Systemic lupus erythematosis

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SYSTEMIC LUPUS ERYTHEMATOSIS

SYSTEMIC LUPUS ERYTHEMATOSUSHistory Evolution Etiology pathopysiology Management & what is new Karunan KannampoyililSeethaprakashPictures by Little Darling K & Novakarun K2014 JanLupus NephritisSLE What is New 1.Introduction2.History3.Epidemiology4.Pathophysiology5.Pathology6.Autoimmunity7.Clinical features8.Diagnosis9.Management10.Future

INTRODUCTION Systemic Lupus Erythematosus (SLE) is a Chronic,usually life-long, potentially fatal autoimmune disease characterized by unpredictable exacerbations & remissions with variable clinical manifestations.Clinical manifestations differ from

one patient to another

Heterogeneous disorder

Over lap can occur

Tissues & cells undergo damage due to binding of auto antibodies and immune complexes.

Altered patterns of immuno regulations producing auto anti bodies and abnormalities of cell mediated immunology(CMI)

Precise etiology unknown & remains to be definedGeneticEnvironmental Hormonal factors

These factors interact to form complex relations between the host, pathogens & the environment Recent advances in genetic research, newly discovered genes confirm, the preexisting concept of pathogenesis. New biologic insights

Burden of the diseaseTwin burden of Lupus

Physical burden of illness & it is potential seriousness

Intense fear which accompanies the illnessSeveral defects of immunological components play a role

Ability to produce pathogenic auto antibodies

Lack of T&B-lymphocyte regulation

Defective clearance of autoantigens & immune complexes

Majority of autoantibodies are directed at intracellular nucleoprotein particles,

Antinuclear antibodies(ANA) 98%

Anti-double-stranded DNA (dsDNA) antibodies are found in 5080%

Auto antibodies are exclusive to lupus.

SLE1.Introduction2.History3.Epidemiology4.Pathophysiology5.Pathology6.Autoimmunity7.Clinical features8.Diagnosis9.Management10.Future

HISTORY

Hippocrates (~400BC) cutaneous ulcers (herpes esthiomenos.

Biett 1833. first clear description of lupus erythematosus

Cazenave and Clausit. 1850s coined 'Lupus Erythemateux They made the first description of the facial rash and skin ulceration resembling 'a bite from a wolf', from which some think lupus (Latin for wolf) derives its name

'.

Eurasian wolf(Canis lupus lupus)

Wolf (Lupus)

LupusWolf mutilates its prey before it eats without killing, in the similar way the SLE does.

Ref:. Graves, Will (2007).Wolves in Russia: Anxiety throughout the ages. Detselig Enterprises.ISBN1550593323 They kill large prey by biting large chunks of flesh from the softperineumarea, causing massiveblood loss. Such bites can cause wounds 1015cm in length, with three such bites to the perineum usually being sufficient to bring down a large deer in optimum healthSLEsecond most common human autoimmune disease in the world.

Ref: Can morbidity and mortality of SLE be improved?AnurekhaBongu ElizabethChang RosalindRamsey-GoldmanBest Practice & Research Clinical Rheumatology Volume 16, Issue 2, April 2002, Pages 313-332 Northwestern University Medical School, ArthritisChicago Ave, Chicago, IL, 60611, USA.Available online 10 June 2002.

SLESLE is the second most common autoimmune disorder (after thyroid disease) in women of childbearing age. Lupus is increasingly being recognized throughout the world's population. The incidence and prevalence of SLE varies among racial and ethnic groups. Lupus patient survival has significantly improved over the past five decades,But a three- to fivefold increased risk of death remains compared with the general population. As lupus patients survive longer, these individuals face a range of complications from the disease itself or consequent to its treatment.Emerging data from epidemiological studies underscore the importance of incorporating race and ethnicity in understanding the risk factors leading to the significant burden of mortality and morbidity associated with this disease; AnurekhaBongu Elizabeth

Prevalence of SLE IndiaA point prevalence of 3.2 per 100 000 (95% CI = 0-6.86 per 100 000).

Ref: Prevalence of Systemic Lupus Erythematosus in India(North) A.N. Malaviyadoi:10.1177/096120339300200209. LupusApril 1993vol. 2no. 2115-118INDIA - FEMALEMajority of the sufferers are females of the menstruating period.

It affects predominantly women in their reproductive years. The median age of onset in IndianSLE is 24.5 years and the sex ratio (F: M) is 11:1Ref: A Kumar J: INDIAN GUIDELINES ON THE MANAGEMENT OF SLE. Indian Rheumatol Assoc 2002 : 10 : 80 - 96

We are still in the dark to find out a cause for this illness but we know that it is an autoimmune disease. Large number of drugs that fight against the illness was already there in the armamentarium and more in the pipe line.

But alas! Nothing found to be use full for the majority of SLE patientsWhos destiny is to land in the dialysis room orKidney transplant arena with end stage Kidney failure and Those who escaped from suffering by reaching at the graveyards in the young age.AmericansAutoimmune diseases are common.

Aaffecting > 23.5 million Americans.

A Leading cause of death and disabilityUnfortunate?Unable to cut short Treatment cost Sufferings Morbidity Mortality

Their future is bleak. Some rays of hope Lande, Christian Goosmann, and various others

Unveiling of the pathologic

Cellular mechanism of the autoimmunity

Ref: 1. Roberto Lande, et al.Peptide Complexes in Systemic Lupus Erythematosus Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA.Sci Transl Med 3, 73ra19 (2011 2. Volker Brinkmann, Britta Laube, Ulrike Abu Abed, Christian Goosmann, Arturo Zychlinsky.Neutrophil Extracellular Traps: How to Generate and Visualize Them. www.youtube.com/poyilil . Video Article 3.M. J. Shlomchik, Activating systemic autoimmunity: Bs, Ts, and tolls. Curr. Opin. Immunol.21, 626633 (2009).AutoimmunityBy the breakdown of tolerance to nuclear self-antigens, which leads to activation of autoreactive Bcells that produce utoantibodies against self-nucleic acids and associated proteins.Autoimmunity in SLE Results from hyper reactive B cells which initiate the T Helper/ suppressor deregulation results in the release of neutrophils characterized by chronic activation of plasmacytoid Dendritic Cells (pDCs) and production of autoantibodies against nuclear self-antigens.

Ref: L. Rnnblom, V. Pascual, The innate immune system in SLE: Type I interferons and dendritic cells. Lupus 17, 394399 (2008). Organ specific expressionsThese autoantibodies bind self-nucleic acids released by dying cells, and form immune complexes that are deposited in different parts of the body, leading to detrimental inflammation and tissue damage.Expressions of basic defects This results in various autoantibody production and deposition of immune complex in various organs. Sir William Osler (1903) first mention

He described 20 young ladies with skin rashes and chest pain resulting from inflammation of the lining of the lung (pleurisy) or heart (pericarditis)

In addition, these patients also had kidney disease, strokes and brain involvement severe enough to be fatal so that 18 had died within two years from presentation

27Over the next 30 yearsPathologic studies documented the existence of nonbacterial verrucous endocarditis (Libman-Sacks disease) & wire-loop lesions in glomerulonephritis.

Kemperer and colleagues in ( 1941) autopsy termed collagen vascular disease

This terminology, persists in usage now fifty years after its introduction

THE MODERN ERAHargraves (1948) discovery of LE cell

Friou, 1950s immunofluorescent test for ANA.

Isenberg. Recognition of antibodies to DNA.

The description of antibodies to extractable nuclear antigens (nuclear ribonucleoprotein (nRNP, Sm, Ro, La).

Hughes. Anticardiolipin antibodies.

Two other major advances in the modern era 1. Development of animal models of lupus The first animal model of systemic lupus was the F1 hybrid New Zealand Black/New Zealand White mouse.16

RECOGNITION OF THE ROLE OF GENETICS Leonhardt in 1954 - familial occurrence

studies by Arnett and Shulman at Johns Hopkins.

Finally, no discussion of the history of lupus is complete without a review of the development of therapyPayne(1894) quinine in lupus.

Four years later, the use of salicylates in conjunction with quinine.

It was not until the middle of this century that adrenocorticotrophic hormone and cortisone by Hench revolutionized SLE treatment.INDIAFirst case 1965 , Then a series of eight cases, till 1969.

1968- clinical immunology laboratory in New Delhi

SLE was extensively studied and reported

Based on these data, the present report describes the clinical and laboratory characteristics of 1366 SLE patients seen in different regions of India

Ref A Kumar , INDIAN GUIDELINES ON THE MANAGEMENT OF SLE, J Indian Rheumatol Assoc 10 : 80 96: 2002. Ref:Malaviya AN, Chandrasekaran AN, Kumar A, Sharma PN. Occasional series-Lupus round the world: systemic lupus Erythematosus in India. Lupus 1997; 6: 690-700.

SLE