Jane G. Schaller

Neonatal interleukin-1β, 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.

Human parvovirus B19-associatedarthritis in children

Human parvovirus B19 (HPV B19) infection has been associated with chronic jointcomplaints 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.

Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex.

In an attempt to map the gene (or genes) controlling the synthesis fo the fourth component of complement (C4), we performed linkage studies in a family with hereditary C4 deficiency. The proband, a seven-year-old boy with lupus erythematosus, consistently lacked deteftable serum C4 by both functional and protein measurements. The complement defect was transmitted as an autosomal recessive disorder. Eight of 15 family members were considered to be heterozygotes, seven because of low C4 levels and one because of genetic data (obligate heterozygote). The gene (or genes) coding for C4 deficiency appeared to be linked to the major histocompatibility complex (A2,B12,DW2 on the maternal side and A2,BW15,LD108 on the paternal side) and to other markers known to be in close proximity to the histocompatibility complex on chromosome 6 (phosphoglucomutase-3, glyoxalase-1 and properdin factor B).

Arthritis as a presenting manifestation of malignancy in children

Arterial thrombosis occurred with about the same frequency in arteries treated with papaverine and placebo. Age (below 1 year or over), sex, race, weight of the child, severity of cardiac status, type of cardiac lesion, site of arteriotomy, or duration of catheterization did not influence the outcome. Seven children had severe arterial spasm as manifested by a cool, pulseless limb and weak oscillations recorded by the oscillometer at the end of the catheterization but with return of the pulse within 4 to 8 hours. In these seven patients, papaverine had been used in three and placebo in four, again demonstrating no particular advantage to the use of topical papaverine.

Comparison of tolmetin sodium and aspirin in the treatment of juvenile rheumatoid arthritis

The Pediatric Rheumatology Collaborative Study Group was established in 1973 to undertake systematic trials of new drugs in the treatment of juvenile rheumatoid arthritis. The first drug evaluated was tolmetin (1-methyl-5-p-toluoylpyrrole-2 acetic acid), a new nonsteroid anti-inflammatory agent. A four-week open trial with 30 patients and a subsequent 12-week double-blind trial against aspirin with 107 patients were conducted. Tolmetin and aspirin had equal anti-inflammatory and analgesic effects in the treatment of JRA. Elevations of transaminase values attributed to aspirin were not found with tolmetin. Adverse effects accompanying administration of tolmetin did not appear to be of major clinical significance.

Arthritis associated with inflammatory bowel disease in children

Arthritis occurred in 23 of 136 (17 per cent) children and teenagers with inflammatory bowel disease, in 18 of 86 (21 per cent) patients with ulcerative colitis, and 5 of 50 (10 per cent) with granulomatous bowel disease. Eighteen children had peripheral arthritis which characteristically affected only a few large joints and was of brief duration and benign outcome. Five boys had spondylitis which was progressive and inseparable clinically from ankylosing spondylitis. Occurrence of joint manifestations was not associated with severity of bowel disease. Anemia and growth retardation occurred frequently. Mucocutaneous lesions were associated with peripheral arthritis but not with spondylitis. No patient had iridocyclitis. The possibility of bowel disease should be considered in children presenting with arthritis, particularly if gastrointestinal complaints, mucocutaneous lesions, anemia, or growth retardation are associated with pauciarticular arthritis. Peripheral arthritis is benign and regresses with improvement of underlying bowel disease but spondylitis is progressive and requires recognition and management for prevention of deformity.

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 childrens 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.

Histocompatibility antigens in childhood-onset arthritis

One hundred and twelve well-studied patients with a prior diagnosis of juvenile rheumatoid arthritis were differentiated into seven clinically distinct subgroups, including a group in whom recognizable ankylosing spondylitis had developed by time of follow-up. An apparent increased prevalence of HLA-B27 in the entire series (26%) was clearly related to its increased prevalence in only two subgroups: patients whose disease had progressed to overt ankylosing spondylitis (five of five patients) and boys with pauciarticular arthritis whose disease would be consistent with early ankylosing spondylitis (11 of 18 patients). There were no significant associations of B27 with systemic onset JRA, polyarticular JRA, pauciarticular JRA in girls, or JRA with chronic iridocyclitis. The only other significant alterations found were increased prevalences of HLA-A2 and HLA-BW15 in patients with polyarticular disease without identifiable rheumatoid factor. This study emphasizes that the clinical disorders included under the category of juvenile rheumatoid arthritis represent more than a single disease and that this heterogeneity must be considered in interpreting studies such as those of histocompatibility typing.

Ankylosing spondylitis with childhood onset.

Seven male patients with childhood-onset ankylosing spondylitis are described. Ankylosingspondylitis should be considered in the differential diagnosis of childhood arthritis, especially if the patient is a male with onset of disease in late childhood, if there are any symptoms referable to the sacroiliac joints or lumbodorsal spine, or if there is transient peripheral arthritis affecting only a few joints. Initial symptoms are characteristically fleeting and recurrent. Early diagnosis and therapy are important for preservation of adequate function. The frequency of hip disease may be greater in individuals with early onset of disease.

Hepatic involvement in juvenile rheumatoid arthritis

Five children with rheumatoid arthritis, in whom the onset was before the age 6 years, had massive hepatomegaly with mild derangement of liver function studies (elevated serum levels of transaminases and bilirubin and bromsulphalein retention). Three patients were originally thought to have malignancy or infections, rather than juvenile rheumatoid arthritis. All have had high spiking fevers and other systemic manifestations. Hepatomegaly occurred at or near the onset of disease in all patients and regressed with its remission. Hepatic histology, studied in 4 of 5 children, showed nonspecific periportal collections of inflammatory cells and hyperplasia of Kupfler cells. No child has had evidence of progressive liver disease. Juvenile rheumatoid arthritis should be considered in the differential diagnosis of hepatomegaly in children, particularly if high fever is associated; and other manifestations of the disease, such as arthritis, rheumatoid rash, splenomegaly, generalized lymphadenopathy, pleuritis, and pericarditis, should be sought.