Pitfalls of Potential Lupus Diagnosis

According to the Systemic Lupus International Collaborating Clinics’ 2012 classification, four or more of the criteria must be met, including at least one clinical sign and one laboratory result. Biopsy-proven lupus nephritis accompanied by a positive ANA or anti-DNA test is also confirmed lupus. These signs don’t have high sensitivity or specificity, though, making early diagnosis challenging.

“At the present time, there are no laboratory tests [that] allow distinguishing patients who will evolve into definite lupus and those who will not. Of course, it will be of great value to identify biomarkers that may allow such an identification,” they say.

Dr. Alarcón

One serious concern is that a patient’s diagnosis of potential or pre-lupus may be misconstrued by a primary care or other provider who’s not as knowledgeable about SLE as a rheumatologist. In their editorial, Drs. Alarcón and Ugarte-Gil refer to a 2004 study that showed that, out of 476 patients referred to an autoimmune disease center at the University of Florida, 203 had been misdiagnosed.³ Of these, 39 patients who were seropositive for ANA but had no autoimmune disease, had been treated with glucocorticoids, some as high as 60 mg a day.

Pretest Predictive Probability

Many patients who are being tested for lupus have a very low pretest predictive probability of actually having the disease. They may have non-specific clinical manifestations of SLE, such as myalgia, fatigue or arthralgia. A primary care provider may treat these symptoms and refer them for lupus testing, but the chances of these patients having lupus is actually quite low, say Drs. Alarcón and Ugarte-Gil.

“That will not be the case for patients with clear-cut manifestations of SLE, such as malar rash, nephritis and the like. If we request a test in a patient with a very low pretest probability of lupus, a positive result does not necessarily mean the patient has SLE. This is particularly true when we use ANA,” they say.

To determine possible scenarios with a higher pretest probability for SLE, Drs. Alarcón and Ugarte-Gil looked at patients from the LUMINA (Lupus in Minorities: Nature Versus Nurture) cohort who developed lupus gradually, and within that group, those who had met three criteria for a while before achieving a fourth.⁴

“Within this group, the most frequent combination was malar rash with photosensitivity plus arthritis plus ANA, followed by arthritis plus a hematologic criterion plus ANA, and photosensitivity plus buccal ulcers plus arthritis,” they say. “Whether such patterns may be helpful in other settings remains to be determined.”

‘At the present time, there are no laboratory tests that allow distinguishing patients who will evolve into definite lupus & those who will not.’ —Drs. Alarcón & Ugarte-Gil

To Test or Not to Test

A lack of adequate biomarker identification means that referring a patient for testing without other clinical signs of SLE could lead to fuzzy or incorrect conclusions. Costly tests cannot be justified unless certain clinical signs are present, too, say Drs. Alarcón and Ugarte-Gil.