for exchange of ppt

1. SLE
diagnosis & management
BY: Mohammed Hussein (IMR II )
MODERATOR: Dr Abel Tenaw ( Internist)

2. Evaluation of the patient
• History and physical examination have paramount importance
• In identifying the constellation of signs and symptoms
• The extent of organ system involvement
• Assessing the social, psychological and functional impact of the disease
• To construct and rule in/out different differential diagnosis
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3. Laboratory testing
• Routine
• CBC with differential
• RFT
• LFT
• Serum electrolyte
• Urinalysis with urine sediment
• ANA (ideally by indirect
immunofluorescence testing)
• Anti-double-stranded DNA (anti-
dsDNA)
• Antiphospholipid antibodies (lupus
anticoagulant [LA], [aCL] antibodies,
and IgG and anti-beta2-GP 1)
• C3 and C4 or CH50 complement levels
• (ESR) and/or (CRP) levels
• Urine protein-to-creatinine ratio
• 24hr urine protein
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4. Antibody testing
 ANA
The hallmark serologic feature
(>98% of patients with recent
methods).
positive test is not sufficient to
establish the diagnosis of SLE.
IF ANA titer is >1:80,determine
more specific, test for more
specific antibodies.
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5. Cont’d
• If the initial ANA test is negative but the clinical suspicion of SLE is high, then
additional antibody testing may still be appropriate.
• ANA negative lupus occurs in less than 2% off cases with the human epithelial
type 2 (Hep-2) cells using assay
• Nevertheless, on rare occasions, the presence of anti-Ro/SSA antibodies may
suggest a systemic autoimmune disease despite the presence of a negative ANA
indirect immunofluorescence.
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6. Additional tests
• Perform the following additional laboratory tests in selected patients:
• Rheumatoid factor and anti-cyclic citrullinated peptide antibodies
• Serologic studies for infection
• Creatine kinase
• Biopsy of an involved organ
• Other imaging tests depending on the dominant complaint
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7. Diagnosis
• Lupus is a multi-organ disease
• May present in many ways
• Can mimic infectious diseases, cancer, autoimmune conditions
• ACR classification criteria facilitates systematic approach
• Focuses on the most common SLE manifestations
• Highly sensitive + specific for classifying SLE
• But patients with mild disease may be missed
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8. 8
Classification criteria
Sensitivity -83%
Specificity - 93%
Sensitivity -92%
Specificity - 83%
Sensitivity -96.1%
Specificity - 93.4%

9. The 1997 ACR criteria
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10. Systemic Lupus International Collaborating Clinic (SLICC)
2012 criteria
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11. ACR/EULAR 2019 CLASSIFICATION CRITERIA
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12. Management
The goals of therapy for patients with systemic lupus erythematosus (SLE) is to:
• Ensure long-term survival
• Achieve remission or the lowest possible disease activity
• Prevent flares and organ damage
• Minimize drug toxicity
• Improve quality of life
• Educate patients about their role in disease management
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13. Cont’d
Treatment of SLE is individualized based upon
• Patient preferences
• Clinical manifestations
• Disease activity and severity
• Comorbidities.
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14. NONPHARMACOLOGIC AND PREVENTIVE INTERVENTIONS
Sun protection
• Patients should avoid exposure to direct or reflected sunlight, and other sources
of UV light (eg, fluorescent and halogen lights).
• Sunscreens that block both UV-A and UV-B, and have a sun protection factor
(SPF) ≥55, are suggested.
• Medications that can cause photosensitivity should also be avoided in patients
with SLE
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15. Diet and nutrition
• Balanced diet consisting of carbohydrates, proteins, and fats.
• Patients with active inflammatory disease and fever may require an increase in
caloric intake.
• Glucocorticoids can enhance appetite, resulting in potentially significant weight gain.
• Vitamin D levels should be monitored periodically and patients with low vitamin D
levels should be treated with supplemental vitamin D.
• In patients with hypertension and/or nephritis, dietary measures such as salt
restriction may be required
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16. Cont’d
• Exercise
• Smoking cessation
• Immunizations
• appropriate immunizations prior to the institution of immunosuppressive
therapies
• Live attenuated vaccines can lead to complications in patients on
immunosuppressive therapy
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17. Treating comorbid conditions
• Accelerated atherosclerosis
• Pulmonary hypertension
• Antiphospholipid syndrome
• Osteopenia or osteoporosis
• Issues with specific medications and therapies — Allergies to antibiotics are
more common among patients with SLE, with up to 30 percent of patients having
an allergy to sulfonamide-containing antibiotics that include sulfamethoxazole in
TMP-SMX]) and other less commonly used sulfonylarylamine antimicrobials
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18. Pharmacologic therapy: General principles
 All patients should be on HCQ regardless of severity.
 Patients with mild lupus manifestation, HCQ.
 Patients with severe or life-threatening manifestations secondary to major organ
involvement require an initial period of intensive immunosuppressive therapy.
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19. Pharmacologic therapy
• Non-organ-threatening disease
• Muco-Cutaneous
• Musculoskeletal
• Constitutional
• Organ-threatening disease
• Renal
• CNS
• Cardiopulmonary
• Hepatic
• Hematology
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20. Anti-malarials
 For all patients
 Benefits
Constitutional symptoms
Musculoskeletal manifestations,
Mucocutaneous manifestations.
Improves survival.
Decrease flare.
• HCQ 200 to 400 mg/day (<5 mg/kg actual
body weight).
• Chloroquine 250 mg/day (≤3.0 mg/kg ideal
body weight).
• Quinacrine 100 to 200 mg/day
 Precautions: ophthalmic toxicity
Keep dose at below 5mg/kg/d
Monitor patients periodically –at baseline,
after 5 years, and yearly thereafter.
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21. Glucocorticoids
• GC provide rapid symptom relief
• Minimize daily dose to ≤7.5 mg/day prednisone equivalent or to discontinue them
• Two approaches can be considered:
(1) use of pulses of intravenous methylprednisolone (MP) allow for a lower
starting dose and faster tapering of PO GC
 High-dose intravenous MP (usually 250–1000 mg/day for 3 days) is often used
in acute, organ-threatening disease (eg, renal, neuropsychiatric) after excluding
infections
(2) early initiation of IS agents, to facilitate tapering and eventual discontinuation
of oral GC
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22. IMMUNOSUPPRESSIVE AND CYTOTOXIC DRUGS
 Indications
 Involvement of major organs or extensive involvement of non-major organs
(skin) refractory to other agents, or both.
 Failure to respond to or inability to taper glucocorticoids to acceptable doses.
The choice of agent depends on prevailing disease manifestations, patient age and
childbearing potential, safety concerns and cost
 Include cyclo, MMF, MTX, CIN, AZA
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23. Methotrexate and azathioprine
• Methotrexate (MTX) and azathioprine (AZA) should be considered inpatients
with poor symptom control after a trial with GC and HCQ or when HCQ alone
is unlikely to be sufficient, due to the large experience gained with their use and
their relatively safe profile.
• Published evidence is generally stronger for MTX than AZA, yet the latter is
compatible with pregnancy contemplation.
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24. Mycophenolate mofetil- MMF
• Potent IS with efficacy in renal and non renal lupus( not in NPSLE)
• In extrarenal SLE enteric coated mycophenolate sodium (EC-MPS) is superior
to AZA in achieving remission and reducing flares
• Teratogenic and needs to be discontinued 6 weeks before conception
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25. Cyclophosphamide
• can be considered in organ-threatening disease (especially renal, cardiopulmonary
or neuropsychiatric) and only as rescue therapy in refractory non-major organ
manifestation.
• Gonadotoxic effects, it should be used with caution in women and men of fertile
age.
• Concomitant use of GnRH analogues attenuates the depletion of ovarian reserve
• Typically has two types of induction dosing regimens
• The NIH protocol - 0.5-1gm/m2 IV monthly for 6 doses
• The EUROlupus protocol- 500mg IV every 2 weeks for 6 doses
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26. Biologicals
Belimumab- anti BAFF
• a human monoclonal antibody that inhibits the soluble form of a B cell survival
factor.
• Extrarenal disease with inadequate control (ongoing disease activity or frequent
flares) to first-line treatments (typically including combination of HCQ and
prednisone with or without IS agents), and inability to taper GC daily dose to
acceptable levels (ie, maximum 7.5 mg/day)
• More likely to respond are patients with
• High disease activity (SLEDAI >10)
• Prednisone dose >7.5 mg/day
• Serological activity (low C3/C4, high antidsDNA titres)
• Cutaneous, musculoskeletal and serological manifestations
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27. Rituximab
• RTX is currently only used off-label, in patients with severe renal or extrarenal (mainly
haematological and neuropsychiatric) disease refractory to other IS agents and/or
belimumab,or in patients with contraindications to these drugs.
• As a general rule, more than one IS drug need to have failed prior to
RTXadministration, except perhaps for cases of severe autoimmune thrombocytopaenia
and haemolytic anaemia, where RTX has demonstrated efficacy both in lupus and in
patients with isolated immune thrombocytopaenia (ITP) .
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28. Cont’d
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29. MANAGEMENT OF SPECIFIC MANIFESTATIONS
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30. Mucocutaneous and joint disease
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31. Haematological disease
Indication of treatment
• Thrombocytopenia with platelet count <30,000 or bleeding sxs
• AIHA with hg <10 g/dl
• Leucopenia with wbc <2500/μL or ANC <1000/μ- rarely needs treatment
(exclude other causes like drug toxicity)
• Moderate to High dose GCs – initial therapy with pulses of IV MP is encouraged
• IS agent as steroid-sparing agent (AZA ,MMF or cyclosporine)
• IV-IGB –severe life threatening case and not responding to the above therapies
• Refractory cases can be treated with rituximab or CYC
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33. MANAGEMENT OF CARDIOPULMONARY MANIFESTATIONS
 Glucocorticoids are the mainstay of the treatment of the inflammatory
cardiopulmonary manifestations.
 Sever life threatening manifestations
Pulse dose of GCS PLUS IV cyclo or MMF.
IVIG, Plasma exchange,
 Milder forms…AZA or MTX
 NSAIDS may suffice for isolated Pleurisy or mild pericarditis.
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34. NPSLE management
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35. Renal disease management
• Induction and maintenance therapy
• Current therapeutic strategies in LN include an initial induction phase, aimed at substantially
improving disease activity (or even attaining remission), followed by a maintenance phase, in
which the goal is to maximize the therapeutic effect, consolidate the response and prevent
relapse.
• Risk stratification, according to renal pathology and patient demographic, clinical,
and laboratory characteristics, enables the identification of patients at risk poor
prognosis who may benefit from more aggressive therapy
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37. 05/23/2025 37

38. For Class I or II lupus nephritis
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39. Class III and IV nephritis
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40. Class V nephritis
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41. Assessing treatment response in lupus Nephritis
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42. Management of inadequate response to TX
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43. Treatment of Renal Flares—Relapsing Disease
• Approximately 30% to 50% of patients with moderate to severe PLN will
relapse after achieving partial or complete remission.
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44. Duration of maintenance therapy
• Gradual withdrawal of treatment (glucocorticoids first, then
immunosuppressive drugs) can be attempted after at least 3 to 5
years therapy in complete clinical response.
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45. Monitoring
• Assessment of disease activity
• Response
• Drug adverse effects
• Co-morbidity
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46. Assessment of disease activity and severity
• Disease activity refers to the manifestations of the underlying inflammatory
process at a point in time in terms of magnitude and intensity.
• Disease severity refers to the type and level of organ dysfunction and its
consequences, often described as mild, moderate, and severe.
• The degree of irreversible organ dysfunction has been referred to as damage
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47. Cont’d
• When evaluating the patient and assessing disease activity, there are generally three
patterns of disease to consider:
• Intermittent disease flares (or relapsing and remitting disease with periods of
disease quiescence in between flares)
• Chronically active disease in terms of patterns of organ involvement
• Quiescent disease
• In clinical practice, disease activity and severity are assessed using a combination of
clinical history, physical examination, laboratory and serologic studies as well
as organ-specific tests
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48. Research tools
• Laboratory tests –(Vit D receptors, urinaryIL-6, and complement activation
markers)
• Disease activity indices- (SLEDAI-2K), the Revised Systemic Lupus Activity
Measure (SLAM-R), the European Consensus Lupus Activity Measurement
(ECLAM).
• Damage indices-The systemic lupus international collaborating clinics
American College of Rheumatology damage index (SLICC/ACR-DI) is used to
measure accumulated damage that has occurred since disease onset
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49. SLEDAI-2k
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50. Cont’d
Total possible score is 105
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51. Interpretation
• Scores:
• No activity (SLEDAI=0),
• Mild activity (SLEDAI=1 to 5),
• Moderate activity (SLEDAI=6 to 10),
• High activity (SLEDAI=11 to 19), and very high activity (SLEDAI≥20).
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52. Cont’d
• The Lupus Low Disease Activity State (LLDAS) is defined currently as
 a SLEDAI-2K score ≤4;
 no new lupus disease activity compared with the previous visit
 physician’s global assessment ≤1 (scale 0–3);
current prednisone dose ≤7.5 mg daily; and
 well-tolerated stable doses of antimalarials and/or immunosuppressives.
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53. Cont’d
• Given the heterogeneity of disease presentation and clinical course among patients
with SLE, an assessment of disease activity should be performed at each clinic
visits.
• Monitoring frequency — The frequency with which monitoring laboratory tests
are performed is tailored to each patient. Factors that should be taken into account
when determining the frequency of visits include the history of the patient's prior
symptoms, current disease activity status, disease severity, and frequency and
severity of prior disease flares.
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54. Flares
• Definition — A flare is 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 increase in treatment.
• Mild
• Moderate
• severe
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55. Predictors flares
• Increased serum titer of anti-dsDNA antibodies and a fall in complement levels
(especially CH50, C3, and C4).
• Persistently low serum levels of complement C1q are also associated with
activity of lupus nephritis.
Factors associated with increased risk of SLE flare-
• Diagnosis of SLE before age 25 as well as patients who have renal,
vasculitic, or neurologic involvement.
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56. Response: target to treat
Remission : SLEDAI score = 0 on antimalarials only
low disease activity states :
• SLEDAI score ≤3 on antimalarials only
• SLEDAI ≤4 with GC ≤7.5 mg of prednisone,HCQ and well tolerated
immunosuppressive agent
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57. Fever in SLE
• Fever is a common manifestation of SLE and can occur in 36-86% of patients
• Among patients with FUO, 5% are diagnosed with SLE
• One of the component in all commonly used disease activity indices
Causes of fever in SLE-
• Flare or disease activity (common cause)
• Infection
• Drugs ( AZA, MMF)
• Malignancy
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58. Cont’d
 Infections:
 Account for 20% to 55% of all deaths in patients with SLE.
 Commonly involved sites
The respiratory system
 urinary tract, and
 the CNS
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59. Flare Vs Infection
• Favors Flare
• Fever in the setting of leukopenia
would be more consistent with
lupus activity
• Fever that responds to analgesics
• High Disease activity
• Favors Infection
• Chils and rigors
• Fever on steroid
• Fever not responding to anti
pyretics
• Leukocystosis plus fever
• ESR:CRP > 15
• hsCRP value >6 mg/dL
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61. Pregnancy and lupus
• Pregnancy may increase disease activity and precipitate the appearance of flares, which
are usually mild; 35% to 50% of lupus patients will have evident disease activity during
pregnancy.
• Risk factors for adverse maternal and fetal outcomes (pre-eclampsia, pregnancy loss,
and preterm birth, among others) are
• Active disease during the last 6 months before conception,
• HCQ discontinuation,
• A history of LN, and the presence of APA, especially lupus anti-coagulant.
• primigravidas
• Pregnancy should be avoided during active disease due to the high risk of miscarriage
and exacerbation of SLE
• Ideally, disease should be quiescent for six months on medications compatible
with pregnancy prior to systemic lupus erythematosus (SLE) patients attempting
conception
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62. Cont’d
• Preconception evaluation — to determine whether pregnancy may pose an
unacceptably high maternal or fetal risk, to initiate interventions to optimize
disease activity, and to adjust medications to those that are least harmful to the
fetus.
• Women should be advised that discontinuation of medications used to control
disease activity increases the risk of lupus flare and pregnancy complications.
Ideally, women considering conception should be maintained on medications that
are compatible with pregnancy and should continue these medications in
pregnancy.
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63. Cont’d
• Risk assessment — The preconception evaluation in women with SLE should
include an assessment of disease activity and major organ involvement, as well as
hypercoagulability or concurrent medical disorders that may impact pregnancy.
• Previous obstetric outcomes should be reviewed, with particular attention paid to
history of small for gestational age fetus, preeclampsia, stillbirth, miscarriage, and
preterm birth.
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64. Cont’d
 All patient should be checked for presence of specific Ab.
anti SS A and anti SS B
‐ ‐ ‐ ‐ : associated with neonatal lupus and congenital heart
block ( 2% of such pregnancies)
If positive monitor for CHB between 16 and 26wks of GA
anti phospholipid antibodies
‐ : early and late trimester miscarriage (25-40%-
spontaneous abortion)
 Mothers should be assessed for disease activity more frequently.
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65. Cont’d
• Regarding breastfeeding, the American Academy of Pediatrics (AAP)
states that nursing is permissible for women receiving GC, but the interval
between dose and nursing should be at least 3 hours if the prednisone dosage is
greater than 20 mg/day.
• Antimalarials and azathioprine may be continued during lactation; cyclosporine
is also considered compatible with breastfeeding, although data are limited
• MTX, MMF, CsA, leflunomide, and CYC are also contraindicated.
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66. Drugs in pregnancy
Selective use allowed during pregnancy
• NSAID
• Glucocorticoids
• Azathipurine
• Cyclosporine
• HCQ
• Antihypertensive medications –
methyldopa, labetelol, nifidipine and
hydralazine
Selective use with caution in pregnancy
• Biologic medications
Contraindicated in pregnancy
• Cyclophosphamide
• MMF
• MTX
• leflunomide
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67. Contraceptives
• The choice of the optimal method of birth control for women with systemic lupus
erythematosus (SLE) and/or antiphospholipid syndrome (APS) depends upon
multiple factors, including patient values and preferences, efficacy and side
effects of contraceptive methods, underlying disease activity, other comorbidities,
thromboembolic risk, and medication interactions
• For patients who want to use a long-acting reversible contraceptive (LARC),
the levonorgestrel (LNg)-containing intrauterine device (IUD) is a safe and
effective option for most patients with SLE and/or positive antiphospholipid
antibodies (aPLs).
• For patients who want to use an oral hormonal contraceptive, the estrogen-
progestin contraceptives may be used in patients with stable low disease activity
and documented negative aPLs.
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68. Cont’d
• The use of estrogen-progestin contraceptives are contraindicated in women
with aPLs with or without SLE, due to the increased risk for thrombosis
• For SLE patients who do not want to use an IUD and have high disease activity,
a positive aPL, or other contraindications to the use of estrogen, we suggest
progestin-only contraceptives such as the progestin-only pill
• Barrier methods are the least effective method of contraception; but can be
considered in the setting if hormone containing methods or IUDs are not
preferred by the woman
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69. Malignancy in SLE
• Patients with SLE have a slightly increased risk for overall cancer development
(standardized incidence ratio [SIR], 1.14 to 1.28.
• Certain types of malignancies occur more commonly in patients with SLE, in particular
non-Hodgkin’s lymphoma (NHL), cervical and lung cancer.
• Immunosuppressive therapy, viral exposures, as well as the disease per se have been
implicated for this altered risk
• On the contrary, patients with lupus seem to have a slightly reduced risk of certain non-
hematologic cancers (breast, ovarian, endometrial, and prostate)
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70. Cont’d
• Cervical dysplasia is increased in women with SLE (pooledOR, 8.7208) as a result of
impaired clearance of HPV.
• Screening cervical cytology with HPV testing is recommended for all female
patients with SLE; for women with detectable HPV DNA, subsequent screening with
cervical cytology should be performed every 6 months.
• For the remaining patients, annual rescreening is sufficient.
• SLE patients under 25 years should receive vaccination against HPV, similar to the general
population
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71. Prognosis
• More than 90% of survival at 5 years
Poor prognostic factors in SLE include:
• Renal disease (especially diffuse proliferative glomerulonephritis)
• Hypertension
• Male sex
• Young age
• Older age at presentation
• Low socioeconomic status
• Being a Black person
• Presence of antiphospholipid antibodies
• Antiphospholipid antibody syndrome
• High overall disease activity
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72. References
• Harrisons text book of internal medicine 21st
edition
• Firestein & Kelley’s Textbook of Rheumatology 11th
edition
• Rheumatology 7th
edition
• EULAR recommendations on management of SLE 2023
• 2024 KIDGO clinical practice guideline for the management of
glomerular diseases
• Up-to-date online matterials
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73. Thank you
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