Defining undifferentiated connective tissue diseases: a challenge for rheumatologists

Abstract

Undifferentiated connective tissue diseases: distinct clinical entities? Classification criteria have been developed by the scientific community to improve communication and facilitate clinical studies. In clinical practice, however, it is not unusual to come across systemic autoimmune diseases that do not meet the existing classification criteria. These diseases have been variously termed as incomplete lupus erythematosus, undifferentiated connective tissue diseases (UCTD) or undifferentiated connective tissue syndromes. 1–18 However, a review of the literature shows that a broad range of conditions including transitory diseases, the initial phases of defined CTD, incomplete forms of defined CTD, and conditions that cannot be classified or diagnosed based on the clinical findings have been classified as UCTD. 4,9,15,19–24 Studies demonstrate that a certain proportion of UCTD patients will eventually develop defined CTD, generally systemic lupus erythematosus (SLE), but others develop conditions such as systemic sclerosis (SSc), Sjogren’s syndrome, mixed connective tissue diseases, rheumatoid arthritis (RA), systemic vasculitis and polydermatomyositis. 2–4,6–9,11–15 The marked discrepancy in the reported rates of such an evolution – ranging from 10% to 70% – may be attributable to the characteristics of the patients recruited in different studies, in particular their disease duration. Higher incidences have been reported during the first 3– 5 years of the disease, and, therefore, studies that include patients with recent onset UCTD are likely to see a larger number evolving to a CTD. In contrast, UCTD of long duration is much less likely to develop into a defined CTD. At the same time, a distinct subgroup of patients can be identified who will maintain an undefined profile during follow-up. 4,6–8,11–15 Their disease can be termed stable UCTD, a condition with low disease activity, a low incidence of flares (7% in our patient population over 1 year; unpublished data) and the absence of severe organ involvement (e.g. pulmonary fibrosis, kidney or neurological impairment). The most common clinical manifestations are non-erosive arthritis; Raynaud’s phenomenon without swollen hands, sclerodactily or nailfold capillaroscopic abnormalities suggestive of SSc; sicca symptoms (but negative salivary gland biopsy and ocular test results) and leucopenia. The serological profile is positive for antinuclear antibodies (ANA), generally with a single autoantibody specificity (anti-Ro/SSA or anti-RNP) and only rarely disease-specific autoantibodies (usually anti