Steroid treatment of idiopathic thrombocytopenic purpura in children. Preliminary results of a randomized cooperative study

Preliminary data from a prospective randomized study of the use of a short course of adrenocorticosteroids in 73 children with ITP demonstrates a significant advantage of moderate dose (60 mg/m2/day p.o. X 21 days) prednisolone therapy in decreasing the duration of severe thrombocytopenia in most patients. The period of risk for serious bleeding, as reflected in the Rumpel-Leede test, was also significantly reduced. The number of children who developed chronic thrombocytopenia, although small in both groups, appeared to be uninfluenced by steroid therapy. No side effects or serious complications were noted in this trial.     

Combined renin angiotensin blockade in childhood steroid‐resistant nephrotic syndrome

Background: Reduced proteinuria results in delayed deterioration of renal function and remission of proteinuria predicts a good long‐term prognosis in steroid‐resistant nephrotic syndrome (SRNS). The aim of this study was to analyze the effects of the combined angiotensin‐converting enzyme inhibitor and angiotensin II receptor blocker in reducing proteinuria in SRNS. Methods: A prospective study of eight patients with SRNS was conducted at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University from September 2003 to December 2007. Enalapril was given at 0.1 mg/kg/day and was increased by 0.1 mg/kg/day every 4 weeks up to 0.6 mg/kg/day (maximum 40 mg/day) and 1 mg/kg/day of losartan was added for 4 weeks and stepped up to 2 mg/kg/day (maximum 100 mg/day) for another 4 weeks. Results: There were five boys (62.5%) and three girls (37.5%). The mean age at diagnosis was 8.3 ± 4.1 years (range 2.05–13 years) and age at enrollment was 11.7 ± 3.8 years (range 6–16 years). Renal histology revealed seven focal segmental glomerulosclerosis and one immunoglobulin M nephropathy. The results showed significant reduction on mean spot urine protein : creatinine ratio from 9.6 ± 2.3 to 3.6 ± 1.6 (P < 0.05) and 24‐h urine protein from 182.8 ± 59.6 to 28.7 ± 8.2 mg/m²/h (P < 0.05). Urine protein reduction ratio at the end of the study was 50% (P= 0.08). Serum cholesterol, albumin, potassium, blood pressure and renal function had no significant change. No clinical and laboratory side‐effects were reported. Conclusion: Combined high‐dose angiotensin II receptor blocker to high‐dose angiotensin‐converting enzyme inhibitor therapy is safe and effective in reducing proteinuria in childhood SRNS. However a large‐scale study should be conducted to validate this result.     

Efficacy of captopril treatment in children with steroid-resistant nephrotic syndrome

We studied the efficacy of captopril, an angiotensin-converting enzyme inhibitor in treating persistent moderate or severe proteinuria in children with various glomerular diseases other than minimal-change nephrotic syndrome. Captopril was administered for 3 months to 15 normotensive and nonazotemic or mildly azotemic patients (12 boys, 3 girls) in whom corticosteroid and cytotoxic treatment had failed to induce remission. Urinary protein excretion decreased from 2873.14±1937.50 (mean ± s.e.m.) to 1684.71 ± 1463.13 mg/day (P < 0.05). The reduction in proteinuria was not related to a significant fall in systemic blood pressure or a change in renal function. Serum albumin did not rise and side effects due to captopril were not observed. We concluded that, in the short term, captopril can be used safely and effectively for decreasing the proteinuria of nephrotic children unresponsive to conventional therapy.     

Extracorporeal leukocyte removal therapy for patients with ulcerative colitis

Background: The purpose of the present paper was to investigate efficacy of leukocytapheresis (LCAP) or granulocytapheresis (GCAP) in pediatric patients with ulcerative colitis (UC), including reduction of the total dose and side‐effects of corticosteroids. Methods: Courses of five Japanese adolescents with UC were analyzed. Four patients had recurrent UC with repeated remissions and exacerbations despite therapy including 5‐aminosalicylic acid in combination with a corticosteroid. The other patient had a first attack. Effectiveness of adding LCAP or GCAP was assessed with regard to short‐term changes in clinical activity, complications, and longer‐term outcome. Results: Clinical improvement was attained in three patients, while the other two did not improve and underwent colectomy. One of the two patients had moderately severe complications from LCAP and showed increased clinical activity during LCAP. The other, who began therapy with LCAP alone, had moderate improvement only after addition of a corticosteroid. Conclusion: Additional studies are needed to determine optimum timing of LCAP or GCAP and initiation of remission‐maintenance therapy.     

Long-term use of zonisamide in refractory childhood-onset epilepsy.

This open label study examined the long-term efficacy and safety of zonisamide as adjunctive therapy in mentally retarded and multiple-handicapped patients with severe childhood-onset epilepsy. The study included 24 patients (mean age 12.5 years, range 2-40 years) which had different severe epilepsy syndromes (75% focal, 12.5% generalized, 12.5% refractory status epilepticus) refractory to at least 6 (median 10) anti-epileptic drugs. All patients were followed for at least 18 months after beginning of zonisamide treatment. Mean duration of zonisamide therapy was 55 weeks (range 5-168 weeks) and mean maintenance dosage was 7.7 mg/kg/day (range: 4-16 mg/kg/day). The patients received an average of 1.9 (range 1-3) concomitant antiepileptic drugs. The initial response rate defined as a > or =50% reduction of seizure frequency after 8 weeks was 58.3% (14 of 24 patients). Four of 14 initial responders developed loss of efficacy during long-term treatment. The retention rate after 18 months was 41.7% (10 of 24 patients). One patient (4.2%) became completely seizure-free after initiation of zonisamide treatment and remained seizure-free for the entire observation period of 18 months. Overall, zonisamide was well tolerated. Side effects were observed in 46% of patients and were mild to moderate. They mostly occurred during titration and subsided in maintenance dosing. Only in two patients (8.3%) zonisamide therapy was discontinued due to side effects (loss of appetite). No serious side effects were observed. These results are similar to the findings of Japanese studies suggesting that long-term use of adjunctive zonisamide therapy may be beneficial for treating mentally retarded, multiple handicapped patients with highly refractory childhood-onset epilepsy.     

Renal‐limited necrotizing granulomatous vasculitis in a pediatric patient

A 10‐year‐old girl presented with mild proteinuria and hypertension. Laboratory data indicated slightly elevated serum creatinine (0.67 mg/dL) and elevated serum IgG (2111 mg/dL). On renal arteriography mild stenosis over the entire length of the right renal artery and irregular stenosis of the interlobar arteries in the right kidney were seen. She was diagnosed with renovascular hypertension, and received conventional anti‐hypertensive therapy, but did not respond to them. The right kidney had atrophy and dysfunction on technetium‐99m‐labeled dimercaptosuccinic acid renal scintigraphy, and was therefore resected. Histopathology of the kidney indicated severe necrotizing granulomatous vasculitis affecting the arteries from the renal hilus to the interlobar area. After nephrectomy plus steroid pulse therapy, blood pressure and urinary protein returned to normal. To our knowledge, this is the first report of necrotizing granulomatous vasculitis limited to the medium‐sized renal arteries.     

Re-treatment for immune globulin-resistant Kawasaki disease: A comparative study of additional immune globulin and steroid pulse therapy

BACKGROUND: We compared the efficacy and safety of additional intravenous immune globulin (IVIG) therapy with steroid pulse therapy in patients with IVIG-resistant Kawasaki disease. METHODS: Two-hundred and sixty-two consecutive patients had been treated with a single dose of IVIG (2 g/kg) and aspirin (30 mg/kg per day). Thirty-five patients (13.4%) were not clinical responders to the initial IVIG treatment. They received an additional IVIG treatment (1 g/kg) within 48 h after the initial treatment. Seventeen patients (6.5%) did not respond to the additional IVIG treatment. We randomly divided these patients into two groups: group 1 consisted of eight patients who were treated with a single additional dose of IVIG (1 g/kg), while group 2 consisted of nine patients who were treated with steroid pulse therapy. RESULTS: The IVIG-resistant patients had a high incidence of coronary artery lesions (CAL; 48.6%). Five patients (62.5%) in group 1 had CAL, including two patients who each had a giant aneurysm and three patients who each had a small aneurysm. Seven patients (77.8%) in group 2 had CAL, including two patients who each had a giant aneurysm, two patients who each had a small coronary aneurysm and three patients who each showed transient dilatation during steroid pulse therapy. There was no significant difference in the incidence of CAL between the two groups. The duration of high fever in group 2 (1.4~0.7 days) was significantly shorter than in group 1 (4.8~3.4 days; P<0.05). The medical costs for the treatment of patients in group 2 (113, 012 yen +/- 22,084) were significantly lower than those for group 1 (144,194 yen +/- 12,914; P<0.05). CONCLUSIONS: Steroid pulse therapy may be useful in the treatment of patients with IVIG-resistant Kawasaki disease who experience prolonged fever. However, transient dilatation of the coronary artery is observed during steroid pulse therapy, so careful echocardiographic examination should be performed for those patients receiving steroid pulse therapy for the sake of early detection of coronary artery abnormalities.     

Successful treatment with pulse cyclophosphamide of a steroid-refractory hepatitic variant of liver acute graft-vs.-host disease in a child

Kawahara Y, Morimoto A, Masuzawa A, Ikeda T, Hayase T, Kashii Y, Nozaki Y, Kanai N, Momoi MY. Successful treatment with pulse cyclophosphamide of a steroid‐refractory hepatitic variant of liver acute graft‐vs.‐host disease in a child.
Pediatr Transplantation 2012: 00: 000–000. © 2012 John Wiley & Sons A/S. Abstract: A 13‐yr‐old boy with recurrent acute myeloid leukemia underwent HSCT using cells from an unrelated donor who matched all HLA antigens except one. Forty‐two days later, the patient developed a steroid‐refractory hepatitic variant of liver GVHD with peak ALT and T.Bil values of 1406 mU/mL and 10.4 mg/dL, respectively. He was successfully treated with pulse Cy (1000 mg/dose × one day) without a change in chimerism being observed or acquiring an infection. All immunosuppressant therapies could be discontinued 12 months after HSCT. Two yr after HSCT, the patient remains in CR without chronic GVHD. This single case report suggests that pulse Cy may be a promising therapy for steroid‐refractory GVHD, especially hepatitic GVHD, but needs to be further tested in clinical trials.     

Short term efficacy of intravenous dexamethasone and methylprednisolone therapy in steroid resistant nephrotic syndrome

OBJECTIVE: To compare the short term efficacy of intravenous pulses of methylprednisolone and dexamethasone in treatment of steroid resistant nephrotic syndrome in children. METHOD: We prospectively treated 81 children with idiopathic steroid resistant nephrotic syndrome with six alternate-day pulses of intravenous dexamethasone (5 mg/kg) or methylprednisolone (30 mg/kg). Fifty-nine patients received dexamethasone and 22 were treated with methylprednisolone. Two patients in dexamethasone and one in methylprednisolone group developed serious infection during administration of alternate-day pulses and could not complete the therapy. RESULTS: The median age at treatment was 38 (36-74.7) months. Of patients who completed therapy, 20 (35.1 percent) (95 PERCNT CI 22.9-48.9) and 7 (33.1 percent) (95 percent CI 14.6-56.9) patients in dexamethasone and methylprednisolone group, respectively achieved complete remission. Following alternate day pu1ses the median urinary albumin to creatinine ratio decreased from 9.2 to 1.5 (P less tha 0.005) in dexamethasone group and from 12.1 to 0.7 (P less than 0.005) in methylprednisolone group. The median reduction in urinary albumin to creatinine ratio was 54.1 PERCNT (95 percent CI 32.7- 83.9) and 63.2 percent (95 percent CI 23.5- 100) in dexamethasone and methylprednisolone group respectively. The chief side effects of therapy were transient hypertension or worsening of preexisting hypertension, which occurred in 31 (54.4 percent) patients in dexamethasone group and 10 (47.6 percent) in the methylprednisolone group. The hypertension was satisfactorily controlled on antihypertensive drugs. One or more side effects were observed in 66.7 percent (95 percent CI 52.9-78.6) children receiving dexamethasone therapy and 61.9percent (95 percent CI 38.4-81.9) receiving methylprednisolone, which was comparable. CONCLUSIONS: We conclude that intravenous dexamethasone is as effective as methylprednisolone in inducing remission in patients with steroid resistant nephrotic syndrome.     

Prophylaxis for ribavirin‐related anemia using eicosapentaenoic acid in chronic hepatitis C patients

Background: Ribavirin‐related anemia is a serious side‐effect of the pegylated interferon and ribavirin therapy used for hepatitis C, and may be cause for a reduction in ribavirin dose or even cessation of treatment. The aim of this study was to evaluate the prophylactic effects of oral eicosapentaenoic acid (EPA) supplementation on ribavirin‐induced hemolytic anemia in pediatric and young adult patients. Methods: Twelve chronic hepatitis C patients ranging in age from 3 to 21 years (mean, 13.9 ± 5.1 years) who received pegylated interferon α‐2b and ribavirin combination therapy were randomized to either the control group (n= 6) or EPA group (n= 6). Blood samples were collected before, and at 4, 8, and 16 weeks after treatment to measure clinical laboratory parameters. Results: The reduction in hemoglobin levels of the EPA group was significantly ameliorated at 8 and 16 weeks when compared to the control group (P < 0.05). There was no significant difference in plasma ribavirin concentrations between the two groups during the treatment. However, one patient in the control group had a reduction in ribavirin dose. Conclusion: EPA supplementation prevented ribavirin‐induced hemolytic anemia during combination therapy with pegylated interferon α‐2b and ribavirin in pediatric and young adult patients.     

Treatment of esophageal caustic injuries: experience with high-dose dexamethasone

Caustic ingestion is one of the most life-threatening events in the pediatric age group. Several types of non-surgical management have been proposed for the esophageal strictures that inevitably follow ingestion. These include esophageal stenting and steroid therapy, which has received much attention in recent years. In this study, high-dose dexamethasone (1 mg/kg daily for 4–6 weeks) was administered to 9 children with endoscopic evidence of lesions equal to or greater than extended second degree who were at high risk of developing esophageal stenosis. Results were compared with those of other groups of children treated with the current protocol of 2 mg/kg daily oral prednisone. Clinical findings demonstrated that dexamethasone exerts a more effective anti-inflammatory action along with reduced cushingoid side effects; this enables children to better tolerate repeated dilatations, which often are necessary to maintain esophageal patency. However, since these treatment protocols were applied mainly to ammonia ingestions, which are known to induce less severe sequelae, further investigations are required in the presence of more serious initial lesions. Correspondence to: S. Cadranel     

Role of methylprednisolone pulse therapy of nephroses in children

Methylprednisolone (MP) pulse therapy (1 g/1.73 m2 x 3) has been used without side effects in 16 children with steroid dependent or resistant nephrosis. MP allowed a complete remission in 6 patients (group I: 37.5%), after a mean duration of 12 days; 2 of them experienced early relapse; the other patients had either a too short or no follow-up. One child was on partial remission (group II: 6%). The other patients were resistant to therapy (group III: 56%); 8 of them had a renal biopsy which showed focal glomerulosclerosis in 6 (75%). The authors point out that the main interest of methylprednisolone pulse therapy is to confirm steroid resistance.     

Eficacia y seguridad de tacrolimus oral para el tratamiento de la enfermedad inflamatoria intestinal pediátrica

BackgroundIn certain clinical situations, such as acute and severe episodes of ulcerative colitis (UC) or Crohn's Disease (CD), that do not respond to conventional intravenous steroid treatment, we need potent, fast-acting drugs to induce clinical remission and avoid surgery.ObjectivesTo evaluate the efficacy and safety of oral tacrolimus treatment of acute and severe UC or CD to induce their remission, and also to assess its efficacy in delaying or avoiding surgery.Material and methodsWe present a retrospective study that included all patients under 18 years of age with acute and severe bouts of CD (colonic or ileocolonic location) or UC who were treated with oral tacrolimus at our institution from January 1998 to December 2007.ResultsWe included a total of 8 patients (4 males and 4 females), 6 presented with UC and 2 had CD. The mean age of our patients at the start of the treatment was 11.8 years (range 2.75–16.58 y) and the mean time from diagnosis to the start of tacrolimus therapy was 4 months (range 1–96 m). An initial response was obtained in 50% of patients. Plasma trough levels of tacrolimus remained between 5–11 ng/ml. Six of the eight patients (75%) required surgery. In one patient with UC and in another with CD, surgery was avoided. In 2 of the 6 patients with UC, surgery was postponed beyond 6 months.ConclusionsTacrolimus is useful in inducing clinical remission in patients with acute and severe bouts of UC or CD, and so can avoid or delay the surgery; it may also be used as a bridging agent until the new maintenance therapy with other immunosuppressants is effective.     

Amiodarone Used Alone or in Combination with Propranolol: A Very Effective Therapy for Tachyarrhythmias in Infants and Children

The aim of the study was to evaluate the efficacy of amiodarone used alone or in combination with propranolol in infants and children affected by life-threatening or drug-resistant tachyarrhythmias. The study included 27 children (median age 3 months), affected by life-threatening and/or drug-resistant supraventricular or ventricular tachyarrhythmias. The loading dose of amiodarone was 10–20 mg/kg/day and the maintenance dose ranged between 3 and 20 mg/kg/day. When amiodarone was ineffective, propranolol was added at a dosage of 2–4 mg/kg/day. The study population was divided into two groups: group A was composed of patients <1 year and group B of patients >1 year. The effectiveness of the therapy was assessed by clinical evaluation, Holter monitoring, exercise testing, and, in patients with reentry tachycardias, electrophysiological testing. Amiodarone used alone was effective or partially effective in 4/14 (28%) patients in group A and in 11/13 (85%) patients in group B (p < 0.006). Among amiodarone-resistant patients, the combined therapy with propranolol was effective in 8/10 patients in group A and 2/2 patients in group B. Therefore, amiodarone used alone or in combination with propranolol was effective in 25/27 (93%) patients. During the follow-up (20.5 ± 13 months) there were no arrhythmic effects but side effects were noted in 5/27 (18.5%) patients. Amiodarone seems to be an effective drug in the control of the life-threatening and/or drug-resistant supraventricular and ventricular tachyarrhythmias in children. The addition of propranolol can significantly enhance the success rate of this class III drug, especially in the treatment of reentry tachycardias due to accessory pathways.     

The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology

The outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid‐resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995–2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re‐LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p < 0.00001). From 2008, three patients underwent LTx for cryptogenic FHF with PVI and conventional IS. PVI was well tolerated, and no relevant severe complications were observed. More strikingly, the patients who received PVI overcame biopsy‐proven immunological events and are all currently doing well with excellent graft function after more than five yr. We conclude that PVI is technically safe and effective for preventing severe rejection in pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications.     

Steroid response in moderate to severe pediatric ulcerative colitis: a single center’s experience

Background  

We aimed to analyze clinical and inflammatory markers of steroid non-response in patients with moderate/severe ulcerative colitis (UC) at the time of diagnosis.     

Steroid pulse therapy prevents restenosis following balloon dilatation for esophageal stricture

Purpose

This study aimed to evaluate the effectiveness of intravenous steroid pulse therapy following balloon dilatation for esophageal stenosis and stricture in children.

Methods

The study enrolled six children, including three with congenital esophageal stenosis and three with anastomotic strictures after surgery for esophageal atresia, all of whom were treated by balloon dilatation combined with high-dose intravenous methylprednisolone pulse therapy. Methylprednisolone was injected intravenously at a dose of 20 mg/kg/day for 2 days, starting from the day of dilatation, followed by 10 mg/kg/day for 2 days, for a total of 4 days.

Results

Esophageal stricture recurred in all three patients with congenital esophageal stenosis despite repeated balloon dilatation without methylprednisolone. However, the symptoms of dysphagia improved and did not recur after systemic steroid pulse therapy following balloon dilatation. Symptoms also resolved in all three patients with anastomotic strictures following balloon dilatation with systemic steroid pulse therapy. All six patients remained asymptomatic after 6–21 months follow-up, with no complications.

Conclusion

Intravenous methylprednisolone pulse therapy following balloon dilatation is safe and effective for the treatment of esophageal stenosis and strictures in children.

     

Pharmacokinetic study of mizoribine in child‐onset glomerulonephritis

Background: Mizoribine (MZR) has been successfully used without serious adverse effects in patients with various types of glomerulonephritis, but there are only a few pharmacokinetic studies of MZR. The purpose of the present paper was to report the results of a pharmacokinetic study of MZR in child‐onset glomerulonephritis. Methods: Nine patients were enrolled. MZR was administered orally at 60–300 mg/day (3.0–8.4 mg/kg bodyweight/day) divided in one or two daily doses. Blood samples were collected 7–10 times before and after drug administration. Urine samples were also collected during the blood sampling periods. Twenty‐three concentration curves of MZR were analyzed in the present study. Pharmacokinetic parameters for mizoribine were estimated using concentration–time profiles. The non‐parametric Spearman correlation coefficient was calculated to determine significant associations between variables. P < 0.05 was considered significant. Results: The obtained pharmacokinetic values at a dose of 3.36 ± 1.91 mg/kg bodyweight were as follows: time to peak serum MZR concentration, 2.94 ± 0.82 h; peak serum MZR concentration, 1.59 ± 1.16 μg/mL; half‐life, 1.96 ± 0.92 h; area under the serum MZR concentration–time curve from time zero to infinity, 9.36 ± 6.58 μg h/mL; volume of the distribution of MZR at a steady state, 2.03 ± 0.80 L/kg; and rate of urinary excretion of MZR, 49.1 ± 18.7%. Conclusions: The parameters estimated in the present study may be useful for the MZR treatment of patients with child‐onset glomerulonephritis.     

Low‐dose vasopressin infusion therapy for refractory hypotension in ELBW infants

Background: Severe hypotension in infants, especially in preterm infants, is associated with poor neurological outcome and high mortality. In adults, low‐dose vasopressin (arginine vasopressin: AVP) infusion therapy has been effective for treating hypotension that is refractory to vasopressors and inotropes. Methods: The effects of AVP infusion therapy for refractory hypotension were retrospectively evaluated in extremely low‐birthweight infants. Between January 2002 and November 2005, 22 infants with refractory hypotension treated with low‐dose AVP infusion were reviewed. The average birthweight was 658 g (±142 g), and the average gestational age was 24.9 weeks (±1.4). The changes in blood pressure, urinary output, and other parameters in response to AVP therapy were analyzed in all the infants. Results: After AVP infusion, systolic blood pressure increased from 30 mmHg to 43 mmHg (P < 0.0001), and the diastolic pressure increased from 15 mmHg to 24 mmHg (P < 0.0001). The urine output dramatically increased from 1.5 mL/kg per h to 4.0 mL/kg per h (P < 0.0001). AVP infusion, however, was not effective in four of the 22 patients (18%). The sodium concentration in the serum decreased mildly after administration. In six patients the serum sodium concentration decreased below 130 mEq/L. Severe mitral regurgitation was observed in two patients. Three infants showed a transient decrease in the platelet count during AVP infusion. Conclusions: Low‐dose AVP therapy should be considered as rescue therapy when high‐dose catecholamine therapy and/or steroid administration do not produce sufficient increase in the blood pressure. Further investigations are required to prove the efficacy and safety of AVP infusion therapy in preterm infants.     

Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis.

OBJECTIVE: To assess the efficacy of low-dose oral methotrexate (MTX) therapy for children with severe iritis. METHODS: MTX in a weekly dose of 7.25 to 12.5 mg/m2 was administered orally to four patients (two with juvenile rheumatoid arthritis [JRA] and two with sarcoidosis) with severe iritis not adequately controlled by topical and systemic corticosteroid therapy. The treatment was initiated with half of the total dose and increased every 2 weeks until the final dose was reached. Iritis was graded from 0 to +4 according to the density of cells in the anterior chamber of the eye. RESULTS: There were three girls and one boy with a mean age of 10.5 years. Two patients were African American and two were Caucasian. The mean age at onset of iritis was 6 years. The mean duration of MTX therapy was 28.8 months. Significant improvement was noted in two of the four patients in ocular inflammation, demonstrated by reduction of cell density from +4 to +1. Two patients had a mild improvement of the iritis. However, corticosteroids were significantly reduced in all patients. One patient was completely off steroids within 30 months of MTX therapy. In the remaining three cases, the steroid dose was successfully tapered from 0.82 mg/kg/d to 0.15 mg/kg/d (mean doses) within a mean duration of 20 months. No side effects were observed with MTX therapy. CONCLUSION: Low-dose MTX therapy was effective and safe, and displayed steroid-sparing properties in four children with severe iritis.