The diagnosis and classification of undifferentiated connective tissue diseases
Introduction
It is a common clinical condition for a rheumatologist to face patients with clinical and serological manifestations strongly suggesting a connective tissue disease but without the possibility to diagnose or classify them as having a specific CTD [1], [2], [3], [4], [5], [6], [7], [8].
It is estimated that up to 50% of patients with CTDs have an unclassifiable profile at disease onset [3]; however, other than merely a classification exercise, the reliable identification of these conditions is a critical clinical point with therapeutic and prognostic impact.
In addition, this situation may arise many questions and doubts in the patient which have to deal with an undefined disease.
It is widely accepted that, with respect to diagnostic criteria, classification criteria primarily serve as a tool to identify homogeneous groups of patients with comparable features so that data obtained by different researchers in different places can be compared and the recruitment into clinical studies standardized; however, the diagnostic support of such instruments is reasonable, leading to a similar use for both classification and diagnostic criteria.
In recent years, growing efforts have been made toward early diagnosis and classification; the introduction of new biomarkers and the availability of advanced imaging diagnostic techniques significantly contributed to this objective. The development of new classification and diagnostic criteria for RA, SSc and SLE are well representative of such an effort.
On the other hand, it can be hypothesized that with the availability of new and more sensitive diagnostic and classification tools, the shape of the UCTD could be drawn more efficiently.
In this review we will go through the more recent evidence on UCTD and we will discuss in what extent the availability of new criteria for the CTDs could interfere with the “UCTD concept”.
Section snippets
UCTD: still a matter of debate?
The term undifferentiated connective tissue disease (UCTD) refers to unclassifiable systemic autoimmune diseases which share clinical and serological manifestations with definite connective tissue diseases (CTDs) such as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), Sjögren Syndrome (SS), dermatomyositis/polymyositis (DM/PM), Mixed Connective Tissue diseases (MCTD) and Rheumatoid Arthritis (RA) but not fulfilling any of the existing classification criteria [9].
Over the last
“Stable UCTD”
The first case is represented by the so called “stable UCTD” (sUCTD). After a long scientific debate, it is now widely accepted that these conditions represent a distinct clinical entity with peculiar clinical findings; the proposed preliminary classification criteria for UCTD include at least one clinical manifestation of CTDs, positive ANA results, and disease duration of at least three years [9].
Several long-term observational cohorts are actually available elucidating the clinical course of
Early or evolving “UCTD”
The second group of undifferentiated diseases refers to patients with recent onset of symptoms and unclassifiable clinical picture; in this group of patients, the undifferentiated condition better refers to a “incomplete”, “atypical” or “mild” disease presentation which is very likely to progress into a definite CTD in the short time or, sometimes, even years after symptoms onset.
Several prognostic factors for evolution into CTDs have been identified and contrasting results have been reported
Can new classification/diagnostic criteria redefine UCTD?
It is well recognized that early diagnosis, identification of prognostic factors for disease severity as well as targeted and timely therapy are the common basis in the management of CTDs in order to prevent late organ damage. However, a delayed identification of the disease, especially in the presence of less defined clinical pictures, can still occur and it can be related with the lack of disease specific assessment and biomarkers.
In RA the development of adequate referral and monitoring
Conclusions
Undifferentiated connective tissue diseases (UCTDs) are conditions characterized by a simplified clinical and serological profile and the absence of severe organ involvement. The development of criteria able to identify early phases of defined CTD, may help in the differentiation of stable UCTD form their early stages and may offer a valuable guide to the treating physician to set up appropriate follow up schedules as well as therapeutic protocols.
This simplified subset of CTD could offer a
References (34)
- et al.
Undifferentiated connective tissue diseases (UCTD): simplified systemic autoimmune diseases
Autoimmun Rev
(2011) - et al.
Undifferentiated CTD: a wide spectrum of autoimmune diseases
Best Pract Res Clin Rheumatol
(2012) - et al.
Systemic lupus erythematosus. Differences between patients who do, and who do not, fulfill classification criteria at the time of diagnosis
Rheumatology
(1980) - et al.
Latent lupus
J Rheumatol
(1989) - et al.
Early undifferentiated connective tissue disease. I. Early clinical manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease
J Rheumatol
(1991) - et al.
Undifferentiated connective tissue disease: natural history and evolution into definite CTD assessed in 84 patients initially diagnosed as early UCTD
Clin Rheumatol
(1998) - et al.
Undifferentiated connective tissue diseases: the clinical and serological profiles in 91 patients followed for at least 1 year
Lupus
(1998) - et al.
Undifferentiated connective tissue disease: analysis of 83 patients with a minimum follow up of 5 years
J Rheumatol
(2002) - et al.
Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria
Clin Exp Rheumatol
(1999) - et al.
Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD)
Clin Exp Rheumatol
(2003)
Analysis of the evolution of UCTD to defined CTD after a long term follow-up
Clin Exp Rheumatol
Five-year follow-up of 165 Italian patients with undifferentiated connective tissue diseases
Clin Exp Rheumatol
Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease?
Am J Respir Crit Care Med
Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function
Lung
Undifferentiated connective tissue disease: a seven-center cross-sectional study of 184 patients
Clin Rheumatol
Quality of life as measured by the short-form 36 (SF-36) questionnaire in patients with early systemic sclerosis and undifferentiated connective tissue disease
Health Qual Life Outcomes
Pregnancy in patients with undifferentiated connective tissue disease: a prospective case-control study
Lupus
Cited by (116)
Clinical patterns of disease: From early systemic lupus erythematosus to late-onset disease
2024, Best Practice and Research: Clinical RheumatologyAutoimmunity in patients with silicone breast implants: An exploratory review
2024, Revista Colombiana de ReumatologiaCapillaroscopic analysis of the microvascular status in mixed versus undifferentiated connective tissue disease
2022, Microvascular ResearchCitation Excerpt :Since its first description, the clinical depiction of the MCTD has changed. Four different classification and diagnostic criteria have been proposed (Sharp, Alarcon-Segovia, Kasukawa and Kahn) and compared in several studies (Amigues et al., 1996; Ortega-Hernandez and Shoenfeld, 2012; Mosca et al., 2014; Antunes et al., 2019). Since none of those criteria is convincingly better than the others, all four sets of criteria may be used (Amigues et al., 1996).
Myocarditis on <sup>18</sup>FDG-PET imaging
2022, Radiology Case ReportsCitation Excerpt :Myocarditis in undifferentiated connective tissue syndromes require high clinical certainty. The term undifferentiated connective tissue disease (UCTD) refers to unclassifiable systemic autoimmune disorders that share clinical and serological manifestations with definite connective tissue diseases (CTDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), SS, dermatomyositis/polymyositis (DM/PM), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA), but not fulfilling any of the existing classification criteria [3]. The most common clinical presentation of this disease entity includes arthralgias, arthritis, and other inflammatory signs.