New HSS study clarifies the clinical manifestations of undifferentiated connective tissue disease

A new study by researchers at Hospital for Special Surgery (HSS) has further clarified the clinical manifestations of undifferentiated connective tissue disease (UCTD). The findings were published as an abstract in the meeting journal of the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress.

We have been interested in studying UCTD because it's commonly encountered in clinical practice but not well characterized. UCTD is inherently challenging to define, but it's very important to understand what features differentiate patients with UCTD from those with defined connective tissue diseases (CTD) such as lupus so that we can better manage patients with this condition and ultimately predict who may go on to develop more severe clinical manifestations."

Caroline Siegel, MD, lead study author, rheumatology fellow at HSS

The study included 89 patients aged 18 years and older treated at HSS between 2018 and 2022 who had rheumatologist-diagnosed UCTD with positive antinuclear antibody and at least one sign or symptom of CTD. The researchers reviewed medical records to identify those who fulfilled established classification criteria for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis, primary Sjögren's, idiopathic inflammatory myopathy, or antiphospholipid syndrome (APS). The researchers compared sociodemographic, clinical, serologic, and treatment variables between 59 patients with UCTD and 30 patients who fulfilled criteria for CTD.

Patients in both groups had similar non-criteria manifestations, most commonly joint pain and fatigue. However, patients with UCTD were less likely to have arthritis, criteria-based hematologic manifestations, anti-double stranded DNA or anti-Smith antibodies, and hypocomplementemia. The frequency of RA, Sjögren's, and APS-related serologies did not differ between groups. Compared to those with CTD, UCTD patients were less likely to have ever received systemic corticosteroids.

"Our main findings were that patients who met a strict definition of UCTD versus those who met classification criteria for other CTDs were less likely to have clinical and laboratory features such as arthritis and hematologic abnormalities, as well as certain autoantibodies that are commonly seen in lupus," said Dr. Siegel. "They were also less likely to have received treatment with steroids," she added.

The results reveal that even among patients diagnosed by their treating physician with UCTD, some may meet classification criteria for other rheumatic diseases. Within this group, patients with strictly defined UCTD may differ in meaningful ways.

"We are starting to recognize features of strictly defined UCTD that will allow us to better identify and manage this condition," said senior study author Medha Barbhaiya MD, MPH, rheumatologist at HSS. "Patients struggle with the uncertainty of a UCTD diagnosis and our study aimed to demonstrate that UCTD may be a distinct entity from other rheumatic conditions. These findings lend support to the claim that patients who have UCTD require separate study, and their disease manifestations warrant further understanding."


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