an infectious trigger were negative. Primary or genetic hemophagocytic syndrome was suspected and immunosuppressive treatment (steroids and cyclosporin) was instituted. A second bone marrow examination performed 1 month later revealed leishmania. The boy was treated with liposomal amphotericin and recovered rapidly. In the second case, a 10-year-old child was hospitalized with fever, pancytopenia, and a tumoral syndrome. He had a history of recurrent infections. The bone marrow biopsy showed leishmania and treatment with liposomal amphotericin was delivered. After 3 days of treatment, the improvement was judged inadequate and the boy presented biological signs of HLH. He was treated with steroids. An underlying primary immunodeficiency (interleukin-12/interferon-γ axis disorder) was secondarily diagnosed.

Topics: Amphotericin B; Antiprotozoal Agents; Child; Cyclosporine; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia

We describe a case of hemophagocytic lymphohistiocytosis related to visceral leishmaniasis in late adulthood. Because clinical features of visceral leishmaniasis can mimic those of hemophagocytic lymphohistiocytosis, diagnosing leishmaniasis as the underlying etiology can be quite challenging. In our case, treatment with amphotericin B resulted in a dramatic resolution of clinical abnormalities.

Topics: Aged; Amphotericin B; Anti-Inflammatory Agents; Antiprotozoal Agents; Dexamethasone; Disseminated Intravascular Coagulation; Hepatomegaly; Humans; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Splenomegaly

We present a case of a 4.5-month-old boy from Turkey with hemophagocytic lymphohistiocytosis (HLH) associated with H1N1 virus and Leishmania spp. coinfection. Because visceral leishmaniasis can mimic hematologic disorders like HLH, it is important to rule out this clinical condition before starting immunosuppressive therapy. In our case, treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities.

Topics: Amphotericin B; Antiprotozoal Agents; Child, Preschool; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male

A 15 month-old girl was admitted after a couple of months' history of illness with remittent fever, increasing pallor and a swollen abdomen. On admission she was highly febrile, with palpably enlarged liver and spleen. Blood tests revealed pancytopenia, a high CRP level and a high serum ferritin level. We describe the diagnostic evaluation, interpretation and treatment.

Topics: Amphotericin B; Antiprotozoal Agents; Bone Marrow; Diagnosis, Differential; Female; Fever; Humans; Infant; Insect Bites and Stings; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Mediterranean Region; Pancytopenia; Travel

Topics: Adalimumab; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Bone Marrow Examination; Histoplasmosis; Humans; Immunocompromised Host; Immunosuppressive Agents; Lymphohistiocytosis, Hemophagocytic; Male; Still's Disease, Adult-Onset; Tumor Necrosis Factor-alpha; Young Adult

Topics: Amphotericin B; Antiprotozoal Agents; Diagnosis, Differential; Female; Humans; Infusions, Intravenous; Leishmania infantum; Leishmaniasis, Visceral; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Splenectomy

Topics: Adrenal Cortex Hormones; Amphotericin B; Animals; Communicable Diseases; Cyclosporine; Diagnosis, Differential; Female; Fever; Hepatomegaly; Humans; Immunosuppressive Agents; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Lymphohistiocytosis, Hemophagocytic; Macrophages; Middle Aged; Neoplasms; Opportunistic Infections; Pancytopenia; Polymerase Chain Reaction; Splenomegaly

Visceral leishmaniasis is a severe form of infection caused by a parasite endemic along the Mediterranean coast. Complications such as infection-associated hemophagocytic syndrome can occur despite correct therapy. We report visceral leishmaniasis-associated infection-associated hemophagocytic syndrome in 3 patients with chronic granulomatous disease.

Topics: Adolescent; Amphotericin B; Animals; Antiprotozoal Agents; Child; Fatal Outcome; Female; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Recombinant Proteins

Haemophagocytic syndrome is a disease diagnosed according to clinical and analytical criteria, related to many infectious diseases. It is exceptionally described in patients infected with Leishmania. Visceral leishmaniasis is an uncommon disease in our country except in some areas where it is endemic. Its diagnosis is sometimes difficult and the use of other methods currently available is needed. Haemophagocytic syndrome treatment is based on established chemotherapy protocols, but when it is secondary to Visceral Leishmaniasis, it may be an exception, since the abnormalities can be resolved by treatment of the infection itself. This treatment has improved recently as Liposomal Amphotericin B has replaced classic antimonials, being more beneficial due to less adverse effects and a shorter treatment time.

Topics: Amphotericin B; Anti-Bacterial Agents; Female; Humans; Infant; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic

We present a case of a 9-month-old girl from Cyprus with hemophagocytic lymphohistiocytosis associated with Epstein Barr virus and Leishmania donovani coinfection. Treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities. To our knowledge, this is the first reported case of a coinfection-associated hemophagocytic lymphohistiocytosis and the first clinical report of visceral leishmaniasis infection in Europe by L. donovani.

Topics: Amphotericin B; Animals; Cyprus; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Infant; Leishmania donovani; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic

The following case illustrates an ileal perforation and reactive hemophagocytic syndrome (RHS) resulting from disseminated histoplasmosis in a patient with Human Immunodeficiency Virus (HIV) from Puerto Rico. Although the diagnosis was established by histopathologic findings and a positive bone marrow culture, Histoplasma capsulatum-specific real-time Polymerase Chain Reaction (PCR) allowed to confirm the diagnosis from formalin-fixed, paraffin-embedded tissue. Interestingly, the Histoplasma antigens in both serum and urine samples were falsely negative. Amphotericin B lipid complex (Abelcet), followed by oral itraconazole, led to a successful response and resolution of symptoms. A short review of the clinical signs and symptoms, diagnostic tests, and therapeutic options for disseminated histoplasmosis is done, with emphasis on the role of Histoplasma-specific real-time PCR as a molecular diagnostic tool and the efficacy of treatment with one of the lipid formulations of amphotericin B.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Combinations; Histoplasma; Histoplasmosis; HIV Infections; HIV-1; Humans; Ileum; Intestinal Perforation; Lymphohistiocytosis, Hemophagocytic; Male; Phosphatidylcholines; Phosphatidylglycerols; Puerto Rico; Treatment Outcome

Visceral leishmaniasis (VL), is a systemic disease caused by the dissemination of protozoan parasite Leishmania throughout the reticuloendothelial system. It may mimic or lead to several types of hematological disorders including hemophagocytosis. Infection associated hemophagocytic syndrome implicating Leishmania is very rare and often difficult to diagnose. Here, we describe a child with hemophagocytic lymphohistiocytosis (HLH) associated with VL.

Topics: Amphotericin B; Antiprotozoal Agents; Child, Preschool; Humans; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia