ACP Case Presentation-Vasculitis

ACP CASE PRESENTATION
Akash Makkar, Makkar,
MD
PGY 3 Categorical
Internal Medicine
University of Louisville

CASE HISTORY
49 yo AA female presented to ER with
increasing weakness, lethargy, poor
appetite and chills for 1 week
nausea and vomiting for ~ 1-2 1 2 days
abdominal pain and left flank pain of
unknown duration
cough, productive, of unknown
duration. No hemoptysis

CASE HISTORY
Recent (1 month prior)
hospitalization at another hospital
with seizures
Medication doses adjusted. No new
medications started

PMH
Depression
Seizures

MEDICATIONS
Escitalopram (Lexapro Lexapro)
Levetiracetam (Keppra Keppra)
Divalproex sodium (Depakote ( Depakote) )
Phenobarbital

SOCIAL HISTORY
Unremarkable for drug use

PHYSICAL EXAMINATION
T : 102.5
HR : 94
RR : 18
BP : 110/63
Sat : 98% RA
Wt : 250 lb
General:
Lethargic but
easily arousable
Skin : No Skin
Rash
HEENT : PERRL,
normal fundus
examination

PHYSICAL EXAMINATION
Neck : supple, no
JVD, normal thyroid
Lymph Nodes :
Inguninal LAD
RS : CTA bilaterally,
no rhonchi, rhonchi,
crackles
CVS : RRR, Normal
S1 & S2, no rub or
murmur
PVS : pulses 2+
bilaterally & equal
Abdomen : soft,
NT, BS+
Extremities : 1+ LE
edema, edema,
full ROM
Neurologic : AAO
X3, CN intact, DTR
2+, Plantars flexor

LAB WORK UP
Na 129 CL 104 BUN 56
K 3.9 Co2 23 Cr 2.9 ( 1.2 1
month prior)
Hgb 11.6 WBC 9.6 Plt 310, no
periph eos
UA >300 prot, prot,
+WBC, +RBC ( no
comment on RBC casts), no urine
eos
FeNA

LAB WORK UP
ALT 16 AST 38 Alk Phos 108 T. bili
0.3
Alb 2.7 T. prot 6.2
CK 714 LDH 762
CRP 23.89
Tox screen + barbiturates

CT ABDOMEN/PELVIS

CT ABDOMEN/PELVIS

CT ABDOMEN/PELVIS

IMAGING
Renal US – R kidney 13.4 cm, L
kidney 13.2, no hydro, mass or
stone

HOSPITAL COURSE
Treated for urosepsis with broad
spectrum abx, abx,
IVFs without significant
improvement
Blood, urine, sputum cx negative
Waxing and waning fevers
Waxing and waning mental status
Worsening Cr to 5.4
Worsening anemia & thrombocytopenia

ADDITIONAL STUDIES
24h urine protein ~ 4gm
SPEP/UPEP negative
ANA, ASO titer, hepatitis B/C, ANCA
negative
C3 C4 Normal
HIV 1,2 negative
RPR negative
LP unsuccessful

MRI BRAIN

ADDITIONAL STUDIES
MRI brain – no acute abnormalities,
cerebellar atrophy
Bone marrow bx - normal cellularity, cellularity,
no lymphoma, leukemia, infectious
process or granulomatous disease
Lymph node bx suggested but
declined by patient and family

GALLIUM SCAN

KIDNEY BIOPSY

PATHOLOGIST’S DIAGNOSIS
Necrotizing arteritis and necrotizing
glomerulonephritis with crescents.
The findings are consistent with a
pauci-immune pauci immune small vessel vasculitis
with low intensity IgA deposits.

PATHOLOGIST’S DIAGNOSIS
Differential diagnosis is between
microscopic polyangiitis and Wegener's
granulomatosis.
granulomatosis
Given the well defined granulomatous
component to the arteritis, arteritis,
a diagnosis
of Wegener's granulomatosis is
justified, even if there is no respiratory
tract involvement.

PAUCI-IMMUNE PAUCI IMMUNE SMALL
VESSEL VASCULITIS

PAUCI-IMMUNE PAUCI IMMUNE SMALL
VESSEL VASCULITIS
Most common primary systemic small-
vessel vasculitis in adults
Preferentially involves venules, venules,
capillaries, and arterioles, may involve
arteries/veins
Similar histology

PAUCI-IMMUNE PAUCI IMMUNE SMALL
VESSEL VASCULITIS
Most common in adults in their 50-60s 50 60s
Men and women affected equally
In US whites > blacks
Rare diseases (2 in 100,000 in UK, 1 in
100,000 in Sweden)

PAUCI-IMMUNE PAUCI IMMUNE SMALL
VESSEL VASCULITIS
Wegener's granulomatosis
Microscopic polyangiitis
Churg-Strauss Churg Strauss syndrome
Renal-limited
Renal limited vasculitis

Disease
WG
MPA
i-NCGN NCGN
CSS
Definition
Granulomatous
inflammation involving
the respiratory tract,
necrotizing vasculitis of
small/medium-sized
small/medium sized
vessels
Necrotizing vasculitis of
small vessels.
Necrotizing GN very
common
Necrotizing and
crescentic GN without
systemic manifestations
Eosinophils-rich
Eosinophils rich
granulomas involving
respiratory tract, and
necrotizing vasulitis of
small/medium-sized
small/medium sized
vessels, asthma and
eosinophilia
ACR Criteria
Nasal /oral inflammation
Abnormal CXR
Urinary sediment
Granulomas on bx
Not available
Not available
Asthma
Eosinophilia (>10%)
Neuropathy
Lung infiltrates
Sinusitis
Extra-vascular
Extra vascular eos
Not available
Euvas Criteria
Clinical/histological evidence of
respiratory tract involvement
(lung nodules, sinusitis, tracheal
stenosis, stenosis,
orbital pseudotumor,
pseudotumor,
etc.)
Necrotizing and crescentic GN
and/or small vessel vasculitis. vasculitis.
No
airway symptoms compatible
with WG
Necrotizing and crescentic GN,
no systemic manifestations,
except for constitutional
symptoms

APPROX. FREQ. OF ORGAN-SYSTEM
ORGAN SYSTEM
MANIFESTATIONS IN SVV (%)
Organ System
Cutaneous
Renal
Pulmonary
Ear, nose, throat
Musculoskeletal
Neurologic
Gastrointestinal
MPA
40
90
50
35
60
30
50
WG
40
80
90
90
60
50
50
CSS
60
45
70
50
50
70
50

ANCA AUTOANTIBODIES
React with antigens in the cytoplasm
of neutrophils and monocytes
First described in 1982 in patients with
necrotizing GN and systemic vasculitis
Davies Davies DJ DJ et et al., al., Br Br Med Med JJ 1982 1982
Association with WG described in 1985
Van Van der der Woude Woude FJ., FJ., Lancet Lancet 1985
1985

ANCA IN SMALL VESSEL
VASCULITIS
Good biomarker for systemic vasculitis
90% of c-ANCA c ANCA are PR3-ANCA PR3 ANCA
90% of p-ANCA p ANCA are MPO-ANCA MPO ANCA

C-ANCA ANCA (PR3-ANCA)
(PR3 ANCA)

P-ANCA ANCA (MPO-ANCA)
(MPO ANCA)

SENSITIVITY AND SPECIFICITY OF
ANCA IN THE DIAGNOSIS OF AASV
Sensitivity and specificity of
combined IIF and ELISA are 72.5%
and 98.4%
Hagen Hagen EC EC et et al., al., Kidney Kidney Int Int 1998 1998
Combined ANCA testing system (anti- (anti
PR3/C-ANCA PR3/C ANCA + anti-MPO/P anti MPO/P-ANCA) ANCA)
has sensitivity of 85.5% and
specificity of 98.6%
Rao Rao JK JK et et al., al., Ann Ann Intern Intern Med Med 1995
1995

ANCA-NEGATIVE ANCA NEGATIVE SMALL
VESSEL VASCULITIS
Up to 40% of patients with limited WG
~10% of patients with severe WG
30% of all patients with MPA
~50% of patients with CSS
20-25% 20 25% of patients with i-NCGN i NCGN
Gullevin Gullevin L L et et al., al., Arthritis Arthritis Rheum Rheum 1999 1999
Sinico Sinico RA RA et et al., al., Arthritis Arthritis Rheum Rheum 2005
2005

PATHOLOGIC LESIONS IN
SMALL VESSEL VASCULITIS
Lytic necrosis of the vessel walls
leading to fibrinoid necrosis
Mural and perivascular influx of
neutrophils
Focal segmental and necrotizing GN,
usually with crescent formation**
formation**
No or little immune deposits by IF
microscopy**
microscopy**
Granuloma formation in WG and CSS

TREATMENT
Induction of remission
IV methylprednisolone /prednisone
IV Cyclophosphamide
Plasmapheresis in severe renal
disease/pulmonary hemorrhage
Complete remission in 75% of
patients with WG, in 80% of
patients with MPA

TREATMENT
Maintenance of remission
Reduce or stop prednisone
Cyclophosphamide vs azathioprine

TREATMENT
Treatment of relapse
Best treatment controversial
Reinstitution of treatment similar to
induction regimen
50% WG relapse within 5 years,
~30% with MPA relapse within 2
years

DRUG-INDUCED DRUG INDUCED VASCULITIS
Systemic manifestation of
hypersensitivity to many drugs
Rash, renal, hepatic, pulmonary
involvement
Granulocytic, sometimes eosinophilic
infiltrates around small vessels on
biopsy
Syndromes usually resolve with
discontinuation of the drug

DRUGS INVOLVED
PTU, methimazole,
methimazole,
carbimazole
Hydralazine
Minocycline
Anticonvulsants (phenytoin ( phenytoin, , valproic acid,
carbamazepine,
carbamazepine,
ethosuximide,
ethosuximide,
primidone, primidone,
trimethadione)
trimethadione
Allopurinol
Penicillamine
Procainamide

CONCLUSIONS
Rare group of disorders
Clinical presentation variable, depends
on the vessel and organ involved
Histology very similar
ANCA-negative ANCA negative status does not rule
out Pauci-immune Pauci immune SVV
Rapid diagnosis important