dermatomyositis university of colorado 硬皮病皮肌炎科罗拉多大学课件

SScSSc 101 101 Julia RhiannonJulia Rhiannon June 2013June 2013 j outline Intro and pathogenesis Classification dcSSc diffuse cutaneous systemic sclerosis organ involvement with 2 cases Rodnan skin scoring lcSSc limited cutaneous systemic sclerosis consider digital sympathectomy if successful Early Skin Changes in Diffuse SSc Initially skin may be edematous Hands only early May have CTS Edema resolves; skin then indurated Extremities, face, trunk may be involved Advancing skin involvement often pruritic Late Skin Changes As disease progresses, skin becomes atrophic Ulcers may develop at pressure points or with trauma Disappearance of finger tips due to resorption or gangrene Secondary joint contractures Other skin changes Other Thickened and tethered Telangiectasia Calcinosis Narrowed oral aperture Case 2 44 y/o male with known dcSSc admitted to MICU for BP 210/150 creatinine 1.5 mg/dl. UA with +2 protein Smear with schistocytes Next step is to give: 1. plasma exchange 2. IV Solu-Medrol 1 mild; 2 moderate; 3 severe thickening summation of 17 body areas Face Upper arm Anterior chest Forearm Hand Fingers Thigh Leg Foot Upper arm Abdomen Forearm Hand Fingers Thigh Leg Foot Uninvolved Mild thickening Moderate thickening Severe thickening 0 1 2 3 Clinical Assessment of Skin Thickening-Modified Rodnan Skin Score Clinical Assessment of Skin Thickening-Modified Rodnan Skin Score (MRSS)(MRSS) Clinical Meaningfulness of Change in Clinical Meaningfulness of Change in MRSSMRSS Increase predicts worsening of Increase predicts worsening of SScSSc Stability predicts reduced new internal Stability predicts reduced new internal involvementinvolvement Improvement predicts improved 5 and 10 year Improvement predicts improved 5 and 10 year survivalsurvival High scores (20) predict renal crisis (OR 6.64)High scores (20) predict renal crisis (OR 6.64) High scores (20) predict mortality (OR 3.39)High scores (20) predict mortality (OR 3.39) Improved score correlates with HAQ-DI, Improved score correlates with HAQ-DI, hemoglobinhemoglobin lcSSc (limited cutaneous systemic sclerosis) Calcinosis, Raynauds, Esophageal dysmotility,Sclerodactly, Telangiectasia Raynauds often present for years prior to skin edema/thickening Skin involvement limited (fingers distal to MCPs) PAH ILD Digital infarcts seen CREST associated with PBC, occasionally also with Sjogrens CalcinosisCalcinosis Case 3 HPI - A 52 y/o women with 10 yrs of Raynauds here w/ recently increasing problems with hands as well as dysphagia. She has also noted small red dots on her face and hands appearing over the last 6 months. Exam - In the office she has active Raynauds and has multiple small red lesions on face, hands, and tongue. 1. Homogeneous 2. Nucleolar 3. Peripheral 4. Centromere 5. Speckled Case 3 What pattern would you expectWhat pattern would you expect to see on ANA testing?to see on ANA testing? Classification of Systemic Sclerosis and Organ Involvement All systemic sclerosis Raynauds Esophageal dysmotility Telangiectasias dcSSc Interstitial Lung disease Renal Crisis Cardiac Involvement GI involvement lcSSc Pulmonary hypertension Calcinosis Overlap syndromes-Sjogrens, RA, SLE, MCTD, PBC homogenous (diffuse) speckled nucleolar ANA pattern matters centromere PAH risk ILD risk Antibodies as clues to phenotype, Antibodies as clues to phenotype, organ organ involvement, prognosisinvolvement, prognosis dcSScdcSSc ANA positive 40-90% with ANA positive 40-90% with nucleolarnucleolar pattern on ANA pattern on ANA Scl-70 (anti-Scl-70 (anti-topoisomerasetopoisomerase 1) with low sensitivity 1) with low sensitivity / high / high specificity for diffuse diseasespecificity for diffuse disease RNA Polymerase RNA Polymerase III - most III - most severe skin severe skin involvinvolv., highest freq of ., highest freq of renal crisis, best overall prognosisrenal crisis, best overall prognosis U3 RNP U3 RNP - diffuse but with PAH +/- ILD, skeletal and cardiac - diffuse but with PAH +/- ILD, skeletal and cardiac muscle invmuscle inv lcSSclcSSc centromerecentromere ANA ANA very specific for CREST/limited disease in up very specific for CREST/limited disease in up to 90% of to 90% of pts; PAHpts; PAH U1 RNP U1 RNP MCTD with MCTD with SScSSc phenotype, risk of PAH phenotype, risk of PAH ThTh/To - PAH +/- ILD; more /To - PAH +/- ILD; more pulmpulm fibrosis and renal crisis than fibrosis and renal crisis than anti-anti-centromerecentromere+ pts+ pts Arthritis Rheum. 2009 Apr;60(4):1112-28. Predominant Features Associated with Scleroderma-Specific Autoantibodies ACATh/ToU1- RNP PmSclU3-RNPTopo1Pol 3 SSc Subset LLLLDDD LungPHILD 77:10-16 1.6% of Ssc pts have a 1st degree relative with SSc (RR=13) 5.9% concordance in identical twins (300 times higher than chance) Strong associations with HLA -A1, -B8, -DR3 haplotype and with DR3/DR52 Strong associations with C4AQ0 and DQA2 Well-defined cluster of Choctaw Indians with diffuse phenotype Epidemiology Prevalence: 276-300 cases per million Incidence: 20 cases per million/year F:M = 4.6:1 Shows relative phenotypic severity in African Americans and Native Americans. Onset peaks between 45-60 yrs of age. Prognosis worsens with increasing age of onset. Treatment overview Htn ACEi, CCB Raynauds CCB PDE5 inhibition nitrates GI Cholinergic agonists PPI, H2B antibiotics for bowel overgrowth Reglan/domperidone Argon coag for GAVE Doxepin for itching Treat depression, anxiety, sleeplessness PAH Bosentan Epoprostenol PDE5 inhibition DMARDS methotrexate MMF (CellCept/Myfortic) Cyclophosphamide Steroids, LD(15mg) N-acetylcysteine Rituximab Stem cell transplant Tyr-kinase inhibition Anti-CTGF “No drug has been shown to be completely worthless until tried in Scleroderma” Eric Bywaters Scleroderma 3K/5K walk June is SSc awareness month Walk is this coming Sat, June 15th, 2013 /steppingoutcherrycreek References Shah, A and F. Wigley, Mayo Clin Proc. 2013 Apr; 88(4):377-393. Klippel, John, et.al., Primer on the R