Transcript MR-AC11

“Everything's got a moral, if only
you can find it.”
- Lewis Carroll,
British author
Alan Chan, MD
Med-peds PGY4
Z A CD
207512
Chief Complaint: altered mental status
and worsening edema
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 hearing
No chest pain, SOA. Vision fine except known cataracts. Denies
weakness, F/C, fatigue, night sweats. No diarrhea, vomiting.
Z A CD
Medications
•
•
•
•
•
•
•
•
Z A CD
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
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, wheeze
No GI issues like diarrhea or vomiting.
Z A CD
No urinary changes.
No recent illnesses.
Unsure of palpitations, orthopnea at home, but patient
is lying 30 deg in bed.
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.
Z A CD
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
Z A CD
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
Z A CD
CC: confusion, LE swelling
Differential Diagnosis
HPI:
80yo with 2 wk of symptoms.
Currently confined to
home.
PMH:
HTN, hyperlipidemia
Exam Findings
edema
Z A CD
Laboratory Data
CBC
BMP
Urinalysis
Cardiac Enzymes
Liver Function Tests
Coagulation
Endocrinology
Serology
Other Serology
Cytology
Pathology
Z A CD
Microbiology
CXR
EKG
Ultrasound
CT Scan
Echo
Other Studies
Truman panel
Clinical Course
Differential Diagnosis
Discussion
Please Press to Return
Z A CD
CBC
8
285
12.5
24.6
Gran 84, L 11 M 5 %
MCV 77 (80-99)
RDW 19 (<14.5)
Z A CD
BMP
139
100
92
4
23
5.5
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)
Z A CD
123
Urine Analysis - cath
color
sp gr
pH
blood
ketone
glu
prot
LE
nitrite
urobil
bili
Z A CD
yellow
1.020
5
mod
X
X
30
X
X
0.2
x
Microscopic
5-10 wbc
10-25 rbc
2-5 Sq epi
tr mucus
Upro/Cr- 1
Cardiac Enzymes
1st – TnI 0.06
Z A CD
Liver Function Tests
AST
ALT
Alk Phos
Albumin
T Bilirubin
D Bilirubin
Protein
Z A CD
19 (15-41)
29 (7-35)
32 (32-91)
2.2 (3.5-4.8)
0.6 (0.3-1.2)
xx (0.1-0.5)
6.1 (6.1-7.9)
Coagulation and stuff
PTT
PT
INR
Retic 2.2
Z A CD
x (21-33)
x (10.3-13.0)
x
Endocrinology
TSH
Free T4
2.4 (0.34-5.6)
X (0.6-1.6)
Folate and B12 normal
Epo 8.3 (4.2-27.8)
A1C 4.9
Ferritin 773 !!
Z A CD
Serology
• MPO >100
• PR3 <3.5
• cANCA <1:20
• pANCA > 1:320
• Anti GBM IgG neg
Z A CD
Pathology
• Normochromic normocytic anemia.
Z A CD
Other Serology
• ESR – 118
• CRP 11
• Ammonia - <16
• C3, C4 wnl
• LDH – 247 (98-192)
• Chol panel - wnl
Z A CD
Microbiology
• UCx Mixed Gram positive flora isolated.
• BCx neg
Z A CD
Z A CD
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.
Z A CD
Z A CD
EKG on admit
• Normal sinus rhythm
• Chest Lead Error
• Moderate voltage criteria for LVH, may be normal
variant
• Borderline ECG
Z A CD
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.
Z A CD
CT studies
CT headCHRONIC 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.
Z A CD
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.
Z A CD
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).
Z A CD
Truman panel
• Cbc, bmp, lft, Cardiac enzymes, CXR, CT head….
All already drawn!
• BNP - 425
Z A CD
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!
Z A CD
Discussion - Goals
•
•
•
•
•
Overview of vasculitis
Classification
MPA
Diagnosis
Treatment
MKSAP Q?
Z A CD
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.
Z A CD
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)
Z A CD
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
Z A CD
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
Z A CD
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
Z A CD
Ask…
•
•
•
•
•
•
•
Z A CD
Patient History and past medical
Other blood work
ANA
Complement
ANCA
EMG
Biopsy
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
Z A CD
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
Z A CD
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%!
Z A CD
Not bad, but could be better
Z A CD
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
Z A CD
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.
Z A CD
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.
Z A CD
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
Z A CD
Treatment – may base on severity
Z A CD
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
Z A CD
•
•
•
•
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
• D – pred with lamivudine
• Polyarteritis nodosa in acute setting with hep B needs
short term high dose corticosteroid with long term
anti-viral
Z A CD
References
•
•
•
•
•
Z A CD
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).
Z A CD
11 and done!