Systemic Lupus Erythematoses

SLE - explained

1. Systemic Lupus Erythematosus (SLE) Dr. Angelo Smith M.D WHPL

2. Autoimmune disease that affects multisystems 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

3. Clinical Manifestations 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

4. Etiology Etiology is unknown Most probable causes Genetic influence Hormones Environmental factors Certain medications

5. Pathogenesis of SLE

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

7. 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.

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

9. 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.

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

11. Malar Rash

12. Discoid Rash

13. Maculopapular eruption

14. Oral Ulcers

15. 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)

16. Vasculitic skin lesion

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

18. Avacular necrosis of bone

19. Clinical Manifestations Cardiopulmonary Tachypnea Pleurisy Dysrhythmias Accelerated CAD Pericarditis

20. 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.

21. 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 pneumocystis carinii infection have been completely excluded.

22. 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

23. 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 .

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

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

26. Lupus nephritis Class I Minimal mesangial Normal light microscopy; abnormal electron microscopy Class II Mesangial proliferative Hypercellular on light microscopy Class III Focal proliferative <50% glomeruli involved Class IV Diffuse proliferative >50% glomeruli involved; segmental/global Class V Membranous Predominantly nephrotic disease Class VI Advanced sclerosing Chronic lesions and sclerosis

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

28. Clinical Manifestations Red blood cells a normochromic , normocytic anemia is frequently found in SLE. They appears to be related to chronic inflammation, drug-related haemorrhage . haemolytic anemia as detected by the Coombs ’ test is the feature of SLE. on rare occasion, a serum antibody may be produced which impairs red cell production.

29. Platelets thrombocytopenia (<100*10 9 /L) appears to be mediated by anti-platelet antibodies or/and anti- phospholipid antibodies.

30. White blood cell leucopenia (<4.0*10 9 /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.

31. 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

32. Diagnostic Studies No specific test SLE is diagnosed primarily on criteria relating to patient history, physical examination, and laboratory findings

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

34. Diagnostic Studies Antinuclear antibodies ANA and other antibodies indicate autoimmune disease Anti-DNA and anti-Smith antibody tests most specific for SLE LE prep can be positive with other rheumatoid diseases ESR & CRP are indicative of inflammatory activity

35. Radiological studies Joint x-rays: no erosions, periarticular osteopenia + soft tissue swelling CXR/CT chest: interstitial lung disease, pneumonitis, pulmonary emboli, alveolar hemorrhage CTBrain or Brain MRI ± angiography: lupus white matter changes, vasculitis or stroke Echo: pericardial effusion, pulmonary hypertension or Libman-Sacks endocarditis

36. Additional work-up Serum cr. and albumin CBC w/ diff U/A ESR Complement levels Renal profile if warranted

37. Invasive procedures LP – nonspecific ↑cells + protein, ↓ glucose Renal biopsy – prognosis and Rx Skin biopsy

38. Diagnostic criteria American College of Rheumatology 4/11 criteria ( sens 85%, specif 95%) “SOAP BRAIN MD” S erositis – heart, lung, peritoneum O ral ulcers – painless esp palate A rthritis – non-erosive P hotosensitivity

39. Diagnostic criteria B lood disorders - ↓RBC (Coombs +), PLT, WCC, Lymphocytes R enal involvement – proteinuria /± casts A NA – titer > 1:160 I mmunologic phenomena – LE cells, anti- dsDNA Ab, anti- Sm Ab, antiphospholipid Ab, false WR + N eurological disorders – seizures/ psychosis M alar rash – cheeks + nasal bridge D iscoid rash – rimmed with scaling, follicular plugging

40. Treatment Treatment plans are based on patient age, sex, health, symptoms, and lifestyle and on disease severity Fever, skin, musculoskeletal and serositis = milder disease CNS and renal involvement – aggressive Rx Goals of treatment are to: -prevent flares -treat flares when they occur -minimize organ damage and complications

41. Collaborative Care Drug therapy NSAIDs Antimalarial drugs Steroid-sparing drugs Corticosteroids Immunosuppressive drugs

42. Conservative management For those w/out major organ involvement. NSAIDs: to control pain, swelling, and fever Caution w/ NSAIDS though. SLE pts are at increased risk for aseptic meningitis Antimalarials : Generally to treat fatigue joint pain, skin rashes, and inflammation of the lungs Commonly used: Hydroxycholorquine Used alone or in combination with other drugs

43. Corticosteroids (Mainstay of SLE treatment) To rapidly suppress inflammation Usually start with high-dose IV pulse and convert to PO steroids with goal of tapering and converting to something else. Commonly used: prednisone, hydrocortisone, methylprednisolone , and dexamethasone

44. Immunosuppressives Primarily for CNS/renal involvement Mycophenolate mofetil ( cellcept ) Azathioprine ( imuran ): requires several months to be effective, effective in smaller percentage of patients MTX: for treatment of dermatitis and arthritis, not life-threatening disease Cyclosporine: used in steroid-resistant SLE, risk of nephrotoxicity Cyclophosphamide ( cytoxan ) Almost all trials performed on patients with nephritis

45. Differential diagnosis Drug induced lupus erythematosis Vasculitis Leukemia HIV Multiple sclerosis Parvovirus or other viral infections

46. Prognosis Benign to rapidly progressive Better for isolated skin + musculoskeletal disease vs renal and CNS Death rate 3X age-comparable general population Mortality Nephritis (most within 5 yrs of symptoms) Infectious (active SLE + Rx – most common) CVS disease (50X more MI than other woman) Malignancy (chronic inflammation + Rx)

47. SLE disease activity index ( SLEDAI ) Clinical feature score seizure , psychosis , organ brain syndrome 8 visual disturbance, cranial nerve disorder 8 lupus headache, cerebrovascular accidents, 8 vasculitis 8 arthritis 4 myositis 4 urinary casts, hematuria , proteinure , pyuria 4 rash, alopecia, mucosal ulcers, 2 pleurisy, pericarditis 2 low complement, increased DNA binding 2 fever 1 thrombocytopenia, leucopenia 1

48. Other therapy Plasma exchange Intravenous Immunoglobulin Stem cell transplantation Immune therapy ( anti-IL10, anti-CD20, and immune tolerance therapy)