*5.1.2 Maintenance phase*

*Lupus - Need to Know*

*Activity Index*

*Chronicity Index*

**5. Management**

**Table 4.**

*5.1.1 Induction phase*

**5.1 Current management strategies**

Fribrinoid necrosis 0 to 3+ (x2) Hyaline deposits 0 to 3+

TOTAL 24

Tubular atrophy 0 to 3+ Interstitial fibrosis 0 to 3+ TOTAL 12

*Modified NIH activity and chronicity scoring system (ISN/RPS 2018).*

Early treatment in LN has been shown to improve outcome; however, effective management remains a challenge. It requires a multidisciplinary team approach (MDT), ideally by rheumatologists, nephrologists and nephropathologists. The cornerstone of treatment entails corticosteroids, antimalarial, and steroid-sparing agents (conventional immunomodulators and/or biological therapies) tailored to individual patients based upon histological class and severity to achieve rapid resolution of inflammation, proteinuria <0.5–0.7 g/day by 12 months (or up to 24 months in baseline nephrotic range proteinuria) [47] and prevention of relapsing episodes.

**Items Score Comment**

Endocapillary hypercellularity 0 to 3+ 0 to 3+ based on % involvement of glomeruli

Cellular/fibrocellular crescents 0 to 3+ (x2) Double weightage for fibrinoid necrosis and cellular/fibrocellular crescent. Interstitial inflammation 0 to 3+

Total glomerulosclerosis score 0 to 3+ 0 to 3+ based on % involvement of glomeruli

2+ = 25–50%, 3+ = > 50%. Fibrous crescent 0 to 3+

2+ = 25–50%, 3+ = > 50%. Neutrophils/karyorrhexis 0 to 3+

or tubulointerstitium. 0 = none, 1+ = <25%,

or tubulointerstitium. 0 = none, 1+ = <25%,

While there is little agreement for class II LN, in active proliferative class III, IV and pure membranous class V (with nephrotic range proteinuria or proteinuria >1 g/ day despite optimal use of renin-angiotensin-aldosterone system (RAAS) blockers), the current recommendation for initial induction treatment options include either low-dose intravenous cyclophosphamide (CYCi; 500 mg fortnightly infusions for 3 months) or mycophenolate mofetil (MMF; 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) [47, 65–68]. This is combined with high-dose pulsed intravenous methylprednisolone followed by oral corticosteroid taper. High-dose CYCi is reserved for patients with severe LN due to its' various unfavourable side effects (mainly severe cytopenias and infection, cystitis, ovarian failure, cervical dysplasia and malignancy). The use of calcineurin inhibitors (CNIs) namely tacrolimus (TAC) and cyclosporin (Cys) either as monotherapy or as part of a multitarget regimen therapy (with MMF/MPA and glucocorticoid) may have a favourable efficacy to induce remission. Meta-analysis in 2017 which included 45 induction trials of diverse participant background confirmed superior efficacy in induction by multitarget

**42**

In the maintenance phase of treatment where less intensive therapy is required, MMF (1-2 g/day or MPA at equivalent dose) or azathioprine (AZA) are the drugs of choice [47, 71, 72] (with or without low dose <7.5 mg/day corticosteroid), depending on the induction regimen and plan for pregnancy. Hydroxychloroquine (HCQ ) is recommended for all LN patients in the absence of contraindications [47]. Due to possible ocular toxicity, the dose should not exceed 5 mg/kg body weight and should be adjusted in patients with renal and liver disease, with regular ophthalmological screening.
