A narrative review shows that diagnosing systemic lupus erythematosus (SLE) requires physicians to keep an open and inquisitive mind.
A recently published narrative review details how systemic lupus erythematosus (SLE) can involve “almost every organ and system.” The report underscores the importance of physician awareness of the possibility that a patient with otherwise unexplained symptoms might have SLE.
Author Ami Schattner, MD, of Hebrew University and Hadassah Medical School, in Israel, wrote that SLE represents a substantial diagnostic challenge due to the heterogeneity of its presentation.
“Presentations may mimic infectious, neoplastic, or other inflammatory conditions,” he wrote. “If autoantibody tests are performed, they may be negative or equivocal, representing the high prevalence of antinuclear antibody (ANA) positivity in diverse conditions and the general population.”
Schattner said as many as 1 in 5 people with early SLE are believed to be undiagnosed, which can lead to a greater likelihood of disease activity and disease-related damage.
“Unusual SLE presentations likely incur even longer delays and patient harm, yet they have never been systematically studied or categorized,” he wrote.
Schattner decided to conduct a comprehensive literature search, seeking reports of unusual SLE presentations between the years 1982 and 2022. The results were varied, and mostly made up of single case reports. The search found no previous effort to summarize or categorize the spectrum of SLE presentations.
In the article, Schattner discusses a wide range of potential presentations reported in the literature, including pulmonary, cardiac, gastrointestinal, hematological, and neuropsychiatric lupus, among others.
For instance, Schattner said gastrointestinal involvement is not listed in the SLE classification criteria, but he wrote that the disease can present with manifestations such as intestinal pseudo-obstructive disorder and acute pancreatitis.
“Gastrointestinal symptoms may take many forms and when they are the initial manifestation of lupus, a considerable delay in the diagnosis is likely,” he wrote.
In addition, Schattner said patients can experience a wide spectrum of neuropsychiatric manifestations, such as psychosis and seizures, but he said many manifestations are difficult to quickly tie to SLE.
“A broader spectrum of mood disorders in early SLE seems frequent, but attribution to SLE is often hard to ascertain,” he said.
Schattner added that there are other uncommon but important ways physicians might identify patients with SLE. One way is through inadvertent detection of autoantibodies. He noted that a retrospective analysis of 130 patients with SLE found 88% had at least 1 SLE autoantibody present in their serum 3.3 years before diagnosis.
A range of other rare presentations include prolonged fever, weight loss, and fatigue. Schattner recounted that a survey of more than 200 people with autoimmune diseases, mostly SLE, showed 76% were initially misdiagnosed. Most commonly, their symptoms were merely categorized as “medically unexplained,” leading to lengthy delays in diagnosis and treatment.
Even with all of the challenges of diagnosing SLE, Schattner said there are certain characteristics of the disease that physicians can use to their advantage. For one, he said, it is important for physicians to remember that the disease almost always presents with multiple systemic or organ manifestations. The challenge is that patients might not always mention all of their symptoms.
“Thus, a targeted history, review of systems, physical examination, and basic laboratory panel may well uncover further involvement suggestive of SLE,” he said.
Additionally, he noted that SLE is both a multi-autoantibody disease and an immune-complex disease.
“Hypocomplementemia is relatively specific for SLE and though less prevalent in early-stage, is important if positive,” he said. “ANA is extremely sensitive for lupus, but has a high prevalence in the normal population.”
Lastly, he said, physicians can identify SLE by closely monitoring patients with unexplained symptoms.
“More revealing criteria items may accumulate over time, often within a year,” he wrote.
Physician awareness of SLE and of its wide-ranging presentation is the first step, however. Without it, many patients will continue to go undiagnosed for long periods of time.
Schattner A. Unusual presentations of systemic lupus erythematosus: a narrative review. Am J Med. Published online June 4, 2022. doi:10.1016/j.amjmed.2022.05.020