SLE by Dr.P.Harischandra MBBS MD FICM 11 Aug 2015

1. SLEbyDr.P.Harischandra MBBS MD FICM11 Aug 2015

2. Introduction • Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage initially mediated by tissue binding autoantibodies and immune complexes •  Annual incidence and prevalance in US and Europe: 2-8/100,000 population and 20-60 cases per 100,000 respectvely

3. Aetiological factors in SLE Genetic factors HLA B8,DR 3,DR 2 Inherited compliment deficiencies -Others: Ig receptors,kinases,signallingmolecules,cytokines

4. 1.5 million cases of lupus • Prevalence of 17 to 48 per 100,000 population • Women > Men - 9:1 ratio • 90% cases are women • African Americans > Whites • Onset usually between ages of 15 and 45 years, but • Can occur in childhood or later in life

5. Ranges from a relatively mild disorder to rapidly progressing, affecting many body systems. • Chronic with relapsing and remitting course. • Most commonly affects the skin / muscles, lining of lungs, heart, nervous tissue, and kidneys

7. Pathogenesis of SLE

8. Non genetic factors -UV light [inflammation & tissue damage] Physical and emotional stress [ neuroendocrine changes affecting immune cell function] Infection-EBV,CMV [molecular mimicry,disturbed immune regulation] Female sex hormones [estrogen],[ prolactin -pregnancy flare] Drugs- sulfonamides,hydralazine,methyldopa,isoniazideetc Environmental factors- smoking,silica

9. Pathogenesis -Hyperreactiviyof B lymphocytes -Hypergammaglobulinaemia Multiple organ specific & non specific autoantibodies Circulating immune complexes Complement activation Leucopenia,thrombocytopenia& monocytosis Breakdown of tolerance to self antigen Increased apoptosis & impaired clearance of apoptotic antibodies Tissue damage is d/t immune cx deposition & direct tissue injury

10. Autoimmune reactions directed against constituents of cell nucleus, DNA • Antibody response related to B and T cell hyperactivity

16. 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.

17. Clinical Manifestations • Infection • Increased susceptibility to infections • Fever should be considered serious • Infections such as pneumonia are a common cause of death

18. Fatigueis 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.

21. Clinical Manifestations • Dermatologic • Cutaneous vascular lesions • Photosensitivity • Butterfly rash (Malar Rash) • Oral/nasopharyngeal ulcers • Alopecia

24. Malar Rash

25. Discoid Rash

26. Maculopapular eruption

27. Oral Ulcers

28. 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)

29. Vasculitic skin lesion

30. Clinical Manifestations • Musculoskeletal (jaccoudarthropathy) • Polyarthralgia with morning stiffness • A vascular necrosis • Arthritis bilateral – hands / wrists / knees • Swan neck fingers • Ulnar deviation • Subluxation with hyperlaxity of joints

32. Avacular necrosis of bone

33. Clinical Manifestations • Cardiopulmonary • Tachypnea • Pleurisy • Dysrhythmias • Accelerated CAD • Pericarditis

34. Pulmonary manifestations • Pleurisy it is the most common manifestation of pulmonary involvement of SLE. The volume of pleural effusions usually is small to moderate and maybe unilateral or bilateral. Large pleural effusion are uncommon. It usually exudative in character. Pleural effusions may also occur in SLE patients with nephrotic syndrome, infection, cardiac failure.

35. Lung 1) acute lupus pneumonitis: fever, dyspnea, cough with scanty sputum, hemoptysis, tachypnea and pleuritic chest pain. 2) pulmonary hemorrhage 3) chronic diffuse interstitial lung disease. the diagnosis should not be made until infectious processes such as viral pneumonia, tuberculosis, and other bacterial, fungal and pneumocystiscarinii infection have been completely excluded.

36. Cardiovascular manifestations • Pericarditis is the most common cardiac manifestation of SLE. • Myocarditis (the clinical features of lupus myocarditis resembles that of viral myocarditis) • Libman-Sacks endocarditis and valvular disease • Hypertension, cardiac failure

37. SLE can be associated with endocarditis. • Shown here is Libman-Sacks endocarditis in which there are many flat, reddish-tan vegetations spreading over the mitral valve and chordae.

38. Clinical Manifestations • Renal • Lupus nephritis • Ranging from mild proteinuria to glomerulonephritis • Primary goal in treatment is slowing the progression

40. Haematuria • Proteinure(>0.5g protein/d or 3+ ) • Cast

41. Lupus nephritis

43. Clinical Manifestations • Nervous system • Generalized/focal seizures • Peripheral neuropathy • Cognitive dysfunction • Disorientation • Memory and reasoning deficits • Psychiatric symptoms – severe depression / psychosis

45. Clinical ManifestationsRed blood cells • Normochromic, normocytic anemia is frequently found in SLE. • They appears to be related to chronic inflammation, drug-related haemorrhage. • Haemolyticanemia as detected by the Coombs’ test is the feature of SLE. • Rare occasion, a serum antibody may be produced which impairs red cell production.

46. Platelets -thrombocytopenia (<100*109/L) appears to be mediated by anti-platelet antibodies or/and anti-phospholipid antibodies.

47. White blood cell -Leucopenia (<4.0*109/L), its cause is probably a combination of destruction of white cells by autoantibodies, decreased marrow production, increased or marginal splenic pooling, and complement activation. -it should also noted that the immunosuppressive drugs used in the treatment of SLE may cause a marked leucopenia.

48. Gastrointestinal and hepatic manifestation • Esophagitis, dysphagia, nausea, vomiting: (drug related in most cases) • Chronic intestinal pseudo-obstruction, mesenteric vasculitis, protein-losing enteropathy • Pancreatitis • Lupus hepatitis

49. On examination • Constitutional – lymphadenopathy, hepatosplenomegaly • Musculoskeletal – Jaccoudarthropathy • Dermatologic - capillaroscopy • Renal • Neuropsychiatric • Cardiopulmonary – friction rubs, pulmonary embolism, Libman-Sacks endocarditis • GIT – peritonitis, pancreatitis, mesenteric vasculitis