Presentation on theme: "SSc 101 Julia Rhiannon June 2013"— Presentation transcript:
SSc 101 Julia Rhiannon June 2013
outline Intro and pathogenesis Classification dcSSc ~ diffuse cutaneous systemic sclerosis –organ involvement with 2 cases –Rodnan skin scoring lcSSc ~ limited cutaneous systemic sclerosis & case Antibodies as clues to phenotype Environmental/genetic contribution and epi Therapy
SSc clinical manifestations result from... Autoimmunity Small vessel obliterative vasculopathy –Raynaud’s, renal crisis, PAH Pathological accumulation of collagen in skin and other organs –Sceroderma, lung parenchymal dz, GI dysmotility
Chicken vs Egg – Pathogenesis and autoantibodies
Gu, S., et.al., Seminars in Arthritis, 2008
Localized Scleroderma Morphea Linear Scleroderma Coup de Sabre
Case 1: Puffy Hands HPI - 45 y/o woman with 5 wks of puffy hands –recently finger turns white while grocery shopping or reaching into refrigerator. Hands feel itchy. Exam - Diffusely swollen hands and wrists. Several fingers cyanotic. Pulses intact.
The next step would be: 1. Check for nailfold changes 2. Doppler study 3. Order ANA panel 4. Order ANCA 5. Skin biopsy 6. Pred 60mg IM x1 7. Tell her to take her husband’s viagra Case: Puffy Hands
Skin: Raynaud’s Classic three color change: -pallor (vasoconstriction) -cyanosis -rubor (least frequent)Classic three color change: -pallor (vasoconstriction) -cyanosis -rubor (least frequent) Triggered by cold and emotionTriggered by cold and emotion
Raynaud’s Raynaud’s affects 3-5% of general population –Most are primary, usually with onset in 20s-30s Raynaud’s assoc with SSc will likely have : –Increased severity in freq/duration/morbidity –Nailfold cap abn (47% PPV) –Positive serologies (ANA 30%PPV) –With stiffness and/or pitting +/- ulcers –Age >35
Treatment of Raynaud’s Central warmth, good gloves, avoid cold exposure, handwarmers Stress reduction Dihydropyridine calcium channel blockers –nifedipine 30mg ER titrate up as tolerated Phosphodiesterase 5 inhibition (sildenafil/revatio/viagra) Topical nitroglycerin for 20 minutes (or more) tid proximal to affected digit Po and IV prostanoids (alprostadil) Endothelin receptor antagonist (Bosentan) Statins Antiplatelet (ASA) and antioxidant (NAC)
Severe Digital Ischemia Treatment of impending digital gangrene requires hospitalization Warm room, pain meds, anxiolytics, high dose Ca channel blockers or trial of IV alprostadil (5 nanograms/kg/min for 6 hours followed by 10 nanograms/kg/min for 66 hours via PICC line), Antibiotics if infection present May try sympathetic block at the wrist; 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 & Cytoxan 3. IV nitroprusside 4. ACEi (enalaprilat or po enalapril) 5. Renal bx STAT
Scleroderma Renal Crisis Defined as accelerated arterial hypertension and/or rapidly progressive oliguric renal failure. Occurs in 10% of patients with scleroderma Occurs in 20-25% of pts with the RNA Pol III Ab Etiology - mimics malignant htn, 2/2 microvasc dz, vasospasm, and tissue ischemia… with elevated renin, and arteriolar fibrotic change Knowledge from clinical studies: –Must keep exquisite control of BP –When in renal crisis use ACEs before ARBs or any other –Corticosteroids thought to predispose patients to renal crisis
Active ILD in SSc likely to be NSIP Depressed FVC or declining FVC by >10% in 4-6mo Bilateral Basal predominant Confluent Ground glass Reticular lines Traction bronchiectasis Will progress to PF without treatment
Cardiac Involvement Myocardial fibrosis –most common manifestation Coronary Artery Disease Conduction System Disease and Arrhythmias Pericardial Disease
Diffuse disease, assessment over time Skin involvement reflects relative risk of new internal organ involvement –Pace –Progression –Extent Must be able to track extent and severity of skin changes Classification and prognosis depends on these determinations in addition to antibodies Rodnan skin score is qualitative –0 normal; 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 Clinical Assessment of Skin Thickening-Modified Rodnan Skin Score (MRSS)
Clinical Meaningfulness of Change in MRSS Increase predicts worsening of SScIncrease predicts worsening of SSc Stability predicts reduced new internal involvementStability predicts reduced new internal involvement Improvement predicts improved 5 and 10 year survivalImprovement predicts improved 5 and 10 year survival 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, hemoglobinImproved score correlates with HAQ-DI, hemoglobin
lcSSc (limited cutaneous systemic sclerosis) C alcinosis, R aynaud’s, E sophageal dysmotility, S clerodactly, T elangiectasia Raynaud’s 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 Sjogren’s Calcinosis
Case 3 HPI - A 52 y/o women with 10 yrs of Raynaud’s 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 Raynaud’s 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 expect to see on ANA testing?
Classification of Systemic Sclerosis and Organ Involvement All systemic sclerosis –Raynaud’s –Esophageal dysmotility –Telangiectasias dcSSc –Interstitial Lung disease –Renal Crisis –Cardiac Involvement –GI involvement lcSSc –Pulmonary hypertension –Calcinosis –Overlap syndromes-Sjogren’s, RA, SLE, MCTD, PBC
Antibodies as clues to phenotype, organ involvement, prognosis dcSScdcSSc –ANA positive 40-90% with nucleolar pattern on ANA –Scl-70 (anti-topoisomerase 1) with low sensitivity / high specificity for diffuse disease –RNA Polymerase III - most severe skin involv., highest freq of renal crisis, best overall prognosis –U3 RNP - diffuse but with PAH +/- ILD, skeletal and cardiac muscle inv lcSSclcSSc –centromere ANA very specific for CREST/limited disease in up to 90% of pts; PAH –U1 RNP – MCTD with SSc phenotype, risk of PAH –Th/To - PAH +/- ILD; more pulm fibrosis and renal crisis than anti-centromere+ pts Arthritis Rheum Apr;60(4):
Env/Occup Genetics Polyvinylchloride s Toxic oil syndrome- Spain - rapeseed oil contaminated with aniline dye SScl like disease contaminated L-tryprophan – “eosinophilia myalgia syndrome” Silica dust - case reports in miners Organic solvents - textile industry / paint thinners and removers Epoxy resins Pesticides Hand/arm vibration Arch Occup Environ Health 2004; 77: % of Ssc pts have a 1 st 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: 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 yrs of age. Prognosis worsens with increasing age of onset.