The most common scleroderma overlap syndromes are
mixed connective tissue disease (
MCTD), scleromyositis and
synthetase syndrome. There is controversy concerning
MCTD as a separate entity due to heterogeneous clinical manifestations, not infrequent transformation into definite CTD and various classification criteria. Our study of 94 adult patients and 20 children, classified according to the criteria of Alarcon-Segovia, and especially a 5, 9-year follow-up showed transformation into SLE or SSc in over 20% of patients, less frequently than reported by others, whereas over half of the cases remained undifferentiated CTD. In several cases ARA criteria for both SSc and SLE were fulfilled, and there is no consensus whether such cases should be recognized as coexistence of both definite diseases or as
MCTD. High titers of U1 RNP
antibodies to 70 kD
epitope were invariably present, whereas, by transformation into distinctive CTD there appeared, in addition,
antibodies characteristic of these CTD. Of 108 cases positive for PM-Scl antibody, 83% were associated with scleromyositis. This scleroderma overlap syndrome differed from
MCTD by coexistent features of
dermatomyositis (
myalgia,
myositis, Gottron sign, heliotrope
rash,
calcinosis) with no component of SLE, characteristic of
MCTD. The course was also chronic and rather benign, as in
MCTD, and all cases responded to low or moderate doses of
corticosteroids. A not infrequent complication was deforming
arthritis of the hands. Our immunogenetic study showed an association of cases positive for PM-Scl antibody with HLA-DQA1x0501 alleles in 100% and with HLA-DRB1x0301 in 94% of cases.
Synthetase syndrome, associated with anti-
histidyl-tRNA synthetase antibodies, studied in 29 patients with
myositis and
interstitial lung disease (ILD), only in single cases had scleroderma-like features. These cases differed from SSc by acute onset with
fever, and by response to moderate doses of
corticosteroids. We also studied overlap of
localized scleroderma with other CTD: 21 cases of
progressive facial hemiatrophy and
linear scleroderma, and 55 (39.5%) of atrophoderma Pasini-Pierini (APP) and
morphea. As in other autoimmune disorders, two or more
connective tissue diseases (CTD) may develop concurrently or sequentially in the same patient. In such overlap syndromes ARA criteria must be fulfilled for each of the disease, and the clinical presentation has features of both. However more frequently overlap syndromes only combine some manifestations of more than one CTD, and present a highly heterogeneous group of disorders with prevailing clinical features of SSc.