SYSTEMIC LUPUS ERYTHEMATOSUS BY DR BASHIR AHMED DAR - PowerPoint PPT Presentation

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SYSTEMIC LUPUS ERYTHEMATOSUS BY DR BASHIR AHMED DAR

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  1. Systemic Lupus Erythematosus By Dr Bashir Ahmed Dar Associate Professor of Medicine Chinkipora Sopore Kashmir Email-- drbashir123@gmail.com

  2. Dr Bashir and Dr yashodhora leading group of medical students to meet noble prize winner in medicine at KL Malaysia

  3. Precious moments with noble prize winner

  4. Dr Bashir at PBL Conference

  5. My Son Yawer Bashir

  6. My Home in Kashmir

  7. SLE is an autoimmune inflammatory disease involving multisystem or multiorgans of the body.

  8. Systemic Lupus Erythematosus • Basically, in autoimmune diseases, the human immune system wrongly recognizes tissues of the body as harmful antigens and so builds a response, targeting self-cells.

  9. Background on Systemic Lupus Erythematosus • Lupus is Latin for wolf, and "erythro" is derived from Greek for "red.“

  10. Background on Systemic Lupus Erythematosus • All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.

  11. Background on Systemic Lupus Erythematosus • In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face.

  12. Background on Systemic Lupus Erythematosus • In other accounts, doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches.

  13. butterfly-shaped malar rash

  14. Background on Systemic Lupus Erythematosus • Another account claims that the term "lupus" did not come from Latin directly, but from the term for a French style of mask that women reportedly wore to conceal the rash on their faces. The mask is called a "loup," French for "wolf."

  15. Background on Systemic Lupus Erythematosus • The term lupus is attributed to 12th-century physician Rogerius, who used it to describe the classic malar rash. • Useful medication for the disease was first found in 1894, when quinine was first reported as an effective therapy.

  16. Background on Systemic Lupus Erythematosus • Four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. • This was the best available treatment until the middle of the twentieth century, when Hench discovered the efficacy of corticosteroids in the treatment of SLE.

  17. Background on Systemic Lupus Erythematosus • Michael Jackson suffered from both SLE and vitiligo.Diagnosed in 1986, and confirmed by his dermatologist, Dr. Arnold Klein, who presented legal documents during court depositions.

  18. Background on Systemic Lupus Erythematosus • Lady Gaga has been tested borderline positive for SLE, however she claims not to be affected by the symptoms yet.Teddi King, American singer, died of SLE complications in

  19. Background on Systemic Lupus Erythematosus • In 1977 Charles Kuralt, former anchor of CBS Sunday Morning, died of SLE complications in 1997.Ferdinand Marcos, former Philippine president, who died of SLE complications in 1989.

  20. Systemic Lupus Erythematosus • Millions of Americans are afflicted with an autoimmune disease, mostly women of childbearing age. Generally, autoimmune diseases are lifelong conditions, although medication and treatment can make quality of life better for the patient.

  21. Systemic Lupus Erythematosus • Predominantly affects females at a rate of almost 9 to 1. • Though disease can affect all ages but most commonly begins from 20-45 years of age. • Common in Hispanic and African-American women than in Caucasian women. • The disease occurs in 1 out of 2,000 Americans and in as many as 1 out of 250 African-American women.

  22. Etiology Heredity/ Genetic Sex hormone status Environmental triggers /Immunological factor s Loss of ‘self-tolerance Complement deficiency

  23. Heredity/ Genetic causes • The most important genes causing SLE are located in the HLA region on chromosome 6, where mutations may occur randomly or may be inherited. HLA class I, class II, are associated with SLE.

  24. Heredity/ Genetic causes • 14 of the genes where linked to SLE patients manifesting a severe form of the disease. • The 14 genes are collectively referred to as the interferon (or IFN) expression signature. The genes are turned on by interferon activity. IFN is a family of proteins that is involved in immune response regulation.

  25. Heredity/ Genetic causes • The data show support for therapies that would block IFN pathways. This may be able to help patients with a more severe form of the disease.

  26. Heredity/ Genetic causes • Genetic predisposition • MHC genes: HLA DR2, DR3, DR4-DIL, DR5- APS • Non-MHC genes: complement component, complement receptor, Fc receptors, CRP, cytokines, apoptotic genes (e.g., FAS)

  27. Heredity/ Genetic causes • Relatives of patients with autoimmune disease often show high incidence of same type of auto-Ab. • And may have some form of autoimmune disease.

  28. But Genetic predisposition is not enough ? need enviroNmental factors

  29. Environmental Factors Causing SLE • These factors not only exacerbate existing SLE conditions but also trigger the initial onset.

  30. Environmental Factors Causing SLE • They include certain medications (such as some antidepressants and antibiotics), extreme stress, exposure to sunlight, hormones, and infections.

  31. Environmental Factors Causing SLE • UV radiation has been shown to trigger the photosensitive lupus rash and some evidence suggests that UV light might be capable of altering the structure of the DNA, leading to the creation of autoantibodies.

  32. Environmental Factors Causing SLE • Researchers have sought to find a connection between certain infectious agents (viruses and bacteria), but no pathogen can be consistently linked to the disease.

  33. Environmental Factors Causing SLE • Some researchers have found that women with silicone gel-filled breast implants have produced antibodies to their own collagen, but it is not known how often these antibodies occur in the general population, and there is no data that show that these antibodies cause connective tissue diseases such as SLE. There is also a small but growing body of evidence linking SLE to lipstick usage,

  34. Environmental Factors Causing SLE • Drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness.

  35. Environmental Factors Causing SLE • Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped. There are about 400 medications that can cause this condition, the most common of which are procainamide, hydralazine, quinidine, and phenytoin.

  36. Environmental Factors Causing SLE • Wide range of possible infection; some genetic combinations result in autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus.

  37. Environmental Factors Causing SLE • Because of genetic variations in different components of the immune system, in some people the immune system attacks these nuclear-related proteins and produces antibodies against them. • In the end, these antibody complexes damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE.

  38. Environmental Factors Causing SLE • Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links.

  39. Environmental Factors Causing SLE • Drugs such as hydralazine, methyldopa, and minocycline can induce lupus not associated with anti-dsDNA. • Drug induced antibodies to histones.

  40. Environmental Factors Causing SLE • Even Provoking factors like • Sunlight, UV light • Infections • Drugs • Isoniacid • Hidantoin • Hydralazin • Procainamide • D penicillinamin • Penicillins • Sulphonamids • TNF alpha blockers • Flare-ups can be induced by the contraceptive pill and hormone replacement therapy (HRT).

  41. HORMONAL FACTORS CAUSING SLE • Estrogen and other female hormones are considered to play a role since women are more likely to be affected. • Progesterone also have been shown to control the activity and production of MMP-9. Surprisingly, MMP-9 activity in females did not correlate strongly with SLE, but did so in male patients.

  42. HORMONAL FACTORS CAUSING SLE • Testosterone reduces immunoglobulin production from peripheral blood as well as mononuclear cells of both normal subjects and patients with SLE. • Improvement of SLE was noted in individual patients who had undergone menopause or ophorectomy.

  43. HORMONAL FACTORS CAUSING SLE • Flares of SLE are well known to occur during periods of rapid hormonal changes. These include pregnancy, puerperium, ovulation stimulation during in vitro fertilisation, and exogenous oestrogen administration.

  44. HORMONAL FACTORS CAUSING SLE • Lupus activity tends to be reduced when patients undergo menopause. It has also been noted that in many women disease flares are more common during the second half of the menstrual cycle, after the midcycle surge of oestrogen.