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.     

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.     

Disseminated Bacillus Calmette-Guerin infection after BCG vaccination

The BCG is administered to all the newborns at birth in Iran. Systemic adverse reactions to BCG vaccine such as osteomyelitis and disseminated BCG infection are rare. This is a retrospective study of 15 cases <72 months who were admitted with systemic syndrome compatible with disseminated mycobacterial disease during 2004-07. Disseminated BCG disease occurred in eight children younger than 6-months old and 12 patient younger than 12-months old. Twelve patients were male. Nine of 15 patients had well known primary immune deficiency disorders including severe combined immunodeficiency, chronic granulomatous disease; cell mediated immune defect and HIV infection. Nine (60%) cases had good response to four anti-mycobacterial drug therapy and interferon gamma. Disseminated BCG disease is a rare but devastating complication of BCG vaccination that should be considered in the appropriate clinical setting. Severe immune-compromised infants are at greatest risk and they respond poorly to standard therapies.     

Fungemia due to Trichosporon asahii in a neutropenic child refractory to amphotericin B: clearance with voriconazole

Disseminated Trichosporon infection in neutropenic patients carries a poor prognosis. Clinical evidence on the use of voriconazole for this infection is limited. The authors report a case of Trichosporon asahii fungemia refractory to liposomal amphotericin B treatment in a boy with acute lymphoblastic leukemia, which resolved after the addition of voriconazole. Both voriconazole and amphotericin B exhibited low minimal inhibitory concentrations and minimal fungicidal concentrations, and their combination was indifferent in vitro. The use of voriconazole for the treatment of trichosporonosis in patients with hematologic malignancies deserves further study.     

Disseminated histoplasmosis

We describe two cases of disseminated histoplasmosis, which are of interest due to their severity and the infrequency of this infection in our environment. Both children were immunocompromised immigrants from Latin America who developed prolonged fever, weight loss, hepatosplenomegaly and pancytopenia. One patient had respiratory symptoms with associated alterations on x-ray, while no radiological alterations were found in the other patient. Despite administration of broad-spectrum antibiotics and extraction of samples for microbiological analysis, both patients had a rapid and fatal outcome and the diagnosis was made post mortem. Because of its severity, disseminated histoplasmosis should be considered in the differential diagnosis of fever, hepatosplenomegaly and pancytopenia, with or without alterations on chest x-ray, in immunosuppressed children who were born in or have visited endemic regions. In these patients, therapy should be started immediately without waiting for the results of diagnostic tests.     

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.     

Disseminated histoplasmosis in a nonendemic area

Health care providers in the areas where histoplasmosis is not endemic can benefit greatly from understanding the clinical presentation, diagnosis and management of disseminated histoplasmosis as patients from the endemic areas may travel to and require medical attention in areas of low disease prevalence. Use of effective diagnostic tools such as Histoplasma antigen detection can aid in providing timely and appropriate therapy.     

Disseminated fusarium infection in two neutropenic children]

Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients.Case report 1. – A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment.Case report 2. – A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia's relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis's recurrence.Conclusion. – Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis.     

Histoplasmosis in children

Histoplamosis is the most common primary systemic mycosis in the USA and is becoming more common as an opportunistic infection in HIV patients worldwide. In children the rate of asymptomatic infection is high. However, in infants with an immature immunological system, disseminated disease may occur. The clinical picture is variable depending on the immunological status. At the onset of the infection clinical manifestations are non specific (headache, fever, cough and nausea). Usually, these symptoms are self-limited and improve without treatment. However, patients with disseminated diseases present with prolonged fever, malaise, cough and weight loss. Hepatosplenomegaly is frequent in infants. Chest radiographs may be normal in 40 to 50% of patients with disseminated disease but findings such as lobar or diffuse infiltrates, cavitations, hilar adenopathy, or any combination of these may be found. Frequently, the clinical presentation is misdiagnosed as tuberculosis. Skin tests, serological reaction and specific cultures are used for diagnosis confirmation. Treatment indications and regimens are similar to those for adults, except that amphotericin B deoxycholate is usually well tolerated in children.     

Follow-up study of auditory brainstem responses in infants with high unbound bilirubin levels treated with albumin infusion therapy

BACKGROUND: Several authors reported that there was a close relationship between unbound bilirubin concentrations and abnormal results of auditory brainstem responses. Full-term infants with high-unbound bilirubin concentrations who were treated with human albumin were followed to evaluate their hearing abilities by using auditory brainstem responses. METHODS: Fifty-eight infants (gestational age, 39.4 +/- 1.4 weeks; birthweight, 3,245 +/- 435 g) with high unbound bilirubin concentrations (> or = 0.9 micro g/dL) were treated with intensive phototherapy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given i.v. human albumin administration (1 g/kg bodyweight) during the first 2 h of phototherapy. The follow-up study of auditory brainstem responses was carried out at 6 and 12 months of age. Development quotient tests were carried out at 18 months of age. RESULTS: Abnormalities of auditory brainstem response were detected in three infants in the albumin-treated group and six infants in the control group at 6 months. Two infants in the albumin-treated group and four infants in the control group had improved at 12 months. The results of the follow-up study at 18 months of age in the both groups were normal with development quotient >85. No patients with hearing disability and cerebral palsy were clinically detected at the age of 2 years. CONCLUSION: The results suggest that albumin priming might be effective for decreasing the rate of auditory brainstem response abnormalities at 6 months.     

Short-term developmental outcome of iron prophylaxis in infants

BACKGROUND: Previous studies on the cognitive effects of iron treatment have focused on anemic or non-anemic iron-deficient infants. The effect of iron supplementation on cognitive development among iron-sufficient infants has not been studied. The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development (BSID) and anthropometric measurement in 6-month-old iron-sufficient healthy infants. METHODS: Healthy, iron-sufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment. Infants were randomly assigned to take ferrous sulfate supplementation (1 mg/kg per day) or no supplementation and were followed for 3 months. Anthropometric measurement, hematologic status and BSID were evaluated on admission and after 3 months. RESULTS: Seven infants in the intervention group and nine in the control group completed the study. No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period. The mean transferrin saturation (TS) level decreased significantly in the control group during the study period (from 15.3+/-2.6 to 7.8+/-5.1%; P = 0.0117), but no such reduction was seen in the intervention group. At the end of the study, the TS of the control group was found to be significantly lower than that of the intervention group (7.8+/-5.1 vs. 19.9+/-7.9%, respectively; P = 0.0033). The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period. CONCLUSIONS: Short-term iron supplementation did not change developmental test scores despite the hematologic response in iron-sufficient healthy infants. The high prevelance of iron-deficiency anemia and its relationship with adverse developmental outcome suggests that prevention of iron-deficiency anemia with prophylaxis needs to be emphasized, rather than treatment.     

A double-masked, randomized control trial of iron supplementation in early infancy in healthy term breast-fed infants

OBJECTIVES: To test whether iron supplementation affects hematologic, biochemical, and developmental status in term breast-fed infants. STUDY DESIGN: Term breast-fed infants (n=77) were randomly selected to receive either 7.5 mg per day of elemental iron as ferrous sulfate or placebo from 1 to 6 months of age. Investigators and families were unaware of group assignment. Complete blood count and ferritin, red cell superoxide dismutase, catalase, plasma ferric reducing antioxidant power, and zinc and copper levels were analyzed at 1, 3.5, 6, and 12 months of age. Bayley mental and psychomotor developmental indexes (MDI and PDI) and visual acuity (with the use of Teller acuity cards) were assessed from 12 to 18 months of age. Analysis performed by analysis of variance and t tests was by intention to treat. RESULTS: Iron supplementation resulted in higher hemoglobin and mean corpuscular volume at 6 months of age and significantly higher visual acuity and PDI at 13 months of age (100+/-12 vs 93+/-9 [+/-SD]). Treatment and placebo groups did not differ in anthropometric indexes, compliance, biochemical status, or demographic characteristics. CONCLUSIONS: Iron supplementation of breast-fed infants appears safe and might have beneficial hematologic and developmental effects for some infants.     

Idiopathic disseminated bacillus Calmette–Guerin infection in three infants

We describe the cases of three infants between 4 and 9 months of age with disseminated bacillus Calmette–Guerin (BCG) infection who developed persistent fever, skin rash, and multiple chest nodules visible on computed tomography 22–34 days after BCG vaccination. These infants were healthy before inoculation, and their detailed immunological profiles, including T cell and neutrophil levels, were within normal range. Most reported BCG cases involve impaired immunity, such as children with chronic granulomatous disease, severe combined immunodeficiency, or human immunodeficiency virus infections. Because of their immature immune systems, BCG vaccination can be hazardous even in early infants without immune abnormalities. Hence, we advise caution when administering BCG vaccines to early infants.     

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.     

Acute disseminated encephalomyelitis

The authors report 6 children with the diagnosis of acute disseminated encephalomyelitis. Diagnosis was based on clinical and radiological findings. The most common presenting symptoms were fever and disturbed consciousness, followed by cranial nerve abnormalities and pyramidal signs. Brain MRI showed hyperintense signals on T2-weighted images, most commonly in the subcortical and periventricular white matter, brainstem, basal ganglia and thalamus. The lesions were bilateral, asymmetrical and highly variable in size and number. A preceding infection was present in 3 of 6 children. Early high-dose corticosteroids were given to all the patients. All patients recovered clinically. Follow-up ranged from 10 months to 2 years. No relapses were observed during this period. Early high-dose steroid therapy seems to be an effective treatment in acute disseminated encephalomyelitis.     

Clinical profile and outcome of clinical BCG disease in infants

Objective

To describe the clinical profile, immunological status and outcome of BCG disease in infants.

Methods

All infants with a diagnosis of BCG disease in a period of 17 months were followed up.

Results

Among 25 infants with BCG disease; 19 had local/regional involvement and 6 had suspected or confirmed distant/disseminated disease, Mean (range) age of presentation was 3.6 (1.5–9) months. Two of 6 infants with disseminated disease required second-line anti-tubercular treatment. One infant with confirmed disseminated disease had INFγR1 receptor deficiency. There was no mortality.

Conclusion

Most infants with BCG- related disease have local or regional disease.     

儿童白血病化疗后合并全身性真菌感染诊断及治疗体会

目的积累和交流白血病化疗病人合并深部真菌感染时临床经验。方法总结2年中明确诊断深部霉菌感染病人的诊断过程、方法、临床特征、治疗反应和转归。结果确诊深部真菌感染者共5例,均为白血病患儿,感染前或感染中白血病达完全缓解,特征性表现为发热,抗菌素治疗>5天无效,轻中度压痛的多发性硬性皮下小结(2/5例)和肝脾肾散布性低密度病灶(3/5例),需四周以上二性霉素治疗,有明显但可以处理的毒性反应。结论发热、抗菌素治疗无效、硬性皮下小结和肝脾肾散布性低密度病灶时应考虑深部真菌感染,并给予4周以上二性霉素治疗。     

儿童白血病化疗后合并全身性真菌感染诊断及治疗体会

目的 积累和交流白血病化疗病人合并深部真菌感染时临床经验.方法 总结2年中明确诊断深部霉菌感染病人的诊断过程、方法、临床特征、治疗反应和转归.结果确诊深部真菌感染者共5例,均为白血病患儿,感染前或感染中白血病达完全缓解,特征性表现为发热,抗菌素治疗＞5天无效,轻中度压痛的多发性硬性皮下小结（2/5例）和肝脾肾散布性低密度病灶（3/5例）,需四周以上二性霉素治疗,有明显但可以处理的毒性反应.结论 发热、抗菌素治疗无效、硬性皮下小结和肝脾肾散布性低密度病灶时应考虑深部真菌感染,并给予4周以上二性霉素治疗.     

新生儿红斑狼疮八例分析

目的提高对新生儿红斑狼疮（neonatal lupus erythematosus,NLE）的认识。方法分析2003年9月至2006年2月诊断为NLE患儿的临床表现、狼疮相关血清学指标及头颅CT等辅助检查,并随访至正常或1．5岁。结果共8例患儿诊断为NLE,其中男3例,女5例,足月小样儿4例,临床表现为皮疹（8例）、肝脾肿大（5例）、血小板减少（4例）、神经系统异常（2例）、Ⅲ度房室传导阻滞（AVB）（1例）等。仅3例患儿的母亲产前诊断为系统性红斑狼疮。患儿均有抗核抗体（ANA）和／或抗干燥综合征A抗体（Ro／SSA）和／或抗干燥综合征B抗体（La／SSB）阳性,母亲均有ANA阳性。所有症状除Ⅲ度AVB外均消失,1例神经系统异常者1．5岁随访时也表现正常。结论需提高对NLE的认识才能避免漏诊,早期神经系统异常者不能轻易下有后遗症的结论。