Updated: 11/11/2018

Scleroderma

Topic
Review Topic
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Questions
5
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Evidence
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Snapshot
  • A 50-year-old woman presents to her physician’s office for a routine checkup. Once at the office, she reports that she has been generally doing well but recently noticed that her fingers tend to turn blue in the cold. She reports feeling a general skin tightening in her face and hands, which makes forming a fist difficult. She also notes that she has had increased acid reflux lately and requests a medication for that. Her past medical history includes autoimmune thyroid disease and alopecia areata. Physical exam reveals sclerodactyly, and tight, hardened skin with limited mobility in her fingers. Her physician sends her for additional autoimmune workup.
Introduction
  • Clinical definition
    • an autoimmune skin disease characterized by progressive hardening and induration of the skin and/or other structures such as the subcutaneous tissues, muscles, and internal organs
      • triad
        • autoimmunity
        • noninflammatory vasculopathy
        • collagen deposition with fibrosis
    • classification
      • localized scleroderma
        • affecting only the skin and muscles
      • systemic scleroderma (systemic sclerosis)
        • affecting internal organs including the kidney, lung, and heart
        • further subdivided into limited and diffuse 
          • limited progresses more slowly and has less internal organ involvement
        • subtype of systemic scleroderma is CREST syndrome
          • Calcinosis cutis
          • anti-Centromere antibody
          • Raynaud phenomenon 
            • ↓ blood flow to skin from either cold temperatures or stress, which causes vasospasms
            • colors of affected area, commonly the digits, change from white (ischemia) to blue (hypoxia) to red (re-perfusion)
          • Esophageal dysmotility
          • Sclerodactyly
          • Telangiectasia
  • Epidemiology
    • demographics
      • female > male
      • African Americans > Caucasian
      • 30-50 years of age but can affect all ages
    • risk factors
      • exposure to potential triggers
  • Etiology
    • multifactorial, including genetic predisposition and environmental triggers
      • possible triggers include silica, solvent (such as benzene), and radiation exposure
  • Pathogenesis
    • sclerosis
      • excessive deposition of collagen and other elements of the extracellular matrix in skin and internal organs
      • fibroproliferation of microvasculature leading to a noninflammatory vasculopathy
      • chronic inflammation with alterations of humoral and cellular immunity
        • increased release of inflammatory cells help initiate and propagate the fibrotic process
    • esophageal dysmotility
      • atrophy of smooth muscles in esophagus can cause ↓ lower esophageal sphincter pressure and dysmotility, leading to increased dysphagia and acid reflux
  • Associated conditions
    • other autoimmune diseases
  • Prognosis
    • systemic scleroderma is rapidly progressive
      • involvement of pulmonary, renal, or cardiac systems indicate a more severe prognosis
      • one of the highest mortalities among systemic autoimmune diseases
    • limited scleroderma is more benign
Presentation
  • Symptoms
    • skin
      • diffuse pruritus
    • gastrointestinal
      • acid reflux
    • respiratory
      • progressive dyspnea
      • dry cough due to restrictive lung disease
    • musculoskeletal
      • myalgias
      • arthralgias
    • cardiac
      • palpitations or irregular heart beats
  • Physical exam
    • skin
      • skin tightness, induration, and hardening
        • affecting the fingers (sclerodactyly)
        • shiny with loss of “wrinkles” from skin folds
      • limited mobility due to skin tightening
      • digital ulceration
      • edema not responsive to diuresis
      • hyper and hypopigmentation
      • telangiectasias on skin and mucosa
    • respiratory
      • dry rales indicative of pulmonary involvement
    • cardiac
      • symptoms of cor pulmonale if there is pulmonary involvement
        • jugular venous distention
        • edema
        • hepatomegaly
    • renal
      • hypertension
Imaging
  • Computerized tomography (CT) scan
    • indications
      • evaluate pulmonary involvement
    • view
      • chest
    • findings
      • ground-glass appearance may indicate early lung fibrosis
      • honeycombing and bronchiolectasis indicate developed interstitial fibrosis
Evaluation
  • Labs 
    • anti-Scl-70 (anti-DNA topoisomerase I) 
      • associated with systemic scleroderma
      • in ~ 30% of patients
    • anti-centromere autoantibody
      • associated with limited scleroderma (CREST syndrome)
      • in ~ 50% of patients
    • antinuclear antibodies
      • in ~ 90-95% of affected patients
      • speckled or centromere pattern
      • nucleolar pattern is specific for systemic sclerosis
    • ↑ inflammatory markers
      • erythrocyte sedimentation rate
      • C-reactive protein
    • serum creatinine
      • to monitor for renal involvement
    • ↑ CXCL4
      • may indicate pulmonary fibrosis
    • ↑ N-terminal probrain natriuretic peptide
      • may indicate early pulmonary hypertension
  • Electrodiagnostics
    • routine EKG to assess for cardiac involvement
  • Pulmonary function test
    • to detect early signs of pulmonary fibrosis
  • Making the diagnosis
    • based on clinical presentation and laboratory studies
Differential
  • Nephrogenic systemic fibrosis
  • Eosinophilic fasciitis
Treatment
  • Management approach
    • largely based on symptomatic relief
  • Medical
    • immunosuppressive therapies
      • indication
        • to prevent progression of sclerosis, especially if pulmonary system is involved
      • drugs
        • methotrexate
        • mycophenolate mofetil
        • cyclophosphamide
          • reserved for when disease is refractory to either methotrexate of mycophenolate mofetil
    • angiotensin-converting enzyme (ACE) inhibitor
      • indication
        • renal involvement of systemic sclerosis
    • anti-histamines
      • indication
        • pruritus
    • calcium-channel blockers 
      • indication
        • Raynaud phenomenon
    • ambrisentan (endothelin receptor antagonist) and tadalafil (phosphodiesterase type 5 inhibitor) combination therapy
      • indication
        • pulmonary hypertension
Complications
  • Digital infarct
  • Pulmonary hypertension 
  • Pulmonary fibrosis
  • Renal failure
 

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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MK.3) A 35-year-old woman comes to your office with a variety of complaints. As part of her evaluation, she undergoes laboratory testing which reveals the presence of anti-centromere antibodies. All of the following symptoms and signs would be expected to be present EXCEPT: Review Topic

QID: 101940
1

Pallor, cyanosis, and erythema of the hands

10%

(9/91)

2

Calcium deposits on digits

7%

(6/91)

3

Blanching vascular abnormalities

7%

(6/91)

4

Hypercoagulable state

49%

(45/91)

5

Heartburn and regurgitation

22%

(20/91)

M1

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