Disease Characteristics of UCTD Differ From CTD, HSS Researchers Find

Undifferentiated connective tissue disease (UCTD) is challenging to define but is a distinct clinical entity from connective tissue diseases (CTD).

Patients with undifferentiated connective tissue disease (UCTD) have a lower frequency of arthritis, hematologic abnormalities, systemic lupus erythematosus (SLE)–specific antibodies, and hypocomplementemia compared with patients who have connective tissue diseases (CTD), according to an abstract published in the meeting journal of the EULAR 2022 Congress.

The findings from researchers at the Hospital for Special Surgery (HSS) clarify the clinical manifestations of UCTD. They recruited 89 patients in order to identify characteristics associated with rheumatologist-diagnosed UCTD. They also applied strict exclusion criteria and compared patients with UCTD with criteria-defined CTD.

“We have been interested in studying UCTD because it’s commonly encountered in clinical practice but not well characterized,” lead study author Caroline Siegel, MD, a rheumatology fellow at HSS, said in a statement. “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, 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.”

The 89 patients were 18 years or older with rheumatologist-diagnosed UCTD and had been seen between 2018 and 2022. These patients had positive antinuclear antibody test and at least 1 sign or symptom of a CTD. The patients had a mean age of 49 years and a majority were White (66.3%) and female (97.8%). Of the 89 patients, 59 (66.3%) had UCTD and 30 (33.7%) had criteria-defined CTD. Of the latter group, 27 patients had SLE, 3 had SLE and rheumatoid arthritis (RA), 1 had RA, and 1 had antiphospholipid syndrome (APS).

Both the UCTD and criteria-defined CTD groups had non-criteria manifestations:

  • 89.8% of patients with UCTD and 83.3% with CTD had arthralgia (P = .50)
  • 55.9% with UCTD and 73.3% with CTD had fatigue (P = .17)

Only 27.1% of patients with UCTD had nonerosive arthritis vs 56.7% of patients with CTD (P = .01). Patients with UTCD were also less likely to have any hematologic manifestation, anti-dsDNA or anti-Smith antibodies, or hypocomplementemia compared with patients with CTD.

The frequency of RA, Sjögren syndrome, and APS-related serologies was similar between the 2 groups.

While 96.7% of patients with CTD had ever received systemic corticosteroids, only 71.2% (P < .01) of patients with UCTD had ever received the treatment. Similarly, patients with UCTD were less likely to ever use any disease-modifying antirheumatic drug compared with patients with CTD (35.6% vs 46.7%, P = .36)

According to the researchers, while rheumatologists diagnose UCTD when criteria are met for other CTDs, the findings show UCTD is “a distinct clinical entity” from CTD.

“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.”


Siegel C, Stamm B, Vega J, et al. Characteristics of patients diagnosed with undifferentiated connective tissue disease. Ann Rheum Dis. 2022;81(Supp 1):1417.

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