HEMOPHAGOCYTIC SYNDROME: A Rare Life-Threatening Complication of Visceral Leishmaniasis in a Young Boy

The authors report a case of hemophagocytic syndrome (HPS) associated with acute visceral leishmaniasis (VL). A 4-year-old boy was admitted with high fever, hepatosplenomegaly, and pancytopenia. Elevated serum ferritin and triglyceride, low fibrinogen levels, and bone-marrow (BM) histiocytic hyperplasia with prominent hemophagocytosis were consistent with a HPS. An initial diagnosis of kala-azar was refuted because of negativity of BM aspiration and serology for this parasite, and the diagnosis of HPS was made. Three months after first admission, reevaluation of the BM aspiration revealed many amastigotes of Leishmania parasites. The serology of VL became positive, finally establishing the diagnosis of VL. Although specific therapy for VL was instituted, the patient died 4 weeks after the diagnosis.     

细针吸取细胞学检查在儿童甲状腺炎诊断中的应用

目的：　探讨细针吸取细胞学 (FNAC)检查对儿童甲状腺炎的诊断价值。方法：　采用FNAC检查法诊断儿童甲状腺。结果：　经细胞学诊断为甲状腺炎共计 10 0例,经临床治疗及其它实验室检查结果相符的98例(98%),只有2例(2%)在分类上出现误差,而血清学(T3 ,T4 ,TG ,TM ,TSH)检查敏感性则相对较低,桥本氏甲状腺炎为63.1%～73.6%,淋巴细胞性甲状腺炎为26.0%～84.7%,其它血清学检查均无意义。结论：　FNAC检查法吸出细胞成分充足,几乎不含血液成分,有利于甲状腺炎的诊断及分类。     

Foamy histiocytes in a patient with visceral leishmaniasis after treatment with liposomal amphotericin B

A seven-year-old patient was admitted to our hospital with the complaints of fever, malaise, and abdominal distention. In the bone marrow aspiration smears, leishmania amastigotes were observed. The patient was diagnosed as having visceral leishmaniasis (VL) and treated with liposomal amphotericin B (L-AMB). The authors report their observation of foamy histiocytes seen in the bone marrow aspiration smears of the patient with VL after L-AMB treatment. This effect of L-AMB needs to be recognized, since L-AMB may represent a further condition in addition to the other diseases that are associated with foamy histiocytes in the bone marrow.     

骨髓转移的高危神经母细胞瘤治疗后骨髓缓解速度与预后关系

目的探讨伴骨髓转移的高危神经母细胞瘤(NB)患者治疗后骨髓缓解速度对预后的影响。方法收集中山大学肿瘤防治中心从2000年1月至2014年12月收治的初诊时已有骨髓转移的Ⅳ期高危NB患者的临床资料。将≤2个疗程化疗后骨髓获得完全缓解(CR)定义为快速骨髓缓解组,2个程化疗后骨髓获得CR定义为缓慢骨髓缓解组。并对综合治疗后获得CR或非常好的部分缓解(VGPR)的73例患者的预后进行单因素和多因素分析。结果纳入分析的73例患者,中位年龄4.0(1.6~9.8)岁,男52例、女2l例。快速骨髓缓解组19例,缓慢骨髓缓解组54例。全组4年无事件生存率(EFS)和总生存率(OS)分别为(15.6±4.9)%和(28.9±6.4)%。快速骨髓缓解组与缓慢骨髓缓解组4年EFS分别为(25.9±12.3)%和(12.4±5.0)%(P=0.033),4年0S分别为(51.6±15.2)%和(22.6±6.6)%(P=0.057)。单因素分析结果显示,骨髓缓慢缓解是影响骨髓转移的高危NB患儿EFS的不良因素(P0.05);无维持药物治疗、N-myc基因扩增是影响0S的不良因素(P0.05)。多因素分析结果示,N-MYC扩增、骨髓缓慢缓解为患者0S的独立不良预后因素(P0.05);仅骨髓缓慢缓解是EFS的独立不良预后因素(P0.05)。年龄≤2岁NB患者骨髓快速缓解的比例高于年龄2岁患者(x~2=5.608,spearman相关系数=0.277,P=0.018)。结论本研究显示骨髓转移的高危NB患者治疗后骨髓快速缓解者预后好于缓慢骨髓缓解者,有可能作为骨髓转移的高危NB患者的预后观察指标之一。     

Pediatric visceral Leishmaniasis in Turkey

BACKGROUND: Visceral Leishmaniasis (VL) type in Turkey is consistent with the Mediterranean type of VL, a fatal debilitating disease, which is mostly seen in infants. METHODS: Hospital records of 19 children with VL were retrospectively reviewed. The period of the study was from January 2000 to December 2003. RESULTS: The median age of the patients was 36 months. None was coinfected with human immunodeficiency virus or known to be immunocompromised. Fever, pallor, hepatomegaly, splenomegaly, thrombocytopenia and elevated C-reactive protein were observed in all cases, anemia in 18 (95%), leucopenia in 17 (89.4%) and elevated erythrocyte sedimentation rate in 14 (77.7%) of the cases. A bone marrow aspirate was obtained in all cases and Leishmania amastigotes were detected in 15 (78.9%). Fifteen patients (78.9%) were treated initially with meglumine antimonate and four (21%) with sodium stibogluconate. The four patients who received sodium stibogluconate suffered from adverse side-effects during treatment and were subsequently treated with lipid formulations of amphotericin B. CONCLUSIONS: Presentation of VL in the pediatric age group in Turkey is characterized by pallor, fever, splenomegaly and hepatomegaly. Hematological and biochemical indices are typical with cytopenias, hypoalbuminemia, and hyperproteinemia. In most of the cases, microscopic examination provided a positive diagnosis and the remaining patients were diagnosed by serology. Lipid formulations of amphotericin B may be useful in cases of treatment failure with antimonials or significant adverse effects of the drug.     

先天性肥厚性幽门狭窄的诊断标准与B超评分系统

目的　探讨一种可靠的先天性肥厚性幽门狭窄 (HPS)的诊断标准。方法　在本研究中测量了 30例正常婴幼儿和 77例HPS患儿的幽门管直径、长度和幽门部肌层厚度 ,通过半效数量分析法 ,得出相对应的评分数值。结果　 30例正常婴幼儿通过B超检查幽门大小 ,平均为 (11.16±1.2 9)mm ,范围 9.0～ 13.0mm ,肌层厚度为 (2 .12± 0 .31)mm ,范围 1.5～ 3.1mm ,幽门管长度 (13.9± 1.4 6 )mm ,范围 10 .0～ 16 .0mm。而 77例HPS婴幼儿B超检查如下 :幽门直径平均 (15 .7± 2 .2 3)mm ,范围 11.0～ 18.0mm ,肌层厚度平均为 (4.90± 0 .85 )mm ,范围 4 .0～ 6 .0mm ,幽门长度平均为18.9± 3.12 ,范围从 15 .0～ 2 2 .0mm。通过建立一个B超评分系统 ,评分≥ 4则为HPS ,若评分≤ 2则排除HPS ,评分 =3则需进一步检查 ,如上消化道造影 (UGI)。结论　B超是一种有效的检查手段 ,建立一个评分系统 ,对HPS的诊断起决定性作用     

Fever of unknown origin in 185 paediatric patients: a single-centre experience

Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died.

Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.     

Visceral leishmaniasis in Malta--an 18 year paediatric, population based study.

BACKGROUND: Visceral leishmaniasis (VL) is a chronic parasitic infection that infects approximately 400,000 individuals annually, with a predilection towards early childhood. AIMS: To study the epidemiology of VL in childhood. METHODS: VL is endemic in Malta, a small archipelago of islands in the centre of the Mediterranean with a total population approaching half a million. Notification of human cases of leishmaniasis is compulsory. Case records of all 81 paediatric patients with VL between 1980 and 1998 were analysed. RESULTS: The annual incidence of VL declined for all cases of VL, and declined significantly for paediatric cases (p = 0.01). For 1994 to 1998, the overall incidence of VL was 0.9 per 100,000 total population and the paediatric incidence was 2.5 per 100,000 population. Median age at presentation was 34 months. Common features at presentation were splenomegaly, hepatomegaly, fever, and pancytopenia with high lymphocyte and monocyte counts. The diagnostic sensitivity of isolated immunofluorescent antibody testing was equivalent to bone marrow aspiration (95%). Blood transfusions for anaemia were required in 93% of patients. Eleven per cent had intercurrent infections. All patients were cured, and were initially treated with intravenous sodium stibogluconate. Defervescence occurred after a median of six days of treatment, and patients continued to be treated on a day case basis. Nine relapsers were retreated with sodium stibogluconate, achieving a cure rate of 94%, but five patients required additional drug therapy. There were no permanent sequelae associated with VL or its treatment. CONCLUSIONS: The decreased incidence is attributed to the eradication of stray dogs which are the disease reservoir.     

Changes in pyloric tumor of infantile hypertrophic pyloric stenosis before and after pyloromyotomy

Sixteen of 24 infants with vomiting were examined by real-time sonography, which established the diagnosis of hypertrophic pyloric stenosis (HPS); 12 underwent surgery. Of the three parameters measured, pyloric muscle wall thickness was the most reliable and accurate for the diagnosis of HPS. We suggest that a muscle wall thickness of 4 mm or more and stenosis index greater than 50% are standard findings in patients with HPS. Serial real-time sonography following pyloromyotomy showed that the pyloric tumor changed significantly during the 1st postoperative week and returned to normal size by the end of the 4th week. Offprint requests to: Z. X. Shen     

Visceral leishmaniasis in Malta--an 18 year paediatric, population based study

BACKGROUND—Visceral leishmaniasis (VL) is a chronic parasitic infection that infects approximately 400 000 individuals annually, with a predilection towards early childhood.AIMS—To study the epidemiology of VL in childhood.METHODS—VL is endemic in Malta, a small archipelago of islands in the centre of the Mediterranean with a total population approaching half a million. Notification of human cases of leishmaniasis is compulsory. Case records of all 81 paediatric patients with VL between 1980 and 1998 were analysed.RESULTS—The annual incidence of VL declined for all cases of VL, and declined significantly for paediatric cases (p = 0.01). For 1994to 1998, the overall incidence of VL was 0.9 per 100 000 total population and the paediatric incidence was 2.5 per 100 000 population. Median age at presentation was 34 months. Common features at presentation were splenomegaly, hepatomegaly, fever, and pancytopenia with high lymphocyte and monocyte counts. The diagnostic sensitivity of isolated immunofluorescent antibody testing was equivalent to bone marrow aspiration (95%). Blood transfusions for anaemia were required in 93% of patients. Eleven per cent had intercurrent infections. All patients were cured, and were initially treated with intravenous sodium stibogluconate. Defervescence occurred after a median of six days of treatment, and patients continued to be treated on a day case basis. Nine relapsers were retreated with sodium stibogluconate, achieving a cure rate of 94%, but five patients required additional drug therapy. There were no permanent sequelae associated with VL or its treatment.CONCLUSIONS—The decreased incidence is attributed to the eradication of stray dogs which are the disease reservoir.     

Brain abscess in hepatopulmonary syndrome associated with biliary atresia

The first‐choice therapy for biliary atresia (BA) is Kasai hepatoportoenterostomy, which has been shown to greatly improve outcome. Various long‐term complications, however, such as portal hypertension and hepatopulmonary syndrome (HPS), can occur in patients with native liver. A rare case of brain abscess in an 11‐year‐old girl with HPS associated with BA is reported. The patient underwent hepatoportoenterostomy for BA at 53 days of age, with resolution of hyperbilirubinemia. At 10 years of age, she was diagnosed with severe HPS with right‐to‐left shunting, and preparations for liver transplantation proceeded. Three months after the diagnosis, she had a right parietal brain abscess. Given that the brain abscess enlarged in size, surgical drainage of the brain abscess was performed. The postoperative course was uneventful, but a slight left hemiplegia remained at discharge. The presumed mechanism of abscess formation in HPS may be right‐to‐left bacterial transit through intrapulmonary vascular dilatations and/or arteriovenous fistulae.     

Diagnostic imaging in hypertrophic pyloric stenosis

This report discusses hypertrophic pyloric stenosis (HPS) and the current approach to diagnostic imaging in the vomiting infant. Signs and symptoms include dehydration and vigorous gastric peristalsis with vomitus. Palpation of an olive-shaped firm muscular tumor is pathognomonic of this condition. The radiographic signs of HPS are well known. Previously published criteria for the sonographic diagnosis of HPS are discussed, these include: measurements of pyloric length, diameter and muscle thickness. The thickened muscle is the most discriminated and accurate one. It was concluded that real-time ultrasound is a simple, and reliable method for the diagnosis of HPS and should be the initial imaging procedure.     

Long‐term outcome and management of hepatopulmonary syndrome in children

Al‐Hussaini A, Taylor RM, Samyn M, Bansal S, Heaton N, Rela M, Mieli‐Vergani G, Dhawan A. Long‐term outcome and management of hepatopulmonary syndrome in children.
Pediatr Transplantation 2010:14:276–282. © 2009 John Wiley & Sons A/S. Abstract: We aim to report a single center experience of the management and long term outcome of HPS in pediatric liver transplant recipients. A retrospective review of children with HPS from 1990 to 2004. Inclusion criteria: liver disease or portal hypertension, hypoxemia (PaO₂ < 70 mmHg or SaO₂ < 95%) and intrapulmonary shunting documented by macroaggregated albumin scan ratio of >4% (classified mild group [<20%], moderate group [20–40%] and severe group [>40%]). Resolution of HPS post‐liver transplant was defined as PaO₂ > 70 mmHg or SaO₂ > 95%. Eighteen children (six male [34%], median age at diagnosis of HPS 8.6 [1–15.5] yr) had HPS: biliary atresia (n = 8), idiopathic biliary cirrhosis (n = 4), progressive intrahepatic cholestasis (n = 2), miscellaneous (n = 4). The majority had mild shunting (n = 8). Fourteen underwent transplantation with resolution of HPS in 13. Six developed complications: hepatic artery thrombosis (n = 4), biliary (n = 2). Four children died (28%), two pretransplant. There was a tendency towards shunt fraction worsening to a slower degree over time. One‐yr survival rate post‐transplant was 93%. Median PaO₂ was significantly lower in non‐survivors compared to survivors (43 vs. 55.2 mmHg, p = 0.03). There was correlation between oxygen parameters pretransplant and time to HPS resolution post‐transplant. HPS is reversible after transplant, but is associated with increasing mortality and morbidity.     

Pyloric stenosis: evolution from pylorospasm?

Over a 10-year period, we have performed pyloromyotomy on 260 infants with hypertrophic pyloric stenosis (HPS), 10 of whom had a history suggestive of pyloric stenosis but initially had neither the physical nor radiological findings to confirm the diagnosis. All 10 demonstrated pylorospasm on upper gastrointestinal series (UGIS), were treated medically without improvement, and subsequently developed classic HPS confirmed by repeat UGIS. Age at diagnosis ranged from 3 to 16 weeks (mean 8 weeks). Vomiting was progressively more projectile and severe from the onset until diagnosis and operation, with a duration of 5–50 days (mean 24 days). In 9 of the 10 patients a second UGIS demonstrated the diagnostic signs of HPS in 8 and suggested an antral web in the 9th. The interval between the two UGIS ranged from 2 to 46 days (mean 13 days). The 10th patient had a palpable hypertrophic pyloric muscle 9 days after the first UGIS and was operated upon without a follow-up UGIS. All 10 patients had classic HPS at operation. We conclude that although most infants with pylorospasm on UGIS improve with medical management, a small but significant number go on to develop HPS. Awareness of this variant of pyloric stenosis and appropriate follow-up UGIS will help to avoid undue delay in correctly diagnosing infants with persistent non-bilious vomiting.     

Our experience in "ad libitum" feeding after pyloromyotomy (review of 97 cases).]

A recent alternative feeding regimen at the progressive feeding (PF) after a pyloromyotomy for hypertrophic pyloric stenosis (HPS) is the so-called ad libitum feeding (AL). The aim of this study was to determine if this new feeding regimen has modified the follow-up of postoperative course in HPS. POPULATION AND METHODS: From January 1998 to December 2003, 97 consecutive neonates have been operated on for HPS in our hospital. This retrospective study was based on the comparison between two groups of patients with different postoperative feeding regimens: group one of 30 neonates with PF regimen and group two of 60 neonates with AL regimen. Seven remaining neonates had had a mucosal perforation and were not included in this comparative study but in a separate group (MP). The clinical, ultrasonographic, operative and postoperative data were compared. RESULTS: There was no difference between the PF and AL groups for sex ratio M/F=4/1, preoperative weight loss ratio, ultrasonographic data and intra-operative difficulties rate. A small difference was found - which was not significative - between the PF and the AL groups for median age at diagnosis (44,6 v 36,7 days, respectively). A statistically significative difference between the PF and the AL groups was observed for time to establish feeding (69 vs 35.6 hours, respectively) (P<0,001), postoperative stay (4.16 vs 2.98 days, respectively) (P<0,001) and total hospital charges. We didn't found any difference in the incidence and severity of postoperative emesis whether slow (PF) or rapid (AL) feeding regimens were used. Furthermore, intra-operative mucosal tear didn't influence postoperative course and the duration of hospital stay. CONCLUSION: We recommend AL regimen for routine feeding in simple cases after pyloromyotomy for HPS. It has a positive impact on length of hospital stay, and decreases hospital charges. Most neonates with MP can be managed with a rapid feeding regimen.     

Sero-epidemological survey on canine visceral leishmaniasis and the distribution of sandfly vectors in northwestern Turkey: prevention strategies for childhood visceral leishmaniasis

Visceral leishmaniasis (VL) caused by Leishmania infantum, is an endemic disease in Aegean and Mediterranean Regions among humans and dogs. In this study, a sero-epidemiological survey for VL and cutaneous leishmaniasis (CL), which both are sporadically reported in the region, were carried out in the villages of Eskisehir, Afyon, and Bilecik cities. The study was designed according to the location of the sporadic cases of VL and CL, and blood samples of 111 dogs were randomly collected. Lymph node aspiration samples were taken from dogs that have popliteal lymphadenopathy. Sand flies were also collected using CDC light traps in the several localities. The sera samples were screened using IFAT, ELISA, rk39 ELISA and dip-stick tests for anti-Leishmania antibodies. A total of 15 (13.51 per cent) dogs out of 111 were found to be seropositive by at least one of the tests. The seropositivity ratios among dogs were found to be 27.5 per cent (8/29), 9.09 per cent (4/44) and 7.8 per cent (3/38) in Afyon, Bilecik and Eskisehir cities respectively. Leishmania amastigotes were detected in 4 of the 14 lymph node aspiration samples (eight seronegative, six seropositive), and all of them were seropositive dogs. One year later, two of the dogs were found to be dead and the other two were severely ill. Among the 179 collected Phlebotomus specimens from, Phlebotomus major was found to be abundant (35.7 per cent) and the other species were P. simici (28.5 per cent), P. similis (34.7 per cent) and P. alexandri (1.1 per cent). In the study area, canine VL is more spread than human VL. Because dogs are playing an important role for VL in Mediterranean Basin, and development of appropriate control measures will be necessary for childhood VL.     

Charcoal is a sensitive, specific, and stable marker for the diagnosis of aspiration in hamsters

The diagnosis of recurrent aspiration in young children is a perpetual challenge because there is no specific gold standard test to be used. The finding of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL) is a sensitive but nonspecific marker for the diagnosis of aspiration. We conducted a short-term study comparing tracheal instillation of saline, milk, or a milk-charcoal mixture in hamsters. BAL cytology, lipid-laden alveolar macrophage index, charcoal alveolar macrophage index, and lung histology were monitored for 10 d. A long-term study was performed, and hamsters were monitored for 92 d after milk-charcoal tracheal instillation. Baseline animals (n = 4) had no tracheal instillation. Saline- and milk-instilled animals had BAL performed after 1 (n = 4), 3 (n = 4), and 10 (n = 4) d. Milk-charcoal-instilled animals had BAL performed after 1 (n = 4), 3 (n = 4), 10 (n = 4), 30 (n = 2), 58 (n = 2), and 92 (n = 2) d after tracheal instillation. Total cell counts and percent neutrophils in BAL fluid increased significantly and similarly after milk and milk-charcoal instillation on d 1 compared with baseline and saline-instilled animals. Lipid-laden alveolar macrophage index increased significantly only on d 3 after milk and milk-charcoal instillation compared with all days in the saline-instillation group. Charcoal alveolar macrophage index increased significantly after milk-charcoal instillation (d 1-58) from baseline or all days in the saline-instillation group. We conclude that charcoal particles instilled in tracheas of hamsters can be easily identified in BAL fluid and in lung parenchyma for as long as 3 mo after a single instillation and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration, although the issue of its applicability to humans is still unsolved.