Connective Tissue Disease Screening Questionnaire May Predict Early SLE

Investigators theorized that this questionnaire, in conjunction with autoantibody determination, could help screen for SLE in the early stages of the disease.

Participants in the Connective Tissue Disease Screening Questionnaire (CSQ) who answered positively to at least 4 systemic lupus erythematosus (SLE)-focused questions had a greater chance of being diagnosed with SLE, according to a study published in Lupus Medicine & Science.1 Investigators theorized that this questionnaire, in conjunction with autoantibody determination, could help screen for SLE in the early stages of the disease.

“The presenting symptoms of the disease are non-specific and diverse, hindering early recognition and resulting in frequent diagnostic delay. 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. Besides clinical symptoms, immunological changes take place before the disease is uncovered, as autoantibodies can be detected in serum many years before diagnosis,” investigators stated. “Hence, there is a window of opportunity for earlier diagnosis of SLE. Early identification of patients with SLE would allow timely diagnosis and treatment, probably preventing organ damage.”

Volunteers of the Dutch Lifelines cohort completed the CSQ, which included 11 questions related to SLE symptoms, such as red rash on the cheeks, sores in the mouth, hair loss, anemia, and protein in the urine. These specific questions showed 96% sensitivity and 86% specificity for detecting SLE. Health, medical history, medications, and nutritional behavior was also assessed.

A general examination and bloodwork were performed and 25% of participants received a connective tissue disease (CTD) autoantibody screen. Only those who completed a follow-up CSQ questionnaire 2 years later were included in the study. CSQ data was collected between 23 and 30 months from baseline, with a median of 25 months.

Multivariate multinominal logistic regression tests were performed to account for confounders.

A total of 85,295 participants completed the SLE-CSQ data. After excluding patients with SLE (n = 46) and other CTDs (n = 80), nearly half (49.1%) of participants had an SLE-CSQ score of 0 and only 2.6% (n = 2210) had a score of ≥4. Of the excluded participants, 73.9% (n = 34) of patients with SLE and 27.8% of patients with CTDs reported scores of 4 or more. Photosensitivity (24%) and hematological symptoms (22%) were the most common symptoms.

Investigators created 4 subgroups for patients with SLE-CSQ scores: 0, 1, 2 or 3, and ≥4. Participants with 4 or more positive answers tended to be female (91%), had a lower body mass index (BMI), were significantly younger (median age 43 years), and were more likely to be smokers. Women in the ≥4 group reported having used oral contraceptive pills (OCP) more frequently; however, current use of OCP was less frequent in those with higher scores.

Positive CTD autoantibodies were the highest in those with higher SLE-CSQ scores (3.5%) when compared with the group that scored 0 (2.2%). Further, leucocytes, thrombocytes, and neutrophils were higher in the ≥4 group, whereas hemoglobin, creatinine, and monocyte counts were lower when compared with the 0 group.

After adjusting for confounders such as BMI, age, gender, and smoking status, patients with a score of ≥4 continued to show higher neutrophil counts and significantly lower hemoglobin levels when compared with those with lower scores. Women with a higher SLE-CSQ score were less likely to be menopausal and were more often nulliparous.

Medical files could not be accessed; therefore, classification criteria could not be verified. The study was limited by a self-reported diagnosis of SLE and CTD by participants. Another limitation was that most of the population self-reported as Caucasian, while levels of SLE are historically higher in people of other ethnicities. Investigators are interested in performing this study in more diverse populations. Selection bias may have occurred as only 51% of participants completed the follow-up questionnaire. Lastly, the questionnaire and blood samples were retrieved at separate times, with a median time of 25 months, which opens up the possibility that autoantibodies could have developed and bloodwork may have changed.

“This study supports the usefulness of further research on screening for SLE in the general population by providing insight into the prevalence of SLE symptoms,” investigators concluded. “This might help in developing a stepwise approach in order to diagnose SLE earlier. However, longer follow-up of this cohort is necessary to show the predictive value of the SLE-CSQ score in combination with other promising variables like autoantibodies in a population-based cohort.”


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