Systemic Sclerosis (SSc)

Systemic sclerosis (SSc) is a multisystem disease that may affect the skin, lungs, blood vessels, heart, kidneys, gastrointestinal tract, and musculoskeletal system.¹ The systemic manifestations and internal organ involvement of SSc are associated with increased mortality.² Defining features of this disease include autoimmune processes, vascular endothelial damage, inflammation, and widespread fibroblast activation.¹ 

The most frequent early signs and symptoms of SSc are Raynaud phenomenon, swelling of the distal extremities (with an insidious onset), and slow thickening of the skin of the fingers. In addition, polyarthralgia is common. Occasionally, the initial symptoms include gastrointestinal problems, such as heartburn and dysphagia, or respiratory problems, such as dyspnea.³ 

Skin and Nail Manifestations

Raynaud phenomenon (RP) is the initial symptom in most patients. Vasospasm, brought on by cold or stress, is a characteristic of RP and most frequently affects the fingers, which turn white and then blue because blood vessel blockage prevents oxygen delivery. Additionally, RP may cause extreme pain and ulceration. The vasospasm abates after a time (often between 15 and 20 minutes), and the fingers turn red as blood flow resumes.⁴

In nearly all cases of SSc, hard and thickened patches of skin develop. In limited cutaneous SSc, the skin of the face, forearms, and lower legs up to the knee is affected. This type of SSc typically starts and progresses slowly. In diffuse cutaneous SSc, the skin of the upper arms, thighs, or trunk may also be affected. The abnormalities usually develop rapidly over a few months, although after 3 to 5 years, the condition ‌often abates.⁵ In the rare form of SSc known as systemic sclerosis sine scleroderma, multiple internal organs (particularly the lungs and gastrointestinal tract) are involved without thickening of the skin.²

Other ways in which SSc affects the skin include⁵: 

• Swelling of the toes and fingers, which is a typical early symptom. Because of this, hand movements may be difficult or painful, and the fingers may resemble sausages.
• Ulcerations on the fingertips
• Chalky, hard swellings in the skin (calcinosis)
• Impairment of skin appendages, including glands, nails, and hair, causing dry and itchy skin 

Read more about SSc diagnosis

Nerves, Muscles, and Joints

Nerve, muscle, or joint problems affect many people with SSc. Muscle involvement can result in sarcopenia, as well as muscular pain and discomfort. The joints may be inflamed, painful, and stiff.⁴ Mild arthritis or polyarthralgias may be evident. Flexion contractures may develop in the fingers, wrists, and elbows. Friction rubs may develop over the joints, tendon sheaths, and large bursae.³

Although nerve involvement is less frequent, it can cause burning, tingling, or numbing sensations. In some cases, the autonomic nervous system may be affected. Symptoms of autonomic nervous system dysfunction include dizziness when standing up (orthostasis),  improper heart rate response to exertion, and inappropriate sweating.⁴

Read more about SSc clinical features

Gastrointestinal Manifestations

Gastrointestinal involvement is noted in all cases of diffuse and limited SSc. Any portion of the gastrointestinal tract can be affected, and symptoms may range from mild to severe, including intestinal dysmotility, mucosal telangiectasias, perioral skin tightening, gastric telangiectasia, and esophageal stricture.²

Signs and symptoms vary depending on which part of the gastrointestinal tract is involved. Upper gastrointestinal tract symptoms include: heartburn or gastroesophageal reflux; dyspepsia; difficulty swallowing; micro-aspiration, which exacerbates lung disease; and early satiety. Lower gastrointestinal tract symptoms include: nausea and vomiting; bloating and distension; pain; alternating diarrhea and constipation; and anorectal sphincter dysfunction causing incontinence.⁶

Read more about SSc complications

Cardiopulmonary Manifestations

SSc can involve the myocardium, pericardium, coronary vessels, and electrical conduction system. The signs and symptoms of cardiac involvement vary depending on which part of the heart is affected and may include‌ chest pain, difficulty breathing, arrhythmias, and heart failure.⁴

Although lung involvement is a frequent cause of death, it usually progresses slowly and varies significantly among individual patients. Interstitial lung disease and lung fibrosis, which are common in patients with SSc, limit gas exchange and cause exertional dyspnea, restrictive disease, and eventually respiratory failure. Acute alveolitis may develop, which responds to treatment. Aspiration pneumonia can result from esophageal dysfunction. Heart failure and pulmonary hypertension are other possible manifestations, both with a dismal prognosis.³

Read more about SSc prognosis

Renal Manifestations

Scleroderma renal crisis (SRC) is the most significant renal manifestation of SSc, characterized by the sudden onset of severe hypertension, proteinuria, and renal failure.⁴ Microangiopathic hemolytic anemia (MAHA), in which excessive clot formation by platelets in small blood vessels leads to hemolysis, often accompanies SRC. MAHA consequently results in reduced levels of platelets and red cells.⁴

Read more about SSc risk factors

Other Signs and Symptoms

Up to 15% of patients with SSc, particularly those with limited cutaneous SSc, have hypothyroidism, which may be a consequence of thyroid fibrosis. Additionally, patients with SSc are more likely to have autoimmune thyroid conditions such as Graves disease and Hashimoto thyroiditis. Secondary Sjögren syndrome and primary biliary cirrhosis are autoimmune disorders that are relatively common in individuals with SSc. Overlap syndromes, in which SSc coexists with polymyositis and rheumatoid arthritis, occur frequently in patients with SSc, as do psychological problems, including depression (noted in up to 50% of patients).²

Fatigue, anxiety, sexual dysfunction, and body image problems are common in patients with SSc. However, many affected people can live long and fulfilling lives despite the elevated risk of mortality associated with this disease.⁴

Read more about SSc life expectancy

References

1. Midhuna PV, Thappa DM. Simplified guidelines for the management of systemic sclerosis. Cosmoderma. 2021;1:24. doi: 10.25259/CSDM_12_2021
2. Adigun R, Goyal A, Hariz A. Systemic sclerosis. StatPearls [Internet]. Updated May 8, 2022. Accessed April 19. 2023.
3. Nevares AM. Systemic sclerosis. MSD Manual Professional Version. Updated October 2022. Accessed April 19, 2023.
4. Systemic scleroderma. NORD (National Organization for Rare Disorders).Updated June 24, 2020. Accessed April 19, 2023.
5. Tidy C, Hezall C. Systemic sclerosis. Causes, symptoms, and treatment. Patient. Updated May 25, 2022. Accessed April 19, 2023.
6. Saracino A Denton C. Systemic sclerosis. DermNet. Updated July 2020. Accessed April 19, 2023.

Reviewed by Debjyoti Talukdar, MD, on 4/22/2023.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.