Intermittent ketoconazole therapy of chronic mucocutaneous candidiasis in childhood

We report the clinical and laboratory findings in two children with chronic mucocutaneous condidiasis (CMC) treated successfully with intermittent long-term ketoconazole therapy. Both had chronic infection of the nails, skin and mucous membranes with positive cultures for candida. Both were resistant to multiple local and systemic antifungal agents. After institution of ketoconazole therapy there was a dramatic improvement with clearing of the oral (one week), skin (two months) and nail lesions (5 months). After 8 months the drug was stopped and clinical remission persisted for 10 and 7 months respectively. Relapse of oral candidiasis was treated with a short course of ketoconazole (4–16 weeks) leading to complete healing of the lesions. Clinical improvement was not related to an amelioration in lymphocyte transformation. There was no change in the progressive deterioration of the lymphocyte responses to candida antigen which was probably due to persisting candida cell wall components (e.g. mannan).Dedicated to Prof. W. Hitzig on the occasion of his 60th birthday     

Ketoconazole treatment of nail infection in chronic mucocutaneous candidiasis

ABSTRACT. Chronic mucocutaneous candidiasis is an immunodeficiency disorder which has significant morbidity due to mucous membrane, skin and nail infection. Attempts at reconstitution of immunological abnormalities have had only limited success. Ketoconazole is a newly available oral antifungal agent with activity against candida species. Prolonged administration of ketoconazole to four children with chronic mucocutaneous candidiasis caused marked improvement at infected sites. Resolution of nail infections took up to 12 months.     

Haemophilus influenzae type D infection and JgG2 deficiency in a patient with chronic mucocutaneous candidiasis

A 14 year old boy with chronic mucocutaneous candidiasis and persistent pulmonary infection caused by Haemophylus influenzae and Streptococcus pneumoniae is reported. Initial bacterial culture studies showed H. influenzae type B and S. pneumoniae as causative agents. H. influenzae type D was constantly isolated from the patient's sputum. Abnormally low levels of serum immunoglobulin G2 (IgG2) found in the patient may have contributed to the pulmonary infection and H. influenzae type D may be an important causative agent in immunodeficient patients.     

IgG2/IgG4 subclass deficiency in a patient with chronic mucocutaneous candidiasis and bronchiectases

A 22-year-old man with chronic mucocutaneous candidiasis (CMC) and hypothyroidism developed severe bronchiectases following recurrent bronchopneumonia. Immunological investigations revealed IgG₂/IgG₄ subclass deficiency and absence of antibodies against pneumococcal and Haemophilus polysaccharides. Under regular immunoglobulin substitution every 3 weeks pulmonary symptoms improved markedly.     

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation

FV is primarily produced in the liver, and congenital FV deficiency is a disorder with an incidence of one in 1 million. Standard care is to treat severe bleeding phenotypes with FFP as there is no recombinant or plasma‐derived FV concentrate. We present a case of a neonate with known severe FV deficiency diagnosed after prolonged bleeding after circumcision who represented at age 2 months with a large left intraparenchymal hemorrhage. His bleed was treated with FFP, platelet transfusion, recombinant VIIa, and emergent evacuation. He was maintained on plasma infusions but was unable to space his infusions beyond 48 hours. Liver transplantation was considered as a definitive treatment for this condition. While awaiting a suitable liver, his FV trough levels occasionally dropped below 5%, and he suffered from a second acute intracranial bleed. He received an orthotopic liver transplant at age 5 months, resulting in correction of his FV levels. He has not required any plasma infusions post‐transplantation and has had no further bleeding episodes. Liver transplantation should be considered as definitive treatment early in the course for patients with severe FV deficiency and first time life‐threatening bleed.     

四氢生物喋呤缺乏症治疗前后神经系统表现及其脑白质病变分析

目的 对比治疗前后四氢生物喋呤缺乏症(tetrahydrobiopterin deficiency,BH4D)的神经系统表现,并观察其治疗前后脑白质的病变,为判断治疗效果提供客观的临床和影象学依据。方法 BH4D患儿11例,男9例,女2例;年龄17周～4岁。给予四氢生物喋呤,美多巴,5-羟色胺口服治疗1年,行头颅MRI检查,采用staudt评估标准,对其脑白质病变进行治疗前后的观察评定,其中8例以Gesell发育量表测量进行量化比较。结果 ①治疗后8例Gesell发育量表发育指数较治疗前改善。②治疗前1l例患儿(100％)均有髓鞘发育延迟,其中额叶11例(100％,),枕叶8例(72．7％),颞叶4例(36．4％),顶叶3例(27．3％),胼胝体发育不良6例(54．5％),1例小脑发育不良,全部病例在双侧侧脑室周围T2加权像(T2WI)上均有弥漫性高信号病灶。治疗后脑白质病变较前好转,但仍存在部分髓鞘发育延迟及T2WI异常高信号。结论 治疗后BH4D患儿发育指数较前好转,临床症状的改善与脑白质病变具有一致性;BH4D患儿脑白质病变具有高发生率,表现为髓鞘发育延迟及异常的T2WI高信号,推测这种损害不仅与高苯丙氨酸血症有关,且与神经递质的合成下降有关;治疗后的脑白质病变较治疗前改善,与临床症状的改善相一致,但依然存在部分脑白质病变,推测与治疗所用的BH4的剂量,及个体差异所造成的血药浓度及透过血脑屏障的浓度不同有关。     

婴儿中枢神经系统白色念珠菌病5例并文献复习

目的 总结婴儿中枢神经系统白色念珠菌病的临床特点和诊断治疗经验.方法 收集首都医科大学附属北京儿童医院2009至2011年收治的婴儿中枢神经系统白色念珠菌病连续病例(5例)的临床资料,总结其临床表现、实验室检查、影像学特征、治疗和随访情况,并文献复习.结果 男4例,女1例,年龄3～5月龄(平均4月龄),均无明显免疫缺陷...     

生长激素缺乏症患儿重组人生长激素治疗前、后肾上腺皮质功能的变化

目的观察生长激素缺乏症(GHD)患儿重组人生长激素(rh GH)治疗前、后肾上腺皮质功能的变化。方法选取72例确诊GHD并接受rh GH治疗6个月以上的患儿,其中32例伴促肾上腺皮质激素(ACTH)缺乏,回顾性分析其在接受rh GH治疗前及治疗后3、6个月时清晨空腹血皮质醇(COR)、ACTH水平的变化。结果 32例伴ACTH缺乏患儿通过外源性补充氢化可的松(HC)使COR达正常水平后,再开始rh GH治疗,治疗前COR水平和使COR达正常下限时的HC剂量呈显著负相关(r=-0.899,P0.01)。单纯HC治疗1个月后COR水平较治疗前明显增高,ACTH水平明显下降,差异均有统计学意义(P0.001);经rh GH和HC替代治疗后3、6个月后COR及ACTH水平与单纯HC治疗1个月差异无统计学意义(P0.05)。40例无ACTH缺乏患儿在rh GH治疗后COR水平显著降低,与治疗前比较差异有统计学意义(P0.01),其中10例MRI显示下丘脑-垂体异常患儿表现为COR水平低下。结论 GHD患儿在rh GH治疗过程中可出现肾上腺皮质功能减低,特别是MRI显示垂体异常的患儿,应注意监测肾上腺皮质功能,及早干预。     

Simulation of the Clinical Course of Viral Hepatitis and Its Immunological Treatment

An analysis of the variations in the clinical course of hepatitis B (HB) was attempted with mathematical simulation. Hepatitis B could be regarded as an ecosystem consisting of liver cell, hepatitis B virus and immunity, which were integrated by Dudley's hypothesis. The reason for the variations in the clinical course of hepatitis B were found to be the variations of immunological power destroying liver cells and of the absorption of HB virus. Non-A non-3 hepatitis with recurrent aggravation was also studied. The effect of treatment with transfer factor and interferon for chronic hepatitis were simulated, and the dynamics of these treatments were analyzed.     

5例STAT1功能获得性基因突变儿童慢性皮肤黏膜念珠菌病 临床特点及生化免疫分析

目的分析STAT1功能获得性儿童慢性皮肤黏膜念珠菌病(CMC)的临床特点、生化及免疫学检查结果。方法回顾分析2016—2019年经基因检查确诊的5例CMC患儿的临床资料。结果 5例患者,男4例,女1例,平均发病年龄(4.2±3.6)月龄(1～10月龄)。5例患儿均有黏膜感染,4例反复呼吸道感染,4例皮肤感染,3例指趾甲反复念珠菌感染,2例桥本甲状腺炎,甲状腺功能低下、甲状旁腺功能减低、肾上腺皮质功能减退、矮小症各1例。5例患儿基因突变位点均为STAT1,分别为c.849GT、c.988CA、c.862AG、c.1154CT、c.974TA。5例患儿的IgG、IgE无异常,2例IgA、IgM降低明显。CD 3+细胞减少;CD3+CD 4+细胞减少、CD19细胞明显减少各1例。5例患儿的血细胞计数均无异常,2例抗甲状腺球蛋白抗体、抗甲状腺过氧化酶抗体明显增高,甲状旁腺激素降低、皮质醇降低各1例。2例G试验阳性,但无侵袭性真菌感染表现。结论反复皮肤、黏膜、指趾甲念珠菌感染是CMC的重要临床表现,免疫功能筛查有提示意义,须基因检测才能确诊。     

Successful treatment of refractory chronic disseminated candidiasis after prolonged administration of caspofungin in a child with acute myeloid leukemia

This report documents the clinical activity of caspofungin in a 13-year-old girl with acute myeloid leukemia (AML) and chronic disseminated candidiasis (CDC), refractory to amphotericin B and fluconazole. Caspofungin was started at 50 mg/d resulting in a temporary response. With no further clinical improvement and radiological progress after 2 months of therapy, the dose of caspofungin was increased to 100 mg/d, leading to a sustained clinical response. Therapy was given for a total of 12 months and had no attributable adverse effects. This approach resulted in successful treatment of refractory CDC with caspofungin.     

Aortic thrombosis in a neonate with hereditary antithrombin III deficiency: successful outcome with thrombolytic and replacement treatment

We report the case of a newborn male who presented an aortic thrombosis during the neonatal period and was subsequently diagnosed as having antithrombin III (AT III) hereditary deficiency type I. This hypercoagulable condition is known to predispose young adults to venous thrombosis, but in our patient the primary thrombotic incident affected the arterial vessels within the first few days of life. Combined treatment with thrombolytic agents and AT III concentrates recovered aortic permeability, suggesting that the use of AT III may be beneficial for the treatment of thrombotic complications during the first few days of life.     

Cardiovascular function before and after iron therapy by echocardiography in patients with iron deficiency anemia

BACKGROUND: The aim of the study was to estimate the left ventricular contractility using the ratio of left ventricular end-systolic wall stress to left ventricular end-systolic volume index in patients with iron deficiency anemia, for which there are no previous reports. METHODS: Cardiovascular functions were evaluated using echocardiography and pulsed Doppler echocardiography in 30 children aged 3-14 years (hemoglobin 4.9-8.5 g/dL), before, during and after iron therapy. We also studied 38 healthy children as a control group. RESULTS: The left ventricular preload was significantly higher and the left ventricular afterload was lower in the patients with anemia before iron therapy. The ratio of left ventricular end-systolic wall stress to left ventricular volume, an index of systolic function that is independent of preload and afterload, was significantly lower in the patients with anemia before iron therapy (before iron therapy 2.13 +/- 0.44, after therapy 3.52 +/- 0.76, healthy controls 3.42 +/- 0.70). Left ventricular early diastolic filling was significantly higher in the patients with anemia before iron therapy. The cardiac index was also significantly higher before therapy because of the increases in preload, heart rate and early diastolic filling, as well as the decrease of afterload. There were no significant differences in the indices of cardiovascular function between anemic patients after iron therapy compared with control subjects. CONCLUSIONS: The ratio of left ventricular end-systolic wall stress to the left ventricular volume index and the cardiac index suggested that a hemoglobin concentration < or = 6 g/dL was associated with left ventricular dysfunction and circulatory congestion.     

Effects of recombinant human insulin-like growth factor I administration in adults with growth hormone deficiency

Recombinant human insulin-like growth factor I (IGF-I), 40 μg/kg/body weight, was administered subcutaneously at 08.00 hours to six adult patients with growth hormone deficiency (GHD). The mean maximal IGF-I concentrations were found 2–6 hours after injection. Concentrations then gradually declined, though mean values were still above basal 24 hours after the injection. Only one patient maintained IGF-I levels above the lower normal range throughout 24 hours. There was a significant decrease in mean IGF-II concentrations when measured 4 and 24 hours after injection of IGF-I. The diurnal variations of insulin and IGF binding protein-1 were preserved. There were no side-effects, and blood glucose remained normal. These results show that in patients with low IGF-I levels resulting from GHD, it is necessary to administer IGF-I at intervals of less than 24 hours to obtain IGF-I levels that are within the normal range.