Undifferentiated connective tissue diseases: the clinical and serological profiles of 91 patients followed for at least 1 year

Abstract

The objective of this work was to evaluate the clinical and serological profiles of patients with undifferentiated connective tissue diseases (UCTD) who had been followed for at least 1 year. The retrospective analysis (1974–95) was based on UCTD patients diagnosed on the basis of clinical manifestations suggestive of a connective tissue disease, and the presence of at least one non-organspecific autoantibody. A total of 91 patients were evaluated. The condition of 79 remained stable during the follow up, while in 12 the UCTD evolved to systemic lupus erythematosus (SLE) within a mean period of 3 years (min. 1 year, max. 8 years, median 2 years) after the onset of the disease. At baseline none of the variables, considered alone, showed an association with the future development of SLE. Multiple regression analysis, however, suggested that the association of sicca symptoms, Raynaud's phenomenon and/or photosensitivity was inversely correlated with the development of SLE (P = 0.0012, Fisher's exact test). The most common clinical manifestations of UCTD included arthritis, arthralgias, Raynaud's phenomenon, xerostomia, xerophthalmia and leukopenia. The stable UCTD patients showed a simple autoantibody profile characterized by a single autoantibody specificity in 82% of the cases 30% with anti-Ro/SSA alone and 28% with anti-RNP alone. This profile remained stable during the follow up. Anti-RNP antibodies alone correlated with the presence of Raynaud's phenomenon and arthritis (P < 0.001 and P < 0.01, respectively), while anti-Ro/SSA antibodies alone correlated with xerostomia and xerophthalmia (P < 0.01). In conclusion, the UCTDs in most of our patients seem to represent distinct clinical entities with a limited autoimmune repertoire rather than the early phases of definite connective tissue diseases. They could therefore provide an ideal model for the study of the clinico-serological correlations in autoimmune diseases.

Keywords

stable undifferentiated connective tissue diseases (UCTDs)defined connective tissue diseases (CTDs)anti-Ro/SSA antibodies anti-RNP antibodies

References

Tan EM et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

Sharp GC et al. Mixed connective tissue disease: An apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA) . Am J Med 1972; 52: 148–159 .

Lazaro MA et al. Clinical and serologic characteristics of patients with overlap syndrome: Is mixed connective tissue disease a distinct clinical entity? Medicine (Balt) 1989; 68: 58–65 .

Masi AT et al. Preliminary criteria for the classification of systemic sclerosis (scleroderma) . Bull Rheum Dis 1971; 31: 1–6 .

Subcommitte for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criterion Committee . Preliminary criteria for the classification of systemic sclerosis (scleroderma) . Arthritis Rheum 1980; 23: 581–590 .

LeRoy EC et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis . J Rheumatol 1988; 15: 202–205 .

Bohan A , Peter JB . Polymyositis and dermatomyositis . N Engl J Med 1965; 292: 344–347 .

Arnett FC et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis . Arthritis Rheum 1988; 31: 315–324 .

Vitali C et al. Preliminary criteria for the classification of Sjögren's syndrome . Arthritis Rheum 1993; 36: 340–347 .

10.

Vitali C . et al. Assessment of the European classification criteria for Sjögren's syndrome in a series of clinically defined cases: Results of a prospective multicentre study . Ann Rheum Dis 1966; 55: 116–121 .

11.

Leroy EC , Maricq HR , Kahaleh MB . Undifferentiated connective tissue syndromes . Arthritis Rheum 1980; 23: 341–343 .

12.

AlarcónGS et al. Early undifferentiated connective tissue diseases. I. Early clinical manifestation in a large cohort of patients with undifferentiated tissue diseases compared with cohorts of well established connective tissue disease . J Rheumatol 1991; 18: 1332–1339 .

13.

Mukerij B , Hardin JG . Undifferentiated, overlapping, and mixed connective tissue diseases . Am J Med Sci 1993; 305: 114–119 .

14.

Moutsopoulos HM , Talal L . Viewpoint.Connective tissue diseases: one disease or many? Lupus 1994; 3: 5–10 .

15.

Calvo-AlénJ et al. Systemic lupus erythematosus: predictors of its occurrence among a cohort of patients with early undifferentiated connective tissue disease: multivariate analyses and identification of risk factors . J Rheumatol 1996; 23: 469–475 .

16.

Bulpitt KJ et al. Early undifferentiated connective tissue disease. III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis) . Ann Intern Med 1993; 118: 602–609 .

17.

Ganczarczyk L , Urowitz MB , Gladman DD . ‘Latent lupus’ . J Rheumatol 1989; 16: 475–478 .

18.

Greer JM , Panush RS . Incomplete lupus . Arch Intern Med 1989; 149: 2437–2436 .

19.

Alarcón GS et al. Early undifferentiated connective tissue disease. IV. Musculoskeletal manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of patients with well-established connective tissue diseases: followup analyses in patients with unexplained polyarthritis and patients with rheumatoid arthritis at baseline . Arthritis Rheum 1996; 39; 403–414 .

20.

Charles PJ , van Venroij WJ , Maini RN and the Consensus Finding Group for Autoantibodies . The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases: 1989-1992 . Clin Exp Rheumatol 1992; 10: 507–513 .

21.

Clegg DO et al. Early undifferentiated connective tissue disease.II. The frequency of circulating antinuclear antibodies in patients with early rheumatic diseases . J Rheumatol 1991; 18: 1340–1343 .

22.

Lom-Orta H , Alarcon-Sgovia D , Diaz-Jouanen E . Systemic lupus erythematosus.Differences between patients who do and do not fulfill classification criteria at the time of diagnosis . J Rheumatol 1980; 7: 831–837 .

23.

Lunberg I , Hedfors E . Clinical course of patients with anti-RNP antibodies .A prospective study of 32 patients . J Rheumatol 1991; 18: 1511–1519 .

24.

Kallemberg CGM , Wouda AA , Hoet MH , van Venrooij WJ . Development of connective tissue disease in patients presenting with Raynauds' phenomenon: A six year follow up with emphasis on the predictive value of antinuclear antibodies detected by immunoblotting . Ann Rheum Dis 1988; 47: 634–641 .

25.

Kallemberg CGM . Early detection of connective tissue disease in patients with Raynaud's phenomenon . Rheum Dis Clin North Am 1990; 16: 11–29 .

26.

Calvo-AlénJ . et al. Identification of patients subsets among those presumptively diagnosed with, referred, and/or followed up for systemic lupus erythematosus at a large tertiary care center . Arthritis Rheum 1995; 10: 1475–1484 .

27.

Bernstein RM et al. The SL autoantibody-antigen system: clinical and biochemical studies . Ann Rheum Dis 1986; 45: 353–358 .