Erum Naqvi obtained her Ph.D. in Molecular Medicine from Hannover Medical School (Germany) after completing her Masters in Biomedical Science and Bachelors in Microbiology from University of Delhi (India). She has several years of experience as a science writer.
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Clinical Features
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by fibrosis and vasculopathy, leading to clinical features such as skin thickening, skin hardening, and damage to internal organs including the lungs, heart, gastrointestinal tract, and kidneys. The extent and depth of organ involvement varies widely among patients with SSc, causing an array of possible clinical features that are individual to each case.1,2
Cutaneous Features
Skin manifestations are the earliest and most apparent feature in patients with SSc. The skin thickens and hardens, particularly the skin of the fingers, hands, and face.1-3
SSc Subtypes
The types of SSc are classified on the basis of skin involvement. In patients with limited cutaneous SSc, skin manifestations are confined to the extremities, face, and neck, with no involvement of the trunk. In patients with diffuse cutaneous SSc, skin proximal to the knees (around the thighs) or elbows (around the upper arms), and trunk, is also involved. In patients with systemic sclerosis sine scleroderma (or SSc without skin involvement), skin thickening is absent.1-3
Read more about SSc types
Phases of Cutaneous Features
In the initial phase, skin thickening usually affects the fingers, causing a “puffy” appearance that may last several months. This occurs in association with inflammation and edema, and patients commonly experience burning pain, itching, and erythema. In addition, loss of the skin appendages, including hair, glands, and nails, makes the skin feel dry and uncomfortable.1-3
Following the skin-thickening phase is the long-lasting fibrotic phase, in which skin thickening and fibrosis begins distally (usually fingers) but then progresses proximally. The skin may undergo ulceration at sites of pressure, such as the extensor surfaces of interphalangeal, metacarpophalangeal, and elbow joints. Skin changes on the face may limit eyelid movement or cause the skin around the mouth to tighten, with the development of radial furrowing and a small oral opening (microstomia).1-3
In the advanced stages of the disease, the skin — particularly on the upper arms and trunk — may become atrophic, soften, and appear relatively normal. However, the underlying subcutaneous tissue remains fibrotic, and mobility may be restricted by hand or finger contractures.1-3
Read more about SSc diagnosis
Digital Vascular Disease
Digital vascular disease ranges from temporary attacks of Raynaud phenomenon to permanent tissue ischemia (digital pitting scars and ulcers).4
Raynaud Phenomenon
Raynaud phenomenon is a common clinical feature, noted in approximately 95% of patients with SSc. It typically manifests as temporary episodes of skin color change and sensory symptoms such as numbness and pain. Raynaud phenomenon is characterized by blood vessel spasms (vasospasms), triggered by exposure to cold temperatures or emotional stress, that cause the skin to turn white as a consequence of ischemia. Subsequent vessel occlusion and deoxygenation result in severe pain and cause the skin to turn blue. Finally, the vasospasms stop after several (15-20) minutes, and the skin becomes red as blood flow is restored (hyperemia).1,4
Raynaud phenomenon frequently affects the fingers but can also occur at other sites, such as the toes, lips, and ears. Raynaud phenomenon may develop at the same time as skin thickening or many years before the onset of skin thickening.1,4
Digital Ulcers
Digital ulcers, which are common in SSc, develop in approximately 50% of patients. They occur most often on the fingertips and over the dorsal (extensor) surfaces of the elbow joint or the small joints (eg, metacarpophalangeal, interphalangeal) of the hands.4
Digital Ischemia
Critical digital ischemia, which is a medical emergency, develops in a minority of patients. In rare cases, it may progress to gangrene, resulting in significant tissue loss and required amputation.4
Other Skin Features
Telangiectasia occurs when dilated cutaneous capillaries and blood vessels appear as red lesions on the skin, commonly on the hands, face, and mucosal surfaces and sometimes the trunk.1,2
Subcutaneous or intracutaneous calcinosis is seen in 20% to 40% of patients with SSc, caused by the accumulation of calcium hydroxyapatite deposits. The calcium deposits occur mainly on areas subjected to pressure or trauma, such as the extensor surfaces of the elbows or knees and finger pads. These deposits can cause skin ulceration or become infected.1,2
Another skin feature of SSc is a “salt-and-pepper-like” appearance, in which areas of depigmentation or hypopigmentation are surrounded by normally pigmented skin.1
Read more about SSc signs and symptoms
Musculoskeletal Features
Common musculoskeletal features range from nonspecific myalgia and arthralgia to overt myositis and arthritis.1,5
Involvement of Joints
Affected joints, usually the metacarpophalangeal, interphalangeal, wrist, ankle, and knee joints, become painful, stiff, swollen, and deformed. The ensuing restriction of joint mobility results in disability. Rapidly progressive fibrosis involving the skin, muscles, joints, and tendons causes joint contractures (in the fingers or elbows), resulting in pain and stiffness, and prevents normal movement.1,5
Involvement of Tendons
Tendon involvement is most commonly seen as tenosynovitis and tendon friction rubs, which are caused by inflammation, swelling (edema), and fibrosis of the tendon sheath.1,5
Myopathy
Involvement of the muscle in patients with SSc causes myopathy, which leads to muscle pain, weakness, and sarcopenia. Myopathy may be caused by inflammation or fibrosis.1,5
Inflammatory Myopathy
Inflammatory myopathy (myositis) involves chronic muscle inflammation, progressive weakness of the proximal muscle, reduced muscle strength, and elevated muscle enzymes.1,5
Fibrosing Myopathy
Fibrosing myopathy occurs in patients with more severe disease. It is caused by fibrosis of the muscle, usually without inflammation.1,5
Involvement of Bones
Bone changes include acro-osteolysis (osteolysis of the distal phalanges of the hands and feet), erosive deformation of the distal interphalangeal joints, and intraosseous calcium deposition. Patients with SSc are at increased risk for osteoporosis.5
Read more about SSc treatment
Gastrointestinal Features
Gastrointestinal (GI) involvement, which occurs in 90% of patients with SSc, may range from mild to serious. Any area of the GI tract, from mouth to anus, can be affected.1,3,5
Oropharyngeal Features
Involvement of the oropharyngeal area includes skin tightening around the mouth, periodontitis, microstomia, xerostomia, and gingivitis. The symptoms can vary from mild to severe. Patients may also suffer from fibrosis of salivary glands, or inflammatory infiltrate, secondary to Sjögren syndrome.1,5
Esophageal Features
The most commonly affected part of the GI tract is the esophagus, where fibrosis causes esophageal dysmotility associated with heartburn and dysphagia. In addition, hypotonia of the lower esophageal sphincter prevents its normal closure, worsening reflux symptoms. Other symptoms of esophageal involvement are painful swallowing, regurgitation, and chronic cough or hoarseness.1,3,5
Gastric Features
Gastric involvement can take the form of gastroparesis, which can lead to premature satiety, nausea, bloating, vomiting, and anorexia. This condition can also cause nutritional deficiencies and loss in weight. Gastric mucosal telangiectasia can cause gastric antral vascular ectasia (GAVE, or “watermelon stomach”), which in turn causes occult or heavy GI bleeding.1,5
Intestinal Features
Fibrosis in the intestine can cause intestinal dysmotility, with pain, bloating, overgrowth of intestinal bacteria, malabsorption, diarrhea, constipation, fecal incontinence, pseudo-obstruction, and later abdominal distension.1
Anal Features
Involvement of the anal region can cause reduced tone of the anal sphincter muscles, resulting in rectal prolapse and fecal incontinence.1
Read more about SSc surgical management
Pulmonary Features
The most common cause of death in patients with SSc is pulmonary disease. Common pulmonary manifestations include interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Other pulmonary manifestations may include aspiration pneumonia, obstructive airway disease, cryptogenic organizing pneumonia, pulmonary hemorrhage, and pleuritis.1,3
Interstitial Lung Disease
ILD is due to fibrosis of the lung tissue, which prevents lung expansion and gas exchange. The main symptoms of ILD are shortness of breath, fatigue, and dry cough. ILD is usually characterized by abnormal breath sounds or basal crackles (often late inspiratory).1,3,6
Pulmonary Arterial Hypertension
PAH occurs late during the course of SSc, usually more than a decade after diagnosis. It can initially lead to shortness of breath, chest pain, and fatigue, and later to right-sided heart failure, lower extremity edema, lightheadedness, and exertional syncope.1,3
Read more about SSc comorbidities
Cardiac Features
Cardiovascular features are common in SSc and life-threatening. Depending on the cardiac region affected (myocardium, pericardium, coronary arteries, or cardiac conduction system), manifestations can include myocardial fibrosis, myositis, coronary heart disease, pericardial effusion, pericarditis, cardiac disease (eg, left ventricular diastolic dysfunction), dyspnea, palpitations, chest pain, or features of heart failure.1,3,5
Myocardial fibrosis can cause dilated cardiomyopathy, which makes it difficult for the heart to pump blood. Fibrosis of the cardiac electrical conduction system can cause intraventricular conduction delays, heart block and supraventricular tachycardia and arrhythmias (commonly premature ventricular contractions).1,3,5
Read more about SSc therapies
Renal Features
The most serious renal complication of SSc, which occurs in approximately 10% of patients, is scleroderma renal crisis due to SSc-associated vasculopathy. This manifests as a hypertensive emergency, characterized by the abrupt onset of severe high blood pressure, renal failure, acute pulmonary edema, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, and microscopic hematuria.1,3,6
Read more about SSc prognosis
Other Features
Other features reported in patients with SSc include hypothyroidism; autoimmune diseases (eg, Graves disease, Hashimoto thyroiditis, primary biliary cirrhosis, secondary Sjögren syndrome); psychological disorders (eg, depression); and overlap syndromes (overlap of SSc with rheumatoid arthritis and polymyositis).1
References
- Adigun R, Goyal A, Hariz A. Systemic sclerosis. StatPearls [Internet]. Updated May 8, 2022. Accessed April 27, 2023.
- Ferreli C, Gasparini G, Parodi A, Cozzani E, Rongioletti F, Atzori L. Cutaneous manifestations of scleroderma and scleroderma-like disorders: a comprehensive review. Clin Rev Allergy Immunol. 2017;53(3):306-336. doi:10.1007/s12016-017-8625-4
- Systemic scleroderma – symptoms, causes, treatment. NORD. Updated June 24, 2020. Accessed April 27, 2023.
- Hughes M, Herrick AL. Systemic sclerosis. Br J Hosp Med (Lond). 2019;80(9):530-536. doi:10.12968/hmed.2019.80.9.530
- Sobolewski P, Maślińska M, Wieczorek M, et al. Systemic sclerosis – multidisciplinary disease: clinical features and treatment. Reumatologia. 2019;57(4):221-233. doi:10.5114/reum.2019.87619
- Herrick AL. Systemic sclerosis: clinical features and management. Medicine. 2022;50(1):60-69. doi.10.1016/J.MPMED.2021.10.010
Reviewed by Debjyoti Talukdar, MD, on 4/29/2023.
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