63: Systemic Sclerosis Flashcards
1
Q
What is systemic sclerosis (SSc) and what are its main characteristics?
A
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by:
- Vasculopathy
- Inflammation
- Fibrosis of the skin and internal organs such as the esophagus, lungs, heart, and kidneys.
2
Q
What are the hallmark complications associated with systemic sclerosis?
A
The hallmark complications of systemic sclerosis include:
1. Hypertensive scleroderma renal crisis (SRC)
2. Pulmonary arterial hypertension (PAH)
3. Pulmonary fibrosis (PF)
4. Gastrointestinal dysmotility
3
Q
What are the two major subtypes of systemic sclerosis based on the extent of skin sclerosis?
A
The two major subtypes of systemic sclerosis are:
- Diffuse cutaneous systemic sclerosis: characterized by rapid skin involvement and early onset of Raynaud phenomenon.
- Limited cutaneous systemic sclerosis: characterized by a long preexisting history of Raynaud phenomenon and skin changes distal to the knees and elbows.
4
Q
What is the significance of Raynaud phenomenon in systemic sclerosis?
A
Raynaud phenomenon is often the initial clinical feature of systemic sclerosis and can precede the disease for many years. It is significant as it indicates vascular involvement and can help in early diagnosis.
5
Q
What criteria were established by the American College of Rheumatology for diagnosing systemic sclerosis?
A
The American College of Rheumatology established preliminary classification criteria for systemic sclerosis that include:
- Major criterion: Scleroderma proximal to the metacarpophalangeal or metatarsophalangeal joints.
- Minor criteria: Sclerodactyly, digital ulcerations, pitting digital scars, and bibasilar pulmonary fibrosis.
Diagnosis is confirmed if either 1 major criterion or at least 2 minor criteria are present.
6
Q
How does the classification of systemic sclerosis (SSc) differ between limited and diffuse cutaneous SSc?
A
The classification of systemic sclerosis (SSc) is based on the extent of skin involvement:
Type of SSc | Characteristics |
|—————————|—————————————————————————————————-|
| Diffuse cutaneous SSc | - Rapid skin involvement of trunk, face, upper arms, and thighs.
- Early onset of Raynaud phenomenon (RP), usually within 1 year of skin thickening.
- Associated with anti-scleroderma 70 (antitopoisomerase-I) or anti-RNA polymerase III antibodies.
- Higher propensity for pulmonary fibrosis, cardiac involvement, and scleroderma renal crisis (SRC). |
| Limited cutaneous SSc | - Long preexisting history of RP and skin changes distal to the knees and elbows, including facial skin.
- Often presents with anticentromere antibodies.
- Frequently associated with isolated pulmonary arterial hypertension (PAH). |
7
Q
What defines early SSc, also known as undifferentiated SSc?
A
Early SSc is defined by positive Raynaud’s phenomenon (RP) and at least one additional feature of systemic sclerosis (SSc), such as nailfold capillary alterations, puffy fingers, or pulmonary hypertension, along with detectable scleroderma-associated autoantibodies without fulfilling the ACR criteria.
8
Q
What are the clinical features of mixed connective tissue disease (MCTD)?
A
MCTD is characterized by high titers of circulating anti-U1RNP antibodies and presents with:
1. Symptoms of systemic lupus erythematosus or rheumatoid arthritis.
2. Raynaud syndrome.
3. Development of sclerodermatous lesions.
4. Swollen fingers and puffy hands.
5. Non-Raynaud symptoms include skin sclerosis at acral regions and internal manifestations.
6. Often associated with intense inflammatory symptoms and heavy arthralgia.
7. Better prognosis with anti-inflammatory/anti-immune therapy compared to classic scleroderma.
9
Q
What is the significance of the modified Rodnan skin score in systemic sclerosis (SSc)?
A
The modified Rodnan skin score is used to assess the extent and severity of skin sclerosis in SSc. It correlates with:
- Disease severity
- Outcome in diffuse cutaneous SSc.
10
Q
What characterizes Raynaud phenomenon (RP) in systemic sclerosis?
A
Raynaud phenomenon (RP) is characterized by:
- Initial onset of RP appearing in more than 90% of SSc patients.
- Recurrent attacks of vasospasm of small digital arterioles/arteries in fingers and toes, often triggered by cold or emotional stress.
- Sudden clinical appearance, often accompanied by painful pallor/ischemia of digits, followed by reactive hyperemia after rewarming, and in some cases, cyanosis (tri-phasic RP).
11
Q
What are the typical skin involvement features in systemic sclerosis (SSc)?
A
Typical skin involvement features in SSc include:
- Cardinal feature: usually appears first in the fingers and hands.
- Development of nonpitting edema (puffy fingers) and increasing induration and skin thickening (sclerodactyly).
- Restricted mobility of joints and potential dermatogenous contractures.
- Facial features: telangiectasias, beak-shaped nose, reduced mouth aperture (microstomia), and a stiff, mask-like facial appearance.
- Cosmetic issues: difficulties with eating and oral hygiene.
- Calcinosis cutis: abnormal deposition of calcium, often over pressure points.
- Hypopigmented and hyperpigmented skin (salt-and-pepper appearance) and loss of hair follicles and sweat glands (hypohidrosis/anhydrosis).
12
Q
What are the clinical features of limited cutaneous systemic sclerosis (SSc)?
A
Features include a long history of Raynaud phenomenon, skin changes distal to the knee and elbow joints, anticentromere antibodies, and frequent association with isolated pulmonary arterial hypertension (PAH).
13
Q
What are the clinical features of diffuse cutaneous systemic sclerosis (SSc)?
A
Features include rapid skin involvement of the trunk, face, upper arms, and thighs, early onset of Raynaud phenomenon, and frequent development of pulmonary fibrosis, cardiac involvement, and scleroderma renal crisis.
14
Q
What are the common complications associated with digital ulcers in systemic sclerosis (SSc)?
A
Common complications include:
- Critical digital ischemia
- Paronychia
- Infections
- Gangrene
- Osteomyelitis
- Finger pulp loss or amputation
15
Q
What are the primary manifestations of cardiopulmonary involvement in systemic sclerosis (SSc)?
A
The primary manifestations include:
- Fibrosis
- Pulmonary Arterial Hypertension (PAH)
PAH is the most common cause of disease-related death in SSc and can occur in both limited and diffuse cutaneous subsets.
16
Q
What gastrointestinal complications are commonly seen in patients with systemic sclerosis (SSc)?
A
Common gastrointestinal complications include:
- Dysphagia and heartburn due to esophageal involvement
- Increased risk for esophagitis, gastric/esophageal ulcerations, and strictures
- Chronic gastroesophageal reflux, potentially leading to Barrett esophagus
- Gastric manifestations such as atrophy of mucous membranes and delayed gastric emptying
- Gastric antral vascular ectasia, which can lead to severe bleeding
- Intestinal issues including atonic dilation, malabsorption, diarrhea, and severe malnutrition.
17
Q
What is the significance of renal involvement in systemic sclerosis (SSc)?
A
Renal involvement in SSc can lead to:
- Scleroderma Renal Crisis (SRC), occurring in 5% to 10% of patients, characterized by abrupt onset of hypertension and renal failure
- Increased serum creatinine, proteinuria, hematuria, and thrombocytopenia
- Chronic vasculopathy with reduced glomerular filtration rate
- End-organ damage, which can result in encephalopathy and pulmonary edema
- Microangiopathic anemia and potential complications from nephrotoxic drugs.
18
Q
What are the major factors involved in the etiology and pathogenesis of systemic sclerosis (SSc)?
A
The major factors involved include:
- Multiple cell types: endothelial cells, epithelial cells, fibroblasts, and lymphocytes
- Inflammation and vasculature changes
- Activation of connective tissue-producing cells
- Genetic factors influencing severity and susceptibility
- Environmental and chemical triggers for the disease.
19
Q
What genetic factors are associated with systemic sclerosis (SSc)?
A
Genetic factors associated with SSc include:
- Familial clustering and twin studies indicating a genetic contribution
- First-degree relatives have a 13-fold higher risk compared to the general population
- Specific autoantibody profiles indicating strong genetic determinants
- Associations with HLA haplotypes, such as HLA-DRB11302 and HLA-DQB10604/0605
- Identification of candidate genes related to immune response and fibrosis.
20
Q
What are the most common internal organ involvements in systemic sclerosis (SSc)?
A
The most common internal organ involvements include the gastrointestinal tract (>60% of patients), lungs (pulmonary fibrosis and PAH), heart (fibrosis and myocarditis), and kidneys (scleroderma renal crisis).
21
Q
What are the common complications associated with digital ulcers in systemic sclerosis (SSc) and their impact on quality of life?
A
Common complications of digital ulcers in SSc include:
- Critical digital ischemia
- Paronychia
- Infections
- Gangrene
- Osteomyelitis
- Finger pulp loss or amputation
These complications can lead to significant local pain and a major impact on the quality of life, affecting daily activities such as dressing and eating.
22
Q
How does pulmonary arterial hypertension (PAH) manifest in patients with systemic sclerosis, and what are the potential cardiac complications?
A
In patients with systemic sclerosis, PAH can manifest as:
- Dyspnea
- Nonproductive cough
- Disturbed diffusion capacity
- Cyanosis
Potential cardiac complications include:
- Diastolic or systolic dysfunction
- Cardiac arrhythmias
- Paroxysmal tachycardia
- Heart block
- Heart insufficiency.
23
Q
What are the manifestations of pulmonary arterial hypertension (PAH) in systemic sclerosis?
A
PAH can manifest as:
- Dyspnea
- Nonproductive cough
- Disturbed diffusion capacity
- Cyanosis
24
Q
What are the potential cardiac complications in systemic sclerosis?
A
Potential cardiac complications include:
- Diastolic or systolic dysfunction
- Cardiac arrhythmias
- Paroxysmal tachycardia
- Heart block
- Heart insufficiency
25
What gastrointestinal complications are associated with systemic sclerosis?
Gastrointestinal complications include:
- Dysphagia and heartburn due to esophageal involvement
- Peptic esophagitis and gastric/esophageal ulcerations
- Delayed gastric emptying
- Gastric antral vascular ectasia, which can lead to severe bleeding
- Intestinal issues such as malabsorption, diarrhea, and constipation
## Footnote
These complications can lead to significant health issues, including severe malnutrition and impaired quality of life.
26
What renal complications are associated with scleroderma renal crisis (SRC) in systemic sclerosis patients?
Renal complications include:
- Abrupt onset of significant systemic hypertension
- Increase in serum creatinine
- Proteinuria
- Hematuria
- Thrombocytopenia
- Acute renal failure
## Footnote
These complications can lead to severe outcomes, including encephalopathy and flash pulmonary edema.
27
What genetic factors contribute to the susceptibility and severity of systemic sclerosis?
Genetic factors include:
- Familial clustering and twin studies indicating a genetic component
- Positive family history as a strong risk factor
- Autoantibody profiles showing strong genetic determinants
- HLA haplotypes associated with specific autoantibodies
- Candidate genes related to immune response and fibrosis
28
What environmental factors are associated with an increased risk of developing systemic sclerosis (SSc)?
Environmental factors linked to SSc include:
- Solvents: vinyl chloride, benzene, toluene, epoxy resins
- Drugs: bleomycin, carbidopa, pentazocine, cocaine, docetaxel, metaphenyl-enediamine
- Occupational exposure: underground coal and gold miners
- Silicosis: Males >40 years exposed to silica have a significantly higher risk of developing SSc compared to those not exposed.
- Polyvinyl chloride exposure: Can lead to a form of scleroderma with specific symptoms.
29
What are the histopathological features of systemic sclerosis (SSc) in its early and later stages?
Histopathological features include:
- Early Stage:
1. Pathological collagen bundles in the reticular dermis appear pale and swollen.
2. Presence of perivascular lymphocytic infiltrate.
3. Possible dilation of capillaries.
- Later Stage:
1. Involved skin becomes more avascular with decreased inflammation.
2. Disappearance of pilosebaceous units and eccrine glands.
3. Collagen bundles appear closely packed, with effacement of rete ridges.
30
What is the role of vasculopathy in systemic sclerosis (SSc)?
Vasculopathy in SSc is characterized by:
- Inappropriate vascular remodeling and repair processes.
- Microcirculation and arterioles involvement, likely a primary event in pathogenesis.
- Vasoconstriction and inflammation leading to thrombosis.
- Enhanced vascular permeability due to an imbalance between vasodilatory and vasoconstrictive mediators.
- Clinical manifestations include early lesions in nailfold capillaries and vasospastic responses in Raynaud's phenomenon (RP).
31
What immune events are observed in patients with systemic sclerosis (SSc)?
Immune events in SSc include:
- Early inflammatory changes in skin and lung.
- First infiltrates: Predominantly monocyte lineage (T cells, macrophages, B cells, mast cells).
- T lymphocytes: Predominantly CD4+ with activation markers and increased T-helper 2 cytokines.
- B cells: Induce ECM production and are involved in autoantibody production.
- Autoantibodies: Associated with defined subsets of the disease and important diagnostic markers.
32
What is the significance of fibrosis in systemic sclerosis (SSc)?
Fibrosis in SSc is significant because:
- SSc is classified as a multisystem fibrotic disease.
- It involves excessive deposition of extracellular matrix (ECM) proteins, particularly collagen.
- Fibrosis contributes to the clinical manifestations and complications of SSc, affecting multiple organ systems.
33
What are the primary histopathological features of systemic sclerosis (SSc)?
Features include fibrosis of the lower dermis and subcutaneous fibrous trabeculae, excessive deposition of extracellular matrix proteins (collagen Types I and III), and perivascular lymphocytic infiltrates in early stages.
34
What are the primary immune events in the pathogenesis of systemic sclerosis (SSc)?
Primary immune events include early inflammatory infiltrates of monocytes, macrophages, T cells, and B cells, with increased serum levels of T-helper 2 cell-derived cytokines (e.g., IL-4, IL-10, IL-13).
35
How does the histopathology of systemic sclerosis (SSc) change from early to later stages?
In the early stages of SSc, histopathological features include:
1. Collagen bundles: Pathologically altered, appearing pale and swollen, with perivascular lymphocytic infiltrate.
2. Vascular changes: Dilation of capillaries and potential endothelial proliferation.
In later stages:
- The skin becomes more avascular with decreased inflammation.
- Pilosebaceous units and eccrine glands disappear, and collagen bundles appear closely packed, indicating advanced fibrosis.
36
What role do immune events play in the pathogenesis of systemic sclerosis (SSc)?
Immune events in SSc involve:
- Early inflammatory changes: Predominantly monocyte lineage cells (T cells, macrophages, B cells, mast cells) infiltrate the skin and lungs.
- T lymphocytes: Predominantly CD4+ T cells with activation markers, suggesting antigen-driven proliferation, and increased levels of T-helper 2 cytokines.
- B cells: Induce ECM production and are involved in autoantibody production, contributing to the disease process.
37
What are the clinical implications of vasculopathy in systemic sclerosis (SSc)?
Vasculopathy in SSc is characterized by:
- Inappropriate vascular remodeling and repair processes leading to vasoconstriction and inflammation.
- Early signs: Enhanced vascular permeability and imbalance between vasodilatory and vasoconstrictive mediators.
- Clinical manifestations: Overt Raynaud's phenomenon (RP) and progressive reduction of blood flow, potentially leading to complications such as pulmonary arterial hypertension (PAH) and digital vasculopathy.
38
What is the significance of autoantibodies in systemic sclerosis (SSc)?
Autoantibodies in SSc are significant because:
- They are associated with defined subsets of the disease and serve as important diagnostic markers.
- Functional significance: Some autoantibodies may have functional roles, such as antiendothelial cell antibodies and antifibrillin antibodies.
- Clinical implications: Certain subsets of SSc patients with specific autoantibodies may have a higher risk of developing malignancies, suggesting a link between autoimmunity and cancer.
39
What is the role of TGF-β in the development of fibrosis in systemic sclerosis (SSc)?
TGF-β plays a central role in the development of fibrosis by inducing the activation of fibroblasts into myofibroblasts, which leads to excessive production of extracellular matrix (ECM) components.
40
What diagnostic methods are used to assess skin involvement in systemic sclerosis?
Skin involvement in systemic sclerosis can be evaluated using the **modified Rodnan Skin Score**, which assesses 17 sites and categorizes skin thickness into grades 1, 2, or 3.
41
What are the methods used to assess skin involvement in systemic sclerosis?
Other methods include:
1. **Ultrasonography** (20-MHz)
2. **MRI**
3. **Durometer, cutometer, and elastometer** for monitoring skin fibrosis
4. **Skin biopsy** for histologic evaluation of dermal thickness.
42
What are the key pulmonary function tests used to assess cardiopulmonary involvement in systemic sclerosis?
Key pulmonary function tests include:
- **Pulmonary function tests** to assess diffusion capacity of the lung for carbon monoxide (DLCO < 75%)
- **HRCT and/or thoracic radiography** to identify interstitial lung involvement
- **Transthoracic Doppler echocardiography** to evaluate right ventricular function
- **Right-heart catheterization** to determine pulmonary arterial hypertension (PAH).
43
What is the significance of early diagnosis in kidney involvement in systemic sclerosis?
Early diagnosis in kidney involvement is crucial for improving outcomes in systemic sclerosis. It involves:
- Regular **blood pressure monitoring**
- **Urine analysis**
- **Microelectrophoresis**
- Determination of **creatinine clearance** to assess kidney function and prevent severe complications.
44
What are some differential diagnoses that can imitate systemic sclerosis?
Differential diagnoses that can imitate systemic sclerosis include:
| Differential Diagnosis | Description |
|-----------------------|-------------|
| | |
45
What is circumscribed scleroderma?
Localized form of scleroderma.
46
What is eosinophilic fasciitis?
Inflammatory condition affecting fascia.
47
What are sclerodermiform genodermatoses?
Genetic skin disorders resembling scleroderma.
48
What is acral dermatitis chronic atrophic?
Chronic skin condition with atrophy.
49
What is environmental factor-induced scleroderma?
Scleroderma-like symptoms due to environmental factors.
50
What is scleroderma adultorum Buschke?
Adult-onset scleroderma.
51
What is nephrogenic fibrosing dermopathy?
Fibrosis related to kidney disease.
52
What is porphyria cutanea tarda?
Skin condition due to porphyrin metabolism.
53
What is graft-versus-host disease?
Immune response post-transplantation.
54
What are scleroderma-like lesions in malignancies?
Skin changes associated with cancer.
55
What diagnostic methods can confirm systemic sclerosis?
Nailfold capillaroscopy, antibody status evaluation, and categorization of capillary changes.
56
What diagnostic tools are recommended for early detection of pulmonary fibrosis in systemic sclerosis?
Pulmonary function tests, high-resolution CT, and transthoracic Doppler echocardiography.
57
What is tricular hypertrophy or pericardial effusion?
Tricular hypertrophy or pericardial effusion refers to conditions affecting the heart's structure and fluid accumulation around it.
58
What are the key cytokines involved in the activation of fibroblasts into myofibroblasts in systemic sclerosis (SSc)?
Key cytokines include TGF-β, connective tissue growth factor, PDGF, and endothelin-1.
## Footnote
TGF-β plays a central role, as shown by expression profiling studies.
59
What diagnostic methods are used to confirm esophageal dysmotility in a patient with systemic sclerosis (SSc)?
Diagnostic methods include upper GI endoscopy with histologic evaluations, scintigraphy following a radiolabeled meal, and 24-hour pH manometry.
60
What are the primary diagnostic tools for assessing skin involvement in systemic sclerosis (SSc)?
Tools include the modified Rodnan Skin Score, 20-MHz ultrasonography, MRI, plicometer methods, and skin biopsy for histologic evaluation.
61
What role does TGF-β play in the development of fibrosis in systemic sclerosis (SSc)?
TGF-β has been shown to play a central role in the development of fibrosis by inducing the activation of fibroblasts into myofibroblasts, leading to excessive deposition of extracellular matrix (ECM) components.
## Footnote
This process is underscored by extensive expression profiling studies in scleroderma patients.
62
How can nailfold capillaroscopy assist in the diagnosis of systemic sclerosis (SSc)?
Nailfold capillaroscopy is a non-invasive technique that helps identify and visualize vascular cutaneous alterations caused by SSc. It categorizes capillary changes into early, active, and late patterns, making it a useful diagnostic and prognostic method for assessing the likelihood of SSc development.
63
What are the key diagnostic procedures for assessing skin involvement in systemic sclerosis?
Key diagnostic procedures for assessing skin involvement in systemic sclerosis include:
1. **Modified Rodnan Skin Score**: Evaluates skin thickness at 17 sites, categorized into grades 1, 2, or 3.
2. **Ultrasonography and MRI**: Useful for assessing skin thickening.
3. **Skin Biopsy**: Provides histologic evaluation of dermal skin thickness and characterization of inflammatory infiltrates.
4. **Durometer, Cutometer, and Elastometer**: Physical procedures to monitor skin fibrosis.
64
What is the significance of pulmonary function tests in patients with systemic sclerosis?
Pulmonary function tests are crucial for determining possible **cardiopulmonary involvement** in systemic sclerosis, as they assess the diffusion capacity of the lung for carbon monoxide (DLCO < 75%). This is an early marker of both lung fibrosis and pulmonary arterial hypertension (PAH).
65
What is the importance of early diagnosis in kidney involvement in systemic sclerosis?
Early diagnosis is critical in kidney involvement in systemic sclerosis as it improves the outcome of scleroderma renal crisis (SRC). Regular monitoring of blood pressure, urine analysis, microelectrophoresis, and creatinine clearance are essential for timely intervention and management.
66
What are the main complications associated with the limited form of systemic sclerosis (SSc)?
The main complications include:
- Development of **digital ulcerations**
- **Pulmonary hypertension**
67
How does the prognosis differ between limited and diffuse forms of systemic sclerosis (SSc)?
In the **limited form** of systemic sclerosis, the prognosis is generally better compared to the diffuse form, which is associated with more severe organ involvement and poorer outcomes.
68
What are the forms of systemic sclerosis (SSc)?
In the **limited form**, skin fibrosis is localized and patients may develop Raynaud's phenomenon years before other symptoms. In contrast, the **diffuse form** shows early fibrosis and inflammation affecting multiple organs, leading to a higher number of deaths and a rapid worsening of the disease in initial years. However, symptoms can improve in later years as disease activity reduces.
69
What is the role of immunosuppression in the management of systemic sclerosis (SSc)?
Immunosuppression can improve skin involvement and interstitial lung disease. The best evidence supports the use of **cyclophosphamide** and **mycophenolate mofetil (MMF)**, which has been shown to be as effective as oral cyclophosphamide. **Rituximab** may also benefit a select group of patients if standard immunosuppression fails.
70
What are the recommended first-line therapies for Raynaud's phenomenon (RP) in systemic sclerosis?
First-line therapies for Raynaud's phenomenon include:
- **Calcium channel blockers**
- **Angiotensin II receptor antagonists**
These agents have the potential for vascular remodeling and/or dilation.
71
What is the significance of early detection of organ-specific complications in systemic sclerosis (SSc)?
Early detection of organ-specific complications is crucial as it enables timely intervention, which can significantly improve the prognosis and quality of life for patients with systemic sclerosis.
72
What are the primary therapeutic approaches for managing Raynaud phenomenon (RP) in systemic sclerosis (SSc)?
Approaches include calcium channel blockers, angiotensin II receptor antagonists, and parenteral prostacyclin derivatives.
73
What are the primary therapeutic approaches for managing digital ischemia in systemic sclerosis (SSc)?
Approaches include antiplatelet agents like aspirin and clopidogrel, and parenteral prostacyclin derivatives.
74
What are the primary therapeutic approaches for managing Raynaud phenomenon (RP) in systemic sclerosis (SSc)?
Therapeutic approaches include avoiding precipitating factors like cold and stress, using calcium channel blockers, angiotensin II receptor antagonists, and parenteral prostacyclin derivatives like iloprost.
75
What are the primary management strategies for digital ulcers in systemic sclerosis (SSc)?
Management includes nonpharmacologic care, antibiotics for infection, analgesia, wound dressings, and agents like iloprost and bosentan to prevent recurrent lesions.
76
What are the key differences in the development and prognosis of limited versus diffuse systemic sclerosis (SSc)?
- **Limited SSc**:
- Develops Raynaud's phenomenon (RP) many years prior to other organ manifestations.
- Skin fibrosis is localized to acral areas.
- Main complications include digital ulcerations and pulmonary hypertension.
- **Diffuse SSc**:
- Fibrosis occurs early and spreads rapidly to almost all parts of the integument.
- Lung, heart, and kidney involvement occurs early, affecting prognosis.
- Higher mortality in the initial years, but symptoms may improve over time.
- Skin can become softer, and contractures may diminish with treatment.
77
What are the current therapeutic strategies for managing systemic sclerosis (SSc) and their implications?
Therapeutic strategies include various medications and interventions aimed at managing symptoms and preventing complications, although specific details are not provided in the text.
78
What are the therapeutic strategies for systemic sclerosis (SSc)?
Vascular therapies and immunomodulation are the main approaches.
79
What medications are effective for skin and lung involvement in SSc?
Cyclophosphamide and mycophenolate mofetil (MMF) are effective.
80
How can rituximab help patients with SSc?
Rituximab may help in patients unresponsive to standard immunosuppression.
81
What is a promising treatment for SSc?
High-intensity immunosuppression with autologous stem cell transplantation shows promise.
82
What challenges exist in antifibrotic treatments for SSc?
Antifibrotic treatments remain a challenge, with no proven agents currently available.
83
What is the impact of early detection and multidisciplinary management in SSc?
Early detection and multidisciplinary management can significantly improve prognosis and quality of life for patients with SSc.
84
What are the recommended first-line therapies for managing Raynaud's phenomenon (RP) in SSc?
Calcium channel blockers promote vascular remodeling and dilation.
85
What are angiotensin II receptor antagonists considered for in SSc?
They are considered for their potential benefits.
86
What nonpharmacologic strategies can be used for RP?
Avoid triggers (e.g., cold, stress), use heated clothing and hand warmers, and regular paraffin wax treatments.
87
What additional treatments are available for SSc?
Iloprost aids in healing digital ulcers. Antiplatelet agents like aspirin and clopidogrel are especially useful in critical digital ischemia.
88
What is the impact of early detection of organ-specific complications in SSc?
Enables timely intervention, which is crucial for improving patient outcomes.
89
How does early detection facilitate patient management in SSc?
Facilitates a multidisciplinary approach to manage complications.
90
What does a multidisciplinary approach facilitate in managing complications?
It facilitates a multidisciplinary approach to manage complications effectively.
91
What can a multidisciplinary approach lead to for patients?
It can lead to a much-improved prognosis and quality of life for patients.
92
How does early identification and treatment of organ-based complications affect morbidity and mortality?
It helps in identifying and treating organ-based complications early, reducing morbidity and mortality associated with systemic sclerosis (SSc).
93
What are the key elements in managing skin involvement in systemic sclerosis (SSc)?
Key elements include:
**Physical therapy** and **regular exercise** to maintain circulation, joint mobility, and muscle strength.
94
What topical treatments are used for skin involvement in systemic sclerosis?
Topical treatments with corticosteroids, cannabinoid agonists, and moisturizing creams.
95
What are systemic therapies for short-term use in systemic sclerosis?
Systemic therapies such as immunosuppressive drugs and systemic steroids.
96
What is the role of phototherapy in managing systemic sclerosis?
Phototherapy (ultraviolet A1 or psoralen and ultraviolet A) is used to inhibit fibrotic and inflammatory processes.
97
How is dry and itching skin managed in systemic sclerosis?
Management of dry and itching skin with topical treatments.
98
What surgical options are available for skin issues in systemic sclerosis?
Surgical options for calcinosis cutis and other skin issues.
99
Why are pulmonary function tests significant in managing systemic sclerosis-related pulmonary fibrosis?
Pulmonary function tests are significant because:
- They help define the extent and severity of **progressive SSc-related pulmonary fibrosis (SSc-PF)**.
100
What is the best predictor of future decline in lung function in systemic sclerosis?
The **extent of disease by HRCT** and a history of **progressive restrictive abnormality** on pulmonary function tests are the best predictors of future decline in lung function.
101
How do pulmonary function tests guide treatment decisions in systemic sclerosis?
These tests guide treatment decisions, particularly regarding the use of **cyclophosphamide** or **MMF** for stabilizing lung function.
102
What are the treatment options for gastrointestinal involvement in systemic sclerosis?
Treatment options for gastrointestinal involvement in systemic sclerosis.
103
What are the treatment options for gastrointestinal involvement in systemic sclerosis?
1. **Proton pump inhibitors** and agents that increase lower esophageal sphincter tone (e.g., domperidone).
2. **Conservative management** for pseudoobstruction, potentially requiring parenteral nutrition.
3. **Broad-spectrum antibiotics** for small intestinal bacterial overgrowth and enzyme supplements for pancreatic insufficiency.
4. **Implanted sacral nerve stimulators** or bioplastic injections for anorectal incontinence.
5. **Diet adjustments** and judicious use of laxatives for chronic constipation.
6. **Defunctioning colostomy** in very limited cases.
104
What role do phosphodiesterase Type 5 inhibitors play in the treatment of digital ulcers in systemic sclerosis?
Phosphodiesterase Type 5 inhibitors, such as **sildenafil** and **tadalafil**, are used for:
- Treatment of **Raynaud's phenomenon** and **digital ulcers**.
- They have shown potential benefits, but **prospective clinical trial data** are not yet available.
- Surgical treatments like **digital microarteriolysis** may also benefit refractory ulcers, while **lumbar sympathectomy** can help with lower limb issues.
105
What are the primary therapeutic approaches for managing gastrointestinal pseudoobstruction in systemic sclerosis (SSc)?
Approaches include conservative management initially, followed by parenteral nutritional supplementation if needed.
106
What are the primary therapeutic approaches for managing small intestinal bacterial overgrowth in systemic sclerosis (SSc)?
Approaches include broad-spectrum antibiotics and pancreatic enzyme supplements if needed.
107
What are the primary therapeutic approaches for managing chronic constipation in systemic sclerosis (SSc)?
Approaches include dietary adjustments and the use of stimulating, softening, or bulking agents.
108
What are the primary therapeutic approaches for managing anorectal incontinence in systemic sclerosis (SSc)?
Approaches include implanted sacral nerve stimulators and bioplastic injections to increase internal anal sphincter bulk.
109
What are the primary therapeutic approaches for managing pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc)?
Approaches include oral endothelin receptor antagonists (e.g., bosentan), phosphodiesterase 5 inhibitors (e.g., sildenafil), and parenteral prostacyclin derivatives for advanced cases.
110
What are the primary therapeutic approaches for managing pulmonary fibrosis in systemic sclerosis (SSc)?
Approaches include cyclophosphamide, mycophenolate mofetil (MMF), and low-dose corticosteroids. HRCT and pulmonary function tests guide therapy decisions.
111
What are the primary therapeutic approaches for managing cardiac involvement in systemic sclerosis (SSc)?
Approaches include immunosuppressive treatment for myocarditis and monitoring left ventricular ejection fraction and circulating troponin levels.
112
What are the primary therapeutic approaches for managing gastrointestinal involvement in systemic sclerosis (SSc)?
Approaches include dietary modifications and medications to manage symptoms.
113
What are eutiс approaches for managing gastrointestinal involvement in systemic sclerosis (SSc)?
Eutic approaches include proton pump inhibitors for esophageal symptoms, antibiotics for small intestinal bacterial overgrowth, and sacral nerve stimulators for anorectal incontinence.
114
What is the role of proton pump inhibitors in SSc?
Proton pump inhibitors are used for managing esophageal symptoms.
115
What is the purpose of antibiotics in the context of SSc?
Antibiotics are used to treat small intestinal bacterial overgrowth.
116
How are sacral nerve stimulators used in SSc?
Sacral nerve stimulators are used for managing anorectal incontinence.
117
What are the primary therapeutic approaches for managing skin fibrosis in systemic sclerosis (SSc)?
Approaches include physical therapy, immunosuppressive drugs (e.g., methotrexate, cyclophosphamide), and phototherapy (e.g., ultraviolet A1).
118
What are the primary therapeutic approaches for managing pulmonary fibrosis in systemic sclerosis (SSc)?
Approaches include cyclophosphamide, mycophenolate mofetil (MMF), and low-dose corticosteroids. HRCT and pulmonary function tests guide therapy decisions.
119
What are the primary therapeutic approaches for managing cardiac involvement in systemic sclerosis (SSc)?
Approaches include immunosuppressive treatment for myocarditis and monitoring left ventricular ejection fraction and circulating troponin levels.
120
What are the primary therapeutic approaches for managing calcinosis cutis in systemic sclerosis (SSc)?
Approaches include local steroid injections, laser therapies, and surgical interventions.
121
What are the primary therapeutic approaches for managing telangiectasias in systemic sclerosis (SSc)?
Approaches include laser therapies and noninvasive methods like camouflage.
122
What are the primary therapeutic approaches for managing hyperpigmentation in systemic sclerosis (SSc)?
Approaches include bleaching agents, salicylic acids, chemical peels, retinoids, and corticosteroids.
123
What are the primary therapeutic approaches for managing hypopigmentation in systemic sclerosis (SSc)?
Approaches include camouflage, retinoids, and corticosteroids.
124
What are the primary therapeutic approaches for managing dry and itching skin in systemic sclerosis (SSc)?
Approaches include moisturizers and topical treatments.
125
What are the approaches for managing itching skin in systemic sclerosis (SSc)?
Approaches include topical corticosteroids, cannabinoid agonists, capsaicin, emollients, and phototherapy.
126
What are the key elements of managing skin involvement in systemic sclerosis (SSc)?
Key elements include:
- **Physical therapy** and **regular exercise** to maintain circulation, joint mobility, and muscle strength.
- **Topical treatments** with corticosteroids, calcineurin inhibitors, and moisturizing creams for skin hardening.
- **Systemic therapies** such as immunosuppressive drugs and systemic steroids for short-term use.
- **Phototherapy** (ultraviolet A1 or psoralen and ultraviolet A) to inhibit fibrotic and inflammatory processes.
- **Management of dry and itching skin** with topical treatments like cannabinoid agonists and emollients.
- **Surgical options** for calcinosis cutis and laser therapies for telangiectases.
127
How does pulmonary arterial hypertension (PAH) relate to systemic sclerosis and its treatment options?
PAH is increasingly recognized in patients with lung fibrosis related to systemic sclerosis.
## Footnote
Treatment options include oral agents like endothelin receptor antagonists (e.g., bosentan) and phosphodiesterase 5 inhibitors (e.g., sildenafil).
128
What is combination therapy in the context of systemic sclerosis?
Combination therapy may be necessary as the disease progresses, including parenteral prostacyclin.
129
What is cyclophosphamide used for in systemic sclerosis?
Cyclophosphamide is commonly used for severe or progressive SSc-related pulmonary fibrosis, with pulmonary function tests guiding treatment decisions.
130
What is the efficacy of MMF therapy compared to cyclophosphamide?
MMF therapy has shown similar efficacy to cyclophosphamide for stabilizing lung function with a better side-effect profile.
131
What are the gastrointestinal complications associated with systemic sclerosis?
Gastrointestinal complications in systemic sclerosis include:
- **Esophageal symptoms** managed with proton pump inhibitors and agents to increase lower esophageal sphincter tone.
- **Pseudoobstruction** may require parenteral nutritional support if conservative management fails.
- **Small intestinal bacterial overgrowth** treated with broad-spectrum antibiotics and enzyme supplements for pancreatic insufficiency.
- **Anorectal incontinence** can be managed with sacral nerve stimulators or bioplastic injections.
- **Chronic constipation** requires dietary adjustments and individualized approaches for effective management.
132
What is the significance of monitoring pulmonary function tests in patients with systemic sclerosis?
Monitoring pulmonary function tests is crucial in systemic sclerosis for several reasons:
- It helps assess the **extent of lung involvement** and guides treatment decisions.
- A history of **progressive restrictive abnormalities** on these tests is the best predictor of future decline in lung function.
- Changes in forced vital capacity can indicate treatment efficacy, particularly in studies comparing cyclophosphamide and placebo.
- Regular assessments can inform the need for **therapeutic interventions** and adjustments in management strategies.
133
What distinguishes scleroderma renal crisis (SRC) from other causes of end-stage renal failure?
The **possibility of late recovery** distinguishes SRC from other causes of end-stage renal failure, as approximately 1/2 of cases eventually recover.
134
What is the recovery rate for failure in scleroderma renal crisis (SRC)?
Approximately 1/2 of cases eventually recover sufficiently to continue dialysis.
135
What is the critical aspect of managing scleroderma renal crisis (SRC)?
The most critical aspect is the **prompt identification and treatment of significant hypertension** in the context of scleroderma, often initiated with angiotensin-converting enzyme inhibitors.
136
What general measures should be taken to support organ-specific therapeutic approaches in scleroderma?
General measures include:
1. Keeping the home and body warm
2. Optimizing nutritional status
3. Providing paraffin waxing and physical therapy
4. Teaching patients to recognize symptoms indicating disease progression and new organ involvement.
137
What should prompt hospitalization in patients with scleroderma renal crisis (SRC)?
Any features of **renal impairment or end-organ damage** should prompt hospitalization, as it is considered a medical emergency.
138
What is the first-line treatment for a patient with systemic sclerosis (SS) developing hypertensive scleroderma renal crisis (SRC)?
The first-line treatment is the prompt initiation of angiotensin-converting enzyme (ACE) inhibitors to manage hypertension and prevent renal failure.
139
What are the key features of scleroderma renal crisis (SRC)?
Key features include abrupt onset of significant systemic hypertension, increased serum creatinine, proteinuria, hematuria, thrombocytopenia, and acute renal failure.
140
What distinguishes scleroderma renal crisis (SRC) from other causes of end-stage renal failure?
The **possibility of late recovery** from renal failure distinguishes SRC from other causes, as approximately 1/2 of cases can recover.
141
What is the recovery rate for patients with scleroderma renal crisis (SRC)?
Approximately 1/2 of cases may recover sufficiently to continue dialysis after 24 months post-crisis.
142
What general measures should be taken to support organ-specific therapeutic approaches in scleroderma patients?
General measures include:
1. Keeping the home and body warm
2. Optimizing nutritional status
3. Providing paraffin waxing and physical therapy
4. Teaching patients to recognize symptoms indicating disease progression and new organ involvement.
143
What should prompt hospitalization in patients with scleroderma renal crisis (SRC)?
Any features of **renal impairment or end-organ damage** should prompt hospitalization, as these are considered medical emergencies in the context of SRC.
144
What is the clinical significance of the association between specific autoantibodies and systemic sclerosis?
The presence of specific autoantibodies in systemic sclerosis is associated with distinct clinical features and outcomes.
## Footnote
Example associations include:
| Autoantibody | Clinical Association |
|---------------|---------------------|
| Centromere | Limited skin sclerosis, pulmonary fibrosis, isolated PAH, calcinosis |
| Scl-70 | Diffuse skin sclerosis, pulmonary fibrosis, increased mortality rate |
| RNA Pol III | Diffuse skin sclerosis, renal crisis, higher mortality rate |
| PM-Scl | Limited skin sclerosis, myositis-scleroderma overlap, calcinosis |
145
What is limited skin sclerosis?
A form of scleroderma that primarily affects the skin.
146
What is myositis-sclerosis overlap?
A condition where features of both myositis and scleroderma are present.
147
What is calcinosis?
The formation of calcium deposits in the skin or other tissues.
148
What is pulmonary fibrosis?
A lung disease that occurs when lung tissue becomes damaged and scarred.
149
How do functional autoantibodies relate to systemic sclerosis?
They are associated with various clinical manifestations and may influence disease progression.
150
What is the frequency of anti-sphingosine-1-phosphate receptor in systemic sclerosis?
30% to 100%
## Footnote
Induces skin fibrosis through activation of fibroblasts and myofibroblasts.
151
What is the frequency of antinuclear antibodies in systemic sclerosis?
44% to 86%
## Footnote
Associated with vascular complications and skin involvement.
152
What is the frequency of antifibroblast antibodies in systemic sclerosis?
20% to 58%
## Footnote
Associated with SSc antibodies and presence of interstitial lung disease.
153
What is the frequency of anti-mitochondrial antibodies in systemic sclerosis?
50% to 52%
## Footnote
Associated with liver disease and systemic symptoms.
154
What is the frequency of angiotensin II type 1 receptor and endothelin type A receptor in systemic sclerosis?
82% to 87%
## Footnote
Associated with extent of fibrosis and lung involvement.
155
What is the clinical significance of anti-Scl-70 antibodies in systemic sclerosis?
They are associated with diffuse skin sclerosis, pulmonary fibrosis, and secondary pulmonary arterial hypertension, correlating with a higher mortality rate.
156
How do anti-centromere antibodies influence clinical presentation in systemic sclerosis?
They are linked to limited cutaneous involvement and a better prognosis.
157
What is limited skin sclerosis?
Anti-centromere antibodies are linked to limited skin sclerosis, esophageal involvement, and isolated pulmonary arterial hypertension (PAH), indicating a milder form of the disease compared to other autoantibodies.
158
What role do functional autoantibodies play in systemic sclerosis?
Functional autoantibodies, such as anti-fibroblast growth factor antibodies, are believed to induce skin fibrosis through the activation of fibroblasts into myofibroblasts, contributing to the fibrotic process in systemic sclerosis.
159
What are the implications of the presence of anti-RNP antibodies in systemic sclerosis patients?
Anti-RNP antibodies are associated with overlap features of systemic lupus erythematosus (SLE) and myositis, indicating a more complex clinical picture and potential for increased morbidity in systemic sclerosis patients.
160
What are the recommended diagnostic procedures for vascular system involvement in systemic sclerosis?
- **Giddiness provocation**
- **Nailfold capillaroscopy**
- **Antinuclear antibody levels**
161
What clinical features are associated with musculoskeletal system involvement in systemic sclerosis?
- **Arthralgia**
- **Synovitis**
- **Muscle weakness**
162
What diagnostic procedures are recommended for gastrointestinal tract involvement in systemic sclerosis?
- **Gastro-esophageal endoscopy**
- **Esophageal scintigraphy, esophagus manometry**
- **Colonoscopy**
163
What are the diagnostic procedures for respiratory system involvement in systemic sclerosis?
- **Lung function test** (carbon monoxide transfer factor)
- **Radiology** (X-ray or high resolution CT)
- **Bronchoalveolar lavage (BAL)**
164
What are the clinical features indicating cardiac system involvement in systemic sclerosis?
**Dyspnea**
**Arrhythmia**
165
What diagnostic procedures are recommended for kidney involvement in systemic sclerosis?
**Regular blood pressure controls** (140/90 mm Hg)
**Ultrasonography**
**Serum levels of creatinine, urine analyses** (protein, albuminuria, microelectrophoresis)
166
How is the Modified Rodnan skin score (mRSS) used in evaluating skin involvement in systemic sclerosis?
The mRSS evaluates skin thickness at 17 different areas, categorizing skin sclerosis into:
**Grade 1**: Mild
**Grade 2**: Moderate
**Grade 3**: Severe
167
What diagnostic procedures are recommended for assessing vascular system involvement in systemic sclerosis?
**Coldness provocation**
**Nailfold capillaroscopy**
**Antinuclear antibody levels**
168
How can gastrointestinal involvement in systemic sclerosis be evaluated?
**Gastro-esophageal endoscopy**
**Esophageal scintigraphy, esophagus manometry**
**Colonoscopy**
169
What are the recommended diagnostic procedures for assessing respiratory system involvement in systemic sclerosis?
**Lung function test** (carbon monoxide transfer factor)
**Radiology** (X-ray or high resolution CT)
**Bronchoalveolar lavage (BAL)** (optional)
170
What clinical features and diagnostic procedures are associated with cardiac system involvement in systemic sclerosis?
**Clinical Features:** Dyspnea, arrhythmia
**Diagnostic Procedures:**
1. **Electrocardiography** (condition blocks)
2. **Echocardiography** (pulmonary artery pressure, diastolic dysfunction)
171
What is the purpose of the Modified Rodnan skin score in systemic sclerosis evaluation?
The **Modified Rodnan skin score** (mRSS) is used to assess skin thickness in 17 different areas to categorize skin sclerosis into:
- **Grade 1:** Mild
- **Grade 2:** Moderate
- **Grade 3:** Severe
172
What are the therapeutic options for managing Raynaud phenomenon in systemic sclerosis?
- Consistent warm keeping, paraffin bath, patient education
- Calcium channel blockers (e.g., nifedipine) by mouth
- Angiotensin receptor antagonists
- Alternatives: selective serotonin reuptake inhibitors (SSRIs), alpha-blockers, sympathomimetics with or without botulinum toxin injection
173
What treatment options are available for pulmonary arterial hypertension in systemic sclerosis?
- Diuretics
- Endothelin receptor blockade (e.g., bosentan by mouth, macitentan)
- Inhaled iloprost
- Phosphodiesterase Type 5 inhibitors (e.g., sildenafil by mouth, tadalafil)
- Epoprostenol by mouth
- Combination of different agents
174
What are the recommended strategies for managing gastrointestinal involvement in systemic sclerosis?
- Dysphagia: H2 receptor antagonists
- Diarrhea, obstipation: Change habit of eating, parenteral nutrition
- Antibiotics (e.g., ciprofloxacin) for infections
175
What are the therapeutic options for managing scleroderma renal crisis?
- Angiotensin-converting enzyme inhibitors and captopril (selective) may be considered, but consider worsening of Raynaud phenomenon
- Diuretics
176
What treatment options are available for managing cardiac involvement in systemic sclerosis?
- Systolic heart failures: Immunosuppressive therapy
177
What are the therapeutic options recommended for managing Raynaud phenomenon in systemic sclerosis?
Consistent warm keeping, paraffin bath, patient education.
178
What are the therapeutic options for managing diastolic heart failure in systemic sclerosis?
Calcium channel inhibitors.
179
What are the therapeutic strategies for managing pulmonary arterial hypertension in systemic sclerosis?
Diuretics.
180
What are the therapeutic options for managing dysphagia in systemic sclerosis?
Change habit of eating, parenteral nutrition.
181
What are the therapeutic options for managing scleroderma renal crisis in systemic sclerosis?
Angiotensin-converting enzyme inhibitors and Hemmer (high-dose).
182
What strategies are recommended for managing dyspnea in patients with systemic sclerosis?
Oxygen, if necessary.
183
What are the therapeutic options for managing systemic sclerosis-related symptoms?
Calcium channel blockers (e.g., nifedipine) by mouth.
184
What are the alternatives for managing Raynaud phenomenon?
Selective serotonin reuptake inhibitors (SSRIs), alpha blockers, sympathectomy with or without botulinum toxin injection.
185
What are the therapeutic options for managing pulmonary arterial hypertension?
Endothelin receptor blockade (e.g., bosentan by mouth, macitentan).
186
What are the therapeutic options for managing dysphagia?
H2 receptor antagonists.
187
What are the therapeutic options for managing renal crisis?
Calcium channel inhibitors.
188
What are the therapeutic options for managing dyspnea?
Cyclophosphamide IV.
189
What are the therapeutic options for managing dysphagia?
Antibiotics (e.g., ciprofloxacin) if necessary.
190
What are the therapeutic options for managing renal crisis?
Combination of different agents.
191
What are the therapeutic options for managing pulmonary arterial hypertension?
Inhaled iloprost.
192
What are the therapeutic options for managing dysphagia?
Glucocorticoids (short duration, if necessary).
