This 23-year-old woman presented with seizures, headaches, weight loss, hair loss, joint pains, and night sweats. On examination, she had a thin scalp with patchy hair loss, numerous lymph nodes, fever, tachycardia, and high blood pressure. Laboratory tests showed anemia, low white blood cell and platelet counts, high sedimentation rate, proteinuria, and red blood cells in her urine. The likely diagnosis is systemic lupus erythematosus (SLE) based on her symptoms and laboratory abnormalities. Further immunological testing including ANA and anti-dsDNA antibodies would help confirm the diagnosis of SLE. She requires admission for treatment and management of her organ-threatening l

1. Systemic Lupus Erythematosus (SLE)
Prepared by Dr. Ruqaya Al-Kathiry
Head of the Medical Department in UST
“It is much simpler to buy books than
to read them & easier to read them than
absorb their content”
Sir William Osler (1849-1919)

2. OBJECTIVES
• Case
• Introduction
• Pathophysiology
• Diagnostic Criteria
• Clinical Features
• Differential Diagnosis
• Investigations
• Treatment

3. A 23 yr old woman is admitted to the emergency
department having had 2 tonic-clonic generalized
seizures, which were witnessed by her mother. Her
mother says that her daughter has been behaving
increasingly strangely & has been hearing voices talking
about her. Recently, she has complained of severe
headaches. She has lost weight & has noticed that her
hair has been falling out. She has also complained of
night sweats & flitting joint pains affecting mainly the
small joints of her hands & feet. She works as a bank
clerk. She smokes 5–10 cigarettes/d & consumes about
10U of alcohol/wk. She is taking no regular medication.
She has no significant medical or psychiatric Hx.

4. She is drowsy but responsive to pain.
There is no neck stiffness.
Her scalp hair is thin & patchy.
She has numerous small palpable LNs.
Her T is 38.5°C, P.R is 104bpm & regular;
B.P is 164/102 mmHg.
Examination of her CVS, resp. & abd.
systems is otherwise NL.
Neurological examination reveals no focal
ABNLity & no papilloedema.

5. AUTOIMMUNE CONNECTIVE TISSUE DISEASES (AICTDS)
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE, ‘LUPUS’)
Pathophysiology
Cause incompletely understood. It is a multifactorial dis. ass. with interactions b/w
susceptibility genes & env. factors result in ABNL immune responses, which vary b/w
different pts.
Most SLE pts have autoAbs or ≥3yrs before the 1st symp. of dis., suggesting that
regulation controls the degree of autoimmunity or years before quantities & qualities
of autoAbs and pathogenic B & cells cause clinical dis.
They share many C/Fs & are ch.ch. by dysregulation of immune responses, autoAb
production that is often directed at components of the cell nucleus & tissue damage.
A rare dis.; but more common than many people realize. It is a chr. inflammatory,
multisystem autoimmune disorder with arthralgia & rashes as the most common C/Fs,
and cerebral & renal dis. as the most serious problems.
Prevalence: highest in African-American & Afro-Caribbean ♀ & lowest in white ♂.
Gender: ♀:♂=9:1; 90% are ♀ with evidence of Ho effects (estrogen-containing OCPs or
HRT) & genes on the X chromosome (TREX-1).
Age: child-bearing years 20-40y.
N.B: people of all genders, ages & ethnic groups are susceptible.

6. Monozygotic
> dizygotic
twins;
1st degree
relatives
(70% of pts)
Smoke
Hos: oestrogens
Chemicals: Si & Hg
Drugs: hydralazine
These cause flares of lupus
3 whole-
genome
analyses
identified
~20 genes
linked to
SLE
When cells die by apoptosis, the cellular remnants appear on the cell surf. as small
blebs that carry self Ags. These Ags include nuclear constituents (DNA & histones),
which are normally hidden from the immune system. In SLE, removal of these blebs
by phagocytes is inefficient, so that they are transferred to lymphoid tiss., where they
can be taken up by APC. The self Ags from these blebs can then be presented to T
cells, which in turn stimulate B cells to produce autoAbs directed against these Ags.

7. C/Fs:
• Onset: 1 or more organs are involved; over time additional C/Fs occur.
• Severity:
o Mild & intermittent
o Severe & fulminant
• Course:
o ̴85% have continuing active dis. (while being Rx)
o ≥1 flares of active dis./yr.
o Permanent complete remissions (absence of symp. with no Rx) → rare.
• Symptoms may be of:
o Flares of dis. activity: fever, prostration, A, wt. loss, mild LAP & anemia ± other
organ-targeted manifestations.
o No dis. activity: fatigue, myalgias/arthralgia very common & can be constant.
The classic presentation of a triad of:
• Fever
• Joint pain
• Rash
in a woman of childbearing age should prompt invx into the
Dx of SLE

8. Clinical Criteria:
2012 SICC Classificstion Criteria of SLE:

10. Immunological Criteria:
Dx:
≥4 criteria, with at least 1 clinical & 1 immunologic, documented at any time during an
individual’s Hx → most likely SLE (Specificity=~93% & sensitivity=~92%) or lupus nephritis
as the sole clinical criterion in the presence of ANA or anti‐dsDNA Abs.

11. The newest criteria from 2019 are a result of collaboration b/w
ACR and European League against Rheumatism (EULAR).
There are 7 clinical & 3 immunologic domains.
Each domain has several criteria, which are weighted.
Within each domain, only the highest weighted criterion is
counted towards the total score.
Pts are classified to have SLE if there is a +ve ANA of ≥1:80, at
least 1 clinical criteria & a score of ≥10.
These classification criteria are unique in the sense that they are
the first weighted criteria for SLE. These criteria are combined
with a comprehensive examination to help guide a Dx of SLE.

12. MSS Symptoms:
• Arthralgia: common symp. (90% of pts).
• Arthritis:
o SITE: Symmetrical small joint (oligo/polyarthritis) Hands, wrists, knees.
o SEVERITY: mild to disabling
o ONSET: insidious over wks or ms (>6wks)
o COURSE: intermittent
o AGGRAVATING & RELIEVING FACTORS: morning stiffness (?)
o ASSOCIATED FACTORS: constitutional symp. (?), extra-articular manifestations (?)
ch.ch. by tissue swelling & tenderness in joints ± tendons.
Jacoud’s arthropathy
• Joint erosions: not a feature.
• Joint deformities: in hands & feet (Jaccoud’s
arthropathy) due to tendon damage rare (10%).
• Tenosynovitis: rare.
• Myalgias: in most pts (50%) esp. during flares.
• Myositis: with m. weakness can occur (5%).
• Avascular Necrosis: of hip/knee is rare complication of dis. or of Rx with corticosteroids.
Vascular Manifestations
• 2ary Raynaud’s Phenomenon: common
o Antedates other symp. by ms/yrs.
o Milder than in scleroderma, if severe → digital ulceration.
• Palmar erythema, dilated nail-fold capillaries, splinter Hages, vasculitis.

13. Cutaneous Manifestations: common in 85%
Typically occur within 24-48 hrs after UV exposure.
Lupus dermatitis can be classified as ac. Subac. & chr.:
• “Butterfly” Rash: classic most common ac. SLE facial rash (20% of pts).
A photosensitive, slightly raised erythema, occ. scaly, painful/itchy. It occurs part. over
the cheeks & nose with sparing of the nasolabial folds (D/D: Rosacea), ears, chin, V
region of neck & chest, upp. back & extensor surf. of the arms. Worsening of this rash
often accompanies flare of systemic dis.
Other presentations: maculopapular rash, urticaria, bullous lupus & a toxic epidermal
necrolysis (TEN)-like rash.
• Discoid Lupus Erythematosus (DLE): most common chr. dermatitis in lupus.
Chr. scarring lesions that heal with hypo/hyperpigmentation. Hyperkeratosis &
follicular plugging can be disfiguring, part. on the face & scalp (scarring alopecia).
• Subacute Cutaneous Lupus Erythematosus (SCLE): rare subac. variant
Non‐scarring scaly red patches (D/D: psoriasis) or circular red-rimmed in areas of the
body exposed to sun.
• Diffuse or patchy non-scarring alopecia: in temporal area or diffuse thinningmay
indicate active dis.
• Livedo Reticularis: a feature of APLS (?)
• Other SLE Rashes:
Urticaria, lichen planus-like dermatitis, bullae, purpura, lupus panniculitis (an
inflammatory involvement of the subcutis & fat), tumid lupus, chilblains.

14. Malar Rash Subacute Cutaneous
Lupus Erythematosus Livedo Reticularis
Discoid Lupus
Erythematosus
Urticarial Eruptions

15. Neuropsychiatric (NPSLE) Manifestations: in 60%
It may involve any area of the nervous system with diffuse or focal involvement due to:
o Vasculitis or immune-complex deposition: Rx by immunosuppression
o Vascular occlusion: embolization from carotid art. plaque or from Libman-Sacks
endocarditis → Rx by ACO
CNS Manifestations of SLE:
• Aseptic meningitis: most common due to NSAIDs use.
• Cerebrovascular dis.: most common due to accelerated atherosclerosis↑ in APLA +ve pts.
• Headache: most common. When excruciating → SLE flare; if mild D/D: migraine/tensionH
• Movement disorders (chorea): Antiphospholipid Abs (anticardiolipin Abs)
• Seizures: most common
• Acute confusional state
• Cognitive dysfunction: most common of diffuse CNS lupus in the absence of active dis.
• Mood disorder: depression related to psychosocial issues not lupus itself.
• Psychosis: can be the dominant manifestation; D/D: glucocorticoid-induced psychosis.
PNS Manifestations of SLE:
• Ac. inflammatory demyelinating polyradiculoneuropathy (Guillain–Barre $)
• Neuropathy: cranial; mononeuropathy (single or multiplex); polyneuropathy
• Myasthenia gravis
• Autonomic disorder
N.B: Exclude & Rx other possible causes (sepsis, drugs, uraemia, severe HTN & metabolic).

16. GIT Manifestations: common in 50%
• Ulcers (45%): common small, painless or painful (2ary infection), oral (hard palate &
buccal mucosa) or nasal; resembling aphthous ulcers. Vaginal ulcers may also occur.
• N ± V & D (50%): manifestations of SLE flare.
• Autoimmune peritonitis ± mesenteric (intestinal) vasculitis: life-threatening.
• Hepatitis (lupus/AIH), sclerosing cholangitis, protein‐losing enteropathy, pancreatitis:
rare
Lung Manifestations: common in 50%
• Pleuritis (?) (serositis) ± pl. effusion (?): most frequent.
• Pulm. Infiltrates: active SLE; difficult to distinguish from infection on imaging.
• Life-threatening: interstitial inflam → fibrosis, shrinking lung $ & diffuse alveolar
Hage.
• ↑risk of TE, esp. in pts with antiphospholipid Abs & pulm. art. hypertension.
Renal Manifestations: in 30%
• It is imp. in prognosis because nephritis & infection are the leading causes of
mortality in the 1st decade of dis.
• As nephritis is asymp. in most lupus pts, urinalysis should be ordered in any person
suspected of having SLE & BP monitored.
• Lupus nephritis is an ongoing dis., with flares requiring re-Rx or ↑Rx over many yrs.
• The classification of lupus nephritis is 1arily histologic.
• Renal biopsy is recommended for every SLE pt with any clinical evidence of
nephritis e.g. proteinuria; results are used for severity & plan Rx (?).

17. Class I: Minimal Mesangial
Class II: Mesangial Proliferative
Class III: Focal Proliferative
Class IV: Diffuse Proliferative Typical renal lesion all pts develop ESRD within 2yrs of Dx
Class V: Membranous
Class VI: Advanced Sclerotic
CVS Manifestations: 25%
• Pericarditis: most common manifestation; rarely tamponade.
• Myocarditis: arrhythmias (rare but serious fatal manifestation).
• Fibrinous Libman-Sacks Endocarditis: very rare non-infective feature of hyper-
coagulability ass. with antiphospholipid Abs → MR & AR or embolic events.
• CAD: ↑risk of MI. This is multifactorial (?) mainly accelerated atherosclerosis.
Haematological Manifestations:
• Anaemia: most frequent hematologic manifestation
o Normochromic normocytic: reflecting chr. illness & AIHA.
o IDA: 2ary to peptic ulceration or gastritis due to NSAIDs.
• Leukopenia: common; almost always lymphopenia, rarely neutropenia.
Lymphopenia rarely predisposes to infections.
• Thrombocytopenia: may be recurrent. If platelet >40,000/μL & no ABNL bleeding.
Ocular Manifestations:
• 2ary Sjögren’s (Sicca) $ & conjunctivitis: common → rarely threaten vision.
• Retinal vasculitis & optic neuritis: less freq. but serious → blindness over ds-wks.

19. D/D:
• Drug-induced lupus
• Rheumatoid arthritis
• Systemic vasculitis
• Scleroderma
• Primary APLS
• Inflammatory myopathies
Frequency (%) of laboratory ABNLities in SLE.
• Viral hepatitis
• Sarcoidosis
• Acute drug reactions

20. Invx:
• Haemoglobin 7.2 g/dL (11.7–15.7 g/Dl)
• Mean corpuscular volume 85 fL (80–99 fL)
• White cell count 2.2 × 109/L (3.5–11.0×109/L)
• Platelets 72 × 109/L (150–440×109/L)
• Erythrocyte sedimentation rate90 mm/h (<10 mm/h)
• Sodium 136 mmol/L (135–145mmol/L)
• Potassium 4.2 mmol/L (3.5–5.0
mmol/L)
• Urea 16.4 mmol/L(2.5–6.7 mmol/L)
• Creatinine 176 μmol/L (70–120
μmol/L)
• Glucose 4.8 mmol/L (4.0–6.0 mmol/L)
• Urinalysis: +++ protein; +++ blood
• Urine microscopy: ++ red cell; red cell casts present
• Chest X-ray: normal
• Electrocardiogram: sinus tachycardia

21. Questions
Q1. What is the D/D?
Q2. What is the likely Dx?
Q3. How would you invx this pt?
Q4. How would you Rx this pt?
When to Refer?
• Appropriate Dx & management → by a rheumatologist.
• Severe organ involvement → refer to subspecialists (nephrologists & pulmonologists)
When to Admit?
• Severe organ-threatening features: in-pt assessment & management RPGN, pulm.
Hage, transverse myelitis.
• Severe infections: part. with the use of immunosuppressant therapy.
• Computed tomography of the brain: normal
• Lumbar puncture:
o Leucocytes 150/mL (<5/mL)
o CSF protein 1.2 g/L (<0.4 g/L)
o CSF glucose 4.1 mmol/L (<70% of plasma glucose)
o CSF Gram stain: negative

22. Invx:
I-Immunology:
A-AutoAbs:
• ANA:
o ANA +ve SLE: in >95% of pts, often with titers ≥1:160 → active SLE.
o ANA -ve SLE: e.g. in presence of Abs to Ro ass. with SCLE.
 A -ve ANA virtually excludes SLE but a +ve result does not confirm it (not specific)
 ANA testing in asymp. individuals is not useful as it can be detected in the healthy,
pts with NL ageing, viral infections, malignancies & other CTD.
• ANA subtypes (anti-dsDNA, anti-ssDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, histone):
Both are specific for SLE but not sensitive.
o Anti-dsDNA Abs: +ve in 60%; correlate with activity.
o Anti-Sm: +ve in 30%; does not correlate with activity.
In women planning pregnancy, it is imp. to check for: anti‐Ro, anti‐La Abs (WHY?), anti-
phospholipid Abs & lupus anticoagulant (WHY?).
B-Complement Levels:
• Low C3: active SLE particularLY glomerular dis. due to complement consumption.
• Low C3 & C4: inherited complement defic. in C1, C2 or C4 that predisposes to SLE.
Studies of other family members can help to differentiate inherited deficiency from
complement consumption.
• Low CH50

24. II-Full blood count (FBC)/Complete blood count (CBC):
• Anaemia: Normochromic normocytic (?) or +ve Direct Coombs test (?)
• Leucopenia: <4,000/μL; Lymphopenia <1,500/μL
• Thrombocytopenia: <100,000/μL
III-Inflammatory Markers:
• ESR: ↑ in disease activity
• CRP: NL in active SLE; ↑ except in lupus pleuritis, arthritis or a coexistent infection.
IV-Biochemistry:
• LFT: ↑AST & ALT are common when SLE is active
• RFT: S. creatinine & Urea only ↑ in advanced renal dis. Estimated GFR is more
reliable than S. creatinine.↓S.albumin or ↑urine albumin/creatinine ratio are
earlier indicators of lupus nephritis.
V-Urinalysis:
• Microscopic haematuria: for RBC casts.
• Proteinuria: urine protein/creatinine ratio ≥500mg/24h; ̴½ develop nephrotic $.
VI-Biopsy & Histology:
Ch.Ch. histological & immunofluorescent ABNLities (deposition of IgG & complement) are
seen in biopsies from the kidney & skin.
VII-Other:
• ECG: for pericarditis (?)
• Echocardiography: for pericardial effusion.

25. VIII-Radiographic Studies:
• CXR & HRCT: lung infilterates & fibrosis or Hages.
• Brain CT scans & MRI: infarcts or Hage with cerebral atrophy; Lesions in white
matter that are not seen on CT.

26. Management: There is no known cure for SLE.
General goals for Rx are to achieve low dis. activity or remission & prevent flares with the least
amount of glucocorticoid use possible.
Non-pharmacological Therapy:
• Stop smoking.
• Reduce stress.
• Avoiding sun exposure during peak hrs: typically midmorning to early evening &
use of long-sleeve shirts and wide-brimmed hats are advisable.
• Sunblock (sun protection factor SPF 25.50-30) regularly for at least 6ms over the
summer or all year. SLE pts should be aware that sun exposure may ppt a dis. flare
• LSM → adequate rest, appropriate exercise & a well‐balanced diet.
• Raynaud’s phenomenon → wear warm clothing (including hats & gloves).
• Avoid & Rx infections → they can ppt flares.
• OCPs that contain oestrogen → use with caution. Barrier methods or progesterone‐
only contraception are preferred.
• Dry eyes → frequent use of artificial tears.
• Dry mouth → taking sips of plain water, sucking ice cubes or eating sugar‐free
sweets. Artificial saliva preparations are disappointing.
 Experimental Therapies:
Rescue by Tx of autologous hematopoietic stem cells for severe & refractory SLE.

27. Pharmacological Therapy:
 Conservative Therapies for Non-Life-Threatening SLE:
• NSAIDs: fever, articular, pleuritis, pericarditis.
• Antimalarials: (?) constitutional, cutaneous, articular C/Fs. Ophthalmologic evaluation
before & during Rx (WHY?).
• Glucocorticoids: topical or oral low-dose prednisolone.
• Immunosuppressants: MTX, AZA, leflunomide (LEF), or mycophenolate mofetil (MMF).
• Belimumab Monoclonal Ab: B-lymphocyte stimulator (BLyS)-specific inhibitor.
Limited to mild to moderate active dis. & should not be used in severe SLE as nephritis
or CNS dis.; still under invx.
 Rx for Severe & Life-Threatening SLE:
Used for renal, CNS, pulm. & cardiac involvement.
• Systemic (oral) Glucocorticoids: High-dose in severe thrombocytopenia (1st episode),
HA (rapid & severe), & severe pulm. manifestations (?).
• Cytotoxic/Immunosuppressive Agents: added to glucocorticoids
o Cyclophosphamide (Cytoxan): (?) 6ms followed by maintenance with: MMF or AZA.
 Mycophenolate mofetil (Cellcept): (?) limited to nephritis.
 Azathioprine (Imuran): (?) may be effective but is slower in inducing response.
 A common regimen is pulsed: Methylprednisolone (?) + cyclophosphamide.
• Rituximab (anti-CD20 Monoclonal Ab): effective in selected refractory cases.

28.  Maintenance Therapy: Continue with the lowest doses to maintain remission.
• Oral prednisolone: 40-60mg/d, ↓gradually to ≤10-15mg/d by 3ms. Screen for (?)
• AZA, MTX or MMF should also be prescribed.
• Control cardiovascular RFs (HTN & hyperlipidaemia).
• Aspirin for cardiac RFs, SLE who have ↑titer APL Abs & in most pregnant women.
• Life-long warfarin → Pts with SLE & the APLS who have had previous thrombosis.
Prognosis:
• Leading causes of death: 1st decade of dis. → systemic dis. activity, renal failure &
infections; subsequently → TE events (CAD & Stroke).
• Poor prognosis; ~50% MR in 10yrs in most is ass. with (at the time of Dx):
• Hx:
o Male sex
o Ethnicity (African American, Hispanic)
o Low S.E status
o HTN
o Invx:
o Anemia (Hb <124g/L OR <12.4g/dL])
o ↑ S. creatinine levels (>124μmol/L OR >1.4mg/dL)
o Hypoalbuminemia
o Hypocomplementemia
o Antiphospholipid antibodies

29. Thank you for your attendance
References:
• Davidson’s Principles & Practice of Medicine, 23E, 2018
• Kumar & Clark's Clinical Medicine, 10E, 2020
• Harrison’s Manual of Internal Medicine, 20E, 2020
• CECIL Essential of Medicine, 10E, 2022
• Macleod's Clinical Examination, 14E, 2018
• Clinical Examination-A Systematic Guide to Physical Diagnosis, 8E, 2018