Disseminated histoplasmosis in infants

BACKGROUND: Disseminated histoplasmosis usually occurs in immunocompromised patients who reside in Histoplasma capsulatum-endemic regions. It has also been described in immunocompetent infants after exposure to a large inoculum of the pathogen resulting in case fatality rates of 40 to 50%. METHODS: From 1983 through 1996 all infants with documented disseminated histoplasmosis were treated with amphotericin B followed by daily ketoconazole for 3 months. Immunologic workups were performed at the time of diagnosis and at 4 to 6 weeks of therapy. Surviving patients were followed for at least 1 year. Time to resolution of signs and symptoms was recorded, as were complications. RESULTS: We managed 40 patients with disseminated histoplasmosis. The age in months at diagnosis was 15.3+/-10.2 (mean +/- SD), and 24 were male. All patients were from endemic regions and they presented with fever, spleen and/or liver enlargement and hematologic abnormalities. Diagnosis was made by histology and culture of bone marrow, spleen, lymph node, bronchoalveolar or liver samples. Twenty patients presented with T cell deficiency that resolved at 4 to 6 weeks of therapy in all of the retested patients, and 10 of 12 tested patients had hyperglobulinemia that resolved. Thirty-five (88%) patients were cured by treatment; 4 died and 1 relapsed. CONCLUSIONS: Disseminated histoplasmosis should be considered in infants from endemic areas who present with fever, hepatosplenomegaly and hematologic abnormalities. These patients develop transient hyperglobulinemia and T cell deficiency that resolve with treatment. Treatment with amphotericin B followed by an oral azole for 3 months is effective in most patients.     

Disseminated histoplasmosis in an adopted infant from El Salvador

An HIV-negative 4-month-old infant recently adopted from El Salvador was admitted for high fever. Hepatosplenomegaly, anaemia, leucopenia, thrombocytopenia, increased transaminases, and diffuse interstitial pulmonary infiltration were present on admission. Granulomas were seen in bone marrow and liver biopsies without any organism. Disseminated histoplasmosis was diagnosed 2 weeks later when bone marrow and blood cultures taken on admission became positive forHistoplasma capsulatum and when histoplasmic antigen was detected in blood. The outcome was good after treatment with amphotericin B followed by itraconazole which was administered for a 6-month period without significant toxicity.Conclusion Disseminated histoplasmosis is very rarely seen in Europe but should be suspected in case of unexplained fever in immigrants from the endemic areas in the world, particularly when hepatosplenomegaly and pancytopenia are present. Bone marrow examination and culture, blood cultures, and antigen testing are the mainstays of the diagnosis.     

Ehrlichiosis infection in a 5-year-old boy with neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly

Ehrlichiosis should be considered in the differential diagnosis of any patient with recent fever, pancytopenia, hepatosplenomegaly, and history of tick exposure. We present a previously healthy 5-year-old boy who was referred to the Hematology-Oncology Clinic to consider a bone marrow etiologic process after his pediatrician discovered progressive neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly accompanied by 2 days of fever. Bone marrow aspirate and biopsy were nonrevealing. Because of the history of a recent tick bite, a diagnosis of ehrlichiosis infection was considered and ultimately confirmed by IgG-specific serum testing. The patient's fever was treated symptomatically with acetaminophen, and symptoms resolved on their own without intervention. Ehrlichiosis is a tick-borne infection that occurs throughout the spring and summer, often causing findings that mimic a malignancy or serious hematologic disorder. The diagnosis should be considered in any person living in tick-infested areas and can be confirmed by polymerase chain reaction or serum antibody titers. Treatment with doxycycline can lead to rapid clinical improvement if the diagnosis is made early.     

Pancytopenia, a rare hematologic manifestation of brucellosis in children

The records of 54 children with brucellosis were evaluated retrospectively. Among them, eight patients (14.8%) with pancytopenia were identified in a 7-year period between 1996 and 2003. Six of the eight patients with pancytopenia had Brucella melitensis isolated from blood cultures, and all eight patients had Brucella agglutination titers of at least 1:320. Agglutination test titers did not correlate with the degree of pancytopenia. Fever was the most common manifestation, followed by malaise, anorexia, sweating, weight loss, and gastrointestinal symptoms. Most patients had hepatosplenomegaly, and bone marrow aspiration specimens showed hyper-cellularity or normocellularity. Hemophagocytosis (3 patients) and histiocytic hyperplasia (4 patients) were observed in bone marrow examinations of eight patients, but bone marrow aplasia and granulomas were not detected. All children recovered completely; the pancytopenia was transient and resolved after the antibiotic treatment of Brucella infection. Brucellosis should be considered as a possible diagnosis among patients with pancytopenia.     

Leishmaniasis with cutaneous and visceral involvement in a 13-month old boy

Leishmaniasis is an anthropozoonosis caused by infection with leishmania parasites with either cutaneous, mucosal or visceral (kala-azar) involvement. While the benign cutaneous form is self-limited death occurs in approximately 80% of children with kala-azar when untreated. The diagnosis of kala-azar should not be missed in children presenting with fever, hepatosplenomegaly and pancytopenia especially with a history of sand fly bites. We report the case of a 13-month-old boy with both cutaneous and visceral involvement.     

Visceral leishmaniasis. Personal observation and review of epidemiology, clinical aspects and therapy

A 5 year old German girl contracted visceral leishmaniasis during a vacation in Spain, either 32 or 20 month prior to the manifestation of disease. She presented with fever, hepatosplenomegaly and pancytopenia. A bone marrow aspirate proved the diagnosis. Therapy with a pentavalent antimony drug brought about immediate improvement. Visceral leishmaniasis has to be suspected in individuals with fever, hepatosplenomegaly and pancytopenia who have resided in endemic areas (Mediterranean countries, India, East Africa, South America) during the previous years. If untreated, visceral leishmaniasis runs a fatal course. Therefore, early diagnosis by morphological and serological means and specific therapy with pentavalent antimony drugs are mandatory.     

Flow cytometry and morphology analysis of bone marrow in a child with brucellosis and hematologic manifestations

Constitutional symptoms and pancytopenia are occasionally the initial presentation of pediatric brucellosis. Therefore, in endemic areas, in children with pancytopenia, both brucellosis and malignancy should be included in the deferential diagnosis. We report here a child with pancytopenia and hepatosplenomegaly as manifestations of brucellosis in whom bone marrow morphology and flow cytometry data revealed hemophagocytosis, left shift in myeloid cells and activation changes in antigenic properties of T and B lymphocytes and monocytes. The patient had an uneventful and complete recovery after appropriate antibiotic therapy. Our report demonstrates that bone marrow and flow cytometry findings in children with brucellosis may include significant reactive changes in hematopoiesis.     

Hematogenous histoplasmosis in the immunocompromised child

Hematogenous (disseminated) histoplasmosis occurred in 31 of 4158 children with cancer or immune deficiency disorders. Approximately half of the 31 patients had pulmonary lesions, reacted to the histoplasmin skin test, and generated complement-fixing antibodies to Histoplasma capsulatum. In a comparative study delayed hypersensitivity to histoplasmin was demonstrated in 36 (5.7%) of 634 children at the time of diagnosis of cancer. Patients with cancer who were reactive to histoplasmin before treatment were at no greater, and possibly less, risk for hematogenous histoplasmosis than were nonreactors. All of the 27 patients who received treatment for greater than 1 day recovered; three had recurrences that responded to treatment.     

Toxicity of amphotericin b in children with cancer.

The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.     

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目的提高对小儿急性淋巴细胞白血病前期(Pre-ALL)的认识。方法对西安市儿童医院1997—2004收治的6例Pre-ALL患儿的临床经过及实验室的特点进行分析,并复习相关文献。结果男4例,女2例,年龄2岁3个月至8岁7个月,6例均有发热、贫血、出血。初诊为再生障碍性贫血(AA)5例、骨髓异常增生综合征(MDS)1例。4例出现肝、脾、淋巴结肿大(非同时),三系细胞减少,骨髓穿刺涂片示:增生减低4例,重度减低2例;骨髓病理活检:4例均示脂肪组织增多,造血组织减少;2例出现干抽的患儿伴有纤维组织增生,2例出现病态造血。经或不经糖皮质激素治疗,在1~9个月内均转变为急性淋巴细胞白血病(ALL)。3例接受VDLP方案治疗获完全缓解。结论6例转变为ALL,对化疗敏感,部分Pre-ALL有形态学异常。     

Malignant Histiocytosis Involving Pancreas at Initial Presentation

A 10-year-old boy with malignant histiocytosis presented with fever, hepatosplenomegaly, and diffuse pancreatic enlargement, mimicking acute pancreatitis. Although malignant histiocytosis involving pancreas at initial presentation is exceptional, this entity should be included in the differential diagnosis of acute pancreatitis, especially when hepatosplenomegaly and pancytopenia are present.     

Griscelli syndrome: a case report

A 10-year-old boy presented with partial albinism and typical clinical features of a macrophage activation syndrome (hepatosplenomegaly, fever, and pancytopenia), suggesting the diagnosis of Griscelli syndrome. The diagnosis was confirmed by light microscopic evaluation of hair that showed characteristic large aggregates of pigment granules irregularly distributed along the hair shaft. Immunosuppressive therapy controlled his macrophage activation syndrome successfully. Since early diagnosis is life saving and simple methods confirm the diagnosis, finding of partial albinism in children should alert clinicians to consider Griscelli syndrome.     

Viszerale Leishmaniose – nicht nur eine Tropenkrankheit

A 10,5 months old child developed visceral leishmaniasis four months after returning from a three week trip to Malta. She had a complete recovery after treatment with liposomal amphotericin B (AmBisome^®). No treatment related side-effects were noted. Visceral leishmaniasis is predominantly a disease of tropical and subtropical regions, but it is also endemic in the mediterranean area. The main symptoms are fever, hepatosplenomegaly and pancytopenia. Children are frequently infected. Diagnostic methods include direct microscopic detection, culture and polymerase chain reaction (PCR) of leishmanias in biopsies of bone-marrow, spleen or lymphnodes as well as immuno-fluorescence serology. Visceral leishmaniasis should be included in the differential diagnosis if a patient presents with fever of unknown origin following even a brief stay in the mediterranean area. The often fatal outcome of the disease can be prevented by liposomal amphotericin B therapy.     

Histoplasmosis in a pediatric oncology center

OBJECTIVE: To understand the presentation and current management of histoplasmosis in a pediatric oncology center.Study design Retrospective review of clinical features of patients with histoplasmosis at a tertiary-care cancer center in an endemic area. RESULTS: Between 1988 and 2001, 57 patients with cancer had 61 episodes of acute histoplasmosis. Of these, 76% were male, and 64% had acute lymphocytic leukemia (ALL). Most were not neutropenic and had nonspecific febrile illnesses. The most rapid and specific tests for histoplasmosis in patients with cancer were histopathologic examination of lung biopsy specimens in patients with localized pulmonary infection and Histoplasma sp. antigen detection in the urine of patients with disseminated histoplasmosis (DH). The mean times to diagnosis were 20.6+/-15.2 days (pulmonary) and 18.6+/-8.2 days (disseminated) after the onset of symptoms. Most patients were treated with amphotericin B (AmB) followed by azole drugs for a mean of 8.5+/-3.1 weeks (pulmonary) and 10.4+/-7.9 weeks (disseminated). No patient died of histoplasmosis, but cancer therapy often was modified because of the infection. Most received unnecessary antibacterial drugs. CONCLUSIONS: Most readily available diagnostic tests for histoplasmosis lack sensitivity in these patients. Delay in diagnosis of histoplasmosis complicates care. No deaths were attributed to histoplasmosis; outcomes after treatment are good.     

Differentiation of lymphoma from histoplasmosis in children with mediastinal masses

The differentiation of mediastinal masses caused by lymphoma from those caused by histoplasmosis may require thoracotomy. We reviewed the medical records of 37 children undergoing initial evaluation for anterior or middle mediastinal masses. Sixteen had biopsy-proved lymphoma, and 21 had histoplasmosis; seven with histoplasmosis underwent thoracotomy. Age, sex, fever, weight loss, duration of illness, anemia, erythrocyte sedimentation rate, nonspecific reactants, and lung infiltrates and calcifications were similar in both groups. Masses were in the middle mediastinum in all patients with histoplasmosis and in 69% with lymphoma. Masses were in the anterior mediastinum in one of 21 (5%) with histoplasmosis and 13 of 16 (81%) with lymphoma. Among patients with lymphoma, histoplasmal complement fixation antibody titers were less than 1:8 in 14 of 15 (93%); a single patient had a titer of 1:16. The CF titers were greater than or equal to 1:32 in 14 of 21 (67%) with histoplasmosis. In children with middle mediastinal masses, a histoplasmal CF yeast or mycelial titer greater than or equal to 1:32 is strongly suggestive of acute histoplasmosis and biopsy is not required. Children not fulfilling these criteria should undergo diagnostic biopsy.     

Haemophagocytic lymphohistiocytosis: a case series from Mumbai

A retrospective review of ten patients (8 girls, 2 boys) admitted over a 9-month period with haemophagocytic lymphohistiocytosis (HLH) is presented. Presenting features included fever and hepatosplenomegaly (10), bleeding manifestations (7), lymphadenopathy (4), skin rash (4), shock (4), jaundice (3), CNS disorder (3), renal failure (2) and arthritis (2). Three infants had familial HLH (FHL) while the other seven patients had acquired (secondary) HLH. Two patients with FHL had very low perforin levels (0 and 0.05%). There was secondary HLH owing to systemic onset juvenile idiopathic arthritis in two patients, and one each had anaplastic large cell lymphoma, measles with pneumonia, disseminated tuberculosis, dengue hemorrhagic fever and lymphoproliferative disorder. Cytopenia affecting two or three lineages in peripheral blood was present in all while haemophagocytosis in bone marrow was documented in nine patients .Other important laboratory parameters were raised ferritin (9), raised LDH (9), hypertriglyceridaemia (7) and hypofibrinogenaemia (5). The patients were treated according to the HLH2004 protocol. Diagnosis of HLH should be considered early in patients presenting with unremitting fever, hepatosplenomegaly and cytopenias as without appropriate treatment HLH is usually fatal.     

Visceral leishmaniasis (Kala-Azar) in a 3-year-old German infant (author's transl)]

The article reports on a case of visceral leishmaniasis in a 3-year-old child of German residents in Rome who had passed two vacations on the isle of Ischia. Initial signs were intermittent temperatures, marked anorexia, hepatosplenomegaly and pancytopenia, with spontaneous recovery after three weeks. At that time, leishmania serology was already positive, whereas no leishmania were found in several bone marrow preparations despite a most thorough search. During the following eight weeks, the patient had chickenpox and mumps. During the mumps, relapse of the visceral leishmaniasis occurred, associated with a dramatic increase of the hepatosplenomegaly and recurring pancytopenia. It was only now that we could discover multiple leishmania infection of the bone marrow. Subsequent therapy with sodium stibogluconate (Pentostam) was effective without any complications, and eventually cured the patient.     

Malignant histiocytosis in childhood. Clinical features and therapeutic results by combination chemotherapy

Ten children, four males and six females, with malignant histiocytosis were treated from July 1980 to July 1984. None of them had an affected sibling with a similar disorder. Septic-type fever, hepatosplenomegaly, lymphadenopathy, pulmonary infiltration, and disseminated intravascular coagulation were common signs and symptoms, and convulsion occurred in four cases. The diagnosis was made from bone marrow smears in all cases. In five cases, biopsy or autopsy specimens confirmed the diagnosis. In five cases studied, proliferating histiocytes in lymph nodes were demonstrated to be S100 protein-positive. All patients were treated with adriamycin, cyclophosphamide, vincristine, and prednisone (ACOP). Complete response was achieved in four patients after two to three courses of ACOP, and another case attained complete remission after further drug treatment. The five complete responders are now alive without evidence of disease after 23-48 months from the onset. Among partial and no responders, four died within 3 months and one has been alive with disease for 2 months. Bone marrow aspiration is useful for prompt diagnosis, and early treatment with intensive combination chemotherapy improves the prognosis of malignant histiocytosis in childhood.     

High-dose melphalan therapy for the treatment of children with refractory neuroblastoma and Ewing's sarcoma

Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.