SLE and other Autoimmune Diseases: An Overview Charito F. Cruz-Bermudez, MD, FPCP, FPRA
OBJECTIVES • To understand the different presentations of the most common CTD’s and other vasculitides. • To be familiar with clinical and laboratory criteria for defining these diseases. • To understand the diagnostic and therapeutic strategies for CTD and other forms of vasculitis.
Case • 23 yr old female • Diagnosed case of rheumatoid arthritis for 4 years • Recent onset of low –moderate grade fever • Anemic, thrombocytopenic • Being treated for recurrent UTI • Decreased breath sounds bibasal • +bipedal edema
Case • What is your initial diagnosis? a. Active rheumatoid arthrtis b. RA with pneumonia c. RA with recurrent UTI d. SLE e. Any of the above
SLE criteria Renal disorder Neurologic disorder Hematologic disorder Immunologic: LAC, antidsDNA, anti-Sm, antiphospholipidAb ANA • Malar rash • Discoid rash • Photosensitivity • Oral ulcer • Arthritis • Serositis
Clinical features • Cardio-pulmonary: pericarditis, valvular insufficiency, pleurisy and pleural effusion; interstitial pneumonitis/fibrosis • Hematologic: anemia, leucopenia, lymphopenia, thrombocytopenia • Gastro-intestinal: nausea, diarrhea, intestinal vasculitis • Ocular: retinal vasculitis • Renal manifestation
Clinical features • Nephritis/Nephrotic syndrome • Idiopathic thrombocytopenic purpura • Autoimmune hemolytic anemia • Fever of undetermined origin • Rheumatoid arthritis
Pathogenesis Abnormal immune response in a susceptible host (gene susceptibility) and environment • Polyclonal and Ag specific T and B lymphocyte hyperactivity defective cell activation, apoptosis and immune complex clearance • Inadequate regulation of that hyperactivity
pathogenesis • Abn. immune response sustained production of pathogenic auto-Ab and immune complexes • Some auto-Ab’s (antidsDNA ) can bind to tissues via charge or cross reactivity, or in immune complexes, and cause complement mediated damage • Some subsets of antidsDNA and anti-RNP can bind and enter living cells altering their function • Other autoAb cause damage by direct binding to cell membranes (RBC’s Platelets) that cause those cells to be phagocytized and destroyed
Drug-induced lupus • Procainamide • Hydralazine • Izsoniazid • Chlorpromazine • D-penicillamine • methyldopa
diagnostics • CBC with platelet • Acute phase reactants: ESR/CRP • Urinalysis • ANA • Other Ab profile: AntiSm,AntidsDNA, Anti-cardiolipin Ab, lupus anti-coagulant (as necessary) • ALT, crea • Renal biopsy: if clinically indicated
Treatment • Corticosteroids • NSAIDS • Antimalarials (hydroxychloroquine, chloroquine) • Cyclophosphamide • Azathioprine, Methotrexate • Mycophenolate mofetil
Prognosis • 90-95% SR at 2 years, 71-80% at 10 years • Poor prognosis: • -high serum crea • -HPN • -nephrotic syndrome • -anemia • -Low albumin • -Low C3
Polymyositis/dermatomyositis • Idiopathic inflammatory myopathies with incidence rate 1 per 100,000; F>M • Diagnostic criteria: • - symmetrical proximal muscle weakness • - typical rash of dermatomyositis (Gottron’s, • Heliotrope rash • - Elevated plasma enzymes • -myopathic changes on EMG • - characterisctic muscle biopsy abn. and the absence of histopath sx of other myopathies
Extra-muscular manifestations • Cardiac: myocarditis, arrythmias • Pulmonary: Pulmo HPN, ILD, aspiration fibrosing alveolitis • Gastro-intestinal: Dysphagia, intestinal vasculitis • Joints: non-deforming arthritis • Renal: ATN, membranous and mesangial GN
diagnostics • Increase muscle enzymes: CPK,AST,LDH,Aldolase • Diagnostics: EMG (electromyography) classic triad • Increased insertional activity and spontaneous fibrillation • Abnormal myopathic, low amplitude short duration polyphasic motor potentials • Bizarre high frequencycharges
Gottron’s papules / collodion patches - Erythematous, scaly flat-topped papules / eruptions over extensor surfaces of IPs joints , can develop central atrophy, with telangiectasia and hypopigmentation. Gottron’s sign or rash - Linear extensor erythema over- lying extensor surface of hands, elbows, knees, medial malleoli.
PM/DM autoantibodies • anti-histidyl T-RNA synthetase Ab / anti-Jo1 autoAb (assoc. with ILD, Raynaud’s, arthritis and mechanic’s hands) • anti-Mi-2 autoAb – acute onset DM with V and shawl rashes • anti-SRP autoantibodies
Muscle biopsy • The definitive test in establishing the dx, and in excluding the many other causes of myopathy • DM: primary lesion in the muscle is located in the blood vessels; cellular infiltrate is perifascicular/perivasvascular; atrophy and fibrosis • PM: cellular infiltrate is within the fascicle with inflam. cells invading the individual muscles
Drug-induced myopathies • Statins • Cyclosporin • Nicotinic acid • Fibrates • Colchicine • Anti-malarials
treatment • Corticosteroids: initial treatment of choice • Other immunosuppressives: • -Azathioprine • -Methotrexate • -Cyclosporin • -CYPT • Experimental: anti-TNF, IFN gamma, • anti-B cell agent(rituximab)
scleroderma • A chronic multi-system disorder of unknown etiology affecting skin and internal organs due to accum. of connective tissues. • Characterized by fibrotic arteriosclerosis of peripheral and visceral vasculature. • Variable degrees of extracellular matrix accumulation (mainly collagen) occur in both skin and viscera. • Associated with specific autoantibodies, most notably anticentromere and anti-Scl-70.
scleroderma • Raynaud’s phenomenon. • Tightening, thickening and non-pitting induration of skin (scleroderma). • Sclerodactyly: above-indicated changes limited to (fingers and toes). • Involvement of internal organs, including gastrointestinal tract, lungs, heart and kidneys, accounts for increased morbidity and mortality. • Risk of internal organ involvement strongly linked to extent and progression of skin thickening.
Categories of SCL • Limited SCL: skin sclerosis restricted/distal to elbows, face, and neck ; includes CREST syndrome ( Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia) -Pulmo HPN after 10-15 years of dse in < 10%. -RP may preceed skin dse by years -anticentromere Ab • Diffuse SCL: extensive skin sclerosis distal and proximal extremities, face and trunk; greater risk of significant renal, lung and cardiac complication. - Raynaud’s onset within 1 year or at time of skin changes -Anti-topoisomerase Ab
Prognosis ♦Px w/ limited SCL esp. those w/ anti-centromere anti-bodies, have a good prognosis. Except in <10% who develop pulmonary HPN later on. ♦Malabsorption syn. and primary biliary cirrhosis are the causes of morbidity and mortality in some px with limited SCL ♦Worse prognosis in px w/ diffuse SCL Death most often occurs from pulmonary cardiac and renal involvement
treatment • DMARDS: D-penicillamine, Methotrexate, cyclosporine, CYPT • Interferon gamma • Steroids for the acute inflammatory phase (tx of myositis); doses >20mg should be avoided—may precipitate SCL renal crisis! • Vasodilators: -prostacyclin analogues; Ca channel blockers; anti-platelet (ASA) for Raynaud’s, pulmo.HPN
MCTD • Undifferentiated CTD • High titers of anti U1RNP distinguishes MCTD from other clinical entities • Presenting features: Raynaud’s, puffy hands, arthralgias, myalgias • Pulmonary HPN is the most common cause of death • 25% develop renal dse (membranous GN) • GI involvement in 70% • Pericarditis in 30%
Vasculitis Syndromes • Primary Vasculitis: Wegener’s granulomatosis, Churg-Strauss Syn.,PAN, MP, GCA, TA, HSP,mixed cryoglobulinemia, Behcet’s syn,isolated vasculitis of the CNS • Secondary Vasculitis: drug-induced, serum sickness, infection, malignancy and rheumatic diseases (rheumatoid vasculitis, lupus vasculitis, Sjogren’s syndrome…)
Mechanism of vessel damage in vasculitis • Pathogenic immune complex formation/deposition -HSP, CVD assoc.vasculitis, serum sickness, Hep B assoc. PAN,HepC asoc. cryoglobulinemia • ANCA production - Wegener’s granulomatosis, microscopic polyangitis,Churg-Strauss syndrome • Pathogenic T lymphocyte response and granuloma formation -GCA, TA, WG, CSS
The Chapel Hill Classification - 1994 • Small Vessel vasculitis: • MPA, CSS, Wegener’s granulomatosis • Medium-vessel vasculitis: • Polyarteritis Nodosa • Large-Vessel Vasculitis: • Giant cell(temporal) arteritis • Takayasu's arteritis • Kawasaki's disease
Classif. of Vasculitis Small vessel vasculitis ANCA associated : • Wegener's granulomatosis • Churg-Strauss syndrome • Microscopic polyangiitis ANCA unassociated • Henoch-Schönlein purpura • Essential cryoglobulinemic vasculitis • Cutaneous leukocytoclastic angiitis
Approach to a patient with vasculitis • Suspect in a px w/ unexplained systemic illness, • Exclude other diseases which may mimic vasculitis Suggestive symptoms: • Palpable purpura • Pulmonary infiltrates • Microscopic hematuria • Chronic inflammatory sinusitis • Mononeuritis multiplex • Unexplained ischemic events • gromerulonephritis
Mimics of vasculitis • Infectious diseases: bacterial endocarditis, dissem.gonococcal infxn., syphilis, pulmonary histoplasmosis • Coagulative microangiopathies: APS, TTP • Neoplasms: atrial myxoma, lymphoma • Drug toxicity: cocaine amphetamines, ergot alakaloids • Sarcoidosis • Atheroembolic disease
Definitive diagnosis and treatment • Biopsy of the involved tissues • Angiogram of the involved organ • * the constellation of clinical, laboratory biopsy and radiologic findings allows for proper categorization to a specific syndrome • Treatment initiated according to the category of specific syndrome.
ACR criteria for Giant Cell Arteritis • Age >50yrs at onset • New type of headache • Elevated ESR • Abnormal temporal artery on clinical examination • Temporal artery biopsy showing vasculitis sensitivity 95% specificty 90.7% *Polymalgia rheumatica and Giant Cell Arteritis: Evidence and Guidelines for diagnosis and management in older people, Age and Aging 2003:32:370-374
GCA Pathogenesis • Activation of circulating monocytes inflammatory cytokines including IL6 acute phase response + systemic Sx • Some of the activated circulating monocyte infiltrate into the walls of large arteries mediated by adhesion molecules prodn. of further inflam.mediators, tissue destruction intimal proliferation and thrombosis vessel occlusion
Giant Cell Arteritis • Clinical: Px >50 who has a new form of headache , abrupt loss of vision, polymyalgia rheumatica, unexplained prolonged fever or anemia, high ESR and palpable tender temporal artery
GCA: Complications • Visual loss: most dreaded complication of GCA • Deaths reported due to acute coronary and cerebral vasculitis • Thoracic aortic aneurysms and aortic dissection, associated with late mortality