Systemic sclerosis (SSc) is an autoimmune disorder of the connective tissue, characterized by increased fibrosis and vascular changes. It typically affects the skin (known as scleroderma, in which the skin becomes tough and thickened), but can also affect the gastrointestinal, cardiac, respiratory, and renal systems.
SSc is a rare condition, affecting around 2.5 million people worldwide. Women are more likely to be affected than men, and the peak onset age is between 35 and 55 years.
There are two main types of SSc:
These forms of SSc should be distinguished from localized scleroderma (also known as morphoea) which only affects the skin.
The exact cause of SSc is unknown. It is believed that activation of fibroblasts after injury to endothelial cells lining the blood vessels leads to the production and deposition of excess collagen within the skin and other organs. Additionally, widespread angiopathy and remodelling of blood vessels is present.
SSc is thought to be connected to both genetic and environmental factors. It can also overlap with other autoimmune conditions.
Those with a family history of SSc are at an increased risk of developing this condition. Particular gene variations involving the human leukocyte antigen (HLA) complex may be a factor.
Exposure to chemicals, drugs and certain infectious diseases have been linked to SSc.
SSc may be correlated with other autoimmune conditions affecting the musculoskeletal system, as 20% of SSc cases coincide with systemic lupus erythematosus, myositis, Sjögren's syndrome or rheumatoid arthritis.
Limited cutaneous systemic sclerosis was formerly called CREST syndrome due to its five cardinal features (see below). However, the acronym CREST is no longer used to differentiate between limited SSc and the diffuse form, as these signs are also commonly appearing in dcSSc.
Systemic sclerosis (SSc) is a connective tissue disorder that can have a range of symptoms. Here are some key features of SSc that can be remembered using the acronym 'CREST':
Patients with limited cutaneous systemic sclerosis (lcSSc) can experience severe Raynaud's phenomenon and mucocutaneous telangiectasia. This condition can cause pulmonary arterial hypertension (PAH). There may be years or even decades between the onset of Raynaud's phenomenon and other symptoms. Patients may complain of cold hands/feet, skin colour changes, swelling of the fingers and/or skin sclerosis.
Diffuse cutaneous systemic sclerosis has a rapid onset and Raynaud's phenomenon may occur simultaneously or after skin involvement. The lungs (pulmonary fibrosis) and kidneys (scleroderma renal crisis) may be more severely affected than other organs.
Systemic sclerosis (SSc) is a relatively rare autoimmune disorder characterised by thickening of the skin and possible internal organ involvement. It has two variants, limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) with common symptoms including tight, dry or itchy skin on the hands, feet, face or trunk; Raynaud's phenomenon, puffy fingers, oesophageal reflux or difficulty swallowing. Shortness of breath or palpitations may be present if internal organs are involved. Due to the potential overlap with other musculoskeletal disorders and connective tissue diseases it is important to obtain a comprehensive rheumatological history.
Clinical examination is necessary to assess individual variability in the disease presentation. A close inspection of the skin is required looking for elements such as: shiny or discoloured skin on the hands with no skin folds; thickened skin; calcinosis; ulcers on the fingers; telangiectasia on the face, hands or mucosal surfaces; microstomia; joint contractures; depigmentation or hyperpigmentation of skin (salt-and-pepper skin). Nailfold capillaroscopy may sometimes be performed to distinguish between primary and secondary Raynaud's phenomenon and determine prognosis.
Important differential diagnoses for systemic sclerosis include: localised scleroderma (patches of thickened skin with no involvement of internal organs and not associated with Raynaud's phenomenon); primary Raynaud's (no underlying disease); and secondary Raynaud's which may be linked to other autoimmune conditions such as rheumatoid arthritis, Sjogren's and systemic lupus erythematosus.
Relevant bedside investigations include: measurement of blood pressure to check for scleroderma renal crisis; ECG to assess for cardiac involvement; Perform spirometry to test for pulmonary involvement; and obtain full blood count, erythrocyte sedimentation rate, C-reactive protein and autoantibodies (anti-nuclear antibody, anti-Ro, anti-La, if appropriate with anti-centromere antibody).
Diagnosis of systemic sclerosis (SSc) is based on clinical findings and specific autoantibodies. These include antinuclear antibodies (ANA), anti-centromere antibodies, anti-Scl 70 antibodies (anti-topoisomerase I), and anti-RNA polymerase III antibodies. Full blood count (FBC), urea and electrolytes (U&Es), echocardiogram, high-resolution CT scan (HRCT), pulmonary function tests, and x-rays of the hand may also be performed.
There are no specific diagnostic criteria, but the classification proposed by the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) is designed to assist clinicians in making a diagnosis and recognising early disease (Table 1). The ACR/EULAR criteria includes vascular changes and skin manifestations, for which a score of 9 is necessary to make a definite diagnosis of SSc.
Table 1. A table showing the ACR/EULAR criteria for diagnosis of systemic sclerosis11
CriteriaScore
Bilateral skin tightening close to metacarpophalangeal joints
9
Sclerodactyly
4
Fingertip pitting scars
3
Raynaud's
3
Presence of specific antibodies
3
Puffy fingers
2
Digital ulcers
2
Telangiectasia
2
Abnormal nail fold capillaroscopy
2
Interstitial lung disease/pulmonary arterial hypertension
2
Currently, there is no cure for SSc, so management is focused on alleviating symptoms, preventing further deterioration and organ involvement. Depending on the patient's symptoms, endoscopy, barium swallow for dysphagia, or oesophageal manometry may be performed. If overlap with other connective tissue diseases is suspected, further investigations, such as measurement of creatinine kinase if myositis is suspected, may be warranted.
To support symptom control and reduce the possibility of complications, non-pharmacological management of systemic sclerosis may include:
Generally, Raynaud's is treated conservatively. If extreme episodes are frequent, vasodilators (for example, calcium channel blockers such as nifedipine or phosphodiesterase inhibitors such as sildenafil), prostacyclin analogues or endothelin receptor antagonists may be administered to enhance blood flow and stop ulcers and ischemia of the fingers.
Systemic agents can be used for the management of skin disease, as well as inner organ involvement:
The usage of corticosteroids in large amounts or long-term can cause a scleroderma renal crisis. They may still be utilized in specific scenarios when immediate anti-inflammatory effects are necessary (for example, for the flare-up of inflammatory arthritis, myositis or alveolitis).
Depending on the patient's symptoms, other medications that may be considered may include:
Since internal organs can be affected, a variety of complications can arise. To diagnose organ involvement early and to stop complications, patients are monitored carefully in secondary care. Annual screening should incorporate pulmonary function tests, urinalysis, ECG and echocardiogram.
Pulmonary artery hypertension (PAH), commonly in patients with lcSSC. It usually occurs after SSc onset (roughly 10 years) but affects up to 30-50% of people. Interstitial lung disease (pulmonary fibrosis) is more common in individuals with dcSSC (50-80%). It presents as bibasilar pulmonary fibrosis which can be symptomless in some.
These two conditions are the primary cause of death in people with SSc.
Oesophageal dysmotility due to fibrosis is common. In addition, oesophagitis, Barrett's oesophagus and oesophageal strictures can appear. Gastroparesis may lead to nausea and early satiety and add to malnutrition and weight loss. Bleeding can take place from telangiectasis of the stomach (‘watermelon stomach’) and intestinal dysmotility can alter bowel motions.
Systemic sclerosis is an autoimmune disease that affects collagen production in the body. It can either be limited (skin changes below the elbows and knees) or diffuse (skin changes distributed over a broader area and involving more internal organs). Common symptoms include tightness and itchiness of the skin, Raynaud's phenomenon and oesophageal symptoms. Typcial examination findings are calcinosis, Raynaud's, sclerodactyly and telangiectasia. Primary investigations include the use of autoantibodies such as antinuclear antibodies, anticentromere antibodies, anti-Scl-70 antibodies and anti RNA polymerase III antibodies. Treatment mainly consists of supportive care to address symptoms related to organ involvement.
Interstital lung disease, pulmonary arterial hypertension and scleroderma renal crisis are among the most important complications of systemic sclerosis. Scleroderma renal crisis is the most severe of the three and is more common among patients with diffuse systemic sclerosis.
Additionally, cardiovascular conditions may arise, such as pericarditis, endocarditis and pericardial effusion. Arrhythmias and heart failure, which may be secondary to pulmonary arterial hypertension, can also occur.
Systemic sclerosis is a chronic systemic connective tissue disorder. It is characterised by involvement of the skin, blood vessels, and multiple internal organs. Several classification criteria have been developed in order to diagnose systemic sclerosis and to distinguish it from other connective tissue diseases.
