Rav Imm Systemic Sclerosis

Front 1

The hallmarks of systemic sclerosis are

Back 1

The hallmarks of systemic sclerosis are microangiopathy and fibrosis of the skin and visceral organs.

Front 2

Common pathophysiologic findings in affected patients include

Back 2

Common pathophysiologic findings in affected patients include endothelial cell dysfunction, abnormal fibroblast function, and autoantibody production.

Front 3

Limited cutaneous systemic sclerosis (lcSSc) is characterized by skin disease that

Back 3

Limited cutaneous systemic sclerosis (lcSSc) is characterized by skin disease that does not progress proximal to the elbows or knees. A subset of this condition is the CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome.

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Diffuse cutaneous systemic sclerosis (dcSSc) is characterized by

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Diffuse cutaneous systemic sclerosis (dcSSc) is characterized by skin thickening that involves areas proximal to the elbows and/or knees.

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Both lcSSc and dcSSc can involve the face and neck
Patients with lcSSc are more likely to develop
Patients with dcSSc are more likely to develop

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Both lcSSc and dcSSc can involve the face and neck. Patients with lcSSc are more likely to develop pulmonary hypertension in the absence of other pulmonary manifestations. Patients with dcSSc are more likely to develop interstitial lung disease (ILD) and/or renal disease.

Front 6

Systemic sclerosis sine scleroderma is characterized

Internal organ involvement in this condition parallels that inb

Back 6

Systemic sclerosis sine scleroderma is characterized by visceral disease in the absence of cutaneous involvement. Internal organ involvement in this condition parallels that in lcSSc or dcSSc, and laboratory findings and survival rates are similar to those in lcSSc.

Front 7

Diagnosis of systemic sclerosis is established in patients with

In the absence of these findings, diagnosis of systemic sclerosis may be established in patients

Back 7

Diagnosis

Diagnosis of systemic sclerosis is established in patients with sclerodermatous skin changes (tightness, thickening, and nonpitting induration) that have sclerodactyly and skin disease that extends proximal to the metacarpophalangeal joints. In the absence of these findings, diagnosis of systemic sclerosis may be established in patients with two of the following features: sclerodactyly (sclerodermatous skin changes limited to the fingers and toes), digital pitting (soft-tissue defects and scarring in the pulp space of the distal phalanges), or or basilar fibrosis visible on chest radiography

Front 8

Antinuclear antibodies


pattern of staining


anticentromere antibody positivity is associated with

Back 8

Antinuclear antibodies are present in more than 95% of patients with systemic sclerosis. A nucleolar pattern of staining is common in patients with either type of systemic sclerosis, whereas anticentromere antibody positivity is associated with lcSSc.

Front 9

what P will have low incidence of ILD

what will
suggests an increased risk for developing ILD and dcSSc.

Back 9

Patients who have anticentromere antibodies appear to have a lower incidence of ILD. Anti-topoisomerase I (anti–Scl-70) antibody positivity suggests an increased risk for developing ILD and dcSSc.

Front 10

Initial cutaneous changes in patients with lcSSc and dcSSc usually reflect an,,,,
what is
another manifestation of this inflammatory reaction

Back 10

Initial cutaneous changes in patients with lcSSc and dcSSc usually reflect an inflammatory response in the dermis that manifests as puffiness or swelling in the hands and fingers. Hypo- or hyperpigmentation is another manifestation of this inflammatory reaction, and pruritus also may develop.

Front 11

Later in the disease course,

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Later in the disease course, induration of the skin typically develops over the fingers and progresses proximally. Telangiectasia and subcutaneous calcinosis occur in patients with dcSSc but are more common findings in patients with lcSSc. Calcinosis usually develops over pressure points such as the fingertips, elbows, buttocks, and knees

Front 12

treatment of skin thickening in systemic sclerosis.

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No agent has yet been shown to be effective in the treatment of skin thickening in systemic sclerosis. However, a study of the efficacy of cyclophosphamide in the treatment of patients with systemic sclerosis–associated lung disease showed that this agent somewhat alleviated skin thickening in this setting compared with placebo.

Front 13

Vascular Involvement

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Raynaud phenomenon due to arterial vasospasm is the initial clinical manifestation in 70% of patients with systemic sclerosis and eventually occurs in more than 95% of these patients. Episodes of Raynaud phenomenon are usually triggered by cold exposure and involve the extremities but may affect nearly any artery or arteriole. Sequelae of Raynaud phenomenon in patients with systemic sclerosis include digital pitting, ulceration, and gangrene

Front 14

Microvascular involvement in systemic sclerosis also manifests

Similar abnormalities may affect the larger arteries, causing conditions

therefore, patients with systemic sclerosis experience both such as

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Microvascular involvement in systemic sclerosis also manifests as intimal proliferation with progressive luminal obliteration. Similar abnormalities may affect the larger arteries, causing conditions such as arterial occlusions and erectile dysfunction. Therefore, patients with systemic sclerosis experience both an anatomic vascular narrowing as well as superimposed vasospasm.

Front 15

Management of Raynaud phenomenon includes the use of


In patients with refractory Raynaud phenomenon,

Back 15

Management of Raynaud phenomenon includes the use of vasodilators such as dihydropyridine calcium channel blockers, α1-antagonists, and topical nitrates.

Antiplatelet agents such as aspirin and dipyridamole also are frequently used, and sildenafil has been shown to be effective in this setting.

In patients with refractory Raynaud phenomenon, surgical revascularization, sympathetic nerve blockade or sympathectomy, prostacyclin analogues, or endothelin antagonists may be warranted.

Front 16

Musculoskeletal Involvement
Myalgia and arthralgia are common in patients with systemic sclerosis but usually are not associated with an

Back 16

Myalgia and arthralgia are common in patients with systemic sclerosis but usually are not associated with an underlying inflammatory arthritis or myopathy. Extensive fibrotic changes in the overlying skin may cause joint flexion contractures.

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Musculoskeletal Involvement
Tendon friction rubs

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Tendon friction rubs also may be present and are usually palpable over the wrists, elbows, knees, and ankles. The presence of tendon friction rubs predicts the development of aggressive diffuse skin involvement and an increased risk of internal organ involvement.

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Musculoskeletal Involvement

nonerosive arthritis. This

Back 18

Patients with systemic sclerosis also may develop an inflammatory, typically nonerosive arthritis. This condition is similar to rheumatoid arthritis and is managed using similar interventions.

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Musculoskeletal Involvemen

noninflammatory myopathy

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Collagen deposition in the muscle in patients with systemic sclerosis may cause a noninflammatory myopathy. This myopathy is associated with only minimal elevations in muscle enzyme levels and typically requires no intervention

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Musculoskeletal Involvemen
tAn overlap syndrome with polymyositis

tx

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An overlap syndrome with polymyositis also may occur and manifests as proximal muscle weakness accompanied by elevated muscle enzyme levels. Treatment of inflammatory myopathy associated with systemic sclerosis is similar to that of polymyositis.

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Gastrointestinal Involvement

....the second most commonly affected organ, after the skin, in patients with systemic sclerosis.

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The esophagus is the second most commonly affected organ, after the skin, in patients with systemic sclerosis.

Front 22

Gastrointestinal Involvement
Smooth muscle dysfunction in the distal esophagus results in...

decreased lower esophageal sphincter pressure causes

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Esophageal dysfunction is the most common gastrointestinal manifestation in this setting and affects at least 80% of patients with this condition. Smooth muscle dysfunction in the distal esophagus results in dysphagia, whereas decreased lower esophageal sphincter pressure causes gastroesophageal reflux.

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Gastrointestinal Involvement
Potential complications of esophageal disease in patients with systemic sclerosis include ...
Management of these conditions includes the use of

Back 23

Potential complications of esophageal disease in patients with systemic sclerosis include
esophagitis, esophageal stricture, Barrett esophagus, and aspiration pneumonitis. Management of these conditions includes the use of
prokinetic agents such as metoclopramide, erythromycin, and octreotide. In addition, gastric acid suppression with proton pump inhibitors is indicated for nearly all patients with systemic sclerosis. Patients with systemic sclerosis also have an increased risk for the development of Barrett esophagus, and screening for this condition is appropriate.

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Gastrointestinal Involvement

Patients with systemic sclerosis also have an increased risk for the

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Patients with systemic sclerosis also have an increased risk for the development of Barrett esophagus, and screening for this condition is appropriate.

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Gastrointestinal Involvement

perioral skin.

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Systemic sclerosis also may cause thickening of the perioral skin. This abnormality results in a narrowed oral aperture, which may compromise the ability of affected patients to eat and drink.

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Gastrointestinal Involvement
Mucosal telangiectasias

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Mucosal telangiectasias may be present throughout the gastrointestinal tract. In the stomach, telangiectasias may result in gastric antral vascular ectasia (watermelon stomach) and may cause significant blood loss

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Gastrointestinal Involvement
Small- and large-bowel involvement in patients with systemic sclerosis m

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Small- and large-bowel involvement in patients with systemic sclerosis may cause intestinal pseudo-obstruction, defined as a functional ileus that manifests as symptoms of bowel obstruction. Management of intestinal pseudo-obstruction is conservative and includes decompression and bowel rest; surgical intervention is not indicated.

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Gastrointestinal Involvement
Bacterial overgrowth

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Bacterial overgrowth due to dysfunctional motility may cause chronic diarrhea, alternating diarrhea and constipation, and/or malabsorption. Manifestations of bacterial overgrowth include bloating, abdominal pain, and steatorrhea. Extended courses of antibiotics are useful in patients with this condition; this therapy often involves rotating among different classes of antibiotics, with the course of each agent lasting several months.

Front 29

Pulmonary Involvemen

The principal clinical manifestations of lung disease in this setting include

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The principal clinical manifestations of lung disease in this setting include ILD and/or pulmonary arterial hypertension (PAH).

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Pulmonary Involvemen
Other manifestations of lung involvement in systemic sclerosis include

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Other manifestations of lung involvement in systemic sclerosis include recurrent aspiration, cryptogenic organizing pneumonia, recurrent aspiration, and hemorrhage due to endobronchial telangiectasia. Patients with systemic sclerosis also have an increased risk of developing carcinoma of the lung. However, the principal clinical manifestations of lung disease in this setting include ILD and PAH.

Front 31

Interstitial Lung DiseaseThis condition is more likely to develop in patients with

Back 31

This condition is more likely to develop in patients with anti-topoisomerase I (anti–Scl-70) antibody positivity compared with the general population.

Front 32

Interstitial Lung DiseasePatients with systemic sclerosis and ILD have a pattern

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Patients with systemic sclerosis and ILD have a restrictive pattern with a decreased FVC and DLCO on pulmonary function testing.

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Interstitial Lung DiseaseiLD associated with systemic sclerosis usually manifests as

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iLD associated with systemic sclerosis usually manifests as dyspnea, dry cough, and decreased exercise tolerance. Fine bibasilar crackles that extend into late inspiration are heard on physical examination.

Front 34

Interstitial Lung Disease CT

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High-resolution CT is more sensitive than chest radiography for ILD and reveals ground-glass and reticular linear opacities, subpleural cysts, and honeycombing in patients with advanced disease.

Front 35

Interstitial Lung Disease tx

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Oral cyclophosphamide may improve pulmonary symptoms and lung volumes in patients with ILD related to systemic sclerosis and has been shown to modestly improve lung function in this setting.

Front 36

Pulmonary Arterial Hypertension


what
causes PAH in patients with systemic sclerosis.

Back 36

Pulmonary vascular disease may manifest as isolated PAH or as a complication of vascular obliteration in patients with ILD. Vascular intimal fibrosis, not vasculitis, causes PAH in patients with systemic sclerosis. Patients with lcSSc have the greatest risk for developing PAH not associated with interstitial lung disease, whereas patients with dcSSc most often develop secondary PAH.

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Pulmonary Arterial Hypertension
clinic

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Patients with PAH may present with fatigue, decreased exercise tolerance, dyspnea, or syncope. Physical examination findings include an increased P2 and a persistently split S2. Chest radiographs are usually normal but may reveal enlarged or prominent pulmonary arteries. A decrease in DLCO in the setting of normal or corrected lung volumes that is not associated with ILD is consistent with PAH. Echocardiography may show elevated right ventricular systolic pressures,

Front 38

Pulmonary Arterial Hypertension
gold standard for determining pulmonary artery pressure

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gold standard for determining pulmonary artery pressure is direct measurement by right heart catheterization

Front 39

Pulmonary Arterial HypertensionTreatment for isolated PAH includes

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Treatment for isolated PAH includes anticoagulation with warfarin; vasodilation; and, if needed, oxygen.

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Pulmonary Arterial Hypertension
Vasodilating agents approved for the treatment of PAH include

Back 40

Vasodilating agents approved for the treatment of PAH include sildenafil; the endothelin antagonists bosentan and ambrisentan; and prostacyclin analogues such as epoprostenol, iloprost, and treprostinil, and these agents have been shown to effectively relieve symptoms of PAH associated with systemic sclerosis.

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Cardiac Involvement
Cardiac disease in patients with systemic sclerosis may manifest as

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Up to 50% of patients with systemic sclerosis have cardiac involvement. Cardiac disease in patients with systemic sclerosis may manifest as cardiomyopathy, pericarditis, and arrhythmias or be clinically silent. Symptomatic cardiac involvement in systemic sclerosis portends a poor prognosis and is associated with a 2-year mortality rate of 60%.

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Cardiac Involvement
Patients with systemic sclerosis may develop

Back 42

Patients with systemic sclerosis may develop myocardial fibrosis and pathologic contraction band necrosis, and these conditions may cause systolic or diastolic dysfunction as well as arrhythmias.

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Cardiac Involvement
Echocardiography in patients with systemic sclerosis commonly reveals

Back 43

Echocardiography in patients with systemic sclerosis commonly reveals effusions but rarely shows cardiac tamponade. Autopsy results in patients with systemic sclerosis frequently reveal pericardial disease.

Front 44

Renal Involvement

Scleroderma renal crisis (SRC)

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Scleroderma renal crisis (SRC) occurs almost exclusively in patients with early dcSSc. This condition is characterized by the acute onset of severe hypertension, renal failure, and microangiopathic hemolytic anemia.

Front 45

Renal Involvement
The presence of a .....is associated with an increased risk of SR

Back 45

The presence of a pericardial effusion is associated with an increased risk of SRC. Use of corticosteroid therapy in the management of inflammatory disease manifestations such as myopathy is classically associated with normotensive renal failure and is also a risk factor for SRC.

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Renal Involvement tx

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ACE inhibitor therapy is currently considered the cornerstone of therapy for this condition. Aggressive dosage titration of ACE inhibitors is indicated at the onset of SRC. Therapy with these agents should continue even in patients with significant renal insufficiency, because renal function has been shown to improve even after months of dialysi

Front 47

Scleroderma Spectrum Disorders
Morphea

Back 47

Morphea involves only the skin in the absence of other systemic manifestations of systemic sclerosis. Eosinophilic fasciitis is characterized by peripheral eosinophilia accompanied by woody induration of the skin that involves the extremities but usually spares the hands and face. Patients with eosinophilic fasciitis do not have Raynaud phenomenon or other features of systemic sclerosis (Table 12 ). Corticosteroid therapy usually is effective in patients with this condition.

Front 48

Scleroderma Spectrum Disorders

Eosinophilic fasciitis

Back 48

Eosinophilic fasciitis is characterized by peripheral eosinophilia accompanied by woody induration of the skin that involves the extremities but usually spares the hands and face. Patients with eosinophilic fasciitis do not have Raynaud phenomenon or other features of systemic sclerosis (Table 12 ). Corticosteroid therapy usually is effective in patients with this condition.

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Pregnancy and Systemic Sclerosis

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Systemic sclerosis does not affect fertility and most likely does not increase the rate of miscarriage. In addition, no good evidence exists to suggest that pregnancy exacerbates systemic sclerosis. However, pregnancy in patients with systemic sclerosis is considered high risk and is associated with an increased risk of small full-term infants and premature births.

Front 50

Pregnancy and Systemic Sclerosis
what does
poses the greatest risk in pregnant patients with systemic sclerosis.

Back 50

SRC poses the greatest risk in pregnant patients with systemic sclerosis. The therapy indicated for this condition, ACE inhibitors, is associated with an increased risk to the fetus. However, the mortality rate of untreated SRC is high enough to warrant the use of these agents in pregnant patients despite the risk to the fetus.