Systemic lupus erythematous with lupus nephritis Diagnosis & Treatment <MGR review> Systemic lupus erythematous with lupus nephritis Diagnosis & Treatment R4 김 광 열

BACKGROUND Definition Prevalence Systemic lupus erythematosus(SLE) is autoimmune disease in which organs and cells undergo damage initially mediated by tissue-binding auto-antibodies and immune complexes in most patients, auto-antibodies are present for a few years before the first clinical symptom apears Clinical manifestation are heterogenous Prevalence 90% women of childbearing year, all genders, ages and ethnic groups are susceptiable In USA, 10~400 per 100,000, highest in black women, lowest in white men Harrison’s principles of internal medicine, 18th

PATHOGENESIS Harrison’s principles of internal medicine, 18th

Harrison’s principles of internal medicine, 18th

Arthritis Rheum 25:1271, 1982; update by MC Hochberg, Arthritis Rheum 40:1725, 1997.

Harrison’s principles of internal medicine, 18th

Ann Rheum Dis 2012;71:1771-1782

Question 1. 71/F, SLE c LN type V 로 진단되어 MPD pulse 1g for 3days 투여 후 다음치료는 어떻게 할 것인가? Cyclophosphamide 500mg iv q2 week for 3month Mycophenolate mofetil 2~3g/day for 6 month Azathiopurine 2 mg/kg/day rituximab

Induction Therapy Maintenance Therapy Refractory disease MMF(mycophenolate mofetil) :2-3g/day for 6month or low-dose CY(cyclophosphamide) : 500mg iv q 2week for 3 month Adverse prognostic factor(+): high dose CY(0.75-1g/m2) for 6month or orally(2-2.5mg/kg/day) for 3 month IV methylprednisolone (MPD) three consecutive pulse (500-750mg)  oral prednisolone (PDL) 0.5mg/kg/day for 4 week  reducing to <10mg/day by 4-6 month Maintenance Therapy MMF 2g/day or AZA(azathiopurine) 2mg/kg/day for at least 3 years + PDL(5-7.5mg/day) Refractory disease Fail teatment with MMF  CY Fail treatment with CY  MMF Rituximab

Adjunct treatment Angiotensin-converting enzyme(ACE) inhibitor or angiotensin receptor blockers (ARB) :proteinuria (UPCR >50mg/mmol) or hypertension Cholesterol -lowering statins : target LDL (100mg/dL) Hydroxychloroquine : reducing renal flare, limiting the accural of renal and cardiovascular damage Acetyl-salicylic acid : anti-phospholipid Ab(+) Calcium, vitamin D Non-live vaccination Anticoagulant treatment

Question 2. 14/F, SLE c LN type IV 로 진단되어 MPD pulse 1g for 3days 투여 후 다음치료는 어떻게 할 것인가? Cyclophosphamide Mycophenolate mofetil Azathiopurine rituximab

Ovarian toxicity Start age Total number of pulse

2008년 당시 cyclophosphamide 와 steroid Tx 가 우선시되며 less severe한 경우 MMF 또는 AZA alternative 하게 사용될 수 있다.

2010년 ACTA review에서는 현시점에서 치료는 CY pulse이지만 최근 성인에서 MMF induction Tx 2010년 ACTA review에서는 현시점에서 치료는 CY pulse이지만 최근 성인에서 MMF induction Tx.의 효과가 CY에 비교하여 떨어지지 않는다는 결과를 보여 주고 있고 소아에서의 MMF 사용이 증가하는 추세라고 저자는 말하고 있음.

2011년 Nelson (19th)에서는 severe SLE의 치료로 CY 를 추천하고 있으며 젊을 수로 gonadal failure의 가능성이 떨어짐을 설명하고 있음. 일부 MMF 가 CY 만큼의 효과를 나타난다는 보고가 있으나 long term therapy f/u이 필요하다고 말하고 있음.

Cyclophosphamide Mycophenolate IV cyclophosphamide : best-documented long-term success rate in children and adults with severe SLE Based upon the Natinal Institute of Health protocol(NIH) :500mg/m2 for 6 month, followed by every 3 months for additional 30 months Very successful in the treatment of children with diffuse proliferative glomerulonephritis Long term safety of IV pulse in children is not well defined. Gonadal toxicity, consider sperm banking or ovarian protection Mycophenolate Used, particularly where there is significant risk to future gonadal function Incidence of stomach upset Requires consistent twice time daily  compliance can become problematic in children