What is Systemic LupusErythematosus (SLE)? S.L.E. Lupus Foundation Educational Program Laura Geraldino, MD January 16th. 2013
Outline• Introduction – Immune system – Autoimmunity• Common manifestations: – Skin and mucosas – Musculo-skeletal – Serositis – Kidneys – Nervous system• Morbidity and mortality
Immune System• Complex collection of organs, cells and cell products that work together to protect the body from foreign substances and disease, caused mainly by pathogens.• Plays a direct role in immunization, infectious diseases, allergies and autoimmune diseases.
Autoimmune Diseases• Disarray in the immune system can lead to an attack of self.• Illnesses that occur when the body tissues are attacked by its own immune system.
SLE SLE is…• Complex autoimmune disease characterized by “self-attacking” antibodies.• Symptoms vary from individual to individual.• Unpredictable course and prognosis.Ruiz-Irastorza G, Khamashta MA, Castellino G, Hughes GR. Systemic lupus erythematosus. Lancet 2001;357:1027–32.
SLE SLE is not…• NOT curable but controlled: – Flares (exacerbation) vs. remission (very few or no symptoms).• NOT transmittable.
ACR Classification Criteria• Malar rash • Glomerulonephritis (kidney)• Discoid rash • Neuropsychiatric Lupus (brain)• Sensitivity to the sun • Low blood cell counts• Ulcers in mouth and nose • Positive ANA• Arthritis • Other antibodies: – Smith Ab, dsDNA Ab,• Pericarditis/pleuritis – anti-Cardiolipin Ig
Malar RashRheumatology e-dition, 4th Edition. Marc C. Hochberg, MD, MPH, Alan J. Silman, MD, Josef S. Smolen, MD, Michael E. Weinblatt, MD and Michael H. Weisman, MD
Cutaneous Discoid lesions Oral UlcersRheumatology e-dition, 4th Edition. Marc C. Hochberg, MD, MPH, Alan J. Silman, MD, Josef S. Smolen, MD, Michael E. Weinblatt, MD and Michael H. Weisman, MD
Arthritis • Joint pain constitute the most common presenting manifestation of SLE.Rheumatology e-dition, 4th Edition. Marc C. Hochberg, MD, MPH, Alan J. Silman, MD, Josef S. Smolen, MD, Michael E. Weinblatt, MD and Michael H. Weisman, MD
“Serositis”• Inflammation of the membranes covering the lungs, heart and abdominal cavity.
Lupus Pleuritis• Recurrent chest pain with breathing occurs in 45% pts.• Pleural effusion (fluid around the lungs) in 30%. Bilateral in 50%. Usually small.• Chest pain and pleural effusions are the initial manifestation in 3% and 1% of pts, respectively. Diagnosis and management of lupus pleuritis. Der-Yuan Wang, MD, FCCP. Current Opinion in Pulmonary Medicine
Lupus Pleuritis • Attacks of this chest pain often lasts several days to several weeks. • Most patients have fever, cough and difficulty breathing.Diagnosis and management of lupus pleuritis. Der-Yuan Wang, MD, FCCP. Current Opinion in Pulmonary Medicine 2002, 8:312–316
Lupus nephritis• Involvement of the kidneys during the course of the disease occurs in up to 60% of cases, resulting in worsening morbidity and mortality. Houssiau FA. Management of lupus nephritis: an update. J Am Soc Nephrol 2004;15:2694–704.
Lupus nephritis • A major feature of lupus in the kidneys is the considerable degree of variation in severity. • Nearly 1/3 progressing to advanced kidney disease, while the others either respond to therapy and follow a milder course. • The course, response to therapy, and outcome are heterogeneous among affected individuals.Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli.Peterson KS, Huang JF, Zhu J, DAgati V, Liu X, Miller N, Erlander MG, Jackson MR, Winchester RJ. J Clin Invest. 2004 Jun;113(12):1722-33.
Lupus Nephritis ClassesClass II (mesangial) Class III (focal proliferative) Class IV (diffuse proliferative) Class V (membranous) Class VI (advanced sclerosis) WHO Classification
Lupus in the Nervous System• Severe nervous system involvement in lupus is relatively uncommon but can lead to significant morbidity and mortality if not managed adequately.• It has been reported to occur in 14% to 80% of lupus patients.Muscal E, Brey RL . Neurologic manifestations of systemic lupus erythematosus in children and adults. Neurol Clin. 2010 Feb;28(1):61-73.KY Fong, J Thumboo. Neuropsychiatric lupus: clinical challenges, brain-reactive autoantibodies and treatment strategies. Lupus 2010 19: 1399
19 Neuropsychiatric Lupus syndromesCentral nervous systemAseptic meningitis Peripheral nervous systemCerebrovascular disease Acute inflammatory demyelinatingDemyelinating syndrome polyradiculoneuropathy (Guillain- Barre´ syndrome)Headache (including migraine and benignintracranial hypertension) Autonomic disorderMovement disorder (chorea) Mononeuropathy, single/multiplexMyelopathy Myasthenia gravisSeizure disorders Neuropathy, cranialAcute confusional state PlexopathyAnxiety disorder PolyneuropathyCognitive dysfunctionMood disorderPsychosis The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999 Apr;42(4):599-608.
“Positive ANA”•Does NOT mean you have lupus.•Good screening test- practically all patientswith lupus. BUT not a specific test.
Other manifestations…•Fatigue•Fever•Hair loss•Purple fingers in the cold•Blood clots
Morbidity •Leading cause of kidney disease, strokes and heart disease in childbearing age women. •35-44 y/o lupus patients are 50 times more likely to have a heart attack. •2X increased risk for carotid plaque (atherosclerosis). (<40y/o) •Disability.(1) Manzi S. et al. Am J Epidemiol. 1997;145;408-415. (2) Esdaile JM et al. Arthritis Rheum. 2001; 44 (10):2331-2337 (3) Roman MJ et al. N Engl J Med. 2003; 349: 2399-2406
Mortality Mortality • Over the past 50y, 5y- survival in lupus pts improved from 50% in 1955 to 82-95% in 1990s. SLE pts in the 1950–1979 cohort. Pop=population; MN-W=Minnesota whites •However, lupus patients have a 3-5X increased mortality compared to the general population. SLE pts in the 1980–1992 cohort.Trends in the incidence and mortality of systemic lupus erythematosus, 1950-1992. Uramoto KM, Michet CJ Jr, Thumboo J, Sunku J, OFallon WM, Gabriel SE. Arthritis Rheum.1999 Jan;42(1):46-50.
NP SLE Related Abs Take home points• SLE (lupus) is a complex autoimmune disease that can affect a large variety of organs and have different manifestations from patient to patient.• Most common initial symptoms are rashes and joint pains.• About 2/3 of patients with lupus have kidney involvement.
NP SLE Related Abs Take home points• The course of the disease and prognosis are unpredictable.• Morbidity and mortality is increased in lupus patients.• Early diagnosis and close disease activity monitoring are essential to achieve better outcomes.
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