- Clinical science
Systemic sclerosis (SSc) is a chronic disease caused by abnormal growth of connective tissue, which leads to diffuse thickening and hardening of the skin and often the inner organs. SSc is categorized into limited SSc and diffuse SSc. The more common, limited form of SSc begins with sclerosis of the fingers, hands, and face, which then progresses to the center of the body. Limited SSc is often associated with symptoms of CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) and may be followed by internal organ involvement as the disease progresses. Diffuse SSc is less common, but more aggressive, with early organ system involvement that may be life-threatening if damage to the heart, lungs, or kidneys occurs. Treatment is symptomatic and based on the extent of skin and organ system involvement. In the case of diffuse inflammation of the skin and/or organs, immunosuppressive drugs (e.g., methotrexate) should be administered. The prognosis varies depending on which organs are involved, with pulmonary arterial hypertension, interstitial lung disease, and cardiac disease significantly increasing the mortality rate.
- ♀ > ♂ (3:1)
- Higher incidence in African Americans
- Peak incidence: 30–50 years
Epidemiological data refers to the US, unless otherwise specified.
- The pathophysiology of SSc is not completely understood
- Autoimmunologic component (see “Diagnostics”)
- Inflammatory synthesis of extracellular matrix: fibroblast proliferation and increased synthesis of normal collagen
- Noninflammatory vasculopathy: underlying mechanism for many of the more severe disease features such as CAD, pulmonary artery hypertension, and renal crisis
- Thickening and hardening of the skin
- Depigmentation of the skin with sparing of perifollicular pigmentation (salt-and-pepper appearance)
- Multiple, painful ischemic digital ulcers
- Loss of expression (mask-like facies)
- Shortened frenulum
- Microstomia accompanied with characteristic perioral wrinkles
- Raynaud's phenomenon
- Fatigue, weakness
- Joint stiffness/pain
- In 90% of cases, Raynaud's phenomenon precedes the onset of other symptoms.
- Skin manifestations are usually restricted to the hands, fingers, and face.
- Extracutaneous organ involvement may occur.
- Often manifests as CREST syndrome:
- C → Calcinosis cutis
- R →
- E → Esophageal hypomotility
- S → Sclerodactyly
- T → Telangiectasia
- Raynaud's phenomenon often coincides with or follows the onset of other symptoms.
- Skin manifestations typically spread proximally from the trunk to the elbow.
Extracutaneous organ manifestations are common
- Arthralgia and myalgia → can result in contractures
- Esophageal dysmotility → dysphagia and reflux
- Small bowel dysmotility → bloating, gas, constipation, and cramping
- Pulmonary disease: pulmonary hypertension and interstitial lung disease; , increased risk of lung cancer
- Cardiac disease:fibrosis, myocarditis, pericarditis
- Renal disease: abnormal collagen deposition → thickening of renal arteriolar walls → decreased renal blood flow → reduced kidney function
- Auto-antibodies: Antinuclear antibodies (ANA) present in about 90% of cases
- Serum protein electrophoresis: ↑ γ-globulins
- Complete blood count and differential
- Chest x-ray: detects possible pulmonary involvement
- Other tests may be indicated based on organ-specific symptoms (e.g., signs of renal crisis).
- Definition: Eosinophilic fasciitis is an uncommon idiopathic disease presenting with symmetrical indurations of the skin.
- Epidemiology: Only a few hundred cases have been described, all of which have manifested in young adults.
- Main symptoms: similar to systemic sclerosis; "peau d'orange" (skin resembling an orange peel); without visceral involvement and with eosinophilia
- Lab diagnostics: Eosinophilia in blood tests and inflammatory parameters (CK, ESR) may be elevated.
- Definition: overlapping symptoms of systemic sclerosis, systemic lupus erythematosus (SLE), and polymyositis
- Clinical presentation
- Diagnosis: : Most patients are positive for ANAs and anti-U1 RNP (see ).
The differential diagnoses listed here are not exhaustive.
Treatment focuses on organ-specific, symptomatic therapy. In the case of diffuse cutaneous disease or severe organ involvement, immunosuppressive therapy is indicated.
- General measures
- Immunosuppressive therapy: : e.g., methotrexate
- Organ-specific therapy: : e.g., PPIs in cases of gastroesophageal reflux disease