Systemic Lupus Erythematosus

Entry criterion: ANA ≥1:80 by HEp-2 IIF (or equivalent positive test) at least once. If absent → do not classify as SLE.

If entry criterion met, apply weighted additive criteria across 7 clinical + 3 immunologic domains. Only count the highest-weighted criterion within each domain. A criterion counts only if not more likely explained by another cause. Classify as SLE if total weighted score ≥10.

Source: Aringer M et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for SLE. Arthritis Rheumatol 2019;71:1400–1412.

SLEDAI-2K — most widely used composite activity index (24 weighted items across 9 organ systems, range 0–105 in practice usually 0–45). General bands used clinically:

• 0 — no activity
• 1–5 — mild
• 6–10 — moderate
• >10 — high/severe activity

Remission / LDA targets (EULAR 2023, treat-to-target):

• Remission: clinical SLEDAI-2K = 0, prednisolone ≤5 mg/day, stable antimalarial/immunosuppressant
• Lupus Low Disease Activity State (LLDAS): SLEDAI-2K ≤4 with no major organ activity, no new activity, prednisolone ≤7.5 mg/day, well-tolerated standard maintenance immunosuppression

Flare management approach

1. Confirm true flare vs damage/infection/non-adherence — check for infection (fever workup), medication adherence (esp. HCQ), and drug/UV triggers before escalating immunosuppression
2. Recheck serology: rising anti-dsDNA + falling C3/C4 supports active flare, especially renal
3. Mild/moderate flare: optimize HCQ adherence; short GC boost (e.g., prednisolone increase to 0.3–0.5mg/kg/day) with plan to re-taper over 4–8 weeks; add/resume conventional immunosuppressant (AZA, MTX, MMF) if flares recurrent on current regimen
4. Severe/organ-threatening flare: IV methylprednisolone pulse 250–1000mg/day ×1–3 days → oral prednisolone 0.5–1mg/kg/day taper; initiate/escalate immunosuppressant per organ involved (see Organ-Specific and Lupus Nephritis sections); consider biologic (belimumab/rituximab) if on background HCQ ± conventional agent alone
5. Reassess background maintenance regimen after flare resolves — recurrent flares indicate need for treatment escalation (add immunosuppressant/biologic) rather than repeated GC bursts, per EULAR 2023 treat-to-target principle

1. Hydroxychloroquine (Plaquenil^®) in all SLE patients unless contraindicated — dose ≤5 mg/kg real body weight/day.
2. Glucocorticoids used as bridging therapy only — minimize to ≤5 mg/day prednisolone-equivalent maintenance; taper/discontinue when possible. Consider IV methylprednisolone pulses instead of prolonged high-dose oral GC for organ-threatening disease.
3. Early initiation of immunosuppressants (methotrexate, azathioprine, mycophenolate) or biologics (belimumab, anifrolumab) to reduce GC exposure and prevent flares/damage, rather than reserving for GC failure.
4. Add belimumab or anifrolumab for inadequate response to HCQ ± immunosuppressant in non-renal disease with high activity.
5. Rituximab considered for organ-threatening disease refractory to standard combination therapy, or severe flare (esp. hematologic, renal), per protocol.

ISN/RPS 2003 Classification (biopsy-based)

• Class I — Minimal mesangial
• Class II — Mesangial proliferative
• Class III — Focal (<50% glomeruli), ± active/chronic lesions (A/C)
• Class IV — Diffuse (≥50% glomeruli), segmental (S) or global (G)
• Class V — Membranous (can coexist with III/IV)
• Class VI — Advanced sclerosing (≥90% globally sclerosed) — immunosuppression not indicated

Biopsy indicated for: persistent proteinuria >0.5g/24h (or UPCR >0.5g/g) especially with active urine sediment, unexplained rise in Cr, or nephrotic syndrome.

• Mycophenolate mofetil 1–2g/day (preferred over azathioprine for higher-risk patients) or Azathioprine (Imuran^®) 1.5–2.5mg/kg/day if MMF not tolerated or pregnancy planned
• Continue triple-regimen add-on (belimumab or CNI) if used for induction
• Prednisolone tapered to ≤5mg/day or discontinued
• Total duration of initial + maintenance immunosuppression ≥36 months before considering withdrawal, and only in sustained complete remission

If nephrotic-range proteinuria or declining function: MMF (or CYC) + GC, similar to proliferative regimens; add ACEi/ARB for proteinuria reduction and BP control regardless of regimen. Non-nephrotic, stable Class V may be managed conservatively with RAAS blockade + HCQ alone.

Per AAO 2016 revised recommendations:

• Dose ≤5.0mg/kg real body weight/day to minimize toxicity risk
• Baseline fundus exam within first year of starting therapy
• Annual screening starting at 5 years of use (sooner — annually from baseline — if major risk factors: renal impairment, concomitant tamoxifen, pre-existing retinal disease, high dose, or cumulative duration >10 years)
• Screening tools: automated visual fields (10-2) + spectral-domain OCT; consider multifocal ERG or fundus autofluorescence at high-volume centers

• Plan pregnancy during sustained remission/LDA (≥6 months); continue HCQ throughout pregnancy (protective, reduces flare/congenital heart block risk)
• Safe in pregnancy: HCQ, azathioprine, tacrolimus, low-dose prednisolone
• Contraindicated: Mycophenolate, methotrexate, cyclophosphamide (except life-threatening indication) — switch ≥3 months pre-conception
• Anti-Ro/La positive → fetal echo surveillance for congenital heart block (weeks 16–26)
• Obstetric APS / high-risk aPL profile → low-dose aspirin ± prophylactic LMWH per APS protocol