Medicine – Systemic Sclerosis (Scleroderma)

Systemic sclerosis, also known as scleroderma, is a chronic autoimmune connective tissue disease characterised by vascular dysfunction, immune activation, and progressive fibrosis of the skin and internal organs. The disease is broadly divided into diffuse systemic sclerosis and limited systemic sclerosis, depending mainly on the extent of skin involvement and the pattern of internal organ disease.

Diffuse Systemic Sclerosis

Diffuse systemic sclerosis is characterised by more extensive skin involvement, typically affecting the trunk, upper arms, forearms, and other proximal areas in addition to the hands and face. Internal organ involvement may occur relatively early and can affect the lungs, kidneys, heart, and gastrointestinal tract.

A proportion of patients have anti-Scl-70 antibodies, also known as anti-topoisomerase I antibodies. These are particularly associated with diffuse disease and with an increased risk of interstitial lung disease and pulmonary fibrosis. Older teaching sources describe anti-Scl-70 antibodies in approximately 30% of patients with diffuse systemic sclerosis.

Limited Systemic Sclerosis

Limited systemic sclerosis generally causes skin thickening confined to the distal extremities and face, particularly the hands, feet, face, and forearms, with little or no truncal involvement. Internal organ disease may still occur, but it often develops more slowly than in diffuse systemic sclerosis.

This form includes CREST syndrome, which is an acronym for calcinosis, Raynaud’s phenomenon, oesophageal involvement, sclerodactyly, and telangiectasia. Limited systemic sclerosis has a strong association with anti-centromere antibodies, which are found in a high proportion of patients, traditionally quoted at around 70–80%.

Clinical Features of Systemic Sclerosis

1. Musculoskeletal Features

Musculoskeletal symptoms are common and may include polyarthralgia, with pain and stiffness affecting several joints. Some patients also develop inflammatory muscle involvement resembling polymyositis, which can produce proximal muscle weakness and contribute to reduced mobility and functional impairment.

2. Skin and Vascular Features

Raynaud’s phenomenon is one of the most common and often earliest manifestations of systemic sclerosis, occurring in almost all patients. Episodic vasospasm causes the fingers to become pale, cyanosed, and then red on reperfusion, particularly after exposure to cold or emotional stress.

Examination of the nail folds may reveal abnormal nail-fold capillaries, reflecting the underlying small-vessel disease. Sclerodactyly develops when the skin of the fingers becomes thickened, tight, and less flexible. Patients may also develop telangiectasia, particularly on the face, lips, and hands.

As fibrosis progresses, the skin may become tight, smooth, waxy, and hyperpigmented, reducing normal skin mobility. Severe vascular compromise can lead to digital or skin ulcers, particularly over the fingertips. Subcutaneous calcification, or calcinosis, may also occur, producing firm calcium deposits beneath the skin.

3. Cardiac Involvement

Systemic sclerosis can affect the heart in several ways. Cardiomyopathy may develop because of myocardial fibrosis or microvascular disease, leading to impaired cardiac function. Pericarditis may also occur and can cause chest pain or a pericardial effusion.

Patients may additionally develop hypertension, particularly in association with renal involvement. Cardiac complications are clinically important because they can contribute to heart failure, rhythm disturbances, and increased morbidity.

4. Pulmonary Involvement

The lungs are frequently affected in systemic sclerosis. Pulmonary fibrosis, usually in the form of interstitial lung disease, can cause progressive breathlessness, dry cough, and impaired gas exchange. This complication is especially associated with diffuse systemic sclerosis and anti-Scl-70 positivity.

Another major pulmonary complication is pulmonary hypertension, which may occur because of disease affecting the pulmonary vasculature. It is particularly associated with limited systemic sclerosis and can present with exertional dyspnoea, fatigue, syncope, and eventually right-sided heart failure.

5. Gastrointestinal Involvement

The gastrointestinal tract is commonly affected because fibrosis and smooth-muscle dysfunction can impair normal motility. Microstomia, or a small oral aperture, may result from tightening of the skin around the mouth and can make eating and dental care difficult.

Oesophageal involvement is particularly common. Patients may develop dysphagia because of impaired oesophageal motility or peptic strictures. Reduced lower oesophageal sphincter pressure predisposes to gastro-oesophageal reflux disease, which may be accompanied by a hiatus hernia and can lead to oesophagitis or stricture formation.

The small and large bowel may also be affected. Patients can develop intestinal diverticula, reduced motility, and stasis. These changes can encourage bacterial overgrowth, which may lead to diarrhoea, bloating, nutrient malabsorption, and weight loss.

6. Renal Involvement

Renal disease is one of the most serious complications of systemic sclerosis. Some patients develop progressive renal impairment, while others may experience an acute scleroderma renal crisis.

A hypertensive renal crisis is characterised by the sudden onset of severe hypertension and rapidly deteriorating renal function. It is a medical emergency and can progress quickly if not recognised and treated promptly. Renal crisis is particularly associated with diffuse systemic sclerosis and may be accompanied by headache, visual disturbance, heart failure, or microangiopathic haemolytic anaemia.

Key Clinical Pattern

Systemic sclerosis can be remembered as a disease of fibrosis, vasculopathy, and internal organ involvement. Diffuse disease tends to have more extensive skin involvement and a greater association with anti-Scl-70 antibodies and pulmonary fibrosis, whereas limited disease is associated with distal skin involvement, CREST features, and anti-centromere antibodies.