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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 [1] - Raynaud's phenomenon* is early manifestation * absence of Raynaud's phenomenon makes systemic sclerosis unlikely [1] 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 Special laboratory: - 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 Differential diagnosis: 1) systemic sclerosis a) scleroderma b) CREST syndrome c) morphea d) systemic sclerosis sine scleroderma 2) scleroderma-like conditions a) eosinophilic fasciitis - edema or 'orange peel' induration of proximal extremities - sparing of hands & face - peripheral eosinophilia - skin biopsy: lymphocytes, plasma cells, eosinophils b) nephrogenic systemic fibrosis - renal insufficiency with exposure to gadolinium (now rare) - wood-like induration of extremities, sparing of digits c) scleredema - indurated plaques or patches on back, shoulder girdle & neck - associated with chronic diabetes mellitus d) scleromyxedema - waxy, yellow-red papules over thickend skin of face, neck, upper trunk & arms - associated with multiple myeloma or AL-amyloidosis e) chronic graft vs host disease - lichen planus like skin lesions or generalized skin thickening - most commonly associated with hematopoietic stem cell transplantation f) adverse drug effect or poisoning from toxin - bleomysin, docetaxel, pentazocine, L-tryptophan, organic solvents 3) 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 [1] 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 [1] - gastric antral ectasia (GAVE, watermelon stomach) - recurrent bleeding, chronic anemia - scleroderma renal crisis - glucocorticoids are a risk factor 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 [1]

Specific

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

General

connective tissue disease; soft tissue disease autoimmune disease sclerosis

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2022 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  2. Chifflot H, Fautrel B, Sordet C, Chatelus E, Sibilia J. Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum. 2008 Feb;37(4):223-35 PMID: 17692364
  3. Johnson SR, Fransen J, Khanna D et al Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res (Hoboken). 2012 Mar;64(3):358-67. PMID: 22052658
  4. Kumar U, Sankalp G, Sreenivas V, Kaur S, Misra D. Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis- related pulmonary artery hypertension and cutaneous vascular complications. Rheumatol Int. 2013 Apr;33(4):1047-52. PMID: 22833239
  5. Walker KM1, Pope J et al Treatment of systemic sclerosis complications: what to use when first-line treatment fails - a consensus of systemic sclerosis experts. Semin Arthritis Rheum. 2012 Aug;42(1):42-55. PMID: 22464314
  6. Gyger G, Baron M. Systemic Sclerosis: Gastrointestinal Disease and Its Management. Rheum Dis Clin North Am. 2015 Aug;41(3):459-73. Review. PMID: 26210129
  7. Mehra S, Walker J, Patterson K, Fritzler MJ. Autoantibodies in systemic sclerosis. Autoimmun Rev. 2013 Jan;12(3):340-54. Review. PMID: 22743034
  8. ARUP consult: Systemic Sclerosis Antibodies https://arupconsult.com/ati/systemic-sclerosis-antibodies