systemic sclerosis

Classification

• diffuse cutaneous systemic sclerosis
  • skin thickening proximal to elbows & knees, including abdomen & thorax
    • may affect lateral face
  • ANA & Scl-70 Ab
  • interstitial lung disease more common
  • risk for scleroderma renal crisis
  • CREST syndrome absent
• limited cutaneous systemic sclerosis
  • skin thickening distaal to elbows & knees
    • may affect lateral face
  • ANA & anticentromere Ab
  • pulmonary hypertension more common
  • scleroderma renal crisis rare to non-existent
  • CREST syndrome possible to probable

Pathology

• skin thickening &/or internal organ fibrosis
• vasculopathy
• esophageal dysmotility with GERD

Clinical manifestations

• swollen fingers & hands are early manifestations
  • skin becomes thickened & atrophic & mobility becomes limited
• Raynaud's phenomenon* is early manifestation

* absence of Raynaud's phenomenon makes systemic sclerosis unlikely

Diagnostic criteria

• characteristic skin manifestations (see scleroderma)
  • skin thickening, tightening (induration)
• one of more of
  • Raynaud phenomenon (most common early manifestation)
  • digital pitting
  • interstitial lung disease
  • sclerodactyly
  • pulmonary hypertension
  • GERD, esophageal dymotility
  • small intestinal pseudo-obstruction
  • malabsorption (bacterial overgrowth)
  • calcinosis (hands, forearms, elbows, gluteal region, iliac crest)
  • inflammatory arthritis (distal interphalangeal joints, wrists)
    • osteolysis of distal phalanges (fingers & toes)
  • kidney disease

Laboratory

• systemic sclerosis panel
• antinuclear antibody (ANA)
• Scl-70 Ab in serum
• anticentromere Ab in serum
• hydrogen breath test can diagnose small intestinal bacterial overgrowth
• serum creatinine
• urine protein*

* 50% with proteinuria, acute kidney injury or chronic renal failure uncommon

Diagnostic procedures

• pulmonary function testing
  • at time of diagnosis
  • every 6-12 months with DLCO
• echocardiography annually or more frequently for new or changing symptoms of pulmonary arterial hypertension
• right heart catheterization required for diagnosis of pulmonary hypertension

Radiology

• high resolution CT of chest at time of diagnosis

Complications

• primary cause of death is pulmonary disease (also see scleroderma)
• complications in pregnant patients
  • gestational hypertension, pre-eclampsia, preterm delivery
• contraindications to pregnancy
  • pulmonary hypertension, severe restrictive lung disease
• gastric antral ectasia (GAVE, watermelon stomach)
  • recurrent bleeding, chronic anemia
• scleroderma renal crisis
  • glucocorticoids are a risk factor

Differential diagnosis

• systemic sclerosis
  • scleroderma
  • CREST syndrome
  • morphea
  • systemic sclerosis sine scleroderma
• scleroderma-like conditions
  • eosinophilic fasciitis
    • edema or 'orange peel' induration of proximal extremities
    • sparing of hands & face
    • peripheral eosinophilia
    • skin biopsy: lymphocytes, plasma cells, eosinophils
  • nephrogenic systemic fibrosis
    • renal insufficiency with exposure to gadolinium (now rare)
    • wood-like induration of extremities, sparing of digits
  • scleredema
    • indurated plaques or patches on back, shoulder girdle & neck
    • associated with chronic diabetes mellitus
  • scleromyxedema
    • waxy, yellow-red papules over thickend skin of face, neck, upper trunk & arms
    • associated with multiple myeloma or AL-amyloidosis
  • chronic graft vs host disease
    • lichen planus like skin lesions or generalized skin thickening
    • most commonly associated with hematopoietic stem cell transplantation
  • adverse drug effect or poisoning from toxin
    • bleomysin, docetaxel, pentazocine, L-tryptophan, organic solvents
• Raynaud disease
  • nailfold capillary destruction & dilated capillary loops distinguish early systemic sclerosis from Raynaud disease
  • skin thickening without Raynaud phenomenon is a scleroderma-like condition & not systemic sclerosis

Management

• largely symptomatic & organ specific
• see specific type
• no disease-modifying therapy available
• Raynaud phenomenon
  • avoid smoking & cold exposure
  • dihydropyridine calcium channel blockers: amlodipine, felodipine, nifedipine
  • sildenafil, niroglycerin
• gastric & intestinal dysmotility
  • proton pump inhibitor for GERD
  • promotility agents (metoclopramide) for gastric & intestinal dysmotility
• scleroderma renal crisis
  • ACE inhibitor regardless of serum creatinine or renal failure
  • glucocorticoids increase risk (do not use)
• bacterial overgrowth
  • rotating broad spectrum antibiotics
• interstitial lung disease or alveolitis
  • mycophenolate, cyclophosphamide, nintedanib + mycophenolate

More general terms

• connective tissue disease; soft tissue disease
• autoimmune disease
• sclerosis

More specific terms

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