Frequent Healthcare Visits Seen as Early Flag for Lupus

In the years preceding diagnosis of systemic lupus erythematosus (SLE), Danish patients saw healthcare providers at about triple the rate of individuals without lupus, researchers found.

Comparing 2,022 lupus patients with 20,019 people from the general population, incidence rate ratios for general practice (GP) visits stood at just below 3.0 during the period 5 to 1.5 years prior to receiving the formal SLE diagnosis, according to Anne Troldborg, MD, PhD, and colleagues at Aarhus University in Denmark.

Soon-to-be lupus patients went to their GPs an average of about 12 times a year during this period, a rate that nearly doubled in the final 6 months before diagnosis, the researchers reported in Annals of the Rheumatic Diseases. Among control individuals, mean GP encounters were right at about 4 per year.

Painkillers, antibiotics, and topical corticosteroids (but not systemic steroids) were all given at significantly higher rates to lupus patients versus controls, even 5 years prior to diagnosis. Blood tests, including but not limited to assays for lupus-related markers, and imaging were also performed at about double the rates seen in controls. No particular type of test, prescription, or procedure stood out, however, as especially increased for the “preclinical” lupus patients. The researchers found, too, that lupus patients were far more likely to see specialists including rheumatologists, dermatologists, and otolaryngologists long before the diagnosis was finally made.

“These findings call for the development of new diagnostic strategies and tools as well as earlier detection efforts to reduce diagnostic delays and improve patient outcomes,” Troldborg and colleagues wrote. “By identifying at-risk patients earlier, healthcare providers can facilitate timely interventions, potentially reducing the risk of irreversible organ damage associated with SLE.”

Diagnosing SLE has been notoriously difficult, as symptoms vary considerably among patients and, in the early stages, are relatively nonspecific. Although, as Troldborg and colleagues observed, autoantibodies “are present in patients with SLE long before the disease is formally diagnosed,” positive test results are not, by themselves, sufficient to make a lupus diagnosis. And even when enough symptoms are present for a clear diagnosis, one recent study found a median of 2 years in “diagnostic delay,” with nearly half of SLE cases initially diagnosed as something else such as antiphospholipid syndrome.

For the current study, Troldborg’s group analyzed Denmark’s national hospitalization records and other registries to identify patients diagnosed with SLE. Each was matched by age, sex, and GP listing to 10 other people, for whom an “index date” was chosen to match that of the corresponding lupus patient’s verification of diagnosis. Their prior healthcare encounters, for up to 5 years before lupus diagnosis (or the index date for controls) were then tracked in these databases.

Mean age was 47 at diagnosis or index date; 84% were women. Patients and controls were relatively well matched in most characteristics, although the lupus patients were more likely to be unemployed or retired (40% vs 33%). Also, two-thirds of patients had comorbidities, versus fewer than half of controls.

Patients’ markedly increased rates for GP visits, tests, and prescriptions, relative to controls, were evident 5 years prior to diagnosis. They remained elevated at about the same degree until 18 months before the SLE diagnosis was confirmed, after which point patients’ healthcare encounters and procedures ramped up even more. In the final 6 months, for example, blood tests were 7.3 times as common among patients than controls (95% CI 6.5-8.2); the rate ratio for diagnostic imaging in those final months was nearly identical (7.1, 95% CI 6.5-7.8).

Notably, although rates of testing for antinuclear antibodies was substantially higher in patients than controls, throughout the study period, absolute rates remained “relatively low,” Troldborg and colleagues noted. Such tests were performed in only a small minority of patients ultimately found to have lupus, until the final 6 months when their clinicians were presumably closing in on the SLE diagnosis.

Visits to private specialists followed a similar pattern. Hospitalizations before diagnosis, however, were only moderately increased — less than doubled — among patients until 1 year before diagnosis. In the final 6 months, patients’ hospitalization rates jumped to a mean 1.5 per year, versus a steady 0.2 per year for controls (ratio 6.8, 95% CI 5.9-7.9).

The study’s most important limitation was that reasons for individuals’ GP visits, tests, and so on were not recorded. Also, Troldborg and colleagues pointed out that, with healthcare utilization already increased 5 years prior to lupus diagnosis, “the diagnostic window” might extend even further back. The focus on the Danish population also means that the results may not be generalized to other countries with more diverse racial-ethnic profiles.

Troldborg and colleagues offered a number of suggestions for future research. “By leveraging healthcare utilization patterns in combination with prescription data, imaging diagnostics, and autoantibody testing, future research could focus on building and validating predictive models for earlier identification of SLE. Integrating artificial intelligence (AI)-driven algorithms into this process may enhance the ability to identify high-risk individuals, offering a more systematic and precise approach to earlier diagnosis,” they wrote.

The group also suggested that primary care clinicians get more training in recognizing SLE in its early stages: “Given the current lack of validated predictive models or AI-based tools for early SLE diagnosis, such efforts could play a crucial role in bridging the gap in primary care.”

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