Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease that is often not diagnosed early as it is rare with heterogeneous presentations and features that can be confused with other diagnoses. SSc occurs in approximately 2/10,000 or less [1,2]. Most patients are diagnosed by rheumatologists, although initial symptoms such as Raynaud's phenomenon (RP), gastroesophageal reflux disease (GERD), or puffy hands/skin thickening may initially present to primary care providers, gastroenterologists, general internists or dermatologists. Some patients see respirologists initially for interstitial lung disease (ILD) and then other features are found which aids in the diagnosis. Diagnostic delay is common, particularly in limited cutaneous disease (lcSSc); where RP is often present for an average of 8 years before other symptoms onset, and even diffuse cutaneous SSc (dcSSc) may have a diagnosis 1–3 years after symptom onset in many studies [3,4] (see Fig. 1).

SSc affects more females compared to males (approximately 4:1 ratio), often presenting between ages 40–60 but can onset at any age but it is even more rare in children. Usually dcSSc onsets in younger patients; compared to lcSSc. The latter subset may present 15 years older than dcSSc patients. SSc is more prevalent and severe among Black and Indigenous populations, with increased an risk of the dcSSc subset and more prevalent and severe internal organ involvement such as ILD. Environmental exposures such as silica dust, and possibly solvents, and epoxy resins; have been implicated in disease pathogenesis. Smoking can increase the risk of SSc and patients who smoke tobacco often have worse disease (ILD, digital ulcers [DU]).

Pathogenic changes in SSc such as microvascular injury, immune dysregulation, and subclinical fibrotic changes may begin months to years before clinical features occur. Many research protocols are studying preclinical or a very early phase of SSc [3,8,9]. This is known as VEDOSS (very early diagnosis of SSc). Many of these patients have early changes that will become lcSSc with puffy fingers, RP and possibly an anti-centromere antibody [8]. However, dcSSc patients are less likely to be detected very early due to the onset of RP around the same time of skin changes (RP onsets usually within 1 year before or after scleroderma changes).

SSc is often divided into two subsets based on the extent of skin thickening [10]. Limited cutaneous SSc (lcSSc) includes only skin thickening distal to the elbows and knees; but may include the face to the clavicles. Many of the lcSSc patients only have finger involvement to the MCPs and facial thickening. The lcSSc subset is associated with an older age of onset, and a long history of RP before the diagnosis is made. Diffuse cutaneous SSc (dcSSc) has skin thickening both distally (such as hands and forearms) and proximally above the elbows and/or knees, or truncally. This subset has a higher chance of ILD, especially early on in the disease course and has more frequent other internal organ involvement (including the heart and scleroderma renal crisis [SRC]). The dcSSc subset has a higher morbidity and mortality in general. Antibodies can help to prognosticate patients. SRC is strongly associated with RNA polymerase III antibodies; ILD is increased but not only in those with topoisomerase 1 (Scl70) antibodies; anticentromere antibodies are present in half of the lcSSc patients and only 3 % of the dcSSc patients [11]. There are patients with SSc without ever having clinical skin thickening (scleroderma) and they are considered SSc sine scleroderma. Their prognosis is similar to lcSSc patients. These patients are likely to have other SSc features such as positive SSc-specific autoantibodies, RP, gastrointestinal dysmotility and they may develop other complications (ILD, pulmonary arterial hypertension [PAH], digital ulcers). Some also classify patients who meet the lcSSc definition but already have skin thickening to the mid forearm or higher and they may be considered as indeterminate or intermediate; as, they frequently progress to the dcSSc subset. Dividing patients by the extent of skin involvement and/or antibodies is important for predicting the natural history, prognosis, and treatment [4,10].

In general recommendations for the treatment of SSc aid in treatment [12] but they likely are conservative for rapidly progressive patients and even patients with established disease due to a lack of evidence in these patients where combination treatments of more effective therapies should possibly be offered earlier. Most treatments in SSc are in groups of patients such as early dcSSc patients to try to change the natural history, or organ treatment including ILD, progressive pulmonary fibrosis (PPF), PAH, RP, DU, and less randomized controlled trials (RCTs) for other manifestations such as GI involvement; and sparse data for cardiac manifestations.

In some centres, nailfold capillaroscopy is used to identify microvascular abnormalities in SSc, particularly in early disease to help with diagnosis and classification [13,14]. Abnormal nailfold capillaries are one of the VEDOSS criteria and increase the likelihood of developing SSc if a patient has these abnormalities and has RP. There are 3 main patterns (early, active and late) and the severity and activity of capillary changes can be quantified. Abnormal findings include giant capillaries, capillary dropout and hemorrhages are associated with a higher risk of progression to definite SSc [4]. However, the benefit of capillaroscopy in ongoing disease monitoring or therapeutic response is not validated for clinical decision-making.