Clujul Medical - Iuliu Haţieganu

Clujul Medical 2006 vol. LXXX - nr. 1
disorders with signs and symptoms not sufficiently evolved to fulfill any of the accepted
classification criteria for the defined connective tissue diseases. These conditions have
been defined as unclassifiable connective tissue syndromes. Other terms used were
latent lupus [4], incomplete lupus, and undifferentiated connective tissue diseases [5, 6,
7, 8].
A fundamental question raised was, whether a proportion of patients with an
undifferentiated profile may see their condition remain undifferentiated or even
experience a remission of all pathologic features, rather than evolving to a definite
connective tissue disease (CTD). A small percentage of patients presenting with an
undifferentiated profile will develop during the first year of follow up a full blown
CTD. In their case, some clinical features of onset are related with the outcome. For
example, the patients with arthritis and arthralgias often develop a SLE. Raynaud's
syndrome is often related to systemic sclerosis. The patients with rash or face edema
more likely turned out to be PM/DM patients [9,10]. Many studies conducted on
undifferentiated diseases have shown that an average of 75% will maintain an
undifferentiated clinical course and they will not develop a defined CTD. These patients
may be defined as having a stable undifferentiated connective tissue disease (UCTD)
[11]. It seems that these conditions exhibit typical clinical and serological
manifestations and a good prognosis. It has been also shown that, about eighty percent
of these patients have a single autoantibody specificity, more frequently anti-Ro and
anti-RNP antibodies. UCTD could therefore offer an ideal clinical model for the study
of single autoantibody specificities, the effects of various factors (such as pregnancy) on
the disease course, and the general pathogenesis of autoimmune conditions. But before
that, more must be discovered about their nature and characteristics, and studies will be
necessary to improve the sensitivity and specificity of the existing preliminary
classification criteria [12].
In an attempt to distinguish true undifferentiated disease from an early stage of
a definite CTD researchers have suggested a preliminary classification criteria set [5],
according to which a patient may be defined as having a UCTD when he shows signs
and symptoms suggestive of a CTD without fulfilling the criteria of any defined CTD;
the patient has to be ANA positive, with a disease duration of at least 3 years.
Another interesting possibility is that of a connective tissue disease which
fulfills more than one classification criteria for the defined connective tissue diseases.
Therefore, an autoimmune rheumatic disease can appear in conjunction with features of
one or more other connective tissue diseases [13]. This is called an “overlap syndrome”
or mixed syndrome. The etiologies of all autoimmune connective tissue diseases are
unknown and the diagnosis depends on patterns of symptoms and signs. The problem is
heightened by the tendency for one disease type to merge with another, resulting in a
continuous spectrum of clinical features among the rheumatic diseases, with the
traditionally accepted entities such as systemic lupus erythematosus (SLE) or systemic
sclerosis occupying only part of the continuum with the overlap syndromes lying
between. To identify an overlap syndrome it is necessary to identify a constellation of
distinctive features which constitute a true syndrome. Mixed connective tissue disease
(MCTD) is the prototype of an overlap syndrome. The relevance of defining MCTD as
a separate disease entity has been challenged. Follow-up studies show that many
patients originally diagnosed with MCTD develop a definite CTD, particularly
scleroderma or systemic lupus erythematosus, within a few years. In patients with
MCTD, primary pulmonary hypertension is an important cause of death. This condition
seems to be associated with anticardiolipin antibodies. A number of case reports suggest
that immunosuppressive treatment is of benefit in this almost always fatal condition.
The most important aspect of MCTD as a separate entity is its association with
antibodies to U1-RNP. Recent studies have suggested that the production of anti-U1-
RNP is an antigen-driven process, but the nature of the trigger for its production has not
been yet elucidated. Retroviral proteins do not appear to be involved. Antibodies to the
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