Methotrexate treatment of Wegener granulomatosis in children.

Wegener granulomatosis traditionally has been treated with glucocorticoids and cyclophosphamide. Both the disease and its treatments are associated with significant morbidity and mortality rates. There has been an effort to find effective but less toxic alternative treatments. We describe three children with Wegener granulomatosis who responded well to treatment with glucocorticoids and methotrexate, similar to a regimen used in adults.

Prolonged fevers of unknown origin in children: patterns of presentation and outcome.

OBJECTIVE: To review the presentation, clinical characteristics, and outcome of children with prolonged fevers of unknown origin who are referred for pediatric rheumatologic evaluation. METHODS: We used a retrospective review of the charts of the 40 children (23 boys and 17 girls, aged 9 months to 14.6 years) with fevers persisting longer than 1 month who were referred to the Pediatric Rheumatology Clinic between 1984 and 1994, in whom evaluation did not result in diagnosis. Follow-up with children's families, pediatricians, or both was done by telephone. RESULTS: Of the 40 children, 29 had periodic fevers, and 11 had daily fevers without pattern. Patients with periodic fever were younger at onset, had longer duration of symptoms before referral, and higher maximum temperatures. The two groups did not differ in frequency of associated symptoms or signs. At follow-up (mean 60.5 +/- 5 months, n = 37), 10 children with daily fevers (within 24 months) and 23 children with periodic fevers (within 48 months) had completely recovered; three patients continue to have periodic fevers. In patients with daily fevers one had Crohn disease (7 months after initial evaluation) and another had uveitis (4 years after evaluation). One patient with periodic fevers had inflammatory bowel disease 3.5 years after the onset of fevers. Petit mal seizures developed in one patient with periodic fever, and another had mitochondrial encephalopathy. Four children with periodic fevers have attention-deficit hyperactivity disorder, and two have developmental delays. CONCLUSIONS: Fevers without an obvious source usually have a benign outcome, although patients should be monitored for changes in symptoms. Of the children with periodic fevers, 29% were later found to have neurologic problems; the relation to the previous fevers is uncertain.

Human parvovirus B19-associated arthritis in children.

Human parvovirus B19 (HPV B19) infection has been associated with chronic joint complaints in adult patients. We now report 22 children with joint complaints associated with recent HPV B19 infection. These children had either erythema infectiosum or serologic evidence of recent infection. Twenty children had arthritis; two had arthralgias. Eleven children had associated constitutional symptoms. Laboratory findings were generally normal. The duration of joint symptoms was less than 4 months in 14 children; however, six children have had persistent arthritis for 2 to 13 months, which would fulfill criteria for the diagnosis of juvenile rheumatoid arthritis. Although HPV B19 is usually associated with acute arthritis of brief duration, in some children infection with HPV B19 may be associated with the development of chronic arthritis.

Neonatal interleukin-1 beta, interleukin-6, and tumor necrosis factor: cord blood levels and cellular production.

In a prospective study, levels of interleukin-1 beta (IL-1 beta), interleukin-6) (IL-6), and tumor necrosis factor (TNF) were measured in a blind fashion in cord blood plasma from 92 neonates by specific immunoassays, and were correlated with the clinical courses of the infants, including type of delivery and perinatal complications. Plasma IL-1 beta concentration was undetectable in infants born by normal vaginal delivery or elective cesarean section but was significantly increased in infants born after induced vaginal deliveries (142 +/- 68 pg/ml) or urgent cesarean section (290 +/- 21 pg/ml; both p less than 0.05 compared with normal deliveries). The IL-1 beta levels were elevated in infants with severe perinatal complications (282 +/- 116 pg/ml; p less than 0.001), whereas TNF and IL-6 levels were not related to these complications. Infants with isolated perinatal infectious complications had elevated levels of plasma IL-6 compared with those of sick neonates without infection (p less than 0.001). In contrast, TNF plasma levels and IL-1 beta production by cord blood leukocytes were decreased in infants with infectious complications alone (both p less than 0.05). These studies suggest that the levels of IL-1 beta, IL-6, and TNF in the cord plasma relate differentially to clinical complications in the perinatal period.

Wegener granulomatosis in pediatric patients.

Wegener granulomatosis is more easily recognized as a distinct clinical entity than other vasculitides because the initial clinical features frequently include granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. Although the disease has been lethal in the past, prolonged survival and avoidance of end-stage kidney disease can now be expected when cyclophosphamide therapy is introduced early in the course. We report four children with Wegener granulomatosis in whom the initial clinical findings suggested Henoch-Schönlein purpura. In two of the patients Wegener granulomatosis was not recognized until after end-stage kidney disease had developed. The course in these patients emphasizes the need for attention to even scant evidence of inflammation of the upper or lower respiratory tract in patients with glomerulonephritis. Appropriate diagnostic studies may then lead to recognition of Wegener granulomatosis and the prompt institution of appropriate treatment.

Transplantation of adult kidney into the very small child: long-term outcome.

Adult kidneys were transplanted into 12 children weighing between 5,400 and 8,800 gm. Ten received parental and two received cadaver grafts. Ten of the 12 children are alive 18 months to 9 years post transplant; eight have their original grafts and two required retransplantation-their original grafts were lost at 4 and 9 years because of chronic rejection. All but these two surviving children had normal or accelerated growth rates despite growth retardation prior to transplant. All children evidenced moderate to severe delay in psychomotor development prior to transplant. Seven of the ten survivors now have normal psychomotor function. Two are behind in school, and one with a degenerative central nervous system disease prior to transplant remains profoundly retarded. We conclude that because of donor availability, capacity for good donor-recipient matching, and minimization of time on dialysis, transplantation of adult kidneys into pediatric patients is preferable to awaiting the relatively uncommon pediatric cadaver donor. We further conclude that the procedure is warranted.