Chapter 63 - Systemic Sclerosis

Question 1

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Limited skin sclerosis, severe gut disease, isolated PAH, calcinosis

Answer 1

Centromere

Question 2

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Diffuse skin sclerosis, pulmonary fibrosis and secondary PAH, increased SSc-related mortality rate

Answer 2

Scl-70

Question 3

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Diffuse skin sclerosis, hypertensive renal crisis, correlated
with a higher mortality rate

Answer 3

RNAP III

Question 4

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Overlap features of SLE, arthritis

Answer 4

nRNP

Question 5

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Limited skin sclerosis, myositis–sclerosis overlap, calcinosis

Answer 5

Pm-Scl

Question 6

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Diffuse skin sclerosis, myositis, PAH, renal disease

Answer 6

Fibrillarin

Question 7

TABLE 63-3
Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis

REACTIVITY

CLINICAL ASSOCIATION
Limited skin sclerosis, pulmonary fibrosis

Answer 7

Th/To

Question 8

TABLE 63-4
Functional Autoantibodies in Systemic Sclerosis and Their Association to Pathophysiology

FUNCTIONAL ANTIBODY

CLINICAL ASSOCIATION
- Seem to induce skin fibrosis as a result of activation of fibroblasts into myofibroblasts and fibroblast-like cells
- First functional antibodies discovered in systemic sclerosis (SSc)

Answer 8

Anti–platelet-derived growth factor receptor

Question 9

TABLE 63-4
Functional Autoantibodies in Systemic Sclerosis and Their Association to Pathophysiology

FUNCTIONAL ANTIBODY

CLINICAL ASSOCIATION
- Mediates endothelial cell damage and activation of fibroblasts resulting from stimulation of proinflammatory and fibrotic cytokines
- Associated with severe organ manifestation
- Associated with perivascular, vascular (digital ulcers [DUs]) and lung involvement (pulmonary arterial hypertension [PAH])
- Also found in other rheumatic diseases

Answer 9

Antiendothelial cell antibodies

Question 10

TABLE 63-4
Functional Autoantibodies in Systemic Sclerosis and Their Association to Pathophysiology

FUNCTIONAL ANTIBODY

CLINICAL ASSOCIATION
- Associated with Scl-70 antibodies and the prevalence of interstitial lung disease and PAH
- Increased prevalence in diffuse cutaneous SSc compared to limited cutaneous SSc

Answer 10

Antifibroblast antibodies

Question 11

TABLE 63-4
Functional Autoantibodies in Systemic Sclerosis and Their Association to Pathophysiology

FUNCTIONAL ANTIBODY

CLINICAL ASSOCIATION
- Activates fibroblasts by stimulation of the release of transforming growth factor-ββ

Answer 11

Antifibrillin-1

Question 12

TABLE 63-4
Functional Autoantibodies in Systemic Sclerosis and Their Association to Pathophysiology

FUNCTIONAL ANTIBODY

CLINICAL ASSOCIATION
- Inhibits the degradation of extracellular matrix proteins, because of an inhibition of MMP collagenase activity
- Correlates with the extent of fibrosis (skin, lung, kidney)

Answer 12

Anti–matrix metalloproteinase (MMP) 1, anti-MMP3

Question 13

TABLE 63-4
Functional Autoantibodies in Systemic Sclerosis and Their Association to Pathophysiology

FUNCTIONAL ANTIBODY

CLINICAL ASSOCIATION
- Simultaneous presence has been described in SSc patients (cross-reactivity)
- Associated with early and severe disease, PAH, DUs, renal crisis, diffuse cutaneous SSc, and lung fibrosis

Answer 13

Angiotensin II Type 1 receptor and endothelin Type A receptor

Question 14

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Raynaud phenomenon (4)
(Vasculopathy)

Answer 14

1. Consistent warm keeping, paraffin-bath, patient education
2. Calcium channel blockers (eg, nifedipine) by mouth
3. Angiotensin receptor antagonists
4. Alternatives: selective serotonin reuptake inhibitors (SSRIs), α-blockers, sympathectomy with or without botulinum toxin injection

Question 15

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Digital ulcers (4)
(Vasculopathy)

Answer 15

1. Prostacyclin (eg, iloprost) IV
2. Endothelin receptor blockade (eg, bosentan by mouth)
3. Phosphodiesterase Type 5 inhibitors (off-label)
4. Wound dressing (hydrocolloid membrane, Mepilex)

Question 16

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Synovitis/myositis (2)
(Musculoskeletal system)

Answer 16

1. Methotrexate (by mouth, IM)
2. Rituximab (off-label)

Question 17

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Reflux (2)
(GI tract)

Answer 17

1. Proton pump inhibitors
2. Prokinetics

Question 18

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Dysphagia (1)
(GI tract)

Answer 18

1. H2-receptor antagonists

Question 19

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Diarrhea, obstipation (3)
(GI tract)

Answer 19

1. Change habit of eating, parenteral nutrition
2. Antibiotics (eg, ciprofloxacin)
3. Symptomatic management with antidiarrheal agents or laxatives

Question 20

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Dyspnea (1)
(Respiratory system)

Answer 20

1. Oxygen, if necessary

Question 21

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Alveolitis/lung fibrosis (3)
(Respiratory system)

Answer 21

1. Cyclophosphamide IV
2. Mycophenolate mofetil by mouth (used as an alternative or after cyclophosphamide)
3. Glucocorticoids (short dated, if necessary)

Question 22

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Pulmonary arterial hypertension (7)
(Cardiac system)

Answer 22

1. Oxygen, if necessary
2. Diuretics
3. Endothelin receptor blockade (eg, bosentan by mouth, macitentan)
4. Inhaled iloprost
5. Phosphodiesterase Type 5 inhibitors (eg, sildenafil by mouth, tadalafil)
6. Epoprostenol by mouth
7. Combination of different agents

Question 23

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Systolic heart failures (3)
(Cardiac system)

Answer 23

1. Immunosuppression with or without pacemaker
2. Cardioverter defibrillator
3. Angiotensin-converting enzyme inhibitors and carvedilol (selective β-blockers may be considered, but consider worsening of Raynaud phenomenon)

Question 24

TABLE 63-7
Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis

Diastolic heart failure (2)
(Cardiac system)

Answer 24

1. Diuretics
2. Calcium channel inhibitors

Question 25

TABLE 63-7 Recommended Therapeutic Strategies for Internal Organ Involvement in Systemic Sclerosis Scleroderma renal crisis (1) (Kidney)

Answer 25

1. Angiotensin-converting enzyme–Hemmer (high-dosed)

Question 26

TABLE 63-8 Therapeutic Options for Skin Involvement in Systemic Sclerosis Skin hardening (5)

Answer 26

1. Lymphatic drainage 2. Physiotherapy 3. Topical treatment with steroids or calcineurin inhibitors 4. Systemic treatment with steroids (short dated) and/or immunosuppressants 5. Phototherapy (psoralen and ultraviolet A, ultraviolet A1, extracorporeal photochemotherapy)

Question 27

TABLE 63-8 Therapeutic Options for Skin Involvement in Systemic Sclerosis Dryness and itching (5)

Answer 27

1. Topical treatment with steroids, capsaicin 2. Cannabinoid agonists 3. Emollients 4. Phototherapy (psoralen and ultraviolet A, ultraviolet A1) 5. Systemic treatment with antihistamines or gabapentin

Question 28

TABLE 63-8 Therapeutic Options for Skin Involvement in Systemic Sclerosis Digital ulcerations (5)

Answer 28

1. IV iloprost 2. Bosentan by mouth 3. Hydrocolloid dressings 4. Skin substitutes 5. Physical therapy

Question 29

TABLE 63-8 Therapeutic Options for Skin Involvement in Systemic Sclerosis Calcifications (4)

Answer 29

1. Bisphosphonate by mouth 2. Local corticosteroid injection 3. Laser therapy 4. Surgery

Question 30

TABLE 63-8 Therapeutic Options for Skin Involvement in Systemic Sclerosis Telangiectases (2)

Answer 30

1. Laser therapy 2. Camouflage

Question 31

TABLE 63-8 Therapeutic Options for Skin Involvement in Systemic Sclerosis Hyperpigmentation and hypopigmentation (3)

Answer 31

1. Bleaching agents, camouflage, sunscreens 2. Salicylic acid and chemical peelings 3. Hydroquinone, retinoids, corticosteroids