Kitty KwokQEH

17 May 2011

Rheumatology Inter-hospital Meeting

Madam Lo•F

/ 46 •F

irst presented to our rheumat clinic on 20 Dec 2010•R

efer from HKEH•O

n and Off left upper eye lid swelling x 2 months•N

ot responded to topical steroid eye drops or antibiotics•A

bnormal serology• ANA 1:640 • ESR 82

•Anaemia• Fe deficient• Known menorrhagia for > 10 years

1st Clinic visit 20th Dec 2010Absence of ….•Skin Rash•Photosensitivity•Arthritis•Oral ulcers•Raynaud Physical Exam• Chest clear • Abdo no organomegaly • no arthritis• no rash• no cervical LN • No gland swelling • Mild Swelling or redness over left Upper lid

CT orbit 23 Dec 2010• Mild proptosis of left globe is noted• Soft tissue thickening is seen at left upper eyelid• No gross collection is found• No retro-bulbar mass is seen• Extra-ocular muscles and optic nerves are not thickened• Superior ophthalmic veins are not dilated• Cavernous sinuses are symmetrical

Call back for early review

• Urine TP/Cr 1.45 g• Hb 6.9

24 Jan 2011Upon clinic visit assessment

•Increased oral & lip ulcers since 17 Jan 2011• Unable to eat solid food

•Sore throat•Ankle edema for 2 weeks•Fever for few days•Generalized weakness • Power shoulder abduction grade 4/5

•Taking “Ling Chi” for 1 year

•ANA 1:640 Homogenous•Anti DNA > 300•ENA –ve•pANCA + Anti MPO <6

•Normal RFT •Alb 36•Hb 6.9 – Lym 0.5•C3 0.56 •CRP < 3.4 ESR 67 •CK 1560

•Urine TP/Cr 1.45•Urine alb 3+ RBC 3+ hyaline cast 8-10 / LPF

•CXR cardiomegaly•ECG SR Low voltage

•Active SLE• Oral ulcers• Leucopenia with fever• Lupus nephritis with generalized edema• Myositis

•SLEDAI score 10 (DNA, fever, proteinuria, ulcers)

•Admitted for further management• Empirical treatment with augmentin• Iv hydrocortisone 100mg iv Q6H• Arrange BMA and renal biopsy

2 days after admission

•Sudden onset of severe abdominal pain

•Not relieved by antacids

p/e • Abdo tender over epigastrium• Bowel gas +• No organomegaly• Toxic looking

•AXR no fluid level

•CXR no gas under diaphragm

•Amylase came back 2997

•ALP 281

•ALT 125

•INR <1.00

•Ms Lo Kept by NPO

•Vigorous rehydration

•Rocephin & Flagyl

•Hydrocortisone continued

•S/B CT abdo arranged

•Surgeon consulted

•Ranson’s score 4 (LDH, AST, Ca, BUN)

CT abdo 27 Jan 2011•P

ancreas diffusely enlarged with peri-pancreatic stranding •G

ross ascities in abdomen & pelvis•C

ompatible with acute pancreatitis•T

iny hypo-enhancing filling defect noted in splenic vein•S

uspicious of splenic vein thrombosis

Progress 28 Jan 2011 (Day 4 after admission)

•Despite medical therapy

•Ms Lo went into Shock (SBP ~ 85)with metabolic acidosis

•Respiratory failure

•Requiring intubation

•Inotropic support

•Surgical: no evidence of biliary causes of pancreatitis

•No surgical intervention can be offered

•Admitted to ICU for close monitoring and support

Managed as Lupus pancreatitis •Pulse steroid• Methylprednisolone 500mg iv daily for 3 days

•Renal shutdown with poor urine output•CVVH was initiated•Plasmapheresis initiated on 29 Jan 2011•Antibiotics & anti-fungal coverage

Despite maximal intensive support…

• Condition further deteriorated • Remained in shock• Metabolic acidosis / DIC • Multiple organ failure• Progressive abdo distension

• Grave prognosis explained to family • For Comfort care / DNAR with morphine infusion • Ms Lo finally succumbed on 30 Jan 2011

Lupus Pancreatitis

Current Opinion in Rheumatology 2000; 12: 379-385

Gastrointestinal Manifestations of systemic lupus erythematosus

Is it common?

Definitely RARE!•F

ewer than 100 cases reported •A

nnual incidence •0

.4-1.1 per 1000 patients • Saab et al. J Rheumatol 1998; 25:801-806

In past 10 years in QEH

•Only 2 -3 cases encountered

•2 out of 3 died

•High mortality with poor prognosis

•Both were young (Age 24 & Age 46)

Prognosis

•Mortality rate of lupus-associated pancreatitis

•Higher than non-SLE-associated pancreatitis

•Significantly lower in group of SLE treated with steroids

How do we define it?•N

o other etiology identified•D

irectly related & caused by SLE•D

iagnosis by EXCLUSION

1st documented by Reifenstein et al in 1939 Arch Intern Med 1939; 63:552-74

L Essaadouni et al. Lupus (2010) 19, 884-887

Nesher G et al. Lupus-associated pancreatitis.Semin Arthritis Rheum 2006; 35 (4): 260-7

Pancreatitis in SLECOMMON causes TO EXCLUDE

As in non-Lupus patients•Obstruction of pancreatic duct•Toxic metabolites•Alcoholic abuse•Hypertriglyceridaemia•Hypercalcaemia•Drugs

Case reports & Series…

17 cases •Pancreatitis as initial presentation•2 had Subacute Cutaneous Lupus Erythromatosus (SCLE)•All were Female•Ass with active SLE

Breuer GS et al. Autoimmun Rev 2006; 5:314-318

•GI symptoms common in SLE

•esp abdo pain (19.2%)

•<5% (0.7 – 4% ) pancreatic disease in Europe & USA

•Mainly acute pancreatitis

•Chronic pancreatitis even more RARE

•Described 3 cases lupus pancreatitis (2001-2005)

One diagnosed by MRCP & EUS2 cases into chronic pancreatitisHappened in generalized flare-up Or in quiescence period Not APS in these 3 casesUsefulness of EUS to achieveEarly diagnosis

Characteristics…•I

n Long standing SLE•M

ulti-organ involvement•A

lready on steroid, diuretic or immunosuppressant

•Occur in generalized flare up & disease quiescence• Latter more likely

•Acute, severe or chronic, self-limiting or fulminant

Marum S et al. Acta Med Port 1998; 11: 779-782

Clinical course •R

esolution of pancreatitis 6.8 days (range 3-15)•I

llness last for only 4.2 days (range 1-7) in control patients•A

mylase & lipase enzyme elevation persisted in SLE•F

or weeks after clinical resolutation

•Contrast to earlier decrease to normal with other causes

How about subclinicalDisease ?

Subclinical pancreatitis•M

ore frequent than clinical pancreatitis

•Elevation of pancreatic enzymes

•Without clinical symptoms

•Hyper-amylasaemia in 30.5% asymptomatic SLE ptsRanson et al. World J Surg 1997; 21: 136-142

Pathogenesis•U

NCLEAR

Mechanisms• Vasculitis•Micro-thrombi formation • Anti-phospholipid Ab• Anti-pancreatic antibodies• Pancreatic inflammation due to T-cell infiltration & complement activation

What damages the pancreas?Vascular Damage •Necrotizing vasculitis syndrome•Occlusion of arteries & arterioles by thrombi • Resulting from severe hypotension or• Antiphospholipid syndrome

•Initimal thickening/proliferation •Immune complex deposition with complement activation • In the wall of pancreatic arteries

Does steroid help?Or a Culprit?

Corticosteroid has a role?

DIFFICULT!!!•Many SLE on steroids, diuretics or immunosuppressive• Implicated in etiology

•Natural coexistence of disease activity with high doses of steroid

•Steroid may improve prognosis of SLE-pancreatitisAutoimmun Rev 2006; 5: 314-318

Corticosteroid as culprit

Hermandex-Cruz Database 18 pts with 26 episodes pancreatitisSLEDAI 6.6 11 severe epidsodes4 died (3 pul hemorrhage, 1 septicaemia)

MOST COMMON CAUSE as medication useOther due to TG, alcohol & cholelithiasis

Arthritis Rheum 1998; 4:S329

Am J Surg 1998; 176:291-294

Steroid as therapy?Saab et al•J Rheumatol 1998; 25:801-806•8 (SLE + pancreatitis)•Evidence showed NO ROLE for steroids in pathogenesis in SLE•Steroid led to improvement of clinical & Laboratory values

•Kapoor et al. J Rheumatol 1999;26:1011-1012•39 year-old lady with lupus nephritis + pancreatitis •Responded to pulse steroid

•Xochitl et al. Arthritis Rheum 1998,4:S330•5 lupus pancreatitis (no obvious cause or due to biliary or alcoholic)

How about Asia experience?

•46 yo lady – lupus diagnosed after pancreatitis

•Somatostatin use in treatment (2 months)

•Methylpred 40mg iv daily started after dx of lupus made (66th day post admission

•Etiology important

•Treatment with steroid after Exclude drug toxicity

Approach

•After excluding common causes of pancreatitis in SLE • Esp drug toxicity

•Reasonable to start steroids or increase the dosage

In non-response cases

•Plasmapheresis

•High-dose IVIG or

•Cytotoxic agents (e.g. Cyclophosphamide)

Lupus (2010) 19, 884-887

Conclusion•L

upus pancreatitis – RARE manifestation in lupus•H

igh Index of suspicion•E

xclude common causes•S

ubclinical pancreatitis more common•S

teroid role

QEH cases

CASE Age Sex Dx (yr)

Rx amylase

Imaging

Death alcohol

DNA

1 26 F 6 Steroid & Aza 1600 CT Y - >300

2 46 F 0.25 No steroid prior

2997 CT Y - >300

Moreover … despite•C

ontribution of immune system to pancreatic disease•N

ot considered autoimmune pancreatitis per se•D

o not fulfill international criteria well documented disease

Japan Pancreas Society. Diagnostic Criteria fro Autoimmune Pancreatitis 2002. Japan Pancreas Soc 2002;17

Mechanism reference