On the occasion of Scleroderma Rheumatic Disease Awareness Week (June 6 - 12) and World Scleroderma Day - June 29, the Organization of Patients with Rheumatological Diseases is organizing an online lecture by the immunologist from the Laboratory of Clinical Immunology of UMBAL "St. Ivan Rilski" Dr. Ekaterina Kurteva, MD We are publishing a part of the presentation of Dr. Kurteva, who in 2019 defended her dissertation work "New immunological indicators in the diagnosis and pathogenetic mechanisms in progressive systemic sclerosis".
What is the disease
Progressive systemic sclerosis (scleroderma) is a severe debilitating connective tissue disease with multifaceted clinical manifestations. It affects both the skin and internal organs. In this disease, connective tissue is deposited in the skin and internal organs. Fibrosis also affects the muscles and skeleton. The most characteristic is the skin involvement, which is called scleroderma.
Localized scleroderma is limited to the skin and subcutaneous tissue, and progressive systemic sclerosis affects the skin and internal organs. Progressive systemic sclerosis has two forms – the first is limited, which manifests itself mainly on the hands, forearms, face and neck, as well as on various internal organs; the second is a diffuse form in which there is severe visceralization.
Possible symptoms
The most common and first clinical manifestation of scleroderma is Raynaud's Syndrome - paleness or blueness of the fingers, redness during cold and stress, a feeling of pain on the tips of the fingers. This syndrome precedes the other symptoms by 2-3 years, but in the diffuse form it appears simultaneously with the other symptoms. However, Raynaud's syndrome is not always a part of scleroderma. But the only solution is to make an appointment with a rheumatologist and conduct the necessary tests.
Another symptom is diffusely swollen fingers. They are very characteristic of the early stage of the disease and lead the doctor to think about progressive systemic sclerosis. In the developed two-step model for early diagnosis, the first step is precisely the presence of edematous compacted fingers. In the corresponding rheumatology center, the second step of the diagnostic process will be carried out - the capillaroscopy of the nail bed and examination in a competent immunological laboratory of systemic sclerosis-specific antinuclear autoantibodies (ANA).
In rheumatology practice in Bulgaria and in Europe, the following antinuclear antibodies are mainly tested for clinical suspicion of systemic sclerosis: ASA, ATA, anti-RNAP III and anti-PM/Scl. In this regard, the Clinical Immunology Laboratory of UMBAL "St. Ivan Rilski", in collaboration with our Rheumatology Clinic, make an exception, since for several years a wider panel of specific antinuclear autoantibodies associated with progressive systemic sclerosis has been routinely examined.
Is scleroderma related to environmental factors
A proven risk factor for scleroderma is exposure to silicon and all silicon derivatives. Silica dust is involved in the occurrence of many diseases, including pulmonary silicosis. Risk groups are workers in gold and coal mines, stonemasons and masons, as well as all those who work with abrasive dust.
Silicone implants are also a risk factor and lead to progressive systemic sclerosis. People with a genetic predisposition to the disease are ten times more likely to develop it if they also have silicone implants. If you have any suspicion of autoimmunity, it is not advisable to put silicone anywhere on the body. The same applies to the implantation of paraffin and paraffin derivatives.
Exposure to aromatic hydrocarbons is also an identified risk factor for scleroderma. "We have quite a few patients who have worked at gas stations or organic solvent plants. Chlorine-containing compounds, such as vinyl chloride, are also a risk factor for the development of systemic sclerosis.
There are also drugs that can lead to the development of the disease. Cocaine has the same effect. The use of the dietary supplement 5-Hydroxytryptophan (precursor of serotonin) is absolutely contraindicated in patients with progressive systemic sclerosis," she explained.
Appetite suppressants are also dangerous
for these patients. Rapeseed oil too, because it is very often contaminated with substances that have carcinogenic potential, as well as to provoke systemic sclerosis. There are studies that prove that exposure to heavy metals - cadmium, mercury, lead, molybdenum, palladium and zinc - are a factor in the development and progression of the disease.
The role of antinuclear antibodies
Over 95% of patients with progressive systemic sclerosis have positive autoantibodies directed against nuclear antigens (antinuclear autoantibodies - ANA), which are a sign of autoimmunity. In addition, some of the autoantibodies found in patients with progressive systemic sclerosis are disease-specific and associated with a particular form of the disease.
For example, in most cases, anticentromeric antibodies (ACA) are detected in patients with limited skin involvement. On the other hand, antitopoisomerase antibodies (ATA) are most often found in patients with diffuse progressive systemic sclerosis. An association between certain autoantibodies characteristic of progressive systemic sclerosis and certain clinical manifestations has been demonstrated.
Patients positive for anti-Th/To autoantibodies have a worse prognosis than patients positive for anticentromeric antibodies (ACA). They have a high incidence of systemic sclerosis associated with pulmonary hypertension, interstitial lung disease, and scleroderma renal crisis. Autoantibodies against fibrillarin (anti-U3 RNP autoantibodies) predominate in scleroderma patients with muscle involvement.
Predicting the development of the disease
Antinuclear antibodies (ANA) in progressive systemic sclerosis are an important immunological marker not only in diagnosis. ANA also have a predictive (predictive) role for the degree of skin involvement, for the type of organ damage and the outcome of the disease. It has been found that ANA in progressive systemic sclerosis can be detected long before the development of clinical symptoms
In a small percentage of patients, ANA becomes negative during immunological follow-up, which is associated with a more favorable prognosis. ANAs specific for progressive systemic sclerosis are rarely seen in other systemic connective tissue diseases and are even less common in non-immune-mediated diseases or in he althy individuals. These ANAs are usually first detected early in the course of progressive systemic sclerosis (scleroderma) and their appearance rarely changes during the course of the disease.
