Systemic Lupus
Erythmatosus
PGR Medicine
Dr. Usama Saleem

Case Presentation
A 30 year old female Known/Case of SLE with lupus nephritis since July 2021
and Post cholecystectomy since 2017 complained of loose stools with fresh
blood dripping on toilet 3 episodes per day,perianal pain,
vomiting 1-2 episodes, for 3 days. Patient also complained of 35 kg
weight loss in last 2 years .On further exploring patient also complaint of loose
stools on and off for last 4 years which are not associated with any Abdominal
pain, Fever , blood , fat or mucus in it.

She complained of odynophagia and dysphagia to both solids and liquids.
Patient denies any joint pain , rash, Dry eyes ,Dry mouth
Patient complained of oral ulcers , photosensitivity and raynaud
phenomenon on and off
> Hospital stay
Patient developed Right knee pain during hospital stay
O/E
Pallor + Pedal edema++. white coated tongue
GCS 15/15. CVS S1+S2+0. RESP NVB+0. ABDOMIN SNT
Power 5/5 in all limbs with b/L downgoing plantars
MSK examination shows no tenderness, swelling , warmth , movement
limitation in any joints .

Past medical Hx. Past Surgical Hx
SLE since july 2021
Lupus Nephritis in Oct 2021
Patient was taking HCQ OD ,
Sunblock cream TDS, CAC 1000 OD ,
Vitamin D3 Monthly
,INOGRAF 0.5mg BD' Zeegap 25mg
HS,Sangobion OD and Deltacortril
5mg OD
Cholecystectomy 2017

Investigations
>Hb 10.2. MCV 79.2 TLC 5.9. Plt 307. ESR 31. Na 132 K 2.5.
>Albumin 1.9. Creatinine 1.2. (eGFR 60 ml/hr) CRP 24.
>Urine C/E 12-15/hpf Protein Nil
>USG ABD;
Hepatic steatosis
>Endoscopy;
Esophageal Candidiasis
Esophageal Ulcers
Stool C/E shows
Bacteria ++
Food +
Mucous Nil
Blood Nil

ANA + Homogenous pattern. Titre 1:320. July 2021
Serum Anti dsDNA IgG positive. July 2021
Serum Antitransglutaminase IgA Neg- July 2021
ENA Profile Negative. OCT 2021
C3 53. C4 24. OCT 2021
SPOT URINE PROTEIN 213
SPOT URINE CREATININE 149
P:C RATIO 1.4. OCT 2021
Creatinine1.0. OCT 2021

Diagnosis
SLE
Acute infectious Gastroenteritis
Anal Fissure
Esophageal candidiasis and ulcers

Treatment
Inj Oxidil 2gm OD
Inj Solumedrol 20mg BD
Tab HCQ 200mg HS
Sunblock cream TDS
Tab CAC1000 Plus OD
Cap inograf 0.5mg BD
Cap Zeegap 100mg HS
Inj R/L 1000cc OD
inj Onset 8mg Sos
Xylocaine and GTN ointment locally
Tab Neo K 2 tabs TDS
Inj Risek 40mg OD
Nilstat oral Drops 2 dropper TDS
Inj Albumin 50 cc OD
Cap Diflucan 50mg BD
Syp Ulsanic 2tsf TDS
Enterogermina PO OD
Tab Levopraid 25mg BD
Tab Rifaxa 550mg bd

Discharge Medications
Tab HCQ 200mg HS
Sunblock cream TDS
Tab CAC1000 Plus OD
Cap Zeegap 100mg HS
Xylocaine and GTN ointment
locally
Nilstat oral Drops 2 dropper TDS
Cap Diflucan 50mg BD
Syp Ulsanic 2tsf TDS
Enterogermina PO OD
Tab Levopraid 25mg BD
Tab Rifaxa 550mg bd
Tab Deltacortril 5mg PO OD

Systemic Lupus
Erythmatosus

Definition. Pathogenesis
SLE is an inflammatory
autoimmune disorder character-
ized by autoantibodies to nuclear
antigens. It can affect multiple
organ systems
>Trapping of antigen-antibody
complexes in capillaries of visceral
structures
>Autoantibody-mediated
destruction of host cells (eg,
thrombocytopenia).

Incidence
It is affected by many factors
>Sex
MORE COMMON IN FEMALES
85% Of the Patients are females
>Race
MORE ,COMMON IN BLACK FEMALES THAN WHITE
SLE occurs in 1:1000 White women but in 1:250 Black women
>Genetic Inheritance
Familial occurrence of SLE has been repeatedly documented, and the
disorder is concordant in 25–70% of identical twins

CRITERIA
American college of
Rheumatology old
criteria
(A patient is classified as
having SLE if any 4 or more of
11 criteria are met.)

SLICC CRITERIA
Presence of any four criteria (must
have at least 1 in each category)
qualifies patient to be classified as
having SLE

EULAR/ACR Updated
Criteria
It consists of seven clinical
domains and three immunologic
domains. Each criterion is
assigned points, ranging from 2
to 10.

Patients with ANA titre greater
than1:80 , at least one clinical
criterion and 10 or more points
are classified as having SLE.
Interpretation

CRITERIA Sensitivity Specificity
ACR 1997 82.8% 93.4%
SLICC 2012 96.7% 83.7%
ACR/EULAR 2019 96.1% 93.4%

Systemic Manifestations of SLE

Non specific symptoms
> Fever
> malaise
> Anorexia
> Weight loss
> Alopecia
> Raynand Phenomenon

Musculoskeletal
Joint symptoms, with or without active synovitis, occur in over 90% of
patients and are often the earliest manifestation. The arthritis can lead
to reversible swan-neck deformities, but radiographic erosions and
subcutaneous nodules are rare

Cutaneous
Most patients have skin lesions at some time;
the characteristic “butterfly” (malar) rash affects less than half of
patients. Other cutaneous manifestations are panniculitis (lupus
profundus), discoid lupus and typical fingertip lesions (periungual
erythema, nail fold infarcts, and splinter hemorrhages)

Malar rash

Pulmonary
Pleurisy and pleural effusion are common.
Pneumonitis, interstitial lung dis-ease, and pulmonary hypertension can
rarely occur.
Alveolar hemorrhage is uncommon but life-threatening

Ocular
Ocular manifestations include keratoconjunctivitis sicca and retinal
vasculopathy (cotton-wool spots, episcleritis, scleritis and optic
neuropathy)

Cardiac
The pericardium is affected in the majority of patients. Heart failure may
result from myocarditis and hypertension. Cardiac arrhythmias are
common. Atypical verrucous endocarditis of Libman-Sacks is usually
clinically silent but occasionally can produce acute or chronic valvular
regurgitation(most commonly mitral regurgitation)

Vascular
The prevalence of transient ischemic attacks, strokes, and myocardial
infarctions is increased in patients with SLE. These vascular events are
increased in, but not exclusive to, SLE patients with antibodies to
phospholipids (antiphospholipid antibodies), which are associated with
hypercoagulability and acute thrombotic events

Neurological
Neurologic complications of SLE include psychosis, cognitive
impairment, seizures, peripheral and cranial neuropathies, transverse
myelitis, and strokes

Renal
Several forms of glomerulonephritis may occur, including mesangial,
focal proliferative, diffuse proliferative, and membranous .Some
patients may also have interstitial nephritis. With appropriate therapy,
the survival rate even for patients with serious kidney disease
(proliferative glomerulonephritis) is favorable, a sub-stantial portion of
patients with severe lupus nephritis develop end-stage kidney disease

Hematological
Hematologic manifestations include
leukopenia, auto-immune hemolytic anemia, immune thrombocytopenia,
and thrombotic thrombocytopenic purpura

Gastroenterology
Nausea, sometimes with vomiting, and diarrhea can be manifestations
of an SLE flare Increases in serum aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) are common when SLE is active.
Occasionally, abdominal pain in active SLE may be directly related to
active lupus, including peritonitis, pancreatitis, mesenteric vasculitis,
and bowel infarction. Rarely, lupus enteritis may be the initial
manifestation of SLE. ]Jaundice due to autoimmune hepatobiliary
disease may also occur.
Mouth ulcers are also common

Investigations
Antinuclear antibody (ANA) tests
based on immunofluorescence
assays nearly 100% SENSITIVE for
SLE but not specific
Antibodies to double-stranded
DNA and to Sm are SPECIFIC for
SLE but not sensitive, since they
are present in only 60% and 30% of
patients, respectively.

Frequency of autoantibodies in SLE
ANA by IF
Anti dsDNA
Anti Sm
RA Factor
Anti SSA
Anti SSB
95-100%
60%.
10-25%,
20%
15-20%
5-20%

Antiphospholipid Antibodies
Anti-cardiolipin antibody 25%
Lupus anticoagulant 7%
Anti–beta-2-glycoprotein 1 25%
These antibodies are associated with increase in thrombotic
complications of SLE eg Stroke and MI

CBC
Anemia (Hemolytic anemia,
anemia of chronic disease)
Leukopenia (WBC <4000/µL )
Thrombocytopenia(<100,000/μL)
Serum complement levels
Depressed
C3 and C4 suggests active disease
ESR and CRP
Durng disease flares, elevations
in the ESR are common, but the
serum CRP is usually normal
Liver function tests
ALT and AST may be raised in
acute SLE or in response to
therapies like NSAIDS or
Azathioprine
Albumin is usually low in case of
proteinuria

Urine complete
examination
Lupus nephritis shows hematuria
with or without casts, and
proteinuria (varying from mild to
nephrotic range) .
Creatinine usually deranged
in active lupus nephritis
P:C Ratio
Spot urine Protein and spot urine
creatinine is used to quantify
proteinuria
Renal biopsy helps to
identify the type of
glomerulonephritis.
it is recommended in all cases of
active Lupus Nephritis unless
there is any contraindications

Classification of Lupus Nephritis ISN/RPS
Class I: Minimal Mesangial Lupus Nephritis mesangial immune deposits by
immunofluorescence only
Class II: Mesangial Proliferative Lupus
Nephritis
mesangial hypercellularity or mesangial
matrix expansion by light microscopy,
Class III: Focal Lupus Nephritis focal, segmental or global
glomerulonephritis involving ≤50% of all
glomeruli,
Class IV: Diffuse Lupus Nephritis focal, segmental or global
glomerulonephritis involving >50% of all
glomeruli,
Class V: Membranous Lupus Nephritis Global or segmental subepithelial immune
deposits
Class VI: Advanced Sclerotic Lupus Nephritis ≥90% of glomeruli globally
sclerosed without residual activity.

Skin Biopsy
Lupus skin rash often
demonstrates inflammatory
infiltrates at the dermoepidermal
junction and vacuolar change in
the basal columnar cells
Arthrocentesis
joint effusions, which can be
inflammatory or noninflammatory.
The cell count may range from
less than 25% polymorphonuclear
neutrophils (PMNs) in
noninflammatory effusions to
more than 50% in inflammatory
effusions

Radiology
Joint radiography
periarticular osteopenia and soft-
tissue swelling without erosions
Chest X ray and HRCT
These modalities can be used to
monitor interstitial lung disease and to
assess for pneumonitis, pulmonary
emboli, and alveolar hemorrhage
Echocardiography
is used to assess for pericardial
effusion, pulmonary hypertension,
or verrucous Libman-Sacks
endocarditis

Treatment

SLE activity often waxes and
wanes, the intensity of drug
therapy used
must be tailored to match
disease severity.
Since the various
manifestations of SLE
affect prognosis differently
drug therapy is chosen
accordingly to induce
remission
GOAL OF THERAPY

NON-LIFE-THREATENING DISEASE
Antimalarials (hydroxychloroquine, )
often reduce dermatitis, arthritis, and
fatigue. They also reduce the incidence
of disease flares and prolong survival in
SLE.
NSAIDs are useful analgesics/
anti-inflammatories, particularly
for arthritis/arthralgias
Patients should be cautioned against sun
exposure and should apply broad-spectrum UVA/
UVB sunscreen while outdoors. Milder skin
lesions often respond to the topical
administration of corticosteroids
Skin and joint symptoms

Systemic Corticosteroids
Corticosteroids are required for the control of certain
complications.
Glomerulonephritis,
Hemolytic anemia,
Myocarditis,
Alveolar hemorrhage,
Central nervous system
involvement,
Severe thrombo-cytopenia
The mainstay of treatment for any inflammatory life-threatening
or organ-threatening manifestations of SLE is systemic
glucocorticoids

For serious manifestations, either methylprednisolone 250–1000 mg
given intrave-nously over 30 minutes daily for 3 days or prednisone
40–60 mg orally is needed initially
However, the lowest dose of corticosteroid that controls the
condition should be used over time to minimize adverse
effects

Immunosuppressive Agents
These are used for long term control of the
disease
Cyclophosphamide,
Mycophenolate mofetil,
Azathioprine,
Methotrexate
Tacrolimus
Belimumab, a monoclonal antibody that
inhibits the activity of a B-cell growth factor, is
FDA approved for treating SLE patients with
active disease who have not responded to
standard therapies (eg, NSAIDs, antimalarials,
or immunosuppressive therapies)

Lupus Nephritis
Lupus Nephritis
Induction Phase
Mycophenolate mofetil and cyclophosphamide are first-
line induction treatments for lupus nephritis and are
generally given with corticosteroids to achieve disease
control
Mycophenolate mofetil is gien 1000 mg or 1500
mg orally twice daily
Cyclophosphamide is usually administered using the
Euro-Lupus regimen (500 mg intravenously every 2 weeks for six doses)
National Institutes of Health regimen (3–6 monthly intravenous pulses [0.5–1 g/
m2] for induction followed by maintenance infusions every 3 months).

Maintenance Phase
Mycophenolate mofetil or azathioprine is typically used for
maintenance therapy for lupus nephritis
Studies shows that Tacrolimus is also an
effective drug for induction and maintenance
of lupus nephritis

SLE IN PREGNANCY
Active SLE in pregnant women should be controlled with
hydroxychloroquine and, if necessary, prednisone/
prednisolone at the lowest effective doses for the shortest
time required. Azathioprine may be added if these
treatments do not suppress disease activity

Lupus and Anti Phospholipid Syndrome
should be managed with long-term anticoagulation
. With warfarin, a target international normalized ratio (INR) of 2.0–2.5 is
recommended for patients with one episode of venous clotting; an INR of
3.0–3.5 is recommended for patients with recurring clots or arterial clotting,

MEDICATION DOSE RANGE ADVERSE EFFECTS
NSAIDs Acc to Salt GI distress
elevated liver enzymes,
decreased renal function,
Glucocorticoids
Oral
Prednisone, prednisolone:
0.5–1 mg/kg per day for
severe SLE 0.07–0.3 mg/kg
per day or qod for milder
disease
infection, hypertension,
hyperglycemia,
hypokalemia, acne, aseptic
necrosis of bone, cushingoid
changes, CHF, fragile skin,
insomnia, menstrual
irregularities, , osteoporosis,
psychosis
Methylprednisolone
sodium
Same
Cyclophosphamide
IV
500 mg every 2 weeks for 6
doses, then begin
maintenance with MMF or
AZA.
Infection, leukopenia,
anemia, thrombocytopenia, ,
, malignancy, alopecia,
cough, diarrhea, fever, GI
symptoms, , hypertension,
hypercholesterolemia,
For severe disease, 0.5-1 g
IV qd × 3 days

Medication Dose Adverse Effects
Mycophenolate
mofetil
2–3 g/d PO total given bid
for induction therapy, 1–2 g/
d total given bid for
maintenance therapy
Same as other
immunosuppressive agents
e.g Cyclophosphamide
Azathioprine 2–3 mg/kg per day PO for
induction;1–2 mg/kg per
day for maintenance;
Infection, VZV infection,
bone marrow suppression, ,
pancreatitis, hepatotoxicity,
malignancy, , fever, flulike
illness, GI symptoms
Belimumab 10 mg/kg IV wks 0, 2, and 4,
then monthly OR
subcutaneous 200mg each
week
Infusion reactions, allergy,
infections. Headache and
diffuse body aching.
Tacrolimus 1-2 mg bid Infection oppurtunistic,
nephrotoxicity, neural
toxicity
HCQ 200-400mg/day Retinopathy ,Myopathy

Patient Summary
Patient Summary
Patient developed different infections like
diarrhea and candidiasis because of prolonged
immunosuppressive medications like
Tacrolimus and steroids

THANKS