Systemic sclerosis: definition, causes, symptoms, diagnosis and treatment

By Cristiano Antonino Last updated Jun 17, 2023

Diffuse fibrosis and vascular abnormalities in the skin, joints and internal organs are some of the consequences of systemic sclerosis, a rare connective tissue disease whose multifactorial genesis continues to generate questions and doubts within the scientific world

The onset of the disease is between 40 and 60 years of age (with more severe forms occurring around 20-25 years of age) and tends to develop more frequently in women than in men with a ratio of 7:1.

Systemic sclerosis: what is it?

Systemic sclerosis, also called scleroderma, is a rare chronic, autoimmune systemic disease of unknown origin.

The main characteristic of this disease is an excessive production of collagen and extra-cellular matrix that causes fibrosis, i.e. thickening, of the skin and internal organs such as the heart, kidneys, intestines and lungs, abnormalities of the immune system and alterations of small-calibre vessels such as capillaries and arterioles, leading to skin ulcers, pulmonary hypertension and irregularities in the motility of the digestive system.

This autoimmune disease can be subdivided into:

Limited systemic sclerosis or CREST syndrome (an acronym for Calcinosis, Raynaud’s phenomenon, Oesophageal motility disorders, Sclerodactyly and Teleangiectasia);
Generalised systemic sclerosis;
Systemic sclerosis without scleroderma.

Limited systemic sclerosis has a gradual onset, progressive thickening of the skin of the face, elbows, knees and patients may suffer from gastroesophageal reflux.

The progression of the disease is very slow and often presents pulmonary hypertension among the complications.

Patients suffering from generalised systemic sclerosis, with diffuse skin involvement, present Rayanaud’s phenomenon and gastrointestinal complications.

The disease evolves very rapidly, involving the internal organs early and presenting interstitial pneumonia and renal crisis among the major complications.

In systemic sclerosis without scleroderma, on the other hand, patients present with antibodies associated with systemic sclerosis and visceral manifestations of the disease, without suffering from thickening of the skin.

What are the causes of this disease?

Although many people are affected by systemic sclerosis, the underlying causes remain unknown to this day. It is speculated that environmental factors such as exposure to organic solvents, toxins or microbial agents may play a role in triggering the onset of the disease.

In general, research has come to the conclusion that the genetic predisposition of the subject plays a key role in the manifestation of the disease.

It should be pointed out, however, that systemic sclerosis is not to be regarded as a hereditary disease, as sufferers do not generally have family members suffering from the same disorder.

Among the hypotheses concerning the triggering causes of the disease is one that speculates that a particular virus (cytomegalovirus) may be involved in the origin of the disease.

This virus, in fact, enters cells by reproducing in an uncontrolled manner and could be the cause of the activation of the immune response against the subject’s tissues and organs.

In addition, it has been observed that contact with certain substances such as vinyl chloride, aromatic hydrocarbons and epoxy resins can lead to fibrosis similar to that of a person with scleroderma.

Symptomatology of systemic sclerosis

The presenting symptoms of systemic sclerosis are extremely varied.

Among the most common symptoms at the onset of the disease is Raynaud’s phenomenon, a condition whereby the extremities of the body (most commonly the hands and feet, but also the nose and ears) become cold and tend to change colour.

Other symptoms of systemic sclerosis are:

Skin and nail manifestations such as: skin swellings that progress to hardening; skin that becomes taut, shiny, hypopigmented or hyperpigmented; amimic face; development of subcutaneous calcifications; development of digital ulcers; capillary abnormalities and microvascular loops at the nail level.
Joint manifestations such as mild arthropathy or polyarthralgia; development of flexion retractions of the elbows, wrists and fingers.
Gastrointestinal manifestations: oesophageal dysfunction (which seems to be the most frequent); dysphagia; retrosternal pyrosis; acid reflux; Berrett’s oesophagus; small intestinal hypomotility; intestinal pneumatosis; peritonitis and, in patients with limited systemic sclerosis, biliary cirrhosis may develop.
Cardiopulmonary manifestations are among the most frequent causes of death. The disease generally involves the lungs in a subtle and variable manner, but can cause disorders such as pulmonary fibrosis and interstitial pneumopathy, which can manifest as dyspnoea on exertion and can develop into respiratory failure. Acute alveolitis, aspiration pneumonia, pulmonary hypertension or heart failure may also develop. In many of these cases, the prognosis is unfortunately not favourable.
Development of a severe and sudden kidney disease, scleroderma renal crisis, which commonly develops in the first 4-5 years especially in patients with diffuse scleroderma. It is most often preceded by severe hypertension, which, however, may also be absent. Skin symptoms may also be absent and, therefore, it is complicated to make a correct diagnosis.

Diagnosis

In the presence of patients with the classic clinical presentation, the diagnosis of systemic sclerosis is fairly easy to formulate.

In fact, systemic sclerosis is suspected in patients presenting with Raynaud’s phenomenon, the typical skin manifestations that characterise the disease and dysphagia that cannot be attributed to another cause, or unexplained visceral signs such as pulmonary fibrosis or pulmonary hypertension.

However, the disease cannot always be diagnosed through clinical analysis and, therefore, the doctor may resort to laboratory investigations as confirmation of the clinical suspicion.

A useful test to check for scleroderma is capillaroscopy.

This simple, non-invasive test allows early diagnosis of this disease and is generally performed in the presence of Raynaud’s phenomenon or other symptoms that may suggest the presence of the disease.

Other investigations that can be performed to diagnose systemic sclerosis are

Spirometry, DLCO and high-resolution chest CT to study pulmonary health.
Holter ECG, echocardiogram and cardiac MRI to investigate any abnormalities in cardiac function.
Oesophageal and rectal manometry, radiography and oesophagogastroduodenoscopy to observe the state of the digestive system.

According to the European Group for the Study of Systemic Sclerosis, EUSTAR, the symptoms that should alert patients and doctors and enable an early diagnosis of the disease are:

Edematous and chubby hands;
Raynaud’s phenomenon;
Presence of anti-Scl70 antibodies or the scleroderma pattern, a typical alteration of the nail capillaries that can be detected by capilaroscopy.

Prognosis

Survival at 10 years after disease onset is 92% for those with limited systemic sclerosis and 65% for those with diffuse systemic sclerosis.

The course of the disease is highly dependent on the type of systemic sclerosis and antibody profiling.

In general, the disease is unpredictable.

Patients suffering from diffuse cutaneous disease tend to have a much more aggressive course and develop visceral complications early in the first three to five years after the onset of the disease.

Many of these complications, including heart failure, ventricular ectopy, etc., can worsen and lead to death.

Treatments

To date, there is no real cure for systemic sclerosis, although there are many efforts by the scientific community to develop effective therapies.

Treatments are geared towards controlling symptoms and visceral dysfunction.

The drugs prescribed to the patient will be useful in treating the specific organic symptoms of the disease.

Corticosteroids are useful in cases of myositis or mixed connectivitis, while other immunosuppressants are useful in cases of pulmonary alveolitis.

Calcium channel blockers such as oral nifedipine may be prescribed for Raynaud’s phenomenon, or drugs such as bosentan, sildenafil and tadalafil for more severe cases.

The prescription of drugs, however, must be evaluated very carefully as they may cure some symptoms but worsen or cause others.

To preserve muscle tone, on the other hand, physiotherapeutic treatments and physical activity are often recommended to patients, but are not very effective in counteracting joint retractions.

Patients suffering from systemic sclerosis are also recommended not to expose themselves to excessively low temperatures, to keep their living quarters at a temperature ranging from 20°C upwards, to cover their extremities and to sleep with the head of the bed elevated or in a semi-sitting position if possible.

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