Snapshot A 45-year-old woman presents to her physician with swollen fingers, joint pains, and a dry cough. She reports that this started a year ago and has not improved. She has a past medical history of vitiligo and primary biliary cholangitis. Physical exam reveals tightened, shiny skin with induration over her face and arms, sclerodactyly, and dry rales in the lungs. There are also telangiectasias on her left cheek. Her physician sends her for additional pulmonary imaging and 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 login to view 3 more bullets classification limited cutaneous scleroderma login to view 10 more bullets systemic or diffuse scleroderma login to view 1 more bullet 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 and includs 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, causing a noninflammatory vasculopathy chronic inflammation with alterations of humoral and cellular immunity login to view 1 more bullet 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 Presentation Symptoms skin diffuse pruritus Raynaud phenomenon gastrointestinal acid reflux respiratory progressive dyspnea dry cough due to restrictive lung disease musculoskeletal mylagias arthralgias cardiac palpitations or irregular heart beats Physical exam skin skin tightness, induration, and hardening login to view 2 more bullets 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 login to view 3 more bullets renal hypertension Imaging Computerized tomography (CT) scan indications to evaluate pulmonary involvement view chest findings ground-glass appearance may indicate early lung fibrosis honeycombing and bronchiolectasis indicate developed interstitial fibrosis STUDIES 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 electrocardiogram to assess for cardiac involvement Manometry aperistalsis in distal esophagus and decreased lower esophageal sphincter tone Pulmonary function test to detect early signs of pulmonary fibrosis Differential Nephrogenic systemic fibrosis Eosinophilic fasciitis DIAGNOSIS Making the diagnosis based on clinical presentation and laboratory studies Treatment Management approach largely based on symptomatic relief Medical immunosuppressive therapies indication login to view 1 more bullet drugs login to view 4 more bullets angiotensin-converting enzyme (ACE) inhibitor indication login to view 2 more bullets anti-histamines indication login to view 1 more bullet calcium-channel blockers indication login to view 1 more bullet ambrisentan (endothelin receptor antagonist) and tadalafil (phosphodiesterase type 5 inhibitor) combination therapy indication login to view 1 more bullet Complications Digital infarct Pulmonary hypertension Pulmonary fibrosis Renal failure 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