SYSTEMIC LUPUS ERYTHEMATOSUS Year 4 Internal Medicine Notes

SYSTEMIC LUPUS ERYTHEMATOSUS Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.3 / NGUGI -- Slide 1 SYSTEMIC LUPUS ERYTHEMATOSUS DR. ROSSLYN NGUGI Slide 2 Systemic Lupus erythematosus ( SLE ) is a syndrome of unknown aetiology most commonly affecting young women. Virtually any organ of the body may be involved. Typically the course of the disease is a series of remissions and exacerbations. With good management, the ten years survival may be over 90%. INTRODUCTION Slide 3 Etiology and Pathogenesis of SLE Slide 4 1. Genetic factor Many studies have described familial aggregation of SLE. 5-13% of lupus have at least one first or second degree relative with lupus It was found a 24-58% concordance in monozygotic twins. 2-5% concordance in dizygotic twins or siblings.. The risk of a child developing lupus born from a mother (or father) with lupus is calculated to be 3-4% at worst. Slide 5 What are the reasons of Genetic susceptibility? It seems likely that most of the genes predisposing to SLE are normal. An individual inherits an unlucky combination of normal genetic polymorphisms, each of which permit a little immune overreponse, or presentation of high quantities of target antigens in certain tissues. The combination of which is just enough to permit SLE to evolve after some environmental stimulus. C2, C4, C1q deficiencies, DR2, DR3, 1q41-42 region, Fc-r RIIA, IL10 and Bcl polymorphisms. Slide 6 2.. Environmental factors UV light, especially UVB, flares SLE in most patients. It is unclear whether exposure to UV light can initiate the lupus, but onset after a sunburn is not unusual. There is good evidence that exposure of skin to UV light alters the location and chemistry of DNA as well as the availability of Ro and RNP antigens. Drug-induced lupus. Drugs ( hydralazine, procainamide, beta-blokers, isoniazid, penicillamine) can induce lupus. Drug-induce lupus may resemble SLE both clinically and serologically. Usually the disease is mild, and renal and neurological complications are rare. Generally, lupus that is caused by a drug exposure goes away once the drug is stopped. Slide 7 Allergy. Does it induce lupus flare? No direct evidence. Infection. There has been continuing interest in the possibility that infectious agents might initiate or flare SLE. Mechanism might include molecular mimicry between external Ag and a self-Ag, epitope spreading, nonspecific activation of T or B cells. There has been recent interest in EB, CMV and other virus. Slide 8 3. Sex hormones Female: Male=9:1 The sex difference is most prominent during the female reproductive years. In mice, castrating females and /or providing androgens or antiestrogens protects from disease,whereas castrating males and providing estrogens accelerates and worsens SLE. Slide 9 The metabolish of sex hormone is abnormal in some lupus patients. Men and women with lupus metabolized testosterone more rapidly than normal, and estrogenic metabolites of estradial persist longer in women. Neuroendocrine system. Hyperprolactinemia, abnormalities in hypothalamic and/or pituitary function. Slide 10 4. Abnormal immune system Sustained presence of autoantigens: increased apoptosis, impaired clearance of apoptosis Hyperactivity in B and T lymphocyte. Increased expression of surface molecules participating in cell activation in both B- and T- cell. Overproduction of IL-6 and IL-10 Defective regulatory mechanism. Slide 11 Autoantibodies to DNA, RNA, and a host of other cell nucleus antigens. Circulating immune complexes are frequently observed and these may deposit in the kidney, skin, brain, lung, and other tissues. It causes inflammation and tissue damage by a number of mechanism, notably fixation and activation of the complement system. Slide 12 Overview of the pathogenesis of SLE Skin cell T cell T cell B cell APC APC Defective IC clearance UV light Infection External Ag Self Ag Ab IC Target Genetic susceptibility Slide 13 Clinical manifestations of SLE Slide 14 The clinical spectrum of SLE is very broad It make SLE both fascinating but potentially difficult to diagnose and manage. Slide 15 General symptoms The most common symptoms listed as initial complaints are fatigue, fever, and weight loss. Fever: fever secondary to active disease was recorded from 50% to 86%. No fever curve or pattern is characteristic. It can be difficult, but very important to distinguish the fever of SLE from that caused by complicating infections. Slide 16 Fatigue is common in patients with SLE, especially during periods of disease activity. It is also often the only symptom that remains after treatment of acute flares. Low grade fever, anemia, or any source of inflammation can result in fatigue. Slide 17 Raynaud’s phenomenon is commonly found in lupus. It lack specificity. (a triphasic reaction of distal digits to cold or emotion, in which the skin colour changes from white to blue to red) Slide 18 Dermatological involvement Up to 85% of SLE Butterfly rash Maculop