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Alan Chan, MD

Med-peds PGY4

“Everything's got a moral, if only you can find it.”

- Lewis Carroll,British author

207512

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HPI: 82yo AA woman with the usual PMHx problems of uncontrolled HTN, hyperlipidemia presents when family notes confusion for 2 weeks. Increasing. Refuses to leave apartment for past 6 weeks, keep rearranging furniture and using umbrella indoors.

Increasing swelling in LE bilaterally, family has noted more in the past 2 weeks and does not think was there earlier. No leg pain

Decreased appetite, only walks around apartment now used to home shopping a little with family. No urinary changes she notes.

Slightly hard of hearingNo chest pain, SOA. Vision fine except known cataracts. Denies

weakness, F/C, fatigue, night sweats. No diarrhea, vomiting.

Chief Complaint: altered mental status and worsening edema

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Medications• Metoprolol 25 mg bid

• Detrol LA 2 mg

• Clonidine 0.2 mg bid

• Verapamil 240 mg bid

• Lisinopril 40 mg

• Lipitor 10 mg

• Claritin 10 mg

• KCl 20 mEq

Allergies

NKDA

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PMH: HTN – uncontrolled, hyperlipidemia, cataracts

PSurgHx: L 5th toe amputation for melanoma

ROS: No chills, fatigue, night sweats. No wt changes. No vision changes No rhinorrhea, sneezing; No dyspnea on exertion, no shortness of breath, wheezeNo GI issues like diarrhea or vomiting.

No urinary changes. No recent illnesses. Unsure of palpitations, orthopnea at home, but patient is lying 30 deg in bed.

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SH: No tob, EtOH, or anything else.

FH: Alzheimer in both parents. Have been deceased for a long time. Family is unaware of anything else.

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VS in ER: Temp 97.1 oral, Resp 18, BP 138/71, Pulse 94. 97% on RA

General: frail appearing woman appears stated age. Confused about location, thinks it’s the Sabetes eye clinic

HEENT: EOMI, PERRL, pale conjunctiva. OP clear, edentatous

Neck: soft, supple, no elevated JAD

Chest: CTA bilat, no wheezing

CVS: reg regular rhythm S1, S2, no murmur

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Abd: BS +, non TTP. No guarding. No CVA tenderness

Ext: at least 2+ pitting edema to knee bilat, 2+ pulses

Neuro: CN 2-12 intact, no focal deficits. 4/5 strength but poor effort throughout.

Skin: old incision site on left foot without signs of infection; no purpuric rash

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Differential Diagnosis

CC: confusion, LE swelling

HPI:80yo with 2 wk of symptoms.

Currently confined to home.

PMH: HTN, hyperlipidemia

Exam Findingsedema

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Laboratory Data

CBC

BMP

Urinalysis

Cardiac Enzymes

Liver Function Tests

Coagulation

Endocrinology

Serology

Other Serology

Cytology

Pathology

Microbiology

CXR

EKG

Ultrasound

CT Scan

Echo

Other Studies

Truman panel

Clinical Course

Differential Diagnosis

Discussion

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CBC

12.58

24.6285

Gran 84, L 11 M 5 %

MCV 77 (80-99)RDW 19 (<14.5)

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BMP

139

4

100

23

92

5.5123

AG 13 (3-15)

Ca 8.7 (8.8-10.5)Mg 2.1 (1.8-2.5)PO4 2.9 (2.4-4.7)

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Urine Analysis - cath

Microscopic5-10 wbc10-25 rbc2-5 Sq epitr mucus

Upro/Cr- 1

color yellow

sp gr 1.020

pH 5

blood mod

ketone X

glu X

prot 30

LE X

nitrite X

urobil 0.2

bili x

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Cardiac Enzymes

1st – TnI 0.06

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Liver Function Tests

AST 19 (15-41)

ALT 29 (7-35)

Alk Phos 32 (32-91)

Albumin 2.2 (3.5-4.8)

T Bilirubin 0.6 (0.3-1.2)

D Bilirubin xx (0.1-0.5)

Protein 6.1 (6.1-7.9)

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Coagulation and stuff

PTT x (21-33)

PT x (10.3-13.0)

INR x

Retic 2.2

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Endocrinology

TSH 2.4 (0.34-5.6)

Free T4 X (0.6-1.6)

Folate and B12 normal

Epo 8.3 (4.2-27.8)

A1C 4.9

Ferritin 773 !!

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Serology

• MPO >100• PR3 <3.5

• cANCA <1:20• pANCA > 1:320

• Anti GBM IgG neg

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Pathology

• Normochromic normocytic anemia.

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Other Serology

• ESR – 118

• CRP 11

• Ammonia - <16

• C3, C4 wnl

• LDH – 247 (98-192)

• Chol panel - wnl

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Microbiology

• UCx Mixed Gram positive flora isolated.

• BCx neg

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Chest X-ray

1. No focal airspace disease.2. Remote granulomatous disease.3. Borderline cardiomegaly.4. Prominence of the ascending aorta which may be seen in aortic valvular disease.

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EKG on admit

• Normal sinus rhythm• Chest Lead Error• Moderate voltage criteria for LVH, may be normal

variant• Borderline ECG

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U/S renal with dopplers

• Impression:

• 1. Right complex renal cyst with an internal nodule vs septation. Recommend triple phase CT renal imaging.

• 2. Left simple renal cyst. • 3. Aortic aneurysm measuring 3.4 cm in greatest caliber

below the level of the renal arteries.• 4. Aortic atherosclerosis.

• Doppler - • This study shows no evidence for renal artery stenosis

bilaterally. There is evidence for small 3-cm abdominal aortic aneurysm. Further clinical correlation is recommended.

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CT head-

CHRONIC CHANGES OF PERIPHERAL CEREBROVASCULAR DISEASE ONLY. NO FINDINGS OF AN ACUTE CEREBROVASCULAR EVENT.

CT chest without contrast

1. Mild aneurysmal dilatation of the aortic arch.

2. Atheromatous changes of the aorta.

3. Granulomatous calcifications.

CT studies

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2-D Echocardiogram

CONCLUSIONS:

1. Severely dilated left atrium by LA volume index calculation. 2. Mild aortic valve sclerosis. 3. Overall left ventricular ejection fraction is estimated at 65%. 4. Mild tricuspid regurgitation. 5. Grade 1 LV diastolic dysfunction. 6. Mildly elevated pulmonary artery systolic pressure.

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MAG scan

• Impression:

• 1. Normal bilateral renal perfusion.

• 2. Diminished renal washout bilaterally suggesting a mild degree of obstruction and associated diminished renal function (given the intermediate T1/2 max values of less than 20).

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Truman panel

• Cbc, bmp, lft, Cardiac enzymes, CXR, CT head…. All already drawn!

• BNP - 425

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Clinical Course

• ARF, FeNa 1.8, wnl U/S except cysts, MAG scan with decreased renal fxn

• uremia• Elevated inflammatory markers – vasculitis?• Renal biopsy not done due to family wishes and

question of patient to tolerate procedure.

• Serology shows a microscopic polyangiitis picture!

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Discussion - Goals

• Overview of vasculitis• Classification• MPA• Diagnosis• Treatment

MKSAP Q?

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Vasculitis - definition

• presence of inflammatory leukocytes in vessel walls leading to damage

•Mechanics still unknown

•Primary or secondary to another disease process

•Treatment in acute phase important because early deaths are due to active disease, but later deaths may be due to treatment complications.

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Classification

• Classically by affect vessel size… but a lot of overlap

•Large – Takayasu (aorta and branches) and giant cell (medium as well)

• Medium – polyarteritis nodosa (med and small), Kawasaski (all sizes with mucocutaneous involvement), primary CNS vasculitis (med and small without extracranial vessels)

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Classification

• Small – – Churg-Strauss (lung and skin muscular arteries),

– Wegener granulomatosis (sm and med of lung and necrotizing pauci immune glomerulonephritis in kidneys)

– microscopic polyarteritis/polyangiitis (like WG spectrum)

– Henoch-Schonlein purpura (tissue deposition of IgA immune complex)

– Hypersensitivity vasculitis – like above, but no IgA

– Essential cryoglobulinemic vasculitis

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More!

• Vasculitis due to connective tissue d/o and some others due to viral infection

• Lots of overlap, this criteria last updated by Am College of Rheumatology in 1990, based on prospective data from the 1980s and only help distinguish from other vasculitides.

• Since the new ANCA testing in 1982, new classification may consider ANCA positive vs negative

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Diagnosis

• Hard to diagnosis• Suspect in systemic symptoms, or if can be

associated in patient’s other diseases• “mononeuritis multiplex” or asymmetric

polyneuropathy… also seen in diabetes• Palpable purpura – HSP, MPA• Pulmonary-renal involvement

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Ask…

• Patient History and past medical• Other blood work• ANA• Complement• ANCA• EMG• Biopsy

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False positives

• Sometimes reported in rheumatic inflammatory disease, but these were before MPO and PR3 testing

• ANCA, typically p type, in UC, but NOT Crohn’s• Also in primary sclerosis cholangitis • Cystic fibrosis patients with lung disease, but non

MPO

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ANCA??

• Include WG, MPA, renal limited vasculitis, Churg Strauss.

• The ACR criteria for WG/MPA – did not differentiate between these 2– Nasal or oral inflammation

– Abnormal CXR with nodules, cavities, or fixed infiltrates

– Abnormal urine sediment (microscopic hematuria +/- rbc casts)

– Granulomatous inflammation on biopsy of an artery

• Two or more 88% sens, and 92% spec

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Other classification

• Chapel Hill Consensus - Defines disease, but no classification and NOT diagnostic, ANCA is not included

• European Medicines Agency algorithm – must exclude Churg Strauss and WG

• Classify by??? --- MP0 ANCA, PR3 ANCA, and seroneg ANCA

• One study suggests specificity of antibodies to PR3/MPO as high as 98.4%!

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Not bad, but could be better

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Labs

• ANCA are directed against the granular and lysosomal parts of neutrophils and monocytes

• IIF (indirect immunofluor) stain or enzyme linked immunosorbent assay in a cytoplasmic or perinuclear pattern

• Target of cANCA is proteinase-3 and pANCA is myeloperoxidase

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ANCA Associated Vasculitis

• Genetic factors on HLA genes of chr6

• Silica – bad stuff. From 22-46% of AAV have had exposure. Brings immune response and inflammatory reactions

• Bacterial infection – S. aureus

• Drugs – also bad – PTU (most common), hydralazine, D-penicillamine, and minocycline.

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Microscopic Polyangiitis

• Originally described in a case series as a type of polyarteritis nodosa with RPGN (rapidly necrotizing glomerulonephritis) and sometimes lung hemorrhage – but has capillary, venule, or arterioles involvement

• Male slightly > female• Avg age of onset > 50 yo• General symptoms may occur months to years

before acute phase.

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Treatment

• If don’t treat, prognosis is bad• Corticosteroids with cyclophosphamide – up to 90%

go into remission• But… Cytoxan long term use side effects –

secondary infections, bone marrow suppresion, hemorrhagic cystitis, and bladder cancer.

• Recommend prophylactic TMP-SMX for PJP• Other trials looking at MTX, rituximab, plasma

exchange, etanercept, mycophenolate mofetil, azathioprine

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Treatment – may base on severity

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Question of the Day

• 53 yo man with 6 wk hx of fatigue, fever, numbness and tingling in the hands and feet, mild abd pain, and a nodular rash on the hands, arms, and legs. Weight lost 9.0 lb.

• Exam – T 100.3 °F, 150/82, HR 96 RR 14. CV exam normal. Hands reveals numerous subcutaneous nodules. There is shotty cervical, axillary, and inguinal LAP. Abd - hepatomegaly and mild diffuse tenderness NO rebound. testes are tender. No synovitis

• Hgb 8.6, wbc15.2, plt 523, esr 113, AST 85, ALT 73• HBsAg POS, HBeAg POS• ANCA, ANA, HIV, anti-Hbs, anti-HCV all neg• Skin bx – necrotizing vasculitis

• A cytoxan• B pred• C pred with cytoxan• D pred with lamivudine

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• D – pred with lamivudine

• Polyarteritis nodosa in acute setting with hep B needs short term high dose corticosteroid with long term anti-viral

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References

• MKSAP 14/15• Uptodate.com “Classification of and approach to the vasculitides in adults”,

“Clinical manifestations and diagnosis of Wegener's granulomatosis and microscopic polyangiitis “. Accessed 6/10/2011.

• Chen, M, Kallenberg CG. ANCA-associated vasculitides—advances in pathogenesis and treatment. Nat Rev Rheumatol. 2010; 6(653-664).

• Kallenbery CG. The Last Classification of Vasculitis. Clinic Rev Allerg Immunol. 2008; 35(5-10)

• Guillevin L, Durand-Gasselin B, Cevallos R, et al. Microscopic Polyangiitis: Clinical and Laboratory findings in 85 patients. Arthritis and Rheumatism. 1999; 42:3 (421-430).

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