HISTORY

▪ The word ‘lupus’ (Latin for

‘wolf’) is attributed to the
thirteenth century physician
Rogerius who used it to
describe erosive facial lesions
that were reminiscent of a
wolf's bite.
 1997 Update of the 1982 American
College of Rheumatology Revised
Criteria for Classification of Systemic
Lupus Erythematosus
1. Malar (butterfly) rash
2. Discoid lesions
3. Photosensitivity
4. Oral or nasopharyngeal ulcers
5. Non-deforming arthritis in two or more
joints
6. Serositis: pleuropericarditis, aseptic
peritonitis
7. Renal: persistent proteinuria › 0.5 g/d or
›3+ or cellular casts
 1997 Update of the 1982 American
College of Rheumatology Revised
Criteria for Classification of Systemic
Lupus Erythematosus

8. Neurologic disorders: seizures, psychosis

9. Heme: hemolytic anemia; leucopenia, lymphopenia,
thrombocytepenia
10.Immune: anti-DNA, or anti-Sm, or APS (ACA IgG,
IgM), or lupus anticoagulant (standard) or false +
VDRL
11.Positive ANA

Definite SLE = 4 or more positive criteria

 New SLICC* Revision of
the ACR Classification
Criteria - Clinical
1. Acute/subacute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral/Nasal ulcers
4. Nonscarring alopecia
5. Inflammatory synovitis with physician-observed
swelling of two or
more joints OR tender joints with morning
stiffness
6. Serositis

*Systemic Lupus International Collaborating Clinics (SLICC)

 New SLICC Revision of
the ACR Classification
Criteria - Clinical
7.Renal: Urine protein/creatinine (or 24 hr urine
protein) representing at least 500 mg of protein/24
hours or red blood cell casts
8.Neurologic: seizures, psychosis, mononeuritis
multiplex, myelitis, peripheral or cranial
neuropathy, cerebritis (acute confusional state)
9.Hemolytic anemia
10.Leukopenia (< 4000/mm3 at least once) OR
Lymphopenia (< 1000/mm3 at least once)
11.Thrombocytopenia (<100,000/mm3) at least
once
 SLICC Revision of the
ACR Classification Criteria –
Immunologic
1. ANA (antinuclear antibody)
2. Anti-dsDNA
3. Anti-Sm (anti-Smith) antibody
4. APS abs: Lupus anticoagulant , false-
positive test for syphilis, anticardiolipin
IgG, IgM, or IgA
5. Low complement: low C3, low C4, low
CH50
6. Direct Coombs test in the absence of
hemolytic
anemia
 Lupus – SLICC New Classification
Criteria: 4 needed

▪At least 1 clinical plus at least 1

immunologic criteria (for a total of
4)

or
▪Lupus nephritis by biopsy as the
sole clinical criterion plus SLE
autoantibodies: (+) ANA or (+) anti-
dsDNA
 Acute/subacute cutaneous
lupus
1) Lupus Malar rash (do not count if
malar discoid)
 Acute/subacute cutaneous
lupus
2) Bullous
lupus
 Acute/subacute cutaneous
lupus
3) Toxic epidermal necrolysis
variant of SLE
 Acute/subacute cutaneous
lupus
4) Maculopapular lupus
rash
 Acute/subacute cutaneous
lupus
5) Photosensitive lupus
rash
 Acute/subacute cutaneous
lupus
6) Subacute cutaneous lupus
Nonindurated psoriaform and/or annular polycyclic lesions that resolve
without scarring
 Chronic cutaneous
lupus
1. Classic discoid rash
 Localized (above the neck)
 Generalized (above and below
the neck)
 Chronic cutaneous
lupus
2. Hypertrophic
(verrucous) lupus
 Chronic cutaneous
3. lupus
Lupus panniculitis
(profundus)
 Chronic cutaneous
4. Mucosal lupus
lupus
 Chronic cutaneous
lupus
5. Lupus erythematosus tumidus
Erythematous, succulent, edematous, nonscarring plaques in
sun-exposed areas
 Chronic cutaneous
lupus
6. Chillblains lupus
Painful inflammation of small blood
vessels
 Chronic cutaneous
7. lupus planus
Discoid lupus/lichen
overlap
 Oral/Nasal
ulcers
▪ Inthe absence of other causes, such as infecti
vasculitis, Behcet’sdisease, on
(herpesvirus), inflammatory bowel disease, reactive arthritis,
and acidic foods
 Nonscarring
alopecia
▪ In the absence of other causes such as alopecia areata, drugs,
iron deficiency, and
androgenic alopecia.
 Arthrit
is
▪ Arthritis of the proximal interphalangeal
(PIP) and metacarpophalangeal (MCP)
joints of the hands, as well as the wrists
▪ Synovitis involving 2 or more joints,
characterized by swelling or effusion OR
tenderness in 2 or more joints and at
least 30 minutes of morning stiffness
▪ Tenderness, edema, and effusions
accompany a polyarthritis that is
symmetric, nonerosive, and usually
▪ Jaccoud
nondeforming
arthropathy is the term used to
describe the nonerosive hand deformities
due to chronic arthritis and tendonitis that
develop in 10% of patients with SLE. Jaccoud
arthropathy
 Serosit
is
▪ Typical pleurisy for more than 1 day
OR pleural
effusions OR
pleural rub
▪ Typical pericardial
pain (pain with
recumbency
improved by sitting
forward) for more
than 1 day
OR pericardial
effusion OR
pericardial rub
 Renal
Manifestations
▪ Urine protein–to-creatinine ratio (or 24-hour urine protein)
representing 500 mg protein/24 hours
▪ Red blood cell casts
 Neurologic
Manifestations
1. Seizures
2. Psychosis
3. Mononeuritis multiplex - In the absence of other known causes
such as primary vasculitis
4. Myelitis
5. Peripheral or cranial neuropathy - In the absence of other known
causes such as primary vasculitis, infection, and diabetes
mellitus
6. Acute confusional state - In the absence of other causes,
including toxic/metabolic,
uremia, drugs
 Haematological
Manifestations
1) Hemolytic anemia
2) Leucopenia (4,000/mm3 at least once)
In the absence of other known causes such as Felty’s syndrome, drugs, and
portal hypertension

OR
Lymphopenia (1,000/mm3 at least once)
In the absence of other known causes such as corticosteroids, drugs, and
infection

3) Thrombocytopenia (100,000/mm3 )
At least once in the absence of other known causes such as drugs, portal
hypertension, and thrombotic thrombocytopenic purpura
 Immunologic
criteria
1.ANA level above laboratory reference range
2.Anti-dsDNA antibody level above laboratory reference range (or 2-fold the
reference range if tested by ELISA)
3.Anti-Sm: presence of antibody to Sm nuclear antigen
4.Antiphospholipid antibody positivity as determined by any of
the following: Positive test result for lupus anticoagulant
False-positive test result for rapid plasma reagin
Medium- or high-titer anticardiolipin antibody level (IgA,
IgG, or IgM) Positive test result for anti–B2-glycoprotein
I (IgA, IgG, or IgM)
5.Low complement - Low C3, Low C4, Low CH50
6.Direct Coombs’ test in the absence of hemolytic anemia
 The Use of ANA for Screening
 Immunofluorescence ANA assay (IF) remains the gold standard for detection of ANA
 Many laboratories perform immunoassays (such as the multiplexed immunobead
assay), for the detection of ANA as it is less labor-intensive
 Data suggest that screening with an immunoassay would result in
misclassification
and potential delay or missed diagnoses
 Immunofluorescence (IF) should remain the preferred assay
for ANA testing - Endorsed by the American College of
Rheumatology (ACR)
 SLE –
Management
▪ EULAR recommendations for the management of systemic lupus
erythematosus. Report of a Task Force of the EULAR Standing
Committee for International Clinical Studies Including Therapeutics -
July 2007
▪ Joint European League Against Rheumatism and European Renal
Association– European Dialysis and Transplant Association
(EULAR/ERA-EDTA) recommendations for the management of adult
and paediatric lupus nephritis - July 31, 2012
▪ American College of Rheumatology Guidelines for Screening, Case
Definition, Treatment and Management of Lupus Nephritis - 2012 June
 Treatment of non-major organ
involvement
▪ Glucocorticoids, Antimalarials, Non-steroid anti-inflammatory drugs
(NSAIDs) and, in severe, refractory cases immunosuppressive agents
are used in the treatment of SLE patients without major-organ
involvement.
▪ Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for
the symptomatic management of arthralgia, mild arthritis, myalgia,
serositis and fever in patients with SLE.
▪ They do not have any immunosuppressive properties and despite their
widespread use in the lupus population there is little trial evidence for
safety or efficacy.
▪ They should be used for short periods of time and with caution
especially in patients
with renal involvement, hypertension and established heart disease.
 Treatment of non-major organ
Hydroxychloroquine involvement
▪ Hydroxychloroquine has emerged as the drug of choice and some
experts advocate its use in all patients provided that there are no
contraindications.
▪ Owing to its anti-inflammatory and immunomodulatory properties, it
has a significant impact on the long-term outcome by modifying the
course of illness through reduction of low-grade flares and hence
slows progression to severe disease requiring more intense
treatment.
▪ Hydroxychloroquine is most useful in the management of
mucocutaneous, musculoskeletal and constitutional symptoms such
as fatigue and fever.
▪ Recently, hydroxychloroquine has been shown to have
cardioprotective properties in several studies, by reducing total
cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides
(TG) and increasing high-density lipoprotein (HDL) cholesterol levels
 Treatment of non-major organ
Hydroxychloroquine involvement
▪ Hydroxychloroquine has a good safety profile and toxicity is
infrequent, mild and largely reversible.
▪ In pregnancy, it is safe with noticeable reduction in SLE activity and
no adverse effects
on the child
▪ Retinal toxicity and macular damage are rare with hydroxychloroquine.
▪ Owing to the remote risk of hydroxychloroquine-related maculopathy,
guidance from the Royal College of Ophthalmology, UK, states that
doses should not exceed 6.5 mg/kg/day and patients should have
yearly visual acuity monitoring.
 Treatment of non-major organ
Corticosteroids involvement
▪ Several studies have shown that a short course of moderate-dose
corticosteroids can not only treat active disease but can also help prevent
flares in clinically stable but serologically active patients.
▪ In mild disease, prednisolone is given in doses starting at 0.1–0.3
mg/kg/day followed by a gradual tapering dose regimen according to
clinical response.
▪ The dose rises to 0.4–0.6 mg/kg/day in moderate disease and as high as
0.7–1.5 mg/kg/day in very severe disease.
▪ At such high doses, pulse therapy with intravenous (IV)
methylprednisolone (MP; 500–1000 mg on one to three occasions) is
deemed by many physicians to be safer with fewer associated side
effects.
▪ Prednisolone is safe in pregnancy as they are inactivated by 11 β-
hydroxysteroid dehydrogenase, so that less than 10% crosses the
placenta
 Treatment of non-major organ
involvement -
Immunosuppressive therapies
▪ In patients with moderate-to-severe disease who require 10mg
prednisolone/day or more to manage their disease, other
immunosuppressive agents should be added to reduce the steroid
requirements.
Azathioprine
▪ Azathioprine is commonly used for the induction of remission and as a
steroid-sparing agent in mild-to-moderate disease.
▪ In severe disease, it is used as maintenance therapy and data from
lupus nephritis trials show significant improvement in disease activity
following induction therapy with cyclophosphamide or mycophenolate
mofetil (MMF)
▪ It is safe in pregnancy, as the foetal liver cannot metabolize
azathioprine to the active metabolites
 Lupus nephritis:
treatment
▪ The treatment of lupus nephritis often consists of a period of intensive
immunosuppressive therapy (induction therapy) followed by a longer
period of less intensive maintenance therapy.
▪ Class I and Class II generally does not require immunosuppressive
treatment
▪ In general, patients with Class III, IV and V require aggressive therapy
with glucocorticoids and immunosuppressive agents.
▪ Class VI (sclerosis of ≥90% of glomeruli) generally requires
preparation for renal
replacement therapy rather than immunosuppression.
▪ Options for induction therapy are either IV Cyclophosphamide or MMF
in combination with pulse Methylprednisolone (Methylprednisolone
alone in pregnancy)
▪ Options for maintenance therapy are azathioprine (AZA), MMF or
Prednisone up to 10
 Lupus nephritis: Adjunctive
Treatments
▪ The Task Force Panel recommended that all SLE patients with nephritis
be treated with a background of hydroxychloroquine (HCQ) (level C),
unless there is a contra- indication.
▪ All lupus nephritis patients with proteinuria ≥ 0.5 g per 24 hours
should have blockade of the renin-angiotensin system
▪ Treatment with either ACEi or ARBs reduces proteinuria approximately
30%, and significantly delays doubling of serum creatinine and
progression to end stage renal disease
▪ The use of combination ACEi/ARB therapies is controversial.
▪ Careful attention should be paid to control of hypertension, with a
target of ≤ 130/80.
▪ Statin therapy be introduced in patients with LDL cholesterol >100
mg/dL
 Lupus nephritis:
▪ Completerenal
Treatment goals
defined as urine
mg/mmolresponse, protein:creatinine
equivalent to proteinuria <0.5 ratio (UPCR)
(roughly g/24 h) and normal or <50
near
• normal(within 10% of normal) GFR.

▪Partial renal response, defined as ≥50% reduction in

proteinuria to subnephrotic levels and normal or near-normal
GFR, should be achieved preferably by 6 months and no later
than 12 months following treatment initiation.
 Treatment of severe
neuropsychiatric lupus
▪ Seizure, peripheral neuropathy, optic neuritis, transverse myelitis,
brainstem disease,
coma and internuclear ophthalmoplegia
▪ Induction therapy with intravenous methylprednisolone (MP) was
followed by either intravenous monthly cyclophosphamide (CY) versus
intravenous MP every 4 months for 1 year and then intravenous CY or
intravenous MP every 3 months for another year.