Cyclosporin A plus prednisone treatment of steroid-sensitive frequently relapsing nephrotic syndrome in children

Recently, there have been numerous reports on the use of cyclosporin A (CyA) in children with nephrotic syndrome (NS). In this prospective study, we wanted to evaluate the efficacy of CyA together with prednisone therapy in children with steroid-sensitive frequently relapsing NS. A total of 11 children (7 boys, 4 girls) with steroid-sensitive NS were included in this study. The patients ranged in age from 3.5 to 15 years (average 8.45 +/- 4.26 years). Renal biopsy showed minimal change disease in five, mesangial proliferation in four, focal glomerulosclerosis in one and membranous glomerulonephritis in one. The NS had lasted from 13 to 113 months (average 50.27 +/- 38.60 months). The number of relapses varied from three to 10 episodes with an average of 5.9 +/- 3.3 episodes. Patients received 5 mg/kg CyA daily in two divided doses for five months and prednisone for a total of eight weeks (30 mg/m2 daily for 4 weeks followed by 30 mg/m2 on alternate days for 4 weeks). After the completion of the treatment protocol, no therapy was given unless a relapse was observed. Mean follow-up period was 14.9 +/- 5.99 months with a range from six to 26 months. Before this combined treatment, there was a mean relapse rate of 0.144 +/- 0.05 relapses month with a range from 0.088 to 0.238. After discontinuation of therapy, the relapse rate dropped to a mean of 0.0179 +/- 0.031 with a range of 0 to 0.083. In conclusion, it would appear that a combination of CyA and prednisone is effective, sustaining the remission in steroid-sensitive NS. Corticosteroids in combination with CyA may be a better approach than conventional steroid treatment in such patients.     

High-dose steroids in childhood acute idiopathic thrombocytopenia purpura

Nine newly diagnosed, previously untreated children (mean age: 4.2 years, range: 1-9 years) with severe acute idiopathic thrombocytopenia purpura (mean platelet count: 5.8 X 10(9)/L, range: 1-12 X 10(9)/L) were treated with high-dose steroids (prednisone 4-8 mg/kg/day). Steroid dose was based on platelet count at presentation: Group I (platelets less than 5 X 10(9)/L) was started on 8 mg/kg/day; Group II (platelets 5-15 X 10(9)/L) received 6 mg/kg/day. All patients had serologic and histologic evidence of acute idiopathic thrombocytopenia purpura. On this protocol, it took a mean number of 1.9 days (1-3 days) to reach a platelet count of at least 20 X 10(9)/L and 9.2 days (3-26 days) to reach a normal platelet count. No significant toxicity was observed except for weight gain ranging from 3-10% and mild behavioral problems. Both groups were on high-dose steroids (4-8 mg/kg/day) for 7.3 +/- 2.1 days. Only one patient had a brief relapse to a platelet count of 18 X 10(9)/L while on therapy (day 14), but responded promptly to an increase in prednisone dose. Presently, all nine patients are in remission and have not required maintenance medication.     

Long-term low-dose cyclosporin A in steroid dependent nephrotic syndrome of childhood

Therapy of steroid-dependent idiopathic nephrotic syndrome is often unsatisfactory. Since 1986 we have treated nine children (six male and three female), aged 3–16 years, with cyclosporin A (CsA) during 2.0–5.2 (median 3.1) years. All had minimal change disease on renal biopsy and had previously received cyclophosphamide. Mean daily dosage of CsA was 4.1 mg/kg (range 2.7–5.8) and mean whole blood trough level was 220ng/ml (range 141–271). The relapse rate decreased from 3.4/patient year before CsA to 0.55 on CsA. Discontinuation of CsA or reduction below 2 mg/kg daily was always followed by a relapse. The overall relapse rate, including the period with very low-dose CsA, was 0.95/patient year. Four patients required additional low-dose alternate-day prednisone. Repeat renal biopsy showed minimal change disease in eight patients and focal segmental glomerulosclerosis in one; CsA-toxicity was mild in two and moderate in one. The latter was the only patient with slightly reduced glomerular filtration rate. Two boys with delayed puberty spontaneously matured and reached expected final height. We conclude that long-term low-dose CsA is very effective and steroid-sparing. Its use is justified in selected patients, particularly in those with numerous relapses and in male patients before and during puberty, as long as renal function and CsA-toxicity are carefully monitored.     

亚硒酸钠及维生素E治疗小儿肾病综合征远期疗效分析

目的评价亚硒酸钠及维生素E(VitE)治疗小儿肾病综合征(NS)远期疗效。方法57例NS患儿在常规使用激素的基础上,37例(NS组)服用亚硒酸钠,0.5mg／d,连服1周,以后每周0.5mg,同时服VitE,50mg／次,3次／d,疗程6个月;20例为对照组。观察两组患儿治疗前后血清硒(Se)、血浆谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛(MDA)及血清免疫球蛋白等指标,随访1.6-7.5年,观察其远期疗效。结果NS组血清Se含量及GSH-Px活力明显增加(P<0.01),MDA显著降低(P<0.05),免疫球蛋白恢复正常。完全缓解NS组33例(89.19％),对照组6例(30.00％);NS组复发3例(9.09％),对照组复发4例(66.67％)。NS组远期疗效显著优于对照组(P<0.05),复发率显著低于对照组(P<0.05)。结论用亚硒酸钠及VitE治疗NS患儿,可提高缓解率,降低复发率;Se含量减少,免疫球蛋白合成不足可能是NS容易感染引起复发的原因之一。     

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome.

OBJECTIVE: Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis. STUDY DESIGN: To study the risks of HPA suppression, a modified low dose synacthen test (0.5 mug) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8-17.6 years) with NS receiving long-term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted. RESULTS: 20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow-up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01). CONCLUSIONS: Children with NS receiving long-term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.     

Pulsed methylprednisolone therapy compared to high dose prednisone in systemic lupus erythematosus nephritis

This study was done to determine whether intravenous methylprednisolone therapy given concomitantly with low-dose daily, oral prednisone would be as effective as highdose daily prednisone in the treatment of patients with active systemic lupus erythematosus (SLE) nephritis.Thirteen patients with active SLE nephritis were started on 2 mg/kg prednisone per day, considered the high prednisone phase. Therapy was continued until remission was achieved. Prednisone administration was then tapered to less than 0.5 but more than 0.2 mg/kg per day. On later relapse, these patients received three doses of methylprednisolone (20 mg/kg per dose) on alternate days and continued on the same daily dose of prednisone (<0.5 >0.2 mg/kg per day) prior to pulse therapy; this was the methylprednisolone phase. The 13 patients were studied in both phases, serving as their own controls.After 1 month of therapy, no significant differences were observed between treatment phases as to improvement in clinical and laboratory findings. A significant increase in the serum concentration of C₃ and C₄ was seen both in the highdose prednisone and methylprednisolone phases, while the serum concentration of anti-ds DNA antibody significantly decreased.Methylprednisolone therapy seems as effective as highdose prednisone in patients with relapse of SLE nephritis. Because side effects are minimal, methylprednisolone administration may be tried as the therapy of choice for these patients.Abbreviation SLE systemic lupus erythematosus     

Pulse Methylprednisolone Therapy in Severe Idiopathic Childhood Nephrotic Syndrome

ABSTRACT. The effect of methyl prednisolone therapy (PM) was studied in 18 children with severe idiopathic nephrotic syndrome (NS). Eight patients were defined as "corticosteroid-resistant" because there was no response to treatment after a minimum of 4 weeks of 2 mg/kg/day of prednisone; 10 patients had a corticosteroid-dependent NS with frequent relapses which occurred under a high threshold dose of prednisone (1 mg/kg/day). Each patient received 4–6 pulses of 1 g/1.73 m² methylprednisolone. Tolerance was generally good. PM therapy permitted a more rapid remission than oral prednisone (average 9±4 days vs. 22±9 days). Remission occurred in 5 of the 8 corticosteroid-resistant patients three of these 5 patients developed corticosteroid-dependent NS. For the children with a corticosteroid-dependent nephrotic syndrome, PM therapy did not affect the threshold dose of prednisone.     

High dose methylprednisolone therapy in nephrotic syndrome

This study was done to determine the efficacy of oral high dose methylprednisolone (HDMP) therapy in the treatment of childhood nephrotic syndrome (NS). Fifteen patients were enrolled in the study. Patients were arbitrarily divided into two groups. Group I received prednisolone (daily 60 mg/m² for 4 weeks, 45, 30, 20, 10, 5 mg/m² on alternate days for 4 weeks) and group II received HDMP (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days, 10 mg/kg/for a week, before 9 am, orally). The patients were followed-up for a duration of 38.0±5.5 months (range 24–68 months) in group I and 42.1±5.5 months (range 16–72 months) in group II. No significant difference was obtained in the duration of remission between both groups (p>0.05), while HDMP induced early remission than prednisolone (p<0.05). The mean relapse rate was 0.8/year in group I and 0.8/year in group II (p>0.05). Although, the number of the patients were limited in the study it can be recommended that patients with NS can be treated with oral HDMP therapy as an alternative to standard oral prednisolone therapy.     

Comparison of Different Regimens of Prednisone Therapy in Frequently Relapsing Nephrotic Syndrome

Abstract. The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was adminstered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received a cumulative dosage of prednisone of 10 mg/m²/day and those with steroid dependency received 19 mg/m²/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75 d); however, they were significantly shorter with short-term prednisone therapy (median 33 d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.     

Double blind placebo controlled trial of low dose oxandrolone in the treatment of boys with constitutional delay of growth and puberty.

Nineteen boys, mean age 14.4 years (range 12.9-16.3), with constitutional delay of growth and puberty were randomised into two groups in a double blind fashion for a three month period. Ten boys received oxandrolone, 2.5 mg per day (mean dose 0.072 mg/kg/day), and nine boys were treated with placebo. Mean growth velocity increased from 4.5 cm/year in the oxandrolone treated group to 9.6 cm/year in three months, and this was sustained at 8.6 cm/year after cessation of treatment. In the placebo treated group, growth rate showed no alteration from 5.1 cm/year to 5.2 cm/year; boys in this group were then treated with oxandrolone, 2.5 mg a day (mean dose 0.073 mg/kg/day) for three months and growth velocity accelerated to 8.6 cm/year. Serum concentrations of insulin-like growth factor -1/somatomedin-C (IGF-1) increased during oxandrolone treatment and continued to rise after treatment had ceased. There was no change in serum IGF-1 concentration during treatment with placebo. Oxandrolone, when used in an appropriate regimen, is an effective, safe treatment for boys with constitutional delay of growth and puberty.     

Renal function and somatic growth in pediatric cadaveric renal transplantation with cyclosporine-prednisone immunosuppression

The posttransplantation courses of 28 consecutive patients (age range, 0.8 to 16 years) who received cadaveric renal allografts and combined cyclosporine-low-dose prednisone immunosuppression were analyzed. The mean follow-up time was 16.5 months (range, four to 42 months). There was one death and the actuarial one-year graft survival was 59%. At follow-up, the group mean (+/- SD) serum creatinine concentration in 14 patients with functioning grafts was nearly double the expected mean value for normal children of similar age and sex (1.13 +/- 0.38 vs 0.61 +/- 0.07 mg/dL), and the mean +/- SD glomerular filtration rate was 76.5 +/- 20.0 mL/min/1.73 sq m (range, 40 to 115.5 mL/min/1.73 sq m). Although rejection accounted for 11 (79%) of 14 graft losses, failure of immunosuppression could be implicated in only four of these patients. Among eight preadolescent patients with good renal function for one year posttransplantation, somatic growth was poor in four and suboptimal in three patients; catch-up growth occurred in one patient. In such patients, the weight-for-height index increased, reflecting the development of obesity after transplantation. We conclude that cyclosporin-low-dose prednisone offers little or no advantage in terms of cadaveric renal allograft survival or stimulation of somatic growth when compared with conventional therapy.     

Final height outcome in girls with Turner syndrome treated with a combination of low dose oestrogen and oxandrolone

Final stature in girls with Turner syndrome treated with combination of low dose oestrogen and oxandrolone. Nineteen prepubertal girls with Turner syndrome (mean age 10.9 years, range, 8.9–14.2 years) were randomly assigned to receive either oxandrolone (0.05 mg/kg/day) or ethinyloestradiol (40 ng/kg/day) for 1 year. Subsequently the alternate therapy was added and the combination given until attainment of final height. Ethinyloestradiol was gradually increased at the age of 12.5 years in order to induce secondary sexual characteristics. The duration of treatment was a mean of 5.2 years (range, 3–7 years) when the 1st year of monotherapy was included. Therapy produced a sustained acceleration in growth rate for a duration of 4 years and eventually has resulted in an increment of mean adult height of 3 cm relative to pre-treatment projected height with mean values of 146.5 cm versus 143.5 cm respectively. The moderate side-effects observed did not cause any of the girls to discontinue treatment. Nevertheless, amelioration of adult height appears to be modest, notably in comparison to published data of growth hormone treatment and 4 girls had a decrease in final height prediction. Conclusion Combination of low dose of oxandrolone and oestrogen may have a moderate but positive impact on final height in girls with Turner syndrome. However, some girls do worse than predicted in term of final height using this regimen. Oestrogen therapy started at low dose around the age of 10 years and increased gradually at approximately 12.5 years to induce secondary sexual characteristics does not have a deleterious effect on adult height in Turner syndrome. In summary, low dose oxandrolone-oestrogen treatment was found to accelerate the tempo of growth in girls with Turner syndrome, but did not appear to have a consistent effect on final height. Received: 22 July 1996 / Accepted: 22 October 1996     

Oxandrolone induces a sustained rise in physiological growth hormone secretion in boys with constitutional delay of growth and puberty

We describe the treatment of 3 boys, mean age 14.9 years (range 13.8-16.1 years) with constitutional delay of growth and puberty using oxandrolone in two dose regimens, 2.5 or 1.25 mg/day for 3 months. Treatment induced an increase in mean height velocity from 5.1 to 8.5 cm/year; this was sustained at 8.8 cm/year in the period following treatment. Growth hormone (GH), luteinising hormone and testosterone secretion were assessed by overnight or 24-hour venous sampling at 15-min intervals before, during treatment and after cessation of treatment. A computer programme was used to analyse GH secretory dynamics. The 3 boys had a mean sustained increase in total GH secretion of 190%. The increase in GH secretion was associated with an increase in amplitude of GH pulses rather than an alteration in pulse frequency.     

Comparison of different regimens of prednisone therapy in frequently relapsing nephrotic syndrome

The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was administered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received 19 mg/m2/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75d); however, they were significantly shorter with short-term prednisone therapy (median 33d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.     

Oxandrolone in Girls with Turner's Syndrome

Twenty-six one-year treatment periods on oxandrolone (0.1 mg/kg/day) were studied in 20 patients with Turner's syndrome. Control patients with Turner's syndrome were matched by using the following criteria: difference in bone age being not greater than 0.S years and difference in the Bayley-Pinneau height prediction not greater than 3 cm. Height and height velocity were compared with standards of girls with Turner's syndrome (10) and expressed in standard deviation scores (SDS). On oxandrolone height velocity increased significantly from −0.3 SDS to +3.0 SDS. The increase in height velocity was negatively correlated to the bone age at onset of treatment ( r = 0.62, p<0.01). Height SDS improved by 0.45 SDS in the treated patients whereas it did not change in the control patients. The bone age velocity during the treatment period (including a six-month period after treatment) was 0.75 year/year in the treated, compared to 0.66 year/year in the control patients (NS). 15 of the 20 patients have reached final height. The difference in final height minus predicted height (Bayley-Pinneau) at onset of treatment was taken as a measure of "gain in final height". Seven of those (mean bone age 12.1 years at onset of treatment) were treated for one year only and had–compared to the matched controls–a mean net gain in final height of 2.5 cm (NS). Eight patients (mean bone age 10.1 years at onset of treatment) were treated for two one-year periods and had a significant mean net gain in final height of 5.2 cm. Height predictions calculated by the method of Lenko (14) gave an identical mean net gain in final height (5.1 cm)     

Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children

Two regimens of steroid treatment for the initial attack of idiopathic nephrotic syndrome (NS) in children were compared in a controlled prospective multicentre study. Long prednisone therapy consisted of 60 mg/m² per 24 h for 6 weeks, followed by alternate day 40 mg/m² per 48 h for 6 weeks. The standard prednisone therapy was 60 mg/m² per 24 h for 4 weeks, followed by 40 mg/m² per 48 h for 4 weeks. A total of 71 children with an initial attack of idiopathic NS were allocated at random to the two groups. The cumulative rate of patients with sustained remissions after 2 years was significantly higher after the long course than after the standard treatment (49% vs 19%,P=0.0079). The mean relapse rate per patient at intervals of 3, 6 and 12 months was lower in the long-course prednisone group than in the standard prednisone group, and the proportion of children with frequent relapses during any subsequent 6 months period was lower in the long-course group than in the standard group (29% vs 57%,P=0.03). Mild side-effects of corticosteroid therapy were observed more frequently after long-course prednisone treatment. It is concluded that long-course prednisone therapy of the initial attack of steroid responsive NS is preferable to the standard regimen because it reduces the rate of subsequent relapses without increasing the risk for severe steroidal side-effects. Contributing investigators and centres were: Prof. F. R. Egli (Basel, Switzerland); Prof. G. Mau, Dr. J. Zimmermann (Braunschweig, Germany); Dr. W. Marg (Bremen, Germany); Dr. R. Mallmann (Bonn, Germany); Dr. K. Witzel (Düsseldorf, Germany); Prof. D. Michalk (Erlangen, Germany); Prof. H. Olbing (Essen, Germany); Dr. E. Bopp (Flensburg, Germany); Prof. J. Dippel (Frankfurt, Germany); Dr. H. Zappel (Göttingen, Germany); Dr. D. Schwarke (Hamburg, Germany) Prof. J. Brodehl (Hannover, Germany); Prof. K. Schärer (Heidelberg, Germany); Prof. F. Schindera (Karlsruhe, Germany); Dr. M. Kirschstein (Lübeck, Germany); Prof. H. P. Weber (Lüdenscheid, Germany); Prof. M. Brandis (Marburg, Germany); Prof. R. Eife (München, Germany); Dr. F. K. Hübner (München, Germany); Dr. K. Gellissen (Neuwied, Germany); Prof. W. Rauh (Trier, Germany).     

The 2000 Burkitt lymphoma trial in Malawi

BACKGROUND: We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity. METHODS: All Malawian children admitted to Queen Elizabeth Central Hospital, from 03/08/2000 to 12/03/2002 with confirmed BL were eligible. A fine needle aspirate, bone marrow aspirate, cerebrospinal fluid cytology, haemoglobin (Hb), white cell count (WCC), malaria smear, ELISA for HIV, and abdominal ultrasound were performed routinely. Murphy staging was used. The first dose of chemotherapy (COP1) consisted of 300 mg cyclophosphamide (CPM), 1 mg vincristine, and 60 mg prednisone given on day 1 and followed by COP2 on day 8 (only for patients with larger tumour volumes, stage III or IV disease). The vincristine dose in COP2 was 2 mg. COMP1 and 2 given on days 22 and 36 consisted of 500 mg CPM, 2 mg vincristine, 60 mg prednisone, and 2 g methotrexate. All doses were calculated per body surface area. Intrathecal methotrexate and hydrocortisone were given with COP1 and 2. RESULTS: Forty-two patients, 30 boys and 12 girls median ages 6 and 7.5 years, respectively, had Murphy stage I(n5), II(n8), III(n21), and IV(n8) disease. The face was involved in 74%, abdomen in 55%, bone marrow in 14%, kidneys in 24%, and 12% had paraplegia. Fourteen children died during or shortly after completion of chemotherapy. Three of these were disease related. Twelve patients suffered a local relapse after 57-328 days, and one a CNS relapse at 76 days. The projected EFS at 12 months is 50% in stage I, 50% in stage II, 24% in stage III, 25% in stage IV, and 33% for all patients. The cumulative mean dose of CPM was 62 mg/kg in survivors and 64 mg/kg in children who relapsed. One third of patients experienced significant marrow suppression, and infections after COMP1. CONCLUSIONS: Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.     

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome

Objective

Children with nephrotic syndrome (NS) are usually treated with long‐term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic‐pituitary‐adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis.

Study design

To study the risks of HPA suppression, a modified low dose synacthen test (0.5 μg) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8–17.6 years) with NS receiving long‐term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted.

Results

20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow‐up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01).

Conclusions

Children with NS receiving long‐term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.     

Five years of growth hormone treatment in children with Prader-Willi syndrome. Swedish National Growth Hormone Advisory Group

The authors have followed 18 prepubertal children (3-12 years of age) with Prader-Willi syndrome during 5 years of growth hormone (GH) treatment. Initially, all the children participated in a randomized, controlled GH trial, conducted to assess the effects of GH treatment on growth, body composition and behaviour. GH was administered to group A (n = 9) at a dose of 0.1 IU/kg/day (0.033 mg/kg/day) for 2 years. Group B (n = 9) was untreated for the first year, but the children were given GH at a dose of 0.2 IU/kg/day (0.066 mg/kg/day) during the second year. Thereafter, all children stopped GH treatment for 6 months and were then restarted with GH at a dose of 0.1 IU/kg/day (0.033 mg/kg/day). During the first year of GH treatment, there was a dramatic increase in height SDS in both groups. The attained height percentile was maintained during the continued GH treatment. Five years after the start of GH treatment, mean height SDS is still above average for age. Four children have reached final height, all within 2 SD of target height. During the first year of GH treatment, body mass index (BMI) SDS decreased significantly from 3.0 to 1.5 SDS in group A and from 2.8 to 1.2 SDS in group B, but it increased again during the 6-month period without treatment. Following the restart of GH treatment, BMI SDS has stabilized at 1.7 SDS for group A and 2.5 SDS for group B. In 16 of 18 patients, fasting insulin, glucose and the A1c fraction of glycosylated haemoglobin remained within normal ranges during 5 years of GH treatment. Following a period of rapid weight gain, two children have developed non-insulin-dependent diabetes mellitus. Glucose homeostasis returned to normal when GH treatment was withdrawn. In conclusion, GH treatment has a proven favourable effect on growth and body composition in patients with Prader-Willi syndrome. Treatment should be individualized, and close surveillance of glucose homeostasis is needed, especially if the patient is severely obese.     

Periodic fever, aphthous stomatitis, pharyngitis and adenitis: PFAPA syndrome in Argentina

IntroductionPFAPA syndrome is a benign, non-hereditary condition, of unknown etiology and pathogenesis. There are few reports of it in South America. The purpose of this article is to communicate the experience in a large pediatric hospital in Argentina.Patients and methodsA total of 18 patients were diagnosed with PFAPA between 2002 and 2009 at the Medium Risk Clinic, Prof. Dr. Juan P. Garrahan Pediatrics Hospital, Buenos Aires City. The modified criteria reported by Thomas et al were used for diagnosis. The follow up continued with evaluations during new febrile episodes, clinic check ups and telephone calls.ResultsThe mean age at onset of symptoms was 2.5 years (range: 0.4–7.5) and the mean lag time from onset of symptoms and diagnosis was 3.2 years (range: 0.4-10.9). Fever episodes lasted for a mean of 4.5 days (range: 2-8), with a mean interval of 23 days (range: 15-30) between the beginning of the attacks. Febrile episodes were treated with methyl prednisone at a dose of 1 mg/kg or betamethasone at a dose of 0.15 mg/kg in a single dose. With a mean follow up of 2.6 years (range: 0.5–5.9) 13 patients remain with febrile episodes at a mean interval of 4.6 months (range: 1-12). Five patients did not have febrile crisis for more than a year during the study period and they are considered cured; in this group the disease lasted a mean of 4.7 years (1-9.7).ConclusionsPFAPA syndrome is a sporadic, difficult to diagnose, condition. Both methyl-prednisone and betamethasone have shown to be effective in controlling the symptoms during the febrile crisis. The definitive remission of the syndrome may occur in the first years of onset, although in most patients the febrile episodes continue with an increase of free intervals and attenuated symptoms, and full recovery in prepuberty or adolescence with no sequelae.