Simplified knowledge about the diagnosis & medical treatment of SLE & APS for undergraduates & GPs.

1. DR. ABD EL AZEIM ALHEFNY. MD
Prof. Internal Medicine, Rheumatology & Immunology
Ain Sham University

2. At the end of this lecture you have to know:-
 SLE definition, shot note on pathophysiology
 Clinical picture
 2012 SLE Classification criteria
 Investigations & follow up
 Prognosis, complications.
 Lines of treatment.

3. SLE
❖ A multi-system inflammatory, autoimmune connective
tissue disease that occurs most commonly in women
during their reproductive age
❖ The hallmark of SLE is its variety of presentation &
autoantibodies.
❖Essentially any organ system can be affected, particularly
the skin, joints, kidneys, and CNS.

4. 4
More common in urban than in rural areas
4 - 5 cases per 10,000
Female：male= 9：1 (adult)
Onset age= 65% between 15-25 ys (late onset ?40-55)
Identical twin：30%
First degree relative：5%
❖ Child of SLE mother has risk of SLE
(with positive anti – Ro/SSA antibody) ≈ 2%
Epidemiology of SLE

5. • The specific cause of SLE is unknown .
Researches suggest many factors contribute to the
immune dysregulation in SLE :-
1) Genetic factors
2) Environmental factors (UV light, stress .. )
3) Hormonal factors ( Estrogen .. )
4) Drugs

6.  There are about 400 medications currently in use that can cause
this condition & most common drugs are :-
 Procainamide, quinidine, hydralazine and isoniazid.
Minocycline, Chlorpromazine, Penicillamine, Methyldopa,
Interferon-α , TNF- α blocker
 DIL is a benign reversible condition .
 DIL mimics SLE, however, symptoms generally disappear once the
pt. stops the offending drug.
 Less serious disease, without nephritis nor cerebritis.
 ANA & Anti-Histone antibodies are +ve; while ds DNA is -ve,

7. • It is a localized form of lupus. The skin is the
only target organ affected by the disease.
• Cutaneous LE is usually provoked by sunlight
• Common Types: discoid lupus, subacute
cutaneous lupus, lupus profundus & neonatal
lupus.

8. III-SLE
PRESENTATION

9. Alopecia
Oral ulcers
& Urinary abnormalities
Nonerosive
<4000
<100,000
Lymphopenia<1500
III- Systemic
Lupus
Erythematosus

11. 1) Acute cutaneous lupus:

12. • Fixed erythema, flat or raised, over the malar
eminence (distribution over the cheeks and
bridge of the nose), sparing the nasolabial
folds (DD: sunburn, Chloasma).
• The rash may precede or accompany other
manifestations of lupus.
• The involved skin feels warm and edematous.
• The rash may last for hours or days, and often
recurs, particularly with sun exposure (UV).
Malar / Butter fly rash
Spare the
nasolabial fold

13. Subacute cutaneous lupus (SCLE):
• a non-itchy dry rash appears on the upper
back and chest, often following sun
exposure.
 Erythematous, slightly scaly, has
annular or polycyclic pattern.

14. • Discoid rash: Erythematous raised patches with adherent keratotic scaling
and atrophic scarring may occur
2) Chronic cutaneous lupus:

15. Photosensitivity
• Development of Skin rash as a result of unusual reaction
to UV-B radiation found in sunlight or fluorescent lights.
• It occurs in 60 – 100% of SLE patients
• The incidence is also greater in those with anti-Ro
antibodies

16. Oral or nasopharyngeal ulceration, usually painless, observed by a
physician
3) Oral & nasal ulcers

17. Localized alopecia Wide spread
4) Non Scaring Alopecia

18. VasculitisRaynaud’s

19. • Arthritis in SLE is nonerosive &
nondeforming involving two or
more peripheral joints,
characterized by tenderness,
swelling or effusion
• Deforming features, such as ulnar
deviation, hyperflexion, and
hyperextension, are generally
reducible.
• These are secondary to
involvement of joint capsule,
ligaments, and tendons, and are
referred to as Jaccoud-arthropathy
5) Arthritis (nonerosive)XR: with the exception of periarticular
osteopenia, joints look good!
5) Arthritis:

20. 20
DD. MUSCULOSKELETAL MANIFESTATIONS IN SLE
SLE RA
Arthralgia Common Common
Arthritis Common Deforming
Symmetry Yes Yes
Joints involved PIP > MCP > wrist > knee MCP > wrist > knee
Synovial hypertrophy Rare Common
Synovial fluid Transudate Exudate
Subcutaneous nodules Rare 35%
Erosions Very rare Common
Morning stiffness Minutes Hours
Myalgia Common Common
Myositis Rare Uncommon
Osteoporosis Variable Common
Avascular necrosis 5-50% Uncommon
Deforming arthritis
Swan neck
Ulnar deviation
Uncommon (Jaccoud's arthr)
10%
5%
Common
Common
Common
MCP= Metacarpophalangeal joint; PIP=proximal interphalangeal joint.

21. • (a) Pleurisy; convincing
history of pleuritic pain or
rub heard by physician or
evidence of pleural effusion
OR
• (b) Pericarditis;
documented by ECG or rub
or evidence of pericardial
effusion
CXR : pleurisy
6) Serositis:

22. Pleural and pericardial effusions
(CT chest)
Importantly, when a young woman presents with shortness of
breath and pleuritic chest pain, the DD must include SLE, and
the patient should be tested for ANA.

23. 23
Pulmonary Involvement In SLE
Pleural disease
Acute lupus pneumonitis
Chronic interstitial lung disease
Pulmonary hemorrhage
Pulmonary embolism
Pulmonary hypertension
Diaphragmatic dysfunction

24. 24
Cardiac manifestation of SLE
Pericardium ： • Pericarditis +/- effusion
• Cardiac tamponade (rare)
• Constrictive perecarditis
Myocardium ： • Myocarditis
Endocardium ： • Libman-Sacks endocarditis
Coronary artery ： • Accelerated atherosclerosis
• Vasculitis

25. Libman-Sacks (sterile) endocarditis

26. • (a) Persistent proteinuria > 0.5g/ day
or > 3+ dipstick OR
• (b) Cellular casts: may be red cell,
hemoglobin, granular, tubular or
mixed
Red cell casts
Granular castGlomerulonephritis
7) Renal:

27. • (a) Seizures: in the absence of
offending drugs or known
metabolic disorder; e.g., uremia,
ketoacidosis, or electrolyte
imbalance
OR
• (b) Psychosis: in the absence
of offending drugs or known
metabolic disorder.
• Symptoms can present alone concomitantly with activity in
other systems.
8) Neurological:

28. 28
NEUROPSYCHIATRIC MANIFESTATIONS IN SLE
Central Nervous System
Diffuse manifestations (35%-60%) Seizures (15%-35%)
Organic brain syndromes
Organic amnestic/cognitive dysfunction
Dementia
Altered consciousness
Grand mal
Focal
Temporal lobe
Petit mal
Psychiatric
Psychosis
Organic mood/anxiety syndromes
Other
Headaches
Aseptic meningitis
Pseudotumor cerebri
Normal pressure hydrocephalus
Focal manifestations (10%-35%)
Cranial neuropathies
Cerebrovascular accidents/strokes
Transverse myelltis
Movement disorders
Peripheral Nervous System
Peripheral Neuropathies (10%-20%) Other
Sensory polyneuropathy
Mononeruitis multiplex
Chronic, relapsing polyneruopathy
Guillien-Barre syndrome
Autonomic noruopathy
Myasthenial gravis
Eaton-Lambert syndrome

29. • (9) Hemolytic anemia: with reticulocytosis
OR
• (10) Leukopenia: < 4000/mm3 total
Lymphopenia: < 1500/mm3 on two or more
occasions
OR
• (11) Thrombocytopenia: < 100,000/mm3 in the
absence of offending drugs
Hematologic disorder

30. 1) ANA
• Abnormal titer of ANA
(≥ 1:160) by
immunofluorescence at
any point in time, in the
absence of drugs known
to be associated with
drug-induced lupus
syndrome
Immunologic criteria
diffuse
nucleolarspeckled
peripheral
ANA immunofluorescent patterns

31. % ANA-positiveCondition
95-98SLE
15-30RA
95-100MCTD
95SCL
80PM/DM
75-90Sjögren's syndrome
60-90▪Autoimmune liver disease
(autoimmune hepatitis ,
primary biliary cirrhosis)
10-30Chronic HCV infection
15-25Neoplasia
15-25Healthy relatives of SLE patients
3-5Normal
20-40Normal elderly (>70 yr.)
Medical conditions associated with
positive ANA

32. • (2) Anti-DNA: antibody to native DNA in abnormal titer
OR
• (3) Anti-SM: presence of antibody to Smith nuclear antigen
OR
• (4) Positive finding of antiphospholipid antibodies based on:-
– (1) an abnormal serum level of IgG or IgM aCL antibodies,
– (2) a positive test result for lupus anticoagulant using a
standard method, or
– (3) a false-positive serologic test for syphilis known to be
positive for at least 6 months and confirmed by Treponema
pallidum immobilization or fluorescent treponemal antibody
absorption test
Immunologic criteria

33. 5) Low complement levels (C3, C4, CH50).
6) Direct Coombs’ test (in the absence of
hemolytic anemia).
Immunologic criteria

35. INVESTIGATIONS

36. CBC
Leukopenia & Anemia in SLE
Possible causes of
leukopenia in SLE
• Immune destruction
• Marrow suppression
• Hypersplenism
• Drugs
Possible causes of
anemia in SLE
 Auto-immune hemolytic
anemia
 Anemia of chronic disease
 Marrow suppression
 Blood loss due to
thrombocytopenia or
NSAID use
 Hypersplenism
 Anemia of renal failure

37. Thrombocytopenia in SLE
• May be:-
– modest (platelet counts of 50,000 –100,000/mm3), chronic and
asymptomatic,
OR
– profound (<20,000/mm3) and acute, with gum bleeding, petechiae,
and other complications.
• Thrombocytopenia in SLE has multiple potential causes, including ITP,
APS, TTP, and active SLE.
• Any young woman presenting with “idiopathic” thrombocytopenia
should be evaluated for SLE.
• Fortunately, there are rarely qualitative defects in the platelets and
therefore life threatening bleeding is unusual.

38. 38
Serological Tests to Aid Diagnosis of SLE

39. LUPUS
NEPHRITIS

40. • LN, one of the most serious manifestations of SLE, usually arises
within 5 years of diagnosis, it increases mortality rate & considered
as independent factor for early atherosclerosis
• It is more severe in blacks than in whites & in men than in ϙ.
Manifestations of LN:-
• Urinary sediment (≥5 red blood cells /HPF, casts),
• Urine protein excretion >0.5 g/day or 3+ on dipstick
• An elevated serum creatinine ≥1.5 mg/dL
• Symptoms related to active nephritis include peripheral edema
secondary to:- HTN or hypoalbuminemia (heavy proteinuria) or
cardiac decompensation.
Lupus nephritis

41. 41
Indications For Renal Biopsy in
LN
1. Increasing serum creatinine without alternative
causes (such as sepsis, hypovolemia, or medication)
2. Confirmed proteinuria of >1.0 gm/24 hours (either
24-hour urine specimens or spot protein/creatinine
ratios are acceptable).
3. Combinations of the following:-
Proteinuria > 0.5 gm/24 hours plus hematuria, (> 5
RBCs/hpf ) or cellular casts.
RBCs: red blood cells; HPF: high-power field. (Hahn et al., 2012)

42. WHO classification of LN
❖ Class I : minimal mesangial GN.
❖ Class II : mesangial proliferative LN.
❖ Class III : focal proliferative nephritis.
❖ Class IV : diffuse proliferative nephritis.
❖ Class V : membranous nephritis.
❖ Class VI : Glomerulosclerosis. ESRD.
 Patients with active LN often have other symptoms of active SLE, including
fatigue, fever, skin rash, arthritis, serositis, or CNS disease (esp. in Class III & IV
LN).
• eGFR 60 ml/minute/1.73 m2 (=s. cr 1.5 mg/dl) is a risk factor for accelerated
atherosclerosis
patients are usually
asymptomatic
Signs of an isolated N.S.
More serious
disease

43. I Mesangial
V Membranous
III Focal Proliferative
IV Diffuse Proliferative

45. Pregnancy and lupus
➢ Lupus does not affect fertility; but SLE pregnancy outcomes are
more likely to be complicated.
➢ For the mother, SLE exacerbation, LN and PE, possible need for preterm
delivery, and an increased rate of CS.
➢ Fetal-neonatal concerns include miscarriage and fetal death, PE, placental
insufficiency and IUGR, preterm birth and its complications and neonatal
lupus.
➢ Patients should avoid pregnancy in the presence of active LN, severe
HTN, serum cr > 2 mg/dl, or proteinuria > 1gm/dl.

47. Neonatal lupus
 Some infants may develop hemolytic anemia, thrombocytopenia,
leucopenia, and hepatosplenomegaly.
 CHB may occur & needs pacemaker, ?lead to CHF, even sudden death
 Very few infants with neonatal lupus develop SLE later in life.
 There is 25% risk for a subsequent pregnancy to be affected (high risk).
▪ NLE is a rare syndrome associated with
maternal antibodies to Ro/SSA and/or La/SSB~7%
▪ Infants develop erythematous macules or
plaques, exacerbated by sun shortly after birth.
▪ The lesions typically resolve without scarring,
but dyspigmentation and telangiectasia may occur.
Pregnancy and lupus

48. Complications of SLE
Disease-related
– Cardiovascular
complications
– ESRD
– Stroke
– Hypercoagulability
with thrombosis
– Cytopenias (disease
flare)
Treatment-related
– Infections (Immunosuppresion)
– Cushengoid, striae rubra (CS)
– Cytopenias (BM depression)
– Bladder toxicity {CYC}
– Premature gonadal failure &Infertility
{CYC}
– Premature atherosclerosis (CS)
– Increased risk of malignancy
– Osteoporosis (CS)
– Avascular necrosis (CS)

49. Avascular necrosis
of neck femur (MRI)

51. TREATMENT
• Earlier screening of the high-risk patient (consumed complement & rising anti-
DNA) might have an impact on subsequent morbidity and mortality.
Preventive measures
 Regular evaluation
 Photo protection (clothing, sunscreens, avoid hot part of day)
 Control of Infection
 Control of BP and hyperlipidemia {ACEI, ARBs- Statins}
 Influenza and pneumococcal vaccination
 Osteoporosis prophylaxis by calcium, vitamin D,+/- bisphosphonate
 Folate supplementation + Low Dose Asp
 Stop smoking (so antimalarials work better & decreases CVD risk)
 Thiazides and sulfonylureas may exacerbate skin disease
 Special attention 6 months before, during pregnancy & PP may help to avoid
disease flares and adverse fetal outcome.

52. TREATMENT
Mild disease (arthralgia & cutaneous disease):-
▪ TOPICAL STERIODS (for discoid lupus, malar rash)
▪ NSAIDs (e.g. ibuprofen..)
▪ Antimalarials (hydroxychloroquine) (5mg/kg/ d)

53. Moderate and severe disease
▪ Steroids (0.5- 1 mg/kg/day)
▪ Cytotoxics
▪ Azathioprin 1-2 mg/kg/day
▪ Cyclosporin A (neoral)
▪ Cyclophosphamid IVI 0.5-1 gm/m / 4weeks x6 Cycles
Can be used
during pregnancy
TREATMENT

54. Management of organ-threatening SLE
• High dose steroid 0.5-1mg/kg/d or pulse
• Immunosuppressive therapies: cyclophosphamide,
mycophenolate mofetil, cyclosporine A
• Plasma pheresis
• Intravenous immunoglobulin (IVIG)
• New Biologic agents
• Stem cell transplantation
54
TREATMENT

55. PULSE STEROID THERAPY
Methyl prednisolone 0.5-1 gm/d 3-5 days is indicated
for:-
• Acute lupus flair (progressive inspite of TTT)
• Active nephritis
• Acute active CNS
• Acute cytopenias (AIHA, AITP)
• Refractory serositis
• Vasculitis
• Severe constitutional manifestations
(fever, fatigue, synovitis, anemia)

56. Follow-up testing
 Lab: Use the CBC, ESR, anti-dsDNA, and C3, C4 to monitor SLE
disease activity.
 Determine renal function, urinalysis, creatinine clearance and 24-
hour urinary protein excretion or P/C every 3 ms.
 Fundus exam & field of vision/6m for HCQ
 CXR /HRCT to assess any pulmonary affection
– Monitor Drugs Commonly Used in treatment
▪ Clinically: Disease activity index (SLEDAI, SLAM) &
Damage Index SLICC

57. APS
DR. ABD EL AZEIM ALHEFNY. MD
Prof. Internal Medicine, Rheumatology & Immunology
Director of Rheumatology Unit
Ain Sham University

58. At the end of this lecture you have to know:-
 APS definition, shot note on pathophysiology
 Clinical picture
 Classification criteria.
 Lines of treatment.

59. is a multisystem autoimmune disorder
characterized by:-
➢ Recurrent venous or arterial thrombosis
➢ Fetal losses/preterm labor.
➢ Persistently elevated levels aCL, LAC
antibody &/or anti beta-2 glycoprotein 1.
It affects mainly females (9:1) in the child bearing period.
It may be primary or secondary to other diseases, eg.SLE
eMedicine > Systemic Rheumatic Disease APS; Aug 10, 2007
APS

60. Coagulatio
n

61. when occurs in patients without evidence of any
definable associated disease.
• 10% of PAPS will develop SLE in 10 years {LAC was added as
immunologic criterion for SLE (in 50-60% of pts)} .
• Secondary APS occur in association with SLE or another rheumatic
or autoimmune disorder.
Primary APS
Secondary APS

62. Clinical Presentation
APS is characterized by specific manifestations
collected in the word "CLOT” :-
• C = CLOTING; (Recurrent A/V thrombosis).
• L = Levido reticularis, exaggerated by cold.
• O = Obstetric losses (recurrent fetal loss).
• T = Thrombocytopenia (22-30%).

63. APS Manifestations Recorded in Order of
Their Frequency
1. DVT (31.7%),
2. Thrombocytopenia-sub clinical (21.9%)
3. Livedo reticularis (20.4%),
4. Stroke (13.1%), AMI in young.
5. Superficial thrombophlebitis (9.1%)
6. Pulmonary embolism (9.0%),
7. Fetal loss (8.3%),
8. TIA (7.0%)
9. Hemolytic anemia (6.6%)

64. Digital infarction

65.  Recurrent fetal loss:
>3 consecutive unexplained <10w,
or >1 in >10w (second or third trimester).
 Pregnancy-induced HTN (PIH) <34w
 High risk Preterm birth
>1 premature births of a morphologically healthy neonate <34w’
gestation because of severe PE or eclampsia or severe placental
insufficiency
 Uteroplacental insufficiency with placental infarcts
(YOU MUST EXAMINE THE PLACENTA)
APS & FETAL OUTCOME

66. Placental infracts

67. 12
12

68. MANAGEMENT
OF APS

69. Thrombosis
– Perform full anticoagulation with IV or SC heparin followed by
warfarin therapy.
– Our target for INR is 2-3 for venous thrombosis and ≈3.0 for
arterial thrombosis.
– Patients with recurrent thrombotic events, may require an INR of
3 -4.
– For severe or refractory cases, a add 100mg aspirin to warfarin.
– Treatment for significant /recurrent thrombotic events in patients
with APS is generally lifelong.
– Hydroxychloroquine 5mg/kg daily, has antithrombotic & lipid
lowering effects.

70. Catastrophic AP syndrome (CAPS)
A rapidly progressive lethal form of PAPS with widespread
vascular occlusions (in medium & small arteries) in multiple
organs (> 3 organs in few days) (mortality rate of approximately
50%).
• Hospitalization in ICU
• Full heparinization
• Plasmapheresis
• IVIG
• Prednisolone
• Cyclophosphamide (especially in
SLE-associated CAPS).
Management of CAPS !?

71. Evaluation
1. New classification criteria for SLE
2. DD between RA & SLE???
3. How can you diagnose APS