Scleroderma

is a disease/condition manifested as   inappropriate scar tissue formation (fibrosis)   throughout the entire body including the   skin, arteries, kidneys, GI tract, lungs and   heart resulting in significant organ dysfunction   and the characteristic skin changes.

Classification of Scleroderma

1.  Localized Scleroderma: morphea and linear scleroderma

2.  Limited Scleroderma (formerly known as CREST):

  C = Calcinosis

  R = Raynaud’s phenomenon

  E = Esophageal dysmotility

  S = Sclerodactyly

  T = Telangectasias

   There is skin tightening of hands, distal forearm,   face and feet.

3.  Diffuse Systemic Sclerosis

  There is skin tightening of the arm, forearm,   hands,   feet and trunk.

Also: Skin Conditions 

Eosinophilic fascitis

  Eosinophilic myalgia syndrome

Raynaud's Phenomenon 

Raynaud’s Phenomenon

  Refers to the distinctive change in color of peripheral tissues   (most   commonly fingers) due to stress induced vasospasm   from (usually cold temperatures but may also include   emotional stress).

  The white to blue to red color change correlates with:   blanching (white) caused by vasospasm, 

  cyanosis (blue) caused by the remaining RBC deoxygenation,   red caused by vasodilatation and new oxygenated RBCs.

  Persistent or recurrent ischemia causes digital (finger) pitting   ulcers, loss of digital pads (known as Sclerodactyly) and can   ultimately result in gangrene and auto amputation.

>90% of Scleroderma patients have Raynaud’s phenomenon.

GI Problems

Entire GI tract is potentially affected.

Mouth:

  There is: decreased oral aperture and

       purse string mouth.

Esophagus:

  Decreased lower esophageal sphincter (LES) tone leads   to reflux esophagitis and stricture formation or   Barrett's esophagus (premalignant).

  Esophageal dysmotility (decreased peristalsis) of lower   1/3 of the esophagus (smooth muscle portion).

Small Intestine

Reduced peristalsis causes:

  stasis,

  malabsorption,

  diarrhea,

  bacterial overgrowth,

  intestine dilatation.

  Psuedo-obstruction is a rare complication resulting   from decreased peristalsis mimicking   a recurrent intestinal obstruction.

Large Intestine

  Thinning of muscular walls of the large intestine causes wide mouth diverticulum.

Liver

  Primary biliary cirrhosis is an autoimmune liver disease associated with limited PSS.

Renal

60-80% of patients with Scleroderma have evidence of   kidney involvement.

50% have some renal dysfunction such as mild proteinuria and mild elevation of Cr and/or hypertension.

Scleroderma Renal crisis is a severe and life threatening   disease that occurs in 10-15% of patients and   manifested as accelerated hypertension and   rapidly progressive renal failure. 

80% of cases of renal crisis occur within the first 5 years after   diagnosis.

worse prognosis in PSS patients with renal crisis if:

  patients are male

  Older age

  Cr > 3 mg/dl

  New anemia

  RNA (anti polymerase III antibody)

Pulmonary 

Pulmonary disease occurs in 70% of Scleroderma patients.

Two main types of lung involvement are:

Cardiac Arrest

Pericarditis and Pericardial effusion occur in 40% of patients.

Fibrosis can develop in the myocardium (known as Band   Necrosis) which contracts and disrupts the   conduction system.

Conduction system abnormalities cause dysrrhymias and may   even cause ventricular arrhythmias and sudden   death. 

Musculoskeletal

Arthralgia

Mild Arthritis which is rarely destructive

Tendon friction rubs

Myositis

Distal phalangeal tuft absorption.

Lab Findings

Antinuclear antibodies are found in most patients   with limited or diffuse disease.

Anticentromere antibodies present in 30-50% of   patients with the limited (formerly    CREST) variant.

Antitopoisomerase 1 antibodies (SCL 70) is present   in 30-40% of patients with diffuse   disease.

Radiographic Findings

GI

1. Abnormal esophageal motility on Barium swallow.

2. Esophageal stricture on Barium swallow.

3. Wide mouth diverticulum.

Chest

1.  Chest x-ray with lower zone interstitial markings

  known as basal reticulo nodular pattern and

  pulmonary reticular fibrosis.

2. HRCT (high resolution CT) with a ground glass

  appearance and reticular pattern assesses

  active inflammation (alveolitis) or fibrosis (scar).

Other Test Results

PFTs

  Restrictive Lung disease with reduced DLCO   (diffusion capacity)

BAL (bronchoalevolar lavage)

  Inflammatory cells

  Lymphocytes are present early.

  Neutrophils when at least 50% lung affected

Nail fold capillary microscopy.

  There is loss of capillary loops with dilatation of   both venular and arteriolar links.

GI Treatment 

Proton pump inhibitors and H2 blockers for the GERD.

Esophageal dilatation of strictures.

Bacterial overgrowth is treated with antibiotics.

Esophageal dysmotility treated with metoclopramide   (Reglan) and/or erythromycin.

Renal Treatment

ACE inhibitors have dramatically altered survival in PSS   because the majority of patients died from   renal crisis and renal failure.

Patients on Ace inhibitors have a 60%  5 year survival   because of their to treat hypertension and   prevent renal failure.

Pulmonary Treatment

Interstitial Lung Disease – is treated with corticosteroids   (when evidence of inflammation is present).

However, steroids have been implicated in causing   Scleroderma Renal crisis.

Steroids are most effective when used in combination with   cyclophosphamide, both IV and oral.

Azathioprine (Imuran) is occasionally substituted for   cyclophosphamide.

Cyclophosphamide is an immunosuppressive drug used as treatment of lung fibrosis.

Pulmonary Hypertension

Epoprostenol (Iloprost)

A prostacyclin analog delivered as a continuous   infusion via an indewelling right atrial catheter   and pump.

Iloprost inhalation therapy.

Bosentan (Tracleer)

A nonselective endothelin receptor antagonist appears   to be safe and effective.

Viagra

Key Points

•Raynaud’s phenomenon is the major vascular manifestation associated with systemic sclerosis.

•Ischemic digital ulcerations occur in systemic sclerosis but not primary Raynaud’s phenomenon.

•Nearly 100% of patients with systemic sclerosis have gastrointestinal involvement that may affect any portion of and/or the entire gastrointestinal tract.

•Management of gastrointestinal conditions associated with systemic sclerosis involves suppression of acid production and may include administration of promotility agents.

•Pulmonary involvement is the primary cause of morbidity and mortality in systemic sclerosis.

•Warfarin, vasodilation  with an endothelin - receptor antagonist, and home oxygen is indicated in patients with isolated pulmonary artery hypertension associated with systemic sclerosis.

•Cardiac involvement in systemic sclerosis may not be clinically evident.

•Corticosteroid therapy is a risk factor for scleroderma normotensive renal crisis.

•Aggressive ACE inhibitor therapy with rapid upward titration is indicated in patients with scleroderma renal crisis.