SYSTEMIC LUPUS

ERYTHEMATOSUS
DEZZA P. MONTEJ O
SPMC FIRST YEAR IM RESIDENT

MODERATOR: CATHERINE MACAPAGAL, MD, FPCP, FPRA

OBJ ECTIVES:

❏ DEFINE SLE AND PRESENT ITS PREVALENCE

❏ BRIEFLY DISCUSS THE PATHOGENESIS OF SYSTEMIC LUPUS
ERYTHEMATOSUS
❏ ELABORATE ON THE DIAGNOSIS AND INITIAL THERAPY OF SLE
❏ RECOGNIZE AND ADDRESS LUPUS FLARE
❏ DISCUSS PREVENTIVE STRATEGIES AND PROGNOSIS
REFERENCES:
CLINICAL SCENARIO
Source: Patient
Realibility: 85%
HISTORY OF
PRESENT OF 2 months PTA
• appearance of
ILLNESS erythematous rash over
the cheeks, shoulders
• bilateral leg edema

1 YEAR PTA INTERIM

• intermittent fever • Progressive pitting bilateral edema
• lower extremity joint • increasing abdominal girth
pains
HISTORY OF
PRESENT OF 2 weeks PTA
• increased swelling of
ILLNESS the right leg compared
to the left leg
• no response to diuresis

1 month PTA 4 days PTA

• admitted due to • Difficult ambulation
cellulitis and persistent • Duplex scan: bilateral leg DVT
bilateral leg edema • Right acute DVT; Left subacute DVT
(-) DM, Bronchial asthma
(-) history of PTB
(-) food, drug allergies

Appendectomy, 201 4
● previous smoker (1 0 sticks per day
for 1 0 years)
● previous alcoholic beverage drinker
● history of marijuana use, 201 6
Physical Examination
Normocephalic, equal hair distribution,
puffiness of the face,pink palpebral
conjuctivae, isocoric pupils;moist lips, ulcer at
the left buccal mucosa; no mucosal bleeding
nor inflamed tonsillopharyngeal wall
Awake, alert, not in No nuchal rigidity, no lymphadenopathies,
trachea at midline, thyroid not palpable
distress
BP: 1 40/90 mmHg Adynamic precordium, regular rhythm, distinct
RR: 1 9 cpm Equal chest
warm, S1expansion,
moist, andmalar
(+) S2, monomurmurs
rash,retractions noted;
slightly raised,
clear breath sounds
T 36.7c excoriated
flabby, lesionsbowels
normoactive at the right shoulder;
sounds, (+) fluid
HR 67 bpm hypopigmented
wave
No test, soft,
abnormal patches at
no tenderness
curvature, the
(-) KPSnor left arm
mass
bilaterally
O2 saturation: 97%

(+) edema, pitting, (-) Homan sign, no

erythema of the legs nor tenderness; CRT <2s
Laboratory Results
CBC 4/3/21(2/25) DUPLEX SCAN UA 4/3/21 (3/15)
Hb 82 (98) Clear
Hct 0.26 (0/29) RIGHT ACUTE DVT LIGHT YELLOW
WBC 9.1 (10.30) -Totally occluding mid to distal femoral, Protein 3+ (2+)
N 91 (93) popliteal, tibioperoneal trunk, ant. and pH 6.0
L 6 (3) post. tibial, peroneal veins Specific Gravity 1.026
M2 -Partially occluding common, deep, Glucose NEGATIVE
E1 proximal femoral veins Micro-Albumin H 3+
B0 Nitrite NEGATIVE
PLT 209 (196) LEFT SUBACUTE PERONEAL DVT Leukocyte Esterase Trace
MCV 81.3 RBC H 60 /uL = 11/hpf (2/hpf)
MCHC 21 WBC 18 /uL = 3/hpf (2/hpf)

Serum creatinine Albumin 8.79 g/L DIRECT URINE MICROSCOPY

4/3/21- 122.3 umol/L 4/9/21
Coarse granular cast
Assessment

DEEP VEIN THROMBOSIS, BILATERAL LEGS

SYSTEMIC LUPUS ERYTHEMATOSUS IN RENAL, HEMATOLOGIC,
MUCOCUTANEOUS FLARE SLEDAI SCORE 1 2
SYSTEMIC LUPUS ERYTHEMATOSUS

❏ An autoimmune disease disease in which organs and cells undergo damage

initially mediated by tissue-binding autobodies and immune complexes
❏ Prevalence in the USA- 20-1 50: 1 00,000 women
❏ Prevalence in Asia Pacific- 3.7-1 27: 1 00,000 (Tanaka, et al., 2020)
❏ Only 1 male out of 1 0 lupus patients (Soccoro, et al., 201 1 )
PATHOGENESIS
 SYSTEMIC
MANIFESTATIONS
MUSCULOSKELETAL MANIFESTATIONS

● Intermittent polyarthritis: most commonly

affects hands, wrists and knees
● “Rhupus”
● Myositis
MUCOCUTANEOUS
RENAL MANIFESTATIONS

● Edema
● Hematuria
● Hypertension
Vascular occlusions

● Strokes
● Myocardial infarction
● Acute thrombotic events
-DVT, Pulmonary embolism
PULMONARY MANIFESTATIONS

● Pleuritis
● Pleural effusion
● interstitial inflammation
● Shrinking lung syndrome
● Intraalveolar hemorrhage
CARDIAC MANIFESTATIONS

● Pericarditis
● Myocarditis
● Endocarditis
○ Libman-Sacks
MANIFESTATIONS
NERVOUS SYSTEM

● Diffuse CNS Lupus: cognitive dysfunction-

memory and reasoning
● Seizure
● Psychosis
● Myelopathy

HEMATOLOGIC

● Anemia: normocytic, normochromic

● Hemolytic
● Leukopenia
● Lymphopenia
● Thrombocytopenia
MANIFESTATIONS
OCULAR

● Sicca syndrome (anti-Ro (SS-A); anti-La

(SS-B)
● Retinal vasculitis
● Optic neuritis

GASTROINTESTINAL

● Nausea, vomiting
● Autoimmune peritonitis
● Intestinal vasculitis
LABORATORY TESTS
TESTS FOR AUTOANTIBODIES
STANDARD TESTS

● Complete blood count

● Urinalysis
RENAL BIOPSY
Renal biospy is recommended for
lupus patients with any clnical
evidence of nephritis.

In patients with ISN III and IV

usually have microscopic
hematuria and proteinuria wherein
a half develop nephrotic syndrome
while most will have hypertension.
In an inadequately treated diffuse
proliferative GN- ESRD may be
expected within 2 years of
diagnosis.
RENAL BIOPSY CRITERIA

Hahn, et al. (201 2) ACR Guidelines for Screening, Treatment

and Management of Lupus Nephritis
DIAGNOSIS
SLICC CRITERIA 201 2

PRESENCE OF ANY FOUR CRITERIA (MUST

HAVE ONE IN EACH CATEGORY) Q UALIFIES
PATIENT TO BE CLASSIFIED AS HAVING SLE

*But this may not be fulfilled in the presence of

lupus nephritis in biopsy plus detected
autoantibody

(93% SPECIFICITY, 92% SENSITIVITY)

201 9 EULAR/ACR Classification Criteria for
Systemic Lupus Erythematosus

(96.1 % SENSITIVITY; 93.4% SPECIFICITY)

qualifier: ANA of AT LEAST 1 :80 PLUS 1 0 tallied

points (at least one in clinical domain)

*fulfills more than one criterion in a single domain-

ACCOUNT THE ONE WITH THE HIGHEST POINTS
LABORATORY TESTS TO
FOLLOW DISEASE
COURSE
● Complete blood count
● Urinalysis
● Serum Creatinine
● Albumin
● Anti-dsDNA levels
● Complement level (C3, most available)
DISEASE SEVERITY INDICES
SLEDAI-2K

Mild: </=6 points

Moderate: 7-1 2 points
Severe: >1 2 points

SLEDAI is a widely used measure of

SLE disease activity; scores >3 reflect
clinically active disease

*measure/compute every 1 0 days

BILAG 2004

encompasses the previous 4 weeks

and manifestatons are scored from
0-4, not present to new onset.

MORE COMPLICATED
MANAGEMENT
CONSERVATIVE THERAPIES FOR NON-LIFE THREATENING DISEASE

● Symptoms: fatigue, pain without major organ involvement

○ NSAIDS , Acetamenophen- analgesics/anti-inflammatories especially for arthralgias/arthritis
○ Anti-malarial- reduces dermatitis, athritis, fatigue; reduces renal damage and thrombogenesis
■ Hydroxycholoroquine <5 mg per kg per day (EULAR); usually 200-400 mg daily;
quinacrine may be added or substituted
■ Annual ophthalmologic evaluation
● Lupus dermatitis
○ Topical sunscreens ( SPF 1 5 at least; 30+ preferred)
○ Anti-malarials
○ Topical glucocorticoids
○ +/-Tacrolimus
LIFE-THREATENING SLE

Mainstay of treatment:

systemic glucocorticoids (0.5–1 mg/kg per day PO or 500–1 000 mg of

methylprednisolone sodium succinate IV daily for 3 days followed by 0.5–1 mg/kg
of daily prednisone or equivalent)
LIFE-THREATENING SLE

● Severe SLE
○ use 4–6 weeks of 0.5–1 mg/kg per day of prednisone or its equivalent
○ Appropriate tapering of dose thereafter to a maintenance of 5-1 0 mg per day of prednisone or
its equivalent
LIFE-THREATENING SLE

● Severe SLE
○ Addition of cytotoxic or immunosuppressive agents (applicable in setting of SLE nephritis)
■ Cyclophosphamide
■ Mycophenolate mofetil
■ Azathioprine
■ For whites and Asians, induction with either mycophenolate mofetil or cyclophosphamide
is acceptable
Cyclophosphamide and mycophenolate responses begin 3–16 weeks after treatment
is initiated, whereas glucocorticoid responses may begin within 24 h.
LIFE-THREATINING SLE

Maintenance Therapy

● Mycophenolate mofetil, Azathioprine - safer than cyclophosphamide

○ incidence of ovarian failure, a common effect of high-dose cyclophosphamide therapy (but
probably not of low-dose therapy),
■ gonadotropin-releasing hormone agonist (e.g., leuprolide 3.75 mg intramuscularly) prior
to each monthly cyclophosphamide dose
LIFE-THREATINING SLE

Maintenance Therapy

● Cyclophosphamide may be discontinued when it is clear that a patient is

improving.
● Mycophenolate mofetil (1 .5–2 g daily) or azathioprine (1 –2.5 mg/kg per day)-
reduce SLE flares
● Azathioprine- may be used to control SLE in pregnant patients
LIFE-THREATINING SLE

Patients with proteinuria > 500 mg daily should receive ACE inhibitors or ARBs, as
they reduce the chance for ESRD
LUPUS NEPHRITIS
Hahn, et al. (201 2) ACR Guidelines for Screening,
Treatment and Management of Lupus Nephritis
Hahn, et al. (201 2) ACR Guidelines for Screening, Treatment and Management of Lupus Nephritis
Hahn, et al. (201 2) ACR Guidelines for Screening, Treatment and Management of Lupus Nephritis
Response criteria for renal function based on ACR

● Estimated GFR
● Urinary protein
● Urinary sediment
Response Criteria
Response Criteria
Response Criteria
HOW TO RECOGNIZE FLARES?
What is an SLE flare?

“A measurable increase in disease activity in one or more organ systems involving

new or worse clinical signs and symptoms and/or laboratory measurements. It must
be considered clinically significant by the assessor and usually there would be at
least consideration of a change or an increase in treatment.”

Adamichou, C. & Bertsias, G. (201 7) Flares in systemic lupus erythematosus: diagnosis, risk factors
and preventive strategies
SLE FLARE

● increase in disease activity score (a 4-point increase in SLEDAI-2 K.)

● appearance of new or worsening of disease manifestations, (e.g., increase in
proteinuria in the case of renal flares)
● change in the physician’s global assessment (PGA) scale towards more
active/severe disease
● need for treatment intensification (e.g., an increase of steroid dosage)

Adamichou, C. & Bertsias, G. (201 7) Flares in systemic lupus erythematosus: diagnosis, risk factors
and preventive strategies
FLARE INDICES

● SELENA-SLEDAI Flare Index

● BILAG 2004 Flare Index
WHEN TO DISCHARGE?

● Improved clinical status

● All medications are taken orally and are well-tolerated
● disease is manageable at home
● avoid prolonged hospital stay as much as possible-- STRESS can also cause
flares.

● follow up: after 1 -2 weeks if with severe disease activity; after 2-4 weeks in
lower disease activity.
● Basic tests to follow disease course: urinalysis and CBC
PREVENTIVE THERAPIES AND PROGNOSIS
Preventive therapies

● Vaccinations
○ Flu, pneumococcal vaccines
○ COVID VACCINE- may give if the patient is stable and is having PREDNISONE <20MG OD or its
equivalent
○ if on MTX,, skip one week of treatment ( MTX USUALLY GIVEN WEEKLY)

● Calcium, Vitamin D supplementation

● Blood pressure monitoring and control
● Strategies for atherosclerosis— statin therapy
PROGNOSIS

● Survival in patients with SLE in the United States, Canada, Europe, and China is
~95% at 5 years, 90% at 1 0 years, and 78% at 20 years.
● As many as 30–50% of patients may achieve low disease activity (defined as
mild activity on hydroxychloroquine with or without low dose glucocorticoids);
● fewer than 1 0% experience remission
LEADING CAUSES OF DEATH IN THE FIRST DECADE

● Systemic disease activity

● Renal failure
● Infections
● Thromboembolic events
POOR PROGNOSTICATORS
● high serum creatinine levels (>1 24
μmol/L [>1 .4 mg/dL]),
● hypertension
● nephrotic syndrome (24-h urine
protein excretion >2.6 g)
● anemia (hemoglobin <1 24 g/L [<1 2.4
g/dL]),
● hypoalbuminemia
● hypocomplementemia
● antiphospholipid antibodies
● male sex
● ethnicity (African American, Hispanic
with mestizo heritage)
● low socioeconomic status
THANK YOU!