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 due to pulmonary hypertension 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