Delays Seen in Diagnosing SLE in Many Children Due to Mildness of Early Symptoms, Large Study Reports

Frequent delays found in diagnosing systemic lupus erythematosus in a large group children were mostly due to mild symptoms at disease onset, while those with evidence of severe and multi-system disease were typically diagnosed in about one month, a study of pediatric lupus patients in Brazil reported.

The study, “Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study,” was published in the journal Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory condition that may involve multiple organs and present with a wide plethora of clinical symptoms. The disease affects both adults and children, and younger patients can have more active disease.

But accurately diagnosing childhood-onset SLE (cSLE) can take months and even years, and researchers don’t fully understand why. Investigators in this study suggested it may be related to symptom severity seen in pediatric patients.

“A short time interval to diagnosis was rarely observed in the present study in cSLE  patients,” except for those with more severe evidence of disease, the researchers said, adding “abrupt, aggressive and acute onset presentation may facilitate a prompt diagnosis by general pediatricians and subspecialists.”

The research team examined data covering 1,555 childhood-onset lupus patients, recruited from 27 different rheumatology centers across Brazil between between September 2016 and May 2017.

The most frequent symptoms reported were fever and arthritis (26%), followed by facial rash (8%), joint pain (7%), accumulation of fluid (edema; 4%), oral ulcers (2%), swelling of the lymph nodes (2%), seizures (1.5%), and abnormal results in the urine test (1.5%).

To determine how symptoms might affect a lupus diagnosis, patients were divided into three groups, based on how quickly they were diagnosed. Those in group A (60 people, mean age at diagnosis 11.1) were diagnosed within one month of symptom onset; group B patients (522; mean age 12) took between one and three months to be diagnosis; and group C (973 patients; mean age 12.5) waited more than three months for a correct diagnosis, and some as many as 12 years.

Group A patients — those diagnosed most quickly —  met “significantly” more diagnostic criteria using the Systemic Lupus International Collaborating Clinics (SLICC) classification method than patients in groups B and C.

Accordingly, these children had a higher frequency of distinct SLE symptoms – like oral ulcers, lung and chest tissue inflammation, kidney inflammation, and neurological problems.

Significantly, more patients in group A also tested positive in blood tests that confirm a lupus diagnosis — with indicators including a low platelet count, low levels of white blood cells, and anti-dsDNA antibodies (specific auto-antibodies used to detect lupus).

Finally, group A patients had the highest evidence of disease activity, measured using the SLE Disease Activity Index 2000 (SLEDAI-2K) , followed by those on group B.

Group C had the least severe disease and milder symptoms. Fewer patients in this group reported severe liquid accumulation and swelling of the joints, connective tissue inflammation, presence of protein in the urine, and lower complement levels – an indicator of disease activity.

“Our study was the first to demonstrate unequivocally that the majority of cSLE patients had a long time interval from the onset of signs and symptoms to diagnosis,”the investigators wrote, adding “the mild lupus manifestations seem to contribute to the diagnosis delay.”

The smallest group of childhood-onset lupus patients with clear evidence of the disease (group A) had a notably “shorter time interval,” likely due to the fact that “active disease and multisystemic severe presentation” facilitates “early recognition of the disease.”