is a chronic systemic autoimmune disease (primarily of the skin) characterized by fibrosis (or hardening), vascular alterations, and autoantibodies. There are two major forms:
Limited systemic sclerosis/scleroderma involves cutaneous manifestations that mainly affect the hands, arms and face. It was previously called CREST syndrome in reference to the following complications:
Additionally, pulmonary arterial hypertension may occur in up to one-third of patients, and is the most serious complication for this form of scleroderma.
Diffuse systemic sclerosis/scleroderma is rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and lungs. This form of scleroderma can be quite disabling. There are no treatments for scleroderma itself, but individual organ system complications are treated.
The cause is unknown. Scleroderma runs in families, but the genes have not been identified. It affects the small blood vessels (arterioles) in all organs. First, the endothelial cells of the arteriole die off, along with smooth muscle cells, by a process of apoptosis. They are replaced by collagen and other fibrous material. Inflammatory cells, particularly CD4+ helper T cells, infiltrate the arteriole, and cause further damage. Many of the inflammatory and destructive protein signals have been identified, and they are potential targets for drugs that could interrupt the process.
Scleroderma is characterized by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile, and which give the appearance of hidebound skin, a disease occurring in both localized and systemic forms:
- Localized scleroderma
- Localized morphea
- Morphea-lichen sclerosus et atrophicus overlap
- Generalized morphea
- Atrophoderma of Pasini and Pierini
- Pansclerotic morphea
- Morphea profunda
- Linear scleroderma
- Systemic scleroderma
- CREST syndrome
- Progressive systemic sclerosis
Typical scleroderma is classically defined as symmetrical skin thickening, with about 90% of cases also presenting with Raynaud’s phenomenon, nail-fold capillary changes, and antinuclear antibodies. Patients may or may not experience systemic organ involvement. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only. Additional symptoms of scleroderma typically present themselves within two years of Raynaud’s phenomenon.
Laboratory testing can show antitopoisomerase antibodies (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form, and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.
Severe complications from scleroderma includes:
Heart: Untreated high blood pressure strains the heart; irregular heart rhythm and enlargement of the heart lead to heart failure.
Kidneys: Scleroderma renal crisis in which malignant hypertension develops and causes acute renal failure was once a common cause of death, but is now treatable with ACE inhibitors.
Lungs: Two-thirds of all patients suffer from respiratory problems, such as shortness of breath, coughing, difficulty breathing, alveolitis(inflammation of lung air sacs), pneumonia, and cancer.
Digestive: Esophagus damage can make it difficult to swallow food, and acid reflux is common. The stomach can develop gastric antral vascular ectasia (GAVE), which occasionally may bleed profusely. A sluggish intestine may cause pain and bloating; undigested food can result in diarrhea, weight loss and anemia.
Skin and joints: Carpal tunnel syndrome is common, as are muscle weakness, joint pain, and stiffness.
Mouth: Flat white patches, loss of attached gingival mucosa, gingival recession, and diffuse widening of the periodontal ligament (PDL) space are seen. Dysphagia may result from collagen deposition in the lingual and esophageal submucosa. Resorption of posterior ramus of the mandible, coronoid process, and condyle are seen due to pressure from abnormal collagen production in adjacent areas. Inelasticity of the mouth may make dentures or dental prostheses difficult to insert and remove.