SLE Case Vignettes-1

Dr. M. Vishnu Vardhan Reddy

 A 32 yr old female with headache & rash

• Background history-
• 1996- diagnosed as SLE with class 5 Lupus nephritis
• Remission on oral steroids
• 1998-Developed bilateral AVN of hips
• 2003 – relapse of Nephrotic syndrome, responded with
Cyclosporine
• From Dec 2004 -off all Immunosuppressants
• June 2005:
• presented with purpuric rash on limbs and headache of 5 days
duration
 Examination

• Conscious and Coherent • CVS

• PR-104/min • ABD
NAD
• RR-20/min • RS
• BP-130/80mmHg • CNS- HMF-normal
• Afebrile • Reflexes-normal
• Pallor • Sensory and motor system
• Nonpalpable purpura and normal
ecchymosis on both UL&LL • Fundus-normal
• No neck rigidity
• Kernig's-negative
 Investigations
• Hb 7.6 gm% • LDH 3840
• TLC 6400/ul • Bil 0.2
• DLC N 75 L 23 • PT 13.2sec
• Plt 22000/ul • aPTT 23.0sec
• Retic 25 %
• PBF- Polychromasia, • C3-105.2mg/dl
fragmented RBC,
• C4-144.2 mg/dl
Spherocytes
• Anti-ds-DNA- 95.8 iu/ml
• DCT & ICT- Negative
• IgM ACL- 2.2 MPL
• Creatinine 1.0
• IgG ACL- 1.54 GPL
• SGOT 230
• Urine- protein-2+
• SGPT 258
hemoglobin-2+
• Alk phos 123
 Database with working diagnosis
• 32 yr female lupus patient
• Thrombocytopenia
• Drop in hemoglobin /Elevated Retics/Fragmented RBC
• Negative Coombs
• Headache
• Normotensive
• Normal renal function
• Normal PT & APTT

Micro Angiopathic Hemolytic Anemia

+ Thrombocytopenia
MAHA + Thrombocytopenia
 Possibilities in this patient

• TTP
• HUS
• DIC
• Malignant hypertension
• CAPS
• HEELP SYNDROME
• Drug induced
 Condition Against
HUS Normal creatinine, no fever at onset

DIC Normal PT & APTT

Malignant hypertension Normal BP & no papilledema

CAPS ACL Ab Negative

HEELP Syndrome Not pregnant

Drugs No history

TTP None
 Fever- amika / ceftazidime
pseudomonas/klebsiella
Seizures- antiepileptics
Hb
CVA

3840
3.17 Lac

1870
Platelet
ventilator
overload
Fluid

2.2 Lac

CYC Pulse
915
1.55 Lac LDH
58000
23000
11000 432

MP X 3 PRDN 1 Mg/kg/d
 Course & Management
Specific Treatment
• Alternate day PE
• 3 pulses- 1 gm MP
• PRDN-1mg/kg/d
• Cyclophosphamide Pulse
• Multiple IV antibiotics
Supportive care
• Anti epileptics
• Potassium supplementation
• Insulin
• Multiple PRBC
• FFPs as plasma exchange
replacement fluid
• RDPs
• Mechanical Ventilation
 Final diagnosis

• Basic disease- SLE with class 5 Lupus nephritis

• Complicating illness- TTP
 CVA- left facial palsy, multiple infarcts
 Status epilepticus -recovered
 Klebsiella sepsis
• Right CSOM-Pseudomonas infection
• Respiratory failure- recovered
 Follow up
At discharge
• Platelet count normalised
• Afebrile
• Clear sensorium
• Nephrotic range proteinuria
persisting
• PRDN-1mg/kg/d
• Antiepileptics
• Oral antibiotics
Present
• Received 12 CYC boluses
• Nephrotic range proteinuria
persisting
• AZA + Low dose steroids
• ACEIs
 Paradigm shift in TTP Diagnosis :
Pentad To Diad

Now ONLY thrombocytopenia and MAHA without an apparent

alternative etiology are required to establish the diagnosis and
initiate plasma exchange
TTP diagnosis
 ADAMTS13
• A Disintegrin-like And Metalloprotease with ThromboSpondin
type 1 repeats
• Protease that cleaves ULVWf (Unusually Large Von Willebrand
factor) in the circulation
• Absent in most idiopathic TTP (because of acquired
autoantibody inhibitors), but not HUS

ADAMTS13 deficiency (<5%) ADAMTS13 inhibitor

predicts: predicts:
• Idiopathic TTP • Prolonged time to complete
• Complete response to plasma response
exchange • Death
• Survival • Relapse
 Clinical course of idiopathic TTP
• 20% dead within with 5 weeks

• 80% complete response in average of 16 days (range, 3-36)

• 40% of responders have exacerbations within one week

• 30% of responders relapse within 2 years

• Relapses usually occur within the first year

• More relapses if pt. has severe ADAMTS13 deficiency or

inhibitor at diagnosis

• 10-year relapse rate of 36%

Rock et al, New Eng J Med 1991; 325: 393-397

TTP- SLE
 Autoimmune pathogenesis of TTP in SLE

• Antibodies against von Willebrand factor cleaving

metalloprotease, endothelial cells and platelets
• Coexistence of TTP and other autoimmune diseases ( RA,
Sjogren’s syndrome etc);
• Successful use of cytotoxic drugs

• Correlation of SLE activity with TTP

 TTP in SLE

• Risk factors for TTP in SLE- SLEDAI(>10), nephritis

• Risk factors for in-hospital mortality- infection, neurologic

symptoms
• The time to complete remission was longer compared with
idiopathic TTP
• Overall prognosis of TTP in SLE is poor

• The tempo of development of TTP in SLE is slower

 Idiopathic TTP – Initial Therapy
Initiate treatment:
• Plasma exchange 60 ml/kg daily
• Plasma infusion if >12 hour delay
• Prednisone 2 mg/kg/day
Don’t forget
Continue PE to complete response: 1.Daily folic acid
• Platelets >150K/µl for 3 days
2.Aspirin after Plt
• and LDH normal count normalized
• and Neurologically stable
After complete response:
• PE every other day for 4 days and stop
• Taper prednisone
• Resume treatment for exacerbation (<30 days) or relapse
(>30 days)
 Idiopathic TTP – Salvage Therapy

Refractory or relapsing disease [10-20% of patients]

• Increase to twice daily Plasma Exchange
• Rituximab +/- cyclophosphamide
• Vincristine
• Intravenous immune globulin
• Cyclosporine ( can cause TTP *)
• Splenectomy
 Areas of Uncertainty
• Use of anti –platelets agents in acute episode
• Efficacy of any therapy to prevent relapse
• Efficacy of Plasma exchange in settings like post HSCT /
typical HUS/drug mediated
• Measurement of ADAMTS 13 activity and its inhibitor
autoantibody
• Best fluid for plasma exchange replacement fluid
• Role of Rituximab upfront along with PE
• Recombinant ADAMTS 13 therapy
• Should asymptomatic patients with ADAMTS13 deficiency be
treated?
 Take home messages
• Consider TTP in all cases of thrombocytopenia in SLE

• If TTP or atypical HUS is on top of your differential in pt. with MAHA

and thrombocytopenia, institute plasma exchange as soon as possible
• Neuro sx’s are seen more often in TTP, while renal failure is seen in
HUS
• Classic/Typical HUS: no need for plasma exchange

• ADAMTS13 deficiency or inhibitor is associated with TTP

• TTP in SLE has more slower onset and a/w poor response to Rx with
increased mortality
• Rituximab is a promising option in refractory cases
Risk factors for TTP
Risk factors for in-hospital mortality in SLE
patients with TTP

Complication Survivors(n=14) Death(n=12) P value

Infection 1/14(17%) 7/12(58.3%) 0.009

Neurologic
symptom 4/14(28.6%) 9/12(75%) 0.047
 Incidence
• Suspected TTP-HUS: 11 cases/million annually
• Idiopathic TTP-HUS: 4.5 cases/million annually
• Severe ADAMTS13 deficiency: 1.7 cases/million annually

- From the Oklahoma TTP-HUS Registry