Managing systemic sclerosis in primary care
Dr Sue-Ann Ng, Associate Consultant at the Department of Rheumatology & Immunology, Singapore General Hospital, speaks to Roshini Claire Anthony on the multisystemic autoimmune disease that is systemic sclerosis (SSc) and the importance of early identification of the condition.
Systemic sclerosis (SSc) is a multisystemic autoimmune disease characterized by immune dysregulation, vasculopathy, and fibrosis. The prevalence of SSc is estimated to be between 20 to 300 people per million worldwide. Prevalence appears to be higher in Caucasian populations (eg, 240 per million persons in the US) than in Asian groups (eg, 21 and 56 per million persons in Japan and Taiwan, respectively). In Singapore, the prevalence is estimated to be about 77 per million persons. Onset of SSc is commonly between the ages of 30 and 50 years, with women four times more likely to develop the condition than men.
The diagnosis of SSc is mainly based on clinical history and examination, laboratory tests for autoantibodies, and nailfold capillaroscopy (NFC). Early recognition of the symptoms of SSc will help facilitate early referral and secure diagnosis of the disease.
There are two subtypes of SSc – limited (LcSSc) or diffuse (DcSSc) cutaneous SSc. In LcSSc, fibrosis is mainly restricted to the fingers, hands, face, forearms (distal to the elbows), and lower legs (distal to the knees). In DcSSc, fibrosis occurs proximal to the elbows and knees, and may involve the trunk. Although both are associated with internal organ involvement, DcSSc patients are at greater risk of developing clinically significant major organ dysfunction. The gastrointestinal (GI) tract, heart, lungs, and kidneys are the most frequent targets.
The first sign of SSc is usually the development of puffy and thickened skin in the fingers and toes. Skin hardening/tightening leads to decreased joint mobility and contractures. Raynaud’s phenomenon (RP) often precedes skin manifestations and is reported to occur in more than 90 percent of SSc patients, but in countries like Singapore with warmer climates, the prevalence is about 80 percent.
GI involvement occurs in up to 90 percent of SSc patients and represents one of the earliest manifestations of SSc. Main symptoms include dysphagia/heartburn (oesophageal involvement), bloating/distension/vomiting (gastroparesis), distension/diarrhoea/constipation (lower GI involvement with dysmotility and bacterial overgrowth), and faecal soilage (anorectal involvement).
Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are leading causes of death in SSc. Early symptoms of PAH are non-specific (eg, dyspnoea, fatigue) and clinical signs are subtle until the advanced stages. Symptoms of ILD include dyspnoea and persistent dry cough. Locally, renal crisis is rare, with a prevalence of about ≤2 percent, and patients may present with renal failure and hypertension.
There is no routine screening for SSc. Risk factors for SSc include genetic factors and certain environmental exposures (eg, vinyl chloride and silica).
SSc is characterized by fibrosis, vasculopathy, and dysregulation of the immune system. The early triad of symptoms and signs reflecting the above processes are puffy fingers, RP, and positive antinuclear antibody (ANA), respectively. If there is clinical suspicion of SSc based on clinical history and examination, one should order baseline blood investigations such as a full blood count, biochemistry, renal function, and ANA. Early referral to a rheumatologist should be made for further evaluation and management.
Early symptoms of SSc can be non-specific, for example, fatigue, musculoskeletal pains, and hand swelling or puffy fingers, and some patients may have mild or no skin manifestations at presentation. Patients often dismiss puffy fingers as this may be intermittent. Specific enquiry on this symptom is needed. Thickened, hardened, or tight skin may be gradual and insidious and patients may not notice the change. Obtaining collateral history from the patient’s next-of-kin is often helpful. It is therefore important that GPs can recognize the clinical features of SSc so that prompt referral to a rheumatologist can be made for further evaluation and management.
Patients diagnosed with SSc and suspected SSc based on RP or puffy fingers, with or without positive autoantibodies, should be referred for further evaluation. The specialist can evaluate further with nailfold capillaroscopy and check for organ involvement.
Currently, there are no curative therapies for SSc. Treatment is aimed at slowing disease progression, improving vasculopathy, and providing supportive symptomatic care. Patients with RP may be given medications such as dihydropyridine calcium channel blockers (eg, amlodipine, long-acting nifedipine), ACE-inhibitors, or angiotensin II receptor blockers to improve blood flow. Patients should be advised to keep their hands warm and to stop smoking.
In patients with GI involvement, lifestyle modifications and medications such as proton-pump inhibitors (PPIs; eg, omeprazole) and prokinetics (eg, domperidone) are used to control gastroesophageal reflux disease in SSc patients. Importantly, SSc patients should be referred to a rheumatologist for further care because management of SSc and its complications requires specialized expertise which has shown to improve health outcomes.
The management of SSc patients is challenging as the management of internal organ complications requires a multidisciplinary approach and disease-associated damage is often difficult to reverse. Hence it is imperative for early referral of SSc patients to a rheumatologist for further care and management.
Potential complications of SSc result from internal organ involvement including ILD, PAH, GI tract involvement, renal crisis, recurrent ulcer/gangrene from vascular complications, increased risk of malignancy, and osteoporosis.
The main international guidelines include the 2013 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria for SSc. This updated classification criteria allows for early recognition of SSc even without overt skin sclerosis, recognizing the importance of SSc-specific autoantibodies (eg, anti-Scl70, anti-centromere, anti-RNA-polymerase III) and abnormalities on nailfold capillaroscopy reflecting vasculopathy. The updated EULAR recommendations for the treatment of SSc is another helpful guide.
GPs are often the first point of contact for patients to seek treatment. As SSc is a relatively rare disease, cases may often be undiagnosed or misdiagnosed, particularly in patients who present with early and non-specific symptoms and who have mild or no skin manifestations. GPs therefore play a pivotal role in recognizing initial symptoms associated with SSc and early referral to a specialist such as a rheumatologist for further evaluation and management. Early identification and appropriate monitoring of patients with SSc is critical so that active disease can be controlled.
Skin changes in systemic sclerosis include taut and thickened skin, digital ulcers, digital pitting, calcinosis and telangiectasiae. Skin hardening/tightening leads to decreased joint mobility and contractures. (Image courtesy of SGH)
2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative
Update of EULAR Recommendations for the Treatment of Systemic Sclerosis