Case Presentation DR EM Klaus 14th June 2010 Department Internal Medicine Division Nephrology Consultant : Prof B van Rensburgh
Presentation: • 26y Female from Hartswater • Divorced; 3 children • Unemployed
History: • Presented to Kimberley hospital: • Pulmonary Oedema • New onset Renal Failure • Started on Hemodialysis at Kimberley and referral for further work-up / renal biopsy • 2 weeks ago hemodialysis
History: • Known to Division Haematology, Universitas Hospital • Evan’s Syndrome (AIHA + ITP) • Dx: May 2009 • Admitted to ICU with low Hb • p/t = 12 • BM = Megakariocytic Thrombocytopenia • ANA Pos Titre 1:640 • Ds DNA Pos • Rx June 2009: DEXA pulse, Prednisone 60mg OD PO + taper • Cerebrovascular Accident – April 2010
Examination: May 2010 Na K Cl C02 BUN Creat AG
Previous Medical History: • Respiratory: • Dyspnoe GII • No cough, pleuritic chestpain, wheezing or hemoptysis • Cardiovascular: • No relevant history • Uro-genital: • Peripheral oedema • Nausea, fatigue • G3P3M0 = no previous miscarriages • Depo Provera since May 2009 - Amenorrhoea
Previous Medical History: • Neurological: • No convulsions or previous episodes of psychosis • No headaches • Abdominal: • No oral ulcers • No epigastric pain • No haematemesis, melena • Derma: • No skin rash • No photosensitivity • Muskuloskeletal: • No arthralgia
Previous Medical History: Previous Medical: • Evan’s Syndrome (AIHA + ITP) • Treatment at Hematology Universitas • Cerebrovascular Accident – April 2010 Previous Surgical: • No operations Allergies: none Social: • 2 cigarettes/ day since 2007 • No alcohol
Medication: • Prednisone 40mg OD PO • Azathioprine 150mg OD PO • HCTZ • Lasix 40mg BID PO • Coversyl • Atenolol • Cardura LX
Examination: May 2010 Mass=52kg; L=151cm BMI=22,8 kg/m² Apyrexial BP=120/70 P=68 General: Bipedal oedema No jaundice, anemia No skin rash Resp: Normal; No crepitations or pleural effusion Abdom: Normal, no organomegaly CVS: Sinus rhythm, Grade 2/6 pan-systolic murmur, radiating to axilla Neuro: normal; no localizing signs, resolved right hemiparesis MS: No vasculitis, synovitis
Examination: May 2010 Side room: Urine Dipstix: menstruating Urinalysis: WBC casts
Examination: Renal U/S(Kimberley) = Bilateral kidney size = 11,3 mm Grade 2 hyperechoic parenchyma NO hydronephrosis
Examination: Echocardiogram(Kimberley) = Mild MI LVEF=53% LVESD=3,9cm; LVEDD=5,4cm LA=4,6cm
Examination: HIV neg RPR neg Hep A,B,C neg ASOT neg; C3, C4 normal ANA + titre 1:160 Ds DNA positive
Problem Statement: 26 y Female • SLE (MI (Libman-Sachs, Evan’s syndrome, Renal involvement, ANA, ds DNA) • Complication: • Secondary Antiphospholipid Syndrome • Renal failure (SLE, APL, UTI)
Renal Biopsy: Safety? Renal size UTI Coagulation profile PT = 12 PTT = 69 BT = 9 p/t = 68 Hb = 7,5
Treatment: Stop Azathioprine Cyclophosphamide 250mg IVI 9th June 2010 Prednisone 50mg OD PO Clexane 20mg BID SC Warfarin 5mg OD PO
APL- Associated Renal Disease Diagnosis Evan’s Syndrome Treatment Evan’s Syndrome Diagnosis APL APL - Renal Impairment
Diagnosis Evan’s Syndrome: Autoimmune hemolytic anemia(AIHA) + Immune (idiopathic) Thrombocytopenia (ITP) = Disorder usually is referred to asEvans syndrome Michel M et al The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009 Oct 8;114(15):3167-72.
Causes Evan’s Syndrome: Most idiopathic 50% associated: SLE Scleroderma Lymphoproliferative disorders Common variable immunodeficiency Allogeneic hematopoietic cell transplantation Michel M et al The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009 Oct 8;114(15):3167-72.
Treatment Evan’s Syndrome: No systematic or randomized studies of the treatment of ES Available literature consists almost entirely of anecdotal case reports and retrospective series
Treatment Evan’s Syndrome: Often either resistant to standard treatment for AIHA or ITP Glucocorticoids IVIG Splenectomy Follows a chronic, relapsing course Michel M et al The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009 Oct 8;114(15):3167-72.
Treatment Evan’s Syndrome: Glucocorticoids IVIG Azathioprine Cyclophosphamide (Steroid-resistant ES Clin Rheumatol. 2001) Mycophenolate mofetil Cyclosporine Rituximab Vincristine Danazol Hematopoietic cell transplantation Splenectomy Insufficient information to choose one of these agents over another, although current literature more reports of success following rituximab use.
68 patients & 4.8y follow-up 32% in remission, off Rx 24% had died Treatment: First line: Prednisone (1 to 2 mg/kg/d) = 80% initial response IVIG = 60% response Second line: (75% of patients) Cyclophosphamide Azathioprine Danazol Vinca alkaloids Rituximab – 16% Splenectomy 28% = initial and long-term response Michel M et al The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009 Oct 8;114(15):3167-72.
Antiphospholipid syndrome (APS): Characterized by antibodies directed against phospholipids or plasma proteins bound to phospholipids Michel M et al The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009 Oct 8;114(15):3167-72.
Antiphospholipid syndrome (APS): Primary APS Secondary APS association with: SLE ( 20 – 47% have APS Ab) other rheumatic diseases (scleroderma, psoriatic arthritis) Infections Bacterial: Septicemia, TB, syphilis, post-streptococcal rheumatic fever, and Klebsiella infections Viral infections: Hepatitis A, B, mumps, HIV, HTLV-I, cytomegalovirus, varicella-zoster, Epstein-Barr virus, adenovirus parvovirus, and rubella. Parasitic: Malaria, Pneumocystis jirovecii, and visceral leishmaniasis (also known as kala-azar) Drugs phenothiazines (chlorpromazine), phenytoin, hydralazine, procainamide, quinidine, quinine, dilantin, ethosuximide, alpha interferon, amoxicillin, chlorothiazide, oral contraceptives, and propranolol Bonnie L Bermas,Peter H Schur Pathogenesis of the antiphospholipid syndrome. UpToDate Desktop 18.1 Last literature review: February 2010
APSantibodies: Beta2-glycoprotein antibodies Anticardiolipin antibodies Lupus anticoagulants Antibodies causing a false positive VDRL
Renal disease in primary APS: Non-inflammatory occlusion of renal blood vessels Type of involved blood vessels: Renal infarction Ischemic changes Thrombotic microangiopathy of glomeruli Large vessel involvement: Unilateral or bilateral flank pain, hematuria, and decreased renal function
Glomerular involvement: Histology resembles Hemolytic-uremic syndrome Thrombotic thrombocytopenic purpura Scleroderma Focal atrophy of the cortex and interstitial fibrosis may be observed If kidney biopsy delayed: FSGS as a residual to the thrombotic microangiopathy, may be a prominent finding
APS associated with SLE: Present with: Systemic thromboses Fetal loss Neurologic disorders Thrombocytopenia False positive VDRL for syphilis Prolonged activated PTT Among such patients, renal disease may result from microthrombi and/or deposits of immune complexes.
Maintenance Hemodialysis: High prevalence of antiphospholipid antibodies Associated with increased thrombotic events Often involving the vascular access
Renal transplant recipients: Substantial number have circulating antiphospholipid antibodies Can damage the allograft