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  • Review Article
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Differentiating between UCTD and early-stage SLE: from definitions to clinical approach

Nature Reviews Rheumatology volume 18, pages 9–21 (2022)Cite this article

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations that can potentially affect every organ and system. SLE is usually identified on the basis of clinical or serological manifestations; however, some individuals can present with signs and symptoms that are consistent with SLE but are not sufficient for a definite diagnosis. Disease in these individuals can either progress over time to definite SLE or remain stable, in which case their disease is often described as intermediate, possible or probable SLE. Alternatively, such individuals might have undifferentiated connective tissue disease (UCTD). Being able to differentiate between those with stable UCTD and those with SLE at an early stage is important to avoid irreversible target-organ damage from occurring. This Review provides insight into existing and evolving perceptions of the early stages of SLE, including clinical and mechanistic considerations, as well as potential paths towards early identification and intervention. Further research into the earliest phases of SLE will be important for the development of targeted diagnostic approaches and biomarkers for the identification of individuals with early disease who are likely to progress to definite SLE.

Key points

  • Systemic lupus erythematosus (SLE) is a complex autoimmune condition characterized by autoantibody production that can precede disease by several years and heterogeneous clinical manifestations.

  • A considerable proportion of individuals have clinical and serological features that are suggestive of a systemic autoimmune disorder, but cannot be diagnosed as having a defined connective tissue disease.

  • Nomenclature used to define such individuals has been inconsistent, with terms such as latent, incomplete, possible and probable SLE being used, as well as undifferentiated connective tissue disease (UCTD).

  • Although discriminating between UCTD and early SLE can be challenging, the presence of some features (such as a malar rash or specific autoantibodies) would tip the diagnosis in favour of SLE.

  • The absence of new clinical and laboratory manifestations over a 3-year period and the lack of a connective tissue disease-specific serological profile could support a diagnosis of UCTD.

  • The specificity of definitions of SLE-spectrum disorders should improve in the future as more molecular data become available with which disease subgroups can be defined.

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Fig. 1: Natural history timeline of the evolution of SLE.
Fig. 2: From screening and diagnosis to patient phenotyping.

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Author notes

  1. These authors contributed equally: Savino Sciascia, Dario Roccatello.

Authors and Affiliations

  1. Center of Research of Immunopathology and Rare Diseases–Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, and SCDU Nephrology and Dialysis (ERNnet Member), San Giovanni Bosco Hospital, Turin, Italy

    Savino Sciascia, Dario Roccatello & Massimo Radin

  2. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    Savino Sciascia, Dario Roccatello & Massimo Radin

  3. Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

    Ioannis Parodis

  4. Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden

    Ioannis Parodis

  5. Department of Rheumatology, UCSF, San Francisco, CA, USA

    Jinoos Yazdany

  6. Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina

    Guillermo Pons-Estel

  7. Department of Clinical and Experimental Medicine, Rheumatology Unit, University of Pisa, Pisa, Italy

    Marta Mosca

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Sciascia, S., Roccatello, D., Radin, M. et al. Differentiating between UCTD and early-stage SLE: from definitions to clinical approach. Nat Rev Rheumatol 18, 9–21 (2022). https://doi.org/10.1038/s41584-021-00710-2

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