Questionnaire May Facilitate Earlier SLE Diagnosis, Study Suggests

Dutch investigators found a screening questionnaire might be a good tool to identify patients warranting further testing for systemic lupus erythematosus (SLE).

A new report suggests it might be possible to identify patients with systemic lupus erythematosus (SLE) more quickly using a symptom questionnaire in combination with autoantibody screening.

The study, published in Lupus Science & Medicine, is based on a population cohort of more than 80,000 people in the Netherlands.

Corresponding author Wietske Lambers, MD, PhD, of University Medical Center Groningen, in the Netherlands, and colleagues, wrote that patients with SLE can present with a variety of symptoms, making it difficult to quickly diagnose the autoimmune disease.

“It has been shown that many patients with SLE had visited the general practitioner prior to diagnosis with fatigue, arthralgia, arthritis, rash, alopecia, sicca symptoms, Raynaud’s phenomenon and/ or serositis,” Lambers and colleagues wrote.

In addition, they said immunological changes often occur prior to diagnosis, with autoantibodies detectable in serum years before diagnosis.

Though a number of criteria exist to diagnose SLE, the investigators noted that the Connective Tissue Disease Screening Questionnaire (CSQ), which was developed to diagnose a range of connective tissue diseases, and in particular the SLE-focused questions,(SLE-CSQ) have been shown to help detect SLE with a high rate of sensitivity and specificity, particularly among patients with close relatives who have been diagnosed with SLE.

“Therefore, the SLE-CSQ might contribute to early recognition of SLE,” they wrote.

Lambers and colleagues decided to find out whether self-reported symptoms from the questionnaire might be able to identify previously undiagnosed patients with SLE if paired with demographic and biochemical data and connective tissue disease autoantibody counts.

The investigators used a large population-based data set as their starting point. The database initially included about 167,000 adult residents of the northern region of the Netherlands, each of whom completed a series of health questionnaires at baseline. Two years later, participants were asked to fill out a CSQ, and the 85,295 people who completed the questionnaire became the initial pool for the study. From that group, participants were excluded if they had already been diagnosed with SLE or another connective tissue disease (126 patients).

After exclusions, the investigators found that nearly half of the people in the cohort (41,781 patients, or 49.1%) had no positively answered questions on the SLE-CSQ. However, 2.6% of people in the cohort (2,210) answered “yes” to at least 4 questions, suggesting that they might have SLE.

Further analysis showed these patients tended to be female, which is notable since females are much more likely than males to be diagnosed with SLE. The patients also tended to be younger, have lower body mass index scores, and smoke. Their counts of leukocytes, neutrophils, and monocytes were also higher, but levels of hemoglobin and creatinine were lower, the investigators said. The patients were also more likely to have connective tissue disease antibodies in serum samples, the authors found.

In their discussion, Lambers and colleagues said their study itself is not sufficient to declare that the SLE-CSQ can predict SLE. They said a longer-term follow-up study would be needed before such a claim could be made. However, they said it is possible that the screening questionnaire could be used as a first-line tool, followed by antinuclear antibody (ANA) tests.

“This questionnaire could be used in first-line medical care, preferably as part of a stepwise design,” they wrote. “The next step would then be to test ANA in individuals with high suspicion for SLE based on the questionnaire.”

Patients with positive ANA could then be referred to a specialist for further testing, they said.


Lambers W, Arends S, Roozendaal C, et al. Prevalence of systemic lupus erythematosus-related symptoms assessed by using the Connective Tissue Disease Screening Questionnaire in a large population-based cohort. Lupus Sci Med. 2021;8(1):e000555. doi:10.1136/lupus-2021-000555

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