Author and year | Patients with suspected very early SSc | Patients with definite SSc | Results on progression from suspected very early SSc to definite SSc | ||
Definition | Total number | Definition | Total number of progressors | ||
Studies evaluating the prognostic value of the presence of SSc-specific autoantibodies on progression to definite SSc | |||||
Bellando-Randone et al, 20219 | RP, ANA positive, puffy fingers, SSc. Specific autoantibody positive, abnormal NC. | 764/1150 patients of whom 553 had one follow-up visit available. Of N=553:
| Fulfilling ACR/EULAR 2013 criteria. | 133 of 254 with 5 years follow-up available. | 126/133 (95%) were ANA-positive. Seventy per cent of the patients with SSc-specific autoantibodies reached the endpoint, which translates to a risk ratio of 5.03 (2.93; 8.66) in univariable logistic regression. Adjusted for the other VEDOSS criteria, the risk ratio of the SSc-specific autoantibodies was 4.20 (2.21; 7.99). The results of the Cox regression models, incorporating the fully available follow-up data, are in line with this. |
Riccardi et al, 202013 14 | RP and either presence of SSc autoantibodies or NC or both. | N=102
| Fulfilling ACR/EULAR 2013 criteria. | 46/102 (45%) in median disease duration of 3 years.1 12 | HR’s for progression to definite SSc:
|
Trapiella-Martinez et al, 201715 | =RP with SSc Ab, ANA positivity or NC. Divided into two groups:
| Of 1632 patients in RESCLE cohort: 36/1632 (2.2%) very early SSc.
111/1632 (6.8%) early SSc.
| Unclear in the article. | 3/36 (8%) very early SSc, of whom two fulfilled. ACR/EULAR 2013 criteria. 31/111 (28%) patients with early SSc, of whom 20 fulfilled. ACR/EULAR 2013 criteria. | Six per cent of the very early patients already fulfilled ACR/EULAR 2013 criteria and 24% of the patients with early SSc. The early subset has a higher risk of progression to definite SSc than the very early subset (OR 4.26 (95% CI: 1.22 to 14.92)). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1 to 47.2). Progressors had ATA more often than no-progressors (19% vs 8%, p=0.113). |
Moinzadeh et al, 201216 | Isolated RP. | N=569
| Clinical features of SSc. | N=8 (1.5%). | 7/8 had an SSc pattern on NC as well as positive ANA’s at first presentation. Progression to a connective tissue disease was not observed in any patient with negative autoimmune serology on more than one visit and normal capillaroscopy score. |
Ingegnoli et al, 201017 | Isolated RP. | N=288
| First non-Raynaud clinical feature of SSc. | N=34 (12%). | The 5-year incidence for SSc was 21% (95% CI: 10% to 32%). Other CTDs developed in 42 patients (11 cases of RA, 25 cases of UCTD, 3 cases of SLE, 2 cases of dermato/polymyositis and 1 case of MCTD). The 5-year incidence for all events was 45.8% (95% CI: 31% to 61%) and. Isolated ANA positivity increased the hazard of an event with an sub-distribution HR of 9.70), then if a patient was also ACA the sub-distribution HR increased with 3.93. ATA positivity did not indicate a further increase in the hazard of SSc (sub-distribution HR 1.37). |
Koenig et al, 20088 | Primary RP: no abnormalities Pre-CTD: +puffy fingers, Ab but not SSc-specific Ab. Early SSc: +SSc specific Ab, SSc NC without displaying clinical manifestations of SSc or another CTD. | Primary RP: N=299 Pre-CTD: N=317 Early SSc: N=168
| Fulfilling ACR 1980 criteria. | Primary RP: N=0. Pre-CTD: n=8 (3%). Early SSc: n=66 (47%). | 71 of the 74 patients (96%) who progressed to definite SSc were ANA-positive. SSc autoantibodies were present in 78.4% of the patients (58 of 74): anti-CENP-B (n=33 (44.6%)) and anti-Th (n=13 (17.6%)) were the most frequent, whereas anti-topo I (n=6 (8.1%)) and anti-RNAP III (n=9 (12.2%)) were the least frequent. The strongest independent predictors of definite SSc were positive ANAs (adjusted HR 5.67), SSc autoantibodies (HR 4.7) and an SSc pattern on NC (HR 4.5). |
Studies evaluating the prognostic value of the levels of SSc-specific autoantibodies on progression to definite SSc | |||||
Van Leeuwen et al, 202110 | ACA-IgG positivity and RP+puffy fingers or nailfold capillaroscopy abnormalities. | N=138
| Fulfilling ACR/EULAR 2013 SSc criteria. | N=48. | 48 patients with very early ACA-positive SSc progressed to definite SSc within 5 years. Progressors were older, had longer follow-up duration and shorter RP duration (2 (1; 5) vs 5 (3; 7), p=0.69) compared with non-progressors. Progression to definite SSc was associated with higher IgG ACA levels at baseline (OR 4.3 (95% CI 1.7 to 10.7) in a logistic regression adjusted for age and disease duration since the first RP symptom. |
Lande et al, 202124 | RP and ATA or ACA. | VEDOSS discovery cohort: n=31
VEDOSS replication cohort: n=48
| Fulfilling ACR/EULAR 2013 SSc criteria. | N=42.
| 17/31 patients in the VEDOSS discovery cohort and 15/48 patients in the VEDOSS replication cohort progressed to definite SSc. SSc progressors showed a similar anti-CXCL4/CXCL4-L1 autoantibody response to SSc non-progressors. |
Ab, autoantibodies; ACA, anti-centromere antibodies; ACR, American College of Rheumatology; ANA, anti-nuclear antibodies; ARA, anti-RNA polymerase III antibodies; ATA, anti-topoisomerase I antibodies; CTD, connective tissue disease; DLCO, diffusing lung capacity for carbon monoxide; DU, digital ulcer; EULAR, European Alliance of Associations for Rheumatology ; ILD, interstitial lung disease; MCTD, mixed connective tissue disease; NC, nailfold capillaroscopy; PAH, pulmonary arterial hypertension; PS, pitting scars; RESCLE, Spanish Scleroderma Registry Cohort; RP, Raynaud’s phenomenon; SLE, systemic lupus erythematosus ; SSc, systemic sclerosis; TE, teleangiectasia; UCTD, undifferentiated connective tissue disease; VEDOSS, very early diagnosis of SSc.