X Linked Agammaglobulinemia: A Single Centre Experience from India

The authors report a series of seven cases of X-linked Agammaglobulinemia, diagnosed and receiving treatment at a tertiary care centre in Mumbai. The ages of the patients ranged from 15 mo to 15 y. After diagnosis at a mean age of 3 ½ y, all were advised intravenous immunoglobulin (IvIg) infusion therapy in doses of 400–600 mg/kg every 3–4 wk. They were followed up for an average duration of 9 y, throughout which the complications and overall response to immunoglobulin therapy have been observed. The clinical profiles of each of these cases were retrospectively analysed with respect to age at diagnosis, frequency and severity of infections before and after initiation of treatment, co-morbidities and response to therapy. The results demonstrate the importance of early diagnosis and its correlation with decreased complications.     

Propranolol Treatment of Complicated Hemangiomas

Objectives

To evaluate laboratory and radiological features of hemangiomas in childhood in addition to efficacy and safety of propranolol as a first-line treatment of complicated hemangiomas retrospectively.

Methods

The files of 60 patients who were diagnosed as capillary hemangioma were evaluated retrospectively. Fourteen children with complicated hemangiomas treated with propranolol were analysed, in terms of side effects, efficacy and duration of treatment.

Results

These fourteen patients (23 %) were treated with propranolol because of ulcerated, infected and/or deep seated localisations. The duration of treatment with propranolol were between 3 and 12 mo (median: 6 mo). Bronchospasm was observed in one patient during treatment. Except for two patients, all of them responded to propranolol treatment with limited side effects.

Conclusions

The present results support that propranolol is safe and effective treatment choice for complicated infantile hemangiomas, because of minimal side effects and encouraging response rates (80 %). In addition, the authors suggest that routine cranial radiological imagings might not be necessary for hemangiomas without any neurological symptoms.     

Immunosuppressive Therapy in Aplastic Anemia

Objective

To assess the response to antithymocyte globulin based immunosuppressive therapy (IST) in pediatric patients with idiopathic aplastic anemia.

Methods

Thirty patients (19 boys and 11 girls) with aplastic anemia received antithymocyte globulin and cyclosporine. Twenty-two patients had severe and 8 had very severe aplastic anemia.

Results

Mean age of the patients was 9.19?±?2.56?y. Three patients died within 1?mo of therapy, two due to sepsis and one due to intracranial hemorrhage. Twenty-seven patients were analyzed for response to therapy. Eight patients (29.7%) responded at 3?mo: 3 complete response (CR) and 5 partial response (PR). Six mo after the therapy, overall response (OR) was seen in 9/27 (33.3%), with one more patient in no response group achieving partial response. At 1?year, patients in CR maintained their status and 1 patient in PR group relapsed. He again achieved partial response with repeat course of ATG. Responders had significantly shorter duration of illness and higher absolute neutrophil count as compared to non responders to IST. None of the patients developed acute leukemia in the follow up.

Conclusions

The treatment of aplastic anemia in pediatric patients is a challenging task. One third of the patients achieved overall response which included both complete and partial response.     

Candidemia in a pediatric intensive care unit.

OBJECTIVE: To examine the incidence, epidemiology, and clinical characteristics of candidemia in a pediatric intensive care unit. DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care unit of a tertiary care teaching and referral hospital in north India. SUBJECTS: All patients with candidemia from March 1993 to December 1996. INTERVENTIONS: Patient-related data were analyzed to study candidemia in relation to reason for fungal culture, underlying medical conditions, predisposing factors, Candida isolates, antimicrobial and antifungal treatment, and deaths. MEASUREMENTS AND MAIN RESULTS: Sixty-four patients with candidemia were identified. The Candida species isolated were Candida tropicalis (48.4%), C. albicans (29.7%), C. guillermondii (14.1%), C. krusei (6.3%), and C. glabrata (1.6%). Thirty-three patients were detected by a high-risk surveillance blood culture, whereas 31 patients were detected while undergoing septic workup. Sixteen (25%) patients were asymptomatic; they recovered without any antifungal therapy and without any sequelae. Of 48 symptomatic patients, 11 died before institution of antifungal therapy; 37 received oral itraconazole (10 mg.kg(-1).day(-1)). Seven (19%) of these 37 patients died. Those who recovered had sterile culture on average by day 14 (range, 4-30) and received the antifungal therapy on average for 24 days (range, 9-42 days). Overall mortality rate was 28.1%, and bivariate analysis showed significant association with Pediatric Risk of Mortality score (p =.0001), presence of symptoms (p =.003), isolation of nonalbicans Candida in general (p =.04) and C. tropicalis specifically (p =.001), and failure to give presumptive antifungal therapy (p =.055). On multivariate analysis, Pediatric Risk of Mortality score and isolation of C. tropicalis were the only significant predictors of mortality. CONCLUSIONS: Nonalbicans Candida accounted for 70% of candidemia in a pediatric intensive care unit. High-risk surveillance blood cultures aided diagnosis in about half the patients. Severity of illness and isolation of C. tropicalis were significant predictors of mortality.     

Propranolol in supraventricular tachycardias of childhood

9 children with supraventricular tachycardias refractory to conventional therapy were treated with propranolol. In 3 children normal sinus rhythm was restored. In 3 others frequency of paroxysmal arrhythmias was decreased. In 1 reduction of ventricular response to the ectopic rhythm was achieved, and in 2 remaining patients, propranolol had no effect. The dosage of propranolol ranged from 0·5 to 4·0 mg/kg per day, given orally, with few side effects. It appears that propranolol can play an important role in treatment of supraventricular arrhythmias of childhood unresponsive to conventional therapy.     

Diabetes mellitus-related autoantibodies in childhood autoimmune hepatitis

OBJECTIVE: To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH). RESEARCH DESIGN AND METHODS: Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone. RESULTS: There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbA1c), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control population. The majority of the patients with HLA-DRB1*03 or DRB1*04, however, were positive for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers. CONCLUSIONS: AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers.     

Factors at onset predictive of lasting remission in pediatric patients with Graves' disease followed for at least three years.

Seventeen pediatric patients (mean age at diagnosis 10 yr and 9 mo +/- 2 yr and 9 mo) with Graves' disease treated with 0.3-0.7 mg/kg/day methimazole and followed for at least three years, during which drug suspension was attempted on attainment of good clinical and metabolic compensation, were retrospectively studied to look for factors predictive of lasting remission present at onset. Lasting remission was defined as a clinical and laboratory picture of euthyroidism lasting at least one year in the absence of treatment at the end of the follow-up. A distinction was drawn between patients who reached remission after one or two courses (groups 1 and 2) and those who never attained a lasting remission (group 3). TRAb (TBIAb) levels at onset were the only factor significantly correlated with the response to treatment. Age at diagnosis, goiter size and fT3 and fT4 concentrations were not significantly correlated with the clinical picture. The series was too small to allow any assessment of the real importance of these factors, though a generally better response was displayed by children over 11 years old, without appreciable or with very small goiter and moderately increased thyroid hormone levels at onset (fT3 < 25 pg/ml in 10/10 in groups 1 and 2 and 2/7 in group 3 patients; fT4 < 40 pg/ml in 7/10 in groups 1 and 2 and 3/7 in group 3 patients). It was also found that better results were obtained when the initial drug course was protracted for at least two years.     

Use of Propranolol for Infantile Hemangiomas

Treating infantile hemangiomas may be associated with significant morbidity. Recently, propranolol, a nonselective β-blocker, has become a reputed and successful treatment modality for infantile hemangiomas. Here, the author presents experience with oral propranolol in treatment of 14 patients with infantile hemangiomas. The drug was tolerated well and no side effects except reversible bronchospasm in 3 were observed during treatment. Eleven of the patients, younger than 1 year, showed a good response, with more than 50% reduction in the size of the hemangiomas. Although there are a limited number of patients, these results showed that oral propranolol therapy is a safe and effective choice in the treatment of infantile hemangiomas before the age of 1 year.     

Use of propranolol for infantile hemangiomas

Treating infantile hemangiomas may be associated with significant morbidity. Recently, propranolol, a nonselective β-blocker, has become a reputed and successful treatment modality for infantile hemangiomas. Here, the author presents experience with oral propranolol in treatment of 14 patients with infantile hemangiomas. The drug was tolerated well and no side effects except reversible bronchospasm in 3 were observed during treatment. Eleven of the patients, younger than 1 year, showed a good response, with more than 50% reduction in the size of the hemangiomas. Although there are a limited number of patients, these results showed that oral propranolol therapy is a safe and effective choice in the treatment of infantile hemangiomas before the age of 1 year.     

The effect of early treatment in children with chronic hepatitis

BACKGROUND: The aim of this study was to compare the efficacy of interferon alpha (IFN) or IFN and ribavirin (IFN+RIB) combination therapy in children with chronic hepatitis C (CHC). Most children were infected during treatment for pediatric malignancies. PATIENTS AND METHODS: We reviewed the charts of 20 patients (11 boys and 9 girls) aged 10.6 +/- 3.7 years with CHC who were treated between 1995 and 2001. Seven patients diagnosed with CHC before 1998 were treated with 3 million units of IFN three times weekly for 6 to 12 months. Thirteen children diagnosed after 1998 were treated with 3 million units of IFN three times weekly plus 15 mg/kg of ribavirin daily for 6 months (IFN+RIB). RESULTS: Demographic and clinical characteristics were not different between the two treatment groups. A sustained complete response defined as serum alanine aminotransferase normalization and hepatitis C virus RNA clearance at 6 and 12 months after termination of treatment occurred in three of seven children (43%) treated with IFN monotherapy compared with 7 of 12 children (54%) in the group treated with IFN+RIB combination therapy (not significant). The only difference between responders and nonresponders was the duration of infection before the initiation of therapy, which was significantly shorter in responders (1 +/- 0.3 vs. 5.6 +/- 2.2; P = 0.001). CONCLUSIONS: In this small cohort of children with CHC, early initiation of antiviral treatment was associated with a sustained response rate independent of treatment type. Regular follow-up of children at risk of acquiring hepatitis C virus infection should assist in the early diagnosis. Early initiation of antiviral treatment may improve the rate of sustained response.     

Effects of propranolol therapy in Moroccan children with infantile hemangioma

Infantile hemangiomas are the most common childhood vascular tumors. Propranolol is a β-adrenergic blocker that has proven effective in the treatment of this tumor. Numerous studies around the world have been published, describing satisfactory responses in pediatric populations with a higher cure rate and fewer adverse effects than when using corticosteroids. The aim of this study was to evaluate the efficacy and adverse effects of propranolol in Moroccan pediatric patients diagnosed with infantile hemangioma who were treated with oral propranolol. A prospective study was conducted from May 2009 to May 2017 in the department of dermatology of a hospital in Casablanca. All the patients who had infantile hemangioma were included. The study comprised 121 patients with infantile hemangioma: 90 girls and 31 boys. The mean age was 6 months. The majority of hemangiomas were mixed (63%) and located on the face and neck. The treatment was well tolerated by all the patients. The dosage of propranolol was gradually increased from 1 mg to 2 mg/kg/day. We noted a decrease in coloration after 48 hours. The healing period for ulcerated hemangiomas was 20 days. A decrease in size was noted after 1 month, while a decrease in palpebral obstruction occurred after 3 days. Treatment with propranolol in this group of Moroccan pediatric patients proved to be safe and effective at a dose of 2 mg/kg/day, reducing the size and coloration of the hemangioma. Treatment should be stopped at an appropriate time, which is determined primarily by the lesion regression rate after propranolol treatment.     

Randomized comparative study of ampicillin/sulbactam vs. ceftriaxone for treatment of soft tissue and skeletal infections in children

In a prospective study 105 children hospitalized with soft tissue infection, 11 children with suppurative arthritis and 9 children with osteomyelitis were treated with either parenterally administered ampicillin/sulbactam or ceftriaxone. Treatment was randomized using a computer-generated table in a 2:1 fashion: 84 patients received ampicillin/sulbactam and 41 patients received ceftriaxone. Organisms isolated from wound site or blood cultures included Staphylococcus aureus (33), Streptococcus pyogenes (19), Haemophilus influenzae (9) including 4 beta-lactamase-positive organisms, Streptococcus pneumoniae (5), Neisseria gonorrhoeae (3) and 9 other organisms. Clinical and bacteriologic response was satisfactory in 100% of the ampicillin/sulbactam-treated patients and in 93% of the ceftriaxone-treated patients. Two patients with S. aureus infections treated with ceftriaxone had a delayed response and required change in therapy to parenterally administered oxacillin. Ampicillin/sulbactam represents a potentially useful single agent for the treatment of cellulitis and bone or joint infections in pediatric patients.     

Autoimmune Hepatitis in Children: Experiences in a Tertiary Center

Objective

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in the children of all ages. The present study aimed to evaluate the clinical and paraclinical presentations, including pattern of autoantibodies, response to treatment, mortality, and liver transplantation outcome in the Iranian children with AIH.

Methods

The medical records of 87 children (56 girls and 31 boy) diagnosed with AIH between 2001 and 2010 were retrospectively analyzed for clinical and paraclinical profiles and also treatment outcome.

Findings

The mean age of the patients was 10.1±4.5 years (64.4% females). The most common clinical findings were jaundice (70.1%), splenomegaly (67.8%), and hepatomegaly (51.7%). Antinuclear, anti-smooth muscle, and anti LKM antibodies were positive in 14/62, 22/53 and 6/40 patients, respectively (36 patients had type 1 AIH, 6 patients had type 2 AIH, 26 patients were seronegative, and autoantibodies were not available in 19 cases). The most common histological finding in the liver biopsies was chronic hepatitis with interface activity that was seen in 65 (74.7%) patients. The complete response was seen in 52 (59.8%) patients and 24 (27.6%) patients underwent liver transplantation. One-year and five-year survival rates were 87.5% and 80% in the transplanted patients.

Conclusion

AIH should be kept in mind in the differential diagnosis of both acute and chronic liver diseases in the children and treatment with combination of corticosteroids and azathioprine is a good treatment option. In the patients with end stage liver cirrhosis that did not respond to medical therapy, liver transplantation is the treatment of choice.     

Long-term outcome after sclerotherapy withor without a beta-blocker for variceal bleeding in children

BACKGROUND: Esophageal variceal bleeding is a life-threatening complication of portal hypertension. Optimal treatment for the prophylaxis of variceal rebleeding in children has not yet been determined. In the present study, we aimed to compare the long-term efficacy of endoscopic sclerotherapy with or without oral beta-blocker therapy in the secondary prophylaxis of variceal bleeding. METHODS: Thirty-eight children who had undergone endoscopic sclerotherapy (EST) sessions for variceal bleeding in the Department of Pediatric Gastroenterology, Istanbul University Istanbul School of Medicine, were entered into this retrospective cohort study. Twenty patients (mean +/- SD age 7.0 +/- 2.7 years) had undergone only sclerotherapy sessions (SG), whereas 18 patients (mean age 6.8 +/- 3.4 years) had received oral propranolol (1-2 mg/kg per day) additionally for 2 years (SPG). The number of patients with successful obliteration, the time required for obliteration and variceal recurrence rate were analyzed as primary indicators of the effectiveness of therapy. RESULTS: Variceal obliteration was achieved in 16 of 20 patients (80%) in the SG group and in 16 of 18 patients (88%) in the SPG group. Time required for variceal obliteration was significantly shorter in the SPG group compared with the SG group (4.1 +/- 1.4 vs 3.2 +/- 0.9 months; P < 0.05). The variceal recurrence rate was 65 and 38.8% in the SG and SPG groups, respectively.Compared with the SG group, less variceal rebleeding was observed during EST in the SPG group (25 vs 16.6%, respectively).However, these differences were not statistically significant. CONCLUSIONS: Endoscopic sclerotherapy combined with oral propranolol treatment shortens the time required for variceal obliteration. However, the other indicators of treatment effectiveness are not influenced statistically by the addition of propranolol to the treatment regimen. Randomized prospective clinical studies in larger pediatric series are needed before offering a combination of EST with oral propranolol as the most rational approach in the secondary treatment of esophageal variceal bleeding in children.     

Propranolol in prevention of portal hypertensive hemorrhage in children: a pilot study.

BACKGROUND: Data regarding the use of propranolol in the prevention of portal hypertensive hemorrhage in pediatric patients are limited despite its widespread use in adults with cirrhosis. The purpose of this study was to evaluate safety and efficacy of propranolol in the management of portal hypertension in the pediatric population. METHODS: Medical information was retrieved from the records of 21 children with portal hypertension who received propranolol either before or after an episode of gastrointestinal bleeding. Data collected included diagnosis, type of portal hypertension, age at initiation of therapy, bleeding episodes before and during propranolol therapy, degree of reduction of heart rate, adherence, and adverse effects. RESULTS: Fourteen of 21 patients did not experience portal hypertensive bleeding while receiving propranolol. Of the seven patients who had bleeding episodes, two had failed to adhere to the medication regimen, and four were receiving doses of less than 1 mg/kg per day. Only one of the four patients who experienced bleeding before initiation of therapy also bled while receiving propranolol, and two of the three patients who had a heart rate reduction of less than 25% each experienced a bleeding episode. Side effects were minimal and did not necessitate discontinuation of therapy in any patient. CONCLUSIONS: Propranolol was well tolerated with minimal side effects in our patients with portal hypertension. Adherence and adequacy of dosage (>1 mg/kg per day, more than twice daily dose frequency) are important determinants of efficacy. A reduction in heart rate of less than 25% may be associated with suboptimal efficacy.     

Herpes simplex virus in febrile neutropenic children undergoing chemotherapy for cancer: a prospective cohort study

BACKGROUND: The primary objective of this study was to determine the prevalence of oral herpes simplex virus (HSV) as detected by polymerase chain reaction, in pediatric oncology patients with febrile neutropenia. Our secondary objectives were to describe the association between oral HSV and prolonged fever, neutropenia, mucositis, and response to initial antimicrobial therapy. METHODS: In this prospective cohort study, we obtained a mouth swab and blood specimen from oncology patients with febrile neutropenia, and tested them for HSV by polymerase chain reaction. Prolonged fever was defined as the presence of fever 48 hours after initiation of broad-spectrum antibiotic therapy. RESULTS: Of the 75 oral and blood specimens obtained, only 7 oral swabs (9%) and 2 blood samples (3%) were positive for HSV. Oral HSV was not associated with prolonged fever or neutropenia. However, oral HSV was associated with longer median duration of mucositis (8 days; interquartile range, 0-12 days) compared with negative episodes (0 days; interquartile range, 0-2.5 days); P = 0.005. Oral HSV also was associated with inferior successful response to initial antimicrobial therapy (1 of 7, 14.3%) compared with negative episodes (51 of 67, 76.1%); P = 0.002. CONCLUSIONS: The prevalence of HSV infection in pediatric oncology patients with febrile neutropenia was low and was not associated with prolonged fever. However, oral HSV was associated with prolonged mucositis and poorer response to initial therapy. It is unknown whether early intervention with acyclovir can alter these associations.     

VIncristine,irinotecan, and temozolomide in children and adolescents with relapsed rhabdomyosarcoma

1 Background

The combination of vincristine, irinotecan, and temozolomide (VIT) is often used to treat children and adolescents with relapsed rhabdomyosarcoma (RMS); however, the outcome of these patients has not been previously described.

2 Procedures

We sought to determine the response rate (RR) and progression‐free survival (PFS) for patients with relapsed RMS treated with VIT by retrospective review of patients treated at five tertiary care hospitals. Prior treatment with irinotecan was permitted.

3 Results

Among 19 patients with a median age of 8 years (range 2–17 years), 12 (63%) were males and 12 (63%) had embryonal histology. Median time to relapse from initial diagnosis was 16 months (range 2.8‐45 months). VIT was used as first, second, third, or fourth line of therapy in four (21%), seven (37%), six (32%), and two (10%) patients, respectively. Four patients received VIT as adjuvant therapy following radiation and/or surgery. Therefore, among 15 evaluable patients, the best response to VIT was 0 (complete response, CR), 0 (partial response, PR), 4 (stable disease, SD), and 11 (progressive disease, PD) for an overall clinical benefit rate (CR + PR + SD) of 26.7% (95% CI: 7.8–55.1%). After a median follow‐up of 8 months, 2 (10%) patients were alive without disease, 3 (16%) were alive with disease, and 14 (74%) patients died of PD. PFS at 3 months was 23% (95% CI: 5.7–46.7%).

4 Conclusions

VIT therapy in combination with adequate local control is associated with some disease control in patients with first relapse RMS and may be another reasonable option to offer patients as salvage therapy.     

以血小板减少为首发症状的婴儿自身免疫性肝炎2例并分析

摘要：目的 总结自身免疫性肝炎婴儿患者临床特点及诊治情况,为该病的诊断、治疗提供依据。方法 分析我院收治的2例婴儿期起病的自身免疫性肝炎患儿的症状、体征、辅助检查,结合文献资料进行分析并提出相应的治疗方案。结果 2例患儿均以血小板减少为首发症状,以肝功能异常、肝脾肿大为主要临床表现,结合肝功能、免疫球蛋白、血清学抗体及肝穿检查结果确诊为自身免疫性肝炎,对激素或联合硫唑嘌呤应答良好。结论 自身免疫性肝炎临床症状可不典型,在婴儿中较少见,临床医师面对合并血小板减少的肝功能异常的婴儿时,需注意考虑是否存在自身免疫性肝炎,应尽早行肝穿以明确诊断,期为治疗、停药、预后提供依据,一旦诊断明确,需积极予激素或联合硫唑嘌呤治疗,以防病情恶化。     

Efficacy and safety of ampicillin/sulbactam and cefuroxime in the treatment of serious skin and skin structure infections in pediatric patients. UNASYN Pediatric Study Group.

BACKGROUND: Pediatric skin and skin structure infections are often polymicrobial and require empiric therapy effective against pathogens that may be resistant to many antimicrobial agents. The present study tested the efficacy and safety of a parenteral beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, and a beta-lactamase-stable cephalosporin, cefuroxime, in serious pediatric skin and skin structure infections requiring hospitalization and parenteral antimicrobial therapy. METHODS: This was a multicenter, randomized, prospective, comparative open label trial that enrolled patients 3 months through 11 years of age. Patients received 150 to 300 mg/kg/day ampicillin/sulbactam in equally divided intravenous doses every 6 h. Cefuroxime was given in a dosage of 50 to 100 mg/kg/day either intravenously or intramuscularly in equally divided doses every 6 or 8 h. Maximum treatment was not to exceed 14 days. Patients could receive subsequent oral antimicrobial treatment at the investigator's discretion. RESULTS: At final evaluation for clinical efficacy, 78.0% (n = 46) of the 59 evaluable patients who received ampicillin/sulbactam were cured and 22.0% (n = 13) were improved. The respective values for the 39 evaluable patients treated with cefuroxime were 76.9% (n = 30) and 23.1% (n = 9). At the end of treatment all pathogens were eradicated from 93.2% (n = 55) of 59 patients treated with ampicillin/sulbactam and from 100% of 39 who received cefuroxime. There were no significant differences between treatments in clinical or bacteriologic efficacy. Both ampicillin/sulbactam and cefuroxime were well-tolerated. CONCLUSION: Both ampicillin/sulbactam and cefuroxime provide safe and effective parenteral antibiotic therapy in pediatric patients with serious skin and skin structure infections.