ss dr kim

Lauren H. Kim M.D.Department of Rheumatology

Legacy Healthcare

Systemic SclerosisSystemic Sclerosis

SclerodermaScleroderma

Scleroderma is a multiorgan system disease.

Patients develop organ dysfunction secondary to a combination of fibrosis and vascular injury in the setting of underlying autoimmunity.


Clinical presentation of disease is extremely diverse:

• Localized scleroderma- morphea, linear scleroderma

• Systemic sclerosis- limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous sclerosis (dcSSc).


More common in women (F:M=3:1) Presents most commonly between ages 35 to 64

but can be seen in childhood and in the elderly Incidence is reported to be anywhere between 0.6-

18.7 per million depending on when the study was done and where

Prevalence highest in the Chocktaw Indians (Oklahoma) at 4690 per million compared to less than 150 per million in the general population in the US

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Let’s talk about diffuse disease first.

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Diffuse SScDiffuse SSc

Often begins with puffiness of the fingers and hands along with diffuse arthralgia/arthritis and fatigue which is commonly misdiagnosed early as RA.

This is quickly followed by skin thickening of the hands with rapid progression to proximal areas including trunk and face.

Associated with ANA and anti-topoisomerase antibody (anti-Scl-70).

Diffuse SScDiffuse SSc

Organ involvement68% GI62% lung20% renal15% cardiac

Renal DiseaseRenal Disease


Historically, renal crisis has been the major cause of mortality for pts with dcSSc until the advent of ACE inhibitor therapy.

In a study of severe organ involvement in pts w/ dcSSc, Steen et al. found that the 9 yr survival of pts w/ renal crisis increased from 40% to 68% with the use of ACE I (A&R 2000).


Due to improvement in the treatment of renal crisis, lung disease has surpassed renal disease as cause of death in pts with dcSSc.

RC is usually seen in pts with rapidly progressive skin disease, especially in the early phase (first 1-4 yrs) and in pts with anti-RNA polymerase III antibody.

Use of corticosteriods have been linked to renal crisis in some studies.

Normal Kidney Scleroderma Kidney


It is crucial to identify the onset of renal crisis early to prevent CRI and RF. This can be done by recognizing the pts at risk.

The pts at risk should be taught to monitor their BP and urine protein by dipstick regularly.

Unexplained anemia can be a clue to pending renal crisis.


Study by Steen et al. (Ann Intern Med 2000), new-onset diastolic HTN was seen in 85% of pts, 90% had elevated in Cr with mean of 2.8 mg/dl and 45% had microscopic hemolytic anemia.

Once a pt is in renal crisis, aggressive ACE inhibitor therapy is the only way to prevent permanent renal damage.

Even with aggressive early therapy, some pts will end up with CRI or on dialysis.

Pulmonary DiseasePulmonary Disease


Inflammatory alveolitisInterstitial fibrosisChest wall restrictionPleural diseasePulmonary hypertension (more frequently

seen in pts w/ lcSSc)Aspiration pneumonitis


Pulmonary evaluationHistory: dyspnea, coughChest X-ray - insensitivePFTs - early changes in DLCOHRCTBALBiopsy


SSc HRCT findings - early diseaseGround glass changesPleural changes Adenopathy Honeycombing Subpleural cysts


BAL can be done to confirm the diagnosis of interstitial lung disease.

High percentage of neutrophils and eosinophils (up to 20% of total cells) are seen in the BAL fluid if disease is active and may be amenable to therapy with immunosuppressive medications.

In late stage fibrosis, the fluid may not be cellular.


High dose corticosteroids and IV monthly cyclophosphamide therapy is the mainstay of therapy although very recent studies on cyclophosphamide for interstitial lung disease in scleroderma patients was somewhat disappointing.

Studies are on-going for the use of less toxic agents such as Cellcept (mycophenolate)

Cardiac DiseaseCardiac Disease


Clinically symptomatic disease is often not seen until late but pathologic specimens and more sensitive diagnostic studies have shown cardiac involvement to be not uncommon.

Both the pericardium and myocardium can develop lesions.


Pericardium can develop fibrosis and occasionally constrictive pericarditis can occur.

Mild pericardial effusion is fairly common and usually asymptomatic. Physiologically significant effusion or tamponade is rare. Presence of a pericardial effusion predicts poor prognosis.


The small vessels of the myocardium undergo intimal proliferation and narrowing, similar that seen in the kidney.

The myocardium sustains ischemic injury and myofibrils are replaced by fibrosis, resulting in contraction band necrosis.

This commonly leads to conduction abnormalities but rarely leads to ischemic chest pain or myocardial infarctions.


Left heart failure can occur related to severe myocardial damage but is rare. More commonly, LHF occurs secondary to RHF, related to pulmonary HTN.

Myocarditis can occur in pts with overlap syndrome of SSc and myositis and can be a cause of sudden death.

Management of cardiac manifestations of SSc is symptomatic.

Skin DiseaseSkin Disease


There are 3 phases of skin disease:Inflammatory edematous phase-few monthsFibrotic phase-few yearsAtrophic phase

The 3 phases are not distinct and pts have varying degrees of each of the stages.


In the edematous stage, there is non-pitting edema of the skin, especially of the hands, forearms and feet.

Fibrotic stage is marked by skin tightening and thickening. Pigment changes (both increase or loss of color) can occur.

There may be intense pruritis of the affected skin which has no effective treatment.

There is reduced sweat and oil production leading to dryness and scaling of the skin.


Pts can have decrease mobility due to fibrinous deposits on tendon sheaths, demonstrated on PE as tendon friction rubs.

It is seen in about 30% of pts with diffuse SSc and is a predictor of worse disease and increased mortality.


In the atrophic stage, skin begins to thin and there is tethering of skin to underlying structures.

Thin skin is especially prone to cuts and ulcers, often leading to infection.

Flexion contractures of the fingers occur with subsequent loss of hand function.


Treatment: Cyclophosphamide Methotrexate D-penicillamine Gleevac (Imatinib) Cellcept

(Mycophenolate)

GI DiseaseGI Disease


Most ubiquitous problem in pts with both limited and diffuse SSc.

Symptoms include:– Esophageal hypomotility - reflux, dysphagia– Bloating, early satiety– Severe diarrhea alternating with constipation– Bacterial overgrowth, malabsorption– Weight loss– GI bleed due to telengiectasias


Abnormal motility is due to abnormal innervation, smooth muscle atrophy, fibrosis of the submucosal and muscular layers of the gut.

There is an association between lcSSc and primary biliary cirrhosis.


Treatment Elevate the head of the bed 30o

Eat multiple small meals throughout the day Inhibit acid with high dose PPI Prokinetic agents Antibiotics for bacterial overgrowth Nutritional supplements Hyperalimentation

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Limited SScLimited SSc

Limited SSc is what is also known as CREST syndrome.

CREST is not an accurate name because it fails to include other internal organs that can be involved such as GI and lung. Doctors not familiar with this may forget to think about important internal organ disease.

We can talk about few of the other features of SSc that may be more important in limited SSc.

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Pulmonary Arterial Pulmonary Arterial HypertensionHypertension

PAHPAH

PAH in scleroderma is insidious in onset and pts are asymptomatic until much of the lung function is lost.

True incidence is unknown, but it is estimated to affect at least 10% of pts with lcSSc and is the leading cause of death in this group.

PAH presents clinically with DOE and fatigue.

PAHPAH

An important clue to PAH is the isolated decrease in diffusion capacity on the PFT.

PAH can develop as a result of a purely vascular disease (intimal proliferation and luminal narrowing) or as an end result of alveolar fibrosis.

PAHPAHTherapy Perenteral epoprostenol (Flolan)- an arachidonic acid,

naturally occurring prostaglandin. Tracleer (Bosanten)- endothelin receptor antagonist (both

ETA and ETB) approved for NYHA Class III and IV symptoms of PAH.

Ambrosantan (Letaris)- also an endothelin receptor blocker but a selective one for ETA. As of yesterday, no longer needs routine liver labs.

Ventavis (Iloprost)- first inhaled prostacyclin approved for use in PAH on December 29th, 2004.

Sildenafil (Revatio)-works by selectively inhibiting phosphodiesterase type 5. Works as a vasodilator.

Raynaud’sRaynaud’s


Due to vasoconstriction of the muscular digital arteries, precapillary arterioles and AV shunts of the skin in response to the cold and neural signals associated with emotional stress.

Repeated episodes of vasoconstriction leads to vascular occlusion and irreversible ischemia of the affected area.

Digital ulcers lead to pain and loss of function.


Treatment Temperature protection Protection from injury Meds:

– calcium channel blocker – direct vasodilator (doxazosin)– sildenofil– Tracleer– epoprostenol

ConclusionConclusion

Progress in Scleroderma Effective treatment for renal crisis - treat early Better drugs for gastrointestinal disease

Inhibitors of acid, Promotility agents Early treatment for lung inflammation Active research underway for skin disease:Anti-

TGF-beta antibody (CAT-92), Endothelin receptor antagonist- Tracleer

Drugs for PHT, severe Raynaud’s

ConclusionConclusion

Survival in SSc

Survival is improvingFrom onset of disease: 91% 5yr; 80% 10 yr

in adultsFrom diagnosis: 82% and 69% at 5/10 yrsRenal, lung and cardiac involvement

determine survival

ss dr kim

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