Systemic scleroderma is a connective tissue disorder, which affects the skin, vessels and organs such as the heart, digestive tract or lungs.
Systemic scleroderma is a condition that affects a multitude of organs and can therefore lead to the onset of various symptoms. The extent of the symptomatology, prognosis and treatment differ, according to the disease type.
In general, systemic scleroderma exhibits 5 different clinical types:
Skin lesions observed in patients with systemic scleroderma change with the time and follow a definite course: they first appear as red-to-purple edematous lesions, then become hardened and ultimately transform into atrophic lesions.
When internal organs are affected, fluctuating symptomatology is expected because systemic sclerosis can lead to alterations in any organ of the body. Involvement of the gastrointestinal tract may produce dysphagia, nausea and weight loss, diarrhea and cramping; palpitations, shortened breath, weakness and thoracic pain may accompany pulmonary hypertension or cardiopulmonary involvement in general. Pain is a symptom commonly experienced by patients and may occur ulcers, Raynaud's phenomenon and a variety of other causes .
Diagnosis depends on the clinical examination and further laboratory tests and imaging techniques.
Laboratory tests may reveal low platelet levels, an elevated erythrocyte sedimentation rate (ESR), microangiopathic hemolytic anemia, elevated c-reactive protein levels (non-specific marker of inflammation) and hypergammaglobulinemia. Creatine phosphokinase levels may also be elevated in cases of affected muscles.
As far as imaging techniques are concerned, they reveal selective findings, according to the affected area. Collagen deposits on the basal pulmonary regions are depicted via plain radiograph in up to 59% of the patients. High-resolution computed tomography (HRCT) or scintigraphy may also help to detect sclerosed alveolar walls. Esophageal manometry can be applied in patients who report a compatible symptomatology; Doppler echocardiography, an electrocardiogram (ECG) and a 24-hour Holter monitoring are excellent tools to evaluate the involvement of the heart, even in patients who have not yet experienced any heart-related symptomatology .
A bronchoalveolar lavage (BAL) can be used to detect white blood cells in the alveoli, as well as increased granulocytes. Pulmonary function tests can also be performed to assess the efficacy of ventilation and perfusion capacity of the lungs.
Systemic scleroderma cannot be cured, since its etiology remains unknown. Therapeutic approaches aim at minimizing symptoms and possibly hindering the rapid progression of the disease and are always individualized.
Characteristic skin lesions can be treated with UVA-1 phototherapy or Psolaren UV-A therapy (PUVA). Alternative treatments include local emollients to soften the skin, camphor and menthol.
Because of the definitive immunologic dysregulation, various immunomodulating drugs have been proposed to treat the disease. The list is extensive and includes methotrexate, corticosteroids, chlorambucil, cyclosporine, FK506 (otherwise known as tacrolimus) and thalidomide. Photophoresis, statins and cyclophosphamide have also been used, in addition to imatinib and nintedanib ; the latter two have been used due to their ability to reverse the fibrotic procedure.
Additional treatment schemes are applied, depending on the affected organs. Raynaud's phenomenon is treated with prevention of exposure to cold, wearing gloves in the winter and avoidance of smoking. Calcium channel blockers, IV prostaglandin and aspirin have also been used . Should the gastrointestinal tract be affected too, proton pump inhibitors and histamine blockers are the recommended treatment. Lung involvement can be treated with calcium channel blockers as well, in addition to prostaglandins, cyclophosphamide and corticosteroids.
Patients diagnosed with systemic scleroderma can be categorized under two wide categories: diffuse systemic sclerosis (dSSc) and limited cutaneous systemic sclerosis (lSSc). The latter involves a clinical picture with profound cutaneous symptomatology and only late involvement of the internal organs; therefore, the prognosis is more favorable when compared to dSSc, which encompasses symptoms from various organs.
DSSc patients experience severe symptomatology, such as pulmonary hypertension, which was observed in 1/4 of the senior patients as opposed to 1/10 younger patients, in a related study . Pulmonary hypertension increases mortality, especially in smokers.
As is the case in all autoimmune disorders, a proven cause of systemic scleroderma has yet to be established. Nevertheless, various stimuli, environmental or not, are known to trigger the onset of the condition.
Silicone, in the form of implants for various aesthetic purposes or injections, is a substance known to trigger autoimmune disorders, including systemic scleroderma . Patients who are affected by such disorders are usually discouraged from undergoing any type of invasive procedure involving the use of silicone. Organic solvents, pesticides and epoxy resin have also been incriminated. Medications such as carbidopa, bleomycin, panicillamine and cocaine are also believed to be involved in some pathogenetic stage of the disease and a restricted type of systemic sclerosis has also been described in cancer patients treated with paclitaxel . Lastly, substances used to minimize appetite and contribute to weight loss (derivatives of phenylethylamine ) are also believed to trigger systemic sclerosis.
Epidemiologic data vary according to each country; the highest prevalence has been observed in the USA, secondarily to European and Asian countries . The United States, it has been estimated that approximately 20 new patients per million adults are diagnosed with the disease annually. A definite predilection exists for female individuals, who are affected 5 times more often than male patients. Cases of systemic scleroderma diagnosed in children are scarce and most of the patients first exhibit symptoms around the age of 50 years old .
The characteristic features of systemic scleroderma include fibrosis of the skin and viscera. Even though the accurate cause remains unknown, it is believed that alterations of the endothelial consistency lead to an autoimmune response and the stimulation of mast cells, macrophages, fibroblasts and other cellular components involved in the immunologic process. Cytokines and enzymes are believed to be activated afterwards, which inadvertently cause alterations of the extracellular matrix (all types of collagen, fibronectin etc). Overproduction of collagen and its deposition on the skin and organs is the ultimate product of the aforementioned procedure. Collagen deposition is believed to be a direct result of the activation of transforming growth factor-beta (TGF-beta) or interleukin-4 (IL-4), while various other molecular substances have also been incriminated .
Another essential alteration caused by systemic scleroderma involves the destruction of small vessels: TGF-beta and platelet-derived growth factor (PDGF) probably mediate this process as well. Generally, systemic scleroderma is an autoimmune disease, and various autoantibodies are responsible for the profound infiltration of the skin and viscera by t and B cells and other components. it has also been proposed that human leukocyte antigens also play a role in the disease's pathogenesis, although their part remains obscure and unconfirmed. Another theoretical suggestion incriminated cellular apoptosis and the production of free radicals as potential culprits.
Systemic scleroderma cannot be prevented.
Systemic scleroderma is otherwise referred to as systemic sclerosis and is classified under the broader category of connective tissue disorders. It causes cutaneous and visceral collagen infiltration and leads to the destruction of the small vessels. It is a chronic disease, which most often begins with symptomatology related to the skin. Typical symptoms that accompany systemic scleroderma are the Raynaud's phenomenon and regionally thickened skin .
A given predilection has been observed for women in their middle age and Raynaud's phenomenon usually precedes the onset of systemic scleroderma. Internal organs most commonly affected include the lungs, kidneys, heart and digestive tract, which produce multiple organ-related symptoms. Systemic scleroderma is an autoimmune disease and minimum visceral involvement at the time of diagnosis is the best and only prognostic factor. Physicians from different medical specialties are required in order to efficiently monitor a patient affected by the disease and treatment options are available with an aim to minimize symptoms. Various drugs are available to improve the outcome, such as endothelin-1 receptor blockers, calcium channel blockers and lifestyle modifications . Despite the plethora of medications and recommendations, treatment remains supportive.
Systemic sclerosis is an autoimmune disease with an unknown cause. It primarily causes lesions of the skin that progressively become hardened and affects various internal organs as well, such as the heart, kidneys and lungs.
Various factors are believed to trigger the disease; they do not, however, cause the disease. Pesticides, organic chemicals and silicon products used in cosmetic procedures are believed to act as triggers. Women are more often affected by the disease than men and the average age of onset is the age of 50 years old.
Symptoms vary depending on the condition's extent and type. Skin lesions originally appear as red and swollen alterations, progress to become hardened and in the end, atrophic. The lungs and heart are also affected: a person may experience shortness of breath, weakness, fatigue and have a cough without the production of sputum. Raynaud's phenomenon is almost always present and is usually observed before the rest of the symptoms. the hands of the patients become white, then blue and eventually red in cold surroundings and may also be painful. Patients may also experience a difficulty to swallow, a symptom closely related to the gastrointestinal tract.
There is generally no cure for systemic scleroderma; treatment options are available to slow the disease down and reduce the symptoms. Local creams can be applied on the lesions, along with UVA-1 therapy (light therapy) and drugs that change the organism's immunologic response are also available. Various medications are also used to treat symptoms related to each system separately, such as the lungs, heart, kidneys and gastrointestinal tract.
Mayes MD, Reveille JD. Epidemiology, demographics, and genetics. In: Clements P, Furst D, ed. Systemic sclerosis, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins. 2004; 89-93.