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 autoimmunity noninflammatory vasculopathy collagen deposition with fibrosis classification limited cutaneous scleroderma usually affecting only the skin subtype is CREST syndrome Calcinosis cutis anti-Centromere antibody Raynaud ↓ 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 systemic or diffuse scleroderma affecting internal organs, including renal, lung, and cardiac 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 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 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 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 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 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 captopril is drug of choice in scleroderma renal crisis 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 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