Elsevier

Journal of Autoimmunity

Volumes 48–49, February–March 2014, Pages 50-52
Journal of Autoimmunity

The diagnosis and classification of undifferentiated connective tissue diseases

https://doi.org/10.1016/j.jaut.2014.01.019Get rights and content

Highlights

  • 50% of systemic autoimmune diseases at onset have an undifferentiated profile.

  • Up to 40% of UCTD patients evolve into defined CTD during follow up.

  • Stable UCTD has a simplified clinical and serological picture.

Abstract

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) but not fulfilling any of the existing classification criteria. 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”. 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 model to study clinic pathological correlations as well as the role of possible environmental factors in the development of autoimmunity.

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

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