summary Scleroderma is an autoimmune skin disease caused by collagen deposition with fibrosis in soft tissue, that presents with progressive hardening and induration of the skin, subcutaneous tissues, muscles, and internal organs. Diagnosis is made based on a constellation of clinical and physical examination findings along with laboratory studies such ANA, anti-centromere antibodies, and anti-Scl-70 antibodies. Treatment is medical management with NSAIDS, immunosuppressive therapies, and calcium channel blockers in the presence of Raynaud's disease. Epidemiology Demographics females > males (3-14:1) African Americans > Caucasians 30-50 years old but can affect all ages can be rapidly progressive in pediatric patients Risk factors genetic predisposition exposure to potential triggers silica, solvents (such as benzene), radiation Etiology Pathophysiology multifactorial includes genetic predisposition and environmental triggers pathophysiology triad collagen deposition with fibrosis excessive deposition of collagen and other elements of the extracellular matrix in skin and internal organs noninflammatory vasculopathy due to fibroproliferation of microvasculature autoimmunity chronic inflammation with alterations of humoral and cellular immunity increased release of inflammatory cells help initiate and propagate the fibrotic process Genetics inheritance pattern usually sporadic mutations HLA STAT4 associated with limited scleroderma IRF5 associated with diffuse scleroderma Associated conditions other autoimmune diseases esophageal dysmotility atrophy of smooth muscles in esophagus can cause decreased lower esophageal sphincter pressure and dysmotility, leading to increased dysphagia and acid reflux Classification Based on extent of involvement limited limited involvement of the skin (mostly affects face and hands) subtype is CREST syndrome Calcinosis cutis/anti-Centromere antibody Raynaud phenomenom Esophageal dysmotility Sclerodactyly Telangiectasia diffuse widespread involvement of the skin affects internal organs (kidneys, lungs, heart) rapidly progressive Presentation Symptoms skin diffuse pruritus Raynaud phenomenon decreased blood flow to skin due to vasospams from either cold temperatures or stress color of affected area, commonly the digits, change from white (ischemia) to blue (hypoxia) to red (reperfusion) musculoskeletal mylagias arthralgias osteolysis (especially calcaneal) gastrointestinal acid reflux respiratory progressive dyspnea dry cough due to restrictive lung disease cardiac palpitations or irregular heart beats renal hypertension Physical exam skin tightness, induration, and hardening affecting the fingers (sclerodactyly) shiny with loss of “wrinkles” from skin folds limited mobility due to skin tightening PIP flexion contractures with compensatory MCP hyperextension 1st webspace adduction contractures digital ulceration edema not responsive to diuresis hyper- and hypopigmentation telangiectasias on skin and mucosa intracutaneous or subcutaneous calcinosis respiratory dry rales if there is pulmonary involvement cardiac symptoms of cor pulmonale if there is pulmonary involvement jugular venous distention edema hepatomegaly Imaging CT indications to evaluate pulmonary involvement findings ground-glass appearance may indicate early lung fibrosis honeycombing and bronchiolectasis indicate developed interstitial fibrosis Angiography findings loss of flow to the digits Studies Labs anti-centromere antibody associated with limited scleroderma (CREST syndrome) seen in ~50% of patients anti-Scl-70 (anti-DNA topoisomerase I) antibody associated with systemic scleroderma seen in ~30% of patients anti-nuclear antibody seen in ~90-95% of affected patients speckled or centromere pattern nucleolar pattern is specific for systemic sclerosis anti-histone antibody also seen in drug-induced lupus, SLE, and RA elevated inflammatory markers (ESR, CRP) serum creatinine to monitor for renal involvement CXCL4 increase may indicate pulmonary fibrosis N-terminal probrain natriuretic peptide increase may indicate early pulmonary hypertension Manometry findings aperistalsis in distal esophagus and decreased lower esophageal sphincter tone Pulmonary function tests used to detect early signs of pulmonary fibrosis EKG perform routine EKG to assess for cardiac involvement Differential Nephrogenic systemic fibrosis Eosinophilic fasciitis Graft-versus-host disease Treatment Nonoperative immunosuppressive therapies indications to prevent progression of sclerosis, especially if the pulmonary system is involved drugs methotrexate mycophenolate mofetil cyclophosphamide reserved for disease refractory to either methotrexate or mycophenolate mofetil angiotensin-converting enzyme (ACE) inhibitor indications renal involvement of systemic sclerosis anti-histamines indications pruritus calcium-channel blockers indications Raynaud phenomenon ambrisentan (endothelin receptor antagonist) and tadalafil (phosphodiesterase type 5 inhibitor) combination therapy indications pulmonary hypertension Operative I&D indications symptomatic calcinosis PIP joint arthrodesis indications fixed PIP joint flexion deformity MCP joint resection arthroplasty indications fixed MCP joint hyperextension deformity adductor pollicis release +/- trapeziectomy indications 1st webspace contracture amputation indications digital gangrene Complications Digital infarct/gangrene Pulmonary hypertension Pulmonary fibrosis Renal failure Prognosis Diffuse scleroderma is rapidly progressive pulmonary, renal, or cardiac involvement indicates a more severe prognosis has one of the highest mortalities among systemic autoimmune diseases