Children with juvenile-onset systemic lupus erythematosus tend to have significant disease activity and high rates of organ involvement with damage accumulation, according to findings from the UK JSLE Cohort Study.

The findings underscore the complex and severe nature of JSLE and the need for pediatric multidisciplinary management that "considers carefully issues related to disease activity and damage and medications, along with growth, puberty, educational development and psychosocial well being," Dr. Louise Watson of the University of Liverpool, England, and her colleagues from the UK JSLE Study Group said online in the Jan. 31 issue of Arthritis & Rheumatism.

In the 198 patients from the cohort who fulfilled four or more American College of Rheumatology SLE criteria and who were followed for 4.5 years, disease progression was evident in multiple organ systems, based on assessment using a pediatric adaptation of the British Isles Lupus Assessment Group (pBILAG2004) disease activity index. For example, renal involvement was present in 47% of the patients at baseline and had progressed to 80% at the time of the latest analysis, the investigators said (Arthritis Rheum. 2012 Jan. 31 [doi:10.1002/art.34410]).

At the last analysis, 82% of patients had musculoskeletal involvement, 91% had hematologic involvement, 54% had immunologic involvement, and 26% had neurologic involvement, as measured by pBILAG2004.

Of note, pBILAG2004, which collects more detailed information about organ-related disease activity than do the ACR criteria, demonstrated markedly greater actual organ involvement than indicated by the respective ACR criteria for various organ systems, they said.

The median pBILAG2004 score decreased from 8.5 at baseline to 2 at 12 months’ follow-up, representing a statistically significant improvement, and the systemic lupus erythematosus disease activity index (SLEDAI) score decreased significantly over 12 months from 12 points to 4 points. Although disease activity improved over time, disease damage accrual secondary to JSLE was notable. Even after only 4.5 years of follow-up, 28% of patients demonstrated disease-associated damage at the time of data analysis.

"There is a predominance of neurological disease damage involving 15 patients, of whom 6 have experienced one or more cerebrovascular accidents," Dr. Watson and her associates wrote, noting that severe scarring alopecia occurred in 20 patients and that 7 had renal damage, including 1 child with renal failure.

The investigators also found that steroid use among the cohort was high at 93%, and that 24% required cyclophosphamide – a finding that underlines the burden of disease in pediatric patients and the importance of developing steroid-sparing regimens following robust randomized controlled trials for new interventions in JSLE. "Alternative therapies to relieve the burden of corticosteroids on this population are urgently required," they added.

The UK JSLE cohort is a multidisciplinary, multicenter collaborative network established in 2006 to determine the clinical characteristics of JSLE and to support clinical translational research. Patients include children with symptom onset prior to age 17 years. The median age at diagnosis was 12.6 years, and the median time from symptom onset to diagnosis was 3.2 months.

There were other findings of note from this analysis of cohort data:

–Important gender differences in disease prevalence and characteristics. A sex distribution of 5.6 females to every male (but only 2.7 females to every male among those under age 10 years) "is typical of childhood-onset disease where a female predominance is less striking than in adult-onset disease," the investigators said.

Males in this cohort also were more likely to present at a younger age than females, and they had a greater likelihood of having a discoid rash and a reduced likelihood of having had arthritis.

–A high incidence (38%) of family history of autoimmune disease. This finding, in the context of the generally more severe JSLE phenotype compared with adult SLE, a very early age of onset, short time exposure to potential environmental triggers of lupus, and the relatively high male-to-female sex ratio compared with adult disease, points to "probable genetic factors being important in the pathogenesis of JSLE compared to later-onset disease," Dr. Watson and her associates noted.