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 login to view 7 more bullets Genetics inheritance pattern usually sporadic mutations HLA STAT4 login to view 1 more bullet IRF5 login to view 1 more bullet 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 login to view 5 more bullets diffuse widespread involvement of the skin affects internal organs (kidneys, lungs, heart) rapidly progressive Presentation Symptoms skin diffuse pruritus Raynaud phenomenon login to view 2 more bullets 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 login to view 5 more bullets 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 login to view 3 more bullets 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 login to view 1 more bullet drugs login to view 4 more bullets angiotensin-converting enzyme (ACE) inhibitor indications login to view 1 more bullet anti-histamines indications login to view 1 more bullet calcium-channel blockers indications login to view 1 more bullet ambrisentan (endothelin receptor antagonist) and tadalafil (phosphodiesterase type 5 inhibitor) combination therapy indications login to view 1 more bullet Operative I&D indications login to view 1 more bullet PIP joint arthrodesis indications login to view 1 more bullet MCP joint resection arthroplasty indications login to view 1 more bullet adductor pollicis release +/- trapeziectomy indications login to view 1 more bullet amputation indications login to view 1 more bullet 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