2013 LUPUS for INTERNIST.

. . .

Reference organization
EULAR
ACR NIH APLAR

European laegue against rheumatism

American college of rheumatology National Institute of Heath bias Asia- Pacific Laegue against Rheumatism

African-American Asia Hispanic

Whats New ??

Development Classification Criteria for SLE

1982

2012 SLICC Classification Criteria :

Diagnosis need : 1) 4 ; at least 1 clinical + 1 immunologic 2) Renal :

aCL

LAC

B2GPI

Figure 2. Necrotizing lesions of the glomerular tuft indicate severe immune aggression in lupus. The necrotizing segments (red arrow) appear fuchsinophilic with the trichrome stains, and they are accompanied by distortion of the tuft and, frequently, by nuclear fragmentation (karyorrhexis) (green arrow). (Massons trichrome, X400).

Lupus nephritis
Evaluate 2 components : 1. Proteinuria (NS) 2. Active GN

IS IT DPLN ??? (diffuse proliferative LN Class 3,4)

1.

SEVERE parameters : 24 hr urine Total protein >3g/day 2. Serum alb <3 3. Rbc sediment >50 cell/HPF 4. Mild HT 5. Acute renal failure

VERY SEVERE parameters : 1. RPGN 2. Accelerated HT 3. ANASARCA

BASIC DATA for decision making

UA : - 24 hr.protein - sediment - alb - Cr

Serum :

HT

- mild - accelerate

Aims of Treatment in Proliferative Lupus Nephritis

1. 2. 3. 4. Not to delay treatment To induce remission To prevent renal flares To minimize the iatrogenic morbidity

Treatment of Proliferative Lupus Nephritis

Induction phase - acute phase, renal remission at presentation and during follow up Maintenance phase - prevent relapse and minimizing the side effects of therapy

Cyclophosphamide
1970s 1980: Mayo Clinic, NIH prospective RCT
Regimens of Cyclophosphamide+prednisolone were more effective than prednisolone alone
Probability of stable renal course

Prednisolone + cyclophosphamide

Prednisolone

10

20

30 40 months

50

Donadio JV,et al . N Engl J Med 299,1978

Probability of Maintaining Life-Supporting Renal Function in 107 patients with Active Lupus nephritis
IVCY
Probability of no renal failure

AZCY POCY AZA PRED Prednisolone vs. IVCY p=0.027

0 20 40 60 80 100 120 Follow up (months) 140 180

Austin HA,et al . N Engl J Med 314 , 1986

NIH study
Therapy Prednisolone Azathioprine Cyclophosphamide AZA+CYC Pts 30 20 18 23 10 yrs Renal survival 40% 72% 80% 88%

IV CYC

20

91%

Austin H, et al. NEJM 1984; 314: 6

CYCLOPHOSPHAMIDE-Long course
PROBABILITY OF NO EXACERBATION

CYCLOPHOSPHAMIDE-Short course

12 24 36 48 FOLLOW UP (Months)

60

Short-course Cy had a higher probability of exacerbations than long-course Cy Boumpas DT, Austin HA, et al. Lancet 340, 1992

Combine Pulse Methylprednisolone and pulse IV Cyclophosphamide :

At Median Follow-up 5 years Probability That Serum Creatinine Level Will Not Dobule
IVCY Combination IVMP IVCY

Probability of Remission

Combination

IVMP

12 24 36 48 60 FOLLOW UP (Months)

72

12 24 36 48 60 FOLLOW UP (Months)

72

Gourley MF,et al . Ann Intern Med 125,1996

Controlled Trial in Lupus Nephritis: IVCY vs. IVMP vs. Combination

Probability That Therapy Would Not Fall

An extended follow-up 11 years

Combination IVCY

IVMP
0 24 48 72 96 Months from Study Entry 120

Illei GG, et al. Ann Intern Med 2001; 135: 248-57

Controlled Trial in Lupus Nephritis: IVCY vs IVMP vs Combination

Cyclophosphamide therapy Avascular necrosis Osteoporosis Premature amenorrhea Infection Herpes zoster infection Death Combination therapy Methylprednisolone therapy

36% 23% 60% 26%

31% 21% 52% 32%

30% 13% 33% 8%

26%
5/27

32%
5/28

7%
1/27

Adding pulse methylprednisolone during the initial phase may be advantage for pt with severe proliferative LN

Illei GG, et al. Ann Intern Med 2001; 135: 248-57.

Treatment DPLN:
with background STEROID Induction phase ( for remission ) maintainace phase ( for prevent relapse ) 1. NIH regimen Monthly IVCY 500-1000 mg*BSA *6 cycle (maybe extended if not remission) 2. EURO LUPUS trial IVCY Every 2 wks 500 mg*BSA 3. ALTERNATIVE MMF 2-3 g/day

ivcy every three months => total course 2 yrs

AZATHIOPRINE (immuran) => Total course 2 yrs

*6 cycle

: MMF,AZA

severity SEVERE parameters : 1.24 hr urine Total protein >3g/day 2.Serum alb <3 3.Rbc sediment >50 cell/HPF 4.Mild HT 5.Acute renal failure No severe parameter Severe parameter -OPD case Severe parameter - IPD case VERY severe parameter

DOSE pred 0.5 MKD (moderate dose) 1.0 MKD (high dose) : no renal failure DEXA 4 mg iv q 6hr/ ivMP IVCY : has renal failure Double pulse : Pulse methyl prednisolone + Pulse IVCY

: EARLY F/U = 2 weeks If clinical run down => step up treatment

Treatment of Lupus class V

Nephrotic range proteinuria :
First line treatment high dose alternate day prednisolone (1-2 mg/kg) for 2 months taper to 0.25 mg/kg alternative days within 3-4 mo Optional adjuncts to prednisolone therapy Cyclosporine A 5 MKD Pulse cyclophosphamide 1 g/m2 every 2 mo Oral cyclophosphamide 2 MKD Oral MMF 2-3 g/day Methylprednisolone/chlorambucil Azathioprine 1-2 mg/kg/day Mixed membranous and proliferative nephropathy: treat as proliferative lupus nephritis

TREATMENT:
Depend on SEVERITY MILD - MODERATE - SEVERE

MILD
Skin / arthritis

MODERATE
peritonism

SEVERE
NEURO symptoms Pericardial effusion Pulmonary hemorrhage

Pleural effusion Mild LN -Leukopenia Mod LN -AIHA without anemic symptom -plt 20,000- 50,000

LN with renal failure -AIHA with anemic symptom -plt < 20,000

-plt 50,000-100,000

Treatment :
-CQ -NSAIDs
Steroid at least 0.5 MKD

High dose steroid endoxan

HEMATOLOGIC ABNORMALITIES
WHEN TO TX ?? duration response

1.LOW WBC : NO TX

2.PLT: 20- 50K oral pred <20K => HIGH DOSE pred
3.AIHA : decrease from baseline

within3-5day

within 1-2 wk

dexamethasone prednisolone methylprednisolone hydrocortisone

25 5 4 1 Equivalent with pred 30 mg =6 tab

Order dose
Prednisolone 0.5 MKD Prednisolone 1MKD DEXA 5 MG IV Q 6hr

High dose
20 mg/day

60 mg = 12 tab 100 mg

DEXA 10 MG IV Q 6hr

Moderately high dose 40 mg/day Very high dose

200 mg
1,000 mg

Pulse methylprednisolone 1g

HOW TO TAPERING STEROID

12 TAB 10 4*3 5*2 % change 16 Q 2 wk.

8 6
5 4 3 2 1 0.5

4*2 3*2
5*1 4*1 3*1 2*1 1*1 1*eod

20 25
33 20 25 33 50 50 Q 3 mo Q 1 mo.

CQ / HCQ :
immunomodurators Anti inflammation Anti platelet , Antithrombotic Anti apoptosis Anti lipid Longer life span

Taper off q 3 mo, because long half-life 1 OD hs -> 1 EOD(4TAB/WK) -> 1tab , (2TAB/WK) -> 1tab/wk (4tab/mo) -> 1 tab d1,16 (2 tab/mo)

Glucocoritcoid induce osteoporosis(GIOP) PROPHYLAXIS

WHEN NEED ? : IF planning PREDNISOLONE >5mg/d More than 3 MO Treat by ? : ca, vit d

 Calcium carbonate normal requirement about 1g /d 1 g absorp 400 mg SO dose :1 tab bid

Vitamin D Normal requirement about 800IU /d (normal liver and renal MTV if insufficiency 1 vit D ) MTV 1tab vit D 400IU, SO dose :1 tab bid

SLE and PREGNANCY

* SHOULD NOT PREGNANCY IN CASE OF
ACTIVE DISEASE CARDIO-PULMO-RENAL INSUFF HT

* SAFE FOR PREG : DZ. REMISSION ABOUT 6 MO. W/WO ANTIMALARIAL (CAN CONTINUE ALONG PREGNANCY)

Lab for pregnancy planning

1.Neonatal lupus :
anti RO (LESS anti LA) -> early FETAL ECHO at GA 16-24 WK.

2.ANTIPHOSPHOLIPID syndrome
( increase risk fetal loss & post partum DVT ) LUPUS ANTICOAGULANT Anti CARDIOLIPIN IgG,IgM >40 Anti B2 GP 1

LAB SLE F/U

CBC, ESR UA BUN, Cr CHOL , ALB, AST, ALT

Any Questions ???