| What is systemic sclerosis? | Chronic multisystem autoimmune disease of CT, characterized by fibrosis of skin and internal organs, vasculopathy (microvasculature and humoral immunity) and part of scleroderma spectrum diseases (localized [morphea, linear scleroderma], or systemic [limited and diffuse]) |
| How is the classification of systemic sclerosis? | Limited cutaneous systemic sclerosis (lcSSc, skin involved only distal to knees and elbows)
Diffuse cutaneous systemic sclerosis (dcSSc, skin thickening proximal to knees and elbows)
SSc sine scleroderma (vascular and serological features without skin involvement)
EUSTAR (Vedoss very early dx of SSc, three red flags (Raynaud's phenomenon, puffy fingers and ANAs plus 1 of (disease-specific autoantibodies [ACA/anti-topo], or microvascular alterations detected by nailfold videocapillaroscopy) |
| How is epidemiology of SSc? | Orphan disease, mainly underestimated |
| How is etiology of SSc? | MHC II, non MHC genes (associated with metabolism of ECM, and coding for proteins involved in innate immunity, macrophage activation and T cell function)
Environmental factors (viruses [CMV, parvo, EBV], induce vascular damage and fibroblast proliferation, drugs, organic solvents [vinyl chloride, silica, nanoparticles]) |
| How is pathophysiology of SSc? | Vascular damage in microcirculation (severe fibroproliferation of small arteries and arterioles)
Immune system activation, autoimmunity and inflammation (alteration of humoral and cellular immunity)
Fibrosis (excess deposits of collagen macromolecules in skin and various internal organs)
So we have etiologic agent that activates genes, lead to endothelial and microvascular alterations lead to chronic inflammation by deposition of fibroblasts into myofibroblasts and lead to vasculopathy and fibrosis |
| How is vascular dysfunction in SSc? | Endothelial activation and damage (loss of normal vasomotor tone regulation by vasodilators decrease and vasoconstrictors increase, chemotraction and adhesion of inflammatory molecules, exposure of subendothelium to blood like platelets, fibrin and intravascular thrombus, activation of vascular muscle cell layer and migration to intima producing myofibroblasts and lead to fibrosis)
So vessel loss occurs due to enhancement of vascular damage, proliferation of vascular intima, narrowing of vessel lumen, reduction of blood flow, digital ischemia and ulcers. |
| How is immune activation/inflammation in SSc? | Inflammation, innate, humoral and cellular immunity alteartion play a role in pathogenesis of SSc.
Humoral (ANA>90%, Anti-Scl-70 [anti topoisomerase 30-40%], ACA [anticentromere, 80-90%], anti RNA pol II and III [rapid progression and internal organ involvement], antifibrillarin, anti-PM-Scl) |
| What are the clinical manifestations of SSc? | Skin (swelling, puffiness irresponsive to diueretics, progressive tightness and induration, sclerodactyly, tightening of face, prominent skin pigmentary change, diffuse pruritis) |
| What are the vascular clinical manifestations of SSc? | Vascular (Raynaud phenomenon [95% develop it during course of disease, very early precedes SSc by months, female-male 4:1, 5-15% of population], healed pitting ulcers in fingers, large fingertup ulcers lead to amputation, cutaneous and mucosal telengectasis, macrovascular non-atherosclerotic MI) |
| What are the GI clinical manifestaions of SSc? | GI (GERD due to lower esophageal sphincter incontinence, dyspepsia, bloating, pseudoobstuction, constipation, diarrhea, fecal incontinence, malnutrition, chronic iron deficiency anemia from occult blood loss, watermelon stomach or GAVE very rare long red vessels limited to gastric antrum) |
| What are the pulmonary clinical manifestations of SSc? | Pulmo (progressive dyspnea, chest pain due to pulmo HTN, dry persistent cough restrictive lung disease/ILD, leading cause of M&M in SSc, alveolitis)
ILD (diffuse, perform CXR, HRCT or PFT, see thickened interlobular septa, subpleural cysts, honeycombing, micronodules, ectasia, ground glass opacities)
PAH (serious and life threat, blood vessels of lung constrict and thicken due to fibrosis, increased resistance lead to HF, we make right heart Cath and cardaic US) |
| What are the musculoskeletal manifestations of SSc? | Arthralgia, myalgia, loss in joint ROM, tendon friction rubs, carpal tunnel syndrome symptoms, muscle weakeness |
| What are the cardiac manifestations of SSc? | Dyspnea due to CHF/myocardial fibrosis, palpitations, irregular heartbeats, syncope due to arrhythmias/conduction abnormality, CHF symptoms/right sided HF, independent risk factor for AMI. |
| What are the renal manifestations of SSc? | HTN, renal crisis, chronic renal insufficiency, hx of high-dose corticosteroid use. |
| How is prognosis of SSc? | No specific tx, poor prognosis related to pulmonary disease, cardiopulmonary transplant in some cases |
