NEW PARADIGM

in
LUPUS ERYTHEMATOSUS SYSTEMIC MANAGEMENT

Erwanto Budi W / Nanang S 

PB Peralmuni - Jakarta
PADI Cabang Bogor
2016
Questionnaire for the diagnosis of systemic lupus erythematosus
Have you ever had arthritis or rheumatism for more than 3 months?
Do your fingers become pale, numb, or uncomfortable in the cold?
Have you had any sores in your mouth for more than 2 weeks?
Have you been told that you have low blood counts (anemia, low WBC
count, or low platelet count)?

Have you ever had a prominent rash on your cheeks for more than 1
month?
Does your skin break out after you have been in the sun (not sunburn)?
Has it ever been painful to take a deep breath for more than a few days
(pleurisy)?
Have you ever been told that you have protein in your urine?
Have you ever had rapid loss of lots of hair?
Have you ever had a seizure, convulsion, or fit?
Courtesy by Sukmana N
 Sex ratios of autoimmune disease
F : M ratio Disease
9:1 Sjorgen
Hashimoto
Graves
Systemic lupus erythematosus
2-3 : 1 Myasthenia gravis
Multiple sclerosis
Rheumatoid arthritis
-1 : 1 Autoimmune hemolytic anemia
Idiopathic thrombocytopenic purpura
Type I diabetes
Vitiligo
Pemphigus
<1:1 Goodpasture
Ankylosing spondylitis
Lockshin MD. Sex differences in autoimmune disease. Lupus 2006 ; 15: 753-756.
How Does The Lupus
Occur?
 Genetic influence

Normal Benign Pathogenic Clinical

Immunity Autoimmunity Autoimmunity Illness

Environmental factors
Arbuckle MR. Development of Auto antibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med
2003;349:1526-33
 Trigger/ Exacerbation
Procainamid
Drugs: Hidralazin UV radiance
Metildopa
CPZ
(320-400 nm)

Abortion Infection
SLE

Pregnancy Surgery
Courtesy by Sukmana N
 Steps in Pathogenesis of SLE
1. Genetic factors/immune
dysfunction
2. Environmental/endogenous
trigger
3. Inflammation
4. Development of Autoimmune
5. Accelerated of Antigen
6. Tissue Damage
7. Clinical Disease

Courtesy by Sukmana N
 Overview of the pathogenesis of SLE
UV light Infection

Self Ag External Ag
Skin cell

APC
Genetic susceptibility

T cell T cell

IC

APC B cell Ab Target

Defective IC clearance
 Drugs implicated in the development of DILE

Vasoo S. Drug-induced lupus: anm update. Lupus 2006 ; 15 :757-761.

Clinical Features Of
SLE
 Clinics Features of SLE
Limphadenopati Fatigue
SSP 12-50% 90%
Panas lama
20%
80-82%
Hepatomepali/
Lost Weight
Splenomegali
60%
20%

Sel cerna
SLE Arthritis/
Arthralgia
18% 90%
Skin
Lung 50-58%
38% Kidney
Hematology 50%
50% Heart Vasculitis
48%
Courtesy by Sukmana N
 Frequency of symptoms of systemic lupus erythematosus

Symptoms Percent at onset Percent at anytime

Fatigue 50 74-100
Fever 36 40->80
Weight loss 21 44->60
Arthritis or arthralgia 62-67 83-95
Skin 73 80-91
Renal 16-38 34-73
Gastrointestinal 18 38-44
Pulmonary 2—12 24-98
Cardiac 15 20-46
Lymphadenopathy 7-16 21-50
Splenomegali 5 9-20
Hepatomegali 2 7-25
Central nervous system 12-21 25-75
Adapted from: Von Feldt, JM, Postgrad Med 1995; 97:79 .
 Heart Manifestation

 Pericarditis
 Myocarditis
 Vasculitis
 Secondary atherosclerotic
coronary artery disease &
myocardial infarction
 Secondary hypertensive disease
 Valvular disease
 Lung Manifestation

 Pleuritis
 Acute lupus pneumonitis
 Chronic intestial lung disease
 Pulmonary hypertension
 Pulmonary embolism
 List of manifestation of CNS
involvement in SLE1
 Manifestation of  Manifestation of
diffuse: local:
 Intractable headaches  Stroke syndromes
 Generalized seizures  Focal seizures
 Aseptic meningitis  Movement disorder
 Psychosis & severe (chorea/transverse
depression myelitis)

 Coma
Courtesy by Sukmana N
 Laboratory
Investigation
 Clinical Monitoring1
 Hematologic abnormalities (Cytopenia)
 Anemia
 Leukopenia
 Lymphocytopenia
 Thrombocytopenia

 Active SLE
 Secondary to drug
 Sepsis associated with SLE

Courtesy by Sukmana N
 Clinical Monitoring2
 ESR, CRP
 ANA
 95% positive → screening test for SLE
 3 - 5% negative
 5 - 25% population positive
 Clinical Monitoring3
 Other Antibodies

 Anti Ro (SS-A)
 Anti La (SS-B)
 Anti Sm
 Anti RNP
 ACA
 ANCA
 Maybe helpful in confirming
a diagnosis (not be used in
monitoring)
 Autoantibodies in SLE
 Antibodies to cell nucleus component
ANA, anti-dsDNA, antibodies to extracellular nuclear antigen (ENA,
anti-Sm, anti-RNP, anti-Jo1)
 Antibodies to cytoplasmic antigens
anti-SSA, anti-SSB
 Cell-specific autoantibodies
lymphocytotoxic antibodies, anti-neurone antibodies, anti-
erythrocyte antibodies, anti-platelet antibodies
 Antibodies to serum components
antiphospholipid antibody
anticoagulants antiglobulin (rheumatoid factor)
How to Diagnose The Lupus
Criterion Definittion
Malar rash Fixed erythema, flat or raised, over the malar eminences,
tending to spare the nasolabial folds
Discoid rash Erythematosus raised patches with adherent keratotic scaling
and follicular plugging; atrophic scarring may occur in older
lesions
Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient
history or physician observation
Oral ulcers Oral or nasopharyngeal ulceration, usually painless, observed
by a physician
Arthritis Nonerosive arthritis involving 2 or more peripheral joints,
characterized by tenderness, swelling, or effusion
Serositis Pleuritis - convincing history of pleuritic pain or rub heard by a
physician or evidence of pleural effusion OR
Pericarditis - documented by EKG, rub or evidence of
pericardial effusion
Renal disorder Persistent proteinuria greater than 0.5 grams per day or greater
than 3+ if quantitation not performed OR
Cellular casts - may be red cell, hemoglobin, granular, tubular,
or mixed
Neurologic disorder Seizures OR psychosis - in the absence of offending drugs or
known metabolic derangements (uremia, ketoacidosis, or
Criterion Definittion
Hematologic disorder Hemolytic anemia - with reticulocytosis OR
Leukopenia - less than 4,000/mm3 total on two or more
occasions OR
Lymphopenia - less than 1,500/mm3 on two or more occasions
OR
Thrombocytopenia - less than 100,000/mm3 in the absence of
offending drugs
Immunologic disorders Positive antiphospholipid antibody OR

Anti-DNA - antibody to native DNA in abnormal titer OR

Anti-Sm - presence of antibody to Sm nuclear antigen OR

False positive serologic test for syphilis known to be positive for

at least six months and confirmed by Treponema pallidum
immobilization or fluorescent treponemal antibody absorption
test

Antinuclear antibody An abnormal titer of antinuclear antibody by

immunofluorescence or an equivalent assay at any point in time
and in the absence of drugs known to be associated with "drug-
induced lupus" syndrome
ACR Criteria
 Using the analogy of the ARA criteria for
the diagnosis of rheumatoid arthritis, we
suggest that patients be classified as
follows:
– Classical SLE — many criteria
– Definite SLE — 4 or more criteria
– Probable SLE — 3 criteria
– Possible SLE — 2 criteria
How To Measure SLE
Activity
Global Measures of Disease Activity
 LACC (Lupus Activity Criteria Count)
 SLAM (The systemic Lupus Activity Measure)
→ clinical features
 BILAG (The british Isles Lupus Activity Group)
– intent to treat approach
 SLEDAI (The systemic Lupus Disease Activity Index)
- prognostic studies → severity (Toronto 1985) / clinical & laboratory
 ECLAM (European Consensus Lupus Activity Measurement)
~ SLEDAI
SLEDAI
Management of Lupus
Erythematosus
 Management SLE
( NANANG SUKMANA)

SUPPORT

CARE TREATMENT

MONITORING
Principles of therapy

1. Remission
2. Organ/ Renal
Survival
3. Patient Survival
4. Complication/
Comorbid
5. Quality of Life
(Cost)
 Which Medication are Right for My Lupus

1. The type and severity of lupus symptoms

2. The person’s response to treatment
3. Risks of drug side effects

Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
 Therapy

 Induction
 Maintenance

Prednison Cyclo MPA

Prednison AZT
MPA
Courtesy by Sukmana N
MPA = Mycophenolic acid
Treatment of SLE: Into the 21st Century
Proteasome
inhibitors PC BAFF
inhibitors
Anti-B cell
Anti-B cell pDC
antibodies
antibodies BR3 sBAFF mBAFF IFN

IFN
TLR cytokines blockade
inhibitors
TLR9 DC TLR
IFN
blockade
B B7.1/2 B7.1/2

CTLA4-Ig
TLR2
TLR4
TLR6
inhibitors
TLR7
CD28
Abatacept TLR8
CD40
IFN
IFN IL-2, 4
IL-10 CXCL13
TNF CD40L CXCR4

pDC
IFN
IL-12p40 T IP-10
S1P
MØ TNF
blockade

TNF
IFN-
Cytokine IL-12
IL-1
Lymphocyte inhibitors IL-23
IL-6

signaling TNF
Chemokine -
inhibitors Lymphocyte IL-6
trafficking blockade
Adapted from Martin & Chan, 2006. Annu. modulators
Rev. Immunol. 24:467-96
 Immunosuppressive Drugs

 Glucocorticosteroids  Calcineurin inhibitors

 Antiproliferative – Cyclosporine
agents – Tacrolimus
– Azathioprine  mTOR inhibitors
– Mycophenolate – Sirolimus
mofetil (MMF) – Everolimus
– Mycophenolic acid
(MPA)
 Class Generic name Uses
Non-steroidal anti- Ibuprofen Relief of Inflammatory pains in
inflammatory drugs muscles, joints, serosae etc

Naproxen
Indomethacin
Celecoxib COX-2 inhibitors (2 less Gr
toxicity)
Rofecoxib
Antimalarias Hydroxychloroquine Autoimmune-related fatigue,
arthropathy and rash;
limited evidence of efficacy
for sicca, thrombophilia and
pain

Reeves. G.E.M. Update on the immunology, diagnosis and management of systemic lupus erythematosus. Internal
Medicine Journal 2004;34:338-347.
 Systemic immunosupressive
Drug Dosage/route Major Indicates Major adverse reactions
Antimetabolites
Methotrexate 7.5-25 mg once JRA, HLA-B27-associated GI upset, stomatitis, hepatotoxicity,
weekly IM, IV, po uveitis, SO,OCP,pars planitis, myelosuppression interstitial
steroid-resistant uveitis pneumonitis
SO, Behcet’s syndrome GI upset, arthralgias, infections,
1-3 mg/kg/d po myelo-suppression, hepatotoxicity
Azathioprine
Infections, malignancies, leucopenia,
Uveitis, scleritis, steroid- nephrotoxicity hepatotoxicity
Mycophenolate
mofetil 1 g bid po sparing agent

Alkylating agents
Chlorambucil 0.1 mg/kg/d po, or 2 Behcet’s syndrome, JRA, SO Infections, GI upset
mg/d increased by steroid-resistant uveitis myelosuppression, gonadal
2 mg/d each week dysfunction, leukimia
for a maximum
daily dose of 18
mg
Cyclophosphamide Wegener’s granulomatosis, Hemorrhagic cystitis, alopecia,
1-2 mg/kg/d/po gonadal dysfunction, leukopenia
scleritis, PUK, Mooren’s ulcer
leukimia

Abbreviations: GI, gastrointestinal; IM, intramuscularly; IV, intravenously; JRA, juvenile rheumatoid arthritis; OCP, ocular cicatricial pemphigoid
 Systemic immunosupressive

Drug Dosage/route Major Indicates Major adverse reactions

Calcineurin inhibitor
Cyclosporine 2-5mg/kg/d IV, po in two equally Behcet’s syndrome, Birdshot Nephrotoxicity, hypertension,
divided doses retinochoroidopathy sarcoid, VKH, hepatotoxicity, tremors
pars planitis, SO, high-risk corneal
0.1-0.15 mg/kg/d/po grafts Nephrotoxicity, tremors, hyperglycemia,
Behcet’s syndrome, VKH, posterior GI upset hypertension,
Tacrolimus uveitis

Biologic
Etanercept 25 mg SC twice weekly, or 50
mg SC once weekly, 0.4
mg/kg/dose SC twice weekly
in children
3-5 mg/kg/d IV repeated 2 & 6
Infliximab then every 8 weeks
1 mg/kg IV once every 14 days
Daclizumab
for a total of 5 doses
HLA-B27-associated uveitis steroid-
resistant uveitis
HLA-B27-associated uveitis Behcet’s
syndrome
Behcet’s syndrome, VKH, sarcoid,
pars planitis, idiopathic panuveitis,
multifocal choroiditis
Rash, flu-like symptoms, heart failure
tuberculosis, sepsis, anaphylaxis,
worsening of multiple sclerosis
Dyspnea headache, rash, heart failure,
reactivation of tuberculosis, sepsis,
hepatoxicity
Hemorrhagic cystitis, alopecia, gonadal
dysfunction, leukopenia leukimia

Abbreviations: IV, intravenously; SC, Subcutaneously; VKH, Vogt_Koyanagi-Harada syndrome

Hemady RK, et al.Immunosuppressive Agents & Nonsteroidal Anti-inflamatory Drugs for Ocular Immune & Inflamatory Di sorder.2005
 Drugs for Any Condition in Lupus Case2
Class Generic name Uses
Corticosteroids Prednisone Serositis, cytopenias, major
organ Involvement; low-dose
transient use for refractory
musculocutaneous features
Potent Azathioprine All potent immunomodulators
Immunomodulators Methotrexate have the following uses: Severe
Cyclosporine organ involvement or
Cyclophosphamide cytopenia, steroid-sparing role
Leflunomide where disease relapses with
Mycophenolate attempted steroid weaning, and
introduced relatively early in
moderate-severe rheumatoid
arthritis to limit joint damage

Reeves. G.E.M. Update on the immunology, diagnosis and management of systemic lupus erythematosus. Internal
Medicine Journal 2004;34:338-347.
 Types of anti malarials

 Hydroxychloroquine (Plaquenil)
 Chloroquine (aralen)
 Quinacrine (atabrine)

Gluck O, Anti-Malarials in The Treatment of Lupus, Lupus Foundation of America. 2001

 Anti - malarials are:
Muscle and joint pain
Inflammation of the lining of the heart
(pericarditis)
Inflammation of the lining of the lung
(pleuritis)
Other symptoms of lupus such as fatigue
and fever

Gluck O, Anti-Malarials in The Treatment of Lupus, Lupus Foundation of America. 2001

 Anti malarials
Other side effects can include:
•Hair loss
•Dry skin
•Loss of appetite
•Abdominal bloating
•Upset stomach
•Stomach cramps
•Nausea, vomiting and diarrhea

Gluck O, Anti-Malarials in The Treatment of Lupus, Lupus Foundation of America. 2001

 Retinal damage that is caused by
Chloroquin (Plaquenil® ) is
sometimes reversible if it is detected
early.
However, damage due to the use of
chloroquine (Aralen) is irreversible

Gluck O, Anti-Malarials in The Treatment of Lupus, Lupus Foundation of America. 2001

 Glucocorticosteroids
 Despite the fact that prednisolone binding to albumin
is not saturable, a low albumin concentration was
related to an increased incidence of prednisolone
related side effect (Jusko & Ludwing 1991)

Greve J. Optimisation of Immunosuppressive Therapy Using Pharmacokinetic Principles. Clin

Pharmacokines. 1992;23(5):380-90.
 Important Anti-Inflammatory and Immunosuppresive
Effects of Glucocorticoids
A. Anti-inflammatory Effects
1. Inhibition of blood vessel dilatation and
permeability
2. Inhibition of neutrophil and monocyte migration
to periphery
3. Inhibition of synthesis of inflammatory mediators
such as eicosanoids by downregulating
phospholipase A2 and COX-2
4. Downregulation of destructive enzymes
5. Alteration of cytokine balance in favor of anti-
inflammatory cytokines whereas proinflammatory
cytokines are suppressed

Wallace J Daniel & Hahn Hannahs Bevra : Dubois’ lupus Erythematosus, Seventh Edition,
Lippincot Williams & Wilkins 2007
B. Immunosuppressive effects
1. Lymphopenia
2. Inhibition of signal transduction events critical for T-cell activation
3. Inhibition of IL2 synthesis and signaling
4. Downregulation of cell surface molecules important for full T-cell
activation and function
5. Inhibition of antigen-presenting cell function. Depletion of
plasmacytoid dendritic cells and production of interferon-alpha
6. Deviation of immune responses towards a Th2-type cytokine
formation
7. Induction of T-cell apoptosis

Wallace J Daniel & Hahn Hannahs Bevra : Dubois’ lupus Erythematosus, Seventh Edition, Lippincot
Williams & Wilkins 2007
 Anti –Inflammatory Drugs
 Anti-inflammatory medication are the most commonly
used drugs for lupus treatment, particularly for
symptoms such as:
o Fever
o Arthritis, or
o Pleurisy
 Improvement in symptoms is generally noted within
several days of beginning treatment
 In the majority of people with lupus, anti-
inflammatory drugs are the only medication that is
ever required to control their lupus
 Prednisone
 Prednisone is an extremely effective drug may be
necessary to control active lupus
 Those individuals with organ-threatening diseases (i.e.,
heart, lung, kidney, liver) usually need steroids in order
to prevent loss of function in the organ.
 People who tolerate steroids poorly or do not respond
optimally often benefit from the addition of steroid-
sparing of immune suppressive drugs

Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
 Prednisone
 It may be givens as often as four times each day, as
frequently as once every other day, or at any frequency

Dose Miligrams
Low Less than 10 mg daily
Moderate 11 to 40 mg daily
High 41 to 100 mg daily

 Occasionally, very large doses of steroids may be given

for a short period of time. This treatment, referred to
as pulse steroids

Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
 1 gr/IV  for 3 days

Indication :
Acute Oliguria (ARF)
Cerebral with coma
Lupus Crisis (acute serious SLE)

Courtesy by Sukmana N
 Side Effect From Glucocorticoid Use
1. Changes in appearance
 Acne
 Development of a round or moon-shaped face
 Weight gain due to increased appetite
 A redistribution of fat, leading to a swollen face and
abdomen, but thin arms and legs
2. Psychologyical problems
 Iritability
 Agitation
 Euphoria or depression
 Insomnia

Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
 Side Effect From Steroids Use
3. An increase in susceptibility to infection may occur
with high doses of steroids
4.Prednisone may aggravate:
 Diabetes
 Glaucoma
 High blood pressure
5.Prednisone often increases levels of:
 Cholesterol
 Triglycerides
6.Steroids also can suppress growth in children
Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
Side Effect From Long-term Use
of Steroids

 Avascular necrosis of bone

 Osteoporosis or thinning of the bones
 Cataracts
 Premature arteriosclerosis

Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
 Management L.N

 Chan et all: MMF 2 gr/ day  6 month

Taper : 1 gr / day
 Ginzler : MMF 3 gr /day
 Contreas : MMF 1,5 – 2 gr / day (max 2 gr)

 6 month  0,25 – 05 gr.

(Pisoni Cn, Karim Y, Cuadrado MJ. Lupus 2005, 14, s9 – s11.)

 Outcome measure in the induction and
maintenance treatment of lupus nephritis
Induction treatment
Remission and response
 Decrease in proteinuria to < 1g/day(or < 0.8 g/day in cases of lupus
nephritis that were diagnosed in the past 6 months) with normal
serum albumin concentrations; inactive urine sediment ; improved
or stable renal function

Partial remission or partial response

 Significant change in proteinuria (i.e. if nephrotic at haseline ≥50%
decrease in proteinuria to <3 g/day; if non-nephrotic at baseline
but not meeting the remission and response criteria decrease to ≤
1g/day) and improved or stable renal function

Boumpas T Dimitrios, Sidropoulus Prodromos, Bertsias George Bertsias, Optimum therapeutic approaches for lupus nephritis:
what therapy and for whom?, Nature publishing group, 2005
 Outcome measure in the induction and
maintenance treatment of lupus nephritis

Treatment failure
 Persistent proteinuria of ≥ 3g/day or any degree of
proteinuria with serum albumin <3g/day or progressive
renal impairment (i.e. a reproducible ≥ 33% or > 0.3 mg/dl
increase from baseline serum creatinine, whichever is
greater) after the first 6-12 months of treatment

Boumpas T Dimitrios, Sidropoulus Prodromos, Bertsias George Bertsias, Optimum therapeutic approaches for lupus
nephritis: what therapy and for whom?, Nature publishing group, 2005
Neuropsychiatric syndromes associated with
SLE
Central nervous system Peripheral nervous system

Aseptic meningitis Guillain-Barré syndrome (acute

Cerebrovascular disease inflammatory polyradiculoneuropathy)
Demyelinating syndrome Autonomic disorder
Headache Mononeuropathy (single/multiplex)
Movement disorders (chorea) Myasthenia gravis
Myelopathy Cranial neuropathy
Seizures and Seizure disorders Plexopathy
Acute confusional state Polyneuropathy
Anxiety disorder
Cognitive dysfunction
Mood disorders
Psychosis

Lau Sing Chak, Atlas of Lupus Erythematosus 2007

 LES Inaktif

NL
• Hematology
50-60% • Urinalisis
• Ureum/Cr/GD
APS Nepritis lupus(NL)
Pregnancy • ACL/LA
• SSA/SSB
• Hipertension • C3/C4
• Preleklamsi • Antids DNA
• 24 jam Urin
Abortus Sc (+) Sc (-) protein

PARTUS

Normal Marformasi C.Heart Block Prematur IUGR

kongenital 8,8% SSA,SSB (+) 60% 30%
Pred (-) 1% SSA,SSB (-)
Sitotoksik (+) Courtesy by Sukmana N
 Drugs In Pregnancy and Lactation

Pregnancy Lactation
NSAIDs Yes (avoid after 32 weeks) Yes
Antimalarials Yes Yes
Corticosteroids Yes Yes
Azathioprine Yes Yes?
Mycophenolate No No
Methotrexate No No
Cyclophosphamide No No
Anti-TNF No No
Warfarin No (with caution after first Yes
trimester)
Heparin Yes Yes
AAS (low dose) Yes Yes

Lupus and Pregnancy : ten questions and some answers. Gruiz-Irastorza and MA Khamashta. Lupus (2008)17, 416-420
 When Should My Doctor Prescribe
Immunosuppressive Drugs?
 These drugs are generally reserved for people
with more serious manifestations of lupus, such
as lupus nephritis or neurologic disease, in whom
treatment with corticosteroids has failed

 It is very important that cytotoxic drugs only be

given by physicians who are experienced with the
use of these medications

Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
 IMURAN
( Azathioprin )
 Prolong life
 Preserve kidney function
 Reduce disease symptoms
 Reduce damage to vital organs, such as the
kidney and lungs
 Sometimes even serve to put the disease
info remission

Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
 Cytoxan (Cyclophosphamide)
 An increasing risk of developing malignancies, including leukimia
and bladder cancer, with long-term Cytoxan use
 Temporary or permanent sterility in both women and men
 Leading to damage of a developing fetus if a woman gets pregnant
while being treated with the drug
 Bleeding from the bladder-this usually can be prevented by
drinking large amounts of water
 Causing a prediposition to develop shingles
 Hair loss
 Like Imuran, causing a prediposition to develop unusual infections,
particularly when given in combination with high doses of steroids

Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
 Immunosuppressive Side Effects
 The drugs have a major effect on cells produced by the bone
marrow, including:
o White blood cells
o Red blood cells
o Platelets
 Thus, people treated with cytotoxic drugs must have regular
complete blood counts (CBCs) to make certain that levels of
these cells do not become too low
 In addition, cytotoxic drugs reduce a person’s ability to fight off
infections
 Those receiving cytotoxic drugs are more likely to contract viral
infections such as shingles (herpes zoster)
Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
 Specific Toxicities
 Cyclophosphamide may cause:
• Hair loss
• Bladder complications
• Sterility
 Azathioprine may cause:
• An allergic –type of hepatitis
• Pancreatitis
 Methotrexate may cause:
• Liver damage, including cirrhosis
• Serious lung toxicity
 Cyclosporine:
• Commonly produce hypertension
• May lead to kidney damage
Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
 Possible Risk Cytotoxic Drugs
 The immune system may be suppressed too much,
which causes an increased susceptibility to infection,
particularly shingles (a painful, blistering skin
condition) and pneumonia
 The bone marrow can be suppressed as well, which
results in reduction in red blood cells, white blood
cells, or clot-forming platelets
 Suppression of hair cell growth may lead to overall lost
of hair
 The cytotoxic effects on gonadal cells can lead sterility
 New Treatment in SLE
(cell surface molecules)
Treatment Mode of action Status
Anti CD20 (Rituximab) B cell depletion Phase II/III trial in
patients SLE is
ongoing
Anti CD22 Modulation of B cell Safe in phase I. Phase
(Epratuzumab) signaling II it is on going

Anti CD40L Blocks T-B cell cross

talk

CTLA4 Ig Block co-stimulation Effective in mice

(abcatacept) of T cells
People with lupus often require other
drugs for:

• Diuretics for fluid retention

• Anti-hypertensive drugs for increased blood
pressure
• Anti convulsants for seizure disorders
• Antibiotics for infections
• Drugs for osteoporosis
 Prognosis in SLE
I. Disease manifestation

II. Disease activity

III. Specific organ damage

IV. Functional status

Thank You