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Systemic Lupus-erythmatosus a detailed review.pdf

  1. Systemic Lupus Erythmatosus PGR Medicine Dr. Usama Saleem
  2. Case Presentation A 30 year old female Known/Case of SLE with lupus nephritis since July 2021 and Post cholecystectomy since 2017 complained of loose stools with fresh blood dripping on toilet 3 episodes per day,perianal pain, vomiting 1-2 episodes, for 3 days. Patient also complained of 35 kg weight loss in last 2 years .On further exploring patient also complaint of loose stools on and off for last 4 years which are not associated with any Abdominal pain, Fever , blood , fat or mucus in it.
  3. She complained of odynophagia and dysphagia to both solids and liquids. Patient denies any joint pain , rash, Dry eyes ,Dry mouth Patient complained of oral ulcers , photosensitivity and raynaud phenomenon on and off > Hospital stay Patient developed Right knee pain during hospital stay O/E Pallor + Pedal edema++. white coated tongue GCS 15/15. CVS S1+S2+0. RESP NVB+0. ABDOMIN SNT Power 5/5 in all limbs with b/L downgoing plantars MSK examination shows no tenderness, swelling , warmth , movement limitation in any joints .
  4. Past medical Hx. Past Surgical Hx SLE since july 2021 Lupus Nephritis in Oct 2021 Patient was taking HCQ OD , Sunblock cream TDS, CAC 1000 OD , Vitamin D3 Monthly ,INOGRAF 0.5mg BD' Zeegap 25mg HS,Sangobion OD and Deltacortril 5mg OD Cholecystectomy 2017
  5. Investigations >Hb 10.2. MCV 79.2 TLC 5.9. Plt 307. ESR 31. Na 132 K 2.5. >Albumin 1.9. Creatinine 1.2. (eGFR 60 ml/hr) CRP 24. >Urine C/E 12-15/hpf Protein Nil >USG ABD; Hepatic steatosis >Endoscopy; Esophageal Candidiasis Esophageal Ulcers Stool C/E shows Bacteria ++ Food + Mucous Nil Blood Nil
  6. ANA + Homogenous pattern. Titre 1:320. July 2021 Serum Anti dsDNA IgG positive. July 2021 Serum Antitransglutaminase IgA Neg- July 2021 ENA Profile Negative. OCT 2021 C3 53. C4 24. OCT 2021 SPOT URINE PROTEIN 213 SPOT URINE CREATININE 149 P:C RATIO 1.4. OCT 2021 Creatinine1.0. OCT 2021
  7. Diagnosis SLE Acute infectious Gastroenteritis Anal Fissure Esophageal candidiasis and ulcers
  8. Treatment Inj Oxidil 2gm OD Inj Solumedrol 20mg BD Tab HCQ 200mg HS Sunblock cream TDS Tab CAC1000 Plus OD Cap inograf 0.5mg BD Cap Zeegap 100mg HS Inj R/L 1000cc OD inj Onset 8mg Sos Xylocaine and GTN ointment locally Tab Neo K 2 tabs TDS Inj Risek 40mg OD Nilstat oral Drops 2 dropper TDS Inj Albumin 50 cc OD Cap Diflucan 50mg BD Syp Ulsanic 2tsf TDS Enterogermina PO OD Tab Levopraid 25mg BD Tab Rifaxa 550mg bd
  9. Discharge Medications Tab HCQ 200mg HS Sunblock cream TDS Tab CAC1000 Plus OD Cap Zeegap 100mg HS Xylocaine and GTN ointment locally Nilstat oral Drops 2 dropper TDS Cap Diflucan 50mg BD Syp Ulsanic 2tsf TDS Enterogermina PO OD Tab Levopraid 25mg BD Tab Rifaxa 550mg bd Tab Deltacortril 5mg PO OD
  10. Systemic Lupus Erythmatosus
  11. Definition. Pathogenesis SLE is an inflammatory autoimmune disorder character- ized by autoantibodies to nuclear antigens. It can affect multiple organ systems >Trapping of antigen-antibody complexes in capillaries of visceral structures >Autoantibody-mediated destruction of host cells (eg, thrombocytopenia).
  12. Incidence It is affected by many factors >Sex MORE COMMON IN FEMALES 85% Of the Patients are females >Race MORE ,COMMON IN BLACK FEMALES THAN WHITE SLE occurs in 1:1000 White women but in 1:250 Black women >Genetic Inheritance Familial occurrence of SLE has been repeatedly documented, and the disorder is concordant in 25–70% of identical twins
  13. CRITERIA American college of Rheumatology old criteria (A patient is classified as having SLE if any 4 or more of 11 criteria are met.)
  14. SLICC CRITERIA Presence of any four criteria (must have at least 1 in each category) qualifies patient to be classified as having SLE
  15. EULAR/ACR Updated Criteria It consists of seven clinical domains and three immunologic domains. Each criterion is assigned points, ranging from 2 to 10.
  16. Patients with ANA titre greater than1:80 , at least one clinical criterion and 10 or more points are classified as having SLE. Interpretation
  17. CRITERIA Sensitivity Specificity ACR 1997 82.8% 93.4% SLICC 2012 96.7% 83.7% ACR/EULAR 2019 96.1% 93.4%
  18. Systemic Manifestations of SLE
  19. Non specific symptoms > Fever > malaise > Anorexia > Weight loss > Alopecia > Raynand Phenomenon
  20. Musculoskeletal Joint symptoms, with or without active synovitis, occur in over 90% of patients and are often the earliest manifestation. The arthritis can lead to reversible swan-neck deformities, but radiographic erosions and subcutaneous nodules are rare
  21. Cutaneous Most patients have skin lesions at some time; the characteristic “butterfly” (malar) rash affects less than half of patients. Other cutaneous manifestations are panniculitis (lupus profundus), discoid lupus and typical fingertip lesions (periungual erythema, nail fold infarcts, and splinter hemorrhages)
  22. Malar rash
  23. Pulmonary Pleurisy and pleural effusion are common. Pneumonitis, interstitial lung dis-ease, and pulmonary hypertension can rarely occur. Alveolar hemorrhage is uncommon but life-threatening
  24. Ocular Ocular manifestations include keratoconjunctivitis sicca and retinal vasculopathy (cotton-wool spots, episcleritis, scleritis and optic neuropathy)
  25. Cardiac The pericardium is affected in the majority of patients. Heart failure may result from myocarditis and hypertension. Cardiac arrhythmias are common. Atypical verrucous endocarditis of Libman-Sacks is usually clinically silent but occasionally can produce acute or chronic valvular regurgitation(most commonly mitral regurgitation)
  26. Vascular The prevalence of transient ischemic attacks, strokes, and myocardial infarctions is increased in patients with SLE. These vascular events are increased in, but not exclusive to, SLE patients with antibodies to phospholipids (antiphospholipid antibodies), which are associated with hypercoagulability and acute thrombotic events
  27. Neurological Neurologic complications of SLE include psychosis, cognitive impairment, seizures, peripheral and cranial neuropathies, transverse myelitis, and strokes
  28. Renal Several forms of glomerulonephritis may occur, including mesangial, focal proliferative, diffuse proliferative, and membranous .Some patients may also have interstitial nephritis. With appropriate therapy, the survival rate even for patients with serious kidney disease (proliferative glomerulonephritis) is favorable, a sub-stantial portion of patients with severe lupus nephritis develop end-stage kidney disease
  29. Hematological Hematologic manifestations include leukopenia, auto-immune hemolytic anemia, immune thrombocytopenia, and thrombotic thrombocytopenic purpura
  30. Gastroenterology Nausea, sometimes with vomiting, and diarrhea can be manifestations of an SLE flare Increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are common when SLE is active. Occasionally, abdominal pain in active SLE may be directly related to active lupus, including peritonitis, pancreatitis, mesenteric vasculitis, and bowel infarction. Rarely, lupus enteritis may be the initial manifestation of SLE. ]Jaundice due to autoimmune hepatobiliary disease may also occur. Mouth ulcers are also common
  31. Investigations Antinuclear antibody (ANA) tests based on immunofluorescence assays nearly 100% SENSITIVE for SLE but not specific Antibodies to double-stranded DNA and to Sm are SPECIFIC for SLE but not sensitive, since they are present in only 60% and 30% of patients, respectively.
  32. Frequency of autoantibodies in SLE ANA by IF Anti dsDNA Anti Sm RA Factor Anti SSA Anti SSB 95-100% 60%. 10-25%, 20% 15-20% 5-20%
  33. Antiphospholipid Antibodies Anti-cardiolipin antibody 25% Lupus anticoagulant 7% Anti–beta-2-glycoprotein 1 25% These antibodies are associated with increase in thrombotic complications of SLE eg Stroke and MI
  34. CBC Anemia (Hemolytic anemia, anemia of chronic disease) Leukopenia (WBC <4000/µL ) Thrombocytopenia(<100,000/μL) Serum complement levels Depressed C3 and C4 suggests active disease ESR and CRP Durng disease flares, elevations in the ESR are common, but the serum CRP is usually normal Liver function tests ALT and AST may be raised in acute SLE or in response to therapies like NSAIDS or Azathioprine Albumin is usually low in case of proteinuria
  35. Urine complete examination Lupus nephritis shows hematuria with or without casts, and proteinuria (varying from mild to nephrotic range) . Creatinine usually deranged in active lupus nephritis P:C Ratio Spot urine Protein and spot urine creatinine is used to quantify proteinuria Renal biopsy helps to identify the type of glomerulonephritis. it is recommended in all cases of active Lupus Nephritis unless there is any contraindications
  36. Classification of Lupus Nephritis ISN/RPS Class I: Minimal Mesangial Lupus Nephritis mesangial immune deposits by immunofluorescence only Class II: Mesangial Proliferative Lupus Nephritis mesangial hypercellularity or mesangial matrix expansion by light microscopy, Class III: Focal Lupus Nephritis focal, segmental or global glomerulonephritis involving ≤50% of all glomeruli, Class IV: Diffuse Lupus Nephritis focal, segmental or global glomerulonephritis involving >50% of all glomeruli, Class V: Membranous Lupus Nephritis Global or segmental subepithelial immune deposits Class VI: Advanced Sclerotic Lupus Nephritis ≥90% of glomeruli globally sclerosed without residual activity.
  37. Skin Biopsy Lupus skin rash often demonstrates inflammatory infiltrates at the dermoepidermal junction and vacuolar change in the basal columnar cells Arthrocentesis joint effusions, which can be inflammatory or noninflammatory. The cell count may range from less than 25% polymorphonuclear neutrophils (PMNs) in noninflammatory effusions to more than 50% in inflammatory effusions
  38. Radiology Joint radiography periarticular osteopenia and soft- tissue swelling without erosions Chest X ray and HRCT These modalities can be used to monitor interstitial lung disease and to assess for pneumonitis, pulmonary emboli, and alveolar hemorrhage Echocardiography is used to assess for pericardial effusion, pulmonary hypertension, or verrucous Libman-Sacks endocarditis
  39. Treatment
  40. SLE activity often waxes and wanes, the intensity of drug therapy used must be tailored to match disease severity. Since the various manifestations of SLE affect prognosis differently drug therapy is chosen accordingly to induce remission GOAL OF THERAPY
  41. NON-LIFE-THREATENING DISEASE Antimalarials (hydroxychloroquine, ) often reduce dermatitis, arthritis, and fatigue. They also reduce the incidence of disease flares and prolong survival in SLE. NSAIDs are useful analgesics/ anti-inflammatories, particularly for arthritis/arthralgias Patients should be cautioned against sun exposure and should apply broad-spectrum UVA/ UVB sunscreen while outdoors. Milder skin lesions often respond to the topical administration of corticosteroids Skin and joint symptoms
  42. Systemic Corticosteroids Corticosteroids are required for the control of certain complications. Glomerulonephritis, Hemolytic anemia, Myocarditis, Alveolar hemorrhage, Central nervous system involvement, Severe thrombo-cytopenia The mainstay of treatment for any inflammatory life-threatening or organ-threatening manifestations of SLE is systemic glucocorticoids
  43. For serious manifestations, either methylprednisolone 250–1000 mg given intrave-nously over 30 minutes daily for 3 days or prednisone 40–60 mg orally is needed initially However, the lowest dose of corticosteroid that controls the condition should be used over time to minimize adverse effects
  44. Immunosuppressive Agents These are used for long term control of the disease Cyclophosphamide, Mycophenolate mofetil, Azathioprine, Methotrexate Tacrolimus Belimumab, a monoclonal antibody that inhibits the activity of a B-cell growth factor, is FDA approved for treating SLE patients with active disease who have not responded to standard therapies (eg, NSAIDs, antimalarials, or immunosuppressive therapies)
  45. Lupus Nephritis Lupus Nephritis Induction Phase Mycophenolate mofetil and cyclophosphamide are first- line induction treatments for lupus nephritis and are generally given with corticosteroids to achieve disease control Mycophenolate mofetil is gien 1000 mg or 1500 mg orally twice daily Cyclophosphamide is usually administered using the Euro-Lupus regimen (500 mg intravenously every 2 weeks for six doses) National Institutes of Health regimen (3–6 monthly intravenous pulses [0.5–1 g/ m2] for induction followed by maintenance infusions every 3 months).
  46. Maintenance Phase Mycophenolate mofetil or azathioprine is typically used for maintenance therapy for lupus nephritis Studies shows that Tacrolimus is also an effective drug for induction and maintenance of lupus nephritis
  47. SLE IN PREGNANCY Active SLE in pregnant women should be controlled with hydroxychloroquine and, if necessary, prednisone/ prednisolone at the lowest effective doses for the shortest time required. Azathioprine may be added if these treatments do not suppress disease activity
  48. Lupus and Anti Phospholipid Syndrome should be managed with long-term anticoagulation . With warfarin, a target international normalized ratio (INR) of 2.0–2.5 is recommended for patients with one episode of venous clotting; an INR of 3.0–3.5 is recommended for patients with recurring clots or arterial clotting,
  49. MEDICATION DOSE RANGE ADVERSE EFFECTS NSAIDs Acc to Salt GI distress elevated liver enzymes, decreased renal function, Glucocorticoids Oral Prednisone, prednisolone: 0.5–1 mg/kg per day for severe SLE 0.07–0.3 mg/kg per day or qod for milder disease infection, hypertension, hyperglycemia, hypokalemia, acne, aseptic necrosis of bone, cushingoid changes, CHF, fragile skin, insomnia, menstrual irregularities, , osteoporosis, psychosis Methylprednisolone sodium Same Cyclophosphamide IV 500 mg every 2 weeks for 6 doses, then begin maintenance with MMF or AZA. Infection, leukopenia, anemia, thrombocytopenia, , , malignancy, alopecia, cough, diarrhea, fever, GI symptoms, , hypertension, hypercholesterolemia, For severe disease, 0.5-1 g IV qd × 3 days
  50. Medication Dose Adverse Effects Mycophenolate mofetil 2–3 g/d PO total given bid for induction therapy, 1–2 g/ d total given bid for maintenance therapy Same as other immunosuppressive agents e.g Cyclophosphamide Azathioprine 2–3 mg/kg per day PO for induction;1–2 mg/kg per day for maintenance; Infection, VZV infection, bone marrow suppression, , pancreatitis, hepatotoxicity, malignancy, , fever, flulike illness, GI symptoms Belimumab 10 mg/kg IV wks 0, 2, and 4, then monthly OR subcutaneous 200mg each week Infusion reactions, allergy, infections. Headache and diffuse body aching. Tacrolimus 1-2 mg bid Infection oppurtunistic, nephrotoxicity, neural toxicity HCQ 200-400mg/day Retinopathy ,Myopathy
  51. Patient Summary Patient Summary Patient developed different infections like diarrhea and candidiasis because of prolonged immunosuppressive medications like Tacrolimus and steroids
  52. THANKS