Systemic lupus erythematosus
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Systemic lupus erythematosus

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Systemic lupus erythematosus Systemic lupus erythematosus Presentation Transcript

  • Systemic Lupus ErythematosusProf DR Dr Ariyanto Harsono SpA(K)Dept Pediatrics, Airlangga University, Surabaya, Indonesia.
  • Definition:SLE is A disease of unknown cause, ischaracterized by auto antibodies directedagainst self-antigen and resulting ininflammatory damage including thekidney, heart, blood cells and the CNS2Prof DR Dr Ariyanto Harsono SpA(K)
  • The diverse presentations of lupus range fromrash and arthritis through anaemia andthrombocytopenia toserositis, nephritis, seizures, and psychosis.Lupus should be part of the differentialdiagnosis in virtually any patient presentingwith one of these clinical problems, especiallyin female patients between 15 and 50 years ofage.Prof DR Dr Ariyanto Harsono SpA(K)
  • Genetic and Environmental Factors Since 90% of patients with lupus are female, animportant role for female hormones seems likely, but aprotective role for male hormones or an effect of geneson the X chromosome is also possible. In ablinded, randomized, controlled trial, menopausalwomen with lupus who received hormone-replacement therapy containingconjugated estrogensand progesterone had a risk of a mild-to-moderatedisease flare that was 1.34 times the risk amongwomen who receivedplacebo (P=0.01). However, trialsof hormonal treatments for lupus, such as dehydroepiandrosterone, have been disappointing.It is unclearhow sex hormones could promote lupus.Prof DR Dr Ariyanto Harsono SpA(K)
  •  Many drugs cause a variant of lupus called drug-induced lupus.The best known of these drugs areprocainamide, hydralazine, isoniazid and quinidine. Patients withdrug-induced lupus usually present with skin and jointmanifestations; renal and neurologic features are very rare. An antecedent viral-like illness may occur at the onset of lupus orimmediately before a flare. Identifying a particular causative virushas proved challenging. Epstein–Barrvirus (EBV) may beimportant, since a temporal association between the onset oflupus and the occurrence of EBV infection has been reported. Acase–control study involving children and young adults showedthat anti-EBV antibodies were present in 99% and EBV DNA waspresent in 100% of patients with lupus — much higherproportions than those in the control group. Ultravioletradiation is the most obvious environmental factorlinked tolupus.Prof DR Dr Ariyanto Harsono SpA(K)
  • 6Prof DR Dr Ariyanto Harsono SpA(K)
  • Prof DR Dr Ariyanto Harsono SpA(K) 7Prof DR Dr Ariyanto Harsono SpA(K)
  • PathogenesisAuto antibodies in Lupus The affected organs in lupus that have been studiedmost intensivelyare the kidneys and the skin. In bothcases, there is inflammation and the deposition ofantibodies and complement. In 1967, kidneys frompatients with lupus nephritis were shown to containantibodiesthat bound native, double-stranded DNA.These antibodies areauto antibodies; that is, they binda normal constituent , double-stranded DNA — of thepatients cellsand tissues. The importance of anti–double-stranded DNA antibodies in the pathogenesis oflupus has been confirmed.Prof DR Dr Ariyanto Harsono SpA(K)
  •  Anti–double-stranded DNA antibodies are highlyspecificfor lupus; they are present in 70% of patientswith lupus butin less than 0.5% of healthy people orpatients with other autoimmunediseases such asrheumatoid arthritis. Levels of anti–ds-DNA antibodiesin serum tend to reflect disease activity, but not in allpatients. Among patients who have both elevatedlevels of anti–double-stranded DNA auto antibodiesandclinically quiescent disease, 80% have disease thatbecomesclinically active within 5 years after thedetection of elevatedlevels of these antibodies.
  •  In a study of renal-biopsy specimens obtained from patients withlupus at autopsy, detected IgG that bound to a number of non-DNAantigens, including Ro (a ribonucleoprotein complex), La (an RNA-binding protein), C1q (a subunit of the C1 complementcomponent), and Sm (nuclear particles consisting of several differentpolypeptides). The detection of antibodies to these antigens inautopsy specimens does not prove that they play a role in thedevelopment of lupus nephritis. Rather than cause theinflammation, these auto-antibodies may establish themselves intissue only after the apoptosis of cells in inflamed kidney tissueexposes nuclear antigens. The strongest evidence concerning themechanism of lupus nephritis relates to anti–double-strandedDNA, anti-nucleosome, and anti– -actinin antibodies. Although anti–double-stranded DNA antibodies are the mostextensively studied auto-antibodies in lupus, others play a roleinclinical manifestations, particularly in autoimmune haemolyticanaemia, thrombocytopenia, skin disease, and neonatal lupus.
  • Tissue Damage by Auto antibodies in LupusMost studies of autoantibody-mediated tissue damage in patientswith lupus have focused on the role of anti–ds-DNA antibodies inpatients with lupus nephritis. There are two main theories; bothstress that the binding of antibodies to double-stranded DNA itselfis probably not the most criticaldeterminant of tissue damage.Extracellular double-stranded DNA occurs mainly in the form ofnucleosomes, which are fragments of chromatin that cells releasewhen they undergo apoptosis. Pathogenic anti–ds-DNA autoantibodies in patients with lupus bind to nucleosomes that haveentered the bloodstream; in turn, these antibody–nucleosomecomplexes settle in the renal glomerular basement membrane.Prof DR Dr Ariyanto Harsono SpA(K)
  • These immune complexes activatecomplement, which initiates theglomerulonephritis. This series of events has beendemonstrated in animal models. Furthermore, IgGantibodies have been shown, by means ofelectron microscopy, to co-localize withextracellularchromatin in lupus nephritis inhumans and mice. Also relevantis the detectionof anti-nucleosome antibodies in the blood andinflamed tissues of patients with lupus.Prof DR Dr Ariyanto Harsono SpA(K)
  • The second model proposes that anti–ds DNA, anti-nucleosomeantibodies, or both cross-react with proteins in the kidney;thus, they have a direct pathogenic effect on renal cells. This is anexample of polyreactivity, whereby the same antibody can bind toantigens with different structuresbecause they have similar surfaceshapes (so-called shared epitopes) or areas of similar charge.Among possible target antigens in the kidney, attention is currentlyfocused on actinin. This protein is critical for maintaining thefunction of renal podocytes,which are constituents of theglomerular filtration barrier.Two studies have shown that mousemonoclonal anti-DNA antibodies that cross-reacted with actinin (aprotein that cross-linksactin, a component of the cytoskeleton)were pathogenic, whereas monoclonal anti-DNA antibodies that didnot cross-react with -actinin were non pathogenicProf DR Dr Ariyanto Harsono SpA(K)
  • Pathogenicity was judged accordingto whetherthe antibodies caused proteinuria and histologicchanges of glomerulonephritis after passivetransfer into recipientmice. Although anti -actinin antibodies are not specificfor lupus, theseantibodies, when present in the serum ofpatientswith lupus, can serve as a marker ofrenal involvement.The detection of anti- -actininantibodies has not been reported in specimensobtained from renal biopsies in patients withlupus.Prof DR Dr Ariyanto Harsono SpA(K)
  • 15Prof DR Dr Ariyanto Harsono SpA(K)Immune Response in SLE
  • Source of the Autoantigens in LupusThe obvious source of nucleosomes is the cellulardebris released as a result of apoptosis. Duringapoptosis, blebs of cellular material form on thesurface of the dying cell. Antigens thatare normallyburied within the cells are exposed on the surfaceof these blebs, and they may trigger an immuneresponse. These exposed antigens includenucleosomes, Ro 62, Ro 50, La, and anionicphospholipids. Antibodies to these antigens occurcommonly in patients with lupus.Prof DR Dr Ariyanto Harsono SpA(K)
  • 17Prof DR Dr Ariyanto Harsono SpA(K)
  • Prof DR Dr Ariyanto Harsono SpA(K) 18Prof DR Dr Ariyanto Harsono SpA(K)
  • Diagnosis
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 20
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 21
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test 22Prof DR Dr Ariyanto Harsono SpA(K)
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 23
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 24
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 25
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 26
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 27
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 28
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 29
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 30• Haemolytic Anemia• Low white blood cellscount• Low thrombcyte count
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 31LE CellProf DR Dr Ariyanto Harsono SpA(K)
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 32LE Cell
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 33LE CellAnti ds-DNA
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 34Anti Ro
  • DIAGNOSIS of SLEACR cRITERIASkin: Malar Rash Discoid rash Oral ulcers Photo sensitive rashSystemic Criteria Arthritis Serositis Kidney Disorder Neurologic Disorder Hematolic DisorderLaboratory Criteria Immunologic Disorder Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 35Anti Nuclesr Antibody
  • Prof DR Dr Ariyanto Harsono SpA(K) 36
  • Prof Ariyanto Harsono MD PhD SpA(K) 37
  • 38Prof Ariyanto Harsono MD PhD SpA(K)
  • 39Prof DR Dr Ariyanto Harsono SpA(K)Anti Nuclear Antibody
  • 40Prof DR Dr Ariyanto Harsono SpA(K)Anti ds_DNA
  • 41Prof DR Dr Ariyanto Harsono SpA(K)Anti Ro
  • Skin Biopsy42Prof DR Dr Ariyanto Harsono SpA(K)Superficial and deep perivascular lymphocyteinfiltrate with increased mucin deposition inthe dermis.
  • Fig. 9-1-3-Autoimmune hepatitis.Lobular inflammation and focal necrosis. 43Prof DR Dr Ariyanto Harsono SpA(K)Prof DR Dr Ariyanto Harsono SpA(K)
  • Giant multinucleated hepatocytes.Inflammatory infiltration in the lobule44
  • Cerebral Lupus45Cerebral ischemia
  • Clinical Manifestation by Target Organ46Prof DR Dr Ariyanto Harsono SpA(K)
  • 47Prof DR Dr Ariyanto Harsono SpA(K)
  • 48Prof DR Dr Ariyanto Harsono SpA(K)
  • Bulous Eruption49Prof DR Dr Ariyanto Harsono SpA(K)
  • Mouth Ulcer50
  • disseminated lupus51Prof DR Dr Ariyanto Harsono SpA(K)
  • Malar Rash52Prof DR Dr Ariyanto Harsono SpA(K)Malar RashProf DR Dr Ariyanto Harsono SpA(K)
  • Alopecia53Prof DR Dr Ariyanto Harsono SpA(K)AlopeciaProf DR Dr Ariyanto Harsono SpA(K)
  • 54Prof DR Dr Ariyanto Harsono SpA(K)
  • Prof DR Dr Ariyanto Harsono SpA(K) 55Prof DR Dr Ariyanto Harsono SpA(K)
  • Deep venous thrombosis. Notice the contrast between the involved left leg andthe normal right leg. Redness, swelling, and warmth combined with discomfort inthe involved leg are cardinal manifestations of a deep venous thrombosis.Prof DR Dr Ariyanto Harsono SpA(K) 56Prof DR Dr Ariyanto Harsono SpA(K)
  • Subacute cutaneous lupus erythematosusLesions, most prominent in sun-damagedskin, consist of non-scarringpapulosquamous lesions which areoften polycyclic. Classic DLE lesionsthough may be found in some patients.Some criteria of SLE may also bepresent.Unlike discoid lupuserythematosus, follicular plugging is nota prominent feature.Arthritis is a common feature.Anti-Ro and anti-La are frequentlypositive.SCLE may be triggered by drugs such ashydrochlorothiazide and griseofulvin.Children born to mothers with SCLE mayhave neonatal LE.Prof DR Dr Ariyanto Harsono SpA(K) 57
  • Discoid Lupus58Prof DR Dr Ariyanto Harsono SpA(K)Discoid rash
  • Raynaud Phenomena59Prof DR Dr Ariyanto Harsono SpA(K)
  • Vasculitis60Prof DR Dr Ariyanto Harsono SpA(K)
  • Lupus profundus61Prof DR Dr Ariyanto Harsono SpA(K)
  • Photosensitive rash62Prof DR Dr Ariyanto Harsono SpA(K)
  • Necrotizing Sleritis, is rare inSLE Retinal involvement in SLE is the secondmost common ocular manifestation63Prof DR Dr Ariyanto Harsono SpA(K)
  • Retinopathy64Prof DR Dr Ariyanto Harsono SpA(K)
  • Serositis65Prof DR Dr Ariyanto Harsono SpA(K)serositis
  • IgA Nephropathy Lupus nephritis66Prof DR Dr Ariyanto Harsono SpA(K)
  • Thrombotic microangiopathy67Prof DR Dr Ariyanto Harsono SpA(K)
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  • lymphadenitis69Prof DR Dr Ariyanto Harsono SpA(K)
  • 70Prof DR Dr Ariyanto Harsono SpA(K)
  • 71
  • Two trials have shown that a strategy of increasing dosesof corticosteroids in response to a specified increase inlevels of anti–double-stranded DNA antibodies leads tolower mean levels of such antibodies and reducedfrequency of severe flares of disease, but one studyindicated that the side effects of corticosteroids were aproblem. Rituximab and abetimus sodium have been usedas specific methods of reducing levels of anti–double-stranded DNA. Rituximab is nonspecific; that is, it is anantibody against CD20, which is found on the surface of allmature B cells.Prof DR Dr Ariyanto Harsono SpA(K)
  • Abetimussodium is designed to deplete only B lymphocytes thatproduceanti–double-stranded DNA antibodies because its foursurfaceoligonucleotides can engage surface anti–double-strandedDNA antibodies on those cells, but it has no epitopes to allowbinding of helper T cells. The B cells therefore undergo apoptosisrather than proliferation, but it is not clear whether this depletingmechanism occurs in patients. Abetimus sodium mayalso work byforming complexes with anti–double-stranded DNAantibodies, which are then cleared from the circulation.Prof DR Dr Ariyanto Harsono SpA(K)
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