Scleroderma/Systemic Sclerosis PDF

SCLERODERMA/SYSTEMIC SCLEROSIS Nov 15, 2024 Steve S Lee, DO, FACR Partner Rheumatologist, Kaiser Permanente, Fontana Associate Clinical Professor Western University of Health Sciences California University of Science and Medicine...

SCLERODERMA/SYSTEMIC SCLEROSIS Nov 15, 2024 Steve S Lee, DO, FACR Partner Rheumatologist, Kaiser Permanente, Fontana Associate Clinical Professor Western University of Health Sciences California University of Science and Medicine Touro University Assistant Clinical Professor Loma Linda University School of Medicine Scleroderma……. Fibrosis Vasculopathy Raynauds Renal crisis PAH ILD OUTLINE Definition/Epidemiology Pathophysiology Classification and diagnosis Clinical Features Differential Diagnoses Treatment Scleroderma (Ssc) - General Rare, acquired multisystem autoimmune condition with abnormal skin, organs, blood vessels Peak: 35-65 female: male 10:1 possible etiologies: parvovirus B19, CMV, silica dust, organic solvents… Scleroderma - Pathophysiology fibroblasts collagen deposition IL-10 and TGFβ blood vessel fibrosis/vasoconstriction proliferation of smooth muscle cells in intimal layer of blood vessels Scleroderma - Pathophysiology fibroblasts collagen deposition IL-10 and TGFβ blood vessel fibrosis/vasoconstriction proliferation of smooth muscle cells in intimal layer of blood vessels  Activation of Fibroblasts in Scleroderma. Gabrielli A et al. N Engl J Med 2009;360:1989-2003. Scleroderma - Pathophysiology Activation of fibroblasts and collagen deposition via IL-10 and TGFβ blood vessel fibrosis/vasoconstriction proliferation of smooth muscle cells in intimal layer of blood vessels  Lesions in Different Stages of Scleroderma. Gabrielli A et al. N Engl J Med 2009;360:1989-2003.  Scleroderma – Clinical Features - Skin Early nonspecific symptoms (years) Swelling, itch and stiffness of the hands Dilated capillary nailfold loops/Raynaud’s/telangiectasiae 2 subsets: Diffuse (anti-scl-70/anti-topoisomerase, RNA polymerase) Limited (CREST SYNDROME)(anti-centromere) calcinosis, raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasia Maurice Raynaud (1834–1881) Early arthritis/”puffy fingers” Digital pits sclerodactyly Late changes of SSC with atrophy Telangiectasia GAVE (gastric antral vascular ectasia) “watermelon stomach” Raynaud’s phenomenon Calcinosis of CREST syndrome  Scleroderma – Clinical Features - Lungs Non-specific interstitial pneumonia (NSIP) alveolitis Usual interstitial pneumonitis (UIP) fibrosis in parenchyma (honeycombing) Dyspnea, decreased lung volumes and/or diffusing capacity Pulmonary artery hypertension (PAH) with or without interstitial lung disease (ILD) Associated with anti-nucleolar antibody Pericarditis, myocardium 10 yr survival 40-70% historically Interstitial lung disease  Scleroderma – Clinical Features - GI commonly involved small oral aperture, dry mucosa, dysphagia, esophagitis decreased peristalsis delayed emptying of the stomach Small intestinal bacterial overgrowth (SIBO) Achlorhydria Pancreatic insufficiency Microbiome Rifaximin  Scleroderma – Clinical Features - Renal Scleroderma renal crisis (SRC) → emergent severe hypertension acute renal failure usually late manifestation of diffuse skin disease  Scleroderma: Differential Dx ?  Scleroderma: Differential Dx Eosinophilic fasciitis spares the hands and face eosinophilia on biopsy Scleredema Idiopathic Diabetes Nephrogenic Fibrosing Dermopathy Morphea  Scleroderma - Treatment “no rheumatic medication should be discarded before trying in scleroderma” penicillamine, methotrexate, chlorambucil, colchicine Symptomatic treatment: Raynaud’s: warming measures, tobacco, calcium channel blockers, topical nitrates, botox GI: PPIs, promotility agents CV/pulm: cytoxan, endothelin antagonists (bosentan/Tracleer), prostacyclin analogs (epoprostenol/Flolan, iloprost/Ventavis) Renal: ACE inhibitors Immunomodulators and signal transduction?: mycophenolate mofetil/Cellcept, rituximab/Rituxan, imatinib/Gleevec Stem Cell Transplant; pirfenidone (Esbriet)? Nintedanib (Ofev) – sept 9, 2019 FDA approval for Scl-ILD Tocilizumab (Actemra) – march 4, 2021 FDA – Scl-ILD Khanna, D. Efficacy and Safety of Tocilizumab for the Treatment of Systemic Sclerosis: Results from a Phase 3 Randomized Controlled Trial. Abstract 898, ACR 2018  Scleroderma: conclusions A chronic multi-system autoimmune condition of fibroblasts and B cells Rheumatology/Pulmonary/Nephrology/Cardiology Emerging therapies Monitoring and follow up: Chest xrays/high resolution CT Pulmonary function testing with DLCO Echocardiography Right sided heart catheterization THANK YOU FOR YOUR ATTENTION!