SURVIVAL RHEUMATOLOGY in KKU

by P noo+

Standing follow-up form of kku

Reference organization
EULAR : european laegue against rheumatism ACR : american college of rheumatology NIH : national institute of heath bias APLAR : asia- pacific laegue against rheumatism

Reference organization
EULAR : european laegue against rheumatism ACR : american college of rheumatology NIH : national institute of heath bias APLAR : asia- pacific laegue against rheumatism

LUPUS NEPHRITIS :1+4+ Class/ parameter 1 2 3 mi me me pro focal u.Alb u.Cell 4+ 1+

SLE c LN
4 5 6 prolifer membra sclero 2+ 4+ 4+ 1+ 2+ 4+

Cr HT s.Alb Rx

N N N steriod

N N N

Inc Inc Low

Inc Inc Low steroid +/- ivcy

(ivcy+steroid)

4 5 3 1

1. 2. 3.

In another clinical trial, 65 patients with severe lupus nephritis (WHO classes III, IV and V) were randomly assigned to monthly pulses of methylprednisolone (MP) for 6 months, monthly pulses of CY for 6 months, monthly pulses of CY for 6 months followed by quarterly pulses of CY for 2 years. At entry, all 3 groups had similar demographics, duration of renal disease, and baseline biochemical values

the probability of doubling the serum creatinine was significantly associated with the histologic presence of cellular crescents and moderate-to-severe

Standard treament -2 phase for LN3-4

Induction phase (for remission ) maintainace phase( for prevent relapse) 1.NIH regimen Induction : Monthly ICVY 500-1000 mg*BSA *6 cycle (maybe extended if not remission) Maitianance : ivcy every three moths => total course 2 yrs

2.EURO LUPUS trial Induction : IVCY Every 2 wks 500 mg*BSA *6 cycle maintainance :AZATHIOPRINE (immuran) => UNTIL TOTAL COURSE 2 yrs

3.ALTERNATIVE Induction : MMF Mainatainance : MMF,AZA

WHEN PULSE ENDOXAN+ PULSE METHYLPRED. 1. RPGN 2. Acute renal failure 3. anasacar SIDE EFFECT : ht emergency : renal failure rising BUN ( monitor for indication dialysis) : hypokalemia =>

When call LN remission

l l l l

24 hrs urine protein less than 500-1000 mg No active urine sediment Stable serum creatinine Normal complement

Indication for kidney biopsy

1. Unknown definite diagnosis 2. Renal failure (for r/o other cause eg. atn, ain) 3. Not response to tx 4. Acute vs chronic pathology

NPSLE 19 entities: CNS

l l l l l l l l l l l l l

Aseptic meningitis Cerebrovascular disease Demyelinating syndrome Headache (including migraine and benign intracranial hypertension) Movement disorder (chorea) Myelopathy PNS Seizure disorders Transverse myelitis Acute confusional state GBS-like Anxiety disorder Multiple sclerosis-like Cognitive dysfunction Mono/polyneuropathy Mood disorder Psychosis

 1.NPSLE 2.CNS infection 3.Steroid induce psychosis 4.Primar psychosis NPSLElab investigation definite diagnosis rule out
approach 3 1. disease active 2. Complication from treament eg. Infection, steroid 3. approach

SLE and GI vasculitis

Clinical depend on vessel size Medium : bowel angina Ix : angiogram

Small : inflammatory diarrhea (stool exam : wbc+), hematochezia Ix :1. full-thickness bowel biopsy 2. CT ang-> target sign (inflamm from mucosa to serosa)

HEMATOLOGIC ABNORMALITIES
WHEN TO TX ?? 1.LOW WBC :NO TX 2.PLT: <50K oral pred within3-5day <20k =>pulse methyl 3.AIHA : within 1-2 wk decrease from baseline duration response

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) * Increase dz. Activity from inc. of estrogen, Prolactin, Th2 DURING PREGNANCY UNTIL 6 WKS POST PARTUM

Lab before pregnancy planning

1.Neonatal lupus: anti RO (LESS -LA) -> FETAL ECHO at GA 16-24 WK. 2.ANTIPHOSPHOLIPID ( increase risk fetal loss & post partum DVT ) l LUPUS ANTICOAGULANT l ANTICARDIOLIPIN IgG,IgM >40 l B2 GP 1

investigation

AUTO antobidy: 5 basic pattern

Rim/peripheral : Specific for SLE DNA,DNP

homogeneous :,histone

Speckle -anti ENA :u1rnp,sm, ro,la

Nucleolar type :SCL-70 ->dcSSc

Centromere :Lc SSc

CYTOPLASMIC pattern

Jo1 anti synthetase syndrome SRP- poor prognotic ,relate c cardiac involvement MI2- Jdm,V-shawl sign

Significant titer 1:160 ANA ve SLE 1.Severe hypoalbuminemia : loss Ig 2.Prozone phenomenon 3.True ve ANA Confirm anti-Ro ab lab auto Ab ANA, dsDNA, ENA , APS

CONFUSING AUTOantibody
Anti Ro /la : sjogren , ana-ve sle, neonatal lupus Anti jo1 : myositis Sle neuro : anti ribosomal P anti neuronal Ab Sle-renal : antidsDNA (TITIER can use for f/u dz. activity) Sle specific : anti Sm(smith) Sle-raynaud : anti u1rnp

Fluid analysis
Pleural,pericardial,ascites active dz. l ANA titer l LE cell SAAG from ascites l >1.1 Portal cause : work up ivc/portal thrombosis l <1.1 non portal cause : active dz. -> serositis

C3,C4 -> r/o -> relate organ immune complex renal skin active relate unique definite cut point active dz.

DRUG

OVERVIEW DRUG USE IN SLE

l TYPE

AND DOSE :Depend on organ and severity with least toxicity basic drug that must use if no contraindicate is CHLOROQUINE

l Essential

CQ as immunomodurators l Anti inflammation

l Anti

platelet l Anti apoptosis l Anti lipid l Longer life span Taper off q 3 mo,because long half-life 1 OD -> 1 EOD(4TAB/WK) -> 1tab ,-> 1tab/wk(4tab/mo) ->1 tab d1,16(2 tab/mo)

Fever, arthalgia, skin : chloroquine Fever, arthalgia Pleural effusion : NSAIDs Pericarditis, AIHA : PRED 1MKD When to use pulse methyl ? - transverse myelitis - Aggressive psychosis, suicidal attempt - lupus pancreatitis
- -

Diffuse alveolar hemorrhage LN C RPGN

Drug side effect : advice pts

Cylcophosphamide
(onsia 8 mg iv) l oliguric renal failure l (related totla dose > 18 gms)
l

10-20 (related total dose > 25 gms) Infection (,,)

2 : 200 500mg 500-1000 mg*BSA 25%

l l Adminitrations

: infusion in 5dw 100 ml for 1 hr.

Azathioprine
1. Bone marrow suppression metabolite TPMT enzyme homo & heterozygous mutation active metabolite bone marrow leukopenia

 CBC 2 1*1 follow up CBC 1*2 (keep wbc > 3500) 2. Hepatitis

How to taper off steroid

4*3 5*2 4*2 3*2 5*1 4*1 3*1 2*1 1*1 12 10 8 6 5 4 3 2 1 Q 2 WKS %change 16 20 (not for DM/PM) 25 33 MONTHLY 20 25 33 2-3 MO 50 3-6 MO

PROPHYLAXIS steroid induce osteoporosis (GIOP)

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

l Calcium

carbonate normal requirement about 1g 1 g absorp400 mg SO dose :1 tab bid D (normal liver and renal MTV if insufficiency 1vit D ) MTV 1tab vitD 400IU, Normal requirement about 800IU SO dose ;1 tab bid
l Vitamin

INDICATION FOR BISPHOSPHANATE :

1. 2.

T-SCORE any site <-2.5 Previous hx of fx any site

f/u BMD Q 2YR after tx for evaluate response Don t forget to stop if duration 5 yr : frizzle bone No role only of ibandronate (no data in GIOP) -use 1.alendronate(fosamax) 2.risedonate (actonel)

Rheumatiod arthritis
Preliminary criteria for dx early RA

Rheumatiod arthritis
Joint
Mod-large*1 *2-10 Small *1-3 *4-10 Total >10,at least is 1-small

0 1 2 3 5

Sero RF / CCP VE At least 1 +ve low titer high titer ESR+CRP :normal ESR/CRP :increase Duration <6wk >6wk

0 2 3

0 1

0 1

Serologic factor
%sensitivity %specificity

RF CCP COMBINE

41 62 33

98 84 99.6

 RA r/o

RA-LIKE

Is it establish RA ?

O R
Is it RA-like ?

DDX RA-like
l 1.crystal

induce l 2.spa : re A, psor A- ra type, undif spa l 3.CNTD : SLE, Ssc, DM/PM, MCTD l 4.viral infection : hep B,C , HIV l 5.paraneoplastic polyA

RA: Extra-articular Disease

l Pulmonary

alveolitis/fibrosis l Scleritis/Keratitis l Sjogren s Syndrome treat symptomatically l Peripheral Neuropathy l Vasculitis (rheumatoid nodules, skin infarcts, leg ulcers)

Radilogic erosion40
3 5 3 0 2 5 2 0 1 5 1 0 5 0

Rational treatment : COBRA TRIAL

mtx

sq e t eun

se -p tpu

ssz

lef

mtx ssz lef

cmbn o ie

Mtx+ssz pred +csa

boo i ilgc

Mtx+biologic

DAS 28
l The

number of swollen joints l The number of tender joints l The ESR/CRP l The patients general health (GH) or global disease activity measured on a Visual Analogue Scale Low dz. Activity =3.2 (VAS) of 100 mm (both are Remission for=2.6 purpose useable this
Good response :delta DAS >1.2

Pre operative evaluation :

l l 1.

Routine investigation Special caution NSIADs : off 7 days before sx (even short or long acting)

2. Steroid
l

1 :not effect to adrenal gland -> no mx 1 hydrocortisone only intra-operative, not continue after sx hydrocortisone when NPO dose severity of stress Major operation -> 300mg Minor operation -> 200 mg

3. DMARDs : off 1 day before sx Restart after total stitch off

4. anti-TNF : off 1 wk before surgery because significant increase risk of infection Restart after total stitch off

 flexion

dens c1

Anterior atlanto-axial subluxation l Lateral-flexion interval >5mm ,if>7 mm -> sx

l

Is it dz of head or hip??

Common DMARDs use

CQ : for non erosive MTX : first line start 3-4tab/wk if >6 tab switch to sc. Injection ,start 12.5 mg (1 amp has 2 ml, 1ml 25 mg) SSZ : titrate 1*1 * 1wk then 1*2 *1 wk then 1*3 * 1wk for avoid s/e nausea,vomitting LEF (ARAVA) : 1*1 EOD or OD (NOT loading dose in THAI)

ALL DMARDs can cause hepatitis : Not forget to R/O 1. VIRAL 2. NSAIDs (sim= sulindac,indomethacin,mefenamic have entrohepatic circulation) 3. herb If not more than 3* -> observe If more than 3* -> off medication

Biologic tx in RA (in THAI)

Anti TNF :next page Anti CD -20 :rituximab

IL-6 mAb :tocilizumab

Anti-TNF alpha : 1.Inflizimab -> monoclonal Ab 2.etanercept ->TNF receptor fusion protein r/o latent TB C/I : heart failure, demyelination

5 subgroup :

SPONDYLO ARTHRITIS

1.Ankylosing spondylitis 2.Psoriatic arthritis 3.Reactive arthritis 4.IBD 5.Undifferentiated spa

BASDI >4 SCORE = ACTIVE DZ. :which is used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue l Spinal pain l Joint pain / swelling l Areas of localized tenderness (also called enthesitis, or inflammation of tendons and ligaments) l Morning stiffness duration l Morning stiffness severity
l

BASDAI: INFLAMMATION
BASDAI
Please tick the box that indicates your answer to each question. All questions refer to last week. 1. How would you describe the overall level of fatigue/tiredness you have experienced?

0
none

10
very severe

2. How would you describe the overall level of AS neck, back or hip pain you have had? none very severe 3. How would you describe the overall level of pain/swelling in the joints other than neck, back or hips you have had? (ie: peripheral joints) none very severe 4. How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure?

10

10

10

none very severe 5. How would you describe the overall level of mourning stiffness you have had from the time you wake up?

10
very severe

none 6. How long does your morning stiffness last from the time you wake up?

0
0 hr

5
1 hr

10
2 or more hours

Osteitis condensan ilii

ENTHESITI S

1.Ankylosing spondylitis
-first line is NSAIDs -peripheral jt involvement => ssz -axial => biologic ,but in THAI poverty country : MTX

2.Psoriatic arthritis
-first line DMARDs : MTX -severe skin lesion : must r/o HIV always because HIV run down -5 clinical subtypes 1. RA like - symmetrical poly 2. DIP involvement- classic pso A. 3. Arthritis multilan (telescopic digit) 4. Asym oligo 5. spondyloarthropathy

70% skin before 15% arthritis before 15% skin concomittent with arthritis

3.Reactive arthritis
-typical rash

First line DMARDs => SSZ

Circinate balanitis

Keratoderma Blenorrhagicum

SCLERODERMA

OUT- patient evaluation

1. modify rodman Skin score

2.General symptom in SSC 3.Thyroid function test at base line 4.Yearly echo : for early detection PHT (early Rx-> longer survival) 5.Yearly cxr 6.pulmonary function test :if clinical suspect : IDL :for early dx alveolitis, -> HRCT

Medication Rx in scleroderma
To date :no specific treatment, except
1.Active alveolitis :endoxan oral + prednisolone 10mg /day

2.Edematous skin (small trial) l Prednisolone l Mtx l cq 3.PHT :

CCB (even vasoreactive +/-) Dorner (beraprost) PG inhibitor Viagra (sildelnafil) -PDE5 I Bosentan (ET1 -RA)

4.Digital gangrene : PHT +/- coumadin 5.Myositis => off drug induce then steroid

bosent an

prostacy clin

silden afil

Symptom base treatment drugs :

l Motilium

: has clinical GERD l Omeprazole : has heart burn l Asa(81),nifecard retard (20) : has raynauds

Scler renal crisis

Purpose mechanism is : RP OF RENAL VASCULAR Dx : 1.sudden anemia with unexplained cause and MAHA blood picture (most early symptom) 2.accelerated HT(10% normotensive) 3.Cr rising Rx : even has renal failure, but can use ACE I captopril challenge, AIM baseline himself

Auto Ab in scleroderma and clinical correlation

Limited : anti centomere Diffused : anti scl-70 GI : TH/T0 RENAL : RNA polymerase III (MCTD : U1RNP)

Poly/dermato myositis

Abnormal capillary nail fold

Tape steroid : only when NORMAL CPK LEVEL longer duration q 1 mo. When need steroid sparing :MTX, AZA - steroid dependent - steroid resistant Look for malignancy : consult l Breast, ovary, lung l Nasopharynx in ASIA

FREQUENT PITFALL
:RAPID TALE OFF STEROID Normal clinical course : not remission before 2 yr.

Poor prognostic factors :

1. 2. 3. 4. 5. 6.

Delay diagnosis Respiratory/pharyngeal involvement Related to malignancy SRP +ve Severe myositis at presentation ILD

Septic arthritis
Proper ATB depend on 2 factors

Abnormal joint -RA -OA -GOUT -prosthetic joint

abnormal host -diabetes -cirrhosis -IVDU

SEPTIC ARTHRITIS
BACTERIAL GC non-GC DZ. : G+6WK non-BACTERIAL : ATB UNDERLYING

G-4WK -DGI : CEFTRAIXONE 1GM IV OD *7 DAY (hemorrhagic pustule , tenosynovitis) -Acute mono : Rx as others septic

Common pitfall
definite diagnosis arthritis cause - tx infection/crystal NSAIDs 1. ATB 2. mask infection joint destruction

PRELIMINARY CRITERIA FOR EARLY DIAGNOSIS RHEUMATIC DISEASE

AIM
Early diagnosis => Better outcome

DISEASES

1. Rheumatiod arthritis 2. Scleroderma 3. Ankylosing spondylitis

Rheumatiod arthritis
Joint
Mod-large*1 *2-10 Small *1-3 *4-10 Total >10,at least is 1-small

0 1 2 3 5

Sero RF / CCP VE At least 1 +ve low titer high titer ESR+CRP :normal ESR/CRP :increase Duration <6wk >6wk

0 2 3

0 1

0 1

Scleroderma

VEDOSS : Very early diagnosis of systemic sclerosis

major 1.Raynauds phenomenon 2.Anti centomere/scl-70 3.Diagnostic nailfold capillaroscope

additional 1.C alcinosis 2.E sophageal dysfunction 3.T elangiectasia 4.P uffy finger 5.D igital ulcer 6.G round glass from HRCT

DIAGNOSIS NEED

1. 3 MAJ 2. 2/3 MAJ + at least 1 additional

Ankylosing spondylitis
DATA SENSE SPEC 76 89 90 96 Likelihood ratio 3.1 3.4 4.0 4.5

Inflammatory 75 back pain Heel enthesitis 37 asym.peripheral 40 arthritis dactylitis 18

DATA

SENSE

SPEC Likelih ood ratio 96 99 95 97 85 80 90 90 2.5 4.0 6.4 7.3 5.1 2.5 9.0 9.0

Psoriasis IBD Family hx Iritis/ant uveitis Good response to NSAIDs Raise ESR/CRP HLA-B27 MRI- sacroiliitis

10 4 32 22 77 50 90 90

 likelihhood

20 80 >200

50 80 90

Inflammatory back pain with normal x-ray of Spine and SI joint

If had clinical >3 If had clinical 1-2 if + ve if - ve => => => => dx axial send HLA dx axial consider spa B-27 spa other dx

If no clinical,but HLA B-27+ve => MRI SI jt. if + ve => dxaxial spa if - ve => consider other dx