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THE MANAGEMENT OF SYSTEMIC

LUPUS ERYTHEMATOSUS

Mulia
September 2011

Introduction
SLE is a chronic inflammatory
autoimmune disease of unknown
etiology, with variable clinical
manifestation, course and prognosis.

It is characterized by periods of
remissions and periods of
exacerbations, which may involve
any organ or system in various
combinations.
erican College
of Rheumatology Ad Hoc Committee on SLE guidelines. Arthritis Rheum 1999;42(9):178

In the USA, the prevalence of SLE is


1 : 1,000
At RSCM, 1.4% of total outpatients
in the Clinic of Rheumatology in 2002
was SLE.

Female : male = 9-14 : 1


The great majority of these patients
are women in their childbearing
erican College of Rheumatology Ad Hoc Committee on SLE guidelines. Arthritis Rheum 1999;42(9):178
tan Reumatologi Indonesia. Paduan diagnosis dan pengelolaan SLE, September 2004.
years.

Survival rates are ~80% at 10 years


after diagnosis and ~65% at 20
years.
A bimodal mortality curve:
Early deaths attributed to active
disease and infections,
Late deaths due to
cardiovascular disease.
Abu-Shakra, et al. J Rheumatol 1995;22:1259-64.
Urowitz MB, et al. Am J Med 1976;60:221-5.

Clinical Features

4/11 criteria

Specificity

Sensitivity

~95%

85%

3 criteria (ANA-positive) almost surely SLE.


3 criteria (ANA-negative) very low
probability.
Only ANA-positive unlikely SLE.

Conditions that may be


confused with SLE
Undifferentiated connected tissue
disease
Sjogrens syndrome
Antiphospholipid anntibody syndrome
Fibromyalgia with ANA (+)
Idiopathic thrombocytopenia purpura
Drug-induces lupus
Early rheumatoid arthritis
Vasculitis

Characteristics of Mild SLE

Severe or Life-threatening
SLE

Severe or Life-threatening
SLE

Assessment of
Disease Activity and Severity
Is important for the establishment of
an appropriate treatment program.
Is needed to closely follow-up the
activity of disease.

Disease Activity Indexes


SLEDAI (SLE Disease Activity Index )
MEX-SLEDAI (The Mexican SLE Disease
Activity Index)

SLAM (SLE Activity Measure)


BILAG Index (The British Isles Lupus
Assessment Group)

LAM-6

MEX-SLEDAI

Neurology disorder (score = 8)


Renal impairment (score = 6)
Vasculitis (score = 4)
Hemolisis / trombositopenia (score = 3)
Miositis (score = 3)
Arthritis (score = 2)
Mucocutaneous impairment (score = 2)
Serositis (score = 2)
Fever > 38C / fatique (score = 1)
Leucophenia / Lymfophenia (score = 1)

Score:

>12 = severe disease activity


3 12 = mild to moderate disease activity
<3
= very mild or no disease activity

The Aims of Management


General

Specific

The Pillar of Treatment

The Treatment of Mild SLE

The Treatment of Mild SLE

Treatment of Serious, Life-threatening,


or Organ-threatening SLE

The pillar of treatment is similar to


mild SLE, except the pharmacological
treatment.

Corticosteroids
Prednisone 5 - 30 mg daily are effective
in treatment of mild-to-moderate SLE,
including cutaneous disease, arthritis,
and serositis.
More severe organ involvement

(nephritis,
pneumonitis, hematologic abnormalities, CNS disease,

require high dosages


of prednisone 1 - 2 mg/kg/day.
and systemic vasculitis)

Corticosteroids
Life-threatening SLE IV pulse MP
(1 g) for 3 days.
Steroid can act as bridging therapy
for the slower-acting
immunomodulatory agents.

Corticosteroids
The dose can then be tapered when
the immunomodulator begins to take
effect.
Once the disease activity is under
control, tapered to none or minimal
daily (prednisone 5 mg/day) or
alternate-day dosing for maintenance
therapy.

Azathioprine
A purine analog.
Azathioprine (22.5 mg/kg/day) is as
an alternative maintenance therapy
to CY in patients with lupus nephritis
and other organ-threatening
manifestations.

Cyclophosphamide
Had significantly
better renal survival
Corticosteroid + intermittent CY
(iv bolus regimens of 0.51
g/m2 BSA)

Corticosteroid alone

C + CY

The NIH regimen the gold standard


.for treatment of diffuse proliferative
GN
Austin H, et al. N Engl J Med 1986;314:614-619.

The traditional CY regimen:


6 to 7 monthly pulse of CY alone or with
pulse MP in the induction, and then quarterly
pulse CY for 2 years.

IV infusion of mesna + rigorous


hydration to prevent hemorrhagic
cystitis and bladder cancer from
acrolein, a toxic metabolite of CY.
Side effects: infertility due to

Mycophenolate Mofetil
RCT MMF appeared to be as effective as
iv CY in inducing short-term remission of
lupus nephritis with a better safety profile.
The role of MMF in improving longterm
outcomes of lupus nephritis remains
unknown.
The dosing range from 500mg to 1500mg twice daily.
Ginzler E, et al. N Engl J Med 2005;353:2219-2228.

Other Drugs and Modalities

Leflunomide
Dehydroepiandrosterone (DHEA)
Thalidomide
Intravenous immunoglobulin (IVIG)
Plasma exchange or plasmapheresis
Autologous Stem Cell
Transplantation

SLE and Pregnancy


Sterility and fertility fates for women
with SLE are comparable to control
groups without disease.
The incidence of flare during
pregnancy or after delivery increase
about 60%, as well as increase risk of
miscarriage or IUFD.

1. Pregnancy outcome is optimal when


disease is in complete clinical remission
for 6 - 12 months.
2. Corticosteroid should be given as low
dose as possible of less than 20 mg daily.
3. Azathioprine can be used during
pregnancy.
Dhar JP, Sokol RJ. Clin Med and Research 2006;4(4):310-21.
Ikatan Reumatologi Indonesia. Paduan diagnosis dan pengelolaan SLE, September 2004.

SLE and APS

1. Eliminate the Antiphospholipid antibodies


by using Immunosuppresive drugs.
2. Improve the risk factors such as cease of
cigarette.
3. Pharmacology:
Low dose (80 mg) daily of Aspirin.
Anticoagulant (UFH, LMWH, or Warfarin)

Lupus Nephritis
Histopathology feature is needed to confirm
the initial treatment corticosteroid alone
versus immunosuppresive/cytotoxic drugs.
Salt restriction if hypertension / edema.
Protein restriction when renal function
impairment of 40%.
Long-term Calcium supplement for those
who on corticosteroid >7.5mg daily.

Lupus Nephritis
Use diuretic as needed.
Avoid NSAIDs.
Monitoring renal function: urinalysis,
creatinine, albumin, C3, anti-dsDNA, 24
hour urinary protein, CrCl 1-2 weekly.
Aggressive treatment of hypertension.

Lupus Cerebral
High morbidity and mortality rate.
The American College of
Rheumatology:
Mild symptoms: headache (including
migraine), reactive psychiatry disorder,
cognitive dysfunction, anxiety disorder.

Severe symptoms: aseptic meningitis,


focal deficit neurology (due to CVD or
demyelization syndrome), chorea,
myelopathy, seizure, acute confusional

The diagnosis is difficult, as there are


no specific laboratory tests.
In severe form (including vasculitis): iv
pulse steroid MP 1 g daily for 3 days.
If no response IV CY 0.75
1.00g/m2 3-6 weekly.
Clinical stable prednisone 1
mg/kg/day in divided dose.

Monitoring SLE
Lifelong monitoring to detect
flares early and institute prompt,
appropriate therapy.
It is important to reduce modifiable
CVD risk factors including tobacco
use, obesity, sedentary lifestyle,
dyslipidemia, and hypertension.

Complement C3, C4
Titer of anti-dsDNA

The frequency of these evaluations


will depend on:
. The activity, severity, and extent o
the SLE.
. The response to treatment.
. The type of treatment

Complement C3, C4
Titer of anti-dsDNA

Changes in the
certain laboratory
results.
A decrease in serum C3,
C4
An increase in anti-dsDNA
A rise in ESR
A decrease in
Haemoglobin or Leukocyte
or Platelet counts
A rise in CPK level
The appearance of
microscopic haematuria or
proteinuria

May precede a
clinical disease
flare.

Modification of
treatment
Significantly
reduce the
chance of flare

THE
TEA
M
APP
RO
ACH

Summary
SLE is a complex disorder with variable
presentations, course, and prognosis.
The pillar management of SLE consists of
education/counseling, exercise/rehabilitation
program, and pharmacological treatment.
Lifelong monitoring is required for most
patients.

Summary
It should be managed by a team
approach.

THANK YOU

Serologic Abnormalities in
SLE

Klippel JH, Dieppe PA, editor. Rheumatology. London: Mosby;1998.

The Pillar of Treatment


Education / counseling,
Exercise / Rehabilitation program,
Pharmacological treatment:
NSAIDs,
Antimalarial drugs,
Glucocorticoids,
Immunosuppresive/cytotoxic drugs.

Mycophenolate Mofetil
MMF is an inactive prodrug of
mycophenolic acid (MPA), which
inhibits inosine
monophosphate dehydrogenase,
lymphocyte proliferation,
and both T- and B-cell function.

Faktor pencetus/eksaserbasi
Procainami
Obat
Obat ::d
Hidralazin
Hidralazin
Metildopa
CPZ,
CPZ, INH
INH

Keguguran
Keguguran

Kehamilan
Kehamilan

Sinar
Sinar UV
UV
(320-400
(320-400 nm)
nm)

SLE

Infeksi
Infeksi

Tindakan
Tindakan
pembedahan
pembedahan

Patients with known renal


disease

A urinalysis,
24-hour urine protein,
Creatinine serum, Crcl
Complete blood
count,
Lipid profile,
Calcium, Phosphate,
Sodium and Potasium.

1/12
at the onset
of nephritis

Patients with known renal


disease

A urinalysis,
24-hour urine protein,
Creatinine serum,
Complete blood
count,
Lipid profile,
Calcium, Phosphate,
Sodium and
Potasium.

1/12
at the onset
of nephritis
More often
If the condition
is unstable