This patient has a history of recurrent deep vein thrombosis and pregnancy losses. She presents with right calf swelling and tenderness and is found to have thrombocytopenia and a prolonged PTT. Testing reveals a positive lupus anticoagulant on two occasions more than 12 weeks apart, meeting criteria for antiphospholipid syndrome which can present as recurrent thrombosis.

1. SYSTEMIC LUPUS
ERYTHEMATOSUS
(SLE)

2. Definition
• SLE is a chronic multisystem disorder that most commonly affects women
during their reproductive years. It is characterized by the presence of
antinuclear antibodies.
• an autoimmune disease mediated by antibodies and immune complexes that
target almost every organ in the body

3. Aetiology
• Unknown
• The interaction of an environmental agent in a
genetically susceptible host is thought to be fundamental
• The strong female occurrence (females 9:1 males) also
suggests a role for hormonal factors

4. Pathophysiology
• Defective Apoptosis is the first step in SLE pathophysiology.
• When cells die and apoptosis is not done properly, the body is sensitized to
nuclear material.
• This Sensitization is the main reason why Antibodies target the persons own
cells and target almost every type of cell
• Antigens picked up by the immune system include nuclear proteins like
Histones, dsDNA, Sm etc…

5. • After sensitization the immune system starts to build auto-antibodies.
• These auto-antibodies can cause a cascade of inflammation and build
complexes causing more cell death.
• Immune memory is built and it is the main reason for flare-ups in SLE
• Usually this cycle is re-initiated by triggers like UV-light, surgery, infections
or pregnancy
• The cyclic nature of (inflammation-cell death-autoimmune sensitization) is
the main factor for FLARE UPS of the disease.

6. how SLE presents
• Fatigue, fever, and weight loss are common symptoms that occur at some
time during the course of the disease.
• Fatigue is common, occurring in 80% to 100% of patients
• Mucocutaneous symptoms (Malar and Discoid rash)
• haematuria, casts (red cell, granular, tubular, or mixed), or proteinuria.

7. how SLE presents
Malar Rash (30-40%) others
• Arthritis (Jaccoud's): tends to be symmetrical and is
typically non-erosive
• Raynaud's phenomenon
• Mouth ulcers
• Cardiovascular manifestations of SLE include
pericarditis, myocarditis, endocarditis, arterial and venous
thrombosis, and premature atherosclerotic coronary
artery disease
• Anaemia, leukopenia, and thrombocytopenia
• Hair loss

8. Why is it called SLE

11. Lupus on the inside Lupus on the outside

12. DOPAMINE RASH
• Discoid rash
• Oral ulcers
• Photosensitivity
• Arthritis
• Malar rash
• Immune critirea (dsDNA, sm etc…)
• Neuro symptoms (lupus cerebritis, seizures
etc..)
• Elevated ESR
• Renal disease
• ANA
• Serositis (Pleural, pericardial effusion)
• Hematological manifestations

13. Old criteria
(1982 American College of Rheumatology revised criteria for the
classification of SLE
revised in 1997)
• Malar rash
• Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds.
• Discoid rash
• Erythematous 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 physician.
• Arthritis
• Non-erosive arthritis involving ≥2 peripheral joints, characterised by tenderness, swelling, or effusion.
• Serositis (one of the following):
• Pleuritis: convincing history of pleuritic pain, pleural rubs on auscultation, or evidence of pleural effusion
• Pericarditis: documented by ECG, pericardial rub, or evidence of pericardial effusion.

14. • Renal disorder (one of the following):
• Persistent proteinuria >0.5 g/day or >3+ if quantification not performed
• Cellular casts: may be red cell, haemoglobin, granular, tubular, or mixed.
• Neurological disorder (one of the following):
• Seizures: in the absence of offending drugs or known metabolic derangements (e.g., uraemia, ketoacidosis, or electrolyte imbalance)
• Psychosis: in the absence of offending drugs or known metabolic derangements (e.g., uraemia, ketoacidosis, or electrolyte imbalance).
• Haematological disorder (one of the following):
• Haemolytic anaemia: with reticulocytes
• Leukopenia: <4000/mm³ on ≥2 occasions
• Lymphopenia: <1500/mm³ on ≥2 occasions
• Thrombocytopenia: <100,000/mm³ in the absence of offending drugs.
• Immunological disorder (one of the following):
• Anti-DNA: presence of antibody to native DNA in abnormal titre
• Anti-Smith: presence of antibody to Smith nuclear antigen
• Positive findings of antiphospholipid antibodies based on:
• An abnormal serum level of IgG or IgM anticardiolipin antibodies
• Positive test result for lupus anticoagulant using a standard method
• A false-positive serological test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilisation or fluorescent treponemal
antibody absorption test.
• Antinuclear antibody
• An abnormal titre 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.

15. These criteria were initially developed to
identify patients for clinical studies and were
based on a white population.
Any ≥4 of the 11 criteria are required to classify a
patient as having SLE. These criteria can be present
serially or simultaneously during any interval of
observation.

16. In 2012, the Systemic Lupus
International Collaborating
Clinics (SLICC) added:
Lupus nephritis can be the sole clinical criterion in the presence
of ANA or anti-dsDNA antibodies.

17. The New Criteria
2019 European League Against Rheumatism/American
College of Rheumatology classification system
• Entry criterion
• Antinuclear antibodies (ANA) at a titre of ≥1:80
• If absent, do not classify as SLE; if present, apply additive criteria

18. Additive criteria
(Criteria need not occur simultaneously.
Within each domain, only the highest criterion is counted toward the score)

19. So when can I
Diagnose?
Scores of 10 or more are classified as systemic
lupus erythematosus if the entry criterion has
been fulfilled.

20. Case #1
Samia is a 32-year-old black female presents to her general practitioner with symptoms of mild
fever, fatigue, musculoskeletal pain, and a facial rash. The rash increases with sunlight exposure,
patient also mentioned being too sensitive to sunlight She is a known case of hypothyroidism on
thyroxin. History of hospital admission 2 years ago for cholecystectomy. She has been facing
difficulty with gardening due to joint stiffness.
non diabetic non hyprtensive
No smoking or alcohol
Significant family history of thyroid problems.

21. Examination
On examination: she is vitally stable, temp: 38.
noted to be thin with malar skin changes. The rash is over her cheeks, including
the nasal bridge and sparing the nasolabial folds.
Tenderness is noted predominantly in small joints of the hand.
No other abnormality is found.

22. Investigations
• CBC: HB normal. WBCs low. Platelets low
• ESR: Elevated
• CRP: normal
• RFT and electrolytes: Normal
• Urinalysis: Normal
• Joint Xray: Symmetrical non erosive inflammatory changes
• TFT: normal

23. Immunology
• ANA: Positive
• AntidsDNA: Positive
• Anti-smith: Positive
• Anti-Histone: Negative
This patient is suffering from a flare up of undiagnosed SLE

24. Autoantibodies

25. Test Description
ANA Screening test; sensitivity 95%; not diagnostic without clinical features
Anti-dsDNA High specificity; sensitivity only 70%; level is variable based on disease activity
Anti-Sm Most specific antibody for SLE; only 30-40% sensitivity
Anti-SSA (Ro) or Anti-SSB (La)
Present in 15% of patients with SLE and other connective-tissue diseases such
as Sjögren syndrome; associated with neonatal lupus
Anti-ribosomal P
Uncommon antibodies that may correlate with risk for CNS disease, including increased
hazards of psychosis in a large inception cohort, although the exact role in clinical
diagnosis is debated [108]
Anti-RNP
Included with anti-Sm, SSA, and SSB in the ENA profile; may indicate mixed connective-
tissue disease with overlap SLE, scleroderma, and myositis
Anticardiolipin
IgG/IgM variants measured with ELISA are among the antiphospholipid antibodies used
to screen for antiphospholipid antibody syndrome and pertinent in SLE diagnosis
Lupus anticoagulant
Multiple tests (eg, direct Russell viper venom test) to screen for inhibitors in the clotting
cascade in antiphospholipid antibody syndrome
Direct Coombs test Coombs test–positive anemia to denote antibodies on RBCs
Anti-histone
Drug-induced lupus ANA antibodies are often of this type (eg, with procainamide or
hydralazine; p-ANCA–positive in minocycline-induced drug-induced lupus)

26. Case #2
• Khadija, a 25-year-old woman presents for follow-up. She has a history of systemic
lupus erythematosus, initially diagnosed 6 years ago, that has manifested as flares of
acute serositis and musculoskeletal pains. She has been hospitalized twice in the past
5 years for lupus-related symptoms and has received immunosuppressive therapy.
On a visit to her rheumatologist a week ago, she complained of frothy/foamy urine.
• She is currently on oral steroids, hydroxychloroquine, and azathioprine, in addition
to oral contraceptives and a multivitamin. She is married and has no children. She
does not smoke or drink alcohol. She denies a family history of autoimmune or
kidney disease

27. Examination
• Physical examination reveals a well-appearing woman who is pale and in no
acute distress. She is vitally stable, except a BP of 160/90. Examination of
the upper extremities reveals 1 ring-shaped, scaly, red lesion on the left
forearm with hand deformity bilaterally. Examination of the lower
extremities finds mild (1+) edema bilaterally. No other skin rashes are noted.
Neurological examination reveals no significant findings, specifically with no
proximal or distal weakness noted in the extremities.

28. Jaccoud Arthropathy
A deforming non-erosive arthropathy characterized by ulnar deviation of the 2nd to 5th fingers
with metacarpophalangeal joint subluxation that is correctable with physical manipulation

29. Thoughts?
In a patient with systemic lupus erythematosus and hypertension
who is found to have proteinuria and/or hematuria, there is a
concern that these findings indicate renal glomerular involvement
by lupus nephritis

30. Invx
• CBC:
• HB Low
• MCV Low
• WBCs Low
• ESR high
• CRP normal
• ANA Positive
• Anti-dsDNA Positive
• Anti Smith Positive

31. Why does Anemia occur in SLE
• The most common explanation for anemia is reduced red cell production. This may be due to a
variety of causes, including:
• Inflammation
• Inadequate erythropoietin, a hormone produced by the kidneys, that stimulates the marrow to
make more red cells
• Iron deficiency also may result from menstrual bleeding or from intestinal bleeding due to non-
steroidal anti-inflammatory drugs. Intestinal bleeding can be obvious if the stool is red, maroon,
or black in color, but often bleeding is so slow and gradual that special stool tests are needed to
detect it.
• Loss of bone marrow caused by certain drugs used to treat lupus (such as azathioprine or
cyclophosphamide)

32. • Urine:
• WBCs 10-15 cells
• RBCs 20-30 cells
• Sugar None
• Protein 0.9g/24hours
• Serum creatinine 2.3 Elevated
• BUN 31 Elevated
• Serum Albumin Low
• K Normal
• Na Normal
• Estimated GFR 35ml/min

33. How to diagnose?
• Tests to diagnose lupus nephritis include:
• Blood and urine tests
• Kidney biopsy. The most definitive test for diagnosing lupus nephritis. It can
also help determine how severe the disease is.

34. After suspecting LUPUS
NEPHRITIS, Next step is?
RENAL BIOPSY

36. Classes
• Class I: minimal mesangial lupus nephritis
• Class II: mesangial proliferative lupus nephritis
• Class III: focal lupus nephritis
• Class III (A): active lesions - focal proliferative lupus nephritis
• Class III (A/C):
• Active and chronic lesions: focal proliferative and sclerosing lupus nephritis class III (C)
• Chronic inactive lesions: focal sclerosing lupus nephritis
• Class IV: diffuse lupus nephritis
• Class V: membranous lupus nephritis
• Class VI: advanced sclerosis lupus nephritis.

37. “
”
Class III Lupus Nephritis
Active lesions found
Light microscopy findings
Active focal glomerulonephritis involving <
50% of all glomeruli
Immunofluorescence electron microscopy
findings
Subendothelial and mesangial immune
deposits

38. Case #3
• Affaf is a 33 year old teacher presented complaining of shortness of breath
and chest pain for 2 months and a mild grade fever. The dysponea is worse
when lying down and is increased by walking or climbing stairs. The chest
pain is on the right side of the chest at the 4-6th rib area, stabbing in nature
not relieved with sitting forward and not increased by lying down, it is only
increased with inspiration. Her fever began 3 months ago, mild and was not
associated with chills or sweating.
• she reports a 3-year history of Raynaud's disease

39. Examination
• Patient looked pale, vitally stable (temp 38). High volume pulse and engorged
neck veins.
• Discoid rash on her jaw and neck
• There is a pan Systolic murmur at the Apex of the heart
• Pitting Edema on the lower limbs bilaterally

40. Fever + Murmur?
• Suspect infective endocarditis
Blood cultures negative
Echocardiography showed:
Irregular borders, heterogeneous echodensity, and an absence of independent
motion (verrucous vegetations) on the cardiac valves and endocardium.
Acoustic shadowing suggesting Valvular regurgitation and Valvular stenosis

41. Endocarditis + Lupus?
Libman-Sacks
Endocarditis
• The lesions typically consist of
accumulations of immune complexes and
mononuclear cells
• mulberrylike clusters of verrucae on the
ventricular surface of the posterior mitral
leaflet
Auto antibodies Positive for LUPUS
Negative culture for IE organisms

42. Case #4
A 35-year-old woman, Ameera, has a history of right sided calf pain and swelling for 2
days, she had this same condition in the past and was treated with anticoagulants.
There is a history of CAG and PCI for MI.
She suffers from Gluten sensitivity and had 3 consecutive pregnancy losses before 12
weeks of pregnancy. She had no other known complications during the pregnancies.
Examination: hot tender swelling in her right calf
Further testing reveals:
• Thrombocytopenia and prolonged PTT
• lupus anticoagulant Positive, which is still present on repeat testing 12 weeks later.

43. AntiPhospholipid Syndrome
• Lupus anticoagulant is present in the plasma on 2 or more occasions, at least 12 weeks apart.
• one third of patients with APS have a lupus anticoagulant, anticardiolipin, and anti-beta2-
glycoprotein I antibodies (i.e., they are triple-positive). Many patients may be positive for
only a lupus anticoagulant or anticardiolipin antibody alone. Thus, it is important to offer all
the assays in a patient's work-up.
• 1 or more clinical episodes of arterial, venous, or small-vessel thrombosis in any
tissue or organ + 1 Lab criteria = APS

44. Drug induced Lupus
hydralazine, procainamide, quinidine, isoniazid, diltiazem,
targeted immunotherapy, and minocycline

45. Goals of Management of SLE
The goals of treatment for patients with SLE are to:
• ensure long-term survival
• achieve the lowest possible disease activity,
• prevent organ damage
• minimise drug toxicity
• improve quality of life

46. Non-pharmacological treatment
• Sun protection
• Diet and nutrition
• Exercise
• Psychological intervention
• Smoking cessation

47. Pharmacological treatment
Common pharmacological treatment for SLE includes NSAIDs, antimalarial
therapy, corticosteroids, immunosuppressive agents
• NSAIDs are frequently used as a first-line measure in SLE to control joint
stiffness as well as musculoskeletal and serosal pain. Naproxen may be the
preferred first-line agent
• Hydroxychloroquine is recommended for all patients with SLE The
beneficial effects of hydroxychloroquine in SLE include the reduction of
constitutional symptoms, and reduced musculoskeletal and mucocutaneous
manifestations. Side effect (Retinal toxicity)

48. Steroids
• Pulse doses of intravenous methylprednisolone are recommended to provide
immediate therapeutic effect in SLE and enable the use of a lower starting
dose of oral corticosteroid
• The recommended dose and route of administration depends on the type
and severity of organ involvement. For chronic maintenance treatment, the
dose of oral corticosteroids should be minimised to <7.5 mg/day and, when
possible, withdrawn

49. Immunosuppressive agents
methotrexate, azathioprine, mycophenolate or cyclophosphamide
considered for the treatment of patients:
with organ-threatening disease
not responding to hydroxychloroquine (alone or in combination with
corticosteroid)
unable to reduce the corticosteroid dose below the acceptable dose for chronic
use.

50. Biological agents
• B-cell targeting agents such as belimumab and rituximab are beneficial for
treating patients with SLE who are refractory to other agents
• Belimumab should be considered as an add-on treatment for patients who
have an inadequate response to combination treatment with
hydroxychloroquine and corticosteroid

51. Vitamin D?
In multiple studies, female patients who were not receiving supplemental
vitamin D showed more fatigue and received more oral corticosteroids than
those with normal levels of vitamin D

52. Treatment of Lupus Nephritis
• A combination of glucocorticoids and immunosuppressive agents to slow the
progression to end-stage renal disease (ESRD).
• Maintaining normal blood pressure levels (ie, target of ≤130/80 mm Hg).
• In general, individuals with class I or II lupus nephritis do not need management
with immunosuppression
• Patients with class III or IV disease, as well as those with a combination of class V
and class III or IV disease, generally undergo aggressive therapy with glucocorticoid
drugs and immunosuppressants (mycophenolate mofetil, cyclophosphamide)

53. Management ofAntiphospholipid syndrome
• Primary Prevention: The European League Against Rheumatism (EULAR)
has noted that low-dose aspirin in individuals with SLE and antiphospholipid
antibodies is potentially useful for primary prevention of thrombosis and
pregnancy loss
• Secondary prevention: Thrombosis in nonpregnant patients with SLE and
thrombosis associated with antiphospholipid syndrome can be managed with
long-term use of oral anticoagulants

55. Follow-up
Periodic follow-up and laboratory testing, including complete blood counts
with differential, creatinine, and urinalyses, are imperative for detecting signs
and symptoms of new organ-system involvement and for monitoring response
and adverse reactions to therapies. At least quarterly visits are recommended in
most cases. Periodic complement levels and dsDNA titers may be used as
adjuncts to clinical evaluation for detecting lupus flares.

56. Thank you
• References:
• BMJ
• MEDSCAPE
• PUBMED
• THE ONLY NOTES
• @LUPUSREFERANCE on twitter