Scleroderma

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Contents 1 More Specific Terms 2 Introduction 3 Etiology 4 Pathology 5 Clinical-manifestations 6 Diagnostic-criteria 7 Laboratory 8 Diagnostic-procedures 9 Radiology 10 Differential-diagnosis 11 Management 12 More General Terms 13 Additional Terms 14 References

More Specific Terms

• CREST syndrome
• morphea (localized cutaneous scleroderma)
• systemic sclerosis sine scleroderma

Introduction

• A systemic disorder of unknown etiology characterized by thickening & hardening of the skin & visceral organs, risk of hypertensive renal crisis, & shortened survival. The CREST syndrome represents a limited form of scleroderma.

Etiology

• unknown
• autoimmune
• agents which may induce some manifestations of scleroderma

• exposure to polyvinyl chloride ( PVC)
• exposure to silica (coal miners)
• bleomycin

Pathology

• microangiopathy & fibrosis of skin & visceral organs
• arterial vasospasm resulting in Raynaud's phenomenon [4]
• gastrointestinal

• atrophy & fibrosis of smooth muscle from esophagus to colon

• cardiac: myocardial fibrosis
• microangiopathic hemolytic anemia
• skin:

• thickening of reticular dermis with excessive collagen deposition
• atrophy of papillar dermis & epidermal rete pegs
• cutaneous vessels show intimal proliferation, collagen deposition in the vessel wall & mild perivascular inflammation

Clinical-manifestations

• vascular

• most manifestations have a vascular basis
• vasculitis is rare
• Raynaud's phenomenon (95%)

• initial presentation in 70% of patients [4]

• telangiectasias on hands, cheeks & lips are common
• nail fold capillary changes
• microangiopathic hemolytic anemia

• cardiac

• conduction disturbances & arrhythmias
• congestive heart failure
• coronary vasospasm
• accentuated P2 heart sound
• may be asymptomatic (for heart disease)
• myocardial fibrosis
• pericardial disease

• pulmonary (80%)

• pulmonary basilar crackles
• diffuse interstitial fibrosis (75% at autopsy)
• pulmonary hypertension (50%)
• cor pulmonale
• pulmonary complications are more severe in the CREST syndrome
• aspiration pneumonia secondary to esophageal dysfunction & gastroesophageal reflux
• pleural involvement ( pleurisy, pleural effusion) is rare

• renal

• nephrosclerosis
• hypertension, including hypertensive crisis
• renal insufficiency
• scleroderma renal crisis occurs almost exclusively in patients with early cutaneous disease

• severe hypertension
• renal failure
• microangiopathic hemolytic anemia

• skin & joints (also see vascular)

• skin thickening, tightening
• joint contractures
• millet size calcifications may develop
• pruritis & ulceration may occur
• distribution:

• fingers ( sclerodactyly), digital ulceration
• dorsum of hand proximal to MCP joints
• forearms, face, legs, trunk

• gastrointestinal (~100%)

• reflux esophagitis ( GERD)
• esophageal strictures
• dysphagia
• decreased bowel motility
• bacterial overgrowth
• malabsorption
• bloating
• abdominal distention
• diverticulosis
• pseudotoxic megacolon

• CREST syndrome

Diagnostic-criteria

• sclerodermatous skin changes that extend proximal to the MCP joints or
• 2 of the following

• sclerodactyly
• digital pitting
• basilar fibrosis visible of chest X-ray

Laboratory

• serology for autoantibodies

• antinuclear antibodies ( ANA)

• present in about 95% of patients
• usually speckled or homogenous pattern
• nucleolar & centromere patterns, less common, but more specific for systemic sclerosis
• centromere pattern most common with limited cutaneous scleroderma

• anti Scl-70

• 20-50% in diffuse scleroderma
• associated with diffuse cutaneous disease & interstitial lung disease [4]

• anti centromere (70-80% in CREST)
• anti RNA polymerase I (4-20%)
• anti RNA polymerase II (4%)
• anti RNA polymerase III (23%)

• anti- POLR3C

• anti fibrillarin ( U3-snRNP)
• anti PM-ScL ( PMSCL1, PMSCL2)
• anti To
• anti NOR-90
• Sjogren's syndrome/scleroderma autoantigen 1
• RPP38

• other autoantigens associated with scleroderma

• SPOP, TEX101, EXOSC9, EXOSC10, RPP30, UBF1, SSSCA1,

• hypergammaglobulinemia (50%)
• complete blood count ( CBC)

• mild eosinophilia (5-10%)
• anemia is generally mild

• esophagitis -> GI bleed -> iron deficiency
• malabsorption -> folate or B12 deficiency

• serum creatinine is generally normal in the absence of hypertension & renal crisis

Diagnostic-procedures

• pulmonary function testing (every 6 months)

• progressive restrictive lung disease
• low diffusion capacity ( DLCO) is earliest manifestation

• echocardiogram to evaluate pulmonary artery pressure & to assess septal fibrosis or pericardial effusions [4] (30% of patients have asymptomatic pericardial effusions)

Radiology

• chest X-ray may show

• interstitial lung disease
• basilar fibrosis

• high-resolution CT to evaluate pulmonary fibrosis [4]

Differential-diagnosis

• eosinophilic fasciitis
• eosinophilia myalgia syndrome
• scleroderma variants

• morphea ( localized cutaneous scleroderma)
• systemic sclerosis sine scleroderma
• CREST

• graft versus host disease
• mycosis fungoides
• primary biliary cirrhosis
• pulmonary hypertension, primary

• idiopathic pulmonary fibrosis

• reflex sympathetic dystrophy
• mixed connective tissue disease
• nephrogenic systemic fibrosis
• Buschke scleredema
• scleromyxedema [4]

Management

• No curative therapy
• problem- oriented approach
• Raynaud's phenomenon

• cessation of smoking
• calcium channel blockers
• anti-platelet agents
• prazosin
• phenoxybenzamine
• reserpine
• guanethidine
• sympathetic ganglion blockade for patients with digital ulceration that have failed conservative management

• skin & joints

• penicillamine
• physical therapy

• gastrointestinal

• reflux esophagitis ( GERD)

• proton pump inhibitor ( omeprazole, lansoprazole)
• H2 receptor antagonists
• sucralfate
• Ca+2-channel antagonists may worsen reflux

• esophageal strictures - dilation
• gut motility - metoclopramide ( cisapride remove from US market)
• bacterial overgrowth [1] tetracycline [2] metronidazole
• bloating & abdominal distention

• metoclopramide

• renal

• aggressive blood pressure control with ACE inhibitor
• high-dose glucocorticoids increase risk of renal crisis
• ACE inhibitor for renal crisis regardless of serum creatinine [4]

• cardiac - standard therapies for specific problems
• pulmonary

• standard therapies for specific problems
• oral cyclophosphamide may improve symptoms

• myositis - prednisone
• pregnancy is high risk

• increased risk of small full-term infants
• increased risk of premature births [4]

• prognosis:

• progressive disease
• 45% 10 year survival for diffuse form

More General Terms

• connective tissue disease
• autoimmune disease

Additional Terms

• eosinophilia-myalgia syndrome (EMS)
• eosinophilic fasciitis (Shulman's syndrome)
• Raynaud's phenomenon
• sclerodactyly
• Sjoegren syndrome/scleroderma autoantigen 1; autoantigen p27 (SSSCA1)

References

1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 525-26
2. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 1018-19
3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 875-76, 788
4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
5. eMedicine: Scleroderma [1]
6. Scleroderma: NIH Institute and Center Resources [2]

scleroderma (systemic sclerosis)