Case Presentation

DR EM Klaus14th June 2010Department Internal MedicineDivision NephrologyConsultant : Prof B van Rensburgh

Case Presentation

Presentation:Presentation:

26y Female from Hartswater

Divorced; 3 children

Unemployed

History: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: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

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Previous Medical History: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


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: Evan’s Syndrome (AIHA + ITP)

Treatment at Hematology Universitas Cerebrovascular Accident – April 2010

Previous Surgical: No operations

Allergies: noneSocial:

2 cigarettes/ day since 2007 No alcohol

Medication:Medication:

1. Prednisone 40mg OD PO2. Azathioprine 150mg OD PO3. HCTZ4. Lasix 40mg BID PO5. Coversyl6. Atenolol7. Cardura LX


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


Side room: Urine Dipstix: menstruating Urinalysis: WBC casts


Examination:


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



Previous results: May 2009




Problem Statement:

26 y Female1. SLE (MI (Libman-Sachs, Evan’s syndrome, Renal involvement, ANA, ds DNA)

Complication: Secondary Antiphospholipid

Syndrome Renal failure (SLE, APL, UTI)

Renal Biopsy:

Safety?1. Renal size2. UTI3. Coagulation profile

1. PT = 122. PTT = 693. BT = 94. p/t = 68

4. Hb = 7,5


Treatment:

1. Stop Azathioprine2. Cyclophosphamide 250mg IVI 9th

June 20103. Prednisone 50mg OD PO4. Clexane 20mg BID SC5. Warfarin 5mg OD PO

1. Diagnosis Evan’s Syndrome2. Treatment Evan’s Syndrome3. Diagnosis APL4. APL - Renal Impairment

APL- Associated Renal Disease

1. Diagnosis Evan’s Syndrome

Diagnosis Evan’s Syndrome:

Autoimmune hemolytic anemia (AIHA)

+

Immune (idiopathic) Thrombocytopenia (ITP)

=

Disorder usually is referred to as Evans 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


2. Treatment Evan’s Syndrome

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


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


3. Diagnosis Antiphospholipid

Syndrome

APS Classification Criteria:> 1 clinical feature + >1 autoantibody

4. Antiphospholipid Syndrome Renal Impairment

Antiphospholipid syndrome (APS):

Characterized by antibodies directed against phospholipids or plasma proteins bound to phospholipids


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

APS antibodies:

1. Beta2-glycoprotein antibodies

2. Anticardiolipin antibodies

3. Lupus anticoagulants

4. 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

Treatment of APS in Renal Disease:

APS treatment the same whether or not renal disease is present

Patients with the following must be treated to avoid life threatening vascular damage:

thrombotic microangiopathy in the glomeruli and small arteries

or thrombi in the larger vessels

Treatment of APS in Renal Disease:

Acute renal failure due to antiphospholipid antibodies may respond:

Plasmapheresis

Or Corticosteroids + chronic anticoagulation

Optimal plasmapheresis regimen uncertain, 3-5

one-plasma volume exchanges over 7d period substantial lowering of antiphospholipid antibody levels

Anticoagulation in APS:

Initial approach to thrombosis : LMWH Warfarin

Chronic management: lifelong anticoagulation

INR 2.0 - 3.0 initial DVT

INR >3.0 initial arterial event OR recurrent

DVT’sCrowther MAet al A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the Antiphospholipid antibody syndrome. N Engl J Med 2003 Sep 18;349(12):1133-8.

1. 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. Epub 2009 Jul 28.

2. Bonnie L Bermas,Peter H Schur Pathogenesis of the antiphospholipid syndrome. UpToDate Desktop 18.1 Last literature review: February 2010

3. Crowther MAet al A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the Antiphospholipid antibody syndrome. N Engl J Med 2003 Sep 18;349(12):1133-8.

4. Gerald B Appel; Antiphospholipid syndrome and the kidney. UpToDate Desktop 18.1 Last literature review: February 2010

5. Bonnie L Bermas; Treatment of the antiphospholipid syndrome. UpToDate Desktop 18.1 Last literature review: February 2010

References:

Disclosure Statement:

No conflict of interest to be declared with this presentation

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